Pancreatic-duct-lavage cytology in candidates for surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas: should the International Consensus Guidelines be revised?

PubMed

Sai, Jin Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio; Maehara, Tadayuki

2009-03-01

The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. Single-center retrospective study. Academic medical center. The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. Single-center and small number of patients. Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.

Accuracy of FNAC and CT in the differentiation of benign and malignant parotid tumours in a case series.

PubMed

Gavín-Clavero, Marina A; Usón-Bouthelier, Tomás; Jariod-Ferrer, Úrsula M; Fernández-Larrañaga, Arancha; Pantilie, Bianca; Lobera-Molina, Fernando; Simón-Sanz, M Victoria; Nadal Cristóbal, Bartolomé

Parotid tumours, in addition to the wide variety of types, are histologically complex. Differentiating between benign and malignant tumours in preoperative diagnosis is important in deciding the type of surgery required. Fine needle aspiration cytology (FNAC) is a simple, quick, low-cost, low-invasive and well-tolerated tool used in the preoperative diagnosis of these tumours. we calculated the sensitivity, specificity, predictive positive value (PPV) and negative predictive value (NPV) of FNAC and computed tomography (CT) in the differentiation of benign and malignant parotid tumours operated between 2010 to 2014 in the oral and maxillofacial surgery department of the University Hospital Miguel Servet. The sensitivity of FNAC is 50%, while the specificity is high, at 98.7%. FNAC offers high reliability in the diagnosis of malignant tumours, despite its low sensitivity. However, when the diagnosis is indeterminate or benign, other than pleomorphic adenoma or Whartin tumour, the reliability to exclude malignancy decreases. The low sensitivity of FNAC to differentiate malignant from benign parotid tumours, means that we cannot rule out other diagnostic tests, clinical symptoms and especially the intraoperative vision of each surgeon. Especially when the diagnosis is indeterminate. Nevertheless, it is a technique used in a systematised way and helps in pre-surgical decision-making. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

An acute multispecies episode of sheep-associated malignant catarrhal fever in captive wild animals in an Italian zoo

USDA-ARS?s Scientific Manuscript database

In July 2011, in a zoological garden in Rome, Italy, malignant catarrhal fever (MCF), a fatal, systemic disease of Artiodactyls, was suspected on the basis of neurological signs and gross lesions observed in a banteng, the first animal to die of this infection. An MCF type-specific, one-step PCR wit...

Occupation and hematopoietic and lymphoproliferative malignancies among women: a linked registry study.

PubMed

Linet, M S; McLaughlin, J K; Malker, H S; Chow, W H; Weiner, J A; Stone, B J; Ericsson, J L; Fraumeni, J F

1994-11-01

Using a nationwide linked registry, we evaluated the incidence of several hematopoietic and lymphoproliferative (HLP) malignancies among Swedish women from 1961 to 1979 by industry and occupation. The risks of one or more types of HLP cancers (including the leukemias, non-Hodgkin's lymphoma, multiple myeloma, and mycosis fungoides) were significantly increased among women working in the agriculture and textile industries, housekeepers, and post office employees. Limitations of these linked-registry data include lack of detailed information on specific exposures and duration of employment, and the relatively small sizes of specific occupational cohorts. Nevertheless, as the proportion of women entering the workforce continues to increase, this data resource may provide additional clues to occupational determinants of HLP and other malignancies.

Extrathymic malignancies in thymoma patients with and without myasthenia gravis.

PubMed

Owe, Jone Furlund; Cvancarova, Milada; Romi, Fredrik; Gilhus, Nils Erik

2010-03-15

The influence of myasthenia gravis (MG) on risk of cancer is uncertain. Using nationwide, comprehensive data, we investigated the association between MG and occurrence of extrathymic malignancies in thymoma patients, and also assessed the risk of consecutive extrathymic malignancies after thymoma diagnosis. Two hundred twelve thymoma patients were identified at the Cancer Registry of Norway between 1969 and 2005. Records on all extrathymic malignancies for these patients were supplied from the Registry's database. Comparisons were made between MG and non-MG patients and between thymoma patients and the general population. The frequency of extrathymic malignancies was similar in MG and non-MG thymoma patients, and so was the survival after thymoma diagnosis. Extrathymic malignancies occurred in 10% of thymoma patients within 10 years following the thymoma diagnosis. Thymoma patients had a significantly increased risk of developing an extrathymic malignancy compared to the general population. This was not linked to any specific kind of cancer. Thymoma morphology was not a significant predictor for an increased risk of consecutive cancer. The immunological process underlying MG does not influence the risk of cancer in thymoma patients. Thymoma patients have a significantly increased risk of extrathymic malignancies. This is an intrinsic effect, being unaffected by a coexisting autoimmune disease such as MG and not specific for any type of cancer. Screening for extrathymic malignancies in thymoma patients is probably not recommendable, but clinicians should be aware of the high rate of extrathymic malignancies occurring in thymoma patients.

Constitutive Uncoupling of Pathways of Gene Expression That Control Growth and Differentiation in Myeloid Leukemia: A Model for the Origin and Progression of Malignancy

NASA Astrophysics Data System (ADS)

Sachs, Leo

1980-10-01

Chemical carcinogens and tumor promoters have pleiotropic effects. Tumor initiators can produce a variety of mutations and tumor promoters can regulate a variety of physiological molecules that control growth and differentiation. The appropriate mutation and the regulation of the appropriate molecules to induce cell growth can initiate and promote the sequence of changes required for transformation of normal cells into malignant cells. After this sequence of changes, some tumors can still be induced to revert with a high frequency from a malignant phenotype to a nonmalignant phenotype. Results obtained from analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, the phenotypic reversion of malignancy by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation-defective leukemic cell mutants have been used to propose a general model for the origin and progression of malignancy. The model states that malignancy originates by changing specific pathways of gene expression required for growth from inducible to constitutive in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant cells, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways can uncouple other controls, which then causes blocks in differentiation and the further progression of malignancy. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells can also explain the expression of fetal proteins, hormones, and some other specialized products of normal development in various types of tumors.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

PubMed

McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

2014-04-01

Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

Chromosomal aberrations in soft tissue tumors. Relevance to diagnosis, classification, and molecular mechanisms.

PubMed Central

Sreekantaiah, C.; Ladanyi, M.; Rodriguez, E.; Chaganti, R. S.

1994-01-01

In recent years, significant progress has been made in identifying characteristic chromosomal rearrangements associated with several solid tumor types, notably sarcomas, a relatively rare subset of human cancer. Most sarcomas analyzed have been found to be characterized by recurrent chromosome translocations that are specific to histological types. We have reviewed published reports of chromosomal aberrations in benign and malignant soft tissue tumors and found an incidence of specific translocations in these neoplasms that ranged from 20% to 93% within histological tumor types. Identification of recurrent chromosomal abnormalities in benign tumors has resulted in a reappraisal of the general concept that benign tumors have a normal (diploid) chromosome constitution. The variety of recurrent changes present in the different tumor types attests to the cytogenetic diversity inherent in these tumors. The chromosomal rearrangements in each of the tumor types were unique and did not correspond to cancer-associated aberrations known from other solid or hematopoietic malignancies. Cytogenetics thus provides an essential adjunct to diagnostic surgical pathology in the case of malignant soft tissue tumors, which often present substantial diagnostic challenges. In addition, it represents another approach to determine the histogenetic origin of some tumors and identifies sites of gene deregulation for molecular analysis. Indeed, recent molecular analyses of several sarcoma-associated translocations have identified novel genes and novel mechanisms of their dysregulation. PMID:8203453

Double stenting with silicone and metallic stents for malignant airway stenosis.

PubMed

Matsumoto, Keitaro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Kamohara, Ryotaro; Hatachi, Go; Nagayasu, Takeshi

2017-08-01

For severe malignant airway stenosis, there are several types of commercially available airway stents, and each has its own advantages and disadvantages. We herein describe the safety and efficacy of combination stenting with silicone and metallic stents for patients with extended malignant airway stenosis. Seven patients with malignant airway stenosis were treated via combination stenting with a silicone stent and a metallic stent for extended airway stenosis from the central to peripheral airways. Five patients were diagnosed with advanced esophageal cancer, two of whom had tracheoesophageal fistulas. One patient had adenoid cystic carcinoma, and another had mediastinal tumor. There were no specific complications related to the double stenting. Combination stenting with silicone and metallic stents proved to be a safe option for patients with severe, extended, and complicated malignant airway stenosis.

Differentiation between cavernous hemangiomas and untreated malignant neoplasms of the liver with free-breathing diffusion-weighted MR imaging: comparison with T2-weighted fast spin-echo MR imaging.

PubMed

Soyer, Philippe; Corno, Lucie; Boudiaf, Mourad; Aout, Mounir; Sirol, Marc; Placé, Vinciane; Duchat, Florent; Guerrache, Youcef; Fargeaudou, Yann; Vicaut, Eric; Pocard, Marc; Hamzi, Lounis

2011-11-01

To test interobserver variability of ADC measurements and compare the diagnostic performances of free-breathing diffusion-weighted (FBDW) with that of T2-weighted FSE (T2WFSE) MR imaging for differentiating between cavernous hemangiomas and untreated malignant hepatic neoplasms. Thirty-five patients with cavernous hemangiomas and 35 with untreated hepatic malignant neoplasms had FBDW and T2WFSE MR imaging. Hepatic lesions were characterized with ADC measurement and visual evaluation. Interobserver agreement for ADC measurement was calculated. Association between ADC value and lesion type was assessed using univariate analysis. Sensitivity, specificity and accuracy of ADC values and visual evaluation of MR images for the diagnosis of untreated malignant hepatic neoplasm were compared. ADC measurements showed excellent interobserver correlation (intraclass correlation coefficient=0.980). Malignant neoplasms had lower ADC values than hemangiomas for the two observers (1.11×10(-3) mm2/s±.21×10(-3) vs. 1.77×10(-3) mm2/s±.29×10(-3) for observer 1 and 1.11×10(-3) mm2/s±.19×10(-3) vs. 1.79×10(-3) mm2/s±.32×10(-3) for observer 2) and univariate analysis found significant correlations between lesion type and ADC values. Depending on ADC threshold value, accuracy for the diagnosis of malignant neoplasm varied from 82.9% to 94.3%. Using visual evaluation, FBDW showed better specificity and accuracy than T2WFSE MR images for the diagnosis of malignant neoplasm (97.1% vs. 77.1% and 94.3% vs. 62.9%, respectively). FBDW imaging provides reproducible quantitative information and surpasses the value of T2WFSE MR imaging for differentiating between cavernous hemangiomas and untreated malignant hepatic neoplasms. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Characterization of breast lesion using T1-perfusion magnetic resonance imaging: Qualitative vs. quantitative analysis.

PubMed

Thakran, S; Gupta, P K; Kabra, V; Saha, I; Jain, P; Gupta, R K; Singh, A

2018-06-14

The objective of this study was to quantify the hemodynamic parameters using first pass analysis of T 1 -perfusion magnetic resonance imaging (MRI) data of human breast and to compare these parameters with the existing tracer kinetic parameters, semi-quantitative and qualitative T 1 -perfusion analysis in terms of lesion characterization. MRI of the breast was performed in 50 women (mean age, 44±11 [SD] years; range: 26-75) years with a total of 15 benign and 35 malignant breast lesions. After pre-processing, T 1 -perfusion MRI data was analyzed using qualitative approach by two radiologists (visual inspection of the kinetic curve into types I, II or III), semi-quantitative (characterization of kinetic curve types using empirical parameters), generalized-tracer-kinetic-model (tracer kinetic parameters) and first pass analysis (hemodynamic-parameters). Chi-squared test, t-test, one-way analysis-of-variance (ANOVA) using Bonferroni post-hoc test and receiver-operating-characteristic (ROC) curve were used for statistical analysis. All quantitative parameters except leakage volume (Ve), qualitative (type-I and III) and semi-quantitative curves (type-I and III) provided significant differences (P<0.05) between benign and malignant lesions. Kinetic parameters, particularly volume transfer coefficient (K trans ) provided a significant difference (P<0.05) between all grades except grade-II vs III. The hemodynamic parameter (relative-leakage-corrected-breast-blood-volume [rBBVcorr) provided a statistically significant difference (P<0.05) between all grades. It also provided highest sensitivity and specificity among all parameters in differentiation between different grades of malignant breast lesions. Quantitative parameters, particularly rBBVcorr and K trans provided similar sensitivity and specificity in differentiating benign from malignant breast lesions for this cohort. Moreover, rBBVcorr provided better differentiation between different grades of malignant breast lesions among all the parameters. Copyright © 2018. Published by Elsevier Masson SAS.

An Immunohistochemical Study on the Expression of Sex Steroid Receptors in Canine Mammary Tumors

PubMed Central

Port Louis, Leena Rajathy; Varshney, Khub Chandra; Nair, Madhavan Gopalakrishnan

2012-01-01

Steroid hormones are found to play a major role in the genesis and progression of mammary tumors. The aim of this study was to immunohistochemically detect the presence of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and progesterone receptor (PR) and also to study the association between these markers in 29 cases of benign (11) and malignant (18) canine mammary tumors. ERα immunostaining was noticed in only one case of carcinosarcoma specifically in the nuclei of epithelial and a few myoepithelial cells. ERβ immunostaining was noticed in the nuclei and cytoplasm of epithelial cells and smooth muscles lining the blood vessels. Immunoexpression of ERβ was 82% in benign tumors and 78% in malignant tumors. PR immunostaining was expressed in the nuclei of epithelial cells in both benign and malignant tumors. Among the 15 PR+ cases, 6 (55%) were of benign type, and 9 (50%) were of malignant type. The most common group of hormone receptor was the ERα−/PR+/ERβ+ (46%) in benign tumors and ERα−/PR−/ERβ+ (38%) in malignant tumors. Although there was no significant association between ERα and PR with ERβ, the findings indicated that ERβ was consistently expressed in both benign and malignant tumors, irrespective of ERα and PR status. PMID:23738123

Role of microRNA-7 in digestive system malignancy.

PubMed

Chen, Wan-Qun; Hu, Ling; Chen, Geng-Xin; Deng, Hai-Xia

2016-01-15

There are several malignancies of the digestive system (including gastric, pancreatic and colorectal cancers, and hepatocellular carcinoma), which are the most common types of cancer and a major cause of death worldwide. MicroRNA (miR)-7 is abundant in the pancreas, playing an important role in pancreatic development and endocrine function. Expression of miR-7 is downregulated in digestive system malignancies compared with normal tissue. Although there are contrasting results for miR-7 expression, almost all research reveals that miR-7 is a tumor suppressor, by targeting various genes in specific pathways. Moreover, miR-7 can target different genes simultaneously in different malignancies of the digestive system. By acting on many cytokines, miR-7 is also involved in many gastrointestinal inflammatory diseases as a significant carcinogenic factor. Consequently, miR-7 might be a biomarker or therapeutic target gene in digestive system malignancies.

Ephs and Ephrins in Cancer: Ephrin-A1 Signaling

PubMed Central

Beauchamp, Amanda; Debinski, Waldemar

2011-01-01

Ephrin-A1 and its primary receptor, EphA2, are involved in numerous physiological processes and have been intensely studied for their roles in malignancy. Ephrin-Eph signalling is complex on its own and is also cell-type dependent, making elucidation of the exact role of ephrin-A1 in neoplasia challenging. Multiple oncogenic signalling pathways, such as MAP/ERK and PI3K are affected by ephrin-A1, and in some cases evidence suggests the promotion of a specific pathway in one cell or cancer type and inhibition of the same pathway in another type of cell or cancer. EphrinA1 also plays an integral role in angiogenesis and tumor neovascularization. Until recently, studies investigating ephrins focused on the ligands as GPI-anchored proteins that required membrane anchoring or artificial clustering for Eph receptor activation. However, recent studies have demonstrated a functional role for soluble, monomeric ephrin-A1. This review will focus on various forms of ephrin-A1-specific signalling in human malignancy. PMID:22040911

Are blood group isoantigens lost from malignant prostatic epithelium? Immunohistochemical support for the preservation of the H isoantigen.

PubMed Central

Vowden, P.; Lowe, A. D.; Lennox, E. S.; Bleehen, N. M.

1986-01-01

Previous studies while demonstrating the presence of blood group isoantigens on normal prostatic epithelium have failed to identify such antigens on malignant prostatic tissue. Using a series of blood group specific monoclonal antibodies directed towards the A, B, H and Y antigens we have reinvestigated blood group isoantigen expression in both benign prostatic hypertrophy and prostatic adenocarcinoma. Results obtained from areas of benign prostatic hypertrophy are in broad agreement with those published however though we were unable to detect either A or B blood group isoantigens Type 2H and Y isoantigens were identified in 10 of the 12 tumours. These findings, while differing from previously reported results, lend support to the suggested connection between ontogenesis, oncogenesis and blood group isoantigen expression and also support the proposed link between Type 2 structures and malignant transformation. Images Figure 1 Figure 2 PMID:2421753

High-Grade Urothelial Carcinoma on Urine Cytology Resembling Umbrella Cells.

PubMed

Renshaw, Andrew A; Gould, Edwin W

2018-01-01

High-grade urothelial carcinoma (UC) cells have many appearances on urine cytology, but according to The Paris System, they can be easily distinguished from umbrella cells. We aimed to define the incidence and appearance of high-grade UC cells that resemble umbrella cells in Cytospin preparations on urine cytology. Cytospin preparations from 331 cases with biopsy follow-up (230 benign/low-grade and 101 malignant [22 carcinoma in situ, 52 papillary, 19 invasive UC, 8 other] cases) were reviewed. A total of 18 cases with malignant cells resembling umbrella cells were identified (17.8% of the malignant cases) and were the only type of malignant cell in 3% of the cases. Two patterns were identified. Tumor cells were either identifiable by at least 20 abnormal cells which were large, had abundant cytoplasm but an elevated nuclear-to-cytoplasmic ratio, and markedly enlarged, round-to-elongated nucleoli, or else rare cells with abundant cytoplasm but obviously malignant nuclei. Cells without nucleoli or obviously malignant nuclei were not specific. Malignant cells resembling umbrella cells can be seen in up to 17% of urine cytology specimens. © 2017 S. Karger AG, Basel.

Activated Dual Specificity Lymphocytes and Their Methods of Use | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of using genetic modifications to generate leukocytes with multiple specificities. This technology represents a potential therapy for a wide variety of malignancies, and because of the genetic modification used, this therapy will be applicable to patients of any MHC type.

Invadopodia formation in blood clots: Not so SLUGgish after all.

PubMed

Knowles, Lynn M; Maranchie, Jodi K; Pilch, Jan

2014-01-01

Blood clotting specifically supports the metastatic dissemination of malignant cells to the lung. We have recently demonstrated that 2 tumor types that are prone to form lung metastases, renal cell carcinoma and soft tissue sarcoma, share specific adhesive mechanisms that support the invasion and colonization of blood clots in the pulmonary vasculature.

Biophotonic markers of malignancy: Discriminating cancers using wavelength-specific biophotons.

PubMed

Murugan, Nirosha J; Rouleau, Nicolas; Karbowski, Lukasz M; Persinger, Michael A

2018-03-01

Early detection is a critically important factor when successfully diagnosing and treating cancer. Whereas contemporary molecular techniques are capable of identifying biomarkers associated with cancer, surgical interventions are required to biopsy tissue. The common imaging alternative, positron-emission tomography (PET), involves the use of nuclear material which poses some risks. Novel, non-invasive techniques to assess the degree to which tissues express malignant properties are now needed. Recent developments in biophoton research have made it possible to discriminate cancerous cells from normal cells both in vitro and in vivo. The current study expands upon a growing body of literature where we classified and characterized malignant and non-malignant cell types according to their biophotonic activity. Using wavelength-exclusion filters, we demonstrate that ratios between infrared and ultraviolet photon emissions differentiate cancer and non-cancer cell types. Further, we identified photon sources associated with three filters (420-nm, 620-nm., and 950-nm) which classified cancer and non-cancer cell types. The temporal increases in biophoton emission within these wavelength bandwidths is shown to be coupled with intrisitic biomolecular events using Cosic's resonant recognition model. Together, the findings suggest that the use of wavelength-exclusion filters in biophotonic measurement can be employed to detect cancer in vitro.

HPASubC: A suite of tools for user subclassification of human protein atlas tissue images.

PubMed

Cornish, Toby C; Chakravarti, Aravinda; Kapoor, Ashish; Halushka, Marc K

2015-01-01

The human protein atlas (HPA) is a powerful proteomic tool for visualizing the distribution of protein expression across most human tissues and many common malignancies. The HPA includes immunohistochemically-stained images from tissue microarrays (TMAs) that cover 48 tissue types and 20 common malignancies. The TMA data are used to provide expression information at the tissue, cellular, and occasionally, subcellular level. The HPA also provides subcellular data from confocal immunofluorescence data on three cell lines. Despite the availability of localization data, many unique patterns of cellular and subcellular expression are not documented. To get at this more granular data, we have developed a suite of Python scripts, HPASubC, to aid in subcellular, and cell-type specific classification of HPA images. This method allows the user to download and optimize specific HPA TMA images for review. Then, using a playstation-style video game controller, a trained observer can rapidly step through 10's of 1000's of images to identify patterns of interest. We have successfully used this method to identify 703 endothelial cell (EC) and/or smooth muscle cell (SMCs) specific proteins discovered within 49,200 heart TMA images. This list will assist us in subdividing cardiac gene or protein array data into expression by one of the predominant cell types of the myocardium: Myocytes, SMCs or ECs. The opportunity to further characterize unique staining patterns across a range of human tissues and malignancies will accelerate our understanding of disease processes and point to novel markers for tissue evaluation in surgical pathology.

HPASubC: A suite of tools for user subclassification of human protein atlas tissue images

PubMed Central

Cornish, Toby C.; Chakravarti, Aravinda; Kapoor, Ashish; Halushka, Marc K.

2015-01-01

Background: The human protein atlas (HPA) is a powerful proteomic tool for visualizing the distribution of protein expression across most human tissues and many common malignancies. The HPA includes immunohistochemically-stained images from tissue microarrays (TMAs) that cover 48 tissue types and 20 common malignancies. The TMA data are used to provide expression information at the tissue, cellular, and occasionally, subcellular level. The HPA also provides subcellular data from confocal immunofluorescence data on three cell lines. Despite the availability of localization data, many unique patterns of cellular and subcellular expression are not documented. Materials and Methods: To get at this more granular data, we have developed a suite of Python scripts, HPASubC, to aid in subcellular, and cell-type specific classification of HPA images. This method allows the user to download and optimize specific HPA TMA images for review. Then, using a playstation-style video game controller, a trained observer can rapidly step through 10's of 1000's of images to identify patterns of interest. Results: We have successfully used this method to identify 703 endothelial cell (EC) and/or smooth muscle cell (SMCs) specific proteins discovered within 49,200 heart TMA images. This list will assist us in subdividing cardiac gene or protein array data into expression by one of the predominant cell types of the myocardium: Myocytes, SMCs or ECs. Conclusions: The opportunity to further characterize unique staining patterns across a range of human tissues and malignancies will accelerate our understanding of disease processes and point to novel markers for tissue evaluation in surgical pathology. PMID:26167380

Specific Immunotherapy in Hymenoptera Venom Allergy and Concomitant Malignancy: A Retrospective Follow-up Focusing on Effectiveness and Safety.

PubMed

Aeberhard, J; Haeberli, G; Müller, U R; Helbling, A

2017-01-01

Malignancies are often considered a contraindication for allergen-specific immunotherapy. Consequently, patients with severe Hymenoptera venom allergy and cancer require specific care. The aim of this retrospective study was to assess patients with Hymenoptera venom allergy and cancer undergoing venom immunotherapy (VIT). The study population comprised all patients referred for evaluation of Hymenoptera venom allergy or for a routine check-up during VIT from January 1, 2004 to December 31, 2008. Of the patients assessed, 2% (51 of 2594) had a documented Hymenoptera venom allergy and cancer (25 female, 26 male; mean age 58 years). Of these, 42 patients received VIT (82%): 25 patients had a previously diagnosed malignancy, 16 were diagnosed with malignancy during VIT, and 1 patient was diagnosed with cancer after completion of VIT. The most frequent type of tumor was breast cancer in female patients (60%) and prostate cancer in male patients (39%). Systemic allergic reactions during VIT were recorded in 7% of patients. A total of 19 patients experienced a field sting or underwent a sting challenge test during VIT: 95% tolerated the sting well. VIT was halted definitively in 9 patients (new diagnosis of cancer in 7 patients, reactivation of cancer in 1, and progressive polyneuropathy in 1). The effectiveness and adverse effects of VIT in patients with Hymenoptera venom allergy and cancer in remission are comparable to those of patients without malignancy. Our findings show that patients with Hymenoptera venom allergy and cancer are eligible for VIT.

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.

PubMed

2017-11-02

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Frozen section pathology for decision making in parotid surgery.

PubMed

Olsen, Kerry D; Moore, Eric J; Lewis, Jean E

2013-12-01

For parotid lesions, the high accuracy and utility of intraoperative frozen section (FS) pathology, compared with permanent section pathology, facilitates intraoperative decision making about the extent of surgery required. To demonstrate the accuracy and utility of FS pathology of parotid lesions as one factor in intraoperative decision making. Retrospective review of patients undergoing parotidectomy at a tertiary care center. Evaluation of the accuracy of FS pathology for parotid surgery by comparing FS pathology results with those of permanent section. Documented changes from FS to permanent section in 1339 parotidectomy pathology reports conducted from January 1, 2000, through December 31, 2009, included 693 benign and 268 primary and metastatic malignant tumors. Changes in diagnosis were found from benign to malignant (n = 11) and malignant to benign (n = 2). Sensitivity and specificity of a malignant diagnosis were 98.5% and 99.0%, respectively. Other changes were for lymphoma vs inflammation or lymphoma typing (n = 89) and for confirmation of or change in tumor type for benign (n = 36) or malignant (n = 69) tumors. No case changed from low- to high-grade malignant tumor. Only 4 cases that changed from FS to permanent section would have affected intraoperative decision making. Three patients underwent additional surgery 2 to 3 weeks later. Overall, only 1 patient was overtreated (lymphoma initially deemed carcinoma). Frozen section pathology for parotid lesions has high accuracy and utility in intraoperative decision making, facilitating timely complete procedures.

The role of CCN family genes in haematological malignancies.

PubMed

Wells, J E; Howlett, M; Cheung, L C; Kees, Ursula R

2015-09-01

Haematological malignancies, although a broad range of specific disease types, continue to show considerable overlap in classification, and patients are treated using similar chemotherapy regimes. In this review we look at the role of the CCN family of matricellular proteins and indicate their role in nine haematological malignancies including both myeloid and lymphoid neoplasms. The potential for further haematological neoplasms with CCN family associations is argued by summarising the demonstrated role of CCN family genes in the differentiation of haematopoietic stem cells (HSC) and mesenchymal stem cells. The expanding field of knowledge encompassing CCN family genes and cancers of the HSC-lineage highlights the importance of extracellular matrix-interactions in both normal physiology and tumorigenesis of the blood, bone marrow and lymph nodes.

Novel Breast Imaging and Machine Learning: Predicting Breast Lesion Malignancy at Cone-Beam CT Using Machine Learning Techniques.

PubMed

Uhlig, Johannes; Uhlig, Annemarie; Kunze, Meike; Beissbarth, Tim; Fischer, Uwe; Lotz, Joachim; Wienbeck, Susanne

2018-05-24

The purpose of this study is to evaluate the diagnostic performance of machine learning techniques for malignancy prediction at breast cone-beam CT (CBCT) and to compare them to human readers. Five machine learning techniques, including random forests, back propagation neural networks (BPN), extreme learning machines, support vector machines, and K-nearest neighbors, were used to train diagnostic models on a clinical breast CBCT dataset with internal validation by repeated 10-fold cross-validation. Two independent blinded human readers with profound experience in breast imaging and breast CBCT analyzed the same CBCT dataset. Diagnostic performance was compared using AUC, sensitivity, and specificity. The clinical dataset comprised 35 patients (American College of Radiology density type C and D breasts) with 81 suspicious breast lesions examined with contrast-enhanced breast CBCT. Forty-five lesions were histopathologically proven to be malignant. Among the machine learning techniques, BPNs provided the best diagnostic performance, with AUC of 0.91, sensitivity of 0.85, and specificity of 0.82. The diagnostic performance of the human readers was AUC of 0.84, sensitivity of 0.89, and specificity of 0.72 for reader 1 and AUC of 0.72, sensitivity of 0.71, and specificity of 0.67 for reader 2. AUC was significantly higher for BPN when compared with both reader 1 (p = 0.01) and reader 2 (p < 0.001). Machine learning techniques provide a high and robust diagnostic performance in the prediction of malignancy in breast lesions identified at CBCT. BPNs showed the best diagnostic performance, surpassing human readers in terms of AUC and specificity.

Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era.

PubMed

Gunnarsson, Niklas; Stenke, Leif; Höglund, Martin; Sandin, Fredrik; Björkholm, Magnus; Dreimane, Arta; Lambe, Mats; Markevärn, Berit; Olsson-Strömberg, Ulla; Richter, Johan; Wadenvik, Hans; Wallvik, Jonas; Själander, Anders

2015-06-01

Given that tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with chronic myeloid leukaemia (CML), we were interested in examining the possible risk of long-term adverse events, such as the emergence of other neoplasms. Therefore, we studied the development of second malignancies in 868 patients diagnosed with CML between 2002 and 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. With a median follow-up of 3·7 (range 0-9·9) years, 65 (7·5%) patients developed 75 second malignancies (non-haematological), 52 of which were of the invasive type. Compared to expected rates in the background population, the risk of second malignancies was higher in the CML cohort, with a standardized incidence ratio (SIR) of 1·52 (95% CI 1·13-1·99). The SIR before and after the second year following diagnosis of CML was 1·58 and 1·47, respectively. Among specific cancer types, gastrointestinal and nose and throat cancer were significantly increased. Founded on a population-based material, our results indicate that CML patients treated in the TKI era are at an increased risk of developing a second malignancy, with indications that this risk may more likely be linked to CML itself rather than to the TKI treatment. © 2015 John Wiley & Sons Ltd.

Malignant Mesothelioma—Health Professional Version

Cancer.gov

Epithelial mesothelioma is the most common type of malignant mesothelioma, which forms in the cells that line organs. The other types begin in spindle-shaped cells called sarcomatoid cells or are a mixture of both cell types. Find evidence-based information on malignant mesothelioma treatment.

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

PubMed

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P < .05); it yielded a high capability for differential diagnosis of atypical subacute thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

PubMed Central

Garg, Abhishek D.; De Ruysscher, Dirk; Agostinis, Patrizia

2016-01-01

ABSTRACT The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale meta-analysis involving 3,983 patients (‘discovery’ dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in ‘validation’ datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICD-derived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) ‘attracted’ highly co-expressing sets of genes or convergent-metagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an ‘attractor’ for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a platform for discovery of novel prognostic metagenes. PMID:27057433

Patients' Characteristics, Histopathological Findings, and Tumor Stage in Different Types of Malignant Melanoma: A Retrospective Multicenter Study.

PubMed

Farahmand, Ali-Mohammad; Ehsani, Amir-Hoshang; Mirzaei, Mojtaba; Mohsenian, Maryam; Ghanadan, Alireza

2017-05-01

Cutaneous malignant melanoma (CMM) is currently the most fatal of skin cancers accounting for 50000 deaths annually. Five distinct melanomas are described histopathologically: superficial spreading, lentigo maligna, nodular, acral lentiginous and mucosal melanoma. The aim of this study was to investigate the characteristics of patients with various types of malignant melanoma and evaluate histopathological findings. In this retrospective study, we obtained our data from the records of 111 patients with melanoma. Biopsied specimens were collected and re-evaluated. Demographic information and histopathological findings were noted. SPSS 16 was used for analyzing data. Chi-square and one-way ANOVA was conducted for comparing categorical and numerical variables respectively. The mean age of patients was 59.33±14.68 years old. Most common melanoma type was acral lentiginous (40.5%), followed by nodular (35.1%) and mucosal (10.8%). The highest tumor thickness was viewed in nodular melanoma followed by mucosal melanoma. The highest rate of metastasis, microsatellitosis, perineural invasion and Clark level of the invasion were reported in nodular and acral lentiginous respectively. The most frequent rate of ulceration and vascular invasion was reported in mucosal melanoma. Distribution of melanoma types varies largely in different regions. Lack of classic presentations in some types necessitate specific public education about warning signs. Histopathological and pathological characteristics in melanoma can aid in better staging and management of the tumor.

Characteristics of Sarcoidosis in Patients with Previous Malignancy: Causality or Coincidence?

PubMed

Arish, Nissim; Kuint, Rottem; Sapir, Eli; Levy, Liran; Abutbul, Avraham; Fridlender, Zvi; Laxer, Uri; Berkman, Neville

2017-01-01

The association between sarcoidosis and malignancy is poorly defined. Sarcoidosis can precede, be diagnosed concurrently with, or follow malignancy. We describe the clinical and radiological features of patients with sarcoidosis following malignancy to determine whether this association is causal or coincidental. We performed a search for all patients with confirmed sarcoidosis following malignancy in our institution during 2001-2015. Clinical and radiological features, bronchoscopic findings, bronchoalveolar lavage cell counts, and pulmonary function tests (PFTs) were reviewed to evaluate patterns of disease involvement. Details of the histological type of cancer, staging, treatment, and follow-up were reviewed. Twenty-nine patients were identified. The most prevalent malignancies were breast cancer and lymphoma (24% each). Based on the incidence of these malignancies, we estimated the incidence of sarcoidosis was 175 times higher after lymphoma and 38 times higher after breast cancer as compared to the general population. Most patients had early stage cancer (stage I, II) (75%), and only 2 patients (7%) had recurrence of their malignancy after diagnosis of sarcoidosis. Sarcoidosis was diagnosed within 5 years of malignancy in over half the patients, 76% were asymptomatic and 69% had normal PFTs. Mediastinal lymphadenopathy was present in 81% of cases, hilar lymphadenopathy in 67%, and pulmonary parenchymal involvement in 41%. Fifty percent of patients had received Adriamycin, 38% cyclophosphamide, and 33% vincristine. Sarcoidosis following malignancy is indistinguishable from "idiopathic" sarcoidosis, although it is frequently asymptomatic. The high frequency of sarcoidosis after specific cancers but not others, suggests a causative association between malignancy and development of sarcoidosis. © 2017 S. Karger AG, Basel.

Role of apparent diffusion coefficients with diffusion-weighted magnetic resonance imaging in differentiating between benign and malignant bone tumors.

PubMed

Wang, Tingting; Wu, Xiangru; Cui, Yanfen; Chu, Caiting; Ren, Gang; Li, Wenhua

2014-11-29

Benign and malignant bone tumors can present similar imaging features. This study aims to evaluate the significance of apparent diffusion coefficients (ADC) in differentiating between benign and malignant bone tumors. A total of 187 patients with 198 bone masses underwent diffusion-weighted (DW) magnetic resonance (MR) imaging. The ADC values in the solid components of the bone masses were assessed. Statistical differences between the mean ADC values in the different tumor types were determined by Student's t-test. Histological analysis showed that 84/198 (42.4%) of the bone masses were benign and 114/198 (57.6%) were malignant. There was a significant difference between the mean ADC values in the benign and malignant bone lesions (P<0.05). However, no significant difference was found in the mean ADC value between non-ossifying fibromas, osteofibrous dysplasia, and malignant bone tumors. When an ADC cutoff value≥1.10×10(-3) mm2/s was applied, malignant bone lesions were excluded with a sensitivity of 89.7%, a specificity of 84.5%, a positive predictive value of 82.6%, and a negative predictive value of 95.3%. The combination of DW imaging with ADC quantification and T2-weighted signal characteristics of the solid components in lesions can facilitate differentiation between benign and malignant bone tumors.

Is There a True Concern Regarding the Use of Hair Dye and Malignancy Development?

PubMed Central

Saitta, Peter; Cook, Christopher E.; Messina, Jane L.; Brancaccio, Ronald; Wu, Benedict C.; Grekin, Steven K.; Holland, Jean

2013-01-01

Many advances in the cosmetic industry have increased our ability to enhance youth and beauty. Hair-coloring products are one such innovation. Over the past several decades, a significant amount of work has been dedicated to understanding the possible long-term side effects associated with hair-dye use, specifically looking at cancer risk. This paper describes the hair-coloring process, highlights the potentially carcinogenic ingredients in various hair-dying products, and reviews the epidemiological evidence relating personal hair-dye use to the risk of developing several types of malignancies. PMID:23320124

Immunotherapy in Gynecologic Cancers: Are We There Yet?

PubMed

Pakish, Janelle B; Jazaeri, Amir A

2017-08-24

Immune-targeted therapies have demonstrated durable responses in many tumor types with limited treatment options and poor overall prognosis. This has led to enthusiasm for expanding such therapies to other tumor types including gynecologic malignancies. The use of immunotherapy in gynecologic malignancies is in the early stages and is an active area of ongoing clinical research. Both cancer vaccines and immune checkpoint inhibitor therapy continue to be extensively studied in gynecologic malignancies. Immune checkpoint inhibitors, in particular, hold promising potential in specific subsets of endometrial cancer that express microsatellite instability. The key to successful treatment with immunotherapy involves identification of the subgroup of patients that will derive benefit. The number of ongoing trials in cervical, ovarian, and endometrial cancer will help to recognize these patients and make treatment more directed. Additionally, a number of studies are combining immunotherapy with standard treatment options and will help to determine combinations that will enhance responses to standard therapy. Overall, there is much enthusiasm for immunotherapy approaches in gynecologic malignancies. However, the emerging data shows that with the exception of microsatellite unstable tumors, the use of single-agent immune checkpoint inhibitors is associated with response rates of 10-15%. More effective and likely combinatorial approaches are needed and will be informed by the findings of ongoing trials.

The value of energy spectral CT in the differential diagnosis between benign and malignant soft tissue masses of the musculoskeletal system.

PubMed

Sun, Xin; Shao, Xiaodong; Chen, Haisong

2015-06-01

To explore the value of energy spectral CT in the differential diagnosis between benign and malignant tumor of the musculoskeletal system. Energy spectral CT scan was performed on 100 patients with soft tissue mass caused by musculoskeletal tumors found by MRI. Solid areas with homogenous density were chosen as region of interests (ROI), avoiding necrosis, hemorrhage and calcification region. Select the optimal keV on single energy images, and then the keV-CT curve was automatically generated. All 100 cases of tumors proved by histological examination were divided into four groups, 38 cases were in benign group, 10 cases in borderline group, 49 cases in malignant group, and 3 cases of lipoma (that were analyzed separately since its curve was arc shaped, significantly different from other curves). The formula used to calculate the slope of spectral curve was as follows: slope=(Hu40 keV-Hu80 keV)/40. As the slope was steep within the range of 40-80 keV based on preliminary observations, 40 keV and 80 keV were used as the reference points to calculate the slope value of the energy spectral curve. Kruskal-Wallis rank sum test was applied for statistical analysis, and P<0.05 was considered to indicate a statistically significant difference. The spectral curve of benign group was gradually falling type with a mean slope of 0.75 ± 0.30, that of malignant group was sharply falling type with a mean slope of 1.64 ± 1.00, and that of borderline group was a falling type between the above two groups with a mean slope of 1.34 ± 0.45. The differences of slopes between benign and malignant group, benign and borderline group were of statistical significance (P<0.05) respectively. The spectral curves of 3 cases of lipoma showed arc shaped rising type with a mean slope of -2.00. Spectral curve is useful in the differential diagnosis of benign and malignant tumor of the musculoskeletal system. Arc shaped curve is a specific sign for tumors containing abundant fat. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Tribbles in normal and malignant haematopoiesis.

PubMed

Stein, Sarah J; Mack, Ethan A; Rome, Kelly S; Pear, Warren S

2015-10-01

The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types. © 2015 Authors; published by Portland Press Limited.

Unusual Long Survival with a Giant Invasive Pheochromocytoma of an Incompatible Patient.

PubMed

Nar, Asli

2018-03-13

Pheochromocytomas (PHEOs) are rare neuroendocrine tumors and about 2-13% of PHEOs are malignant. Predicting malignancy in PHEO cases with invasion but without metastasis is still controversial in the literature. This study presents an unusual long survival with a giant invasive PHEO in an incompatible patient and a review of the literature. In 1989, a 23-year-old female patient was operated for a giant adrenal mass with a pathological final diagnosis of PHEO. Information to the patient's family was provided about the short life span of the patient in the postoperative period because the tumor could not be totally resected. The patient started using regular antihypertensive drugs only after 1994. In 1994, 3700 mBq 131-I-metaiodobenzylguanidine (MIBG) treatment was given. Since then, no specific treatment was administered for PHEO due to patient incompatibility. She was diagnosed with type 2 diabetes mellitus at the age of 40 years and had a cerebrovascular accident due to hypertension at the age of 42. New abdominal computed tomography (CT) showed a right-sided 75 x 37 mm irregular and heterogeneous mass lesion extending inferiorly from the diaphragmatic crus level located in the right adrenal locus compatible with local recurrence. There was no I-123-MIBG uptake. She refused to have advanced workup and further treatment options. Malignant PHEOs reduce overall survival as a consequence of excessive catecholamine release, large tumor burden, and malignancy-related complications. Currently, the treatment of a malignant PHEO still has difficulties for both patients and doctors. Main treatment options for malignant PHEOs are primarily surgical excision. The effect of radionuclide therapy on survival time still remains to be determined. Efforts should be made to identify clinical, biochemical, and pathological criteria for malignancy and to develop new therapies in these patients with malignancy. The clinical course of malignant PHEOs is remarkably variable. Disease-specific survival rate changes from 58 to 88.1% at five years in the literature. Recent discoveries have enhanced new options for treatment, from radionuclide therapy and targeted molecular therapy to immunotherapy. A multidisciplinary approach is needed to individualize treatment in patients with malignant and invasive PHEO.

An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain–Containing 7A–Specific Antibodies in Membranous Nephropathy

PubMed Central

Hoxha, Elion; Beck, Laurence H.; Wiech, Thorsten; Tomas, Nicola M.; Probst, Christian; Mindorf, Swantje; Meyer-Schwesinger, Catherine; Zahner, Gunther; Stahl, Phillip R.; Schöpper, Ruth; Panzer, Ulf; Harendza, Sigrid; Helmchen, Udo; Salant, David J.

2017-01-01

Thrombospondin type 1 domain–containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A2 receptor 1 (PLA2R1). The prevalence of THSD7A-Ab–positive patients is unknown, and it is unclear whether the clinical presentation differs between patients positive for PLA2R1-Ab or THSD7A-Ab. We screened serum samples of 1276 patients with MN from three different cohorts for the presence of THSD7A-Ab by Western blot analysis and a newly developed indirect immunofluorescence test (IFT). Compared with Western blot analysis, the IFT had a 92% sensitivity and a 100% specificity. The prevalence of THSD7A-associated MN in a prospective cohort of 345 patients with MN was 2.6%, and most were women. In this cohort, the percentage of patients with THSD7A-associated MN and malignant disease significantly exceeded that of patients with PLA2R1-associated MN and malignant disease. In all cohorts, we identified 40 patients with THSD7A-associated MN, eight of whom developed a malignancy within a median time of 3 months from diagnosis of MN. In one patient with THSD7A-associated MN and metastases of an endometrial carcinoma, immunohistochemistry showed THSD7A expression on the metastatic cells and within follicular dendritic cells of the metastasis–infiltrated lymph node. We conclude that the IFT allows sensitive and specific measurement of circulating THSD7A-Ab in patients with MN. Patients with THSD7A-associated MN differ in their clinical characteristics from patients with PLA2R1-associated MN, and more intensive screening for the presence of malignancies may be warranted in those with THSD7A-associated MN. PMID:27436855

Branchial arch anomalies: Recurrence, malignant degeneration and operative complications.

PubMed

Al-Mufarrej, Faisal; Stoddard, David; Bite, Uldis

2017-06-01

Branchial arch anomalies (BAA) represent one of the commonest pediatric neck masses, but large case series are lacking with none specifically examining risk of recurrence, surgical complications, and malignancy. Retrospective study of patients with BAA at Mayo Clinic from 1/1/1976-7/29/2011. Features studied include age, gender, location, BAA type, symptoms, recurrence, preoperative management, extent of surgery, pathology as well as presence of tracts. Associations with tracts, operative complications, and recurrence were evaluated. 421 subjects underwent BAA excision during the study period at our institution. Subjects with tracts were symptomatic earlier. Four cases (mean age 60.3 years) of malignancy were identified. Among the 358 (non-remenant) BAA patients with no previous excision, 3.6% recurred at a mean of 47.1 months following surgery. Patients who underwent incision and drainage prior to BAA excision were 3.4 times more likely to recur. 2% experienced complications. Age, BAA type, preoperative imaging and extent of surgery did not affect recurrence or complication rates. Patients with history of preoperative incision and drainage should be followed closely for recurrence the first four years. Early BAA excision is not associated with higher complication rate. Extent of resection should be determined by gross margins of BAA. Malignant degeneration was not seen in children. Malignancies have been seen in older patients (over 45 years) diagnosed with BAA, and a thorough work-up is important for correct diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Endometriosis, in vitro fertilisation and the risk of gynaecological malignancies, including ovarian and breast cancer.

PubMed

Vlahos, Nikos F; Economopoulos, Konstantinos P; Fotiou, Stylianos

2010-02-01

There is evidence that endometriosis as well as drugs used in the process of in vitro fertilisation appear to associate with increased risk for gynaecological cancer. In this review, we attempt to describe this relationship according to the most recent epidemiologic data and to present the possible mechanisms on the molecular level that could potentially explain this correlation. There are data to support that ovarian endometriosis could have the potential for malignant transformation. Epidemiologic and genetic studies support this notion. It seems that endometriosis is associated with specific types of ovarian cancer (endometrioid and clear cell). There is no clear association between endometriosis and breast or endometrial cancer. More studies are needed to establish the risk factors that may lead to malignant transformation of this condition and to identify predisposed individuals who may require closer surveillance. Currently, there is no proven relationship between any type of gynaecological cancer and drugs used for infertility treatment. In principle, infertile women have increased risk for gynaecologic malignancies. Nulligravidas who received treatment are at increased risk for malignancy compared with women who had conceived after treatment. There is limited evidence that clomiphene citrate use for more than six cycles or 900mg or treatment of women over the age of 40 could increase their risk for ovarian and breast cancer. More studies with the appropriate statistical power and follow-up time are required to evaluate accurately the long-term effects of these drugs and procedures.

Time to enhancement derived from ultrafast breast MRI as a novel parameter to discriminate benign from malignant breast lesions.

PubMed

Mus, Roel D; Borelli, Cristina; Bult, Peter; Weiland, Elisabeth; Karssemeijer, Nico; Barentsz, Jelle O; Gubern-Mérida, Albert; Platel, Bram; Mann, Ritse M

2017-04-01

To investigate time to enhancement (TTE) as novel dynamic parameter for lesion classification in breast magnetic resonance imaging (MRI). In this retrospective study, 157 women with 195 enhancing abnormalities (99 malignant and 96 benign) were included. All patients underwent a bi-temporal MRI protocol that included ultrafast time-resolved angiography with stochastic trajectory (TWIST) acquisitions (1.0×0.9×2.5mm, temporal resolution 4.32s), during the inflow of contrast agent. TTE derived from TWIST series and relative enhancement versus time curve type derived from volumetric interpolated breath-hold examination (VIBE) series were assessed and combined with basic morphological information to differentiate benign from malignant lesions. Receiver operating characteristic analysis and kappa statistics were applied. TTE had a significantly better discriminative ability than curve type (p<0.001 and p=0.026 for reader 1 and 2, respectively). Including morphology, sensitivity of TWIST and VIBE assessment was equivalent (p=0.549 and p=0.344, respectively). Specificity and diagnostic accuracy were significantly higher for TWIST than for VIBE assessment (p<0.001). Inter-reader agreement in differentiating malignant from benign lesions was almost perfect for TWIST evaluation (κ=0.86) and substantial for conventional assessment (κ=0.75). TTE derived from ultrafast TWIST acquisitions is a valuable parameter that allows robust differentiation between malignant and benign breast lesions with high accuracy. Copyright © 2017 Elsevier B.V. All rights reserved.

Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.

PubMed

Zhang, Allen W; McPherson, Andrew; Milne, Katy; Kroeger, David R; Hamilton, Phineas T; Miranda, Alex; Funnell, Tyler; Little, Nicole; de Souza, Camila P E; Laan, Sonya; LeDoux, Stacey; Cochrane, Dawn R; Lim, Jamie L P; Yang, Winnie; Roth, Andrew; Smith, Maia A; Ho, Julie; Tse, Kane; Zeng, Thomas; Shlafman, Inna; Mayo, Michael R; Moore, Richard; Failmezger, Henrik; Heindl, Andreas; Wang, Yi Kan; Bashashati, Ali; Grewal, Diljot S; Brown, Scott D; Lai, Daniel; Wan, Adrian N C; Nielsen, Cydney B; Huebner, Curtis; Tessier-Cloutier, Basile; Anglesio, Michael S; Bouchard-Côté, Alexandre; Yuan, Yinyin; Wasserman, Wyeth W; Gilks, C Blake; Karnezis, Anthony N; Aparicio, Samuel; McAlpine, Jessica N; Huntsman, David G; Holt, Robert A; Nelson, Brad H; Shah, Sohrab P

2018-05-07

High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity. Epithelial CD8+ TILs negatively associated with malignant diversity, reflecting immunological pruning of tumor clones inferred by neoantigen depletion, HLA I loss of heterozygosity, and spatial tracking between T cell and tumor clones. In addition, combinatorial prognostic effects of mutational processes and immune properties were observed, illuminating how specific genomic aberration types associate with immune response and impact survival. We conclude that within-patient spatial immune microenvironment variation shapes intraperitoneal malignant spread, provoking new evolutionary perspectives on HGSC clonal dispersion. Copyright © 2018 Elsevier Inc. All rights reserved.

Studying the MicroRNA role as a survival predictor and revealing its part in malignancy level determination in patients with supratentorial gliomas of brain

NASA Astrophysics Data System (ADS)

Stupak, E. V.; Veryaskina, Yu. A.; Titov, S. E.; Achmerova, L. G.; Stupak, V. V.; Dolzhenko, D. A.; Rabinovich, S. S.; Narodov, A. A.; Ivanov, M. K.; Zhimulev, I. F.; Kolesnikov, N. N.

2017-09-01

The numerous data show, that microRNA (miRNA) are direct participants of carcinogenesis. Also miRNA plays the role of a diagnostic and prognostic marker for different types of cancer, including gliomas. The aim of this research is to make the comparative analysis of 10 micro RNA (miR-124, -125b, -16, -181b, -191, -21, -221, -223, -31 and -451) expression profiles. The analysis was made for gliomas with different malignancy degree, then compared with the samples of the adjacent not changed tissues (n = 90). During the study the specific profiles of miRNA expression for various histotypes of tumors were revealed. It was determined, that miRNA acts as a predictor of patient survival in the cases with malignant supratentorial brain tumors. The diagnostic approaches based on miRNA expression profile were designed. It will help to determine the malignancy level and to predict the course of the disease.

Secretion of intelectin-1 from malignant pleural mesothelioma into pleural effusion.

PubMed

Tsuji, S; Tsuura, Y; Morohoshi, T; Shinohara, T; Oshita, F; Yamada, K; Kameda, Y; Ohtsu, T; Nakamura, Y; Miyagi, Y

2010-08-10

Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion. In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients. These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM.

mHealth App for Risk Assessment of Pigmented and Nonpigmented Skin Lesions-A Study on Sensitivity and Specificity in Detecting Malignancy.

PubMed

Thissen, Monique; Udrea, Andreea; Hacking, Michelle; von Braunmuehl, Tanja; Ruzicka, Thomas

2017-12-01

With the advent of smartphone devices, an increasing number of mHealth applications that target melanoma identification have been developed, but none addresses the general context of melanoma and nonmelanoma skin cancer identification. In this study a smartphone application using fractal and classical image analysis for the risk assessment of skin lesions is systematically evaluated to determine its sensitivity and specificity in the diagnosis of melanoma and nonmelanoma skin cancer along with actinic keratosis and Bowen's disease. In the Department of Dermatology, Catharina Hospital Eindhoven, The Netherlands, 341 melanocytic and nonmelanocytic lesions were imaged using SkinVision app; 239 underwent histopathological examination, while the rest of 102 lesions were clinically diagnosed as clearly benign and not removed. The algorithm has been calibrated using the images of the first 233 lesions. The calibrated version of the algorithm was used in a subset of 108 lesions, and the obtained results were compared with the medical findings. On the 108 cases used for evaluation the algorithm scored 80% sensitivity and 78% specificity in detecting (pre)malignant conditions. Although less accurate than the dermatologist's clinical eye, the app may offer support to other professionals who are less familiar with differentiating between benign and malignant lesions. An mHealth application for the risk assessment of skin lesions was evaluated. It adds value to diagnosis tools of its type by taking into consideration pigmented and nonpigmented lesions all together and detecting signs of malignancy with high sensitivity.

The epidemiology of neonatal tumours. Report of an international working group.

PubMed

Moore, S W; Satgé, D; Sasco, A J; Zimmermann, A; Plaschkes, J

2003-09-01

Neonatal tumours occur every 12,500-27,500 live births and comprise 2% of childhood malignancies, but there is little clarity as to their real prevalence, sites of origin and pathological nature as reported series vary. As an entity, neonatal tumours provide a unique window of opportunity to study tumours in which minimal environmental interference has occurred. The majority of tumours present with a mass at birth (e.g., teratomas, neuroblastomas, mesoblastic nephroma, fibromatosis), which are not infrequently identified on antenatal ultrasound. Histologically, teratoma and neuroblastoma remain the two main tumour types encountered with soft tissue sarcoma, renal tumours, CNS tumours and leukaemia being the next most common tumour types identified. Malignant tumours are uncommon in the neonatal period per se and benign tumours may have malignant potential. A particular problem exists in clinical classification, as histological features of malignancy do not always correlate with clinical behaviour. Benign tumours may also be life threatening because of their size and location. Other tumours may demonstrate local invasiveness, but no metastatic potential, and tumours that are clearly malignant may demonstrate unpredictable or uncertain behaviour. Screening programmes have brought more tumours to light, but do not appear to affect the overall prognosis. They may provide clues to the stage at which tumours develop in foetu. The aetiology of cancer in children is multifactorial and includes both genetic and environmental factors. The association between congenital abnormalities and tumours is well established (15% of neonatal tumours). Genetic defects are highly likely in neonatal tumours and include those with a high risk of malignancy (e.g., retinoblastoma), but also genetically determined syndromes with an increased risk of malignancy and complex genetic rearrangements. Tumours are mostly genetically related at a cellular level and factors influencing cellular maturation or apoptosis within the developing foetus may continue to operate in the neonatal period. Cytogenetics of neonatal neoplasms appear to differ from neoplasms in older children, thus possibly explaining some of the observed differences in clinical behaviour. Certain constitutional chromosome anomalies, however, specifically favour tumours occurring in the foetal and neonatal period. In support of this hypothesis, certain cytogenetic anomalies appear to be specific to neonates, and a number of examples are explored. Other environmental associations include ionizing radiation, drugs taken during pregnancy, infections, tumours in the mother and environmental exposure.

Dynamic contrast-enhanced MRI for differentiation of major salivary glands neoplasms, a 3-T MRI study

PubMed Central

Aghaghazvini, L; Salahshour, F; Yazdani, N; Kooraki, S; Pakravan, M; Shakiba, M

2015-01-01

Objectives: Pre-operative differentiation of salivary gland neoplasms is of great importance. This study was designed to evaluate the use of dynamic contrast-enhanced MRI (DCE-MRI) for differentiation between malignant, Warthin and benign non-Warthin (BNW) neoplasms of major salivary glands. Methods: 46 major salivary gland tumours (SGTs) underwent pre-operative DCE-MRI. Post-surgical histopathological evaluation showed 30 BNW, 6 Warthin and 10 malignant tumours. Time–signal intensity curves (TICs) were categorized as (a) Tpeak >43 s and washout ratio at 180 s (WR180) <4.6%; (b) Tpeak <43 s and WR >22%; (c) Tpeak >43 s and WR180 = 4.6–22.0% Results: Accuracy of Tpeak was 98.9% for differentiation between BNW and Warthin tumours, 83.7% between BNW and malignant and 80% between malignant and Warthin tumours. All Warthin tumours showed Tpeak ≤43 s, while one BNW had Tpeak <43 s. A Tpeak <63.5 s differentiated 8/10 (80%) malignant tumours from BNW tumours, whereas 4/30 of BNW tumours had a Tpeak <63.5 s. Two malignant tumours had Tpeak <43 s. WR180 had an accuracy of 100% for differentiation between Warthin and BNW tumours, 87.3% between BNW and malignant, and 93.3% between Warthin and malignant tumours. 29 (96.7%) BNW tumours had a washout <4.60%, while 8 (80%) malignant tumours had a washout >4.60%. All Warthin tumours had a WR180 >22%, while two malignant tumours had a WR180 >22%. 29/30 of BNW tumours demonstrated TIC curve Type A and 1 tumour demonstrated Type C. 6/10 of malignant tumours had TIC Type C, 2 had TIC Type A and 2 Type B. All Warthin tumours were categorized as Type B. Conclusions: This study showed that DCE-MRI could be helpful in pre-operative differentiation of SGTs; especially for discrimination between Warthin and BNW tumours. PMID:25299931

A new scoring model for characterization of adnexal masses based on two-dimensional gray-scale and colour Doppler sonographic features

PubMed Central

Abbas, A.M.; Zahran, K.M.; Nasr, A.; Kamel, H.S.

2014-01-01

Objective: To determine the most discriminating two-dimensional gray-scale and colour Doppler sonographic features that allow differentiation between malignant and benign adnexal masses, and to develop a scoring model that would enable more accurate diagnosis with those features. Methods: A cross sectional prospective study was conducted on patients scheduled for surgery due to presence of adnexal masses at Woman’s Health Center, Assiut University, Egypt between October 2012 and October 2013. All patients were evaluated by 2D ultrasound for morphological features of the masses combined with colour Doppler examination of their vessels. The final diagnosis, based on histopathological analysis, was used as a gold standard. Results: One hundred forty-six patients were recruited, 104 with benign masses, 42 with malignant masses. Features that allowed statistically significant discrimination of benignity from malignancy were; volume of mass, type of mass, presence and thickness of septae, presence and length of papillary projections, location of vessels at colour Doppler and colour score. A scoring model was formulated combining these features together; Assiut Scoring Model (ASM). The cut-off level with the highest accuracy in detection of malignancy, was ≥6, had a sensitivity of 93.5% and specificity of 92.2%. Conclusion: Our Scoring Model; a multiparameter scoring using four gray-scale ultrasound and two colour Doppler features, had shown a high sensitivity and specificity for prediction of malignancy in adnexal masses compared with previous scoring systems. PMID:25009729

The Microenvironment in Epstein-Barr Virus-Associated Malignancies.

PubMed

Tan, Geok Wee; Visser, Lydia; Tan, Lu Ping; van den Berg, Anke; Diepstra, Arjan

2018-04-13

The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an aspecific reaction to the tumor cells. In fact, latent EBV-infected tumor cells utilize several specific mechanisms to form and shape the TME to their own benefit. These mechanisms have been studied largely in the context of EBV+ Hodgkin lymphoma, undifferentiated nasopharyngeal carcinoma, and EBV+ gastric cancer. This review describes the composition, immune escape mechanisms, and tumor cell promoting properties of the TME in these three malignancies. Mechanisms of susceptibility which regularly involve genes related to immune system function are also discussed, as only a small proportion of EBV-infected individuals develops an EBV-associated malignancy.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of non-lymph node thoracic lesions

PubMed Central

Yang, Huizhen; Zhao, Heng; Garfield, David H.; Teng, Jiajun; Han, Baohui; Sun, Jiayuan

2013-01-01

AIMS: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has shown excellent diagnostic capabilities for mediastinal and hilar lymphadenopathy. However, its value in thoracic non-lymph node lesions is less clear. This study was designed to assess the value of EBUS-TBNA in distinguishing malignant from benign thoracic non-lymph node lesions. METHODS: From October 2009 to August 2011, 552 patients underwent EBUS-TBNA under local anesthesia and with conscious sedation. We retrospectively reviewed 81 of these patients who had tracheobronchial wall-adjacent intrapulmonary or isolated mediastinal non-lymph node lesions. On-site cytological evaluation was not used. Immunohistochemistry (IHC) was performed to distinguish the origin or type of malignancy when necessary. RESULTS: EBUS-TBNA was performed in 68 tracheobronchial wall-adjacent intrapulmonary and 13 isolated mediastinal non-lymph node lesions. Of the 81 patients, 77 (95.1%, 60 malignancies and 17 benignancies) were diagnosed through EBUS-TBNA, including 57 primary lung cancers, 2 mediastinal tumors, 1 pulmonary metastatic adenocarcinoma, 7 inflammation, 5 tuberculosis, 3 mediastinal cysts, 1 esophageal schwannoma, and 1 focal fibrosis. There were four false-negative cases (4.9%). Of the 60 malignancies, there were 9 (15.0%) which originally had no definite histologic origin or type. Thus, IHC was performed, with 7 (77.8%) being subsequently confirmed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in distinguishing malignant from benign lesions were 93.4% (60/64), 100% (17/17), 100% (60/60), 81.0% (17/21), and 95.1% (77/81), respectively. CONCLUSION: EBUS-TBNA is a safe procedure with a high sensitivity for distinguishing malignant from benign thoracic non-lymph node lesions within the reach of EBUS-TBNA, with IHC usually providing a more definitive diagnosis. PMID:23439919

Mucorales-Specific T Cells in Patients with Hematologic Malignancies.

PubMed

Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Gilioli, Andrea; Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Lewis, Russell E; Luppi, Mario

2016-01-01

Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

Soluble Mesothelin Related Peptide (SMRP) and Osteopontin (OPN) as Early Detection Markers for Malignant Mesothelioma (MM) — EDRN Public Portal

Cancer.gov

Phase I: - Identification and assemblage of representative cohorts of individuals with MM, no malignancies but increased risk for MM due to asbestos exposure, and (optionally) lung malignancies other than MM Phase II (A) - Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals with a clinical diagnosis of malignant mesothelioma from individuals who are asbestos-exposed but without a clinical diagnosis of malignant mesothelioma. Phase II (B) – Determine the comparability of analyte values across contributing centers and determine covariates that influence analyte levels Phase II (C) – Determine the sensitivity and specificity of SMRP and OPN, alone and in combination, in distinguishing individuals with MM from those without. Phase III. Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals who would subsequently develop malignant mesothelioma from matched individuals who did not subsequently develop malignant mesothelioma. Phase IV. Determine the sensitivity and specificity of SMRP and OPN in other populations of interest.

The microenvironmental landscape of brain tumors

PubMed Central

Quail, Daniela F.; Joyce, Johanna A.

2017-01-01

The brain tumor microenvironment (TME) is emerging as a critical regulator of cancer progression in primary and metastatic brain malignancies. The unique properties of this organ require a specific framework for designing TME-targeted interventions. Here we discuss a number of these distinct features, including brain-resident cell types, the blood-brain barrier, and various aspects of the immune-suppressive environment. We also highlight recent advances in therapeutically targeting the brain TME in cancer. By developing a comprehensive understanding of the complex and interconnected microenvironmental landscape of brain malignancies we will greatly expand the range of therapeutic strategies available to target these deadly diseases. PMID:28292436

Chimeric antigen receptor T cells: power tools to wipe out leukemia and lymphoma.

PubMed

Riet, Tobias; Abken, Hinrich

2015-08-01

Adoptive cell therapy for malignant diseases is showing promise in recent early-phase trials in the treatment of B cell leukemia/lymphoma. Genetically engineered with a tumor-specific chimeric antigen receptor, patient's T cells produce lasting and complete leukemia regression. However, treatment is associated with some toxicity which needs our attention and the field still faces some hurdles at the scientific, technologic and clinical levels. Surmounting these obstacles will establish chimeric antigen receptor T cell therapy as a powerful approach to cure hematologic malignancies, paving the way for the treatment of other common types of cancer in the future.

Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2016-04-01

Page 1 AWARD NUMBER: W81XWH-14-1-0073 TITLE: Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral...COVERED 04/01/2015 to 03/31/2016 4. TITLE AND SUBTITLE Prevention and Treatment of Neurofibromatosis Type 1- 5a. CONTRACT NUMBER W81XWH-14-1-0073...ABSTRACT The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is malignant peripheral nerve sheath tumor (MPNST). MPNSTs are

Multidetector CT features of pulmonary focal ground-glass opacity: differences between benign and malignant

PubMed Central

Fan, L; Liu, S-Y; Li, Q-C; Yu, H; Xiao, X-S

2012-01-01

Objective To evaluate different features between benign and malignant pulmonary focal ground-glass opacity (fGGO) on multidetector CT (MDCT). Methods 82 pathologically or clinically confirmed fGGOs were retrospectively analysed with regard to demographic data, lesion size and location, attenuation value and MDCT features including shape, margin, interface, internal characteristics and adjacent structure. Differences between benign and malignant fGGOs were analysed using a χ2 test, Fisher's exact test or Mann–Whitney U-test. Morphological characteristics were analysed by binary logistic regression analysis to estimate the likelihood of malignancy. Results There were 21 benign and 61 malignant lesions. No statistical differences were found between benign and malignant fGGOs in terms of demographic data, size, location and attenuation value. The frequency of lobulation (p=0.000), spiculation (p=0.008), spine-like process (p=0.004), well-defined but coarse interface (p=0.000), bronchus cut-off (p=0.003), other air-containing space (p=0.000), pleural indentation (p=0.000) and vascular convergence (p=0.006) was significantly higher in malignant fGGOs than that in benign fGGOs. Binary logistic regression analysis showed that lobulation, interface and pleural indentation were important indicators for malignant diagnosis of fGGO, with the corresponding odds ratios of 8.122, 3.139 and 9.076, respectively. In addition, a well-defined but coarse interface was the most important indicator of malignancy among all interface types. With all three important indicators considered, the diagnostic sensitivity, specificity and accuracy were 93.4%, 66.7% and 86.6%, respectively. Conclusion An fGGO with lobulation, a well-defined but coarse interface and pleural indentation gives a greater than average likelihood of being malignant. PMID:22128130

Malignant transformation of thymoma in recipient rats by heterotopic thymus transplantation from HTLV-I transgenic rats.

PubMed

Tsuji, Takahiro; Ikeda, Hitoshi; Tsuchikawa, Takahiro; Kikuchi, Kazunori; Baba, Tomohisa; Ishizu, Akihiro; Yoshiki, Takashi

2005-07-01

Transgenic rats expressing the pX gene of human T lymphocyte virus type-I (HTLV-I) under control of the rat lymphocyte-specific protein tyrosine kinase type-I promoter (lck-pX rats) developed benign epithelial thymomas. When the thymuses of newborn lck-pX rats were transplanted into the subcapsular space of the kidney in other thymectomized lck-pX rats, similar tumors developed in the transplanted thymuses. Following the tumor growth, dissemination in the abdominal cavity and distant metastasis occurred. The tumors were histopathologically similar to the original thymomas, but prominent nuclear atypia and high mitotic activity were present. The Ki-67 index was twice as high as that in the originals. The tumors were transplantable into the subcutis of lck-pX rats, although transplantation of the originals never succeeded. All evidence indicated that malignant transformation of thymoma was induced by the heterotopic transplantation. Expression of the pX transgene in the transformed tumors were significantly reduced. Among host genes, the expression of p16ink4a/ARF, which was significantly upregulated in the originals, was never detected in the transformed tumors. Genomic Southern blots and PCR suggest that homozygous deletion of the p16ink4a/ARF gene may play important roles in malignant transformation in this model. Our model described here is a useful unique model for in vivo malignant transformation.

A cryptic translocation leading to NUP98-PHF23 fusion in AML.

PubMed

Ning, Yi

2016-12-01

Chromosome translocations leading to gene fusions have emerged as important oncogenic drivers of various types of malignancies. Detection and characterization of these fusion genes not only help diagnosis and management of specific malignancies, but also contribute to our understanding of the genetic basis and pathogenesis of these diseases. NUP98 gene encodes a 98 kDa nucleoporin, which is a component of the nuclear pore complex that mediates transport of mRNA and proteins between the nucleus and the cytoplasm. Due to its participation in translocations leading to the formation of fusion with at least 29 different partner genes, NUP98 is considered one of the most promiscuous fusion genes in hematologic malignancies. We discuss our identification and characterization of a NUP98-PHF23 fusion from a cryptic translocation in patients with acute myeloid leukemia (AML). Copyright © 2016 Elsevier Ltd. All rights reserved.

Combined autofluorescence and Raman spectroscopy method for skin tumor detection in visible and near infrared regions

NASA Astrophysics Data System (ADS)

Zakharov, V. P.; Bratchenko, I. A.; Artemyev, D. N.; Myakinin, O. O.; Khristoforova, Y. A.; Kozlov, S. V.; Moryatov, A. A.

2015-07-01

The combined application of Raman and autofluorescence spectroscopy in visible and near infrared regions for the analysis of malignant neoplasms of human skin was demonstrated. Ex vivo experiments were performed for 130 skin tissue samples: 28 malignant melanomas, 19 basal cell carcinomas, 15 benign tumors, 9 nevi and 59 normal tissues. Proposed method of Raman spectra analysis allows for malignant melanoma differentiating from other skin tissues with accuracy of 84% (sensitivity of 97%, specificity of 72%). Autofluorescence analysis in near infrared and visible regions helped us to increase the diagnostic accuracy by 5-10%. Registration of autofluorescence in near infrared region is realized in one optical unit with Raman spectroscopy. Thus, the proposed method of combined skin tissues study makes possible simultaneous large skin area study with autofluorescence spectra analysis and precise neoplasm type determination with Raman spectroscopy.

Lung nodule malignancy prediction using multi-task convolutional neural network

NASA Astrophysics Data System (ADS)

Li, Xiuli; Kao, Yueying; Shen, Wei; Li, Xiang; Xie, Guotong

2017-03-01

In this paper, we investigated the problem of diagnostic lung nodule malignancy prediction using thoracic Computed Tomography (CT) screening. Unlike most existing studies classify the nodules into two types benign and malignancy, we interpreted the nodule malignancy prediction as a regression problem to predict continuous malignancy level. We proposed a joint multi-task learning algorithm using Convolutional Neural Network (CNN) to capture nodule heterogeneity by extracting discriminative features from alternatingly stacked layers. We trained a CNN regression model to predict the nodule malignancy, and designed a multi-task learning mechanism to simultaneously share knowledge among 9 different nodule characteristics (Subtlety, Calcification, Sphericity, Margin, Lobulation, Spiculation, Texture, Diameter and Malignancy), and improved the final prediction result. Each CNN would generate characteristic-specific feature representations, and then we applied multi-task learning on the features to predict the corresponding likelihood for that characteristic. We evaluated the proposed method on 2620 nodules CT scans from LIDC-IDRI dataset with the 5-fold cross validation strategy. The multitask CNN regression result for regression RMSE and mapped classification ACC were 0.830 and 83.03%, while the results for single task regression RMSE 0.894 and mapped classification ACC 74.9%. Experiments show that the proposed method could predict the lung nodule malignancy likelihood effectively and outperforms the state-of-the-art methods. The learning framework could easily be applied in other anomaly likelihood prediction problem, such as skin cancer and breast cancer. It demonstrated the possibility of our method facilitating the radiologists for nodule staging assessment and individual therapeutic planning.

Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma.

PubMed

Kung, P C; Long, J C; McCaffrey, R P; Ratliff, R L; Harrison, T A; Baltimore, D

1978-05-01

Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

Is "prepectoral edema" a morphologic sign for malignant breast tumors?

PubMed

Kaiser, Clemens G; Herold, Michael; Baltzer, Pascal A T; Dietzel, Matthias; Krammer, Julia; Gajda, Mieczyslaw; Camara, Oumar; Schoenberg, Stefan O; Kaiser, Werner A; Wasser, Klaus

2015-06-01

A variety of morphologic and kinetic signs of benign or malignant breast lesions contribute to a final diagnosis and differential diagnosis in magnetic resonance (MR) mammography (MRM). As a new sign, prepectoral edema (PE) in patients without any history of previous biopsy, operation, radiation, or chemotherapy was detected during routine breast MR examinations. The purpose of this study was to retrospectively evaluate the role of this morphologic sign in the differential diagnosis of breast lesions. Between January 2005 and October 2006, a total of 1109 consecutive MRM examinations have been performed in our institution. In this study, only patients who would later be biopsied or operated in our own hospital were included. They had no previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy, or previous mastitis. In total, 162 patients with 180 lesions were included, histologically correlated later-on by open biopsy (124 patients and 136 lesions) or core biopsy (38 patients and 44 lesions). The evaluations were performed by four experienced radiologists in consensus. One hundred eighty evaluated lesions included 104 malignant lesions (93 invasive and 11 noninvasive cancers) and 76 benign lesions. PE was detected in 2.6% of benign lesions (2 of 76), in none of the Ductal cacinoma in situ (DCIS) cases (0 of 11), and in 25.8% of malignant lesions (24 of 93; P < .000). PE was found significantly more frequently in presence of malignant tumors >2 cm in diameter (48.5%, 17 of 35 vs. 13.8%, 8 of 58; P < .001). PE was not statistically associated to malignant tumor type, presence or absence of additional DCIS, and number of lesions. This resulted in the following diagnostic parameters for PE as an indicator for malignancy: sensitivity of 19.3%, specificity of 97.3%, positive predictive value (PPV) of 92.3%, negative predictive value of 48%, and accuracy of 57.7%. In case of occurrence, the "PE sign" seems to be a specific indicator for malignant tumors with a high PPV, independent from its entity. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

How have advances in our understanding of the molecular genetics of paediatric leukaemia led to improved targeted therapies for these diseases?

PubMed

Szychot, Elwira; Brodkiewicz, Andrzej; Peregud-Pogorzelski, Jarosław

2014-01-01

The term "leukaemia" refers to a large and heterogenous group of diseases, with treatment response and outcome dependent on the specific type of malignancy. New molecular methods allow us to specifically evaluate the type of disorder, and provide treatment of necessary intensity. The aim of this review is to provide insight into the progress in leukaemia treatment that had been possible due to advances in molecular genetics over the last few decades. Those new sophisticated diagnostic methods have allowed us not only to predict patients' prognosis but also to provide a specific therapy depending on the molecular and genetic characteristics of patients. Our review is based on 25 articles regarding novel diagnostic and therapeutic methods as well as prognostic factors, released between 1992 and 2011. Those articles focus mostly on molecular and cytogenetic testing allowing revolutionary methods of patient classification and individual therapy for this highly heterogeneous group of disorders. Implementation of molecular genetic testing to evaluate the type of leukaemia allowed paediatric oncologists and haematologists to adjust the intensity of treatment, improve outcome, minimize toxicity of therapies and considerably lower the risk of side effects. In the last few decades there has been a great improvement in survival among children suffering from haematopoietic malignancies. Progress made in molecular genetics allowed the creation of new treatment protocols that are designed to maintain a high cure rate for children with leukaemia while reducing toxicity.

Surface-enhanced Raman spectroscopy for differentiation between benign and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Li, Zuanfang; Li, Chao; Lin, Duo; Huang, Zufang; Pan, Jianji; Chen, Guannan; Lin, Juqiang; Liu, Nenrong; Yu, Yun; Feng, Shangyuan; Chen, Rong

2014-04-01

The aim of this study was to evaluate the potential of applying silver nano-particle based surface-enhanced Raman scattering (SERS) to discriminate different types of human thyroid tissues. SERS measurements were performed on three groups of tissue samples including thyroid cancers (n = 32), nodular goiters (n = 20) and normal thyroid tissues (n = 25). Tentative assignments of the measured tissue SERS spectra suggest interesting cancer specific biomolecular differences. The principal component analysis (PCA) and linear discriminate analysis (LDA) together with the leave-one-out, cross-validated technique yielded diagnostic sensitivities of 92%, 75% and 87.5%; and specificities of 82.6%, 89.4% and 84.4%, respectively, for differentiation among normal, nodular and malignant thyroid tissue samples. This work demonstrates that tissue SERS spectroscopy associated with multivariate analysis diagnostic algorithms has great potential for detection of thyroid cancer at the molecular level.

Added value of semi-quantitative breast-specific gamma imaging in the work-up of suspicious breast lesions compared to mammography, ultrasound and 3-T MRI

PubMed Central

Seymer, A; Keinrath, P; Holzmannhofer, J; Pirich, C; Hergan, K; Meissnitzer, M W

2015-01-01

Objective: To prospectively analyse the diagnostic value of semi-quantitative breast-specific gamma imaging (BSGI) in the work-up of suspicious breast lesions compared with that of mammography (MG), breast ultrasound and MRI of the breast. Methods: Within a 15-month period, 67 patients with 92 breast lesions rated as Category IV or V according to the breast imaging reporting and data system detected with MG and/or ultrasound were included into the study. After the injection of 740–1110 MBq of Technetium-99m (99mTc) SestaMIBI intravenously, scintigrams were obtained in two projections comparable to MG. The BSGI was analysed visually and semi-quantitatively by calculating a relative uptake factor (X). With the exception of two patients with cardiac pacemakers, all patients underwent 3-T breast MRI. Biopsy results were obtained as the reference standard in all patients. Sensitivity, specificity, positive- and negative-predictive values, accuracy and area under the curve were calculated for each modality. Results: Among the 92 lesions, 67 (72.8%) were malignant. 60 of the 67 cancers of any size were detected by BSGI with an overall sensitivity of 90%, only exceeded by ultrasound with a sensitivity of 99%. The sensitivity of BSGI for lesions <1 cm declined significantly to 60%. Overall specificity of ultrasound was only 20%. Specificity, accuracy and positive-predictive value were the highest for BSGI (56%, 80% and 85%, respectively). X was significantly higher for malignant lesions (mean, 4.27) and differed significantly between ductal types (mean, 4.53) and the other histopathological entities (mean, 3.12). Conclusion: Semi-quantitative BSGI with calculation of the relative uptake factor (X) can help to characterize breast lesions. BSGI negativity may obviate the need for biopsy of breast lesions >1 cm with low or intermediate prevalence for malignancy. Advances in knowledge: Compared with morphological imaging modalities, specificity, positive-predictive value for malignancy and accuracy were the highest for BSGI in our study. BSGI negativity may support the decision not to biopsy in selected lesions with a low or low-to-moderate pre-test probability for malignancy. PMID:25882690

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

DTIC Science & Technology

2017-05-01

DATE : May 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE May 2017 2. REPORT TYPE Annual 3. DATES COVERED...chemistry efforts to synthesize a non-radioactive tethered Hsp90 inhibitor, methods developed for stannylation of the molecule such that it can be

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

DTIC Science & Technology

2017-05-01

REPORT DATE : May 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE May 2017 2. REPORT TYPE Annual 3. DATES ... methods developed for stannylation of the molecule such that it can be effectively radioiodinated with either 131I or 124I. Two paths of synthesis

Mortality and causes of death in a national sample of type 2 diabetic patients in Korea from 2002 to 2013.

PubMed

Kang, Yu Mi; Kim, Ye-Jee; Park, Joong-Yeol; Lee, Woo Je; Jung, Chang Hee

2016-09-13

We aimed to investigate the mortality rate (MR), causes of death and standardized mortality ratio (SMR) in Korean type 2 diabetic patients from 2002 to 2013 using data from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC). From this NHIS-NSC, we identified 29,807 type 2 diabetic subjects from 2002 to 2004. Type 2 diabetes was defined as a current medication history of anti-diabetic drugs and the presence of International Classification of Diseases (ICD)-10 codes (E11-E14) as diagnosis. Specific causes of death were recorded according to ICD-10 codes as the following: diabetes, malignant neoplasm, disease of the circulatory system, and other causes. A total of 7103 (23.8 %) deaths were recorded. The MR tended to increase with age. In particular, the ratio of MR for men versus women was the highest in their 40s-50s. The overall SMR was 2.32 and the SMRs attenuated with increasing age. The causes of death ascribed to diabetes, malignant neoplasm, ischemic heart disease, cerebrovascular disease, and other causes were 22.0, 24.8, 6.2, 11.2 and 31.3 %, respectively. The SMRs according to each cause of death were 9.73, 1.76, 2.60, 2.04 and 1.89, respectively. The MRs among type 2 diabetic subjects increased with age, and diabetic men exhibited a higher mortality risk than diabetic women in Korea. Subjects with type 2 diabetes exhibited an excess mortality when compared with the general population. Approximately 78.0 % of the diabetes-related deaths was not ascribed to diabetes, and malignant neoplasm was the most common cause of death among those not recorded as diabetes.

Expression of microphthalmia transcription factor, S100 protein, and HMB-45 in malignant melanoma and pigmented nevi.

PubMed

Xia, Jianxin; Wang, Yanlong; Li, Fuqiu; Wang, Jinfeng; Mu, Yan; Mei, Xianglin; Li, Xue; Zhu, Wenjing; Jin, Xianhua; Yu, Kai

2016-09-01

Malignant melanoma (MM) is a type of malignant tumor, which originates from neural crest melanocytes. MM progresses rapidly and results in a high mortality rate. The present study aims to investigate the expression of microphthalmia transcription factor (MITF), the S100 protein, and HMB-45 in MM and pigmented nevi. A total of 32 MM samples (including three skin metastasis, three lymph node metastasis and two spindle cell MM samples), two Spitz nevus samples, four pigmented nevus samples and two blue nevus samples were collected. The expression levels of S100 protein, HMB-45, and MITF were observed via immunostaining. The S100 protein exhibited high positive rates in MM and pigment disorders (96.7 and 100%, respectively), but with low specificity. The S100 protein was also expressed in fibroblasts, myoepithelial cells, histocytes and Langerhans cells in normal skin samples. HMB-45 had high specificity. Its positive expression was only confined to MM cells and junctional nevus cells. Furthermore, HMB-45 was not expressed in melanocytes in the normal tissue samples around the tumor or in the benign intradermal nevus cells. MITF exhibited high specificity and high sensitivity. It was expressed in the nuclei of melanocytes, MM cells and nevus cells. It was observed to be strongly expressed in metastatic MM and spindle cell MMs. Thus, MITF may present as a specific immunomarker for the diagnosis and differential diagnosis of MM.

Postirradiation malignant fibrous histiocytoma of the lung. Demonstration of alpha 1-antitrypsin-like material in neoplastic cells.

PubMed

Chowdhury, L N; Swerdlow, M A; Jao, W; Kathpalia, S; Desser, R K

1980-12-01

A metastasizing fibrous histiocytoma arising in the lung of a patient who received radiation therapy and long-term chemotherapy for malignant lymphoma is presented. Ultrastructural studies revealed fibroblast-like and histiocyte-like cells, cells of intermediate type showing ultrastructural features of both fibroblast-like and histiocyte-like cells, primitive mesenchymal cells, multinucleate tumor cells, and xanthomatous cells. The neoplastic cells showed dilated rough endoplasmic reticula with intracisternal accumulation of electron-dense material forming lattice-like structures. Direct immunofluorescence staining of the neoplastic cells using antihuman alpha 1-antitrypsin showed specific activity, with fluorescent deposits exhibiting interlacing globular formations. These findings and their implications are discussed.

Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

PubMed

Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-03-01

The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The usefulness of adding p53 immunocytochemistry to bile drainage cytology for the diagnosis of malignant biliary strictures.

PubMed

Yeo, Min-Kyung; Kim, Kyung-Hee; Lee, Yong-Moon; Lee, Byung Seok; Choi, Song-Yi

2017-07-01

Obstructive jaundice is frequently caused by bile duct strictures. Determination of malignant strictures is crucial for the initiation of appropriate treatment. Cytologic examination of bile drainage fluid is an easy and reproducible method of detecting malignant cells. This method, however, frequently yields indeterminate results, such as atypia or suspicious of malignancy, due to difficulties in differentiating malignancy from benign atypia. Immunocytochemical assessment of p53 expression by cells in bile drainage fluid may enhance the ability to detect malignancy. A total of 139 samples of bile drainage fluid were obtained from 80 patients. Following cytologic examination, the samples were incubated with antibody to p53. The performance of cytology with and without p53 immunocytochemistry was evaluated, with reference to surgical or clinical findings of benign and malignant biliary strictures. Bile drainage cytology alone had a sensitivity of 31.6% and a specificity of 98.4% in the identification of malignant strictures, whereas the combination of p53 immunocytochemistry and bile drainage cytology had a sensitivity of 80.3% and a specificity of 92.1%. P53 immunocytochemistry alone had a sensitivity of 64.5% and a specificity of 92.7% for the identification of malignant strictures in bile drainage samples with atypical cytology, and a sensitivity of 85.0% and a specificity of 100.0% in samples with suspicious of malignancy. The addition of p53 immunocytochemistry to bile drainage cytology can be useful in identifying malignant strictures in samples showing indeterminate results on bile drainage cytology. Diagn. Cytopathol. 2017;45:592-597. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Metabolomic analysis based on 1H-nuclear magnetic resonance spectroscopy metabolic profiles in tuberculous, malignant and transudative pleural effusion

PubMed Central

Wang, Cheng; Peng, Jingjin; Kuang, Yanling; Zhang, Jiaqiang; Dai, Luming

2017-01-01

Pleural effusion is a common clinical manifestation with various causes. Current diagnostic and therapeutic methods have exhibited numerous limitations. By involving the analysis of dynamic changes in low molecular weight catabolites, metabolomics has been widely applied in various types of disease and have provided platforms to distinguish many novel biomarkers. However, to the best of our knowledge, there are few studies regarding the metabolic profiling for pleural effusion. In the current study, 58 pleural effusion samples were collected, among which 20 were malignant pleural effusions, 20 were tuberculous pleural effusions and 18 were transudative pleural effusions. The small molecule metabolite spectrums were obtained by adopting 1H nuclear magnetic resonance technology, and pattern-recognition multi-variable statistical analysis was used to screen out different metabolites. One-way analysis of variance, and Student-Newman-Keuls and the Kruskal-Wallis test were adopted for statistical analysis. Over 400 metabolites were identified in the untargeted metabolomic analysis and 26 metabolites were identified as significantly different among tuberculous, malignant and transudative pleural effusions. These metabolites were predominantly involved in the metabolic pathways of amino acids metabolism, glycometabolism and lipid metabolism. Statistical analysis revealed that eight metabolites contributed to the distinction between the three groups: Tuberculous, malignant and transudative pleural effusion. In the current study, the feasibility of identifying small molecule biochemical profiles in different types of pleural effusion were investigated reveal novel biological insights into the underlying mechanisms. The results provide specific insights into the biology of tubercular, malignant and transudative pleural effusion and may offer novel strategies for the diagnosis and therapy of associated diseases, including tuberculosis, advanced lung cancer and congestive heart failure. PMID:28627685

Targeting Histone Deacetylases in Malignant Melanoma: A Future Therapeutic Agent or Just Great Expectations?

PubMed

Garmpis, Nikolaos; Damaskos, Christos; Garmpi, Anna; Dimitroulis, Dimitrios; Spartalis, Eleftherios; Margonis, Georgios-Antonios; Schizas, Dimitrios; Deskou, Irini; Doula, Chrysoula; Magkouti, Eleni; Andreatos, Nikolaos; Antoniou, Efstathios A; Nonni, Afroditi; Kontzoglou, Konstantinos; Mantas, Dimitrios

2017-10-01

Malignant melanoma is the most aggressive type of skin cancer, with increasing frequency and mortality. Melanoma is characterized by rapid proliferation and metastases. Malignant transformation of normal melanocytes is associated with imbalance between oncogenes' action and tumor suppressor genes. Mutations or inactivation of these genes plays an important role in the pathogenesis of malignant melanoma. Many target-specific agents improved progression-free survival but unfortunately metastatic melanoma remains incurable, so new therapeutic strategies are needed. The balance of histones' acetylation affects cell cycle progression, differentiation and apoptosis. Histone deacetylases (HDAC) are associated with different types of cancer. Histone deacetylase inhibitors (HDACI) are enzymes that inhibit the action of HDAC, resulting in block of tumor cell proliferation. A small number of these enzymes has been studied regarding their anticancer effects in melanoma. The purpose of this article was to review the therapeutic effect of HDACI against malignant melanoma, enlightening the molecular mechanisms of their action. The MEDLINE database was used. The keywords/ phrases were; HDACI, melanoma, targeted therapies for melanoma. Our final conclusions were based on studies that didn't refer solely to melanoma due to their wider experimental data. Thirty-two articles were selected from the total number of the search's results. Only English articles published until March 2017 were used. Molecules, such as valproid acid (VPA), LBH589, LAQ824 (dacinostat), vorinostat, tubacin, sirtinol and tx-527, suberoyl bis-hydroxamic acid (SBHA), depsipeptide and Trichostatin A (TSA) have shown promising antineoplastic effects against melanoma. HDACI represent a promising agent for targeted therapy. More trials are required. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years

PubMed Central

Engelhardt, Monika; Ihorst, Gabriele; Landgren, Ola; Pantic, Milena; Reinhardt, Heike; Waldschmidt, Johannes; May, Annette M.; Schumacher, Martin; Kleber, Martina; Wäsch, Ralph

2015-01-01

Additional malignancies in multiple myeloma patients after first-line and maintenance treatment have been observed, questioning whether specific risks exist. Second primary malignancies have also gained attention since randomized data showed associations to newer drugs. We have conducted this large registry analysis in 744 consecutive patients and analyzed: 1) frequency and onset of additional malignancies; and 2) second primary malignancy- and myeloma-specific risks. We assessed the frequency of additional malignancies in terms of host-, myeloma- and treatment-specific characteristics. To compare these risks, we estimated cumulative incidence rates for second malignancies and myeloma with Fine and Gray regression models taking into account competing risks. Additional malignancies were found in 118 patients: prior or synchronous malignancies in 63% and subsequent in 37%. Cumulative incidence rates for second malignancies were increased in IgG-myeloma and decreased in bortezomib-treated patients (P<0.05). Cumulative incidence rates for myeloma death were increased with higher stage and age, but decreased in IgG-subtypes and due to anti-myeloma treatment (P<0.05). Cytogenetics in patients acquiring second primary malignancies were predominantly favorable, suggesting that indolent myeloma and long disease latency may allow the manifestation of additional malignancies. An assessment of the Surveillance, Epidemiology, and End Result Program of the National Cancer Institute and our data with long-term follow up of 25 years confirmed a prevalence of second malignancy of 10% at 25 years, whereas death from myeloma decreased from 90% to 83%, respectively. Our important findings widen our knowledge of second malignancies and show that they are of increasing relevance as the prognosis in myeloma improves and mortality rates decrease. PMID:26160877

Symptoms and signs associated with benign and malignant proximal fibular tumors: a clinicopathological analysis of 52 cases.

PubMed

Sun, Tao; Wang, Lingxiang; Guo, Changzhi; Zhang, Guochuan; Hu, Wenhai

2017-05-02

Malignant tumors in the proximal fibula are rare but life-threatening; however, biopsy is not routine due to the high risk of peroneal nerve injury. Our aim was to determine preoperative clinical indicators of malignancy. Between 2004 and 2016, 52 consecutive patients with proximal fibular tumors were retrospectively reviewed. Details of the clinicopathological characteristics including age, gender, location of tumors, the presenting symptoms, the duration of symptoms, and pathological diagnosis were collected. Descriptive statistics were calculated, and univariate and multivariate regression were performed. Of these 52 patients, 84.6% had benign tumors and 15.4% malignant tumors. The most common benign tumors were osteochondromas (46.2%), followed by enchondromas (13.5%) and giant cell tumors (13.5%). The most common malignancy was osteosarcomas (11.5%). The most common presenting symptoms were a palpable mass (52.0%) and pain (46.2%). Pain was the most sensitive (100%) and fourth specific (64%); both high skin temperature and peroneal nerve compression had the highest specificity (98%) and third sensitivity (64%); change in symptoms had the second highest specificity (89%) while 50% sensitivity. Using multivariate regression, palpable pain, high skin temperature, and peroneal nerve compression symptoms were predictors of malignancy. Most tumors in the proximal fibula are benign, and the malignancy is rare. Palpable pain, peroneal nerve compression symptoms, and high skin temperature were specific in predicting malignancy.

Mucorales-Specific T Cells in Patients with Hematologic Malignancies

PubMed Central

Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Luppi, Mario

2016-01-01

Background Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. Methods and Findings By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Conclusions Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM. PMID:26871570

Hospital end-of-life care in haematological malignancies.

PubMed

Beaussant, Yvan; Daguindau, Etienne; Chauchet, Adrien; Rochigneux, Philippe; Tournigand, Christophe; Aubry, Régis; Morin, Lucas

2018-02-06

To investigate patterns of care during the last months of life of hospitalised patients who died from different haematological malignancies. Nationwide register-based study, including all hospitalised adults ≥20 years who died from haematological malignancies in France in 2010-2013. Outcomes included use of invasive cancer treatments and referral to palliative care. Percentages are adjusted for sex and age using direct standardisation. Of 46 629 inpatients who died with haematological malignancies, 24.5% received chemotherapy during the last month before death, 48.5% received blood transfusion, 12.3% were under invasive ventilation and 18.1% died in intensive care units. We found important variations between haematological malignancies. The use of chemotherapy during the last month of life varied from 8.6% among patients with chronic myeloid leukaemia up to 30.1% among those with non-Hodgkin's lymphoma (P<0.001). Invasive ventilation was used in 10.2% of patients with acute leukaemia but in 19.0% of patients with Hodgkin's lymphoma (P<0.001). Palliative status was reported 30 days before death in only 14.8% of patients, and at time of death in 46.9% of cases. Overall, 5.5% of haematology patients died in palliative care units. A high proportion of patients who died from haematological malignancies receive specific treatments near the end of life. There is a need for a better and earlier integration of the palliative care approach in the standard practice of haematology. However, substantial variation according to the type of haematological malignancy suggests that the patients should not be considered as one homogeneous group. Implementation of palliative care should account for differences across haematological malignancies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Contrast-enhanced color Doppler ultrasonography increases diagnostic accuracy for soft tissue tumors.

PubMed

Oebisu, Naoto; Hoshi, Manabu; Ieguchi, Makoto; Takada, Jun; Iwai, Tadashi; Ohsawa, Masahiko; Nakamura, Hiroaki

2014-10-01

Resolution of ultrasonography (US) has undergone marked development. Additionally, a new-generation contrast medium (Sonazoid) used for US is newly available. Contrast-enhanced US has been widely used for evaluating several types of cancer. In the present study, we evaluated the ability of color Doppler US (CDUS) and Sonazoid to differentiate between benign and malignant soft tissue tumors. A total of 180 patients (87 male, 93 female) were enrolled in the present study. The patient ages ranged from 1 to 91 years (mean 58.1±20.0 years). The maximum size, depth, tumor margins, shape, echogenicity and textural pattern were measured on gray-scale images. CDUS was used to evaluate the intratumoral blood flow with and without Sonazoid. Peak systolic flow velocity (Vp), mean flow velocity (Vm), resistivity index (RI) and pulsatility index (PI) of each detected intratumoral artery were automatically calculated with power Doppler US (PDUS). The present study included 118 benign and 62 malignant tumors. Statistical significances were found in size, depth, tumor margin and textural pattern but not in shape or echogenicity on gray-scale images. Before Sonazoid injection, CDUS findings showed 55% sensitivity, 77% specificity and 69% accuracy, whereas contrast-enhanced CDUS showed 87% sensitivity, 68% specificity and 74% accuracy. There were no statistically significant differences between malignant and benign tumors regarding the mean Vp, Vm, RI and PI values determined on PDUS. In conclusion, contrast-enhanced CDUS proved to be a reliable diagnostic tool for detecting malignant potential in soft tissue tumors.

Cystic pancreatic neoplasms evaluation by CT and magnetic resonance cholangiopancreatography.

PubMed

Sahani, Dushyant; Prasad, Srinivasa; Saini, Sanjay; Mueller, Peter

2002-10-01

CT provides limited assistance in the differentiation between serous and mucinous neoplasms. Because of the variability in the radiographic appearance of serous cystadenomas and overlap in CT characteristics with mucinous neoplasms, most serous neoplasms still require ancillary testing such as biopsy to reach a definitive diagnosis. MRCP is useful in differentiating benign and malignant mucinous tumors including IPMT of the pancreas. The presence of mural nodules is suggestive of malignancy; however, the absence of mural nodules does not indicate that the tumor is benign. A maximum main pancreatic duct diameter of greater than 15 mm and diffuse dilatation of the main pancreatic duct are suggestive of malignancy in main duct-type tumors. Among branch duct-type tumors, malignant tumors tend to be larger than benign tumors; however, this finding is variable. The presence of main pancreatic duct dilatation may be helpful in determining malignancy of branch duct-type tumors.

Adrenal Gland Cancer

MedlinePlus

... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

Histopathology of malignant salivary gland tumours.

PubMed

Seifert, G

1992-07-01

This report is based upon the Salivary Gland Register in Hamburg and on the second revised edition of the WHO Histological Typing of Salivary Gland Tumours. The group of malignant salivary gland tumours contains carcinomas, malignant non-epithelial tumours, malignant lymphomas and secondary tumours. The various carcinomas are classified in a continuous separate listing because the different types are distinguished not only by histopathology, but also by differences in prognosis and treatment. The term "tumour" is replaced by "carcinoma" in two entities: acinic cell carcinoma and mucoepidermoid carcinoma. New entities are: polymorphous low-grade adenocarcinoma, basal cell adenocarcinoma, salivary duct carcinoma and malignant myoepithelioma. Carcinoma in pleomorphic adenoma can be distinguished as non-invasive and invasive carcinoma, and carcinosarcoma. Malignant non-epithelial tumours are mostly malignant fibrous histiocytoma, malignant schwannoma and rhabdomyosarcoma. The large majority of malignant lymphomas are non-Hodgkin-lymphomas with high differentiation. Many lymphomas are associated with chronic immunosialadenitis (Sjögren's syndrome). Secondary tumours are mostly metastases from primary squamous cell carcinomas or from melanomas of the skin (head and neck area). Haematogeneous metastases are very rare (mainly from lung, kidney or breast).

Clinical effects of vinorelbine administration in the management of various malignant tumor types in dogs: 58 cases (1997–2012)

PubMed Central

Wouda, Raelene M.; Miller, Mairin E.; Chon, Esther; Stein, Timothy J.

2016-01-01

Objective To evaluate the effectiveness of vinorelbine in the management of various malignant tumor types in dogs. Design Retrospective case series. Animals 58 dogs with malignant tumors, including pulmonary carcinoma (n = 31), histiocytic sarcoma (9), mast cell tumor (5), lymphoma (4), melanoma (2), and 7 other tumor types (1 each). Procedures Medical records of dogs treated with vinorelbine from December 1997 to December 2012 were reviewed for data regarding signalment, clinical signs, physical examination findings, clinicopathologic test results, diagnostic imaging results, vinorelbine doses and dose frequency, surgery and radiotherapy details when applicable, other chemotherapeutics administered, and outcomes. Descriptive, comparative, and survival statistics were computed for all dogs and for dogs by histologic subgroup of tumors. Results Vinorelbine was administered palliatively to 44 (76%) dogs. One (2%) dog had a complete response for 162 days, 5 (11%) dogs had a partial response for a median duration of 91 days, 19 (43%) dogs had stable disease for a median duration of 68 days, and 19 (43%) dogs developed progressive disease after a median duration of 21 days. Clinical benefit was more difficult to assess in the remaining 14 (24%) dogs that received vinorelbine as an adjuvant treatment. Overall median time to tumor progression was 103 days (range, 5 to 1,533 days). Conclusions and Clinical Relevance Vinorelbine appeared to be effective in the treatment of several tumor types in dogs. Follow-up prospective studies of the clinical benefit of the drug in specific clinical scenarios will be necessary to support this conclusion. PMID:25970220

Diagnostic value of high-resolution B-mode and power-mode sonography in the follow-up of thyroid cancer.

PubMed

Görges, Rainer; Eising, E G; Fotescu, D; Renzing-Köhler, K; Frilling, A; Schmid, K W; Bockisch, A; Dirsch, O

2003-02-01

Ultrasonography is an established diagnostic modality in the follow-up of thyroid cancer. Color flow Doppler has been proposed by some authors as an additional tool for differentiating benign from malignant cervical lesions in various types of head and neck cancer. Over the last few years, a new generation of high-resolution ultrasound platforms with the "power-mode" feature has become available, that also enables the imaging of small vessel blood flow. The objective of our study was to find ways of optimizing the differentiation of benign and malignant cervical tumors in thyroid cancer follow-up by means of sonography. Hundred and twelve cervical lesions in 90 patients with thyroid cancer were evaluated by high-end ultrasonography (Sonoline Elegra, Siemens) using a small-part transducer (7.5 L 40, Siemens). B-mode sonography was performed at a frequency of 8 MHz. The Solbiati index (SI= ratio of largest to smallest diameter), configuration, echogenicity, intranodular structures, and margins were assessed. Perinodular and intranodular blood flow was evaluated by color flow Doppler (PRF 1250 Hz for conventional color flow Doppler, 868 Hz for power-mode Doppler). Possible malignancy was validated by histology, cytology, scintigraphy, and follow-up. Thirty five lesions were benign (diameter 0.4-3.0 cm) and 77 were malignant (0.4-5.4 cm). The patients were randomized into a test group and a learning group to determine the diagnostic value of various ultrasound criteria by means of statistical analysis. In the learning group, decision rules based on the dichotomized criteria were developed using a logistic regression model. Sensitivity and specificity of these decision rules were then evaluated in the test group. The presence of an echocomplex pattern or irregular hyperechoic small intranodular structures (criterion A) and the presence of an irregular diffuse intranodular blood flow (criterion B) are the best indicators of malignancy, whereas an SI >2 is highly indicative of benign changes. Color flow Doppler is a useful addition to B-mode scanning for distinguishing benign and malignant neoplasms in the follow-up of thyroid cancer. Power-mode Doppler sonography significantly improves imaging of perinodular and intranodular blood flow when compared with conventional color flow Doppler. We propose the following decision rules based on a combination of the criteria above: (A) and (B) fulfilled: malignant, if SI< or =4; (B) but not (A) fulfilled: malignant, if SI< or =3; (A) but not (B) fulfilled: malignant, if SI< or =2; neither (A) nor (B) fulfilled: malignant, if SI approximately equal to 1 (sensitivity: 90%; specificity: 82%; accuracy 88%).

Cancer in Children

MedlinePlus

Cancer is a group related diseases. In all types of cancer, some of the body's cells begin to divide ... can be benign or malignant. Benign tumorsaren't cancer while malignant ones are. Cells from malignant tumors ...

Nanotechnology applications in hematological malignancies (Review).

PubMed

Samir, Ahmed; Elgamal, Basma M; Gabr, Hala; Sabaawy, Hatem E

2015-09-01

A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up.

Nanotechnology applications in hematological malignancies (Review)

PubMed Central

SAMIR, AHMED; ELGAMAL, BASMA M; GABR, HALA; SABAAWY, HATEM E

2015-01-01

A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID:26134389

Oncolytic Herpes Simplex Viral Therapy: A Stride toward Selective Targeting of Cancer Cells.

PubMed

Sanchala, Dhaval S; Bhatt, Lokesh K; Prabhavalkar, Kedar S

2017-01-01

Oncolytic viral therapy, which makes use of replication-competent lytic viruses, has emerged as a promising modality to treat malignancies. It has shown meaningful outcomes in both solid tumor and hematologic malignancies. Advancements during the last decade, mainly genetic engineering of oncolytic viruses have resulted in improved specificity and efficacy of oncolytic viruses in cancer therapeutics. Oncolytic viral therapy for treating cancer with herpes simplex virus-1 has been of particular interest owing to its range of benefits like: (a) large genome and power to infiltrate in the tumor, (b) easy access to manipulation with the flexibility to insert multiple transgenes, (c) infecting majority of the malignant cell types with quick replication in the infected cells and (d) as Anti-HSV agent to terminate HSV replication. This review provides an exhaustive list of oncolytic herpes simplex virus-1 along with their genetic alterations. It also encompasses the major developments in oncolytic herpes simplex-1 viral therapy and outlines the limitations and drawbacks of oncolytic herpes simplex viral therapy.

Estrogen Enhances Malignant Phenotypes in Human Salivary Adenoid Cystic Carcinoma Cells.

PubMed

Sumida, Tomoki; Ishikawa, Akiko; Kamata, Y U; Nakano, Hiroyuki; Yamada, Tomohiro; Mori, Yoshihide

2016-06-01

Adenoid cystic carcinoma (SGC) is a common type of salivary gland cancer (SGC). Surgery is the first treatment choice because chemoradiotherapy is usually not effective. Therefore, new treatment modalities are urgently needed. In this study, it was investigated whether the estrogen axis could be a treatment target or not. Adenoid cystic carcinoma (ACC) ACCM cells, were used. The specific cell line lacks estrogen receptor (ER). ER was introduced in ACCM cells, and the effect of 17β-estradiol (E2) was investigated on cell proliferation, cell-cycle distribution, and cell motility. E2 induced cell proliferation, and the S-phase fraction increased in a dose-dependent manner. Cell motility was also up-regulated compared to control cells. The estrogen/ER system up-regulated malignant phenotypes in ER-positive ACC, and hormone therapy may have a potential as effective treatment for this malignancy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Notch signaling: switching an oncogene to a tumor suppressor

PubMed Central

Lobry, Camille; Oh, Philmo; Mansour, Marc R.; Look, A. Thomas

2014-01-01

The Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types. Notch is a binary cell-fate determinant, and its hyperactivation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL). Recently, several studies also unraveled tumor-suppressor roles for Notch signaling in different tissues, including tissues where it was before recognized as an oncogene in specific lineages. Whereas involvement of Notch as an oncogene in several lymphoid malignancies (T-ALL, B-chronic lymphocytic leukemia, splenic marginal zone lymphoma) is well characterized, there is growing evidence involving Notch signaling as a tumor suppressor in myeloid malignancies. It therefore appears that Notch signaling pathway’s oncogenic or tumor-suppressor abilities are highly context dependent. In this review, we summarize and discuss latest advances in the understanding of this dual role in hematopoiesis and the possible consequences for the treatment of hematologic malignancies. PMID:24608975

VpreB gene expression in hematopoietic malignancies: a lineage- and stage-restricted marker for B-cell precursor leukemias.

PubMed

Bauer, S R; Kubagawa, H; Maclennan, I; Melchers, F

1991-09-15

We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage.

Cloudy and starry milia-like cysts: how well do they distinguish seborrheic keratoses from malignant melanomas?

PubMed

Stricklin, S M; Stoecker, W V; Oliviero, M C; Rabinovitz, H S; Mahajan, S K

2011-10-01

Seborrheic keratoses are the most common skin lesions known to contain small white or yellow structures called milia-like cysts (MLCs). Varied appearances can sometimes make it difficult to differentiate benign lesions from malignant lesions such as melanoma, the deadliest form of skin cancer found in humans. The purpose of this study was to determine the statistical occurrence of MLCs in benign vs. malignant lesions. A medical student with 10 months experience in examining approximately 1000 dermoscopy images and a dermoscopy-naïve observer analysed contact non-polarized dermoscopy images of 221 malignant melanomas and 175 seborrheic keratoses for presence of MLCs. The observers found two different types of MLCs present: large ones described as cloudy and smaller ones described as starry. Starry MLCs were found to be prevalent in both seborrheic keratoses and melanomas. Cloudy MLCs, however, were found to have 99.1% specificity for seborrheic keratoses among this group of seborrheic keratoses and melanomas. Cloudy MLCs can be a useful tool for differentiating between seborrheic keratoses and melanomas. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Cloudy and starry milia-like cysts: how well do they distinguish seborrheic keratoses from malignant melanomas?

PubMed Central

Stricklin, S.M.; Stoecker, W.V.; Oliviero, M.C.; Rabinovitz, H.S.; Mahajan, S.K.

2011-01-01

Background Seborrheic keratoses are the most common skin lesions known to contain small white or yellow structures called milia-like cysts (MLCs). Varied appearances can sometimes make it difficult to differentiate benign lesions from malignant lesions such as melanoma, the deadliest form of skin cancer found in humans. Objective The purpose of this study was to determine the statistical occurrence of MLCs in benign vs. malignant lesions. Methods A medical student with 10 months experience in examining approximately 1000 dermoscopy images and a dermoscopy-naïve observer analysed contact non-polarized dermoscopy images of 221 malignant melanomas and 175 seborrheic keratoses for presence of MLCs. Results The observers found two different types of MLCs present: large ones described as cloudy and smaller ones described as starry. Starry MLCs were found to be prevalent in both seborrheic keratoses and melanomas. Cloudy MLCs, however, were found to have 99.1% specificity for seborrheic keratoses among this group of seborrheic keratoses and melanomas. Conclusion Cloudy MLCs can be a useful tool for differentiating between seborrheic keratoses and melanomas. Received: 18 June 2010; Accepted: 27 October 2010 PMID:21923811

Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies.

PubMed

Sun, Chuang; Dotti, Gianpietro; Savoldo, Barbara

2016-06-30

Hematologic malignancies provide a suitable testing environment for cell-based immunotherapies, which were pioneered by the development of allogeneic hematopoietic stem cell transplant. All types of cell-based therapies, from donor lymphocyte infusion to dendritic cell vaccines, and adoptive transfer of tumor-specific cytotoxic T cells and natural killer cells, have been clinically translated for hematologic malignancies. The recent success of chimeric antigen receptor-modified T lymphocytes in B-cell malignancies has stimulated the development of this approach toward other hematologic tumors. Similarly, the remarkable activity of checkpoint inhibitors as single agents has created enthusiasm for potential combinations with other cell-based immune therapies. However, tumor cells continuously develop various strategies to evade their immune-mediated elimination. Meanwhile, the recruitment of immunosuppressive cells and the release of inhibitory factors contribute to the development of a tumor microenvironment that hampers the initiation of effective immune responses or blocks the functions of immune effector cells. Understanding how tumor cells escape from immune attack and favor immunosuppression is essential for the improvement of immune cell-based therapies and the development of rational combination approaches. © 2016 by The American Society of Hematology.

HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.

PubMed

Napolitano, Andrea; Antoine, Daniel J; Pellegrini, Laura; Baumann, Francine; Pagano, Ian; Pastorino, Sandra; Goparaju, Chandra M; Prokrym, Kirill; Canino, Claudia; Pass, Harvey I; Carbone, Michele; Yang, Haining

2016-06-15

To determine whether serum levels of high mobility group box protein 1 (HMGB1) could differentiate malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Hyperacetylated and nonacetylated HMGB1 (together referred to as total HMGB1) were blindly measured in blood collected from malignant mesothelioma patients (n = 22), individuals with verified chronic asbestos exposure (n = 20), patients with benign pleural effusions (n = 13) or malignant pleural effusions not due to malignant mesothelioma (n = 25), and healthy controls (n = 20). Blood levels of previously proposed malignant mesothelioma biomarkers fibulin-3, mesothelin, and osteopontin were also measured in nonhealthy individuals. HMGB1 serum levels reliably distinguished malignant mesothelioma patients, asbestos-exposed individuals, and unexposed controls. Total HMGB1 was significantly higher in malignant mesothelioma patients and asbestos-exposed individuals compared with healthy controls. Hyperacetylated HMGB1 was significantly higher in malignant mesothelioma patients compared with asbestos-exposed individuals and healthy controls, and did not vary with tumor stage. At the cut-off value of 2.00 ng/mL, the sensitivity and specificity of serum hyperacetylated HMGB1 in differentiating malignant mesothelioma patients from asbestos-exposed individuals and healthy controls was 100%, outperforming other previously proposed biomarkers. Combining HMGB1 and fibulin-3 provided increased sensitivity and specificity in differentiating malignant mesothelioma patients from patients with cytologically benign or malignant non-mesothelioma pleural effusion. Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyperacetylated HMGB1 is an accurate biomarker to differentiate malignant mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls. A trial to independently validate these findings will start soon. Clin Cancer Res; 22(12); 3087-96. ©2016 AACR. ©2016 American Association for Cancer Research.

Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells

PubMed Central

2013-01-01

Introduction Malignant pleural mesothelioma (MPM) is an incurable malignant disease, which results from chronic exposition to asbestos in at least 70% of the cases. Fibroblast activation protein (FAP) is predominantly expressed on the surface of reactive tumor-associated fibroblasts as well as on particular cancer types. Because of its expression on the cell surface, FAP is an attractive target for adoptive T cell therapy. T cells can be re-directed by retroviral transfer of chimeric antigen receptors (CAR) against tumor-associated antigens (TAA) and therefore represent a therapeutic strategy of adoptive immunotherapy. Methods To evaluate FAP expression immunohistochemistry was performed in tumor tissue from MPM patients. CD8+ human T cells were retrovirally transduced with an anti-FAP-F19-∆CD28/CD3ζ-CAR. T cell function was evaluated in vitro by cytokine release and cytotoxicity assays. In vivo function was tested with an intraperitoneal xenograft tumor model in immunodeficient mice. Results FAP was found to be expressed in all subtypes of MPM. Additionally, FAP expression was evaluated in healthy adult tissue samples and was only detected in specific areas in the pancreas, the placenta and very weakly for cervix and uterus. Expression of the anti-FAP-F19-∆CD28/CD3ζ-CAR in CD8+ T cells resulted in antigen-specific IFNγ release. Additionally, FAP-specific re-directed T cells lysed FAP positive mesothelioma cells and inflammatory fibroblasts in an antigen-specific manner in vitro. Furthermore, FAP-specific re-directed T cells inhibited the growth of FAP positive human tumor cells in the peritoneal cavity of mice and significantly prolonged survival of mice. Conclusion FAP re-directed CD8+ T cells showed antigen-specific functionality in vitro and in vivo. Furthermore, FAP expression was verified in all MPM histotypes. Therefore, our data support performing a phase I clinical trial in which MPM patients are treated with adoptively transferred FAP-specific re-directed T cells. PMID:23937772

Photoacoustic image patterns of breast carcinoma and comparisons with Magnetic Resonance Imaging and vascular stained histopathology

NASA Astrophysics Data System (ADS)

Heijblom, M.; Piras, D.; Brinkhuis, M.; van Hespen, J. C. G.; van den Engh, F. M.; van der Schaaf, M.; Klaase, J. M.; van Leeuwen, T. G.; Steenbergen, W.; Manohar, S.

2015-07-01

Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images, and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies, and first insights were gained into the relationship with tumor vascularity.

Polarization speckle imaging as a potential technique for in vivo skin cancer detection.

PubMed

Tchvialeva, Lioudmila; Dhadwal, Gurbir; Lui, Harvey; Kalia, Sunil; Zeng, Haishan; McLean, David I; Lee, Tim K

2013-06-01

Skin cancer is the most common cancer in the Western world. In order to accurately detect the disease, especially malignant melanoma-the most fatal form of skin cancer-at an early stage when the prognosis is excellent, there is an urgent need to develop noninvasive early detection methods. We believe that polarization speckle patterns, defined as a spatial distribution of depolarization ratio of traditional speckle patterns, can be an important tool for skin cancer detection. To demonstrate our technique, we conduct a large in vivo clinical study of 214 skin lesions, and show that statistical moments of the polarization speckle pattern could differentiate different types of skin lesions, including three common types of skin cancers, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and two benign lesions, melanocytic nevus and seborrheic keratoses. In particular, the fourth order moment achieves better or similar sensitivity and specificity than many well-known and accepted optical techniques used to differentiate melanoma and seborrheic keratosis.

Polarization speckle imaging as a potential technique for in vivo skin cancer detection

NASA Astrophysics Data System (ADS)

Tchvialeva, Lioudmila; Dhadwal, Gurbir; Lui, Harvey; Kalia, Sunil; Zeng, Haishan; McLean, David I.; Lee, Tim K.

2013-06-01

Skin cancer is the most common cancer in the Western world. In order to accurately detect the disease, especially malignant melanoma-the most fatal form of skin cancer-at an early stage when the prognosis is excellent, there is an urgent need to develop noninvasive early detection methods. We believe that polarization speckle patterns, defined as a spatial distribution of depolarization ratio of traditional speckle patterns, can be an important tool for skin cancer detection. To demonstrate our technique, we conduct a large in vivo clinical study of 214 skin lesions, and show that statistical moments of the polarization speckle pattern could differentiate different types of skin lesions, including three common types of skin cancers, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and two benign lesions, melanocytic nevus and seborrheic keratoses. In particular, the fourth order moment achieves better or similar sensitivity and specificity than many well-known and accepted optical techniques used to differentiate melanoma and seborrheic keratosis.

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models.

PubMed

Ng, Samuel Y; Yoshida, Noriaki; Christie, Amanda L; Ghandi, Mahmoud; Dharia, Neekesh V; Dempster, Joshua; Murakami, Mark; Shigemori, Kay; Morrow, Sara N; Van Scoyk, Alexandria; Cordero, Nicolas A; Stevenson, Kristen E; Puligandla, Maneka; Haas, Brian; Lo, Christopher; Meyers, Robin; Gao, Galen; Cherniack, Andrew; Louissaint, Abner; Nardi, Valentina; Thorner, Aaron R; Long, Henry; Qiu, Xintao; Morgan, Elizabeth A; Dorfman, David M; Fiore, Danilo; Jang, Julie; Epstein, Alan L; Dogan, Ahmet; Zhang, Yanming; Horwitz, Steven M; Jacobsen, Eric D; Santiago, Solimar; Ren, Jian-Guo; Guerlavais, Vincent; Annis, D Allen; Aivado, Manuel; Saleh, Mansoor N; Mehta, Amitkumar; Tsherniak, Aviad; Root, David; Vazquez, Francisca; Hahn, William C; Inghirami, Giorgio; Aster, Jon C; Weinstock, David M; Koch, Raphael

2018-05-22

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models.

Risks of malignancies related to tofacitinib and biological drugs in rheumatoid arthritis: Systematic review, meta-analysis, and network meta-analysis.

PubMed

Maneiro, José Ramón; Souto, Alejandro; Gomez-Reino, Juan J

2017-10-01

To summarize and compare the risks of malignancies accompanying biologic DMARDs (b-DMARDs) and tofacitinib in rheumatoid arthritis (RA) in randomized clinical trials (RCTs) and long-term extension studies (LTEs). Articles in Medline, Embase, Cochrane Library, and the Web of Science dated from 2000 to February 2015. Selection criteria were as follows: (1) focus on RCTs or LTEs in RA; (2) treatment with b-DMARDs or tofacitinib; (3) data on malignancies; and (4) a minimum follow-up of 12 weeks. Data included publication details, study design, risk of bias, number and types of malignancies, and patient characteristics and treatments. Of 113 articles and one updated report that were meta-analyzed, overall malignancies in RCTs showed odds ratio (95% confidence intervals) of 1.01 (0.72, 1.42) for all TNF antagonists, 1.12 (0.33, 3.81) for abatacept, 0.54 (0.20, 1.50) for rituximab, 0.70 (0.20, 2.41) for tocilizumab, and 2.39 (0.50, 11.5) for tofacitinib. Network meta-analysis of overall malignancies showed odds ratio (95% predictive intervals) of 1.68 (0.48-5.92) for infliximab, 0.79 (0.44-1.40) for etanercept, 0.93 (0.43-2.03) for adalimumab, 0.87 (0.28-2.75) for certolizumab, 0.87 (0.39-1.95) for golimumab, 1.04 (0.32-3.32) for abatacept, 0.58 (0.21-1.56) for rituximab, 0.60 (0.16-2.28) for tocilizumab, and 1.15 (0.24-5.47) for tofacitinib. Marginal numerical differences in the incidence rate of solid and hematological malignancies and non-melanoma skin cancers appeared in LTEs. In RCTs, treatment of RA with b-DMARDs or tofacitinib does not increase the risk for malignancies. Generalizability of the differences in the rate of specific malignancies encountered in LTEs requires continuous pharmacovigilance of real-world patients. Copyright © 2017. Published by Elsevier Inc.

Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy.

PubMed

Eickhoff, L; Golpon, H; Zardo, P; Suhling, H; Welte, T; Jonigk, D; Gottlieb, J; Fuehner, T

2018-05-22

 Endobronchial ultrasound (EBUS) bronchoscopy with transbronchial needle aspiration (TBNA) is a well-established tool in mediastinal staging in lung cancer and gains importance in exploration of non-malignant lymphadenopathy. The aim of this study was to evaluate the role of EBUS-TBNA in suspected non-malignant diseases.  A retrospective, single-center, observation analysis of endobronchial ultrasound bronchoscopy procedures was performed in a university medical center between March 2013 and July 2015. All patients with suspected non-malignant mediastinal lymphadenopathy were included. Cytopathological and microbiological results of EBUS were compared to clinical diagnosis 6 months after procedure and performance of EBUS was contrasted to malignant indications.  During study period, 333 EBUS bronchoscopies in 315 patients with mediastinal lymphadenopathy were performed. 111 out of 315 (35 %) patients had neither primary signs nor history of a malignant disease, categorised as patients with suspected non-malignant disease. 245 lymph nodes were sampled (median size 15 mm [IQR10 - 19]). Preferred station for TBNA was lymph node station 7 (38 %). Cytopathological findings revealed non-specific inflammation (n = 81; 70 %), carcinoma (n = 7; 6 %), epithelioid cell granulomas (n = 20; 17 %). 7 samples (6 %) were non-representative. Microbiologic testing of lymph nodes identified 3 infections (Mycobacteria tuberculosis [n = 2] and Nocardia nova [n = 1]) relevant to antibiotic therapy. Minor adverse events were observed in 9 out of 115 (8 %) patients. Sensitivity of EBUS-TBNA intervention in suspected non-malignant disease was 76 % and specificity 96 %.  EBUS-TBNA revealed a specific cause for suspected non-malignant lymphadenopathy in one-third of cases and was associated with excellent specificity. Predominant specific causes were granuloma, besides from tumor. In 3 patients pathogen could be isolated by TBNA. © Georg Thieme Verlag KG Stuttgart · New York.

Detection of survivin 2α gene expression in thyroid nodules.

PubMed

Kyani, Keyhaneh; Babaei, Esmaeil; Feizi, Mohammad Ali Hosseinpour; Vandghanooni, Somayeh; Montazeri, Vahid; Halimi, Monireh

2014-01-01

Functional studies of the survivin splice variants have been performed almost exclusively in various types of cancer and produced remarkable advances in our understanding of cancer biology and cancer genetics. To observation the expression of survivin 2α in thyroid nodules and estimate its potential as a new molecular marker in thyroid nodules screening and malignant thyroid, as well. We detected the expression of a splice variant of survivin, survivin 2α, in thyroid nodules. Expression of survivin 2α mRNA was evaluated with specific primers by Hemi-Nested RT-PCR in 77 thyroid nodules including malignant and benign tumors, non-tumoral (goiter and thyroiditis) as well as surgical margin, non-neoplastic normal tissues adjacent to the malignant lesions. Our data revealed for the first time the expression of survivin 2α in thyroid nodules. It was detected in 85.7% of non-neoplastic surgical margin tissues, 71.4% of non tumoral, 63.2% of tumoral samples. Also, the expression of survivin 2α in benign tumor samples (64.2%) is more than malignant groups (62.8%). Survivin 2α expression is the highest in non-neoplastic surgical margin rather than other samples and the lowest expression was that of malignancy. According to the results, it can be concluded that survivin 2α protein may be has a vital protective effect throw survivin quenching due to the high expression in normal tissue compared with lesions.

Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma

PubMed Central

Kim, Yongbo; Che, Lihua; Kim, Jeong Beom; Chang, Gyeong Eon; Cheong, Eunji; Kang, Seok-Gu; Ha, Yoon

2017-01-01

Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule–induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs. PMID:29161257

A deep learning framework for supporting the classification of breast lesions in ultrasound images.

PubMed

Han, Seokmin; Kang, Ho-Kyung; Jeong, Ja-Yeon; Park, Moon-Ho; Kim, Wonsik; Bang, Won-Chul; Seong, Yeong-Kyeong

2017-09-15

In this research, we exploited the deep learning framework to differentiate the distinctive types of lesions and nodules in breast acquired with ultrasound imaging. A biopsy-proven benchmarking dataset was built from 5151 patients cases containing a total of 7408 ultrasound breast images, representative of semi-automatically segmented lesions associated with masses. The dataset comprised 4254 benign and 3154 malignant lesions. The developed method includes histogram equalization, image cropping and margin augmentation. The GoogLeNet convolutionary neural network was trained to the database to differentiate benign and malignant tumors. The networks were trained on the data with augmentation and the data without augmentation. Both of them showed an area under the curve of over 0.9. The networks showed an accuracy of about 0.9 (90%), a sensitivity of 0.86 and a specificity of 0.96. Although target regions of interest (ROIs) were selected by radiologists, meaning that radiologists still have to point out the location of the ROI, the classification of malignant lesions showed promising results. If this method is used by radiologists in clinical situations it can classify malignant lesions in a short time and support the diagnosis of radiologists in discriminating malignant lesions. Therefore, the proposed method can work in tandem with human radiologists to improve performance, which is a fundamental purpose of computer-aided diagnosis.

A deep learning framework for supporting the classification of breast lesions in ultrasound images

NASA Astrophysics Data System (ADS)

Han, Seokmin; Kang, Ho-Kyung; Jeong, Ja-Yeon; Park, Moon-Ho; Kim, Wonsik; Bang, Won-Chul; Seong, Yeong-Kyeong

2017-10-01

In this research, we exploited the deep learning framework to differentiate the distinctive types of lesions and nodules in breast acquired with ultrasound imaging. A biopsy-proven benchmarking dataset was built from 5151 patients cases containing a total of 7408 ultrasound breast images, representative of semi-automatically segmented lesions associated with masses. The dataset comprised 4254 benign and 3154 malignant lesions. The developed method includes histogram equalization, image cropping and margin augmentation. The GoogLeNet convolutionary neural network was trained to the database to differentiate benign and malignant tumors. The networks were trained on the data with augmentation and the data without augmentation. Both of them showed an area under the curve of over 0.9. The networks showed an accuracy of about 0.9 (90%), a sensitivity of 0.86 and a specificity of 0.96. Although target regions of interest (ROIs) were selected by radiologists, meaning that radiologists still have to point out the location of the ROI, the classification of malignant lesions showed promising results. If this method is used by radiologists in clinical situations it can classify malignant lesions in a short time and support the diagnosis of radiologists in discriminating malignant lesions. Therefore, the proposed method can work in tandem with human radiologists to improve performance, which is a fundamental purpose of computer-aided diagnosis.

Comb-push ultrasound shear elastography of breast masses: initial results show promise.

PubMed

Denis, Max; Mehrmohammadi, Mohammad; Song, Pengfei; Meixner, Duane D; Fazzio, Robert T; Pruthi, Sandhya; Whaley, Dana H; Chen, Shigao; Fatemi, Mostafa; Alizad, Azra

2015-01-01

To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE) for classification of breast masses. CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF) beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results. Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s) in comparison to benign masses (3.65 ± 1.36 m/s). Therefore, the stiffness of the mass quantified by the Young's modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC), the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC). CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses.

The characteristic ultrasound features of specific types of ovarian pathology (Review)

PubMed Central

SAYASNEH, AHMAD; EKECHI, CHRISTINE; FERRARA, LAURA; KAIJSER, JEROEN; STALDER, CATRIONA; SUR, SHYAMALY; TIMMERMAN, DIRK; BOURNE, TOM

2015-01-01

Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner’s subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images. PMID:25406094

Expression of MUC4 mucin is observed mainly in the intestinal type of intraductal papillary mucinous neoplasm of the pancreas.

PubMed

Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K; Goto, Masamichi; Yonezawa, Suguru

2013-10-01

This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). We performed immunohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of 2 anti-MUC4 monoclonal antibodies, 8G7 and 1G8, in cancer cell lines. Monoclonal antibody 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 messenger RNA. However, IHC signals detected by both monoclonal antibodies were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential.

Imaging in gynaecology: How good are we in identifying endometriomas?

PubMed Central

Van Holsbeke, C.; Van Calster, B.; Guerriero, S.; Savelli, L.; Leone, F.; Fischerova, D; Czekierdowski, A.; Fruscio, R.; Veldman, J.; Van de Putte, G.; Testa, A.C.; Bourne, T.; Valentin, L.; Timmerman, D.

2009-01-01

Aim: To evaluate the performance of subjective evaluation of ultrasound findings (pattern recognition) to discriminate endometriomas from other types of adnexal masses and to compare the demographic and ultrasound characteristics of the true positive cases with those cases that were presumed to be an endometrioma but proved to have a different histology (false positive cases) and the endometriomas missed by pattern recognition (false negative cases). Methods: All patients in the International Ovarian Tumor Analysis (IOTA ) studies were included for analysis. In the IOTA studies, patients with an adnexal mass that were preoperatively examined by expert sonologists following the same standardized ultrasound protocol were prospectively included in 21 international centres. Sensitivity and specificity to discriminate endometriomas from other types of adnexal masses using pattern recognition were calculated. Ultrasound and some demographic variables of the masses presumed to be an endometrioma were analysed (true positives and false positives) and compared with the variables of the endometriomas missed by pattern recognition (false negatives) as well as the true negatives. Results: IOTA phase 1, 1b and 2 included 3511 patients of which 2560 were benign (73%) and 951 malignant (27%). The dataset included 713 endometriomas. Sensitivity and specificity for pattern recognition were 81% (577/713) and 97% (2723/2798). The true positives were more often unilocular with ground glass echogenicity than the masses in any other category. Among the 75 false positive cases, 66 were benign but 9 were malignant (5 borderline tumours, 1 rare primary invasive tumour and 3 endometrioid adenocarcinomas). The presumed diagnosis suggested by the sonologist in case of a missed endometrioma was mostly functional cyst or cystadenoma. Conclusion: Expert sonologists can quite accurately discriminate endometriomas from other types of adnexal masses, but in this dataset 1% of the masses that were classified as endometrioma by pattern recognition proved to be malignancies. PMID:25478066

Pulmonary tumor types induced in Wistar rats of the so-called "19-dust study".

PubMed

Mohr, Ulrich; Ernst, Heinrich; Roller, Markus; Pott, Friedrich

2006-08-01

The incidences of primary lung tumor types histologically diagnosed in 28 groups of Wistar rats of the so-called "19-dust study" are described, the total study having been already presented by Pott and Roller (Carcinogenicity study with nineteen granular dusts in rats. Eur J Oncol, 2005; 10: 249-81). Each exposed group was repeatedly instilled intratracheally with a suspension of one type and dose of 13 non-mining dusts differing in at least one of the following properties: chemical composition, density, specific surface area, and mean particle size. Eleven of the 13 dusts were classified as respirable granular bio-durable particles without known significant specific toxicity (abbreviation of the nine-word definition: GBP). In 579 (58%) lungs of 1002 rats which survived more than 26 weeks after the first instillation of GBP, at least one primary lung tumor type was observed, and in 306 (31%) at least two types. Three benign tumor types were diagnosed in the 579 tumor-bearing rats: bronchiolo-alveolar adenoma in 46%, cystic keratinizing epithelioma in 53%, and non-keratinizing epithelioma in 2.6% of the rats. Two of three malignant tumor types (bronchiolo-alveolar carcinoma and squamous cell carcinoma) occurred in 46% and 31% of the tumor-bearing rats, respectively, and adenosquamous carcinoma was diagnosed in 0.9%. Numerous lungs with a malignant tumor also showed one or more benign tumor types. In addition, single or multiple metastases from primary tumors of other sites (mainly carcinoma of the uterus) were diagnosed in 14% of the 1002 lungs. The proportionate incidences of the four predominantly diagnosed tumor types were compared with three summarized experimental groups which were exposed either to carbon black (two size classes), to titanium dioxide (two size classes), or to the total of the other nine GBP. A significant difference was not detected. The combination of dust volume with particle size correlated best with the carcinogenic effect, in contrast to dust mass and surface area.

Demographics of Head and Neck Cancer Patients: A Single Institution Experience

PubMed Central

Kitanova, Martina; Dzhenkov, Deyan L; Ghenev, Peter; Sapundzhiev, Nikolay

2017-01-01

Introduction Head and neck cancer (HNC) comprises a diverse group of oncological entities, originating from various tissue types and organ localizations, situated in the topographical regions of the head and neck (H&N). This single institution retrospective study was aimed at establishing the HNC patient demographics and categorizing the individual incidence of H&N malignancies, regarding their organ of origin and main histopathological type. Materials and methods All histologically verified cases of HNC from a single tertiary referral center were reviewed in a descriptive retrospective manner. Data sampling period was 47 months. Results Male to female ratio of the registered HNC cases was 3.24:1. The mean age of diagnosis was 63.84 ± 12.65 years, median 65 years. The most common HNC locations include the larynx 30.37% (n = 188), lips and oral cavity 29.08% (n = 180), pharynx 20.03% (n = 124) and salivary glands 10.94% (n = 68), with other locations such as the external nose, nasal cavity and sinuses and auricle and external ear canal harboring a minority of the cases. The main histopathological groups include squamous cell carcinoma 76.74% (n = 475) and adenocarcinoma 6.14% (n = 38), with other malignant entries such as other epithelial malignancies, primary tonsillar, mucosa-associated lymphoid tissue or parenchymal lymphomas, connective tissue neoplasias, neuroendocrine and vascular malignancies diagnosed in a minority of cases. Conclusion Considered to be relatively rare, HNC represents a diverse group of oncological entities with individual and specific demographic characteristics. The reported single institution results appear representative of the national incidence and characteristics of HNC. PMID:28875091

[Herpes simplex virus and malignancies of female genital organs].

PubMed

Cokić-Damjanović, J; Horvat, E; Balog, A

2001-01-01

Primary herpes simplex virus (HSV) infections of female genital tract usually end with remission, while the virus remains in the organism--almost in the sacral ganglion in a latent form, protected from humoral and cellular immunity. Stress induces the virus and the result is recurrent genital infection. Frequent exacerbations damage some parts of vital cellular structures without cytolysis, but stimulate malignant transformations. Vulvar (portio vaginalis uteri) and endometrial tumor tissue samples were analyzed for HSV by direct and indirect fluorescent antibody technique (FAT). Pre and postoperative sera samples were analyzed for presence of anti-HSV antibodies--IgM and IgG by Elisa-Enzygnost method. Acellular filtrates obtained by ultrasonic destruction of malignant tissues were used as inoculum for rabbit corneal scarification. Out of 63 tissue samples, 42 were positive for HSV antigen i.e. 67.3%. According to location 50% of vulvar, 76% PVU and 65% of endometrial tissues were positive. This antigen induces production of virus specific antibodies. Two types of antigens are known: the so-called T-antigen persisting in the cell nucleus and cell-surface antigen--product of the viral genome and can be evidenced by immunofluorescence method. Anti HSV antibodies were present in 63 preoperative serum samples and belonged to IgG group, but not one to IgM, implying a long and chronic course of infection excluding acute primary. Out of 38 postoperative serums the titer of antibodies decreased in 36 evidently, but in two samples remained unchanged. Two samples of endometrial and one from PVU origin contained HSV antigen type one. In the remaining 16 samples HSV 2 antigen was present. Rabbit corneal scarification was the proof of complete infectious virus in malignant tissues. Acellular filtrate of malignant tissues served as inoculum. Corneas of examined rabbits showed a mild inflammation after 24 hours which disappeared in the next 24 hours. We could not isolate the infectious virus by rabbit corneal scarification. Instead of herpetic changes, mild inflammation was evident. This abortive, incomplete symptomatology was probably caused by nonstructural early protein, which is a product of viral genome incorporated in malignant cells. On the basis of our results, we can conclude that HSV can have, beside other factors, a very important, maybe an initial role in development of malignant changes of female genital tract, not only on vulva and PVU, but on endometrium as well. HSV I can cause genital infections and have some role in malignant changes as well as HSV 2. However, complete infective virion couldn't be isolated from malignant tissues.

Solitary fibrous tumour of pleura: CT differentiation of benign and malignant types.

PubMed

Gupta, A; Souza, C A; Sekhon, H S; Gomes, M M; Hare, S S; Agarwal, P P; Kanne, J P; Seely, J M

2017-09-01

To analyse and compare the computed tomography (CT) features of benign and malignant types of histopathologically proven cases of solitary fibrous tumours of pleura (SFTP). Retrospective analysis of preoperative CT images of 28 cases of histopathologically proven and classified SFTP from three participating institutions was performed. Patient demographics and lesion characteristics including size, borders, presence of a pedicle, extension into the fissure, attenuation, enhancement, pleural effusion, and calcifications were recorded and correlated with the final histopathological diagnosis. Type and results of preoperative biopsy were also recorded. Follow-up imaging and the clinical charts were reviewed to identify recurrence. Out of 28 cases (15 women and 13 men), 18 were proven to be benign and 10 were malignant. The mean age of patients was 58.1±15.9 and 66.5±11.8 years (p=0.1564) for benign and malignant tumours, respectively. The median (interquartile range) diameter was 6.05 (3.2-10.9) cm for benign and 15.7 (7.1-17.5) cm for malignant type tumours (p=0.0291). Tumours had lobulate borders in 28% (5/18) of benign cases and in 80% (8/10) of malignant cases (p=0.0163). Extension into adjacent fissure was seen in 22% (4/18) of benign lesions and 40% (4/10) of malignant lesions (p=0.40). A pedicle was present in 17% (3/18) of benign and 10% (1/10) of malignant lesions (p=1). Heterogeneous attenuation was present in 61% (11/18) of benign and 90% (9/10) of malignant lesions (p=0.19). Calcification was present in 17% (3/18) of benign tumours and in 70% (7/10) of malignant tumours (p=0.0113). Pleural effusion was present in 6% (1/18) of benign and 40% (4/10) of malignant lesions (p=0.04). Only 1/13 preoperative fine-needle aspirates yielded diagnosis of SFTP. Preoperative diagnosis of SFTP was made in all cases (11/11) with core biopsies. At follow-up (1-10 years, mean 3 years), local recurrence occurred in 3/6 (50%) patients with malignant SFTP and in none of the 10 patients with benign SFTP. No definite imaging feature to differentiate benign from malignant SFTP was found. Large size, lobulate borders, presence of calcification, and ipsilateral pleural effusion were the only CT features predictive of malignancy. In suspected cases, core biopsies should be performed rather than fine-needle aspiration. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Hepatitis C: a possible etiology for cryoglobulinaemia type II.

PubMed Central

Pechère-Bertschi, A; Perrin, L; de Saussure, P; Widmann, J J; Giostra, E; Schifferli, J A

1992-01-01

Out of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa/IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II. PMID:1381302

Prescriptions of traditional Chinese medicine are specific to cancer types and adjustable to temperature changes.

PubMed

Chiu, Pei-Hsun; Hsieh, Hsin-Ying; Wang, Sun-Chong

2012-01-01

Targeted cancer therapies, with specific molecular targets, ameliorate the side effect issue of radiation and chemotherapy and also point to the development of personalized medicine. Combination of drugs targeting multiple pathways of carcinogenesis is potentially more fruitful. Traditional Chinese medicine (TCM) has been tailoring herbal mixtures for individualized healthcare for two thousand years. A systematic study of the patterns of TCM formulas and herbs prescribed to cancers is valuable. We analysed a total of 187,230 TCM prescriptions to 30 types of cancer in Taiwan in 2007, a year's worth of collection from the National Health Insurance reimbursement database (Taiwan). We found that a TCM cancer prescription consists on average of two formulas and four herbs. We show that the percentage weights of TCM formulas and herbs in a TCM prescription follow Zipf's law with an exponent around 0.6. TCM prescriptions to benign neoplasms have a larger Zipf's exponent than those to malignant cancers. Furthermore, we show that TCM prescriptions, via weighted combination of formulas and herbs, are specific to not only the malignancy of neoplasms but also the sites of origins of malignant cancers. From the effects of formulas and natures of herbs that were heavily prescribed to cancers, that cancers are a 'warm and stagnant' syndrome in TCM can be proposed, suggesting anti-inflammatory regimens for better prevention and treatment of cancers. We show that TCM incorporated relevant formulas to the prescriptions to cancer patients with a secondary morbidity. We compared TCM prescriptions made in different seasons and identified temperatures as the environmental factor that correlates with changes in TCM prescriptions in Taiwan. Lung cancer patients were among the patients whose prescriptions were adjusted when temperatures drop. The findings of our study provide insight to TCM cancer treatment, helping dialogue between modern western medicine and TCM for better cancer care.

Prescriptions of Traditional Chinese Medicine Are Specific to Cancer Types and Adjustable to Temperature Changes

PubMed Central

Chiu, Pei-Hsun; Hsieh, Hsin-Ying; Wang, Sun-Chong

2012-01-01

Targeted cancer therapies, with specific molecular targets, ameliorate the side effect issue of radiation and chemotherapy and also point to the development of personalized medicine. Combination of drugs targeting multiple pathways of carcinogenesis is potentially more fruitful. Traditional Chinese medicine (TCM) has been tailoring herbal mixtures for individualized healthcare for two thousand years. A systematic study of the patterns of TCM formulas and herbs prescribed to cancers is valuable. We analysed a total of 187,230 TCM prescriptions to 30 types of cancer in Taiwan in 2007, a year's worth of collection from the National Health Insurance reimbursement database (Taiwan). We found that a TCM cancer prescription consists on average of two formulas and four herbs. We show that the percentage weights of TCM formulas and herbs in a TCM prescription follow Zipf's law with an exponent around 0.6. TCM prescriptions to benign neoplasms have a larger Zipf's exponent than those to malignant cancers. Furthermore, we show that TCM prescriptions, via weighted combination of formulas and herbs, are specific to not only the malignancy of neoplasms but also the sites of origins of malignant cancers. From the effects of formulas and natures of herbs that were heavily prescribed to cancers, that cancers are a ‘warm and stagnant’ syndrome in TCM can be proposed, suggesting anti-inflammatory regimens for better prevention and treatment of cancers. We show that TCM incorporated relevant formulas to the prescriptions to cancer patients with a secondary morbidity. We compared TCM prescriptions made in different seasons and identified temperatures as the environmental factor that correlates with changes in TCM prescriptions in Taiwan. Lung cancer patients were among the patients whose prescriptions were adjusted when temperatures drop. The findings of our study provide insight to TCM cancer treatment, helping dialogue between modern western medicine and TCM for better cancer care. PMID:22359613

What is the best way to diagnose and stage malignant pleural mesothelioma?

PubMed

Zahid, Imran; Sharif, Sumera; Routledge, Tom; Scarci, Marco

2011-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was which diagnostic modality [computed tomography (CT), positron emission tomography (PET), combination PET/CT and magnetic resonance imaging (MRI)] provides the best diagnostic and staging information in patients with malignant pleural mesothelioma (MPM). Overall, 61 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that fluorodeoxyglucose (FDG)-PET is superior to MRI and CT but inferior to PET-CT, in terms of diagnostic specificity, sensitivity and staging of MPM. Four studies reported outcomes using FDG-PET to diagnose MPM. PET diagnosed MPM with high sensitivity (92%) and specificity (87.9%). Mean standardised uptake value (SUV) was higher in malignant than benign disease (4.91 vs. 1.41, P<0.0001). Lymph node metastases were detected with higher accuracy (80% vs. 66.7%) compared to extrathoracic disease. Three studies assessed the utility of PET-CT to diagnose MPM. Mean SUV was higher in malignant than benign disease (6.5 vs. 0.8, P<0.001). MPM was diagnosed with high sensitivity (88.2%), specificity (92.9%) and accuracy (88.9%). PET-CT had low sensitivity for stage N2 (38%) and T4 (67%) disease. CT-guided needle biopsy definitively diagnosed MPM after just one biopsy (100% vs. 9%) much more often than a 'blind' approach. CT had a lower success rate (92% vs. 100%) than thoracoscopic pleural biopsy but was equivalent to MRI in terms of detection of lymph node metastases (P=0.85) and visceral pleural tumour (P=0.64). CT had a lower specificity for stage II (77% vs. 100%, P<0.01) and stage III (75% vs. 100%, P<0.01) disease compared to PET-CT. Overall, the high specificity and sensitivity rates seen with open pleural biopsy make it a superior diagnostic modality to CT, MRI or PET for diagnosing patients with MPM.

Women with Gynecologic Malignancies Have a Greater Incidence of Suicide than Women with Other Cancer Types

ERIC Educational Resources Information Center

Ward, Kristy K.; Roncancio, Angelica M.; Plaxe, Steven C.

2013-01-01

To evaluate risk of suicide of women with invasive gynecologic malignancies, the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (1973-2007) was queried. Suicide per 100,000 women with gynecologic malignancies was compared with that of women with other malignancies; suicide was 30% more likely in those with…

Differential Diagnosis of Benign and Malignant Intraductal Papillary Mucinous Tumors of the Pancreas: MR Cholangiopancreatography and MR Angiography

PubMed Central

Choi, Byung Se; Kim, Ah Young; Kim, Kyoung Won; Park, Sung Won; Kim, Pyo Nyun; Ha, Hyun Kwon; Lee, Moon-Gyu; Kim, Song Cheol

2003-01-01

Objective To compare the usefulness of magnetic resonance cholangiopancreatography (MRCP) and MR angiography (MRA) in differentiating malignant from benign intraductal papillary mucinous tumors of the pancreas (IPMTs), and to determine the findings which suggest malignancy. Materials and Methods During a 6-year period, 46 patients with IPMT underwent MRCP. Morphologically, tumor type was classified as main duct, branch duct, or combined. The diameter of the main pancreatic duct (MPD), the extent of the dilated MPD, and the location and size of the cystic lesion, septum, and communicating channel were assessed. For all types of IPMTs, enhanced mural nodules and portal vein narrowing were evaluated at MRA. Results Combined-type IPMTs were more frequently malignant (78%) than benign (42%) (p < 0.05). Compared with benign lesions, malignant lesions were larger, and the caliber of the communicating channel was also larger (p < 0.05). Their dilated MPD was more extensive and of greater diameter (p < 0.05), and the presence of mural nodules was more frequent (p < 0.001). Conclusion Combined MRCP and MRA might be useful for the differential diagnosis of malignant and benign IPMTs of the pancreas. PMID:14530644

Malignant Mesothelioma Treatment (PDQ®)—Patient Version

Cancer.gov

Treatment for malignant mesothelioma may include surgery, radiation therapy, and chemotherapy, as well as targeted therapy. The type of treatment you receive depends on where the cancer is found and at what stage. Find out about treatment options for malignant mesothelioma.

The risk of cancer in patients with congenital heart disease: a nationwide population-based cohort study in Taiwan.

PubMed

Lee, Yu-Sheng; Chen, Yung-Tai; Jeng, Mei-Jy; Tsao, Pei-Chen; Yen, Hsiu-Ju; Lee, Pi-Chang; Li, Szu-Yuan; Liu, Chia-Jen; Chen, Tzeng-Ji; Chou, Pesus; Soong, Wen-Jue

2015-01-01

The relationship between congenital heart disease (CHD) and malignancies has not been determined. This study aimed to explore the association of CHD with malignancies and examine the risk factors for the development of cancer after a diagnosis of CHD. This nationwide, population-based cohort study on cancer risk evaluated 31,961 patients with newly diagnosed CHD using the Taiwan National Health Insurance Research Database (NHIRD) between 1998 and 2006. The standardized incidence ratios (SIRs) for all and specific cancer types were analyzed, while the Cox proportional hazard model was used to evaluate risk factors of cancer occurrence. Among patients with newly diagnosed CHD regardless of ages, 187 (0.6%) subsequently developed cancers after a diagnosis of CHD. Patients with CHD had increased risk of cancer (SIR, 1.45; 95% CI, 1.25-1.67), as well as significantly elevated risks of hematologic (SIR, 4.04; 95% CI, 2.76-5.70), central nervous system (CNS) (SIR, 3.51; 95% CI, 1.92-5.89), and head and neck (SIR, 1.81; 95% CI, 1.03-2.94) malignancies. Age (HR, 1.06; 95% CI, 1.05-1.06) and co-morbid chronic liver disease (HR, 1.91; 95% CI, 1.27-2.87) were independent risk factors for cancer occurrence among CHD patients. Patients with CHD have significantly increased cancer risk, particularly hematologic, CNS, and head and neck malignancies. Physicians who care for patients with CHD should be aware of their predisposition to malignancy after the diagnosis of CHD. Further studies are warranted to clarify the association between CHD and malignancies.

Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues.

PubMed

Laskin, William B; Miettinen, Markku

2002-04-01

Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).

Periocular Skin Cancer in Solid Organ Transplant Recipients.

PubMed

Perry, Julian D; Polito, Sara C; Chundury, Rao V; Singh, Arun D; Fritz, Michael A; Vidimos, Allison T; Gastman, Brian R; Koyfman, Shlomo A

2016-01-01

To determine the proportion of solid organ transplant recipients developing periocular nonmelanoma skin cancer and to describe the morbidity of these cancers in transplant recipients. Cohort study. Consecutive patients undergoing solid organ transplantation at the Cleveland Clinic between 1990 and 2008. The charts of all patients receiving a solid organ transplant from 1990-2008 evaluated in the dermatology department for a subsequent biopsy-proven head and neck malignancy through April 2015 were reviewed. Patients with a periocular region nonmelanoma skin cancer (NMSC) or a nonperiocular NMSC causing a complication requiring eyelid surgery were included. Charts were reviewed for demographic data; transplant date, type, and source; immunosuppressive agents received at diagnosis; and type of NMSC, number of nonperiocular NMSCs, ophthalmologic findings, and periocular sequelae after the repair. Primary outcome measures included the type, location, final defect size, tumor-node-metastasis classification, presence of perineural invasion, and reconstruction technique(s) used for each periocular NMSC. Secondary outcome measures included the type and treatment of ocular sequelae due to nonperiocular facial NMSC. A total of 3489 patients underwent solid organ transplantation between 1990 and 2008. Of these, 420 patients were evaluated in the dermatology clinic for biopsy-proven NMSC of the head and neck during the study period, and 11 patients (15 malignancies) met inclusion criteria. Nine patients developed 12 periocular malignancies and 3 patients required eyelid surgery for facial malignancies outside the periocular zone. All 11 patients developed a squamous cell carcinoma (14 malignancies), and 1 patient (1 malignancy) also developed a periocular basal cell carcinoma. There was orbital invasion in 4 cases and paranasal and/or cavernous sinus invasion in 3 cases. Two patients underwent exenteration. Seven cases required reconstruction with a free flap or graft. Periocular sequelae included lower eyelid ectropion (6 malignancies), dry eye and/or exposure symptoms (8 malignancies), unilateral vision loss (3 malignancies), and facial nerve paresis (5 malignancies). Squamous cell carcinoma affecting the periocular region represents a risk of solid organ transplantation and may produce significant ocular morbidity, including the need for major eyelid reconstruction, globe loss, and disfiguring surgery. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Anti-ALK Antibodies in Patients with ALK-Positive Malignancies Not Expressing NPM-ALK

PubMed Central

Damm-Welk, Christine; Siddiqi, Faraz; Fischer, Matthias; Hero, Barbara; Narayanan, Vignesh; Camidge, David Ross; Harris, Michael; Burke, Amos; Lehrnbecher, Thomas; Pulford, Karen; Oschlies, Ilske; Siebert, Reiner; Turner, Suzanne; Woessmann, Wilhelm

2016-01-01

Patients with Nucleophosmin (NPM)- Anaplastic Lymphoma Kinase (ALK) fusion positive Anaplastic Large Cell Lymphoma produce autoantibodies against ALK indicative of an immune response against epitopes of the chimeric fusion protein. We asked whether ALK-expression in other malignancies induces specific antibodies. Antibodies against ALK were detected in sera of one of 50 analysed ALK-expressing neuroblastoma patients, 13 of 21 ALK positive non-small cell lung carcinoma (NSCLC) patients, 13 of 22 ALK translocation-positive, but NPM-ALK-negative lymphoma patients and one of one ALK-positive rhabdomyosarcoma patient, but not in 20 healthy adults. These data suggest that boosting a pre-existent anti-ALK immune response may be more feasible for patients with ALK-positive NSCLC, lymphomas and rhabdomyosarcomas than for tumours expressing wild-type ALK. PMID:27471553

Multimodal diagnosis and visualisation of oncologic pathologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zakharov, V P; Bratchenko, I A; Myakinin, O O

2014-08-31

The combined application of optical coherence tomography, Raman and autofluorescence spectroscopy of biotissues for the analysis of human malignant neoplasms is demonstrated. Rapid investigation of vast biotissue regions (at the scale of entire organs) is possible using the autofluorescence response. After selection of possible zones of pathologies one can visualise the neoplasm topology in the zone of interest with micron precision by using optical coherence tomography. In the case of suspecting the malignancy the analysis of the biotissue Raman spectrum is carried out that allows identification of the neoplasm type with the sensitivity and specificity ∼85%. An experimental scheme ismore » proposed with the combined use of the abovementioned methods, which is a prototype of the medical system for complex analysis of neoplasms. (laser biophotonics)« less

Is Serum Prostate-specific Antigen a Diagnostic Marker for Benign and Malignant Breast Tumors in Women.

PubMed

Razavi, Seyed Hasan Emami; Ghajarzadeh, Mahsa; Abdollahi, Alireza; Taran, Ludmila; Shoar, Saeed; Omranipour, Ramesh

2015-06-01

Breast cancer is the most common cancer in women. Prostrate-specific antigen (PSA) is a marker of prostate gland malignancy which has been considered in cases with breast cancer in recent years. The goal of this study was to determine total and free PSA levels in cases with malignant and benign breast lesions. Ninety women with histological proved malignant breast masses and 90 with benign breast masses were enrolled. Total and free PSA levels along with histological grade and conditions of vascular and perinural invasion, status of hormonal tumor receptors, immune-histo-chemistry markers recorded for all cases. Total and free PSA levels were assessed after treatment in cases with malignant masses. Total and free PSA levels were significantly higher in cases with malignant masses. The best cut off point for total PSA to differentiate benign and malignant masses was 0.31 and the best cut off point for free PSA to differentiate benign and malignant masses was 0.19. After treatment, mean free PSA level was significantly lower than free PSA before treatment (0.23 vs 0.3, p<0.001). Serum PSA level could be applied for differentiating benign and malignant breast masses.

Perspectives on testicular germ cell neoplasms.

PubMed

Cheng, Liang; Lyu, Bingjian; Roth, Lawrence M

2017-01-01

Our knowledge of testicular germ cell neoplasms has progressed in the last few decades due to the description of germ cell neoplasia in situ (GCNIS) and a variety of specific forms of intratubular germ cell neoplasia, the discovery of isochromosome 12p and its importance in the development of invasiveness in germ cell tumors (GCTs), the identification of specific transcription factors for GCTs, and the recognition that a teratomatous component in mixed GCT represents terminal differentiation. Isochromosome 12p and 12p overrepresentation, collectively referred to as 12p amplification, are fundamental abnormalities that account for many types of malignant GCTs of the testis. Embryonal carcinoma is common in the testis but rare in the ovary, whereas the converse is true for mature cystic teratoma. Spermatocytic tumor occurs only in the testis; it has not been described in the ovary or extragonadal sites. The origin of ovarian mature cystic teratoma is similar to that of prepubertal-type testicular teratoma and dermoid cyst at any age in that it arises from a nontransformed germ cell, whereas postpubertal-type testicular teratoma arises from a malignant germ cell, most commonly through the intermediary of GCNIS. Somatic neoplasms, often referred to as monodermal teratomas, arise not infrequently from mature cystic teratoma of the ovary, whereas such neoplasms are rare in testicular teratoma with the exception of carcinoid. Integration of classical morphologic observations and emerging novel molecular studies will result in better understanding of the pathogenesis of GCTs and will optimize patient therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort.

PubMed

Bruyand, Mathias; Thiébaut, Rodolphe; Lawson-Ayayi, Sylvie; Joly, Pierre; Sasco, Annie Jeanne; Mercié, Patrick; Pellegrin, Jean Luc; Neau, Didier; Dabis, François; Morlat, Philippe; Chêne, Geneviève; Bonnet, Fabrice

2009-10-01

Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies. Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry. The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P<.001] and 3.30 [P<.001], respectively) and (2) both longer and current exposure to a CD4(+) cell count <200 cells/mm(3) (HR, 1.36 per year [P<.001] and 6.33 [P<.001], respectively). A higher incidence of non-AIDS-defining malignancies (144 cases) was independently associated with longer and current exposure to a CD4(+) cell count <500 cells/mm(3) (HR, 1.13 per year [P=.01] and 2.07 [P<.001], respectively) and male sex (HR, 1.69; P=.02) but not with plasma HIV RNA level (P=.49 and P=.10 for cumulative and current exposures, respectively). Uncontrolled plasma HIV RNA level was independently associated with a higher likelihood of developing AIDS-defining malignancies, whereas immunosuppression was associated with a higher risk of developing any type of malignancies. Antiretroviral treatment should aim at reaching and maintaining a CD4(+) count >500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.

ADC as a useful diagnostic tool for differentiating benign and malignant vertebral bone marrow lesions and compression fractures: a systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Yun, Seong Jong; Jin, Wook; Lee, Sun Hwa; Park, So Young; Ryu, Chang-Woo

2018-07-01

To assess the sensitivity and specificity of quantitative assessment of the apparent diffusion coefficient (ADC) for differentiating benign and malignant vertebral bone marrow lesions (BMLs) and compression fractures (CFs) METHODS: An electronic literature search of MEDLINE and EMBASE was conducted. Bivariate modelling and hierarchical summary receiver operating characteristic modelling were performed to evaluate the diagnostic performance of ADC for differentiating vertebral BMLs. Subgroup analysis was performed for differentiating benign and malignant vertebral CFs. Meta-regression analyses according to subject, study and diffusion-weighted imaging (DWI) characteristics were performed. Twelve eligible studies (748 lesions, 661 patients) were included. The ADC exhibited a pooled sensitivity of 0.89 (95% confidence interval [CI] 0.80-0.94) and a pooled specificity of 0.87 (95% CI 0.78-0.93) for differentiating benign and malignant vertebral BMLs. In addition, the pooled sensitivity and specificity for differentiating benign and malignant CFs were 0.92 (95% CI 0.82-0.97) and 0.91 (95% CI 0.87-0.94), respectively. In the meta-regression analysis, the DWI slice thickness was a significant factor affecting heterogeneity (p < 0.01); thinner slice thickness (< 5 mm) showed higher specificity (95%) than thicker slice thickness (81%). Quantitative assessment of ADC is a useful diagnostic tool for differentiating benign and malignant vertebral BMLs and CFs. • Quantitative assessment of ADC is useful in differentiating vertebral BMLs. • Quantitative ADC assessment for BMLs had sensitivity of 89%, specificity of 87%. • Quantitative ADC assessment for CFs had sensitivity of 92%, specificity of 91%. • The specificity is highest (95%) with thinner (< 5 mm) DWI slice thickness.

The association between thyroid malignancy and chronic lymphocytic thyroiditis: should it alter the surgical approach?

PubMed

Büyükaşık, Oktay; Hasdemir, Ahmet Oğuz; Yalçın, Erol; Celep, Bahadır; Sengül, Serkan; Yandakçı, Kemal; Tunç, Gündüz; Küçükpınar, Tevfik; Alkoy, Seval; Cöl, Cavit

2011-01-01

The relation between thyroid neoplasms and chronic lymphocytic thyroiditis (CLT) is controversial. While it is accepted that focal lymphocytic thyroiditis develops secondarily to malignancy, it is not clear whether diffuse lymphocytic thyroiditis has a tendency to develop into thyroid cancer. The aim of this study was to investigate the relation between CLT and malignant tumours of the thyroid and evaluate the surgical approach to CLT cases. In this study, 917 patients operated on for thyroid diseases were investigated retrospectively. Seventy-seven (8.4%) patients histopathologically diagnosed as having CLT (either non-specific or Hashimoto's thyroiditis) were investigated for any concurrent malignant neoplasm. Fifteen patients in whom CLT and thyroid malignancy were coexisting were included in the study. In the pathological evaluation of 917 cases, malignancy in the thyroid was found in 97 (10.6%) cases. Seventy-seven cases were categorised as CLT. Of these 77, 16 (20.8%) were Hashimoto's thyroiditis (specific CLT) and the other 61 (79.2%) were non-specific CLT. In 15 cases, thyroid malignancy was found to be concurrent with CLT. Of the malignities, nine (60%) were papillary carcinoma, three (20%) medullar carcinoma, one (6.6%) follicular carcinoma, one (6.6%) Hurthle cell carcinoma, and one (6.6%) lymphoma. In our series, the rate of the development of malignancy against the background of CLT was 19.48%, while the rate in the groups without CLT was 9.76%, with a statistically significant difference between the groups (p = 0.008). CLT cases should be evaluated more carefully in terms of malignancy. If a nodule is detected on thyroiditis, the minimal surgical intervention should be lobectomy. Total thyroidectomy should be considered as preferable to subtotal thyroidectomy because of its many advantages such as controlling thyroiditis, removing the probability of reoperation, and hormonal stability.

Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

PubMed

Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

2014-12-01

Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

The development of a malignant tumor is due to a desperate asexual self-cloning process in which cancer stem cells develop the ability to mimic the genetic program of germline cells

PubMed Central

Vinnitsky, Vladimir

2014-01-01

To date there is no explanation why the development of almost all types of solid tumors occurs sharing a similar scenario: (1) creation of a cancer stem cell (CSC), (2) CSC multiplication and formation of a multicellular tumor spheroid (TS), (3) vascularization of the TS and its transformation into a vascularized primary tumor, (4) metastatic spreading of CSCs, (5) formation of a metastatic TSs and its transformation into metastatic tumors, and (6) potentially endless repetition of this cycle of events. The above gaps in our knowledge are related to the biology of cancer and specifically to tumorigenesis, which covers the process from the creation of a CSC to the formation of a malignant tumor and the development of metastases. My Oncogerminative Theory of Tumorigenesis considers tumor formation as a dynamic self-organizing process that mimics a self-organizing process of early embryo development. In the initial step in that process, gene mutations combined with epigenetic dysregulation cause somatic cells to be reprogrammed into CSCs, which are immortal pseudo-germline cells. Mimicking the behavior of fertilized germline cells, the CSC achieves immortality by passing through the stages of its life-cycle and developing into a pseudo-blastula-stage embryo, which manifests in the body as a malignant tumor. In this view, the development of a malignant tumor from a CSC is a phenomenon of developmental biology, which we named a desperate asexual self-cloning event. The theory explains seven core characteristics of malignant tumors: (1) CSC immortality, (2) multistep development of a malignant tumor from a single CSC, (3) heterogeneity of malignant tumor cell populations, (4) metastatic spread of CSCs, (5) invasive growth, (6) malignant progression, and (7) selective immune tolerance toward cancer cells. The Oncogerminative Theory of Tumorigenesis suggests new avenues for discovery of revolutionary therapies to treat, prevent, and eradicate cancer. PMID:28232878

Fine-needle aspiration cytology of postirradiation sarcomas, including angiosarcoma, with immunocytochemical confirmation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silverman, J.F.; Lannin, D.L.; Larkin, E.W.

1989-01-01

Postirradiation sarcomas are an unusual but well-recognized late effect of cancer therapy. In this article, a fine-needle aspiration (FNA) series of four cases is presented. There were three female patients and one male patient, with an age range of 28-55 yr (mean, 41). Two of the patients were irradiated for uterine cervical carcinoma while the other two received irradiation for malignant lymphoma. The time interval to the development of the postirradiation sarcoma ranged from 10 to greater than 20 yr. There were a postirradiation synovial sarcoma of the buttock region, malignant fibrous histiocytoma of the bone (femur), and rhabdomyosarcoma andmore » angiosarcoma of the retroperitoneum. A spectrum of cytologic findings was encountered, reflecting the specific types of sarcomas. Immunocytochemical studies performed on the aspirated material from the angiosarcoma demonstrated the utility of immunoperoxidase stains for ULEX europaeus agglutinin-1 (UEA-1) and, to a lesser degree, factor VIII-related antigen antibody, confirming the vascular nature of this malignancy. The FNA findings from all four cases demonstrated cytologic features that allowed recognition of this unusual complication of irradiation treatment. This article confirms the utility of FNA cytology in following patients with previous malignancies and differentiating a postirradiation sarcoma from recurrent carcinoma.« less

Cutaneous amelanotic signet-ring cell malignant melanoma with interspersed myofibroblastic differentiation in a young cat.

PubMed

Hirz, Manuela; Herden, Christiane

2016-07-01

The diagnosis of malignant melanoma can be difficult because these tumors can be amelanotic and may contain diverse variants and divergent differentiations, of which the signet-ring cell subtype is very rare and has only been described in humans, dogs, cats, and a hamster. We describe herein histopathologic and immunohistochemical approaches taken to diagnose a case of signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. A tumor within the abdominal skin of a 2-year-old cat was composed of signet-ring cells and irregularly interwoven streams of spindle cells. Both neoplastic cell types were periodic-acid-Schiff, Fontana, and Sudan black B negative. Signet-ring cells strongly expressed vimentin and S100 protein. Spindle cells strongly expressed vimentin and smooth muscle actin; some cells expressed S100, moderately neuron-specific enolase, and others variably actin and desmin. A few round cells expressed melan A, and a few plump spindle cells expressed melan A and PNL2, confirming the diagnosis of amelanotic signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. Differential diagnoses were excluded, including signet-ring cell forms of adenocarcinomas, lymphomas, liposarcomas, leiomyosarcomas, squamous cell carcinomas, basal cell carcinomas, and adnexal tumors. © 2016 The Author(s).

[(99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and malignant lung tumors].

PubMed

Liu, Haiyan; Li, Sijin; Yang, Suyun; Wu, Zhifang

2014-01-01

To investigate the value of (99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and malignant lung tumors. CT scan, early (20 to 30 min) and delayed (2 h) imaging of NOET SPECT were performed on 61 patients suspected of lung lesions before operation. The results were compared with the pathological findings. All cases were not treated with radiotherapy, chemotherapy or surgery before checks. Moreover, all patients had pathological diagnosis. To determine the value in differential diagnosis of tumors by analyzing the tumor uptake and excretion of (99)Tc(m)N-NOET, and the results were compared with that of CT. The value of early T/N ratio (ER) in the malignant (G1) and benign (G2) groups was 1.25 ± 0.15 and 1.09 ± 0.11 (P < 0.001), respectively, and delayed T/N ratio (DR) was 1.40 ± 0.17 and 1.18 ± 0.21 (P < 0.001). The retention index (RI) of groups G1 was (12.22 ± 6.38)% and group G2 was (8.3 ± 10.91)%, with a non-significant difference between them (P > 0.05). The ER, DR and RI of NOET SPECT in the malignant patients were not significantly correlated with TNM staging, pathological types, tumor diameter, cavity in the lung tumor mass, history of smoking, tumor size and patient gender (P > 0.05). The sensitivity of NOET dual-phase SPECT and CT in the differential diagnosis of benign and malignant lung tumors was 94.1% vs. 90.2%, specificity was 70.0% vs. 80.0% , positive predictive value (PPV) was 94.1% vs. 95.8%, negative predictive value (NPV) was 70.0% vs. 61.5 %, and accuracy was 90.2%. vs. 88.5% (P > 0.05 for all). (99)Tc(m)N- NOET dual-phase SPECT could be used in differential diagnosis of benign and malignant lung tumors, with no significant differences compared with the efficacy of CT imaging. The semiquantitative indexes (ER, DR and RI) of NOET SPECT can also be used in differential diagnosis of benign and malignant lung tumors, and are not significantly correlated with TNM staging, pathological types, tumor diameter, cavity of the lung tumor mass, history of smoking, tumor size and patient gender.

Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2015-04-01

AWARD NUMBER: W81XWH-14-1-0073 TITLE: Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath...Annual 3. DATES COVERED 1 Apr 2014 - 31 Mar 2015 4. TITLE AND SUBTITLE Prevention and Treatment of Neurofibromatosis Type 1- 5a. CONTRACT NUMBER...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is

NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies.

PubMed

Ponti, Giovanni; Martorana, Davide; Pellacani, Giovanni; Ruini, Cristel; Loschi, Pietro; Baccarani, Alessio; De Santis, Giorgio; Pollio, Annamaria; Neri, Tauro Maria; Mandel, Victor Desmond; Maiorana, Antonio; Maccio, Livia; Maccaferri, Monia; Tomasi, Aldo

2014-06-01

Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Differentiation of benign from malignant liver masses with Acoustic Radiation Force Impulse technique.

PubMed

Yu, Hojun; Wilson, Stephanie R

2011-12-01

The objective of the study was to determine the performance of Acoustic Radiation Force Impulse (ARFI) imaging to differentiate benign from malignant liver masses, both of hepatocellular origin and metastases, by quantification of their stiffness. This study has institutional review board approval and informed consent. Eighty-nine patients (42 female and 47 male patients) with 105 liver masses had ARFI evaluation on ultrasound, S2000 (Siemens, Mountain View, Calif). Mean age of the patients was 53.67 years (range, 27-83 years). Mean diameter of the masses was 2.77 cm (range, 1.0-13.0 cm). Final diagnoses, confirmed by imaging on contrast-enhanced computed tomography, magnetic resonance, or ultrasound or biopsy, include hepatocellular carcinoma (n = 28), metastasis (n = 13), hemangioma (n = 35), focal nodular hyperplasia (n = 15), focal fat sparing (n = 8), focal fat deposit (n = 4), and adenoma (n = 2). Receiver operating characteristic analysis was performed to evaluate the diagnostic accuracy of the ARFI measurement and to extract the optimal cutoff values in the differentiation of benign from malignant disease. Acoustic Radiation Force Impulse values showed a statistically significant difference between benign (1.73 [SD, 0.8] m/sec) and malignant masses (2.57 [SD, 1.01] m/sec) (P < 0.001). However, the area under the receiver operating characteristic curve was 0.744, suggesting only fair accuracy. For differentiation of malignant from benign masses, the sensitivity, specificity, positive predictive value, and negative predictive value were 68% (28/41), 69% (44/64), 58% (28/48), and 77% (44/57), respectively, when 1.9 m/sec was chosen as a cutoff value, reflective of a wide variation of ARFI values in each diagnosis. For differentiation of metastasis from benign masses, sensitivity, specificity, positive predictive value, and NPV were 69% (9/13), 89% (57/64), 56% (9/16), and 93% (57/61), respectively, when 2.72 m/sec was chosen as a cutoff value. Acoustic Radiation Force Impulse measurement may be helpful to differentiate benign masses from metastases, in particular. Otherwise, ARFI measurements alone do not differentiate benign and malignant masses because of variations in stiffness of all types of masses.

Impact of Risk Factors for Specific Causes of Death in the First and Subsequent Years of Antiretroviral Therapy Among HIV-Infected Patients

PubMed Central

Ingle, Suzanne M.; May, Margaret T.; Gill, M. John; Mugavero, Michael J.; Lewden, Charlotte; Abgrall, Sophie; Fätkenheuer, Gerd; Reiss, Peter; Saag, Michael S.; Manzardo, Christian; Grabar, Sophie; Bruyand, Mathias; Moore, David; Mocroft, Amanda; Sterling, Timothy R.; D'Arminio Monforte, Antonella; Hernando, Victoria; Teira, Ramon; Guest, Jodie; Cavassini, Matthias; Crane, Heidi M.; Sterne, Jonathan A. C.

2014-01-01

Background. Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). Methods. Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART. Results. A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0–1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2–52.7] during the first year of ART and 9.1 [95% CI, 5.8–14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. Conclusions. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management. PMID:24771333

Cancer treatment by photodynamic therapy combined with NK-cell-line-based adoptive immunotherapy

NASA Astrophysics Data System (ADS)

Korbelik, Mladen; Sun, Jinghai

1998-05-01

Treatment of solid cancers by photodynamic therapy (PDT) triggers a strong acute inflammatory reaction localized to the illuminated malignant tissue. This event is regulated by a massive release of various potent mediators which have a profound effect not only on local host cell populations, but also attract different types of immune cells to the treated tumor. Phagocytosis of PDT-damaged cancerous cells by antigen presenting cells, such as activated tumor associated macrophages, enables the recognition of even poorly immunogenic tumors by specific immune effector cells and the generation of immune memory populations. Because of its inflammatory/immune character, PDT is exceptionally responsive to adjuvant treatments with various types of immunotherapy. Combining PDT with immuneactivators, such as cytokines or other specific or non-specific immune agents, rendered marked improvements in tumor cures with various cancer models. Another clinically attractive strategy is adoptive immunotherapy, and the prospects of its use in conjunction with PDT are outlined.

The diagnostic performance of shear wave elastography for malignant cervical lymph nodes: A systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Choi, Young Jun; Baek, Jung Hwan; Lee, Jeong Hyun

2017-01-01

To evaluate the diagnostic performance of shear wave elastography for malignant cervical lymph nodes. We searched the Ovid-MEDLINE and EMBASE databases for published studies regarding the use of shear wave elastography for diagnosing malignant cervical lymph nodes. The diagnostic performance of shear wave elastography was assessed using bivariate modelling and hierarchical summary receiver operating characteristic modelling. Meta-regression analysis and subgroup analysis according to acoustic radiation force impulse imaging (ARFI) and Supersonic shear imaging (SSI) were also performed. Eight eligible studies which included a total sample size of 481 patients with 647 cervical lymph nodes, were included. Shear wave elastography showed a summary sensitivity of 81 % (95 % CI: 72-88 %) and specificity of 85 % (95 % CI: 70-93 %). The results of meta-regression analysis revealed that the prevalence of malignant lymph nodes was a significant factor affecting study heterogeneity (p < .01). According to the subgroup analysis, the summary estimates of the sensitivity and specificity did not differ between ARFI and SSI (p = .93). Shear wave elastography is an acceptable imaging modality for diagnosing malignant cervical lymph nodes. We believe that both ARFI and SSI may have a complementary role for diagnosing malignant cervical lymph nodes. • Shear wave elastography is acceptable modality for diagnosing malignant cervical lymph nodes. • Shear wave elastography demonstrated summary sensitivity of 81 % and specificity of 85 %. • ARFI and SSI have complementary roles for diagnosing malignant cervical lymph nodes.

Implementation of mechanism of action biology-driven early drug development for children with cancer.

PubMed

Pearson, Andrew D J; Herold, Ralf; Rousseau, Raphaël; Copland, Chris; Bradley-Garelik, Brigid; Binner, Debbie; Capdeville, Renaud; Caron, Hubert; Carleer, Jacqueline; Chesler, Louis; Geoerger, Birgit; Kearns, Pamela; Marshall, Lynley V; Pfister, Stefan M; Schleiermacher, Gudrun; Skolnik, Jeffrey; Spadoni, Cesare; Sterba, Jaroslav; van den Berg, Hendrick; Uttenreuther-Fischer, Martina; Witt, Olaf; Norga, Koen; Vassal, Gilles

2016-07-01

An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large-scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric malignancies, are evaluated in early phase clinical trials, and that this approach to generate pre-clinical and clinical data is systematically pursued by academia, sponsors, industry, and regulatory bodies to bring new paediatric oncology drugs to front-line therapy more rapidly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses.

PubMed

Di Legge, A; Testa, A C; Ameye, L; Van Calster, B; Lissoni, A A; Leone, F P G; Savelli, L; Franchi, D; Czekierdowski, A; Trio, D; Van Holsbeke, C; Ferrazzi, E; Scambia, G; Timmerman, D; Valentin, L

2012-09-01

To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter ≥ 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiver-operating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium-sized tumors and 74-95% in large tumors) while specificity was lowest in large tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 7-11 cm. Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Regulation of the oncodevelopmental expression of type 1 chain ABH and Lewis(b) blood group antigens in human colon by alpha-2-L-fucosylation.

PubMed Central

Orntoft, T F; Greenwell, P; Clausen, H; Watkins, W M

1991-01-01

Blood group antigen expression in the distal human colon is related to the development of the organ and is modified by malignant transformation. To elucidate the biochemical basis for these changes, we have (a) analysed the activity of glycosyltransferases coded for by the H, Se, Le, X, and A genes, in tissue biopsy specimens from normal and malignant proximal and distal human colon; (b) characterised the glycosphingolipids expressed in the various regions of normal and malignant colon by immunostaining of high performance thin layer chromatography plates; and (c) located the antigens on tissue sections from the same subjects by immunohistochemistry. In both secretors and non-secretors we found a significantly higher activity of alpha-2-L-fucosyltransferases in carcinomatous rectal tissue than in tissue from normal subjects, whereas the other transferase activities studied showed no significant differences. The acceptor substrate specificity suggested that both the Se and the H gene dependent alpha-2-L-fucosyltransferases are increased in carcinomas. In non-malignant tissue the only enzyme which showed appreciably higher activity in caecum than in rectum was alpha-2-L-fucosyltransferase. Immunochemistry and immunohistochemistry showed alpha-2-L-fucosylated structures in normal caecum from secretors and in tumour tissue from both secretors and non-secretors. We conclude that the alpha-2-L-fucosyltransferases control the expression of ABH, and Lewis(b) structures in normal and malignant colon. Images Figure 4 PMID:1826491

Comb-Push Ultrasound Shear Elastography of Breast Masses: Initial Results Show Promise

PubMed Central

Song, Pengfei; Fazzio, Robert T.; Pruthi, Sandhya; Whaley, Dana H.; Chen, Shigao; Fatemi, Mostafa

2015-01-01

Purpose or Objective To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE) for classification of breast masses. Materials and Methods CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF) beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results. Results Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s) in comparison to benign masses (3.65 ± 1.36 m/s). Therefore, the stiffness of the mass quantified by the Young’s modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC), the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC). Conclusion CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses. PMID:25774978

Active and passive immunization for cancer.

PubMed

Baxter, David

2014-01-01

Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers - proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types - the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review.

Fine needle aspiration cytology of breast cancer in women aged 70 years and older.

PubMed

Tse, Gary M K; Somali, Anjali; Chan, Anthony W H; Chaiwun, Benjaporn; Lui, Philip C W; Moriya, Takuya; Hwang, Jacqueline S G; Chan, Norman H L; Tan, Puay Hoon

2008-10-01

Elderly breast cancers are associated with a more favourable biological marker profile and higher proportion of specific subtypes, some of which are of low histological grade. We reviewed the fine needle aspiration cytology (FNAC) to assess the cytological characteristics and any clues to assist in the diagnosis. The aspirates of 140 cancers of various histological types and grades and 39 benign lesions were evaluated for 13 cytological parameters including cellularity of the direct and cytospin smears, epithelial cell clusters, cellular atypism, cytoplasmic features, vacuoles, mitotic figures, presence of myoepithelial cells, single background epithelial cells, the presence of naked nuclei, stromal fragments and necrosis. We found that the presence of background single epithelial cells, atypism of such cells, absence of benign appearing epithelial fragments, nuclear atypism of the epithelial cells within the fragments, presence of moderate amount of cytoplasm of these cells, absence of myoepithelial cells within the cluster, and absence of bipolar nuclei in the background have a strong association with malignancy. Scoring only the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei in a scoring system can differentiate between benign and malignant aspirates with high (>90%) sensitivity and specificity. Assessing the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei facilitates identification of malignancy in the aspiration of breast lesions from elderly patients.

Active and passive immunization for cancer

PubMed Central

Baxter, David

2014-01-01

Vaccination started around the 10th century AD as a means of preventing smallpox. By the end of the 19th century such therapeutic vaccines were well established with both active and passive preparations being used in clinical practice. Active immunization involved administering an immunogen that might be live/ attenuated, killed/ inactivated, toxoid or subunit in origin. Passive immunization involved giving pre-formed antibodies, usually to very recently exposed individuals. At about the same time such approaches were also tried to treat a variety of cancers – proof of principle for the protective role of the immune response against malignancy was established by the observation that tumors transplanted into syngeneic hosts were rejected by the host innate and adaptive responses. The impact of these therapeutic vaccination has taken a considerable time to become established - in part because target antigens against which an adaptive response can be directed do not appear to be uniquely expressed on malignant transformed cells; and also because tumor cells are able to manipulate their environment to downregulate the host immune response. Therapeutic cancer vaccines are also divided into active and passive types – the latter being subdivided into specific and non-specific vaccines. Active immunization utilizes an immunogen to generate a host response designed to eliminate the malignant cells, whereas in passive immunization preformed antibodies or cells are administered to directly eliminate the transformed cells - examples of each are considered in this review. PMID:25424829

RNAi screen for rapid therapeutic target identification in leukemia patients

PubMed Central

Tyner, Jeffrey W.; Deininger, Michael W.; Loriaux, Marc M.; Chang, Bill H.; Gotlib, Jason R.; Willis, Stephanie G.; Erickson, Heidi; Kovacsovics, Tibor; O'Hare, Thomas; Heinrich, Michael C.; Druker, Brian J.

2009-01-01

Targeted therapy has vastly improved outcomes in certain types of cancer. Extension of this paradigm across a broad spectrum of malignancies will require an efficient method to determine the molecular vulnerabilities of cancerous cells. Improvements in sequencing technology will soon enable high-throughput sequencing of entire genomes of cancer patients; however, determining the relevance of identified sequence variants will require complementary functional analyses. Here, we report an RNAi-assisted protein target identification (RAPID) technology that individually assesses targeting of each member of the tyrosine kinase gene family. We demonstrate that RAPID screening of primary leukemia cells from 30 patients identifies targets that are critical to survival of the malignant cells from 10 of these individuals. We identify known, activating mutations in JAK2 and K-RAS, as well as patient-specific sensitivity to down-regulation of FLT1, CSF1R, PDGFR, ROR1, EPHA4/5, JAK1/3, LMTK3, LYN, FYN, PTK2B, and N-RAS. We also describe a previously undescribed, somatic, activating mutation in the thrombopoietin receptor that is sensitive to down-stream pharmacologic inhibition. Hence, the RAPID technique can quickly identify molecular vulnerabilities in malignant cells. Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients. PMID:19433805

Role of microRNA221 in regulating normal mammary epithelial hierarchy and breast cancer stem-like cells.

PubMed

Ke, Jia; Zhao, Zhiju; Hong, Su-Hyung; Bai, Shoumin; He, Zhen; Malik, Fayaz; Xu, Jiahui; Zhou, Lei; Chen, Weilong; Martin-Trevino, Rachel; Wu, Xiaojian; Lan, Ping; Yi, Yongju; Ginestier, Christophe; Ibarra, Ingrid; Shang, Li; McDermott, Sean; Luther, Tahra; Clouthier, Shawn G; Wicha, Max S; Liu, Suling

2015-02-28

Increasing evidence suggests that lineage specific subpopulations and stem-like cells exist in normal and malignant breast tissues. Epigenetic mechanisms maintaining this hierarchical homeostasis remain to be investigated. In this study, we found the level of microRNA221 (miR-221) was higher in stem-like and myoepithelial cells than in luminal cells isolated from normal and malignant breast tissue. In normal breast cells, over-expression of miR-221 generated more myoepithelial cells whereas knock-down of miR-221 increased luminal cells. Over-expression of miR-221 stimulated stem-like cells in luminal type of cancer and the miR-221 level was correlated with clinical outcome in breast cancer patients. Epithelial-mesenchymal transition (EMT) was induced by overexpression of miR-221 in normal and breast cancer cells. The EMT related gene ATXN1 was found to be a miR-221 target gene regulating breast cell hierarchy. In conclusion, we propose that miR-221 contributes to lineage homeostasis of normal and malignant breast epithelium.

NF-κB and the link between inflammation and cancer.

PubMed

DiDonato, Joseph A; Mercurio, Frank; Karin, Michael

2012-03-01

The nuclear factor-κB (NF-κB) transcription factor family has been considered the central mediator of the inflammatory process and a key participant in innate and adaptive immune responses. Coincident with the molecular cloning of NF-κB/RelA and identification of its kinship to the v-Rel oncogene, it was anticipated that NF-κB itself would be involved in cancer development. Oncogenic activating mutations in NF-κB genes are rare and have been identified only in some lymphoid malignancies, while most NF-κB activating mutations in lymphoid malignancies occur in upstream signaling components that feed into NF-κB. NF-κB activation is also prevalent in carcinomas, in which NF-κB activation is mainly driven by inflammatory cytokines within the tumor microenvironment. Importantly, however, in all malignancies, NF-κB acts in a cell type-specific manner: activating survival genes within cancer cells and inflammation-promoting genes in components of the tumor microenvironment. Yet, the complex biological functions of NF-κB have made its therapeutic targeting a challenge. © 2012 John Wiley & Sons A/S.

High Prevalence of Vitamin D Deficiency in Patients with Bone Tumors.

PubMed

Horas, Konstantin; Maier, Gerrit; Jakob, Franz; Maus, Uwe; Kurth, Andreas; Jakuscheit, Axel; Rudert, Maximilian; Holzapfel, Boris Michael

2017-09-14

The aim of this study was to evaluate the prevalence of vitamin D deficiency in patients with different types of bone tumors and to elucidate whether or not there are differences in prediagnostic vitamin D levels in patients with malignant compared to benign bone tumors. Prediagnostic serum 25(OH)D levels of 105 consecutive patients that presented with bone tumors and tumor-like lesions to two Orthopedic Level I University Centers in Germany between 2011 and 2016 were measured on admission. We found an alarming and widespread rate of vitamin D deficiency in patients with bone tumors. Specifically, 83% of all patients had low vitamin D levels with a mean 25(OH)D level of 19.82 ng/ml. Notably, patients diagnosed with malignant bone tumors had significantly lower vitamin D levels compared to patients with benign bone lesions (p = 0.0008). In conclusion, it is essential to assess vitamin D levels in patients with tumors involving bone. In addition, there might be an association between vitamin D deficiency and the onset or course of primary malignant bone tumors.

Specific Detection of CD56 (NCAM) Isoforms for the Identification of Aggressive Malignant Neoplasms with Progressive Development

PubMed Central

Gattenlöhner, Stefan; Stühmer, Thorsten; Leich, Ellen; Reinhard, Matthias; Etschmann, Benjamin; Völker, Hans-Ulrich; Rosenwald, Andreas; Serfling, Edgar; Christian Bargou, Ralf; Ertl, Georg; Einsele, Hermann; Müller-Hermelink, Hans-Konrad

2009-01-01

Alternative splicing of transcripts from many cancer-associated genes is believed to play a major role in carcinogenesis as well as in tumor progression. Alternative splicing of one such gene, the neural cell adhesion molecule CD56 (NCAM), impacts the progression, inadequate therapeutic response, and reduced total survival of patients who suffer from numerous malignant neoplasms. Although previous investigations have determined that CD56 exists in three major isoforms (CD56120kD, CD56140kD, and CD56180kD) with individual structural and functional properties, neither the expression profiles nor the functional relevance of these isoforms in malignant tumors have been consistently investigated. Using new quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) strategies and novel CD56 isoform-specific antibodies, CD56140kD was shown to be exclusively expressed in a number of highly malignant CD56+ neoplasms and was associated with the progression of CD56+ precursor lesions of unclear malignant potential. Moreover, only CD56140kD induced antiapoptotic/proliferative pathways and specifically phosphorylated calcium-dependent kinases that are relevant for tumorigenesis. We conclude, therefore, that the specific detection of CD56 isoforms will help to elucidate their individual functions in the pathogenesis and progression of malignant neoplasms and may have a positive impact on the development of CD56-based immunotherapeutic strategies. PMID:19246644

[CHARACTERISTICS AND INCIDENCE OF HEAD AND NECK SKIN MALIGNANT NEOPLASMS IN THE POPULATION OF THE OSIJEK-BARANYA COUNTY 2004-2012].

PubMed

Orkić, Želimir; Puntarić, Dinko; Puntarić, Eda; Puntarić, Ida; Vidosavljević, Domagoj; Gvozdić, Vlatka; Mayer, Dijana

2015-03-01

The aim of this study was to investigate the incidence and characteristics of malignant neoplasms of the skin of the head and neck region in the Osijek-Baranya County during the 2004-2012 period according to gender, age, place of residence, place of work, occupation, type and location of the neoplasm, and phenotypic characteristics of patients. The study included all subjects with the diagnosis confirmed by histopathology finding and residents of the Osijek-Baranya County. The study included a total of 2952 persons, 1487 (50.4%) male and 1465 (49.6%) female, yielding an approximate annual incidence of 104/100,000. Mean age was 72 years. Respondents were mostly from rural areas (n = 1952, 66.2%). There were 2137 (72.4%) of respondents mostly working outdoors, mainly farmers (n = 907, 42.4%) and construction workers (n = 889, 41.6%). According to the type of neoplasm, the basal cell type was most common with 2160 (73.2%) patients. Ninety-three (3.1 %) patients had malignant melanoma. According to localization, face was the most common site of malignant neoplasms with 839 (28.7%) and nose with 643 (22.0%) patients. Squamous cell carcinoma was significantly more common in men (n = 341, 56.6%) as compared with women (n = 262, (43.4%; p = 0.005). Subjects with malignant melanoma were significantly younger, with median age of 67 years. There were no significant differences according to the type of malignant neoplasms and place of residence, place of business, and occupation with regard to working outdoors or indoors. According to localization, significantly more squamous cell malignancies were found on the ears and lips (p = 0.039 and p < 0.001, respectively), malignant melanomas on the neck, head and eyes (p = 0.004, p < 0.001 and p = 0.026, respectively), and basal cell neoplasms on the nose (p = 0.002). There were no significant differences in the type and frequency of malignant neoplasms according to hair and eye color. It is obvious that the disease occurs after a decades-long incubation period and the cumulative effect of exposure to risk factors, with direct sun exposure, seems to have a significant role. Additional research is needed.

Expression of MUC4 mucin is observed mainly in the intestinal-type of intraductal papillary mucinous neoplasm of the pancreas

PubMed Central

Kitazono, Iwao; Higashi, Michiyo; Kitamoto, Sho; Yokoyama, Seiya; Horinouchi, Michiko; Osako, Masahiko; Shimizu, Takeshi; Tabata, Mineo; Batra, Surinder K.; Goto, Masamichi; Yonezawa, Suguru

2013-01-01

Objectives This study aimed to examine expression profile of MUC4 in intraductal papillary mucinous neoplasm of the pancreas (IPMN). Methods We performed immonohistochemistry (IHC) of MUC4 in 142 IPMNs, with evaluation of the specificity of two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, in cancer cell lines. Results MAb 8G7 showed a clear immunoreactivity, whereas MAb 1G8 did not show any immunoreactivity, in the Western blotting and IHC for human pancreatic carcinoma cell lines expressing MUC4 mRNA. However, IHC signals detected by both MAbs were observed in the tissue specimens. The expression rates of MUC4/8G7 detected by MAb 8G7 and MUC4/1G8 detected by MAb 1G8 in the intestinal-type IPMNs were significantly higher than those in the gastric-type IPMNs. In the intestinal-type IPMNs, MUC4/8G7 was expressed mainly in the cytoplasm of the neoplastic cells, whereas MUC4/1G8 was expressed mainly at the cell apexes. Even in the gastric-type IPMNs with rare MUC4 expression in the low-grade dysplasia, both MUC4 expression rates increased when dysplasia advanced. Conclusions A significantly higher expression of MUC4 in intestinal-type IPMNs than in gastric-type IPMNs will be one of the biomarkers to discriminate between the intestinal-type IPMNs with high malignancy potential from gastric-type IPMNs with low malignancy potential. PMID:23921963

18F-FDG PET/CT in the detection of asymptomatic malignant melanoma recurrence.

PubMed

Lawal, Ismaheel; Lengana, Thabo; Ololade, Kehinde; Boshomane, Tebatso; Reyneke, Florette; Modiselle, Moshe; Vorster, Mariza; Sathekge, Mike

2017-06-12

To evaluate the diagnostic accuracy of FDG PET/CT in the detection of asymptomatic recurrence in patients with malignant melanoma who have had resection of their primary lesion. We also aimed to determine the pattern and factors predisposing to disease recurrence. Patients with malignant melanoma who have had surgical resection of their disease and without any clinical evidence of disease recurrence were followed-up with FDG PET/CT. The diagnostic accuracy of FDG PET/CT, pattern of recurrence and factors predictive of disease recurrence were determined. A total of 144 patients were followed-up for a median period of 50.50 months. Asymptomatic recurrence was seen in 37 patients (25.7 %) with a median time to recurrence of 20 months. Lymph node was the commonest site of asymptomatic recurrence. Sex, tumour depth, histology type and presence of nodal metastasis were significant predictors of tumour recurrence. Age, race, site of primary lesion, type of lymph node resection were not significant predictors of disease recurrence. Race has a significant effect on the histological subtype of tumour (nodular maligna was more common in Caucasian while acral lentiginous was more prevalent in the Blacks) and the site of the primary lesion (lower limb in Blacks and trunk in Caucasians). Sensitivity, specificity and accuracy of FDG PET/CT for the detection of disease recurrence were 94.5 %, 87.6 % and 89.6 % respectively. FDG PET/CT is a suitable modality for early detection of asymptomatic recurrence of malignant melanoma. Asymptomatic recurrence most commonly occurs in lymph nodes. Sex, nodal metastasis and tumour pathologic features are predictors of recurrence.

Determination of malignancy and characterization of hepatic tumor type with diffusion-weighted magnetic resonance imaging: comparison of apparent diffusion coefficient and intravoxel incoherent motion-derived measurements.

PubMed

Doblas, Sabrina; Wagner, Mathilde; Leitao, Helena S; Daire, Jean-Luc; Sinkus, Ralph; Vilgrain, Valérie; Van Beers, Bernard E

2013-10-01

The objective of this study was to compare the value of the apparent diffusion coefficient (ADC) determined with 3 b values and the intravoxel incoherent motion (IVIM)-derived parameters in the determination of malignancy and characterization of hepatic tumor type. Seventy-six patients with 86 solid hepatic lesions, including 8 hemangiomas, 20 lesions of focal nodular hyperplasia, 9 adenomas, 30 hepatocellular carcinomas, 13 metastases, and 6 cholangiocarcinomas, were assessed in this prospective study. Diffusion-weighted images were acquired with 11 b values to measure the ADCs (with b = 0, 150, and 500 s/mm) and the IVIM-derived parameters, namely, the pure diffusion coefficient and the perfusion-related diffusion fraction and coefficient. The diffusion parameters were compared between benign and malignant tumors and between tumor types, and their diagnostic value in identifying tumor malignancy was assessed. The apparent and pure diffusion coefficients were significantly higher in benign than in malignant tumors (benign: 2.32 [0.87] × 10 mm/s and 1.42 [0.37] × 10 mm/s vs malignant: 1.64 [0.51] × 10 mm/s and 1.14 [0.28] × 10 mm/s, respectively; P < 0.0001 and P = 0.0005), whereas the perfusion-related diffusion parameters did not differ significantly between the 2 groups. The apparent and pure diffusion coefficients provided similar accuracy in assessing tumor malignancy (areas under the receiver operating characteristic curve of 0.770 and 0.723, respectively). In the multigroup analysis, the ADC was found to be significantly higher in hemangiomas than in hepatocellular carcinomas, metastases, and cholangiocarcinomas. In the same manner, it was higher in lesions of focal nodular hyperplasia than in metastases and cholangiocarcinomas. However, the pure diffusion coefficient was significantly higher only in hemangiomas versus hepatocellular and cholangiocellular carcinomas. Compared with the ADC, the diffusion parameters derived from the IVIM model did not improve the determination of malignancy and characterization of hepatic tumor type.

[Malignant tumors of thyroid gland].

PubMed

Uhliarová, B; Bugová, G; Hajtman, A

2015-01-01

The incidence of thyroid cancer has been increasing. The aim of this work was to determine risk factors, diagnostic methods and extent of surgical treatment of malignant goiter. The authors retrospectively analyzed patients who were surgically treated for thyroid disease at the Department of Otorhinolaryngology, Head and Neck Surgery, Comenius University, Jessenius Faculty of Medicine, Teaching Hospital in Martin, Slovakia, from the January 1st, 2006 to December 31st, 2013, for thyroid disease. The incidence, risk factors of malignant thyroid tumors, indication for surgery and its complications were evaluated. A total of 1,620 adult patients were surgically treated for thyroid disease at the Department of ENT, Head and Neck Surgery, CU JMF, UH in Martin, Slovakia, between 2006- 2013. Malignant tumors were identified in 238 patients (15%). Microcarcinoma (incidentally detected malignant tumor 1 cm) occurred in 78 cases (5%). Malignant thyroid tumor was more common in younger patients (p = 0.002). Newly created and larger nodules positively correlated with the occurrence of malignancy (p = 0.003, p = 0.041, resp.). Gender, family history of thyroid disorder, previous radiation therapy, and previous malignancy did not affect the incidence of malignant tumor of thyroid gland. High sensitivity and specificity in the dia-gnosis of malignant thyroid nodule was observed using aspiration cytology (75%, 97%, resp.) and intraoperative histopathological examination (88%, 100%, resp.). Malignant tumor of thyroid gland is more common in younger patients with newly developed nodule. The risk factors of malignancy increase with the size of the thyroid nodule. Aspiration cytology and peroperative histopathology have high sensitivity and specificity in the dia-gnosis of malignant thyroid tumor; therefore, they should be a standard method in the dia-gnosis of nodular goiter. The method of choice in the treatment of thyroid malignancy is total thyroidectomy.

Typical thyroid-type carcinoma arising in struma ovarii: a report of 4 cases and review of the literature.

PubMed

Roth, Lawrence M; Miller, Alexander W; Talerman, Aleksander

2008-10-01

Struma ovarii has elicited considerable interest because of its many unique features since Ludwig Pick first elucidated its relationship to teratoma in the early part of the 20th century. In this article, we report 3 cases of papillary and 1 of follicular thyroid carcinoma; 2 of these cases were associated with mature cystic teratoma. Metastases occurred in 2 patients, and 1 died of neoplasm. In regard to the occurrence of thyroid-type carcinoma in struma ovarii, precise terminology should be used, and the expression malignant struma ovarii was avoided as a diagnostic term. Upon review of the literature, papillary carcinoma and follicular carcinoma are the most frequent types of malignancy to occur in ovarian struma; other forms of thyroid carcinoma occur only rarely. The diagnostic criteria for cases of papillary carcinoma are similar to those described in the cervical thyroid gland and are based primarily on nuclear and architectural features. In reference to follicular carcinoma, invasion into the surrounding ovarian tissue, vascular invasion, or metastasis is evidence of malignancy. Histological malignancy in a struma does not necessarily equate with biological malignancy, and the majority of thyroid-type carcinomas do not spread beyond the ovary. Occasionally, metastases of ovarian struma have an innocuous histological appearance, and such cases are referred to as highly differentiated follicular carcinoma of ovarian origin (HDFCO). Because its histological appearance resembles that of nonneoplastic thyroid, HDFCO characteristically cannot be diagnosed until the neoplasm spreads beyond the ovary. In this article, we apply the term typical thyroid carcinoma to those forms of thyroid malignancy arising in ovarian struma that closely resemble the types described in the cervical thyroid gland to distinguish them from HDFCO. Typical follicular carcinoma is more aggressive than the somewhat more common papillary carcinoma, and HDFCO is the least aggressive of these tumor types. Cases of thyroid-type carcinoma arising in the ovary sometimes lack evidence of preexisting struma. The more aggressive thyroid-type neoplasms can arise in thyroid tissue within a mature cystic teratoma, or they may overgrow and replace the struma. Primary thyroid-type carcinoma must be distinguished from rare instances of ovarian metastases that originate in the cervical thyroid gland and the less differentiated forms from other ovarian neoplasms such as clear cell adenocarcinoma and tumors with an oxyphilic appearance. In the differential diagnosis with other ovarian neoplasms, cases of thyroid-type carcinoma associated with strumal carcinoid should not be diagnosed as malignant strumal carcinoid because the latter diagnosis might lead to suboptimal therapy.

Apparent diffusion coefficient mapping using diffusion-weighted MRI: impact of background parenchymal enhancement, amount of fibroglandular tissue and menopausal status on breast cancer diagnosis.

PubMed

Horvat, Joao V; Durando, Manuela; Milans, Soledad; Patil, Sujata; Massler, Jessica; Gibbons, Girard; Giri, Dilip; Pinker, Katja; Morris, Elizabeth A; Thakur, Sunitha B

2018-06-01

To investigate the impact of background parenchymal enhancement (BPE), amount of fibroglandular tissue (FGT) and menopausal status on apparent diffusion coefficient (ADC) values in differentiation between malignant and benign lesions. In this HIPAA-compliant study, mean ADC values of 218 malignant and 130 benign lesions from 288 patients were retrospectively evaluated. The differences in mean ADC values between benign and malignant lesions were calculated within groups stratified by BPE level (high/low), amount of FGT (dense/non-dense) and menopausal status (premenopausal/postmenopausal). Sensitivities and specificities for distinguishing malignant from benign lesions within different groups were compared for statistical significance. The mean ADC value for malignant lesions was significantly lower compared to that for benign lesions (1.07±0.21 x 10 -3 mm 2 /s vs. 1.53±0.26 x 10 -3 mm 2 /s) (p<0.0001). Using the optimal cut-off point of 1.30 x 10 -3 mm 2 /s, an area under the curve of 0.918 was obtained, with sensitivity and specificity both of 87 %. There was no statistically significant difference in sensitivities and specificities of ADC values between different groups stratified by BPE level, amount of FGT or menopausal status. Differentiation between benign and malignant lesions on ADC values is not significantly affected by BPE level, amount of FGT or menopausal status. • ADC allows differentiation between benign and malignant lesions. • ADC is useful for breast cancer diagnosis despite different patient characteristics. • BPE, FGT or menopause do not significantly affect sensitivity and specificity.

T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells

PubMed Central

Witkover, Aviva; Tanaka, Yuetsu; Fields, Paul; Bangham, Charles R. M.

2016-01-01

There is growing evidence that CD8+ cytotoxic T lymphocyte (CTL) responses can contribute to long-term remission of many malignancies. The etiological agent of adult T-cell leukemia/lymphoma (ATL), human T lymphotropic virus type-1 (HTLV-1), contains highly immunogenic CTL epitopes, but ATL patients typically have low frequencies of cytokine-producing HTLV-1-specific CD8+ cells in the circulation. It remains unclear whether patients with ATL possess CTLs that can kill the malignant HTLV-1 infected clone. Here we used flow cytometric staining of TCRVβ and cell adhesion molecule-1 (CADM1) to identify monoclonal populations of HTLV-1-infected T cells in the peripheral blood of patients with ATL. Thus, we quantified the rate of CD8+-mediated killing of the putative malignant clone in ex vivo blood samples. We observed that CD8+ cells from ATL patients were unable to lyse autologous ATL clones when tested directly ex vivo. However, short in vitro culture restored the ability of CD8+ cells to kill ex vivo ATL clones in some donors. The capacity of CD8+ cells to lyse HTLV-1 infected cells which expressed the viral sense strand gene products was significantly enhanced after in vitro culture, and donors with an ATL clone that expressed the HTLV-1 Tax gene were most likely to make a detectable lytic CD8+ response to the ATL cells. We conclude that some patients with ATL possess functional tumour-specific CTLs which could be exploited to contribute to control of the disease. PMID:27893842

Investigation of serum Ki-67 as a biomarker in tumor-bearing dogs.

PubMed

Neumann, Stephan; Schuettler, Julia; Frenz, Meike; Kaup, Franz-Josef; Gessler, Frank

2017-02-01

Because of the limited number of tumor markers in veterinary medicine, there is need for identifying new markers. Ki-67 has been investigated as a tissue marker of malignant alterations. We hypothesized that Ki-67 would also be measurable in serum and should therefore be elevated in cases of malignancy. The purpose of this prospective study was to measure Ki-67 in clinically healthy dogs, dogs with nonmalignant diseases, and dogs with malignant tumors. Samples from 8 healthy dogs, 13 dogs with nonmalignant diseases, and 20 dogs with malignant tumors were collected. Ki-67 was measured using the commercially available canine-specific ELISA. Results demonstrated undetectable Ki-67 serum concentrations in healthy dogs. Dogs with nonmalignant diseases displayed low Ki-67 serum concentrations. In contrast, dogs with malignancies showed significantly increased serum Ki-67 concentrations compared with the healthy (p<0.001) or nonmalignant diseased dogs (p<0.001). The degree of malignancy had a positive influence on serum Ki-67 levels. In contrast, no influence of tumor size on Ki-67 serum concentration was observed (p>0.05). Comparing healthy dogs and tumor bearing dogs a sensitivity of 0.75 and a specificity of 1.0 can be calculated using a Ki-67 cut-off value of 5.5pg/mL. When dogs with a low degree of malignancy were compared with dogs of moderate-to-severe degree malignant tumors a sensitivity of 1.0 and a specificity of 1.0 can be observed at a Ki-67 cut-off value of 19.25pg/mL. In conclusion, our results demonstrate an association of malignancies with elevated Ki-67 serum concentrations in dogs. Published by Elsevier Ltd.

Proteomic study of benign and malignant pleural effusion.

PubMed

Li, Hongqing; Tang, Zhonghao; Zhu, Huili; Ge, Haiyan; Cui, Shilei; Jiang, Weiping

2016-06-01

Lung adenocarcinoma can easily cause malignant pleural effusion which was difficult to discriminate from benign pleural effusion. Now there was no biomarker with high sensitivity and specificity for the malignant pleural effusion. This study used proteomics technology to acquire and analyze the protein profiles of the benign and malignant pleural effusion, to seek useful protein biomarkers with diagnostic value and to establish the diagnostic model. We chose the weak cationic-exchanger magnetic bead (WCX-MB) to purify peptides in the pleural effusion, used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to obtain peptide expression profiles from the benign and malignant pleural effusion samples, established and validated the diagnostic model through a genetic algorithm (GA) and finally identified the most promising protein biomarker. A GA diagnostic model was established with spectra of 3930.9 and 2942.8 m/z in the training set including 25 malignant pleural effusion and 26 benign pleural effusion samples, yielding both 100 % sensitivity and 100 % specificity. The accuracy of diagnostic prediction was validated in the independent testing set with 58 malignant pleural effusion and 34 benign pleural effusion samples. Blind evaluation was as follows: the sensitivity was 89.6 %, specificity 88.2 %, PPV 92.8 %, NPV 83.3 % and accuracy 89.1 % in the independent testing set. The most promising peptide biomarker was identified successfully: Isoform 1 of caspase recruitment domain-containing protein 9 (CARD9), with 3930.9 m/z, was decreased in the malignant pleural effusion. This model is suitable to discriminate benign and malignant pleural effusion and CARD9 can be used as a new peptide biomarker.

[Contrastive study on conventional ultrasound, compression elastography and acoustic radiation force impulse imaging in the differential diagnosis of benign and malignant breast tumors].

PubMed

Zhang, Lu; Zhou, Ping; Deng, Jin; Tian, Shuangming; Qian, Ying; Wu, Xiaomin; Ma, Shuhua; Li, Jiale

2014-12-01

To evaluate the diagnostic performance of conventional ultrasound, compression elastography (CE) and acoustic radiation force impulse imaging (ARFI) in differential diagnosis of benign and malignant breast tumors. A total of 98 patients with liver lesions were included in the study. The images of conventional ultrasound, CE and the values of virtual touch tissue quantification (VTQ) of breast lesions were obtained. The diagnostic performance of conventional ultrasound, CE and ARFI were assessed by using pathology as the gold standard, and then evaluate the diagnosis efficiency of these three approaches in differential diagnosing benign and malignant breast tumors. The specificity, sensitivity and accuracy in the diagnosis of malignant breast tumors for conventional ultrasound were 80.0%, 81.1% and 81.7%, respectively, whereas for CE elastic score were 85.7%, 86.7% and 86.3%, respectively. With a cutoff value of 3.71 for the SR, the sensitivity, specificity, accuracy in diagnosis of malignant breast tumors were 97.1%, 83.3% and 88.4%, respectively. With a cutoff value of 3.78 m/s for VTQ, the sensitivity, specificity, accuracy in diagnosis of malignant breast tumors were 94.3%, 91.7% and 92.6%, respectively. The difference in diagnosis efficiency among ARFI, CE and conventional ultrasound in differential diagnosis of benign and malignant breast tumors was significant (P< 0.05). Conventional ultrasound, CE and ARFI are all useful for the differential diagnosis of benign and malignant breast tumors. But the diagnosis efficiency of ARFI is superior to CE and conventional ultrasound. The three approaches can help each other in differential diagnosis of benign and malignant breast tumors.

Inferring the 1985-2014 impact of mobile phone use on selected brain cancer subtypes using Bayesian structural time series and synthetic controls.

PubMed

de Vocht, Frank

2016-12-01

Mobile phone use has been increasing rapidly in the past decades and, in parallel, so has the annual incidence of certain types of brain cancers. However, it remains unclear whether this correlation is coincidental or whether use of mobile phones may cause the development, promotion or progression of specific cancers. The 1985-2014 incidence of selected brain cancer subtypes in England were analyzed and compared to counterfactual 'synthetic control' timeseries. Annual 1985-2014 incidence of malignant glioma, glioblastoma multiforme, and malignant neoplasms of the temporal and parietal lobes in England were modelled based on population-level covariates using Bayesian structural time series models assuming 5,10 and 15year minimal latency periods. Post-latency counterfactual 'synthetic England' timeseries were nowcast based on covariate trends. The impact of mobile phone use was inferred from differences between measured and modelled time series. There is no evidence of an increase in malignant glioma, glioblastoma multiforme, or malignant neoplasms of the parietal lobe not predicted in the 'synthetic England' time series. Malignant neoplasms of the temporal lobe however, have increased faster than expected. A latency period of 10years reflected the earliest latency period when this was measurable and related to mobile phone penetration rates, and indicated an additional increase of 35% (95% Credible Interval 9%:59%) during 2005-2014; corresponding to an additional 188 (95%CI 48-324) cases annually. A causal factor, of which mobile phone use (and possibly other wireless equipment) is in agreement with the hypothesized temporal association, is related to an increased risk of developing malignant neoplasms in the temporal lobe. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic Prognostic Factors on Survival.

PubMed

Göde, Sercan; Turhal, Göksel; Tarhan, Ceyda; Yaman, Banu; Kandiloğlu, Gülşen; Öztürk, Kerem; Kaya, İsa; Midilli, Raşit; Karcı, Bülent

2017-05-05

Mucosal melanoma is a rare malignancy arising from melanocytes of the mucosal surfaces. The pattern and frequency of oncogenic mutations and histopathological biomarkers have a role on distinct tumour behaviour and survival. To assess the rate of C-KIT positivity and its effect on survival of surgically treated sinonasal malignant melanoma patients with other histopathological biomarkers and clinical features. Retrospective cross-sectional study. Seventeen sinonasal malignant melanoma patients with a mean age of 65.41 (39-86) years were included. Overall survival and disease-specific survival rates were calculated. The impact of age, gender, stage and extent of the disease, type of surgery, and adjuvant therapies were also taken into consideration. The effect of mitotic index, pigmentation, S100, HMB-45, Melan-A and C-KIT on survival were evaluated. Median tumour size was 20 mm (interquartile range=27.5 mm). Pigmentation was present in 7 (41.2%) cases. Median number of mitoses per millimetre squared was 11 (interquartile range=13). Melan A was positive in 7 (41.2%) patients, ulceration was present in 6 cases (35.3%), and necrosis was present in (47.1%) 8 cases. Six patients (35.3%) were positive for S100, 14 (82.4%) specimens stained positive for HMB-45 and C-KIT (CD117) was positive in 9 cases (52.9%). Three patients (16.7%) developed distant metastasis. Five year overall and disease free survival rates were 61.4% and 43.8%, respectively. Although C-KIT positive sinonasal malignant melanoma patients (52.9%) can be candidates for targeted tumour therapies, the studied clinical or histopathological features along with C-KIT seem to have no significant effect on survival in a small group of patients with sinonasal malignant melanoma.

Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis group.

PubMed

Timmerman, Dirk; Van Calster, Ben; Testa, Antonia; Savelli, Luca; Fischerova, Daniela; Froyman, Wouter; Wynants, Laure; Van Holsbeke, Caroline; Epstein, Elisabeth; Franchi, Dorella; Kaijser, Jeroen; Czekierdowski, Artur; Guerriero, Stefano; Fruscio, Robert; Leone, Francesco P G; Rossi, Alberto; Landolfo, Chiara; Vergote, Ignace; Bourne, Tom; Valentin, Lil

2016-04-01

Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant. We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules. This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), negative predictive value (NPV), and calibration curves. Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901-0.931) and other centers (0.916; 95% confidence interval, 0.873-0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (<1%) and 48% had a high estimated risk (≥30%). For the 1% risk cutoff, sensitivity was 99.7%, specificity 33.7%, LR+ 1.5, LR- 0.010, PPV 44.8%, and NPV 98.9%. For the 30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LR+ 5.8, LR- 0.13, PPV 75.4%, and NPV 93.9%. Quantification of the risk of malignancy based on the Simple Rules has good diagnostic performance both in oncology centers and other centers. A simple classification based on these risk estimates may form the basis of a clinical management system. Patients with a high risk may benefit from surgery by a gynecological oncologist, while patients with a lower risk may be managed locally. Copyright © 2016 Elsevier Inc. All rights reserved.

Detection of monoclonal immunoglobulin heavy chain gene rearrangement (FR3) in Thai malignant lymphoma by High Resolution Melting curve analysis.

PubMed

Kummalue, Tanawan; Chuphrom, Anchalee; Sukpanichanant, Sanya; Pongpruttipan, Tawatchai; Sukpanichanant, Sathien

2010-05-19

Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Detection of antigen receptor gene rearrangement including T cell receptor (TCR) and immunoglobulin heavy chain (IgH) by polymerase chain reaction followed by heteroduplex has currently become standard whereas fluorescent fragment analysis (GeneScan) has been used for confirmation test. In this study, three techniques had been compared: thermocycler polymerase chain reaction (PCR) followed by heteroduplex and polyacrylamide gel electrophoresis, GeneScan analysis, and real time PCR with High Resolution Melting curve analysis (HRM). The comparison was carried out with DNA extracted from paraffin embedded tissues diagnosed as B- cell non-Hodgkin lymphoma. Specific PCR primers sequences for IgH gene variable region 3, including fluorescence labeled IgH primers were used and results were compared with HRM. In conclusion, the detection IgH gene rearrangement by HRM in the LightCycler System showed potential for distinguishing monoclonality from polyclonality in B-cell non-Hodgkin lymphoma. Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The incidence rate as reported by Ministry of Public Health is 3.1 per 100,000 population in female whereas the rate in male is 4.5 per 100,000 population 1. At Siriraj Hospital, the new cases diagnosed as malignant lymphoma were 214.6 cases/year 2. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Therefore, detection of antigen receptor gene rearrangement including T cell receptor (TCR) and immunoglobulin heavy chain (IgH) by polymerase chain reaction (PCR) assay has recently become a standard laboratory test for discrimination of reactive from malignant clonal lymphoproliferation 34. Analyzing DNA extracted from formalin-fixed, paraffin-embedded tissues by multiplex PCR techniques is more rapid, accurate and highly sensitive. Measuring the size of the amplicon from PCR analysis could be used to diagnose malignant lymphoma with monoclonal pattern showing specific and distinct bands detected on acrylamide gel electrophoresis. However, this technique has some limitations and some patients might require a further confirmation test such as GeneScan or fragment analysis 56.GeneScan technique or fragment analysis reflects size and peak of DNA by using capillary gel electrophoresis. This technique is highly sensitive and can detect 0.5-1% of clonal lymphoid cells. It measures the amplicons by using various fluorescently labeled primers at forward or reverse sides and a specific size standard. Using a Genetic Analyzer machine and GeneMapper software (Applied Bioscience, USA), the monoclonal pattern revealed one single, sharp and high peak at the specific size corresponding to acrylamide gel pattern, whereas the polyclonal pattern showed multiple and small peak condensed at the same size standard. This technique is the most sensitive and accurate technique; however, it usually requires high technical experience and is also of high cost 7. Therefore, rapid and more cost effective technique are being sought.LightCycler PCR performs the diagnostic detection of amplicon via melting curve analysis within 2 hours with the use of a specific dye 89. This dye consists of two types: one known as SYBR-Green I which is non specific and the other named as High Resolution Melting analysis (HRM) which is highly sensitive, more accurate and stable. Several reports demonstrated that this new instrument combined with DNA intercalating dyes can be used to discriminate sequence changes in PCR amplicon without manual handling of PCR product 1011. Therefore, current investigations using melting curve analysis are being developed 1213.In this study, three different techniques were compared to evaluate the suitability of LightCycler PCR with HRM as the clonal diagnostic tool for IgH gene rearrangement in B-cell non-Hogdkin lymphoma, i.e. thermocycler PCR followed by heteroduplex analysis and PAGE, GeneScan analysis and LightCycler PCR with HRM.

The pathobiology and mechanisms of infection of HPV.

PubMed

Wood, N H; Khammissa, R A G; Chikte, U M E; Meyerov, R; Lemmer, J; Feller, L

2010-04-01

There are more than 120 types of low-risk and high-risk human papillomaviruses, all of which are epitheliotropic. HPV infection may be latent, or active in a subclinical form or a symptomatic form, the latter manifesting as benign or malignant neoplasms. In basal cells with non-productive HPV infection some early HPV proteins are expressed independently of cell maturation: the productive cycle of HPV replication depends upon specific cellular factors of the maturation of the infected keratinocytes. In HPV-mediated oncogenesis, the combined pathobiological effects of E6 and E7 oncoproteins of high-risk HPV culminate in cellular genomic instability and transformation of persistently infected cells, that progress to the development of a malignant phenotype. In this article we provide insights into the stages of HPV infection, and into the viral genomic organization and replicative cycle.

The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies.

PubMed

Li, Alvin W; Yin, Emily S; Stahl, Maximilian; Kim, Tae Kon; Panse, Gauri; Zeidan, Amer M; Leventhal, Jonathan S

2017-11-01

Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. In addition, infections with cutaneous involvement are common in immunocompromised patients with myeloid disease. Given the varying presentations, dermatologic findings associated with myeloid malignancies can pose diagnostic challenges for hematologists and dermatologists. In this clinical review intended for the practicing hematologist/oncologist, we discuss the presentation, diagnosis, treatment, and prognostic value of the most common cutaneous manifestations associated with myeloid malignancies using illustrative macro- and microscopic figures and with a special emphasis on practical considerations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis.

PubMed

Mondal, Bikash; Maulik, Dhrubajyoti; Mandal, Mousumi; Sarkar, Gautam Narayan; Sengupta, Sanjay; Ghosh, Debidas

2017-12-01

Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy. Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone. EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001), cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C groups. The presence of these heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones. Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.

Leuloplakia - Review of A Potentially Malignant Disorder

PubMed Central

Abidullah, Mohammed; Gaddikeri, Kavitha; Raghoji, Swetha; Ravishankar T, Shilpa

2014-01-01

Leukoplakias are oral white lesions that have not been diagnosed as any other specific disease. They are grouped under premalignant lesions, now redesignated as potentially malignant disorders. Their significance lies in the fact that they have propensity for malignant transformation at a higher rate when compared to other oral lesions. This article reviews aetiology, epidemiology, clinical characteristics, histopathologic features, malignant potential and treatment of oral leukoplakia. PMID:25302287

Mycoplasma CG- and GATC-specific DNA methyltransferases selectively and efficiently methylate the host genome and alter the epigenetic landscape in human cells

PubMed Central

Chernov, Andrei V; Reyes, Leticia; Xu, Zhenkang; Gonzalez, Beatriz; Golovko, Georgiy; Peterson, Scott; Perucho, Manuel; Fofanov, Yuriy; Strongin, Alex Y

2015-01-01

Aberrant DNA methylation is frequently observed in disease, including many cancer types, yet the underlying mechanisms remain unclear. Because germline and somatic mutations in the genes that are responsible for DNA methylation are infrequent in malignancies, additional mechanisms must be considered. Mycoplasmas spp., including Mycoplasma hyorhinis, efficiently colonize human cells and may serve as a vehicle for delivery of enzymatically active microbial proteins into the intracellular milieu. Here, we performed, for the first time, genome-wide and individual gene mapping of methylation marks generated by the M. hyorhinis CG- and GATC-specific DNA cytosine methyltransferases (MTases) in human cells. Our results demonstrated that, upon expression in human cells, MTases readily translocated to the cell nucleus. In the nucleus, MTases selectively and efficiently methylated the host genome at the DNA sequence sites free from pre-existing endogenous methylation, including those in a variety of cancer-associated genes. We also established that mycoplasma is widespread in colorectal cancers, suggesting that either the infection contributed to malignancy onset or, alternatively, that tumors provide a favorable environment for mycoplasma growth. In the human genome, ∼11% of GATC sites overlap with CGs (e.g., CGATmCG); therefore, the methylated status of these sites can be perpetuated by human DNMT1. Based on these results, we now suggest that the GATC-specific methylation represents a novel type of infection-specific epigenetic mark that originates in human cells with a previous exposure to infection. Overall, our findings unveil an entirely new panorama of interactions between the human microbiome and epigenome with a potential impact in disease etiology. PMID:25695131

Diagnostic value of ultrasound indicators of neoplastic risk in preoperative differentiation of adnexal masses

PubMed Central

Bachanek, Michał; Trojanowski, Seweryn; Cendrowski, Krzysztof; Sawicki, Włodzimierz

2013-01-01

Aim To assess the diagnostic value of the risk of malignancy indices and simple ultrasound- based rules in preoperative differentiation of adnexal masses. Material and methods Retrospective examination of 87 patients admitted to hospital due to adnexal tumors. The lesions were evaluated on the basis of international ultrasound classification of ovarian tumors and four risk of malignancy indices were calculated based on ultrasound examination, concentration of CA 125 and menopausal status. Results The patients were aged between 17 and 79, the mean age was 44.5 (standard deviation SD=16.6). Most of the patients (60.91%) were before their menopause. The sensitivity of the simple ultrasound-based rules in the diagnosis of malignancies equaled 64.71% and the specificity constituted 90.00%. A significant statistical difference in the presence of the malignant process was demonstrated in relation to age, menopausal status, CA 125 concentration and analyzed ultrasound score. All indices were characterized by similar sensitivity and specificity. The highest specificity and predictive value of malignant lesions out of the assessed ones was demonstrated by the risk of malignancy index proposed by Yamamoto. The risk of malignancy index according to Jacobs, however, showed the highest predictive value in the case of non-malignant lesions. Conclusions The multiparametric ultrasound examination may facilitate the selection of patients with adnexal tumors to provide them with an appropriate treatment – observation, laparotomy and laparoscopy. These parameters constitute a simple ambulatory method of determining the character of adnexal masses before recommending appropriate treatment. PMID:26674849

Increased level of annexin A1 in bronchoalveolar lavage fluid as a potential diagnostic indicator for lung cancer.

PubMed

Biaoxue, Rong; Xiguang, Cai; Hua, Liu; Tian, Fu; Wenlong, Gao

2017-03-02

Annexin A1 has been implicated in various tumor types, but few studies have investigated its involvement in lung cancer. The purpose of this investigation was to quantify the annexin A1 level in bronchoalveolar lavage fluid (BALF) and analyze its usefulness in lung cancer diagnosis. Annexin A1 expression was measured by immunohistochemistry and enzyme immunoassay. The sensitivity and specificity of annexin A1 for distinguishing lung cancer were determined by receiver operator characteristic (ROC) curves. Tumor tissues, BALF and serum of patients with lung cancer contained higher levels of annexin A1 than those of the control group of patients with benign lung diseases. Moreover, an increased level of BALF annexin A1 was closely correlated with lymphatic invasion and malignant progression of lung cancer. The sensitivity and specificity of BALF annexin A1 for distinguishing lung cancer were 94.2% and 90.2%, respectively. Increased annexin A1 in BALF was correlated with lymphatic invasion and malignant progression of lung cancer, suggesting that it could be an indicator for discerning lung cancer and predicting outcome.

Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer.

PubMed

Ahrens, Bradley J; Li, Lin; Ciminera, Alexandra K; Chea, Junie; Poku, Erasmus; Bading, James R; Weist, Michael R; Miller, Marcia M; Colcher, David M; Shively, John E

2017-09-01

The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64 Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64 Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64 Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague-Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64 Cu-DOTA-alendronate. Results: 64 Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64 Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64 Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64 Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64 Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as well as the differentiation of malignant versus benign tumors based on absolute labeling uptake. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer

PubMed Central

Ahrens, Bradley J.; Li, Lin; Ciminera, Alexandra K.; Chea, Junie; Poku, Erasmus; Bading, James R.; Weist, Michael R.; Miller, Marcia M.; Colcher, David M.

2017-01-01

The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague–Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64Cu-DOTA-alendronate. Results: 64Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as well as the differentiation of malignant versus benign tumors based on absolute labeling uptake. PMID:28450564

The use of sonographic subjective tumor assessment, IOTA logistic regression model 1, IOTA Simple Rules and GI-RADS system in the preoperative prediction of malignancy in women with adnexal masses.

PubMed

Koneczny, Jarosław; Czekierdowski, Artur; Florczak, Marek; Poziemski, Paweł; Stachowicz, Norbert; Borowski, Dariusz

2017-01-01

Sonography based methods with various tumor markers are currently used to discriminate the type of adnexal masses. To compare the predictive value of selected sonography-based models along with subjective assessment in ovarian cancer prediction. We analyzed data of 271 women operated because of adnexal masses. All masses were verified by histological examination. Preoperative sonography was performed in all patients and various predictive models includ¬ing IOTA group logistic regression model LR1 (LR1), IOTA simple ultrasound-based rules by IOTA (SR), GI-RADS and risk of malignancy index (RMI3) were used. ROC curves were constructed and respective AUC's with 95% CI's were compared. Of 271 masses 78 proved to be malignant including 6 borderline tumors. LR1 had sensitivity of 91.0%, specificity of 91.2%, AUC = 0.95 (95% CI: 0.92-0.98). Sensitivity for GI-RADS for 271 patients was 88.5% with specificity of 85% and AUC = 0.91 (95% CI: 0.88-0.95). Subjective assessment yielded sensitivity and specificity of 85.9% and 96.9%, respectively with AUC = 0.97 (95% CI: 0.94-0.99). SR were applicable in 236 masses and had sensitivity of 90.6% with specificity of 95.3% and AUC = 0.93 (95% CI 0.89-0.97). RMI3 was calculated only in 104 women who had CA125 available and had sensitivity of 55.3%, specificity of 94% and AUC = 0.85 (95% CI: 0.77-0.93). Although subjective assessment by the ultrasound expert remains the best current method of adnexal tumors preoperative discrimination, the simplicity and high predictive value favor the IOTA SR method, and when not applicable, the IOTA LR1 or GI-RADS models to be primarily and effectively used.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review

PubMed Central

Fiorino, Sirio; Bacchi-Reggiani, Letizia; de Biase, Dario; Fornelli, Adele; Masetti, Michele; Tura, Andrea; Grizzi, Fabio; Zanello, Matteo; Mastrangelo, Laura; Lombardi, Raffaele; Acquaviva, Giorgia; di Tommaso, Luca; Bondi, Arrigo; Visani, Michela; Sabbatani, Sergio; Pontoriero, Laura; Fabbri, Carlo; Cuppini, Andrea; Pession, Annalisa; Jovine, Elio

2015-01-01

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association. PMID:26668515

Modulation of the malignant phenotype with the urokinase-type plasminogen activator and the type I plasminogen activator inhibitor.

PubMed

Sordat, B; Reiter, L; Cajot, J F

1990-12-02

Gene transfer techniques were utilized to evaluate the role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in enhancing or preventing the expression of the invasive malignant phenotype, respectively. Mouse L-cell transfectants expressing human uPA or human PAI-1 as well as mouse B16 transfectants expressing mouse uPA or human PAI-1 were generated. These transfectants were tested using a variety of experimental methods including smooth muscle cell matrix solubilization in vitro, lung colony formation in vivo and co-cultures of antagonist-expressing cells in vitro. Results from these studies provide direct evidence for an enhancing role of uPA in malignant invasion and experimental metastasis and for a modulatory role of PAI-1 in tumor cell-mediated breakdown of extracellular matrices.

Proposed Nomogram Predicting the Individual Risk of Malignancy in the Patients With Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas.

PubMed

Jang, Jin-Young; Park, Taesung; Lee, Selyeong; Kim, Yongkang; Lee, Seung Yeoun; Kim, Sun-Whe; Kim, Song-Cheol; Song, Ki-Byung; Yamamoto, Masakazu; Hatori, Takashi; Hirono, Seiko; Satoi, Sohei; Fujii, Tsutomu; Hirano, Satoshi; Hashimoto, Yasushi; Shimizu, Yashuhiro; Choi, Dong Wook; Choi, Seong Ho; Heo, Jin Seok; Motoi, Fuyuhiko; Matsumoto, Ippei; Lee, Woo Jung; Kang, Chang Moo; Han, Ho-Seong; Yoon, Yoo-Seok; Sho, Masayuki; Nagano, Hiroaki; Honda, Goro; Kim, Sang Geol; Yu, Hee Chul; Chung, Jun Chul; Nagakawa, Yuichi; Seo, Hyung Il; Yamaue, Hiroki

2017-12-01

This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded. The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test. A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Relation between diabetes, metformin treatment and the occurrence of malignancies in a Belgian primary care setting.

PubMed

Geraldine, Ngwana; Marc, Aerts; Carla, Truyers; Chantal, Mathieu; Stefaan, Bartholomeeusen; Welcome, Wami; Frank, Buntinx

2012-08-01

Associations between type 2 diabetic patients and a higher risk of developing cancer have been reported worldwide. Recently, a protective effect of metformin has been described. To examine in the Belgian primary care population the relation between presence of type 2 diabetes with and without metformin treatment and the occurrence of malignancies. Retrospective cohort study, based on the Intego database, an ongoing Belgian general practice-based morbidity registry, covering 90 general practitioners and including about 1.5 million patient-years between 1994 and 2008. Cox proportional hazard analysis comparing emergence of malignancy in patients with and without type 2 diabetes, and among patients with diabetes comparing emergence of malignancy in those treated with various antidiabetic drugs. Malignancies occurred more in type 2 diabetic patients compared to non-diabetic controls (HR=1.84; 95% CI=1.51-2.24), adjusted for age, gender and weight. Treatment with both metformin and 'other' antidiabetic agents was related to decreased cancer risk (HR=0.24 and 0.22) compared to diet only in men but not in women. In this Belgian primary care setting, diabetic patients have higher cancer prevalences than non-diabetic patients. Moreover, in diabetic men, not only metformin but also other antidiabetic agents were associated with lower cancer risks. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Differentiation and diagnosis of benign and malignant testicular lesions using 18F-FDG PET/CT.

PubMed

Shao, Dan; Gao, Qiang; Tian, Xu-Wei; Wang, Si-Yun; Liang, Chang-Hong; Wang, Shu-Xia

2017-08-01

The purpose of this study was to evaluate the differential diagnostic value of 18 F-fluorodeoxy glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for benign and malignant testicular lesions. The PET/CT scans of 53 patients with testicular lesions confirmed by biopsy or surgical pathology were retrospectively analyzed. There were 32 cases of malignant tumors and 21 cases of benign lesions. Differences in the maximum standardized uptake value (SUVmax) measurements and the SUVmax lesion/background ratios between benign and malignant lesions were analyzed. The diagnostic value of this PET/CT modality for the differential diagnosis of benign versus malignant testicular lesions was calculated. The differences in the SUVmax measurements and the SUVmax lesion/background ratios between benign and malignant lesions were statistically significant (SUVmax: Z=-4.295, p=0.000; SUVmax lesion/background ratio: Z=-5.219, p=0.000); specifically, both of these indicators were higher in malignant lesions compared to benign lesions. An SUVmax of 3.75 was the optimal cutoff value to differentiate between benign and malignant testicular lesions. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this PET/CT modality in the differential diagnosis of benign versus malignant testicular lesions were 90.6%, 80.9%, 86.8%, 87.9%, and 85.0%, respectively. 18 F-FDG PET/CT can accurately identify benign and malignant testicular lesions. Copyright © 2017 Elsevier B.V. All rights reserved.

Specific detection of soluble EphA2 fragments in blood as a new biomarker for pancreatic cancer.

PubMed

Koshikawa, Naohiko; Minegishi, Tomoko; Kiyokawa, Hirofumi; Seiki, Motoharu

2017-10-26

Because membrane type 1-matrix metalloproteinase 1 (MT1-MMP) and erythropoietin-producing hepatocellular receptor 2 (EphA2) expression are upregulated by the Ras/mitogen-activated protein kinase pathway, they are frequently coexpressed in malignant tumors. MT1-MMP cleaves the N-terminal ligand-binding domain of EphA2 and inactivates its ligand-dependent tumor-suppressing activity. Therefore, specific detection of the cleaved N-terminal EphA2 fragment in blood might be an effective biomarker to diagnose malignant tumors. To evaluate this possibility, we developed three monoclonal antibodies against the soluble EphA2 fragment. One of them recognized this fragment specifically, with negligible cross-reactivity to the intact form. We used the cleaved form-specific antibody to develop a quantitative enzyme-linked immunosorbent assay and confirmed the linear reactivity to the recombinant fragment. We applied this assay on commercially available serum specimens obtained from patients with several types of cancer including gastric, pancreatic, esophageal, gastroesophageal, and head-and-neck cancers, and healthy donors. Soluble EphA2 fragment levels in cancer-patient sera were higher than those in healthy donors (n=50). In particular, levels of eight out of nine (89%) pancreatic cancer patients and ten out of seventeen (59%) gastric cancer patients significantly exceeded cutoff values obtained from the healthy donors, whereas those of esophageal and head-and-neck cancer-patient sera were low. The preliminary receiver operating characteristic curve analysis for pancreatic cancer demonstrated that the sensitivity and specificity were 89.0% and 90.0%, respectively, whereas those of the conventional digestive tumor marker CA19-9 were 88.9% and 72.0%, respectively. These results indicated that specific detection of soluble EphA2 fragment levels in serum could be potentially useful as a biomarker to diagnose pancreatic cancer.

Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer

ClinicalTrials.gov

2017-12-11

Acute Undifferentiated Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia; Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Hairy Cell Leukemia; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Neoplasm of Uncertain Malignant Potential; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

The Potential of Cellular- and Viral-Based Immunotherapies for Malignant Glioma-Dendritic Cell Vaccines, Adoptive Cell Transfer, and Oncolytic Viruses.

PubMed

Maxwell, Russell; Luksik, Andrew S; Garzon-Muvdi, Tomas; Lim, Michael

2017-06-01

Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses. Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma. Due to their successes in the preclinical arena, many of these therapies have undergone phase I and II clinical testing. These early clinical trials have demonstrated the feasibility, safety, and efficacy of these immunotherapies. Dendritic cell vaccines, adoptive cell transfer, and oncolytic viruses may have a potential role in the treatment of malignant glioma. However, these modalities must be investigated in well-designed phase III trials to prove their efficacy.

Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data.

PubMed

Racle, Julien; de Jonge, Kaat; Baumgaertner, Petra; Speiser, Daniel E; Gfeller, David

2017-11-13

Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type-specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research (http://epic.gfellerlab.org).

Evaluation of IOTA Simple Ultrasound Rules to Distinguish Benign and Malignant Ovarian Tumours.

PubMed

Garg, Sugandha; Kaur, Amarjit; Mohi, Jaswinder Kaur; Sibia, Preet Kanwal; Kaur, Navkiran

2017-08-01

IOTA stands for International Ovarian Tumour Analysis group. Ovarian cancer is one of the common cancers in women and is diagnosed at later stage in majority. The limiting factor for early diagnosis is lack of standardized terms and procedures in gynaecological sonography. Introduction of IOTA rules has provided some consistency in defining morphological features of ovarian masses through a standardized examination technique. To evaluate the efficacy of IOTA simple ultrasound rules in distinguishing benign and malignant ovarian tumours and establishing their use as a tool in early diagnosis of ovarian malignancy. A hospital based case control prospective study was conducted. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analysed using chi-square test and kappa statistical method. Out of initial 55 patients, 50 patients were included in the final analysis who underwent surgery. IOTA simple rules were applicable in 45 out of these 50 patients (90%). The sensitivity for the detection of malignancy in cases where IOTA simple rules were applicable was 91.66% and the specificity was 84.84%. Accuracy was 86.66%. Classifying inconclusive cases as malignant, the sensitivity and specificity was 93% and 80% respectively. High level of agreement was found between USG and histopathological diagnosis with Kappa value as 0.323. IOTA simple ultrasound rules were highly sensitive and specific in predicting ovarian malignancy preoperatively yet being reproducible, easy to train and use.

Thyroid nodule classification using ultrasound elastography via linear discriminant analysis.

PubMed

Luo, Si; Kim, Eung-Hun; Dighe, Manjiri; Kim, Yongmin

2011-05-01

The non-surgical diagnosis of thyroid nodules is currently made via a fine needle aspiration (FNA) biopsy. It is estimated that somewhere between 250,000 and 300,000 thyroid FNA biopsies are performed in the United States annually. However, a large percentage (approximately 70%) of these biopsies turn out to be benign. Since the aggressive FNA management of thyroid nodules is costly, quantitative risk assessment and stratification of a nodule's malignancy is of value in triage and more appropriate healthcare resources utilization. In this paper, we introduce a new method for classifying the thyroid nodules based on the ultrasound (US) elastography features. Unlike approaches to assess the stiffness of a thyroid nodule by visually inspecting the pseudo-color pattern in the strain image, we use a classification algorithm to stratify the nodule by using the power spectrum of strain rate waveform extracted from the US elastography image sequence. Pulsation from the carotid artery was used to compress the thyroid nodules. Ultrasound data previously acquired from 98 thyroid nodules were used in this retrospective study to evaluate our classification algorithm. A classifier was developed based on the linear discriminant analysis (LDA) and used to differentiate the thyroid nodules into two types: (I) no FNA (observation-only) and (II) FNA. Using our method, 62 nodules were classified as type I, all of which were benign, while 36 nodules were classified as Type-II, 16 malignant and 20 benign, resulting in a sensitivity of 100% and specificity of 75.6% in detecting malignant thyroid nodules. This indicates that our triage method based on US elastography has the potential to substantially reduce the number of FNA biopsies (63.3%) by detecting benign nodules and managing them via follow-up observations rather than an FNA biopsy. Published by Elsevier B.V.

Canine gastric carcinoma: immunohistochemical expression of cell cycle proteins (p53, p21, and p16) and heat shock proteins (Hsp27 and Hsp70).

PubMed

Carrasco, V; Canfrán, S; Rodríguez-Franco, F; Benito, A; Sáinz, A; Rodríguez-Bertos, A

2011-01-01

Immunohistochemical staining for cell cycle proteins and heat shock proteins was performed on 17 canine gastric carcinomas. The immunoexpression of p53, p21, p16, Hsp27, and Hsp70 was investigated. A study was conducted to determine the histological type and parameters related to tumor malignancy. Possible associations and trends were assessed between the immunoexpression of each protein and tumor type as well as specific parameters of malignancy. High intratumor frequency of cellular p53 immunostaining was observed (61.96% average), but lower frequencies of p21 and p16 expression were present (34.65% and 10.41%, respectively). The p53 overexpression was associated with tumor infiltration (P = .0258). Expression of p21 was lower in undifferentiated carcinomas, and the loss of expression was associated with histopathological parameters characteristic of a poor prognosis such as lymphatic vessel invasion (P = .0258). The lack of p16 immunoreactivity was related to histopathological characteristics of malignancy such as the presence of evident and multiple nucleoli (P = .0475). In contrast, deep tumor infiltration was observed in those carcinomas with a high p16 index (P = .0475). Hsp70 appeared to be overexpressed in all gastric neoplasms included in this study. This is in contrast to Hsp27, because a group of tumors showed complete lack of Hsp27 immunoexpression, whereas the others displayed extensive Hsp27 immunostaining. The differences in Hsp27 did not correlate with any of the histopathological parameters, but Hsp27 immunoexpression was higher in the undifferentiated carcinoma. No significant differences in the expression of the proteins were found in canine gastric carcinomas according to their histological type. These findings may be useful for establishing a prognosis for canine gastric carcinoma.

CUP Syndrome-Metastatic Malignancy with Unknown Primary Tumor.

PubMed

Zaun, Gregor; Schuler, Martin; Herrmann, Ken; Tannapfel, Andrea

2018-03-09

2-4% of newly diagnosed cases of malignant disease involve cancer of unknown primary (CUP). This mixed entity is one of the 6 most common types of malignant disease in Germany. Highly refined treatment strategies can now be offered to patients with CUP. This review is based on pertinent publications retrieved by a selective search in PubMed with an emphasis on articles from the past decade. The current guidelines and recommendations of specialty societies were also considered in the evaluation. CUP most commonly manifests itself as metastases to the lymph nodes, lungs, liver, or bones. With the aid of imaging studies, including functional hybrid imaging and further medical examination, a primary tumor can be discovered in up to 40% of patients initially diagnosed with CUP. Immunohistochemistry guided by histomorphology often enables precise characterization of the lesion and can be supplemented, in selected cases, by molecular-genetic diagnostic evaluation. The most commonly detected types of primary tumor are cancers of the lung, pancreas, liver, and biliary system. For patients with local metastases, surgical resection or radiotherapy with curative intent is usually indicated, sometimes in the framework of a multimodal treatment concept. The median 2-year survival of patients with disseminated CUP is only 20%. For such patients, specific types of systemic therapy are recommended on the basis of the diagnostic characterization of the disease. Immune-modulatory antibodies can be effective, particularly in the treatment of CUP that has been characterized with biomarkers, but should still be considered experimental at present. A combination of conventional and innovative diagnostic methods enables the provision of highly refined therapeutic strategies to patients with CUP who are undergoing treatment in interdisciplinary cancer centers.

Diagnostic Quality of Magnetic Resonance Imaging Interpretation for Peripheral Nerve Sheath Tumors: Can Malignancy Be Determined?

PubMed

Karsy, Michael; Guan, Jian; Ravindra, Vijay M; Stilwill, Sarah; Mahan, Mark A

2016-11-01

Background Optimal management of peripheral nerve sheath tumors including neurofibromas, schwannomas, and malignant peripheral sheath tumors (MPNSTs) is predicated on knowing the specific pathology. Magnetic resonance imagining (MRI) has the potential to provide insight in the tumor type, yet imprecision in diagnosis remains. We assessed the accuracy of preoperative imaging diagnoses by comparing them with postoperative histopathologic diagnoses. We specifically focus on erroneous diagnosis of MPNSTs. Methods We reviewed all pathologically confirmed cases of nerve sheath tumors treated at our institution retrospectively from 2007 to 2015. Pre- and postoperative imaging data were reviewed for imaging-based diagnosis and compared with postresection pathologic diagnosis. Results The study included 127 patients: 82 diagnosed with neurofibroma, 17 with schwannoma, 24 with MPNST, and 4 with other histology types. A mean age of 40.8 ± 20.4 years, mean tumor size of 4.3 ± 3.6 cm, and mean follow-up of 29.1 ± 21.6 months were recorded. A family history of neurofibromatosis type 1 (NF1) was seen in 58 patients (46%). A discordant diagnosis from preoperative imaging and postoperative pathology was found in 65 individuals (51%). Most discordant diagnoses ( n  = 34) were inconclusive interpretation of preoperative imaging; however, 10 patients were diagnosed with a benign or unknown lesion on preoperative imaging but had an MPNST on histopathology. Patients with MPNST were more likely than those with benign pathologies to have larger lesions (7.6 ± 4.8 cm versus 3.5 ± 3.3 cm; p  = 0.004); however, a statistically acceptable threshold value could not be found to separate benign from malignant lesions. Clinical factors, such as NF1 status, did not meaningfully improve preoperative diagnosis. Conclusions These results suggest that routine MRI is insufficient to guide surgical decision making reliably. Additional imaging techniques may be necessary to delineate the radiologic features of nerve sheath tumors to determine pathology more precisely. Georg Thieme Verlag KG Stuttgart · New York.

Diagnostic values of vascular endothelial growth factor and epidermal growth factor receptor for benign and malignant hydrothorax.

PubMed

Gu, Yan; Zhang, Min; Li, Guo-Hua; Gao, Jun-Zhen; Guo, Liping; Qiao, Xiao-Juan; Wang, Li-Hong; He, Lan; Wang, Mei-Ling; Yan, Li; Fu, Xiu-Hua

2015-02-05

Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this study was to analyze the correlation between levels of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in patients with benign and malignant hydrothorax. The contents of VEGF in the pleural effusion and serum of the patients with malignant pleural effusion (n = 35) and benign pleural effusion (n = 30) were detected by double antibody sandwich enzyme linked immunosorbent assay. The gene copy number level of EGFR in pleural effusion was detected by fluorescence in situ hybridization (FISH). The points with the highest sensitivity and specificity were selected as the critical values to calculate the diagnostic value of the VEGF in pleural effusion and serum, and EGFR gene copy number in pleural effusion. The contents of VEGF in pleural effusion and serum of patients with malignant hydrothorax were (384.91 ± 120.18), and (129.62 ± 46.35) ng/L, respectively, which were significantly higher than those of the patients with benign hydrothorax (207.97 ± 64.04), (63.49 ± 24.58) ng/L (P < 0.01). The sensitivity and specificity of detecting VEGF in pleural effusion were 80.0% and 96.7% (the boundary value was 297.06 ng/L), respectively for diagnosing benign and malignant hydrothorax. The sensitivity and specificity of serum were 74.3% and 96.7%, respectively (the boundary value was 99.21 ng/L) for diagnosing benign and malignant hydrothorax. The diagnostic efficiencies of EGFR and VEGF in hydrothorax were similar. There was a significant correlation between EGFR and VEGF in hydrothorax (P < 0.01). VEGF and EGFR play important roles in the formation of pleural effusion. VEGF differed significantly in benign and malignant pleural effusions, which contributed to differential diagnosis results of benign and malignant pleural effusions. It is feasible to detect the gene copy number of the pleural effusion cell mass EGFR by FISH technique. Joint detection can improve the diagnostic sensitivity.

Diagnostic Values of Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor for Benign and Malignant Hydrothorax

PubMed Central

Gu, Yan; Zhang, Min; Li, Guo-Hua; Gao, Jun-Zhen; Guo, Liping; Qiao, Xiao-Juan; Wang, Li-Hong; He, Lan; Wang, Mei-Ling; Yan, Li; Fu, Xiu-Hua

2015-01-01

Background: Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this study was to analyze the correlation between levels of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in patients with benign and malignant hydrothorax. Methods: The contents of VEGF in the pleural effusion and serum of the patients with malignant pleural effusion (n = 35) and benign pleural effusion (n = 30) were detected by double antibody sandwich enzyme linked immunosorbent assay. The gene copy number level of EGFR in pleural effusion was detected by fluorescence in situ hybridization (FISH). The points with the highest sensitivity and specificity were selected as the critical values to calculate the diagnostic value of the VEGF in pleural effusion and serum, and EGFR gene copy number in pleural effusion. Results: The contents of VEGF in pleural effusion and serum of patients with malignant hydrothorax were (384.91 ± 120.18), and (129.62 ± 46.35) ng/L, respectively, which were significantly higher than those of the patients with benign hydrothorax (207.97 ± 64.04), (63.49 ± 24.58) ng/L (P < 0.01). The sensitivity and specificity of detecting VEGF in pleural effusion were 80.0% and 96.7% (the boundary value was 297.06 ng/L), respectively for diagnosing benign and malignant hydrothorax. The sensitivity and specificity of serum were 74.3% and 96.7%, respectively (the boundary value was 99.21 ng/L) for diagnosing benign and malignant hydrothorax. The diagnostic efficiencies of EGFR and VEGF in hydrothorax were similar. There was a significant correlation between EGFR and VEGF in hydrothorax (P < 0.01). Conclusions: VEGF and EGFR play important roles in the formation of pleural effusion. VEGF differed significantly in benign and malignant pleural effusions, which contributed to differential diagnosis results of benign and malignant pleural effusions. It is feasible to detect the gene copy number of the pleural effusion cell mass EGFR by FISH technique. Joint detection can improve the diagnostic sensitivity. PMID:25635424

Performance of FDG-PET/CT in solitary pulmonary nodule based on pre-test likelihood of malignancy: results from the ITALIAN retrospective multicenter trial.

PubMed

Evangelista, Laura; Cuocolo, Alberto; Pace, Leonardo; Mansi, Luigi; Del Vecchio, Silvana; Miletto, Paolo; Sanfilippo, Silvia; Pellegrino, Sara; Guerra, Luca; Pepe, Giovanna; Peluso, Giuseppina; Salvatore, Marco; Galicchio, Rosj; Zuffante, Michele; Annunziata, Salvatore; Farsad, Mohsen; Chiaravalloti, Agostino; Spadafora, Marco

2018-05-07

The aim of this study was to determine the performance of 18 F-FDG-PET/CT in patients with solitary pulmonary nodule (SPN), stratifying the risk according to the likelihood of pulmonary malignancy. FDG-PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. FDG uptake in SPN was assessed by a 4-point scoring system and semiquantitative analysis using the ratio between SUVmax in SPN and SUVmean in mediastinal blood pool (BP) and between SUVmax in SPN and SUVmean in liver (L). Histopathology and/or follow-up data were used as standard of reference. SPN was malignant in 180 (36%) patients, benign in 175 (35%), and indeterminate in 147 (29%). The 355 patients with a definitive SPN nature (malignant or benign) were considered for the analysis. Considering FDG uptake ≥ 2, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were 85.6%, 85.7%, 86%, 85.2%, and 85.6% respectively. Sensitivity and PPV were higher (P < 0.05) in intermediate and high-risk patients, while specificity and NPV were higher (P < 0.05) in low-risk patients. On receiver operating characteristic curve analysis, the cut-offs for better discrimination between benign and malignant SPN were 1.56 (sensitivity 81% and specificity 87%) and 1.12 (sensitivity 81% and specificity 86%) for SUVmax/SUVmeanBP and SUVmax/SUVmeanL respectively. In intermediate and high-risk patients, including the SUVmax/SUVmeanBP, the specificity shifted from 85% and 50% to 100%. Visual FDG-PET/CT has an acceptable performance in patients with SPN, but accuracy improves when SUVratios are considered, particularly in patients with intermediate and high risk of malignancy.

Renal mass biopsy using Raman spectroscopy identifies malignant and benign renal tumors: potential for pre-operative diagnosis.

PubMed

Liu, Yufei; Du, Zhebin; Zhang, Jin; Jiang, Haowen

2017-05-30

The accuracy of renal mass biopsy to diagnose malignancy can be affected by multiple factors. Here, we investigated the feasibility of Raman spectroscopy to distinguish malignant and benign renal tumors using biopsy specimens. Samples were collected from 63 patients who received radical or partial nephrectomy, mass suspicious of cancer and distal parenchyma were obtained from resected kidney using an 18-gauge biopsy needle. Four Raman spectra were obtained for each sample, and Discriminant Analysis was applied for data analysis. A total of 383 Raman spectra were eventually gathered and each type of tumor had its characteristic spectrum. Raman could separate tumoral and normal tissues with an accuracy of 82.53%, and distinguish malignant and benign tumors with a sensitivity of 91.79% and specificity of 71.15%. It could classify low-grade and high-grade tumors with an accuracy of 86.98%. Besides, clear cell renal carcinoma was differentiated with oncocytoma and angiomyolipoma with accuracy of 100% and 89.25%, respectively. And histological subtypes of cell carcinoma were distinguished with an accuracy of 93.48%. When compared with final pathology and biopsy, Raman spectroscopy was able to correctly identify 7 of 11 "missed" biopsy diagnoses. These results suggested that Raman may serve as a promising non-invasive approach in the future for pre-operative diagnosis.

A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy.

PubMed

Chen, Zhiqiang; Zhang, Long; Han, Guoyong; Zuo, Xueliang; Zhang, Yao; Zhu, Qin; Wu, Jindao; Wang, Xuehao

2018-01-01

Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been found to be dysregulated in various cancers. However, the clinical application value of these circRNAs in digestive system cancers remains to be clarified. We aimed to comprehensively explore the potential role of circRNAs as diagnostic indicators in digestive system malignancies. Relevant studies were systematically retrieved from PubMed, Web of Science and the Cochrane Library. The data that were required to complete 2 × 2 contingency tables were obtained from the included studies. Stratified analyses by cancer type, sample size and publication year were performed. Thirteen studies with 2,276 individuals were included in the meta-analysis. The pooled sensitivity and specificity of circRNAs in the diagnosis of digestive system malignancy were 0.72 [95% confidence interval (CI): 0.65-0.77] and 0.77 (95% CI: 0.72-0.81), respectively. The overall positive likelihood ratio was 3.09 (95% CI: 2.64-3.62), and the overall negative likelihood ratio was 0.37 (95% CI: 0.31-0.44). The pooled diagnostic odds ratio was 8.38 (95% CI: 6.86-10.25), and the overall area under the curve was 0.81 (95% CI: 0.77-0.84), indicating good discriminative ability of circRNAs as biomarkers for digestive system malignancy. circRNAs distinguish patients with digestive system cancer from controls with relatively high diagnostic accuracy. circRNAs may be used as potential biomarkers for the diagnosis of digestive system malignancy. © 2018 The Author(s). Published by S. Karger AG, Basel.

NY-BR-1 Antigen Expression and anti-NY-BR-1 IgG in Egyptian Breast Cancer Patients: Clinicopathological and Prognostic Significance.

PubMed

Abu El-Nazar, Salma Y; Ghazy, Amany A; Ghoneim, Hossam E; Zoheir, Malak; Ahmed, Ahmed S; Sorour, Sally S; Abouelella, Amira M

2015-01-01

Breast cancer is the most common gynecological malignancy in the world. In Egypt, it ranks the first among female malignancies with incidence of 37.7%. Over the last decades, the integration of prognostic and predictive markers in treatment decisions has led to more individualized and optimized therapy. NY-BR-1 antigen has been shown to be frequently expressed in breast cancers. The study aimed to assess the tissue expression of NY-BR-1 antigen and serum IgG antibody to this antigen in Egyptian breast cancer females. The study was conducted on 60 females (10 healthy, 10 having benign breast lesions, 40 with malignant breast cancer). NY-BR-1 Ag expression was evaluated by immunohistochemistry and anti-NY-BR-1 IgG was assessed by ELISA. Results revealed a significant difference in NY-BR-1 Ag expression between benign and malignant breast cancer patients. There was a significant correlation between NY-BR-1 antigen expression and estrogen receptor's status (P = 0.019), stage of the disease (P = 0.008), menopausal status (P = 0.008), lymph node involvement (P = 0.022) and anti-NY-BR-1 IgG (P = 0.032) among the studied individuals. In addition, there was a statistically significant increase in anti-NY-BR-1 IgG O.D. results among malignant breast cancer group. It is correlated with tumor type (P < 0.001) and progesterone receptor status (P = 0.038). In conclusion, our work may represent a step towards identification of a new prognostic marker specific for breast cancer.

Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

PubMed Central

Kaneko, Sadahiro

2016-01-01

Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer

PubMed Central

2014-01-01

Background Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments. Results ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle. Conclusions The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women. PMID:24758163

Correlating the ground truth of mammographic histology with the success or failure of imaging.

PubMed

Tot, Tibor

2005-02-01

Detailed and systematic mammographic-pathologic correlation is essential for evaluation of the advantages and disadvantages of mammography as an imaging method as well as for establishing the role of additional methods or alternatives. Two- and three-dimensional large section histopathology represents an ideal tool for this correlation. This kind of interdisciplinary approach ("mammographic histology") is slowly but irrevocably becoming accepted as the new golden standard in diagnosing breast abnormalities. In this review, upon summarizing the theoretical background and our practical experience in routine diagnostic use of these advantageous techniques, we report on the accuracy of the preoperative radiological diagnosis. As compared to the final diagnostic outcome, stellate lesions on the mammogram and microcalcifications of casting type indicate malignancy with very high accuracy while predicting malignancy in cases of powdery and crushed stone type microcalcifications is problematic. The extent of the disease is regularly underestimated on the mammogram by the radiologist. Combining different radiological signs, and comparing repeated static images taken in regular intervals in screening or postoperative follow-up, the mammographer may type and grade the lesions properly in a considerable number of cases. Regular mammographic-pathologic correlation may increase the specificity and sensitivity of mammographic diagnosis. This correlation is essential for establishing the proper pre- and postoperative histological diagnosis, too.

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia.

PubMed

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS.

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia

PubMed Central

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

2016-01-01

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS. PMID:27725556

Posttransplant malignancies in renal transplant recipients: 22-years experience from a single center in Pakistan.

PubMed

Yunus, Mahira; Aziz, Tahir; Mubarak, Muhammed

2012-01-01

To study the incidence, types and distribution pattern of malignant tumors in renal transplant recipients at a single center in Pakistan. This retrospective study was conducted at Sindh Institute of Urology and Transplantation (SIUT) and included all transplant patients on regular follow-up from November 1986 to December 2008. The original biopsy reports and case files of all patients who developed posttransplant malignancies were reviewed and relevant demographic, clinical, radiological, and histopathological data were retrieved and analyzed. SPSS version 10.0 was used for statistical analysis. Over 22 years of study period, 1816 renal transplants were carried out at our center. Among these, 44 patients developed malignancies constituting an overall incidence rate of 2.4%. All patients in this study were males with a mean age of 34.9±9.5 years (range: 9 to 60 years). The most common type of malignancy was lymphoma (27 patients, 61.4%), followed by Kaposi's sarcoma (11 patients, 25%) and skin malignancies (3 patients, 6.8%). One case each of adenocarcinoma of the gallbladder, acute myeloid leukemia (AML), conjunctival carcinoma-in-situ and seminoma were also diagnosed. Posttransplant malignancies occurring in our renal transplant recipients show different incidence rates and patterns as compared with western studies.

Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-Analysis

PubMed Central

Hollevoet, Kevin; Reitsma, Johannes B.; Creaney, Jenette; Grigoriu, Bogdan D.; Robinson, Bruce W.; Scherpereel, Arnaud; Cristaudo, Alfonso; Pass, Harvey I.; Nackaerts, Kristiaan; Rodríguez Portal, José A.; Schneider, Joachim; Muley, Thomas; Di Serio, Francesca; Baas, Paul; Tomasetti, Marco; Rai, Alex J.; van Meerbeeck, Jan P.

2012-01-01

Purpose Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. Methods The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. Results At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). Conclusion In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research. PMID:22412141

Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies.

PubMed

Sharma, Raghava; Huang, Xianming; Brekken, Rolf A; Schroit, Alan J

2017-08-08

There has been increasing interest in the detection of tumour exosomes in blood for cancer diagnostics. Most studies have focussed on miRNA and protein signatures that are surrogate markers for specific tumour types. Because tumour cells and tumour-derived exosomes display phosphatidylserine (PS) in their outer membrane leaflet, we developed a highly sensitive ELISA-based system that detects picogram amounts of exosomal phospholipid in plasma as a cancer biomarker. This report describes the development of a highly specific and sensitive ELISA for the capture of PS-expressing tumour exosomes in the blood of tumour-bearing mice. To monitor the relationship between tumour burden and tumour exosome plasma concentrations, plasma from one transplantable breast cancer model (MDA-MB-231) and three genetic mouse models (MMTV-PyMT; breast and KIC and KPC; pancreatic) were screened for captured exosomal phospholipid. We show that quantitative assessment of PS-expressing tumour exosomes detected very early-stage malignancies before clinical evidence of disease in all four model systems. Tumour exosome levels showed significant increases by day 7 after tumour implantation in the MDA-MB-231 model while palpable tumours appeared only after day 27. For the MMTV-PyMT and KIC models, tumour exosome levels increased significantly by day 49 (P⩽0.0002) and day 21 (P⩽0.001) while tumours developed only after days 60 and 40, respectively. For the KPC model, a significant increase in blood exosome levels was detected by day 70 (P=0.023) when only preinvasive lesions are microscopically detectable. These data indicate that blood PS exosome levels is a specific indicator of cancer and suggest that blood PS is a biomarker for early-stage malignancies.

Immunological Outcome in Haploidentical-HSC Transplanted Patients Treated with IL-10-Anergized Donor T Cells

PubMed Central

Bacchetta, Rosa; Lucarelli, Barbarella; Sartirana, Claudia; Gregori, Silvia; Lupo Stanghellini, Maria T.; Miqueu, Patrick; Tomiuk, Stefan; Hernandez-Fuentes, Maria; Gianolini, Monica E.; Greco, Raffaella; Bernardi, Massimo; Zappone, Elisabetta; Rossini, Silvano; Janssen, Uwe; Ambrosi, Alessandro; Salomoni, Monica; Peccatori, Jacopo; Ciceri, Fabio; Roncarolo, Maria-Grazia

2013-01-01

T-cell therapy after hematopoietic stem cell transplantation (HSCT) has been used alone or in combination with immunosuppression to cure hematologic malignancies and to prevent disease recurrence. Here, we describe the outcome of patients with high-risk/advanced stage hematologic malignancies, who received T-cell depleted (TCD) haploidentical-HSCT (haplo-HSCT) combined with donor T lymphocytes pretreated with IL-10 (ALT-TEN trial). IL-10-anergized donor T cells (IL-10-DLI) contained T regulatory type 1 (Tr1) cells specific for the host alloantigens, limiting donor-vs.-host-reactivity, and memory T cells able to respond to pathogens. IL-10-DLI were infused in 12 patients with the goal of improving immune reconstitution after haplo-HSCT without increasing the risk of graft-versus-host-disease (GvHD). IL-10-DLI led to fast immune reconstitution in five patients. In four out of the five patients, total T-cell counts, TCR-Vβ repertoire and T-cell functions progressively normalized after IL-10-DLI. These four patients are alive, in complete disease remission and immunosuppression-free at 7.2 years (median follow-up) after haplo-HSCT. Transient GvHD was observed in the immune reconstituted (IR) patients, despite persistent host-specific hypo-responsiveness of donor T cells in vitro and enrichment of cells with Tr1-specific biomarkers in vivo. Gene-expression profiles of IR patients showed a common signature of tolerance. This study provides the first indication of the feasibility of Tr1 cell-based therapy and paves way for the use of these Tr1 cells as adjuvant treatment for malignancies and immune-mediated disorders. PMID:24550909

Rare pancreatic neoplasms: the utility of endoscopic ultrasound-guided fine-needle aspiration-a large single center study.

PubMed

Imaoka, Hiroshi; Yamao, Kenji; Bhatia, Vikram; Shimizu, Yasuhiro; Yatabe, Yasushi; Koshikawa, Takashi; Kinoshita, Yoshikazu

2009-01-01

Tumors other than ductal adenocarcinomas constitute 10%-15% of all pancreatic tumors. We describe the performance and pitfalls of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosis of these rare pancreatic tumors and their characteristic cytopathological features. The records of 455 pancreatic fine-needle aspiration procedures done between March 1997 and August 2006 at Aichi Cancer Center, Nagoya, Japan, were reviewed. Besides cytology, aspirated material was routinely submitted in formalin for cell-block analysis. The reference standard for final diagnosis was surgical pathology from resected specimens. Twenty-eight rare (nonductal adenocarcinomas) pancreatic tumors were identified. Overall, EUS-FNA with the results of cytology, cell-block processing, and immunohistochemistry could correctly diagnose the type of neoplasm in 19 (67.9%) cases. EUS-FNA could distinguish benign from malignant rare tumors with a sensitivity of 69.2%, a specificity of 100%, positive predictive value of 100%, negative predictive value of 79.0%, and accuracy of 85.7%. None of three malignant pancreatic endocrine neoplasms could be diagnosed as malignant. An adequate core tissue sample could be obtained in 21 cases (75.0%) and provide a histopathological diagnosis in 19 (67.9%) cases. EUS-FNA could change the presumptive diagnosis in 11 (39.3%) cases. Specific immunochemical studies were useful adjuncts to the diagnosis. No major or minor complication was noted in any patient. Pancreatic neoplasms other than ductal adenocarcinomas have diverse imaging and histopathological features. EUS-FNA is accurate and safe for their identification.

Update: the status of clinical trials with kinase inhibitors in thyroid cancer.

PubMed

Wells, Samuel A; Santoro, Massimo

2014-05-01

Thyroid cancer is usually cured by timely thyroidectomy; however, the treatment of patients with advanced disease is challenging because their tumors are mostly unresponsive to conventional therapies. Recently, the malignancy has attracted much interest for two reasons: the dramatic increase in its incidence over the last three decades, and the discovery of the genetic mutations or chromosomal rearrangements causing most histological types of thyroid cancer. This update reviews the molecular genetics of thyroid cancer and the clinical trials evaluating kinase inhibitors (KIs) in patients with locally advanced or metastatic disease. The update also reviews studies in other malignancies, which have identified mechanisms of efficacy, and also resistance, to specific KIs. This information has been critical both to the development of effective second-generation drugs and to the design of combinatorial therapeutic regimens. Finally, the update addresses the major challenges facing clinicians who seek to develop more effective therapy for patients with thyroid cancer. PubMed was searched from January 2000 to November 2013 using the following terms: thyroid cancer, treatment of thyroid cancer, clinical trials in thyroid cancer, small molecule therapeutics, kinase inhibitors, and next generation sequencing. A new era in cancer therapy has emerged based on the introduction of KIs for the treatment of patients with liquid and solid organ malignancies. Patients with thyroid cancer have benefited from this advance and will continue to do so with the development of drugs having greater specificity and with the implementation of clinical trials of combined therapeutics to overcome drug resistance.

Estimating canine cancer incidence: findings from a population-based tumour registry in northwestern Italy.

PubMed

Baioni, Elisa; Scanziani, Eugenio; Vincenti, Maria Claudia; Leschiera, Mauro; Bozzetta, Elena; Pezzolato, Marzia; Desiato, Rosanna; Bertolini, Silvia; Maurella, Cristiana; Ru, Giuseppe

2017-06-28

Canine cancer registry data can be put to good use in epidemiological studies. Quantitative comparison of tumour types may reveal unusual cancer frequencies, providing directions for research and generation of hypotheses of cancer causation in a specific area, and suggest leads for identifying risk factors. Here we report canine cancer incidence rates calculated from a population-based registry in an area without any known specific environmental hazard. In its 90 months of operation from 2001 to 2008 (the observation period in this study), the population-based Piedmont Canine Cancer Registry collected data on 1175 tumours confirmed by histopathological diagnosis. The incidence rate was 804 per 100,000 dog-years for malignant tumours and 897 per 100,000 dog-years for benign tumours. Higher rates for all cancers were observed in purebred dogs, particularly in Yorkshire terrier and Boxer. The most prevalent malignant neoplasms were cutaneous mastocytoma and hemangiopericytoma, and mammary gland complex carcinoma and simplex carcinoma. The Piedmont canine cancer registry is one of few of its kind whose operations have been consistently supported by long-term public funding. The registry-based cancer incidence rates were estimated with particular attention to the validity of data collection, thus minimizing the potential for bias. The findings on cancer incidence rates may provide a reliable reference for comparison studies. Researches conducted on dogs, used as sentinels for community exposure to environmental carcinogens, can be useful to detect excess risks in the incidence of malignant tumours in the human population.

Clinicopathological Profile and Malignant Transformation in Oral Lichen Planus: A Retrospective Study

PubMed Central

Bandyopadhyay, Alokenath; Behura, Shyam Sundar; Nishat, Roquaiya; Dash, Kailash Chandra; Bhuyan, Lipsa; Ramachandra, Sujatha

2017-01-01

Objectives: The aim of this study was to analyze the histopathologically diagnosed cases of oral lichen planus (OLP) in terms of age, gender, clinical variant, site, hyperpigmentation, systemic illness, grade of dysplasia, and associated malignant transformation. This study also intended to do a review of reported cases of OLP with malignant transformation. Materials and Methods: One hundred and forty-three cases of histopathologically diagnosed OLP between 2010 and 2016 were retrospectively reviewed. Demographic and clinicopathological data including malignant transformation were obtained. The data obtained were analyzed using the Statistical Package for the Social Sciences (SPSS) software for Windows version 20.0 (IBM SPSS, SPSS Inc., Chicago, IL, USA). A review of published literature on OLP with malignant transformation was also done from 1988 to 2017 and tabulated. Results: OLP in this study showed a male predilection with most of the patients in the third decade. The buccal mucosa (bilateral presentation) was the most common site (79.72%), and reticular type was the most common clinical type (79.02%) followed by erosive type (20.98%). The majority (92.31%) of cases were diagnosed with OLP without dysplasia. The rest (7.69%) of dysplastic cases were predominantly seen in the buccal mucosa of 58 years and above, female patients manifesting mainly as erosive type. Two patients (1.4%) previously diagnosed clinically and histopathologically as OLP developed oral squamous cell carcinoma. Conclusion: The present investigation revealed the predominance of OLP among middle-aged male population and the prevalence of bilateral involvement of buccal mucosa. Two of our cases showed malignant transformation over an average period of 3.5 years. The outcome of this study emphasizes the role of clinical follow-up of patients with OLP. PMID:28584781

Clinicopathological Profile and Malignant Transformation in Oral Lichen Planus: A Retrospective Study.

PubMed

Bandyopadhyay, Alokenath; Behura, Shyam Sundar; Nishat, Roquaiya; Dash, Kailash Chandra; Bhuyan, Lipsa; Ramachandra, Sujatha

2017-01-01

The aim of this study was to analyze the histopathologically diagnosed cases of oral lichen planus (OLP) in terms of age, gender, clinical variant, site, hyperpigmentation, systemic illness, grade of dysplasia, and associated malignant transformation. This study also intended to do a review of reported cases of OLP with malignant transformation. One hundred and forty-three cases of histopathologically diagnosed OLP between 2010 and 2016 were retrospectively reviewed. Demographic and clinicopathological data including malignant transformation were obtained. The data obtained were analyzed using the Statistical Package for the Social Sciences (SPSS) software for Windows version 20.0 (IBM SPSS, SPSS Inc., Chicago, IL, USA). A review of published literature on OLP with malignant transformation was also done from 1988 to 2017 and tabulated. OLP in this study showed a male predilection with most of the patients in the third decade. The buccal mucosa (bilateral presentation) was the most common site (79.72%), and reticular type was the most common clinical type (79.02%) followed by erosive type (20.98%). The majority (92.31%) of cases were diagnosed with OLP without dysplasia. The rest (7.69%) of dysplastic cases were predominantly seen in the buccal mucosa of 58 years and above, female patients manifesting mainly as erosive type. Two patients (1.4%) previously diagnosed clinically and histopathologically as OLP developed oral squamous cell carcinoma. The present investigation revealed the predominance of OLP among middle-aged male population and the prevalence of bilateral involvement of buccal mucosa. Two of our cases showed malignant transformation over an average period of 3.5 years. The outcome of this study emphasizes the role of clinical follow-up of patients with OLP.

Inhibitors of Angiogenesis.

PubMed

Büning, H; Hacker, U T

Angiogenesis plays a pivotal role in malignant, ischemic, inflammatory, infectious and immune disorders. The increasing molecular understanding of angiogenic processes fostered the development of strategies to induce or inhibit angiogenesis for therapeutic purposes. Here, we focus on anti-angiogenic therapies, which represent a standard of care in the treatment of different cancer types and in neovascular age-related macular degeneration. Specifically, strategies related to the blockade of angiogenic proteins and receptors will be outlined covering both preclinical and clinical aspects. Finally, examples of gene therapy based anti-angiogenic approaches are presented.

Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2017-04-01

MPNST. Specifically, we are examining the mechanisms of action and in vivo utility of two classes of drugs , BH3 mimetics and lysosomotropic agents...on MPNSTs. The drugs that we are testing are approved for human use and could be rapidly advanced into human MPNST clinical trials if our pre...and BH3-mimetics, such as ABT-263, and to determine if combinations of these drugs might be more effective in killing MPNST cells in vitro. As

Epstein-Barr virus and renal transplantation.

PubMed

Le, Jade; Durand, Christine M; Agha, Irfan; Brennan, Daniel C

2017-01-01

Epstein-Barr virus (EBV) is a gamma herpesvirus associated with diseases ranging from asymptomatic viremia to post-transplant malignancies in kidney transplant recipients. EBV specifically is associated with post-transplantation lymphoproliferative disorder (PTLD), in kidney transplant recipients, with increased risk in EBV seronegative patients with EBV seropositive donors on intensified immunosuppression. The diagnosis of PTLD relies on clinical suspicion plus tissue biopsy with polymerase chain reaction (PCR) testing of blood currently used for risk determination in high-risk recipients. Therapeutic strategies for PTLD include reduction of immunosuppression, chemotherapy and rituximab, and consideration of sirolimus-based immunosuppression. Antivirals such as ganciclovir are used to prevent reactivation of cytomegalovirus and other herpes viruses but are not onco-therapeutic. Radiation therapy or surgery is indicated for bulky, disseminated or recalcitrant disease. Prognosis varies depending on the type of malignancy identified and stage of disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Kinase gene fusions in defined subsets of melanoma.

PubMed

Turner, Jacqueline; Couts, Kasey; Sheren, Jamie; Saichaemchan, Siriwimon; Ariyawutyakorn, Witthawat; Avolio, Izabela; Cabral, Ethan; Glogowska, Magdelena; Amato, Carol; Robinson, Steven; Hintzsche, Jennifer; Applegate, Allison; Seelenfreund, Eric; Gonzalez, Rita; Wells, Keith; Bagby, Stacey; Tentler, John; Tan, Aik-Choon; Wisell, Joshua; Varella-Garcia, Marileila; Robinson, William

2017-01-01

Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kinase Gene Fusions in Defined Subsets of Melanoma

PubMed Central

Turner, Jacqueline; Couts, Kasey; Sheren, Jamie; Saichaemchan, Siriwimon; Ariyawutyakorn, Witthawat; Avolio, Izabela; Cabral, Ethan; Glogowska, Magdelena; Amato, Carol; Robinson, Steven; Hintzsche, Jennifer; Applegate, Allison; Seelenfreund, Eric; Gonzalez, Rita; Wells, Keith; Bagby, Stacey; Tentler, John; Tan, Aik-Choon; Wisell, Joshua; Varella-Garcia, Marileila; Robinson, William

2017-01-01

Summary Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in-situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by IHC or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought-and should be further explored particularly in melanomas lacking known driver mutations. PMID:27864876

[Cytomegalovirus-associated infectious mononucleosis-like syndrome accompanied by transient monoclonal expansion of CD8+ T-cells].

PubMed

Yonezawa, Akihito; Onaka, Takashi; Imada, Kazunori

2009-08-01

Most cases of infectious mononucleosis (IM) are caused by Epstein-Barr virus (EBV). Other pathogens have been reported to cause heterophile-negative mononucleosis-like syndrome, including cytomegalovirus (CMV) and human immunodeficiency virus type-1 (HIV-1). Primary CMV infection is often asymptomatic in immunocompetent individuals. In this article, we describe a patient with prolonged fever and fatigue, who developed transient monoclonal CD8+ T-cell lymphocytosis after primary CMV infection. Monoclonal gene rearrangement of T-cell receptor (TCR) beta locus was transiently detected in DNA from peripheral lymphocytes. Monoclonal rearrangement and atypical lymphocytosis disappeared after treatment with anti-viral agents. These observations imply that monoclonal expansion of T-cells could be a reactive phenomenon of primary CMV infection and TCR gene rearrangement is not specific for malignancy. Physicians should carefully follow patients with monoclonal expansion of CD8+ T-cells after CMV-IM in order to rule out T cell malignancy.

Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

PubMed

Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

2018-02-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

HDAC Inhibitors as Novel Anti-Cancer Therapeutics.

PubMed

De Souza, Cristabelle; Chatterji, Biswa Prasun

2015-01-01

Malignant growth of cells is a condition characterized by unchecked cellular proliferation, genetic instability and epigenetic dysregulation. Up-regulated HDAC (Histone Deacetylase) enzyme activity is associated with a closed chromatin assembly and subsequent gene repression, forming a characteristic feature of malignantly transformed cells. Novel therapeutics are now targeting the zinc containing HDAC enzymes for treating various types of cancers. Recently, a spate of drugs acting via HDAC inhibition have been undergoing clinical trials and several patents present exciting molecules like PCI-24781 (Abexinostat), ITF- 2357 (Givinostat); MS-275 (Entinostat), MGCD 0103 (Mocetinostat), LBH-589 (Panobinostat), FK228 (Romidepsin), PXD-101 (Belinostat) and Valproic Acid to be used as alternatives or adjuvants to traditional chemotherapeutics. However, only three HDAC inhibitors have acquired FDA approval till date. Recently, PXD-101 obtained FDA approval for the treatment of Refractory or Relapsed Peripheral T cell lymphoma. The current article reviews patents that have introduced novel molecules that are HDAC isoform specific, superior to first generation HDAC inhibitors like SAHA (Suberoylanilide Hydroxamic Acid) and TSA (Trichostatin A) and can be modified structurally to reduce toxic side effects and increase specificity. These molecules can combine the best characteristics of an ideal HDAC inhibiting drug either as monotherapy or in combinatorial therapy for cancer treatment thus, indicating promise to be included in the next generation of target specific HDAC inhibiting drugs.

Diagnosis of human malignancies using laser-induced breakdown spectroscopy in combination with chemometric methods

NASA Astrophysics Data System (ADS)

Chen, Xue; Li, Xiaohui; Yu, Xin; Chen, Deying; Liu, Aichun

2018-01-01

Diagnosis of malignancies is a challenging clinical issue. In this work, we present quick and robust diagnosis and discrimination of lymphoma and multiple myeloma (MM) using laser-induced breakdown spectroscopy (LIBS) conducted on human serum samples, in combination with chemometric methods. The serum samples collected from lymphoma and MM cancer patients and healthy controls were deposited on filter papers and ablated with a pulsed 1064 nm Nd:YAG laser. 24 atomic lines of Ca, Na, K, H, O, and N were selected for malignancy diagnosis. Principal component analysis (PCA), linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and k nearest neighbors (kNN) classification were applied to build the malignancy diagnosis and discrimination models. The performances of the models were evaluated using 10-fold cross validation. The discrimination accuracy, confusion matrix and receiver operating characteristic (ROC) curves were obtained. The values of area under the ROC curve (AUC), sensitivity and specificity at the cut-points were determined. The kNN model exhibits the best performances with overall discrimination accuracy of 96.0%. Distinct discrimination between malignancies and healthy controls has been achieved with AUC, sensitivity and specificity for healthy controls all approaching 1. For lymphoma, the best discrimination performance values are AUC = 0.990, sensitivity = 0.970 and specificity = 0.956. For MM, the corresponding values are AUC = 0.986, sensitivity = 0.892 and specificity = 0.994. The results show that the serum-LIBS technique can serve as a quick, less invasive and robust method for diagnosis and discrimination of human malignancies.

[The distribution of B-lymphocytes in lymphoepithelial tissues as well as in tumors of the neck-, nose-, and throat region derived from lymphoreticular and lymphoepithelial tissues (author's transl)].

PubMed

Uhlmann, C; Krüger, G R; Sesterhenn, K; Wustrow, F; Fisher, R

1975-08-28

B-Lymphocytes carrying IgG-, IgM,- and IgA-surface receptors were estimated by fluorescence microscopy in the palatine tonsil of 50 patients aged 3 to 18 years as well as in 44 patients with various types of malignant lymphoms and lymphoepithelial carcinomas. Hyperplastic tonsillartissue contains large numbers of B-cells with a marked variability in concentration (4-30% IgG-cells, medium 12,9%;6-36 IgM-cells, medium 23.4%;3-38% IgA cells, medium 20.8%). There appears to exist an age-dependent increase in IgM-cells and an increase in IgG-and IgA-cells in patients with numerous recurrent infections of the upper respiratory tract. Malignant lymphomas can be grouped into three main categories: Such with a predominance of one B-cell line (above 75-80% of one immunological cell type); these include primarily malignant lymphomas of the well differentiated lymphocytic type (IgM and IgA receptors). Secondly, such with a significant decrease in B-cells (below 10%) which include primarily malignant lymphomas of the poorly differentiated lymphocytic type. Thirdly, such with an increased B-cell content but with more than one cell line participating in cell proliferation. The latter ones comprise certain cases of Hodkin's lymphomas. Lymphoepithial carcinomas are charactersized by a significant decrease in total B-cell content, except for IgE- and IgD-cells which were not investigated. The results show that the immunologic classification of malignant lymphomas correlates only to a certain degree with the morphologic classification; i.e. the same morphologic type of tumor may possess different immunologic characteristics. Since the immunologic characteristics may reflect a certain functional potential of these tumors as well as probably a certain kind of immunologic incompetence prior to tumor development, it is suggested, that future morphologic investigations of malignant lymphomas and lymphoepithelial carcinomas are combined with immunologic classifications.

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription.

PubMed

Singh, Prashant K; Long, Mark D; Battaglia, Sebastiano; Hu, Qiang; Liu, Song; Sucheston-Campbell, Lara E; Campbell, Moray J

2015-01-01

The Vitamin D Receptor (VDR) is a member of the nuclear receptor superfamily and is of therapeutic interest in cancer and other settings. Regulation of microRNA (miRNA) by the VDR appears to be important to mediate its actions, for example, to control cell growth. To identify if and to what extent VDR-regulated miRNA patterns change in prostate cancer progression, we undertook miRNA microarray analyses in 7 cell models representing non-malignant and malignant prostate cells (RWPE-1, RWPE-2, HPr1, HPr1AR, LNCaP, LNCaP-C4-2, and PC-3). To focus on primary VDR regulatory events, we undertook expression analyses after 30 minutes treatment with 1α,25(OH)2D3. Across all models, 111 miRNAs were significantly modulated by 1α,25(OH)2D3 treatment. Of these, only 5 miRNAs were modulated in more than one cell model, and of these, only 3 miRNAs were modulated in the same direction. The patterns of miRNA regulation, and the networks they targeted, significantly distinguished the different cell types. Integration of 1α,25(OH)2D3-regulated miRNAs with published VDR ChIP-seq data showed significant enrichment of VDR peaks in flanking regions of miRNAs. Furthermore, mRNA and miRNA expression analyses in non-malignant RWPE-1 cells revealed patterns of miRNA and mRNA co-regulation; specifically, 13 significant reciprocal patterns were identified and these patterns were also observed in TCGA prostate cancer data. Lastly, motif search analysis revealed differential motif enrichment within VDR peaks flanking mRNA compared to miRNA genes. Together, this study revealed that miRNAs are rapidly regulated in a highly cell-type specific manner, and are significantly co-integrated with mRNA regulation.

Extracellular Vesicles in Hematological Malignancies: From Biology to Therapy

PubMed Central

Caivano, Antonella; La Rocca, Francesco; Laurenzana, Ilaria; Trino, Stefania; De Luca, Luciana; Lamorte, Daniela; Del Vecchio, Luigi; Musto, Pellegrino

2017-01-01

Extracellular vesicles (EVs) are a heterogeneous group of particles, between 15 nanometers and 10 microns in diameter, released by almost all cell types in physiological and pathological conditions, including tumors. EVs have recently emerged as particularly interesting informative vehicles, so that they could be considered a true “cell biopsy”. Indeed, EV cargo, including proteins, lipids, and nucleic acids, generally reflects the nature and status of the origin cells. In some cases, EVs are enriched of peculiar molecular cargo, thus suggesting at least a degree of specific cellular packaging. EVs are identified as important and critical players in intercellular communications in short and long distance interplays. Here, we examine the physiological role of EVs and their activity in cross-talk between bone marrow microenvironment and neoplastic cells in hematological malignancies (HMs). In these diseases, HM EVs can modify tumor and bone marrow microenvironment, making the latter “stronger” in supporting malignancy, inducing drug resistance, and suppressing the immune system. Moreover, EVs are abundant in biologic fluids and protect their molecular cargo against degradation. For these and other “natural” characteristics, EVs could be potential biomarkers in a context of HM liquid biopsy and therapeutic tools. These aspects will be also analyzed in this review. PMID:28574430

Identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using single-source dual energy CT

PubMed Central

Gao, Shun-Yu; Zhang, Xiao-Yan; Wei, Wei; Li, Xiao-Ting; Li, Yan-Ling; Xu, Min; Sun, Ying-Shi; Zhang, Xiao-Peng

2016-01-01

Abstract This study proposed to determine whether in vivo iodine concentration measurement by single-source dual energy (SSDE) CT can improve differentiation between benign and malignant thyroid nodules. In total, 53 patients presenting with thyroid nodules underwent SSDE CT scanning. Iodine concentrations were measured for each nodule and normal thyroid tissue using the GSI-viewer image analysis software. A total of 26 thyroid nodules were malignant in 26 patients and confirmed by surgery; 33 nodules from 27 patients were benign, with 10 confirmed by surgery and others after follow-up. Iodine concentrations with plain CT were significantly lower in malignant than benign nodules (0.47 ± 0.20 vs 1.17 ± 0.38 mg/mL, P = 0.00). Receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.93; with a cutoff of 0.67, iodine concentration showed 92.3% sensitivity and 88.5% specificity in diagnosing malignancy. Iodine concentration obtained by enhanced and plain CT were significantly higher in malignant than benign nodules (9.05 ± 3.35 vs 3.46 ± 2.24 mg/mL, P = 0.00). ROC curve analysis showed an AUC of 0.93; with a cutoff value of 3.37, iodine concentration displayed 78% sensitivity, 95% specificity in diagnosing malignancy. Combining unenhanced with enhanced iodine concentrations, the diagnostic equation was: Y = –8.641 × unenhanced iodine concentration + 0.663 × iodine concentration. ROC curve showed an AUC of 0.98 (95% CI, 0.94, 1.00). With Y ≥ –2 considered malignancy, diagnostic sensitivity and specificity were 96%, 96.3%, respectively. This study concluded that SSDE CT can detect the differences in iodine uptake and blood supply between benign and malignant thyroid lesions. PMID:27684811

Early diagnosis of tongue malignancy using laser induced fluorescence spectroscopy technique

NASA Astrophysics Data System (ADS)

Patil, Ajeetkumar; Unnikrishnan V., K.; Ongole, Ravikiran; Pai, Keerthilatha M.; Kartha, V. B.; Chidangil, Santhosh

2015-07-01

Oral cancer together with pharyngeal cancer is the sixth most common malignancy reported worldwide and one with high mortality ratio among all malignancies [1]. Worldwide 450,000 new cases are estimated in 2014[2]. About 90% are a type of cancer called squamous cell carcinoma (SCC). SCC of the tongue is the most common oral malignancy accounting for approximately 40% of all oral carcinomas. One of the important factors for successful therapy of any malignancy is early diagnosis. Although considerable progress has been made in understanding the cellular and molecular mechanisms of tumorigenesis, lack of reliable diagnostic methods for early detection leading to delay in therapy is an important factor responsible for the increase in the mortality rate in various types of cancers. Spectroscopy techniques are extremely sensitive for the analysis of biochemical changes in cellular systems. These techniques can provide a valuable information on alterations that occur during the development of cancer. This is especially important in oral cancer, where "tumor detection is complicated by a tendency towards field cancerization, leading to multi-centric lesions" and "current techniques detect malignant change too late" [3], and "biopsies are not representative of the whole premalignant lesion". [4

The differences in imaging features of malignant and benign branch duct type of Intraductal Papillary Mucinous Tumor.

PubMed

Zhang, Hui-mao; Yao, Fang; Liu, Gui-feng; Wang, Xiao-bin; Xiu, Dian-hui; Gen, Iinuma

2011-12-01

To investigate the difference in the radiological features of malignant and benign branch duct type of IPMT (Intraductal Papillary Mucinous Tumor) of the pancreas. Thirty-six patients who were referred for operation with branch duct type of IPMT of the pancreas were included in this study. All cases underwent both CT and MRI with contrast enhancement. The size of the cystic lesions, the presence and size of mural nodules, and the amount of dilatation of the MPD were assessed by two independent radiologists, and the results were compared with pathological findings. Histological examination revealed adenoma in 8 cases, AH (atypical hyperplasia) in 8 cases, CIS (carcinoma in situ) in 8 cases and invasive carcinoma in 12 cases. Patients of the malignant group were older than those in the benign group (mean age: 67 yrs vs 60 yrs, respectively), but no statistically significant (p=0.05). Males (16/4 vs 10/6) more often complained weight loss and jaundice. The malignant tumor was more frequently located in the head-body and body. Compared with the benign group, the mean sizes of the cyst, mural nodules, MPD of the malignant group were 44 mm, 13 mm, 7.5 mm and benign group were 31 mm, 5 mm, 3.5 mm respectively. All these difference are statistically significant (p<0.05). In 4 cases of the 20 in the malignant group, soft tissue suggesting spread of disease into the adjacent viscera and peritoneum was detected. Cyst size over 30 mm and mural nodule over 8 mm, irregular thick septa, dilatation of the MPD, and accompany with soft tissue mass may be helpful factors in determining malignancy. Copyright © 2011. Published by Elsevier Ireland Ltd.

Role of human papillomavirus and its detection in potentially malignant and malignant head and neck lesions: updated review.

PubMed

Chaudhary, Ajay Kumar; Singh, Mamta; Sundaram, Shanthy; Mehrotra, Ravi

2009-06-25

Head and neck malignancies are characterized by a multiphasic and multifactorial etiopathogenesis. Tobacco and alcohol consumption are the most common risk factors for head and neck malignancy. Other factors, including DNA viruses, especially human papilloma virus (HPV), may also play a role in the initiation or development of these lesions. The pathways of HPV transmission in the head and neck mucosal lesions include oral-genital contact, more than one sexual partner and perinatal transmission of HPV to the neonatal child. The increase in prevalence of HPV infection in these lesions may be due to wider acceptance of oral sex among teenagers and adults as this is perceived to be a form of safe sex. The prevalence of HPV in benign lesions as well as malignancies has been assessed by many techniques. Among these, the polymerase chain reaction is the most sensitive method. Review of literature reveals that HPV may be a risk factor for malignancies, but not in all cases. For confirmation of the role of HPV in head and neck squamous cell carcinoma, large population studies are necessary in an assortment of clinical settings. Prophylactic vaccination against high-risk HPV types eventually may prevent a significant number of cervical carcinomas. Of the two vaccines currently available, Gardasil (Merck & Co., Inc.) protects against HPV types 6, 11, 16 and 18, while the other vaccine, Cervarix (GlaxoSmithKline, Rixensart, Belgium) protects against HPV types 16 and 18 only. However, the HPV vaccine has, to the best of our knowledge, not been tried in head and neck carcinoma. The role of HPV in etiopathogenesis, prevalence in benign and malignant lesions of this area and vaccination strategies are briefly reviewed here.

Cutaneous changes in internal malignancy: Study from a tertiary care center.

PubMed

Hassan, Iffat; Zeerak, Sumaya; Kuchay, Sanaullah; Bashir, Safia; Bhat, Yasmeen J; Mubashir, Syed; Rasool, Farhan; Sheikh, Gousia; Sajad, Peerzada

2017-01-01

A wide variety of systemic diseases and internal malignancies have cutaneous manifestations. In the context of internal malignancy, many cutaneous changes are highly specific to the underlying malignancy, while other changes are nonspecific. Some changes are also due to the modalities employed in the treatment of malignancies. Two hundred and fifty patients who were diagnosed with internal malignancy and who were attending the department of radiation oncology, were evaluated at the Department of Dermatology, Sexually Transmitted Diseases and Leprosy of Government Medical College, Srinagar. The study was conducted over a period of 5 months. Relevant investigations, wherever needed, were carried out. Among the 250 cases examined, nonspecific cutaneous changes were seen in 39 (15.6%) cases, whereas specific skin lesions in the form of cutaneous metastases were seen in two (0.8%) patients. Nail changes and hair changes were also seen in some patients. As this was a cross-sectional study and most of the patients were lost to follow up, we could not assess the outcome of the dermatological changes seen in the affected patients. Many dermatological changes are noticed early in the course of malignancy, reflecting a strong association of the cutaneous change with malignancy. Few manifestations occur late in the course of the disease, indicating dissemination or immunosuppression. Some changes reflect radiation-induced or chemotherapy-induced toxicity, indicating the need for treatment modifications.

Evaluation of IOTA Simple Ultrasound Rules to Distinguish Benign and Malignant Ovarian Tumours

PubMed Central

Kaur, Amarjit; Mohi, Jaswinder Kaur; Sibia, Preet Kanwal; Kaur, Navkiran

2017-01-01

Introduction IOTA stands for International Ovarian Tumour Analysis group. Ovarian cancer is one of the common cancers in women and is diagnosed at later stage in majority. The limiting factor for early diagnosis is lack of standardized terms and procedures in gynaecological sonography. Introduction of IOTA rules has provided some consistency in defining morphological features of ovarian masses through a standardized examination technique. Aim To evaluate the efficacy of IOTA simple ultrasound rules in distinguishing benign and malignant ovarian tumours and establishing their use as a tool in early diagnosis of ovarian malignancy. Materials and Methods A hospital based case control prospective study was conducted. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analysed using chi-square test and kappa statistical method. Results Out of initial 55 patients, 50 patients were included in the final analysis who underwent surgery. IOTA simple rules were applicable in 45 out of these 50 patients (90%). The sensitivity for the detection of malignancy in cases where IOTA simple rules were applicable was 91.66% and the specificity was 84.84%. Accuracy was 86.66%. Classifying inconclusive cases as malignant, the sensitivity and specificity was 93% and 80% respectively. High level of agreement was found between USG and histopathological diagnosis with Kappa value as 0.323. Conclusion IOTA simple ultrasound rules were highly sensitive and specific in predicting ovarian malignancy preoperatively yet being reproducible, easy to train and use. PMID:28969237

Ecstacy-induced delayed rhabdomyolysis and neuroleptic malignant syndrome in a patient with a novel variant in the ryanodine receptor type 1 gene.

PubMed

Russell, T; Riazi, S; Kraeva, N; Steel, A C; Hawryluck, L A

2012-09-01

We present the case of a 20-year-old woman who developed rhabdomyolysis, disseminated intravascular coagulopathy and multi-organ failure induced by ecstasy. Following initial improvement, she developed delayed rhabdomyolysis then haloperidol-induced neuroleptic malignant syndrome, which was treated with a total of 50 mg.kg(-1) dantrolene. Subsequent genetic testing revealed a novel potentially pathogenic variant in the ryanodine receptor type 1 gene. However, caffeine-halothane contracture testing of the patient's mother who carried the same gene variant was negative for malignant hyperthermia. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Comparative cytogenetic and cytologic study in malignant lymphomas.

PubMed

Răileanu-Motoiu, I; Gociu, M; Leahu, S; Berceanu, S

1976-01-01

The possibility of a cytogenetic-cytologic correlation with implications in the diagnosis, evolutivity and prognosis of malignant lymphomas was studied. Cytogenetic investigations were carried out comparatively in the lymph node and spleen lymphoid cells from 25 patients with malignant lymphomas and in normal subjects or patients with malignant tumors. The dominant malignant cellular type was found to correspond genotypically to the abnormal clone. In lymphomas with more differentiated cells the chormosomal abnormalities were limited to a single chromosomal group, while in those with less differentiated cells there were many clonal chromozomal abnormalities. The pathogenic significance of an extra-chromosome in the C-group (observed in most of the cases) is discussed.

Treatment Options for Ovarian Low Malignant Potential Tumors

MedlinePlus

... ovarian low malignant potential tumor . The type of surgery usually depends on whether a woman plans to have children. For women who plan to have children, surgery is either: unilateral salpingo-oophorectomy ; or partial oophorectomy . ...

Treatment Option Overview (Ovarian Low Malignant Potential Tumors)

MedlinePlus

... ovarian low malignant potential tumor . The type of surgery usually depends on whether a woman plans to have children. For women who plan to have children, surgery is either: unilateral salpingo-oophorectomy ; or partial oophorectomy . ...

Stages of Ovarian Low Malignant Potential Tumors

MedlinePlus

... ovarian low malignant potential tumor . The type of surgery usually depends on whether a woman plans to have children. For women who plan to have children, surgery is either: unilateral salpingo-oophorectomy ; or partial oophorectomy . ...

Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data

PubMed Central

Racle, Julien; de Jonge, Kaat; Baumgaertner, Petra; Speiser, Daniel E

2017-01-01

Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type-specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research (http://epic.gfellerlab.org). PMID:29130882

Chromosomal localization and structure of the human type II IMP dehydrogenase gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glesne, D.; Huberman, E.; Collart, F.

1994-05-01

We determined the chromosomal localization and structure of the gene encoding human type II inosine 5{prime}-monophosphate dehydrogenase (IMPDH, EC 1.1.1.205), an enzyme associated with cellular proliferation, malignant transformation, and differentiation. Using polymerase chain reaction (PCR) primers specific for type II IMPDH, we screened a panel of human-Chinese hamster cell somatic hybrids and a separate deletion panel of chromosome 3 hybrids and localized the gene to 3p21.1{yields}p24.2. Two overlapping yeast artificial chromosome clones containing the full gene for type II IMPDH were isolated and a physical map of 117 kb of human genomic DNA in this region of chromosome 3 wasmore » constructed. The gene for type II IMPDH was localized and oriented on this map and found to span no more than 12.5 kb.« less

Biological therapy of hematologic malignancies: toward a chemotherapy-free era.

PubMed

Klener, Pavel; Etrych, Tomas; Klener, Pavel

2017-10-06

Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short. Despite great successes, however, conventional genotoxic cytostatics suffered from an inherently narrow therapeutic index and extensive toxicity, which in many instances limited their clinical utilization. In the last decade of the 20th century, increasing knowledge on the biology of certain malignancies resulted in the conception and development of first molecularly targeted agents designed to inhibit specific druggable molecules involved in the survival of cancer cells. Advances in technology and genetic engineering enabled the production of structurally complex anticancer macromolecules called biologicals, including therapeutic monoclonal antibodies, antibody-drug conjugates and antibody fragments. The development of drug delivery systems (DDSs), in which conventional drugs were attached to various types of carriers including nanoparticles, liposomes or biodegradable polymers, represented an alternative approach to the development of new anticancer agents. Despite the fact that the antitumor activity of drugs attached to DDSs was not fundamentally different, the improved pharmacokinetic profiles, decreased toxic side effects and significantly increased therapeutic indexes resulted in their enhanced antitumor efficacy compared to conventional (unbound) drugs. Approval of the first immune checkpoint inhibitor for the treatment of cancer in 2011 initiated the era of cancer immunotherapy. Checkpoint inhibitors, bispecific T-cell engagers, adoptive T-cell approaches and cancer vaccines have joined the platform so far, represented mainly by recombinant cytokines, therapeutic monoclonal antibodies and immunomodulatory agents. In specific clinical indications, conventional drugs have already been supplanted by multi-agent, chemotherapy-free regimens comprising diverse immunotherapy and/or targeted agents. The very distinct mechanisms of the anticancer activity of new immunotherapy approaches not only call for novel response criteria, but also might fundamental change treatment paradigms of certain types of hematologic malignancies in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Rare case of malignant craniopharyngioma reactive to adjunctive stereotactic radiotherapy and chemotherapy; Case report and review.

PubMed

Nomura, Shunsunke; Aihara, Yasuo; Amano, Kosaku; Eguchi, Seiichiro; Chiba, Kentaro; Komori, Takashi; Kawamata, Takakazu

2018-06-19

Malignant craniopharyngioma or anaplastic craniopharyngioma was first reported in 1987 by Akachi. It has a malignant clinical and histological feature; remarkably rapid progression, atypical pathology like squamous cell carcinoma and poor prognosis. To date seventeen cases of malignant craniopharyngioma have been reported and of these cases, most were of secondary malignant tumor in nature. With respect to traditional benign craniopharyngioma, adjunctive treatment after gross total removal is not necessary, but in the case of malignant types of the tumor, adjunctive treatment is important. This paper presents the first case of malignant craniopharyngioma reactive to adjunctive Gamma knife stereotactic radiosurgery and chemotherapy. Malignant craniopharyngioma is very rare, and we report Gamma knife stereotactic radiosurgery and chemotherapy (Carboplatine and etoposide chemotherapy), as well as Temozolomide chemotherapy were effective and could control progression of the tumor temporarily. Since adjunctive Gamma knife stereotactic radiosurgery and chemotherapy of malignant craniopharyngioma cases affects follow-up strategies, we propose supporting the need to a revision to the WHO classification regarding malignancy evaluation of craniopharyngioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Immunohistochemical detection of p53 protein in ameloblastoma types.

PubMed

el-Sissy, N A

1999-05-01

Overexpression of p53 protein in unicystic ameloblastoma (uAB) is denser than in the conventional ameloblastoma (cAB) type, indicating increased wild type p53--suppressing the growth potential of uAB and denoting the early event of neoplastic transformation, probably of a previous odontogenic cyst. Overexpression of p53 in borderline cAB and malignant ameloblastoma (mAB) types might reflect a mutational p53 protein playing an oncogenic role, promoting tumour growth. Overexpression of p53 protein could be a valid screening method for predicting underlying malignant genetic changes in AB types, through increased frequency of immunoreactive cells or increased staining density.

Insight into the number of pre-malignancies and malignancies of the skin in a hospital population in the Netherlands.

PubMed

van Rijsingen, Margit; Seubring, Inge; Maessen-Visch, Birgitte; Lavrijsen, Sjan; van Bergen, Bert; Groenewoud, Johannes; Gerritsen, Marie-Jeanne

2015-01-01

Skin cancer incidence is rising, placing a burden on healthcare systems worldwide. This problem may even be more extensive than expected, since registration of (pre)malignancies of the skin is poor. To provide insight into the numbers of (pre)malignancies in patients with actinic keratosis (AK) or basal cell carcinoma (BCC) in 2 university and 2 general hospitals. The types and numbers of previous tumours and of tumours during a two-year follow-up were collected from 574 patients. Mean time between the first diagnosed (pre)malignancy and time of inclusion was 6.6 years. Overall, 60% had multiple types of (pre)malignancies. In BCC patients, 61% had multiple BCCs, in patients with squamous cell carcinoma (SCC), 40% had multiple SCCs. The combination 'BCC and SCC' occurred in 10%, 'BCC and AK' in 47%, 'SCC and AK' in 14%. High numbers of patients with multiple (pre)malignancies were found in this patient population in university and general hospitals, which may well reflect the Dutch hospital population. We conclude that skin cancer patients are more extensively affected than was expected up till now. Consequently, the management of skin cancer may be in need of adaptation in near future and the question arises whether dermatologists have the capacity for providing care for all these patients.

Surgical lung biopsy in patients with hematological malignancy or hematopoietic stem cell transplantation and unexplained pulmonary infiltrates: improved outcome with specific diagnosis.

PubMed

Zihlif, Mamoon; Khanchandani, Geeta; Ahmed, Huma P; Soubani, Ayman O

2005-02-01

Using a retrospective review of medical records, we sought the findings of surgical lung biopsy (SLB) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) and unexplained pulmonary infiltrates and to determine the impact of this procedure on management and outcome of these patients. Sixty-two patients who underwent SLB were evaluated; 31 patients had underlying hematological malignancy and 31 patients were HSCT recipients; 58% of whom underwent allogeneic HSCT. Thirty-three patients (53%) had focal infiltrates on chest CT scan while 29 (47%) had diffuse infiltrates. Thirteen patients were mechanically ventilated prior to SLB, and 27 (43%) were neutropenic. There were 66 diagnoses in the 62 patients, 44 (67%) were specific and 22 (33%) were nonspecific. The most common specific diagnoses were infection (29%), malignancy (27%), and inflammatory conditions (11%). Aspergillosis was the most common diagnosis of all biopsies (21%). SLB led to a change in therapy in 40% of patients and was associated with complications in 7 patients (11%). Specific diagnosis was more likely to lead to a change in therapy (48% vs. 27%, P = 0.06) and was associated with a lower mortality when compared to a nonspecific finding (30% vs. 59%, P = 0.02). Nonspecific diagnosis, on the other hand, was seen more in patients on mechanical ventilation prior to SLB compared to those off mechanical ventilation (69% vs. 27%, P = 0.02). SLB provides a specific diagnosis in the majority of patients with hematologic malignancy or HSCT recipients and unexplained pulmonary infiltrates. Specific diagnosis is more likely to lead to a change in therapy and is associated with a better outcome. Copyright 2005 Wiley-Liss, Inc.

Endoscopic bilateral stent-in-stent placement for malignant hilar obstruction using a large cell type stent.

PubMed

Park, Jin Myung; Lee, Sang Hyub; Chung, Kwang Hyun; Jang, Dong Kee; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Min; Paik, Woo Hyun

2016-12-01

Bilateral stent-in-stent (SIS) self-expandable metal stent placement is technically challenging for palliation of unresectable malignant hilar obstruction. In the SIS technique, the uniform large cell type biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent. This study aimed to assess the technical success and clinical effectiveness of this technique with a uniform large cell type biliary stent. Thirty-one patients who underwent bilateral SIS placement using a large cell type stent were reviewed retrospectively. All patients showed malignant hilar obstruction (Bismuth types II, III, IV) with different etiologies. Sixteen (51.6%) patients were male. The mean age of the patients was 67.0+/-14.0 years. Most patients were diagnosed as having hilar cholangiocarcinoma (58.1%) and gallbladder cancer (29.0%). Technical success rate was 83.9%. Success was achieved more frequently in patients without masses obstructing the biliary confluence (MOC) than those with MOC (95.2% vs 60.0%, P=0.03). Functional success rate was 77.4%. Complications occurred in 29.0% of the patients. These tended to occur more frequently in patients with MOC (50.0% vs 19.0%, P=0.11). Median time to recurrent biliary obstruction was 188 days and median survival was 175 days. The large cell type stent can be used efficiently for bilateral SIS placement in malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution is needed to prevent complications for these patients.

Epithelial-to-endothelial transition and cancer stem cells: two cornerstones of vasculogenic mimicry in malignant tumors.

PubMed

Sun, Baocun; Zhang, Danfang; Zhao, Nan; Zhao, Xiulan

2017-05-02

Vasculogenic mimicry (VM) is a functional microcirculation pattern in malignant tumors accompanied by endothelium-dependent vessels and mosaic vessels. VM has been identified in more than 15 solid tumor types and is associated with poor differentiation, late clinical stage and poor prognosis. Classic anti-angiogenic agents do not target endothelium-dependent vessels and are not efficacious against tumors exhibiting VM. Further insight into the molecular signaling that triggers and promotes VM formation could improve anti-angiogenic therapeutics. Recent studies have shown that cancer stem cells (CSCs) and epithelium-to-endothelium transition (EET), a subtype of epithelial-to-mesenchymal transition (EMT), accelerate VM formation by stimulating tumor cell plasticity, remodeling the extracellular matrix (ECM) and connecting VM channels with host blood vessels. VM channel-lining cells originate from CSCs due to expression of EMT inducers such as Twist1, which promote EET and ECM remodeling. Hypoxia and high interstitial fluid pressure in the tumor microenvironment induce a specific type of cell death, linearly patterned programmed cell necrosis (LPPCN), which spatially guides VM and endothelium-dependent vessel networks. This review focuses on the roles of CSCs and EET in VM, and on possible novel anti-angiogenic strategies against alternative tumor vascularization.

Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma.

PubMed

Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; de Azevedo, Ricardo Bentes

2014-01-01

Malignant melanoma is the most aggressive form of skin cancer and has been traditionally considered difficult to treat. The worldwide incidence of melanoma has been increasing faster than any other type of cancer. Early detection, surgery, and adjuvant therapy enable improved outcomes; nonetheless, the prognosis of metastatic melanoma remains poor. Several therapies have been investigated for the treatment of melanoma; however, current treatment options for patients with metastatic disease are limited and non-curative in the majority of cases. Photodynamic therapy (PDT) has been proposed as a promising minimally invasive therapeutic procedure that employs three essential elements to induce cell death: a photosensitizer, light of a specific wavelength, and molecular oxygen. However, classical PDT has shown some drawbacks that limit its clinical application. In view of this, the use of nanotechnology has been considered since it provides many tools that can be applied to PDT to circumvent these limitations and bring new perspectives for the application of this therapy for different types of diseases. On that ground, this review focuses on the potential use of developing nanotechnologies able to bring significant benefits for anticancer PDT, aiming to reach higher efficacy and safety for patients with malignant melanoma.

Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma

PubMed Central

Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; de Azevedo, Ricardo Bentes

2014-01-01

Malignant melanoma is the most aggressive form of skin cancer and has been traditionally considered difficult to treat. The worldwide incidence of melanoma has been increasing faster than any other type of cancer. Early detection, surgery, and adjuvant therapy enable improved outcomes; nonetheless, the prognosis of metastatic melanoma remains poor. Several therapies have been investigated for the treatment of melanoma; however, current treatment options for patients with metastatic disease are limited and non-curative in the majority of cases. Photodynamic therapy (PDT) has been proposed as a promising minimally invasive therapeutic procedure that employs three essential elements to induce cell death: a photosensitizer, light of a specific wavelength, and molecular oxygen. However, classical PDT has shown some drawbacks that limit its clinical application. In view of this, the use of nanotechnology has been considered since it provides many tools that can be applied to PDT to circumvent these limitations and bring new perspectives for the application of this therapy for different types of diseases. On that ground, this review focuses on the potential use of developing nanotechnologies able to bring significant benefits for anticancer PDT, aiming to reach higher efficacy and safety for patients with malignant melanoma. PMID:25317253

The Origin and Significance of Mammary Intraductal Foam Cells

DTIC Science & Technology

2005-09-01

hematopoeitic origin developed in mammary tissue with both benign and malignant differentiation, depending on environmental cues. Progression of the cells...contribution of hematopoeitic precursors to the heterogeneity of cell types in benign and malignant mammary tissue.

Malignant histiocytosis in childhood: morphologic considerations.

PubMed

Jurco, S; Starling, K; Hawkins, E P

1983-12-01

Eight cases diagnosed over a ten-year period as malignant histiocytosis (MH; histiocytic medullary reticulosis) were reviewed to clarify diagnostic criteria for the childhood disease and to identify sources of diagnostic confusion. Five of the eight cases met the authors' criteria for diagnosis; i.e., they were characterized by loose mixed infiltrates composed of three cell types--well-differentiated histiocytes, prohistiocytes, and malignant histiocytes--and they had no leukemic phase. Three cases did not share these features and were reclassified. The liver was found to be the organ most useful in premortem diagnosis, and immunoperoxidase staining for immunoglobulins and lysozyme was also helpful. The clinical and morphologic features of the five cases confirm the authors' view that diagnoses of MH should be limited to cases in which there is a loose pleomorphic population of all three types of histiocytes and that cases with monomorphous populations of aggregated malignant cells should be classified as lymphomas.

Adhesive interactions of human multiple myeloma cell lines with different extracellular matrix molecules.

PubMed

Kibler, C; Schermutzki, F; Waller, H D; Timpl, R; Müller, C A; Klein, G

1998-06-01

Multiple myeloma represents a human B cell malignancy which is characterized by a predominant localization of the malignant cell clone within the bone marrow. With the exception of the terminal stage of the disease the myeloma tumor cells do not circulate in the peripheral blood. The bone marrow microenvironment is believed to play an important role in homing, proliferation and terminal differentiation of myeloma cells. Here we have studied the expression of several extracellular matrix (ECM) molecules in the bone marrow of multiple myeloma patients and analyzed their adhesive capacities with four different human myeloma-derived cell lines. All ECM molecules analyzed (tenascin, laminin, fibronectin, collagen types I, III, V and VI) could be detected in bone marrow cryostat sections of multiple myeloma patients. Adhesion assays showed that only laminin, the microfibrillar collagen type VI and fibronectin were strong adhesive components for the myeloma cell lines U266, IM-9, OPM-2 and NCI-H929. Tenascin and collagen type I were only weak adhesive substrates for these myeloma cells. Adhesion to laminin and fibronectin was beta 1-integrin-mediated since addition of anti-beta 1-integrin antibodies could inhibit the binding of the four different cell types to both matrix molecules. In contrast, integrins do not seem to be involved in binding of the myeloma cells to collagen type VI. Instead, inhibition of binding by heparin suggested that membrane-bound heparan sulfate proteoglycans are responsible ligands for binding to collagen type VI. Adhesion assays with several B-cell lines resembling earlier differentiation stages revealed only weak interactions with tenascin and no interactions with collagen type VI, laminin or fibronectin. In summary, the interactions of human myeloma cells with the extracellular matrix may explain the specific retention of the plasma cells within the bone marrow.

Comparison of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in the evaluation of unclear solid renal lesions.

PubMed

Rübenthaler, J; Paprottka, K; Marcon, J; Hameister, E; Hoffmann, K; Joiko, N; Reiser, M; Clevert, D A

2016-01-01

To compare the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) in the evaluation of unclear renal lesions to the histopathological outcome. A total of 36 patients with a single unclear solid renal lesion with initial imaging studies between 2005 and 2015 were included. CEUS and MRI were used for determining malignancy or benignancy and initial findings were correlated with the histopathological outcome. Out of the 36 renal masses a total of 28 lesions were malignant (77.8%) and 8 were found to be benign (22.2%). Diagnostic accuracy was testes by using the histopathological diagnosis as the gold standard. CEUS showed a sensitivity of 96.4%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 88,9%. MRI showed a sensitivity of 96.4%, a specificity of 75.0%, a PPV of 93.1% and a NPV of 85.7%. Out of the 28 malignant lesions a total of 18 clear cell renal carcinomas, 6 papillary renal cell carcinomas and 4 other malignant lesions, e.g. metastases, were diagnosed. Out of the 8 benign lesions a total 3 angiomyolipomas, 2 oncocytomas, 1 benign renal cyst and 2 other benign lesions, e.g. renal adenomas were diagnosed. Using CEUS, 1 lesion was falsely identified as benign. Using MRI, 2 lesions were falsely identified as benign and 1 lesion was falsely identified as malignant. CEUS is an useful method which can be additionally used to clinically differentiate between malignant and benign renal lesions. CEUS shows a comparable sensitivity, specificity, PPV and NPV to MRI. In daily clinical routine, patients with contraindications for other imaging modalities can particularly benefit using this method.

Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Land, C.E.; Saku, Takashi; Tokuoka, Shoji

1996-07-01

A wide-ranging seach for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR{sub 1}Sv, with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7)more » for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR{sub 1Sv} - 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin`s tumor [12 cases, RR{sub 1Sv} = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR{sub 1Sv} = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin`s tumor [RR{sub 1Sv} = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study. 33 refs., 3 figs., 7 tabs.« less

Diagnostic Pitfalls in Papillary Lesions of the Breast: Experience from a Single Tertiary Care Center

PubMed Central

Basavaiah, Sridevi Hanaganahalli; Sreeram, Saraswathy; Suresh, Pooja Kundapur; Kini, Hema; Adiga, Deepa; Sahu, Kausalya Kumari; Pai, Radha R

2016-01-01

Introduction Papillary neoplasms are a group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant. Aims This study was conducted to analyse the clinicopathological characteristics of papillary lesions of the breast. Materials and Methods A retrospective and prospective analysis of 34 cases of papillary lesions received over a period of 7 years from 2009 to 2015 was done. The patient’s clinical details were collected from medical archives and the histopathological findings were reviewed. The lesions were classified into benign, atypical and malignant categories. Results During the study period, there were 34 cases of papillary lesions of breast. The mean age was 58 years. The central quadrant was the most common location (66.6%). The most common presenting complaint was lump (76.5% cases). Papillary lesions presented more commonly as solitary lump (82.4%) rather than multifocal disease. Benign papillary lesions were more common than the atypical and malignant lesions. The most common papillary lesion accounting for 43% of the cases was intraductal papilloma. Malignant lesions accounted for 41.2% cases with intraductal papillary carcinoma and invasive papillary carcinoma constituting 14.7% cases each. Conclusion Diagnosis of papillary carcinoma is challenging and its classification includes different entities that have specific diagnostic criteria. Due to their heterozygosity in morphology with benign, atypical and malignant subtypes, morphological features such as type of fibrovascular core and continuity of myoepithelial layer along with immunohistochemical stains for myoepithelial cells should be considered for proper and accurate diagnosis. PMID:27656446

Exploring Therapeutic Potentials of Baicalin and Its Aglycone Baicalein for Hematological Malignancies

PubMed Central

Chen, Haijun; Gao, Yu; Wu, Jianlei; Chen, Yingyu; Chen, Buyuan; Hu, Jianda; Zhou, Jia

2014-01-01

Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. PMID:25128647

A probable risk factor of female breast cancer: study on benign and malignant breast tissue samples.

PubMed

Rehman, Sohaila; Husnain, Syed M

2014-01-01

The study reports enhanced Fe, Cu, and Zn contents in breast tissues, a probable risk factor of breast cancer in females. Forty-one formalin-fixed breast tissues were analyzed using atomic absorption spectrophotometry. Twenty malignant, six adjacent to malignant and 15 benign tissues samples were investigated. The malignant tissues samples were of grade 11 and type invasive ductal carcinoma. The quantitative comparison between the elemental levels measured in the two types of specimen (benign and malignant) tissues (removed after surgery) suggests significant elevation of these metals (Fe, Cu, and Zn) in the malignant tissue. The specimens were collected just after mastectomy of women aged 19 to 59 years from the hospitals of Islamabad and Rawalpindi, Pakistan. Most of the patients belong to urban areas of Pakistan. Findings of study depict that these elements have a promising role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu, and Zn was observed. The results showed the excessive accumulation of Fe (229 ± 121 mg/L) in malignant breast tissue samples of patients (p < 0.05) to that in benign tissues samples (49.1 ± 11.4 mg/L). Findings indicated that excess accumulation of iron in malignant tissues can be a risk factor of breast cancer. In order to validate our method of analysis, certified reference material muscle tissue lyophilized (IAEA) MA-M-2/TM was analyzed for metal studied. Determined concentrations were quite in good agreement with certified levels. Asymmetric concentration distribution for Fe, Cu, and Zn was observed in both malignant and benign tissue samples.

Hashimoto thyroiditis: Part 2, sonographic analysis of benign and malignant nodules in patients with diffuse Hashimoto thyroiditis.

PubMed

Anderson, Lauren; Middleton, William D; Teefey, Sharlene A; Reading, Carl C; Langer, Jill E; Desser, Terry; Szabunio, Margaret M; Mandel, Susan J; Hildebolt, Charles F; Cronan, John J

2010-07-01

The purpose of this article is to compare sonographic features of benign and malignant nodules in patients with diffuse Hashimoto thyroiditis. As part of an ongoing multiinstitutional study, patients who underwent ultrasound and fine-needle aspiration of one or more thyroid nodules were analyzed for a variety of predetermined sonographic features. Patients with a sonographic appearance consistent with diffuse Hashimoto thyroiditis and with coexisting nodules that could be confirmed to be benign or malignant by fine-needle aspiration or surgical pathologic analysis were included in the study. Among nodules within diffuse Hashimoto thyroiditis, 84% (69/82) were benign (35 nodular Hashimoto thyroiditis, 32 nodular hyperplasia, and two follicular adenoma), and 16% (13/82) were malignant (12 papillary carcinoma and one lymphoma). Malignant nodules were more likely to be solid and hypoechoic (62% vs 19%). All types of calcifications were more prevalent among malignant nodules, including microcalcifications (39% vs 0%), nonspecific tiny bright reflectors (39% vs 6%), macrocalcifications (15% vs 3%), and eggshell (15% vs 2%). Benign nodules were more likely to be hyperechoic (46% vs 9%), to have a halo (39% vs 15%), and to lack calcifications (88% vs 23%). Benign nodules more often had ill-defined margins (36% vs 8%). Sonographic features of benign and malignant nodules within diffuse Hashimoto thyroiditis are generally similar to the features typical of benign and malignant nodules in the general population. If calcifications of any type are added to the list of malignant sonographic features, the decision to biopsy a nodule in patients with diffuse Hashimoto thyroiditis can be based on recommendations that have been published previously.

Classification of breast tumour using electrical impedance and machine learning techniques.

PubMed

Al Amin, Abdullah; Parvin, Shahnaj; Kadir, M A; Tahmid, Tasmia; Alam, S Kaisar; Siddique-e Rabbani, K

2014-06-01

When a breast lump is detected through palpation, mammography or ultrasonography, the final test for characterization of the tumour, whether it is malignant or benign, is biopsy. This is invasive and carries hazards associated with any surgical procedures. The present work was undertaken to study the feasibility for such characterization using non-invasive electrical impedance measurements and machine learning techniques. Because of changes in cell morphology of malignant and benign tumours, changes are expected in impedance at a fixed frequency, and versus frequency of measurement. Tetrapolar impedance measurement (TPIM) using four electrodes at the corners of a square region of sides 4 cm was used for zone localization. Data of impedance in two orthogonal directions, measured at 5 and 200 kHz from 19 subjects, and their respective slopes with frequency were subjected to machine learning procedures through the use of feature plots. These patients had single or multiple tumours of various types in one or both breasts, and four of them had malignant tumours, as diagnosed by core biopsy. Although size and depth of the tumours are expected to affect the measurements, this preliminary work ignored these effects. Selecting 12 features from the above measurements, feature plots were drawn for the 19 patients, which displayed considerable overlap between malignant and benign cases. However, based on observed qualitative trend of the measured values, when all the feature values were divided by respective ages, the two types of tumours separated out reasonably well. Using K-NN classification method the results obtained are, positive prediction value: 60%, negative prediction value: 93%, sensitivity: 75%, specificity: 87% and efficacy: 84%, which are very good for such a test on a small sample size. Study on a larger sample is expected to give confidence in this technique, and further improvement of the technique may have the ability to replace biopsy.

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2007-10-01

in NF1 and NF2 Patients. Persons with NF1 are predisposed to benign neurofibromas, optic nerve gliomas, and to specific malignant neoplasms ...anatomic location. The malignant neoplasms seen in NF1 patients include astrocytoma, malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, and...hematopoietic cells results in a progressive myeloproliferative disorder. Blood 2004; 103: 4243-4250. Reilly KM, Tuskan RG, Christy E, Loisel DA

Novel targets for ATM-deficient malignancies

PubMed Central

Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

2014-01-01

Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

Capture of mesothelioma cells with 'universal' CTC-chip.

PubMed

Yoneda, Kazue; Chikaishi, Yasuhiro; Kuwata, Taiji; Ohnaga, Takashi; Tanaka, Fumihiro

2018-02-01

Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.

Outcomes and risk factors for cancer patients undergoing endoscopic intervention of malignant biliary obstruction.

PubMed

Haag, Georg-Martin; Herrmann, Thomas; Jaeger, Dirk; Stremmel, Wolfgang; Schemmer, Peter; Sauer, Peter; Gotthardt, Daniel Nils

2015-12-04

Malignant bile duct obstruction is a common problem among cancer patients with hepatic or lymphatic metastases. Endoscopic retrograde cholangiography (ERC) with the placement of a stent is the method of choice to improve biliary flow. Only little data exist concerning the outcome of patients with malignant biliary obstruction in relationship to microbial isolates from bile. Bile samples were taken during the ERC procedure in tumor patients with biliary obstruction. Clinical data including laboratory values, tumor-specific treatment and outcome data were prospectively collected. 206 ERC interventions in 163 patients were recorded. In 43 % of the patients, systemic treatment was (re-) initiated after successful biliary drainage. A variety of bacteria and fungi was detected in the bile samples. One-year survival was significantly worse in patients from whom multiresistant pathogens were isolated than in patients, in whom other species were detected. Increased levels of inflammatory markers were associated with a poor one-year survival. The negative impact of these two factors was confirmed in multivariate analysis. In patients with pancreatic cancer, univariate analysis showed a negative impact on one-year survival in case of detection of Candida species in the bile. Multivariate analysis confirmed the negative prognostic impact of Candida in the bile in pancreatic cancer patients. Outcome in tumor patients with malignant bile obstruction is associated with the type of microbial biliary colonization. The proof of multiresistant pathogens or Candida, as well as the level of inflammation markers, have an impact on the prognosis of the underlying tumor disease.

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up.

PubMed

Vanoli, Alessandro; La Rosa, Stefano; Miceli, Emanuela; Klersy, Catherine; Maragliano, Roberta; Capuano, Francesca; Persichella, Andrea; Martino, Michele; Inzani, Frediano; Luinetti, Ombretta; Di Sabatino, Antonio; Sessa, Fausto; Paulli, Marco; Corazza, Gino Roberto; Rindi, Guido; Bordi, Cesare; Capella, Carlo; Solcia, Enrico

2018-06-12

Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs. Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival. Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs. Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease. © 2018 S. Karger AG, Basel.

Identification of miRNA-103 in the Cellular Fraction of Human Peripheral Blood as a Potential Biomarker for Malignant Mesothelioma – A Pilot Study

PubMed Central

Weber, Daniel G.; Johnen, Georg; Bryk, Oleksandr; Jöckel, Karl-Heinz; Brüning, Thomas

2012-01-01

Background To date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma. Methodology/Principal Findings Using oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%. Conclusions/Significance The results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study. PMID:22253921

Lumbar Osteophyte Avid on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Jochumsen, Mads Ryø; Madsen, Michael Alle; Gammelgaard, Lise; Bouchelouche, Kirsten

2018-06-01

A 75-year-old man with recently diagnosed high-risk prostate cancer was referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. The scan revealed intense Ga-PSMA uptake in a lumbar osteophyte on the right side of level L2/L3, whereas several other spinal osteophytes showed no Ga-PSMA uptake. MRI findings in the L3 vertebra was consistent with a benign Modic type 1 lesion, but MRI showed no signs of malignancy in the osteophyte with high Ga-PMSA uptake. This case presents an osteophyte as an addition to the list of potential benign pitfalls to be aware of when interpreting Ga-PSMA PET/CT.

Utility of contrast-enhanced harmonic EUS in the diagnosis of malignant gallbladder polyps (with videos).

PubMed

Choi, Jun-Ho; Seo, Dong-Wan; Choi, Joon Hyuk; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2013-09-01

The differential diagnosis between benign and malignant polyps of the gallbladder (GB) is often challenging. To evaluate whether contrast-enhanced harmonic EUS (CEH-EUS) might be an accurate method for discriminating malignant GB polyps from benign polyps. Observational study. Tertiary care medical center. Ninety-three patients with GB polyps larger than 10 mm in diameter that were detected by conventional EUS underwent CEH-EUS for evaluation of microvasculature. CEH-EUS was performed using a radial echoendoscope and the extended pure harmonic detection mode. The abilities of conventional EUS and CEH-EUS to diagnose malignant polyp were compared. Two blinded reviewers classified the perfusion images into 3 categories: diffuse enhancement, perfusion defect, or nonenhancement. The vessel images were categorized as having a regular spotty vessel, an irregular vessel, or no vessels. An irregular vessel pattern determined by CEH-EUS aided in the diagnosis of malignant polyps with a sensitivity and specificity of 90.3% and 96.6%, respectively. The presence of perfusion defects, determined by CEH-EUS, was calculated to diagnose malignant polyps with a sensitivity and specificity of 90.3% and 94.9%, respectively. Based on the definitely determined diagnosis, sensitivity and specificity for CEH-EUS were 93.5% and 93.2% versus 90.0% and 91.1% for conventional EUS. In 8 cases, management changed after CEH-EUS. A tertiary medical center with a limited number of patients. The presence of irregular intratumoral vessels or perfusion defects seen on CEH-EUS may be sensitive and accurate predictors of malignant GB polyps. CEH-EUS offers slightly improved diagnostic accuracy compared with EUS. Copyright © 2013 American Society for Gastrointestinal Endoscopy. All rights reserved.

Optical imaging for the diagnosis of oral cancer and oral potentially malignant disorders

NASA Astrophysics Data System (ADS)

Yoshida, K.

2016-03-01

Optical Imaging is being conducted as a therapeutic non-invasive. Many kinds of the light source are selected for this purpose. Recently the oral cancer screening is conducted by using light-induced tissue autofluorescence examination such as several kinds of handheld devices. However, the mechanism of its action is still not clear. Therefore basic experimental research was conducted. One of auto fluorescence Imaging (AFI) device, VELscopeTM and near-infrared (NIR) fluorescence imaging using ICG-labeled antibody as a probe were compared using oral squamous cell carcinoma (OSCC) mouse models. The experiments revealed that intracutaneous tumor was successfully visualized as low density image by VELscopeTM and high density image by NIR image. In addition, VELscopeTM showed higher sensitivity and lower specificity than that of NIR fluorescence imaging and the sensitivity of identification of carcinoma areas with the VELscopeTM was good results. However, further more studies were needed to enhance the screening and diagnostic uses, sensitivity and specificity for detecting malignant lesions and differentiation from premalignant or benign lesions. Therefore, additional studies were conducted using a new developed near infrared (NIR) fluorescence imaging method targeting podoplanine (PDPN) which consists of indocyanine green (ICG)-labeled anti-human podoplanin antibody as a probe and IVIS imaging system or a handy realtime ICG imaging device that is overexpressed in oral malignant neoplasm to improve imaging for detection of early oral malignant neoplasm. Then evaluated for its sensitivity and specificity for detection of oral malignant neoplasm in xenografted mice model and compared with VELscopeTM. The results revealed that ICG fluorescence imaging method and VELscopeTM had the almost the same sensitivity for detection of oral malignant neoplasm. The current topics of optical imaging about oral malignant neoplasm were reviewed.

Improvement of diagnostic efficiency in distinguishing the benign and malignant thyroid nodules via conventional ultrasound combined with ultrasound contrast and elastography

PubMed Central

Liu, Mei-Juan; Men, Yan-Ming; Zhang, Yong-Lin; Zhang, Yu-Xi; Liu, Hao

2017-01-01

We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio <1, microcalcification and irregular peripheral echo halo, and there were statistically significant differences compared with the benign nodules (P<0.05). UE showed that the differences between benign and malignant nodules in 2, 3 and 4 points were statistically significant (P<0.05). The manifestations of malignant nodules in UC were mostly the irregular shape, obscure boundary, no obvious enhancement, heterogeneous enhancement and visible perfusion defects, and there were statistically significant differences compared with the benign nodules (P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC were superior to those of conventional US. AUC was the largest (AUC = 0.908) and the diagnostic value was the highest in the conventional US combined with UE and UC. Conventional US combined with elastography and UC can significantly improve the sensitivity, specificity and accuracy of diagnosis of benign and malignant thyroid nodules. PMID:28693244

Improvement of diagnostic efficiency in distinguishing the benign and malignant thyroid nodules via conventional ultrasound combined with ultrasound contrast and elastography.

PubMed

Liu, Mei-Juan; Men, Yan-Ming; Zhang, Yong-Lin; Zhang, Yu-Xi; Liu, Hao

2017-07-01

We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio <1, microcalcification and irregular peripheral echo halo, and there were statistically significant differences compared with the benign nodules (P<0.05). UE showed that the differences between benign and malignant nodules in 2, 3 and 4 points were statistically significant (P<0.05). The manifestations of malignant nodules in UC were mostly the irregular shape, obscure boundary, no obvious enhancement, heterogeneous enhancement and visible perfusion defects, and there were statistically significant differences compared with the benign nodules (P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC were superior to those of conventional US. AUC was the largest (AUC = 0.908) and the diagnostic value was the highest in the conventional US combined with UE and UC. Conventional US combined with elastography and UC can significantly improve the sensitivity, specificity and accuracy of diagnosis of benign and malignant thyroid nodules.

Adding the power of iodinated contrast media to the credibility of mammography in breast cancer diagnosis.

PubMed

Tsigginou, Alexandra; Gkali, Christina; Chalazonitis, Athanasios; Feida, Eleni; Vlachos, Dimitrios Efthymios; Zagouri, Flora; Rellias, Ioannis; Dimitrakakis, Constantine

2016-11-01

Dual-energy contrast-enhanced spectral mammography (CESM) represents a relatively new diagnostic tool adjunct to mammography. The aim of this study was to strengthen the breast imaging-reporting and data system (BIRADS) classification score in order to improve early breast cancer diagnosis. For this reason, we propose a sum score, termed malignancy potential score (MPS), incorporating the standard BIRADS score and our proposed CESM score. From September 2014 to September 2015, 216 females (age range, 26-85 years; mean age 54.6 years) underwent CESM evaluation of mammographic findings that were primarily assessed as BIRADS 2-5. 10 of these patients had bilateral findings; a total of 226 lesions were examined. High-energy image evaluation was based on the intensity of contrast enhancement of the lesion compared with background enhancement, categorized as Type -1, 0, 1 or 2 enhancement. Histopathology reports were compared with imaging assessment. 98 of 226 lesions were malignant and 128 of 226 lesions were benign. The area under the curve was 0.843, 0.888 and 0.917 for mammographic BIRADS score, CESM score and MPS, respectively, with p-value < 0.05. The sensitivity, specificity and accuracy rates were 91.83, 80.47 and 85.40%, respectively, when a best MPS cut-off point of 4 was used. The malignancy potential score (MPS) has higher diagnostic performance than digital mammography or CESM alone. MPS empowers the credibility of the digital mammography BIRADS score and our proposed type of enhancement in dual-energy CESM and is a diagnostic tool that increases the accuracy rate in early breast cancer diagnosis.

Benign and malignant skull-involved lesions: discriminative value of conventional CT and MRI combined with diffusion-weighted MRI.

PubMed

Tu, Zhanhai; Xiao, Zebin; Zheng, Yingyan; Huang, Hongjie; Yang, Libin; Cao, Dairong

2018-01-01

Background Little is known about the value of computed tomography (CT) and magnetic resonance imaging (MRI) combined with diffusion-weighted imaging (DWI) in distinguishing malignant from benign skull-involved lesions. Purpose To evaluate the discriminative value of DWI combined with conventional CT and MRI for differentiating between benign and malignant skull-involved lesions. Material and Methods CT and MRI findings of 58 patients with pathologically proven skull-involved lesions (43 benign and 15 malignant) were retrospectively reviewed. Conventional CT and MRI characteristics and apparent diffusion coefficient (ADC) value of the two groups were evaluated and compared. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the differential performance of each parameter separately and together. Results The presence of cortical defects or break-through and ill-defined margins were associated with malignant skull-involved lesions (both P < 0.05). Malignant skull-involved lesions demonstrated a significantly lower ADC ( P = 0.016) than benign lesions. ROC curve analyses indicated that a combination of CT, MRI, and DWI with an ADC ≤ 0.703 × 10 -3 mm 2 /s showed optimal sensitivity, while DWI along showed optimal specificity of 88.4% in differentiating between benign and malignant skull-involved lesions. Conclusion The combination of CT, MRI, and DWI can help to differentiate malignant from benign skull-involved lesions. CT + MRI + DWI offers optimal sensitivity, while DWI offers optimal specificity.

Differential diagnosis of breast masses in South Korean premenopausal women using diffuse optical spectroscopic imaging

NASA Astrophysics Data System (ADS)

Leproux, Anaïs; Kim, You Me; Min, Jun Won; McLaren, Christine E.; Chen, Wen-Pin; O'Sullivan, Thomas D.; Lee, Seung-ha; Chung, Phil-Sang; Tromberg, Bruce J.

2016-07-01

Young patients with dense breasts have a relatively low-positive biopsy rate for breast cancer (˜1 in 7). South Korean women have higher breast density than Westerners. We investigated the benefit of using a functional and metabolic imaging technique, diffuse optical spectroscopic imaging (DOSI), to help the standard of care imaging tools to distinguish benign from malignant lesions in premenopausal Korean women. DOSI uses near-infrared light to measure breast tissue composition by quantifying tissue concentrations of water (ctH2O), bulk lipid (ctLipid), deoxygenated (ctHHb), and oxygenated (ctHbO2) hemoglobin. DOSI spectral signatures specific to abnormal tissue and absent in healthy tissue were also used to form a malignancy index. This study included 19 premenopausal subjects (average age 41±9), corresponding to 11 benign and 10 malignant lesions. Elevated lesion to normal ratio of ctH2O, ctHHb, ctHbO2, total hemoglobin (THb=ctHHb+ctHbO2), and tissue optical index (ctHHb×ctH2O/ctLipid) were observed in the malignant lesions compared to the benign lesions (p<0.02). THb and malignancy index were the two best single predictors of malignancy, with >90% sensitivity and specificity. Malignant lesions showed significantly higher metabolism and perfusion than benign lesions. DOSI spectral features showed high discriminatory power for distinguishing malignant and benign lesions in dense breasts of the Korean population.

The relationship between cancer and rheumatoid arthritis: still a large research agenda.

PubMed

Love, Thorvardur; Solomon, Daniel H

2008-01-01

The association between rheumatoid arthritis (RA) and malignancies has received increased attention in recent years. Reports suggesting that tumor necrosis factor blockers might elevate the risk of malignancy in RA patients have prompted researchers to look at the incidence of malignancies in all RA patients. In a recent issue of Arthritis Research & Therapy, Smitten and colleagues suggest that previous reports of a standardized incidence ratio close to one for malignancies in RA may reflect an increased risk for some site-specific malignancies and a reduced risk for others. Here we discuss these findings and suggest what issues could be addressed in future studies.

Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor

PubMed Central

Jena, Bipulendu; Dotti, Gianpietro

2010-01-01

Infusions of antigen-specific T cells have yielded therapeutic responses in patients with pathogens and tumors. To broaden the clinical application of adoptive immunotherapy against malignancies, investigators have developed robust systems for the genetic modification and characterization of T cells expressing introduced chimeric antigen receptors (CARs) to redirect specificity. Human trials are under way in patients with aggressive malignancies to test the hypothesis that manipulating the recipient and reprogramming T cells before adoptive transfer may improve their therapeutic effect. These examples of personalized medicine infuse T cells designed to meet patients' needs by redirecting their specificity to target molecular determinants on the underlying malignancy. The generation of clinical grade CAR+ T cells is an example of bench-to-bedside translational science that has been accomplished using investigator-initiated trials operating largely without industry support. The next-generation trials will deliver designer T cells with improved homing, CAR-mediated signaling, and replicative potential, as investigators move from the bedside to the bench and back again. PMID:20439624

Lung malignancy: Diagnostic accuracies of bronchoalveolar lavage, bronchial brushing, and fine needle aspiration cytology

PubMed Central

Sareen, Rateesh; Pandey, C L

2016-01-01

Background: Early diagnosis of lung cancer plays a pivotal role in reducing lung cancer death rate. Cytological techniques are safer, economical and provide quick results. Bronchoscopic washing, brushing and fine needle aspirations not only complement tissue biopsies in the diagnosis of lung cancer but also comparable. Objectives: (1) To find out diagnostic yields of bronchioalveolar lavage, bronchial brushings, FNAC in diagnosis of lung malignancy. (2) To compare relative accuracy of these three cytological techniques. (3) To correlate the cytologic diagnosis with clinical, bronchoscopic and CT findings. (4) Cytological and histopathological correlation of lung lesions. Methods: All the patients who came with clinical or radiological suspicion of lung malignancy in two and a half year period were included in study. Bronchoalveolar lavage was the most common type of cytological specimen (82.36%), followed by CT guided FNAC (9.45%) and bronchial brushings (8.19%). Sensitivity, specificity, positive and negative predictive value for all techniques and correlation with histopathology was done using standard formulas. Results: The most sensitive technique was CT FNAC – (87.25%) followed by brushings (77.78%) and BAL (72.69%). CT FNAC had highest diagnostic yield (90.38%), followed by brushings (86.67%) and BAL (83.67%). Specificity and positive predictive value were 100 % each of all techniques. Lowest false negatives were obtained in CT FNAC (12.5%) and highest in BAL (27.3%). Highest negative predictive value was of BAL 76.95 % followed by BB 75.59% and CT FNAC 70.59%. Conclusion: Before administering antitubercular treatment every effort should be made to rule out malignancy. CT FNAC had highest diagnostic yield among three cytological techniques. BAL is an important tool in screening central as well as in accessible lesions. It can be used at places where CT guided FNAC is not available or could not be done due to technical or financial limitations PMID:27890992

Knowledge of human papillomavirus and its association with head and neck benign and malignant lesions in a group of dental patients in pakistan.

PubMed

Gichki, Abdul Samad; Buajeeb, Waranun; Doungudomdacha, Sombhun; Khovidhunkit, Siribang-On Pibooniyom

2015-01-01

Human papillomaviruses (HPVs) remain a serious world health problem due to their association with cervical and head and neck cancers. While over 100 HPV types have been identified, only a few subtypes are associated with malignancies. HPV 16 and 18 are the most prevalent oncogenic types in head and neck cancers. Although it has been proven that some subsets of benign and malignant head and neck lesions are associated with HPV, the general population have very little awareness and knowledge of their association with HPV. Therefore, the purpose of this study was to determine the knowledge of HPV and its links with head and neck benign and malignant lesions in a group of Pakistani dental patients who attended the Dental Department of the Sandeman provincial hospital in Quetta, Pakistan. One hundred and ninety-two patients were recruited and requested to answer a questionnaire. It was revealed that there was a low level of knowledge about HPV and its association with head and neck benign and malignant lesions among the participants. This result suggested that more education regarding the relationship of HPV in inducing head and neck benign and malignant lesions is required in this group of patients.

Fertility-sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report.

PubMed

Ghalleb, Montassar; Bouzaiene, Hatem; Slim, Skander; Hadiji, Achraf; Hechiche, Monia; Ben Hassouna, Jamel; Rahal, Khaled

2017-12-17

Malignant ovarian germ cell tumor is a rare type of disease, which generally has a good prognosis due to the high chemosensitivity of this type of tumor. Fertility preservation is an important issue because malignant ovarian germ cell tumor commonly affects young women. Although conservation is the standard for early stage, it becomes more debatable as the disease progresses to more advanced stages. Report the case of a patient with an International Federation of Gynecology and Obstetrics Stage IIIc malignant ovarian germ cell tumor, who had conservative surgery and chemotherapy with a good fertility outcome. A 23-year-old North African woman with a left malignant ovarian germ cell tumor stage IIIc was treated by left adnexectomy and omentectomy followed by chemotherapy. A 15-year follow-up showed no signs of relapse, and she completed three full-term natural pregnancies. Malignant ovarian germ cell tumor is a rare ovarian tumor with a good prognosis. It is usually associated with a good fertility outcome in early stages. However, due to the rarity of the disease in advanced stages, the fertility outcome for this group of patients is not clear. This lack of data surrounding advanced stages points to the need for a meta-analysis of all published cases.

Malignant mixed germ cell tumour of ovary--an unusual combination and review of literature.

PubMed

Goyal, Lajya Devi; Kaur, Sharanjit; Kawatra, Kanwardeep

2014-11-04

Mixed germ cell tumours of the ovary are malignant neoplasms of the ovary comprising of two or more types of germ cell components. Most of the malignant mixed germ cell tumours consists of dysgerminoma accompanied by endodermal sinus tumours, immature teratoma or choriocarcinoma. There are only few case reports of mixed germ cell tumours with different combinations of malignant components. We report a very rare case of mixed germ cell tumours consisted of malignant components of endodermal sinus tumour, emryonal carcinoma, and benign component of teratomatuos and trophoblastic differentiation. This is the first case report in the literature with both benign and malignant component of type described to best of our knowledge. Patient was an 18 year old girl, who presented with pain abdomen, abdominal mass and irregular bleeding. Ultrasound and CT scan showed a huge mass with solid and cystic component. Tumour markers i.e alpha feto- protein (AFP), human chorionic gonadotropin (hCG), lactate dehydrogenate (LDH) and Ca-125 were raised. We performed fertility sparing surgery by preserving one ovary, tube and uterus. Conclusion: Malingnant mixed germ cell tumours of ovary are highly aggressive neoplasm and early intervention and fertility sparing surgery is required for any adolescent girl presenting with rapidly enlarging pelvic mass.

Ultrasonographic Evaluation of Cervical Lymph Nodes in Thyroid Cancer.

PubMed

Machado, Maria Regina Marrocos; Tavares, Marcos Roberto; Buchpiguel, Carlos Alberto; Chammas, Maria Cristina

2017-02-01

Objective To determine what ultrasonographic features can identify metastatic cervical lymph nodes, both preoperatively and in recurrences after complete thyroidectomy. Study Design Prospective. Setting Outpatient clinic, Department of Head and Neck Surgery, School of Medicine, University of São Paulo, Brazil. Subjects and Methods A total of 1976 lymph nodes were evaluated in 118 patients submitted to total thyroidectomy with or without cervical lymph node dissection. All the patients were examined by cervical ultrasonography, preoperatively and/or postoperatively. The following factors were assessed: number, size, shape, margins, presence of fatty hilum, cortex, echotexture, echogenicity, presence of microcalcification, presence of necrosis, and type of vascularity. The specificity, sensitivity, positive predictive value, and negative predictive value of each variable were calculated. Univariate and multivariate logistic regression analyses were conducted. A receiver operator characteristic (ROC) curve was plotted to determine the best cutoff value for the number of variables to discriminate malignant lymph nodes. Results Significant differences were found between metastatic and benign lymph nodes with regard to all of the variables evaluated ( P < .05). Logistic regression analysis revealed that size and echogenicity were the best combination of altered variables (odds ratio, 40.080 and 7.288, respectively) in discriminating malignancy. The ROC curve analysis showed that 4 was the best cutoff value for the number of altered variables to discriminate malignant lymph nodes, with a combined specificity of 85.7%, sensitivity of 96.4%, and efficiency of 91.0%. Conclusion Greater diagnostic accuracy was achieved by associating the ultrasonographic variables assessed rather than by considering them individually.

Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group

PubMed Central

Ameye, Lieveke; Fischerova, Daniela; Epstein, Elisabeth; Melis, Gian Benedetto; Guerriero, Stefano; Van Holsbeke, Caroline; Savelli, Luca; Fruscio, Robert; Lissoni, Andrea Alberto; Testa, Antonia Carla; Veldman, Joan; Vergote, Ignace; Van Huffel, Sabine; Bourne, Tom; Valentin, Lil

2010-01-01

Objectives To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result. Design Prospective temporal and external validation of simple ultrasound rules to distinguish benign from malignant adnexal masses. The rules comprised five ultrasonic features (including shape, size, solidity, and results of colour Doppler examination) to predict a malignant tumour (M features) and five to predict a benign tumour (B features). If one or more M features were present in the absence of a B feature, the mass was classified as malignant. If one or more B features were present in the absence of an M feature, it was classified as benign. If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive. Setting 19 ultrasound centres in eight countries. Participants 1938 women with an adnexal mass examined with ultrasound by the principal investigator at each centre with a standardised research protocol. Reference standard Histological classification of the excised adnexal mass as benign or malignant. Main outcome measures Diagnostic sensitivity and specificity. Results Of the 1938 patients with an adnexal mass, 1396 (72%) had benign tumours, 373 (19.2%) had primary invasive tumours, 111 (5.7%) had borderline malignant tumours, and 58 (3%) had metastatic tumours in the ovary. The simple rules yielded a conclusive result in 1501 (77%) masses, for which they resulted in a sensitivity of 92% (95% confidence interval 89% to 94%) and a specificity of 96% (94% to 97%). The corresponding sensitivity and specificity of subjective assessment were 91% (88% to 94%) and 96% (94% to 97%). In the 357 masses for which the simple rules yielded an inconclusive result and with available results of CA-125 measurements, the sensitivities were 89% (83% to 93%) for subjective assessment, 50% (42% to 58%) for the risk of malignancy index, 89% (83% to 93%) for logistic regression model 1, and 82% (75% to 87%) for logistic regression model 2; the corresponding specificities were 78% (72% to 83%), 84% (78% to 88%), 44% (38% to 51%), and 48% (42% to 55%). Use of the simple rules as a triage test and subjective assessment for those masses for which the simple rules yielded an inconclusive result gave a sensitivity of 91% (88% to 93%) and a specificity of 93% (91% to 94%), compared with a sensitivity of 90% (88% to 93%) and a specificity of 93% (91% to 94%) when subjective assessment was used in all masses. Conclusions The use of the simple rules has the potential to improve the management of women with adnexal masses. In adnexal masses for which the rules yielded an inconclusive result, subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate diagnostic test; the risk of malignancy index and the two regression models were not useful. PMID:21156740

Different expression of FoxM1 in human benign and malignant pleural effusion.

PubMed

Tang, Zhonghao; Li, Hongqing; Zhu, Huili; Bai, Chunxue

2015-01-01

The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural effusions. FoxM1 expression level could provide evidence for diagnosis and treatment of malignant pleural effusions and lung cancer.

Diagnostic Performance of (18)F-Fluorodeoxyglucose in 162 Small Pulmonary Nodules Incidentally Detected in Subjects Without a History of Malignancy.

PubMed

Calcagni, Maria Lucia; Taralli, Silvia; Cardillo, Giuseppe; Graziano, Paolo; Ialongo, Pasquale; Mattoli, Maria Vittoria; Di Franco, Davide; Caldarella, Carmelo; Carleo, Francesco; Indovina, Luca; Giordano, Alessandro

2016-04-01

Solitary pulmonary nodule (SPN) still represents a diagnostic challenge. The aim of our study was to evaluate the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography in one of the largest samples of small SPNs, incidentally detected in subjects without a history of malignancy (nonscreening population) and undetermined at computed tomography. One-hundred and sixty-two small (>0.8 to 1.5 cm) and, for comparison, 206 large nodules (>1.5 to 3 cm) were retrospectively evaluated. Diagnostic performance of (18)F-fluorodeoxyglucose visual analysis, receiver-operating characteristic (ROC) analysis for maximum standardized uptake value (SUVmax), and Bayesian analysis were assessed using histology or radiological follow-up as a golden standard. In 162 small nodules, (18)F-fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.3) provided 72.6% and 77.4% sensitivity and 88.0% and 82.0% specificity, respectively. The prevalence of malignancy was 38%; Bayesian analysis provided 78.8% positive and 16.0% negative posttest probabilities of malignancy. In 206 large nodules (18)F-fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.9) provided 89.5% and 85.1% sensitivity and 70.8% and 79.2% specificity, respectively. The prevalence of malignancy was 65%; Bayesian analysis provided 85.0% positive and 21.6% negative posttest probabilities of malignancy. In both groups, malignant nodules had a significant higher SUVmax (p < 0.0001) than benign nodules. Only in the small group, malignant nodules were significantly larger (p = 0.0054) than benign ones. (18)F-fluorodeoxyglucose can be clinically relevant to rule in and rule out malignancy in undetermined small SPNs, incidentally detected in nonscreening population with intermediate pretest probability of malignancy, as well as in larger ones. Visual analysis can be considered an optimal diagnostic criterion, adequately detecting a wide range of malignant nodules with different metabolic activity. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Identifying Malignant Pleural Effusion by A Cancer Ratio (Serum LDH: Pleural Fluid ADA Ratio).

PubMed

Verma, Akash; Abisheganaden, John; Light, R W

2016-02-01

We studied the diagnostic potential of serum lactate dehydrogenase (LDH) in malignant pleural effusion. Retrospective analysis of patients hospitalized with exudative pleural effusion in 2013. Serum LDH and serum LDH: pleural fluid ADA ratio was significantly higher in cancer patients presenting with exudative pleural effusion. In multivariate logistic regression analysis, pleural fluid ADA was negatively correlated 0.62 (0.45-0.85, p = 0.003) with malignancy, whereas serum LDH 1.02 (1.0-1.03, p = 0.004) and serum LDH: pleural fluid ADA ratio 0.94 (0.99-1.0, p = 0.04) was correlated positively with malignant pleural effusion. For serum LDH: pleural fluid ADA ratio, a cut-off level of >20 showed sensitivity, specificity of 0.98 (95 % CI 0.92-0.99) and 0.94 (95 % CI 0.83-0.98), respectively. The positive likelihood ratio was 32.6 (95 % CI 10.7-99.6), while the negative likelihood ratio at this cut-off was 0.03 (95 % CI 0.01-0.15). Higher serum LDH and serum LDH: pleural fluid ADA ratio in patients presenting with exudative pleural effusion can distinguish between malignant and non-malignant effusion on the first day of hospitalization. The cut-off level for serum LDH: pleural fluid ADA ratio of >20 is highly predictive of malignancy in patients with exudative pleural effusion (whether lymphocytic or neutrophilic) with high sensitivity and specificity.

Diagnostic Criteria and Accuracy of Categorizing Malignant Thyroid Nodules by Ultrasonography and Ultrasound Elastography with Pathologic Correlation.

PubMed

Elsayed, Naglaa Mostafa; Elkhatib, Yasser Atta

2016-03-01

Thyroid nodules are a common medical and surgical concern. Thyroid ultrasound (US) is the primary imaging modality used for initial evaluation and assortment of nodules for fine needle aspiration (FNA) cytology/biopsy. Ultrasound elastography (USE) is believed to improve the diagnostic accuracy of US in distinguishing benign from malignant nodules. The aim of the work described here is to evaluate the diagnostic criteria and accuracy of US and USE in the diagnosis of malignant thyroid nodules. A prospective study of 88 patients who have thyroid nodules was performed. US, color Doppler, and USE were evaluated using a Philips iU22 equipped with a 5 to 12 MHz, linear transducer, followed by FNA of the each scanned nodule. The most sensitive US criteria for malignant nodules were a height-to-width ratio greater than one and the absence of a halo sign (sensitivity 0.875% and 1.000%, respectively). The most specific criteria for malignancy were a spiculated/blurred margin and the presence of microcalcifications (specificity 0.968% and 0.888%, respectively). The receiver operating characteristic curve showed that the cutoff diagnostic criteria of malignancy are two US characteristics and an elastography score of 4. The diagnostic accuracy of US for malignant thyroid nodules increases by combining US and USE. © The Author(s) 2015.

Engineered Herpes Simplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2014-09-01

patients with neurofibromatosis type I (NF-1) will develop benign neurofibromas in their peripheral nerves that will progress to malignant tumors that...lines to activate anti-viral signaling pathways. Keywords: MPNST, neurofibromatosis , oncolytic virus, HSV-1, IL-12 In the first year of research, we...lysis and immune recruitment. As rare and aggressive tumors of glial origin, MPNSTs frequently arise from patients with type-1 neurofibromatosis , but

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2006-10-01

Patients. Persons with NF1 are predisposed to benign neurofibromas, optic nerve gliomas, and to specific malignant neoplasms . Individuals with NF1...malignant neoplasms seen in NF1 patients include astrocytoma, malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, and juvenile...Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci U S A 2004;101(2):597-602. 14. Chan IT, Kutok JL

Regulatory Control of Breast Tumor Cell Poly (ADP-Ribose) Polymerase

DTIC Science & Technology

2002-08-01

DNA replication complex (designated the DNA synthesome) from a variety of non-malignant and malignant tumor cells including breast cancer cells. We have shown that poly(ADP-ribose) polymerase PARP is among the components of the DNA synthesome. The transformation of a non-malignant human breast cell to a malignant state was accompanied by a significant alteration in the 2-D PAGE profile of specific protein components of the DNA synthesome (such as PCNA) together with a 6-8 decrease in the replication fidelity of the DNA

Localized malignant pleural mesothelioma: report of two cases.

PubMed

Tanzi, Silvia; Tiseo, Marcello; Internullo, Eveline; Cacciani, Giancarlo; Capra, Roberto; Carbognani, Paolo; Rusca, Michele; Rindi, Guido; Ardizzoni, Andrea

2009-08-01

Localized malignant pleural mesothelioma is very rare tumor disease. There are sporadic reports in the literature showing that this entity has a different biologic behavior compared with diffuse pleural mesothelioma. We report two cases of radically resected localized pleural malignant mesothelioma, with a previous history of asbestos exposure. Both cases showed a microscopic and immunohistochemical findings of malignant mesothelioma, biphasic and sarcomatoid lympho-histiocitoid variant type, respectively, without evidence of diffuse pleural spread. The first is very peculiar case of bilateral localized malignant pleural mesothelioma with complete response to chemotherapy and localized late recurrence, radically resected and treated with adjuvant radiotherapy. The second case revealed as a solitary localized mass, underwent a complete en bloc resection and adjuvant radiotherapy. Both cases demonstrate that the localized malignant mesothelioma should be distinguished from diffuse form and that complete resection is associated with good prognosis.

Quantification of photoacoustic microscopy images for ovarian cancer detection

NASA Astrophysics Data System (ADS)

Wang, Tianheng; Yang, Yi; Alqasemi, Umar; Kumavor, Patrick D.; Wang, Xiaohong; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2014-03-01

In this paper, human ovarian tissues with malignant and benign features were imaged ex vivo by using an opticalresolution photoacoustic microscopy (OR-PAM) system. Several features were quantitatively extracted from PAM images to describe photoacoustic signal distributions and fluctuations. 106 PAM images from 18 human ovaries were classified by applying those extracted features to a logistic prediction model. 57 images from 9 ovaries were used as a training set to train the logistic model, and 49 images from another 9 ovaries were used to test our prediction model. We assumed that if one image from one malignant ovary was classified as malignant, it is sufficient to classify this ovary as malignant. For the training set, we achieved 100% sensitivity and 83.3% specificity; for testing set, we achieved 100% sensitivity and 66.7% specificity. These preliminary results demonstrate that PAM could be extremely valuable in assisting and guiding surgeons for in vivo evaluation of ovarian tissue.

Combined value of Virtual Touch tissue quantification and conventional sonographic features for differentiating benign and malignant thyroid nodules smaller than 10 mm.

PubMed

Zhang, Huiping; Shi, Qiusheng; Gu, Jiying; Jiang, Luying; Bai, Min; Liu, Long; Wu, Ying; Du, Lianfang

2014-02-01

This study aimed to investigate the value of sonographic features including Virtual Touch tissue quantification (VTQ; Siemens Medical Solutions, Mountain View, CA) for differentiating benign and malignant thyroid nodules smaller than 10 mm. Seventy-one thyroid nodules smaller than 10 mm with pathologic diagnoses were included in this study. The conventional sonographic features and quantitative elasticity features (VTQ) were observed and compared between benign and malignant nodules. There were 39 benign and 32 malignant nodules according to histopathologic examination. When compared with benign nodules, malignant nodules were more frequently taller than wide, poorly defined, and markedly hypoechoic (P < .05). Color Doppler sonographic features were not significantly different between benign and malignant nodules. The VTQ value for malignant nodules (mean ± SD 3.260 ± 0.725 m/s) was significantly higher than that of benign ones (2.108 ± 0.455 m/s; P < .001). The cutoff point for the differential diagnosis was 2.910 m/s, with sensitivity, specificity, a positive predictive value, a negative predictive value, and diagnostic accuracy of 71.9%, 100%, 100%, 81.2%, and 87.3% respectively. Logistic regression analysis showed that a taller-than-wide shape, a poorly defined boundary, marked hypoechogenicity, and a VTQ value greater than 2.910 m/s were independent risk factors for malignancy, with odds ratios of 69.366, 41.864, 5.945, and 64.991. The combination of VTQ with a taller-than-wide shape had the highest sensitivity and specificity of 90.6% and 97.4%. The shape, margin, echogenicity, and VTQ value are useful sonographic criteria for differentiating benign and malignant thyroid nodules smaller than 10 mm. When VTQ was combined with B-mode sonographic features, the sensitivity was improved significantly.

Differentiation of benign from malignant cervical lymph nodes in patients with head and neck cancer using PET/CT imaging.

PubMed

Payabvash, Seyedmehdi; Meric, Kaan; Cayci, Zuzan

2016-01-01

To differentiate malignant from benign cervical lymph nodes in patients with head/neck cancer. In this retrospective study, 39 patients with primary head/neck cancer who underwent Positron Emission Tomography (PET)/Computerized Tomography (CT) and image-guided lymph node biopsy were included. Overall, 23 (59%) patients had biopsy-proven malignant cervical lymphadenopathy. Malignant lymph nodes had higher maximum standardized uptake (SUV-max) value (P<.001) and short-axis diameter (P=.015) compared to benign nodes. An SUV-max of ≥2.5 was 100% sensitive, and an SUV-max ≥5.5 was 100% specific for malignant lymphadenopathy. The PET/CT SUV-max value can help with differentiation of malignant cervical lymph nodes in patients with head/neck cancer. Published by Elsevier Inc.

Malignancy, weight loss, and the small intestinal mucosa

PubMed Central

Barry, R. E.

1974-01-01

The mucosal architecture and mucosal dynamics of the small bowel have been studied in patients with malignant disease not of the gastrointestinal tract but associated with severe weight loss. Mucosal changes in malignant disease are demonstrated by stereomicroscopy, mucosal architectural measurement, and decreased lactose utilization. Measurement of the epithelial DNA loss rate indicates, in association with mucosal measurement, that the architectural changes are caused by a hypoplasia of the epithelium. Similar findings are demonstrated in patients with profound weight loss due to other non-malignant wasting diseases. Although mucosal changes undoubtedly occur in malignant disease, the changes are not specific for malignancy and the concept of `cancer enteropathy' is not tenable. It is suggested that mucosal changes are the effect of and not the cause of cachexia. ImagesFig 1 PMID:4430474

Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.

PubMed

Panagopoulou, Maria; Lambropoulou, Maria; Balgkouranidou, Ioanna; Nena, Evangelia; Karaglani, Makrina; Nicolaidou, Christina; Asimaki, Anthi; Konstantinidis, Theocharis; Constantinidis, Theodoros C; Kolios, George; Kakolyris, Stylianos; Agorastos, Theodoros; Chatzaki, Ekaterini

2017-04-01

Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus-infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus-free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus-induced carcinogenesis in uterine cervix and is worthy of further investigation.

Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, E.; Huntrakoon, M.; Wetzel, L.H.

Malignant peripheral nerve-sheath neoplasms frequently complicate neurofibromatosis causing pain, enlarging masses, or neurologic deficits. However, similar findings sometimes also occur with benign nerve neoplasms. Our study was done retrospectively to determine if imaging techniques can differentiate malignant from benign nerve tumors in neurofibromatosis. Eight patients with symptomatic neoplasms (three benign, five malignant) were studied by CT in eight, MR in six, and /sup 67/Ga-citrate scintigraphy in seven. Uptake of /sup 67/Ga occurred in all five malignant lesions but not in two benign neoplasms studied. On CT or MR, all eight lesions, including three benign neoplasms, showed inhomogeneities. Of five lesionsmore » with irregular, infiltrative margins on CT or MR, four were malignant and one was benign. Of three lesions with smooth margins, one was malignant and two were benign. One malignant neoplasm caused irregular bone destruction. Accordingly, CT and MR could not generally distinguish malignant from benign lesions with certainty. However, both CT and MR provided structural delineation to help surgical planning for both types of lesion. /sup 67/Ga scintigraphy appears promising as a screening technique to identify lesions with malignant degeneration in patients with neurofibromatosis. Any area of abnormal radiogallium uptake suggests malignancy warranting further evaluation by CT or MR. Biopsy of any questionable lesion is essential.« less

Bovine Papillomavirus in Brazil: Detection of Coinfection of Unusual Types by a PCR-RFLP Method

PubMed Central

Carvalho, R. F.; Sakata, S. T.; Giovanni, D. N. S.; Mori, E.; Brandão, P. E.; Richtzenhain, L. J.; Pozzi, C. R.; Arcaro, J. R. P.; Miranda, M. S.; Mazzuchelli-de-Souza, J.; Melo, T. C.; Comenale, G.; Assaf, S. L. M. R.; Beçak, W.; Stocco, R. C.

2013-01-01

Bovine papillomavirus (BPV) is recognized as a causal agent of benign and malignant tumors in cattle. Thirteen types of BPV are currently characterized and classified into three distinct genera, associated with different pathological outcomes. The described BPV types as well as other putative ones have been demonstrated by molecular biology methods, mainly by the employment of degenerated PCR primers. Specifically, divergences in the nucleotide sequence of the L1 gene are useful for the identification and classification of new papillomavirus types. On the present work, a method based on the PCR-RFLP technique and DNA sequencing was evaluated as a screening tool, allowing for the detection of two relatively rare types of BPV in lesions samples from a six-year-old Holstein dairy cow, chronically affected with cutaneous papillomatosis. These findings point to the dissemination of BPVs with unclear pathogenic potential, since two relatively rare, new described BPV types, which were first characterized in Japan, were also detected in Brazil. PMID:23865043

Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection.

PubMed

Alimova, Alexandra; Katz, A; Sriramoju, Vidyasagar; Budansky, Yuri; Bykov, Alexei A; Zeylikovich, Roman; Alfano, R R

2007-01-01

Fluorescence and phosphorescence measurements are performed on normal and malignant ex vivo human breast tissues using UV LED and xenon lamp excitation. Tryptophan (trp) phosphorescence intensity is higher in both normal glandular and adipose tissue when compared to malignant tissue. An algorithm based on the ratio of trp fluorescence intensity at 345 nm to phosphorescence intensity at 500 nm is successfully used to separate normal from malignant tissue types. Normal specimens consistently exhibited a low I(345)I(500) ratio (<10), while for malignant specimens, the I(345)I(500) ratio is consistently high (>15). The ratio analysis correlates well with histopathology. Intensity ratio maps with a spatial resolution of 0.5 mm are generated in which local regions of malignancy could be identified.

Epigenetic Alterations in Epstein-Barr Virus-Associated Diseases.

PubMed

Niller, Hans Helmut; Banati, Ferenc; Salamon, Daniel; Minarovits, Janos

2016-01-01

Latent Epstein-Bar virus genomes undergo epigenetic modifications which are dependent on the respective tissue type and cellular phenotype. These define distinct viral epigenotypes corresponding with latent viral gene expression profiles. Viral Latent Membrane Proteins 1 and 2A can induce cellular DNA methyltransferases, thereby influencing the methylation status of the viral and cellular genomes. Therefore, not only the viral genomes carry epigenetic modifications, but also the cellular genomes adopt major epigenetic alterations upon EBV infection. The distinct cellular epigenotypes of EBV-infected cells differ from the epigenotypes of their normal counterparts. In Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC) significant changes in the host cell methylome with a strong tendency towards CpG island hypermethylation are observed. Hypermethylated genes unique for EBVaGC suggest the existence of an EBV-specific "epigenetic signature". Contrary to the primary malignancies carrying latent EBV genomes, lymphoblastoid cells (LCs) established by EBV infection of peripheral B cells in vitro are characterized by a massive genome-wide demethylation and a significant decrease and redistribution of heterochromatic histone marks. Establishing complete epigenomes of the diverse EBV-associated malignancies shall clarify their similarities and differences and further clarify the contribution of EBV to the pathogenesis, especially for the epithelial malignancies, NPC and EBVaGC.

Cloned cytolytic T-effector cells and their malignant variants produce an extracellular matrix degrading trypsin-like serine proteinase.

PubMed Central

Simon, M M; Simon, H G; Fruth, U; Epplen, J; Müller-Hermelink, H K; Kramer, M D

1987-01-01

This report describes the distribution of a trypsin-like proteinase in defined homogeneous cytolytic T-cell lines (CTLL) and their in vitro and in vivo derived malignant T-lymphoma variants. By means of chromogenic peptide substrates, we found the enzyme to attack preferentially at the carboxy terminus of arginine, in particular when non-polar amino acids were present in the amino terminal neighbouring position. The enzyme was identified by means of various inhibitors as a serine type proteinase having a pH optimum around 8 X 5. Affinity chromatography in connection with molecular sieving resulted in a 200-fold purification and indicated a molecular weight (MW) of about 50,000 for the proteinase. The enzyme was found to be highly expressed in antigen-specific CTLL as well as in their tumorigenic variants. Both intact lymphocytes of all CTLL tested and Triton X-100 lysates or enriched proteinase preparations thereof were able to degrade a high molecular weight protein (casein) and to release high molecular weight split products from the sulphated proteoglycans in subendothelial extracellular matrix. The results are discussed with respect to the invasiveness of normal and malignant T lymphocytes and the proteinase is suggested to be crucially involved in the process of cellular migration in vivo. Images Figure 1 PMID:3546101

To resect or not to resect: a review of pancreatic cyst disease management.

PubMed

Harrison, Jon M; Castillo, Carlos Fernandez-Del

2018-06-13

With recent advances in radiographic testing, there have been increases in the incidental identification of pancreatic cysts. Determining management, specifically, which cysts can be watched versus intervened upon has significant impact on at the patient-physician level as well as globally on resource allocation and healthcare expenditures. This review focuses on the three main guidelines (Fukuoka guidelines, European consensus, and American Gastroenterological Association recommendations) for management of pancreatic cystic disease after incidental identification. There are iterant revisions to each set of recommendations every few years as new data is published on the subject. This review encompasses the most up-to-date recommendations for management while also providing a framework for conceptualizing work-up for varying types of pancreatic cystic disease before and after incidental identification. Pancreatic cystic disease should be approached in thoughtful clinical manner, and each cyst should be evaluated in the context of patient's health and healthcare goals. All cysts, however, should be considered malignant until proven otherwise. Applications of different diagnostic modalities like MRI and EUS with FNA can better characterize cystic lesions and assess malignant potential. Resection should always be considered in cysts with concerning features. If deferred, surveillance should be continued indefinitely. Early termination of surveillance risks future malignant progression.

The role of the human papillomavirus in the pathogenesis of Schneiderian inverted papillomas: an analytic overview of the evidence.

PubMed

Lawson, William; Schlecht, Nicolas F; Brandwein-Gensler, Margaret

2008-06-01

Evidence of an etiological role for human papillomavirus (HPV) in Schneiderian inverted papillomas IP arose in the late 1980's; yet almost three decades later, the association between HPV and IP has yet to be universally accepted. This is probably due to the disparate HPV detection rates in IP reported in the literature. We analyzed the weight of published data in order to address the following questions: why do the HPV detection rates in IP vary so greatly? What is the relationship between low-risk (LR) and high-risk (HR) HPV types and HPV detection rates in IP? Is there a relationship between the presence and type of HPV in IP and recurrence and malignant progression? A search using the Pubmed search engine was performed to identify studies published in English from 01/87 through 12/06 using the MeSH terms ''HPV'' and ''Inverted", "Exophytic", "Oncocytic Schneiderian" or "Fungiform papilloma''. Data was abstracted from publications including histology, HPV target, HPV type, method of detection, etc. HPV results were stratified by histology and other variables. Tests for heterogeneity (between-study variability) were conducted, and weighted prevalence (WP) estimates and 95% confidence intervals (CI) were calculated using a random-effects inverse-variance model stratified on study. The association between HPV IP recurrence was estimated by random-effects inverse-variance weighted odds ratio (OR). Weighted estimates revealed similar detection rates across detection methods, 26.8% (95%CI 16.4-37.2%) by ISH, 25.2% (95%CI 14.7-35.6%) by consensus PCR, and 23.6% (95%CI 12.2-35.0%) by type-specific PCR. A preponderance of HPV 6/11 is found in IP as compared to HPV 16/18; the overall unadjusted ratio of LR to high-risk HR HPV types is 2.8:1 The HPV detection rates significantly increase (Wald t-test P < 0.02) in IPs with high-grade dysplasia (WP 55.8%, 95%CI 30.5-81.0%) and carcinoma (WP 55.1%, 95%CI 37.0-73.2%) as compared to IPs with no dysplasia or mild dysplasia (WP 22.3%, 95%CI 15.9-28.6%). Furthermore, the preponderance of LR HPV in benign IP (ratio LR/HR = 4.8:1) shifts in dysplastic and malignant IP. The LR/HR ratio is 1.1:1 for IPs with high-grade dysplasias, this ratio is inverted to favor HR HPV (1:2.4) for malignant IP. Recurrences developed in 44 of 236 patients; HPV was detected in 27 of 44 IPs (WP 57.9%, 95%CI 31.6-84.2%) that developed recurrences and in 24 of 192 IPs (WP 9.7%, 95%CI 4.4-15.0%) that did not develop recurrence. The presence of HPV was significantly associated with the likelihood of developing recurrence (weighted OR of 10.2, 95%CI 3.2-32.8). We hypothesize that LR HPV may induce IP formation, and then are lost as infected cells are shed, as a "hit and run" phenomenon. HPV detection rates increase in dysplastic IP and SCC-ex-IP with increasing ratio of HR to LR HPV types, compared to nondysplastic IP. We believe that one explanation for the variation in HPV detection rates between different studies may be the actual histologic composition of the cohort. That is, if one series contains a higher frequency of dysplastic and malignant IP, it may have a higher detection rate than another series which contains only nondysplastic IP. We hypothesize that the higher rates of HPV detection in dysplastic and malignant IP may be related to HPV integration. The implication of this is that HPV sub-type testing may identify patients at risk for recurrence, or progression to dysplasia and malignancy, and thus may impact surveillance protocols.

Focal fluorine-18 fluorodeoxyglucose-avid lesions without computed tomography correlate at whole-body positron emission tomography-computed tomography in oncology patients: how often are they malignant?

PubMed

Kumar, Rahi; Hawkins, Randall A; Yeh, Benjamin M; Wang, Zhen Jane

2011-09-01

To retrospectively evaluate the rate of malignancy of focal fluorine-18 fluorodeoxyglucose (18F-FDG)-avid lesions without computed tomography (CT) correlate at whole-body positron emission tomography (PET)-CT in oncology patients, because better defining these abnormalities could potentially lead to improved patient management algorithms that rely on PET-CT for detection, staging, and treatment monitoring of malignancies. We performed a computer search of all PET-CT studies performed at our institution from 2006 to 2009, and identified 87 studies with findings of focal 18F-FDG-avid lesions without correlate at CT. The rate of malignancy of such lesions was determined by reviewing findings at follow-up imaging or by clinical or histopathological follow-up. Rates of malignancy were categorized and compared by lesion location and by the type of primary malignancy. The most common locations for focal 18F-FDG-avid lesions without CT correlate were: lymph node location (without visible lymph nodes; 27/87), bone (21/87), soft tissue (17/87), liver (9/87), and gastrointestinal tract (8/87). Forty-one percent (36/87) of the focal FDG-avid lesions without CT correlate were malignant (either metastatic disease or a second malignancy) at follow-up (mean follow-up: 5 months, range: 1-25 months). Focal FDG-avid lesions in lymph node location and in bone without CT correlate had higher rates of malignancy (56%, 15/27 and 52%, 11/21, respectively) than lesions in all other locations (26%, 10/39, P=0.028). In 15 of 87 cases, the only significant finding at PET-CT was an FDG-avid lesion without CT correlate. Of those, 53% (8/15) was positive for malignancy. There were no significant differences in the rates of malignancy for the focal FDG-avid lesions without CT correlate when stratified by the type of primary malignancy in this series. Focal FDG avid lesions without CT correlate were malignant in 41% of cases in our series of oncology patients. Lesions in lymph node location and in bones had the highest rates of malignancy. Knowledge of the patterns and risk of malignancy of focal FDG-avid lesions without CT correlate in oncology patients may facilitate the management of oncology patients with such lesions on PET-CT, and could lead to an improved interpretation of PET-CT scans by imaging specialists.

The role of magnetic resonance imaging and ultrasound in patients with adnexal masses.

PubMed

Sohaib, S A; Mills, T D; Sahdev, A; Webb, J A W; Vantrappen, P O; Jacobs, I J; Reznek, R H

2005-03-01

To evaluate the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in characterizing adnexal masses, and to determine which patients may benefit from MRI. We prospectively studied 72 women (mean age 53 years, range 19 to 86 years) with clinically suspected adnexal masses. A single experienced sonographer performed transabdominal and transvaginal greyscale spectral and colour Doppler examinations. MRI was carried out on a 1.5T system using T1, T2 and fat-suppressed T1-weighted sequences before and after intravenous injection of gadolinium. The adnexal masses were categorized as benign or malignant without knowledge of clinical details, according to the imaging features which were compared with the surgical and pathological findings. For characterizing lesions as malignant, the sensitivity, specificity and accuracy of MRI were 96.6%, 83.7% and 88.9%, respectively, and of US were 100%, 39.5% and 63.9%, respectively. MRI was more specific (p<0.05) than US. Both MRI and US correctly diagnosed 17 (24%) cases with benign and 28 (39%) cases with malignant masses. MRI correctly diagnosed 19 (26%) cases with benign lesion(s), which on US were thought to be malignant. The age, menopausal status and CA-125 levels in these women made benign disease likely, but US features were suggestive of malignancy (large masses and solid-cystic lesions with nodules). MRI is more specific and accurate than US and Doppler assessment for characterizing adnexal masses. Women who clinically have a relatively low risk of malignancy but who have complex sonographic features may benefit from MRI.

Utility of DWI with quantitative ADC values in ovarian tumors: a meta-analysis of diagnostic test performance.

PubMed

Pi, Shan; Cao, Rong; Qiang, Jin Wei; Guo, Yan Hui

2018-01-01

Background Diffusion-weighted imaging (DWI) and quantitative apparent diffusion coefficient (ADC) values are widely used in the differential diagnosis of ovarian tumors. Purpose To assess the diagnostic performance of quantitative ADC values in ovarian tumors. Material and Methods PubMed, Embase, the Cochrane Library, and local databases were searched for studies assessing ovarian tumors using quantitative ADC values. We quantitatively analyzed the diagnostic performances for two clinical problems: benign vs. malignant tumors and borderline vs. malignant tumors. We evaluated diagnostic performances by the pooled sensitivity and specificity values and by summary receiver operating characteristic (SROC) curves. Subgroup analyses were used to analyze study heterogeneity. Results From the 742 studies identified in the search results, 16 studies met our inclusion criteria. A total of ten studies evaluated malignant vs. benign ovarian tumors and six studies assessed malignant vs. borderline ovarian tumors. Regarding the diagnostic accuracy of quantitative ADC values for distinguishing between malignant and benign ovarian tumors, the pooled sensitivity and specificity values were 0.91 and 0.91, respectively. The area under the SROC curve (AUC) was 0.96. For differentiating borderline from malignant tumors, the pooled sensitivity and specificity values were 0.89 and 0.79, and the AUC was 0.91. The methodological quality of the included studies was moderate. Conclusion Quantitative ADC values could serve as useful preoperative markers for predicting the nature of ovarian tumors. Nevertheless, prospective trials focused on standardized imaging parameters are needed to evaluate the clinical value of quantitative ADC values in ovarian tumors.

FDG-PET/CT and FLT-PET/CT for differentiating between lipid-poor benign and malignant adrenal tumours.

PubMed

Nakajo, Masatoyo; Jinguji, Megumi; Fukukura, Yoshihiko; Kajiya, Yoriko; Tani, Atushi; Nakajo, Masayuki; Nakabeppu, Yoshiaki; Arimura, Hiroshi; Nishio, Yoshihiko; Nakamura, Fumihiko; Yoshiura, Takashi

2015-12-01

To compare F-18-fluorodeoxyglucose (FDG) and F-18-fluorothymidine (FLT) PET/CT examinations for differentiating between benign and malignant adrenal tumours. Thirty lipid-poor benign and 11 malignant tumours of 40 patients were included. FDG- and FLT-based indices including visual score, maximum standardized uptake value (SUVmax) and FDG adrenal lesion/liver SUVmax (A/L SUVmax) or FLT adrenal lesion/back muscle SUVmax (A/B SUVmax) ratio were compared between benign and malignant tumours using the Mann-Whitney's U or Wilcoxon signed-rank test, and their diagnostic performances were evaluated by means of the area under the curve (AUC) values derived from the receiver operating characteristic analysis. All indices were significantly higher in malignant than benign tumours on both images (p < 0.05 each). On FDG-PET/CT, the sensitivity, specificity, and accuracy were 91 %, 63 % and 71 % for visual score, 91 %, 67 % and 73 % for SUVmax, and 100 %, 70 % and 78 % for A/L SUVmax ratio, respectively. On FLT-PET/CT, they were 100 %, 97 % and 98 % for visual score, SUVmax and A/B SUVmax ratio, respectively. All FLT indices were significantly higher than those of FDG in AUC (p < 0.05 each). FLT-PET/CT may be superior to FDG-PET/CT in differentiating lipid-poor benign from malignant adrenal tumours because of higher specificity and accuracy. • All FDG indices were significantly higher in malignant than in benign tumours. • All FLT indices were significantly higher in malignant than in benign tumours. • All FLT indices were significantly higher than those of FDG in AUC.

Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer

PubMed Central

Tabe, Yoko; Takemura, Hiroyuki; Kimura, Konobu; Takahashi, Toshihiro; Yang, Haeun; Tsuchiya, Koji; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Ohsaka, Akimichi

2018-01-01

Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode “XN-BF gating algorithm” to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples. PMID:29425230

Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer.

PubMed

Ai, Tomohiko; Tabe, Yoko; Takemura, Hiroyuki; Kimura, Konobu; Takahashi, Toshihiro; Yang, Haeun; Tsuchiya, Koji; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Ohsaka, Akimichi

2018-01-01

Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode "XN-BF gating algorithm" to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples.

Use of shear wave elastography to differentiate benign and malignant breast lesions.

PubMed

Çebi Olgun, Deniz; Korkmazer, Bora; Kılıç, Fahrettin; Dikici, Atilla Süleyman; Velidedeoğlu, Mehmet; Aydoğan, Fatih; Kantarcı, Fatih; Yılmaz, Mehmet Halit

2014-01-01

We aimed to determine the correlations between the elasticity values of solid breast masses and histopathological findings to define cutoff elasticity values differentiating malignant from benign lesions. A total of 115 solid breast lesions of 109 consecutive patients were evaluated prospectively using shear wave elastography (SWE). Two orthogonal elastographic images of each lesion were obtained. Minimum, mean, and maximum elasticity values were calculated in regions of interest placed over the stiffest areas on the two images; we also calculated mass/fat elasticity ratios. Correlation of elastographic measurements with histopathological results were studied. Eighty-three benign and thirty-two malignant lesions were histopathologically diagnosed. The minimum, mean, and maximum elasticity values, and the mass/fat elasticity ratios of malignant lesions, were significantly higher than those of benign lesions. The cutoff value was 45.7 kPa for mean elasticity (sensitivity, 96%; specificity, 95%), 54.3 kPa for maximum elasticity (sensitivity, 95%; specificity, 94%), 37.1 kPa for minimum elasticity (sensitivity, 96%; specificity, 95%), and 4.6 for the mass/fat elasticity ratio (sensitivity, 97%; specificity, 95%). SWE yields additional valuable quantitative data to ultrasonographic examination on solid breast lesions. SWE may serve as a complementary tool for diagnosis of breast lesions. Long-term clinical studies are required to accurately select lesions requiring biopsy.

Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.

PubMed

Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A; Hackett, Perry B; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E; Cooper, Laurence J N

2012-05-01

Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources.

Single-chain antibody-delivered Livin siRNA inhibits human malignant melanoma growth in vitro and in vivo.

PubMed

Wang, Hao; Yang, Yifei; Wang, Wei; Guan, Bing; Xun, Meng; Zhang, Hai; Wang, Ziling; Zhao, Yong

2017-05-01

Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody-mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine-single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma.

Elastography for the differentiation of benign and malignant liver lesions: a meta-analysis.

PubMed

Ma, Xuelei; Zhan, Wenli; Zhang, Binglan; Wei, Benling; Wu, Xin; Zhou, Min; Liu, Lei; Li, Ping

2014-05-01

The objective of this paper was to evaluate the overall accuracy of elastography in the diagnosis of benign and malignant liver lesions by liver biopsy as the gold standard. Literature databases were searched. The studies which were related to evaluate the diagnostic value of elastography for differentiation in benign and malignant liver lesions in English or Chinese were included. The summary receiver operating characteristic (SROC) curve was performed, and the areas under the curve (AUC) were also calculated to present the accuracy of the elastography for the diagnosis of benign and malignant liver lesions. Six studies which included a total of 448 liver lesions in 384 patients were analyzed. The summary sensitivity and specificity of elastography for the differentiation of malignant liver lesions were 85% (95% CI, 80 to 89%) and 84% (95% CI, 80 to 88%), respectively. And the summary diagnostic odds ratio was 46.33 (95% CI, 15.22 to 141.02), and the SROC was 0.9328. Elastography has a high sensitivity and specificity differentiation for benign and malignant liver lesions. As a non-invasive method, it is promising to be applied to clinical practice. To estimate elastography objectively, a large, prospective, international, and multi-center study is still needed.

A novel method of forceps biopsy improves the diagnosis of proximal biliary malignancies.

PubMed

Kulaksiz, Hasan; Strnad, Pavel; Römpp, Achim; von Figura, Guido; Barth, Thomas; Esposito, Irene; Schirmacher, Peter; Henne-Bruns, Doris; Adler, Guido; Stiehl, Adolf

2011-02-01

Tissue specimen collection represents a cornerstone in diagnosis of proximal biliary tract malignancies offering great specificity, but only limited sensitivity. To improve the tumor detection rate, we developed a new method of forceps biopsy and compared it prospectively with endoscopic transpapillary brush cytology. 43 patients with proximal biliary stenoses, which were suspect for malignancy, undergoing endoscopic retrograde cholangiography were prospectively recruited and subjected to both biopsy [using a double-balloon enteroscopy (DBE) forceps under a guidance of a pusher and guiding catheter with guidewire] and transpapillary brush cytology. The cytological/histological findings were compared with the final clinical diagnosis. 35 out of 43 patients had a malignant disease (33 cholangiocarcinomas, 1 hepatocellular carcinoma, 1 gallbladder carcinoma). The sensitivity of cytology and biopsy in these patients was 49 and 69%, respectively. The method with DBE forceps allowed a pinpoint biopsy of the biliary stenoses. Both methods had 100% specificity, and, when combined, 80% of malignant processes were detected. All patients with non-malignant conditions were correctly assigned by both methods. No clinically relevant complications were observed. The combination of forceps biopsy and transpapillary brush cytology is safe and offers superior detection rates compared to both methods alone, and therefore represents a promising approach in evaluation of proximal biliary tract processes.

Comparison of fine-needle aspiration and core needle biopsy under ultrasonographic guidance for detecting malignancy and for the tissue-specific diagnosis of salivary gland tumors.

PubMed

Eom, H-J; Lee, J H; Ko, M-S; Choi, Y J; Yoon, R G; Cho, K J; Nam, S Y; Baek, J H

2015-06-01

Diagnostic test accuracy studies for ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy have shown inconclusive results due to their heterogenous study designs. Our aim was to compare the diagnostic accuracy of ultrasonography-guided fine-needle aspiration versus ultrasonography-guided core needle biopsy for detecting malignant tumors of the salivary gland and for the tissue-specific diagnosis of salivary gland tumors in a single tertiary hospital. This retrospective study was approved by our institutional review board and informed consent was waived. Four hundred twelve patients who underwent ultrasonography-guided fine-needle aspiration (n = 155) or ultrasonography-guided core needle biopsy (n = 257) with subsequent surgical confirmation or clinical follow-up were enrolled. We compared the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy regarding malignant salivary gland tumors and the correct tissue-specific diagnosis of benign and malignant tumors. We also tested the difference between these procedures according to the operator's experience and lesion characteristics. The inconclusive rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 19% and 4%, respectively (P < .001). The overall accuracy of ultrasonography-guided core needle biopsy for diagnosing malignant tumors was significantly higher than that of ultrasonography-guided fine-needle aspiration (P = .024). The correct tissue-specific diagnosis rates of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy were 95% versus 97% for benign tumors (P = .648) and 67% versus 80% for malignant tumors (P = .310). Trainees showed significantly lower accuracy with ultrasonography-guided fine-needle aspiration than with ultrasonography-guided core needle biopsy for diagnosing malignant tumors (P = .021). There was no difference between the diagnostic accuracy of ultrasonography-guided fine-needle aspiration and ultrasonography-guided core needle biopsy according to the internal composition of the lesions. There were no complications requiring intervention or hospitalization in our patients. Ultrasonography-guided core needle biopsy is superior to ultrasonography-guided fine-needle aspiration in detecting and characterizing malignant tumors of the salivary gland and could emerge as the diagnostic method of choice for patients presenting with a salivary gland mass. © 2015 by American Journal of Neuroradiology.

Detection and Elimination of Oncogenic Signalling Networks in Premalignant and Malignant Cells with Magnetic Resonance Imaging

DTIC Science & Technology

2015-10-01

DATE : October 2015 TYPE OF REPORT: Annual Report PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702...not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE...Annual 3. DATES COVERED 30Sep2014 - 29Sep2015 Detection and Elimination of Oncogenic Signaling Networks in Premalignant and Malignant Cells with

Detection and Elimination of Oncogenic Signaling Networks in Premalignant and Malignant Cells with Magnetic Resonance Imaging

DTIC Science & Technology

2015-10-01

DATE : October 2015 TYPE OF REPORT: Annual Report PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702...not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE...Annual 3. DATES COVERED 30Sep2014 - 29Sep2015 Detection and Elimination of Oncogenic Signaling Networks in Premalignant and Malignant Cells with

The split personality of NKT cells in malignancy, autoimmune and allergic disorders

PubMed Central

Subleski, Jeff J; Jiang, Qun; Weiss, Jonathan M; Wiltrout, Robert H

2011-01-01

NKT cells are a heterogeneous subset of specialized, self-reactive T cells, with innate and adaptive immune properties, which allow them to bridge innate and adaptive immunity and profoundly influence autoimmune and malignant disease outcomes. NKT cells mediate these activities through their ability to rapidly express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. Not only do NKT cells regulate the functions of other cell types, but experimental evidence has found NKT cell subsets can modulate the functions of other NKT subsets. Depending on underlying mechanisms, NKT cells can inhibit or exacerbate autoimmunity and malignancy, making them potential targets for disease intervention. NKT cells can respond to foreign and endogenous antigenic glycolipid signals that are expressed during pathogenic invasion or ongoing inflammation, respectively, allowing them to rapidly react to and influence a broad array of diseases. In this article we review the unique development and activation pathways of NKT cells and focus on how these attributes augment or exacerbate autoimmune disorders and malignancy. We also examine the growing evidence that NKT cells are involved in liver inflammatory conditions that can contribute to the development of malignancy. PMID:21995570

Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry

PubMed Central

2009-01-01

Background Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM) is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model. Methods Canine cases entered in the Danish Veterinary Cancer Registry (DVCR) from May 15th 2005 through February 29th 2008 were included in this study. Fisher's exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC). Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher's exact test. Results A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown) were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128). Of these, 64 (50%) were malignant and 44 (34%) benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant), OMM (13; 20% of malignant), soft tissue sarcoma (11; 17% of malignant) and adenocarcinoma (5; 11% of malignant). The most common types of benign neoplasms were adenoma (7; 16% of benign), polyps (6; 14% of benign) and fibroma (5; 11% of benign). Conclusions In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans. Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and could be a clinical model for OMM in humans. PMID:20021647

Dedifferentiated liposarcoma of thigh with chondrosarcomatous dedifferentiated component.

PubMed

Yoon, Richard S; Benevenia, Joseph; Beebe, Kathleen S; Hameed, Meera

2010-11-01

Liposarcomas are common soft-issue sarcomas arising predominantly in deep soft tissue and the retroperitoneum with varied mortality and recurrence rates, largely dependent on histologic type. Thought to arise de novo, liposarcomas typically are classified into 5 types based on strict morphologic characteristics: well-differentiated, dedifferentiated, myxoid, round cell, and pleomorphic. More specifically, dedifferentiated liposarcoma, a common type most prevalent in the retroperitoneum, often has 2 distinct components, a well-differentiated lipomatous component and a dedifferentiated nonlipomatous component composed of sarcomas, such as myxofibrosarcomas or other spindle-cell sarcomas. Morphology typically ranges from low- to high-grade components, most commonly exhibiting myxofibrosarcoma and malignant fibrous histiocytoma components. However, the case reported in this article is unique-the dedifferentiated component exhibited only chondrosarcomatous differentiation-and it is, to our knowledge, the first such case to be described.

[Clinical validation of multiple biomarkers suspension array technology for ovarian cancer].

PubMed

Zhao, B B; Yang, Z J; Wang, Q; Pan, Z M; Zhang, W; Li, L

2017-01-25

Objective: To investigates the diagnostic value of combined detection serum CCL18, CXCL1 antigen, C1D, TM4SF1, FXR1, TIZ IgG autoantibody by suspension array for ovarian cancer. Methods: Suspension array was used to detect CCL18, CXCL1 antigen, C1D, TM4SF1, FXR1, TIZ IgG autoantibody in 120 cases of healthy women, 204 cases of patients with benign pelvic tumors, 119 cases of pelvic malignant tumor patients, and 40 cases with breast cancer, lung cancer oroliver cancer, respectively. Constructed diagnosis model of combined detection six biomarkers for diagnosis of ovarian malignant tumor. Constructed diagnosis model of combined detection autoantibodies to diagnose epithelial ovarian cancer. Analysed the value of detecting six biomarkers for diagnosis of ovarian malignant tumor and detecting autoantibodies for diagnosis of epithelial ovarian cancer. Analysed diagnostic value of detecting six biomarkers to diagnose stage Ⅰ and Ⅱepithelial ovarian cancer. Compared diagnostic value of detecting six biomarkers in diagnosis of tissue types and pathologic grading with that of CA(125). Results: Model of combined detecting six biomarkers to diagnose ovarian malignant tumor was logit ( P ) =-11.151+0.008×C1D+0.011×TM4SF1+0.011×TIZ-0.008×FXR1+0.021×CCL18+0.200×CXCL1. Model of combined detection autoantibodies to diagnose epithelial ovarian cancer was logit ( P ) =-5.137+0.013×C1D+0.014×TM4SF1+0.060×TIZ-0.060×FXR1. Sensitivity and specificity of detecting six biomarker to diagnose ovarian malignant tumor was 90.6% and 98.7%. Sensitivity and specificity of detecting autoantibodies to diagnose epithelial ovarian cancer was 75.8% and 96.7%. Combined detection for six biomarkers to diagnose serous and mucinous ovarian cancer was statistically no better than those of CA(125) ( P =0.196 and P =0.602, respectively); there was significantly difference in diagnosis of ovarian cancer ( P =0.023), and there was no significantly difference in diagnosis of different pathological grading ( P =0.089 and P =0.169, respectively). Conclusions: Constructing diagnosis model of combined detection six biomarker to diagnose ovarian malignant tumor and constructed diagnosis model of combined detectionautoantibodies to diagnose epithelial ovarian cancer. Combined detection six biomarkers to diagnose serous and mucinous ovarian tumors is better than that of CA(125).

The efficacy of oral brush biopsy with computer-assisted analysis in identifying precancerous and cancerous lesions

PubMed Central

2011-01-01

Background Cancer of the oral cavity is the sixth most common malignancy reported worldwide and one with the highest mortality rate among all malignancies. There is a paucity of reliable diagnostic methods to detect early malignancies. This study was performed to evaluate the sensitivity and specificity of brush biopsy in identifying oral premalignant and malignant lesions. Methods Oral brush and scalpel biopsies were performed on 85 consecutive patients presenting with an oral lesion deemed to be minimally suspicious by clinical examination and the results were compared. Results Of 79 patients with adequate brush biopsy samples with matching scalpel biopsies, 27 revealed histopathologic evidence of dysplasia or carcinoma, 26 of which were independently identified with the oral brush biopsy (sensitivity: 96.3% - 95% CI, 87%-100%). 52 oral lesions did not reveal any histopathologic evidence of dysplasia or carcinoma and of these, brush biopsy reported 47 as "negative" and 5 as "atypical"(specificity of "positive" brush biopsy result is 100%- 95% CI, 93%-100%; specificity for "atypical" brush biopsy result is 90.4%- 95% CI, 82%-97%. The positive predictive value of an abnormal oral brush biopsy was 84% and the negative predictive value was 98%. Conclusion Our study demonstrated that the oral brush biopsy is an accurate test in identifying oral premalignant and malignant lesions, even if minimally suspicious. PMID:21864339

Risk of malignancy in ankylosing spondylitis: a systematic review and meta-analysis.

PubMed

Deng, Chuiwen; Li, Wenli; Fei, Yunyun; Li, Yongzhe; Zhang, Fengchun

2016-08-18

Current knowledge about the overall and site-specific risk of malignancy associated with ankylosing spondylitis (AS) is inconsistent. We conducted a systematic review and meta-analysis to address this knowledge gap. Five databases (PubMed, EMBASE, Web of Science, the Cochrane library and the virtual health library) were systematically searched. A manual search of publications within the last 2 years in key journals in the field (Annals of the Rheumatic Diseases, Rheumatology and Arthritis &rheumatology) was also performed. STATA 11.2 software was used to conduct the meta-analysis. After screening, twenty-three studies, of different designs, were eligible for meta-analysis. AS is associated with a 14% (pooled RR 1.14; 95% CI 1.03-1.25) increase in the overall risk for malignancy. Compared to controls, patients with AS are at a specific increased risk for malignancy of the digestive system (pooled RR 1.20; 95% CI 1.01 to 1.42), multiple myelomas (pooled RR 1.92; 95% CI 1.37 to 3.69) and lymphomas (pooled RR 1.32; 95% CI 1.11 to 1.57). On subgroup analysis, evidence from high quality cohort studies indicated that AS patients from Asia are at highest risk for malignancy overall. Confirmation of findings from large-scale longitudinal studies is needed to identify specific risk factors and to evaluate treatment effects.

Development of tumor-targeted near infrared probes for fluorescence guided surgery.

PubMed

Kelderhouse, Lindsay E; Chelvam, Venkatesh; Wayua, Charity; Mahalingam, Sakkarapalayam; Poh, Scott; Kularatne, Sumith A; Low, Philip S

2013-06-19

Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.

Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies

PubMed Central

Firor, Amelia E.; Pinz, Kevin G.; Jares, Alexander; Liu, Hua; Salman, Huda; Golightly, Marc; Lan, Fengshuo; Jiang, Xun; Ma, Yupo

2016-01-01

Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design. We engineered a robust 3rd generation anti-CD3 CAR construct (CD3CAR) into an NK cell line (NK-92). We found that CD3CAR NK-92 cells specifically and potently lysed diverse CD3+ human PTCL primary samples as well as T-cell leukemia cells lines ex vivo. Furthermore, CD3CAR NK-92 cells effectively controlled and suppressed Jurkat tumor cell growth in vivo and significantly prolonged survival. In this study, we present the CAR directed targeting of a novel target - CD3 using CAR modified NK-92 cells with an emphasis on efficacy, specificity, and potential for new therapeutic approaches that could improve the current standard of care for PTCLs. PMID:27494836

Diagnostic potential of real-time elastography (RTE) and shear wave elastography (SWE) to differentiate benign and malignant thyroid nodules: A systematic review and meta-analysis.

PubMed

Hu, Xiangdong; Liu, Yujiang; Qian, Linxue

2017-10-01

Real-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies. Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted. Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01). The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules.

Diagnostic potential of real-time elastography (RTE) and shear wave elastography (SWE) to differentiate benign and malignant thyroid nodules

PubMed Central

Hu, Xiangdong; Liu, Yujiang; Qian, Linxue

2017-01-01

Abstract Background: Real-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies. Methods: Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted. Results: Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01). Conclusion: The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules. PMID:29068996

The RET p.G533C mutation confers predisposition to multiple endocrine neoplasia type 2A in a Brazilian kindred and is able to induce a malignant phenotype in vitro and in vivo.

PubMed

Oliveira, Mariana N L; Hemerly, Jefferson P; Bastos, André U; Tamanaha, Rosana; Latini, Flavia R M; Camacho, Cléber P; Impellizzeri, Anelise; Maciel, Rui M B; Cerutti, Janete M

2011-09-01

We have previously described a p.G533C substitution in the rearranged during transfection (RET) oncogene in a large family with medullary thyroid carcinoma. Here, we explore the functional transforming potential of RET p.G533C mutation. Plasmids expressing RET mutants (p.G533C and p.C634Y) and RET wild type were stable transfected into a rat thyroid cell line (PCCL3). Biological and biochemical effects of RET p.G533C were investigated both in vitro and in vivo. Moreover, we report the first case of pheochromocytoma among the RET p.G533C-carriers in this Brazilian family and explore the RET mutational status in DNA isolated from pheochromocytoma. Ectopic expression of RET p.G533C and p.C634Y activates RET/MAPK/ERK pathway at similar levels and significantly increased cell proliferation, compared with RET wild type. We additionally show that p.G533C increased cell viability, anchorage-independent growth, and micronuclei formation while reducing apoptosis, hallmarks of the malignant phenotype. RET p.G533C down-regulates the expression of thyroid specific genes in PCCL3. Moreover, RET p.G533C-expressing cells were able to induce liver metastasis in nude mice. Finally, we described two novel RET variants (G548V and S556T) in the DNA isolated from pheochromocytoma while they were absent in the DNA isolated from blood. Our in vitro and in vivo analysis indicates that this mutation confers a malignant phenotype to PCCL3 cells. These findings, in association with the report of first case of pheochromocytoma in the Brazilian kindred, suggest that this noncysteine mutation may be more aggressive than was initially considered.

Increased expression of sex determining region Y-box 11 (SOX11) in cutaneous malignant melanoma.

PubMed

Jian, Jiao; Guoying, Wang; Jing, Zhao

2013-08-01

To observe sex determining region Y-box 11 (SOX11) gene expression in cutaneous malignant melanoma and its effect on tumour cell proliferation. Clinicopathological data and tissue samples from patients with cutaneous malignant melanoma, together with tissue samples from healthy volunteers (controls), were retrospectively reviewed. Protein levels of SOX11 and the antigen identified by monoclonal antibody Ki-67 (Ki-67) in skin lesions were analysed using immunohistochemistry. The correlation between protein levels and clinipathological parameters was investigated. Out of 40 patient samples, 25 (62.5%) were positive for SOX11 protein in malignant melanoma tissue. This was significantly higher than in 40 control tissue samples, in which no SOX11 protein was detected. Presence of SOX11 protein was positively related to the proliferation index of cutaneous malignant melanoma tumour cells. Presence of SOX11 protein in cutaneous malignant melanoma was related to tumour type, tumour location, lymph node metastasis and 5-year survival rate. Human cutaneous malignant melanoma tissues expressed high levels of SOX11 compared with healthy controls, suggesting that SOX11 may be a new prognostic marker for malignant melanoma.

Clinicopathological analysis of 598 malignant lymphomas in Taiwan: seven-year experience in a single institution.

PubMed

Lee, Ming-Yuan; Tan, Tran-Der; Feng, An-Chen; Liu, Mei-Ching

2006-08-01

The clinicopathological characteristics of malignant lymphomas vary according to geography. The purpose of this study is to determine the distribution and clinicopathological characteristics of malignant lymphomas in Taiwan. Archival tissue from 598 malignant lymphomas during the period of 1995-2002 was retrieved. They were reclassified according to the World Health Organization classification system. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized. There were 330 males and 268 females. The median age at onset of disease was 56 years for B-cell lymphoma (BCL), 50 years for T/NK-cell lymphoma (TCL), and 26 years for Hodgkin's lymphoma (HL). BCL accounted for 80.6%, TCL for 12.4%, and HL for 7%. The major subtypes of non-HL were diffuse large B-cell lymphoma, follicular lymphoma, plasma cell myeloma, marginal zone lymphoma of mucosa-associated lymphoid tissue type, mantle cell lymphoma, unspecified peripheral TCL, and nasal type T/NK-cell lymphoma. Nodular sclerosing subtype was the most common in HL. The frequencies of TCL and HL were relatively low. For histological subtype, enteropathy-type TCL and primary bone marrow HL had higher frequency and poorer prognosis. The 5-year overall survival of BCL, TCL, and HL was 58.9, 34.7, and 83.5%, respectively. To the best of our knowledge, this is the largest series study of malignant lymphoma in Taiwan. Immunophenotype, histological subtype, and clinical stage play significant roles in prognosis (P < 0.05).

Pre-Cancerous Lesions in the Oral and Maxillofacial Region: A Literature Review with Special Focus on Etiopathogenesis

PubMed Central

Irani, Soussan

2016-01-01

Many types of cancers develop in the oral and maxillofacial region. Squamous cell carcinoma is the most common cancer and constitutes over 90 percent of these tumors. Malignant transformation is a genetic process, which later makes a phenotyping change at the cellular level. Some cancers such as oral squamous cell carcinomas (OSCCs) develop from pre-malignant lesions and conditions. Despite advances in the treatment of OSCC, the 5-year survival rate remains approximately 50% due to inability of early detection of OSCC and precursor lesions. Early detection of oral cancer, especially in the premalignant stage, can decrease mortality and morbidity significantly. This article reviews some clinical, histopathological features and etiopathogenesis of pre-cancerous lesions of the oral cavity and skin of face and lip vermilion. A relevant English literature search in Pubmed, Science Direct, and Google Scholar was performed from 1930 to 2015. Full text of 191 articles met the specific inclusion criteria for this review. PMID:28855922

Risk of metastatic ovarian involvement in nongynecologic malignancies.

PubMed

Kim, Kidong; Cho, Soo Youn; Park, Sang-Il; Kang, Hye Jin; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Ryu, Sang-Young; Lee, Eui-Don

2012-01-01

The objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors. The eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test. In 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers. One hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

Expression of prostaglandin- and vitamin D-metabolising enzymes in benign and malignant breast cells.

PubMed

Thill, Marc; Hoellen, Friederike; Becker, Steffi; Dittmer, Christine; Fischer, Dorothea; Kümmel, Sherko; Salehin, Darius; Friedrich, Michael; Köster, Frank; Diedrich, Klaus; Cordes, Tim

2012-01-01

Cyclooxygenase-2 (COX-2) plays a crucial role in prognosis of malignancy and has been associated with carcinogenesis, particularly neoangiogenesis and tumor progression. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumour suppressor in cancer. The antiproliferative effects of calcitriol [1,25(OH)(2)D(3)] mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. The expression of prostaglandin (PG)-metabolizing enzymes, vitamin D-metabolising enzymes and VDR were determined in benign and malignant breast cell lines using western blot analysis. We detected an inverse correlation between the two types of metabolism, a reduced VDR expression in the malignant breast cell lines, and therefore an insufficient induction of 24-hydroxylase in the malignant cells. We suggest the possibility of dysregulation of vitamin D-metabolizing enzymes in malignant breast cell lines.

The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

PubMed

Hastrup, N; Osterlind, A; Drzewiecki, K T; Hou-Jensen, K

1991-08-01

We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

Comparison of Dynamic Contrast-Enhanced MRI and PET/CT in the Evaluation of Laryngeal Cancer After Inadequate CT Results.

PubMed

Citil, Serdal; Dogan, Serap; Atilgan, Hasan Ikbal; Menzilcioglu, Mehmet Sait; Sahin, Tuna; Abdulrezzak, Ummuhan; Duymus, Mahmut; Ozturk, Mustafa

2015-01-01

To investigate the diagnostic value of dynamic magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) for laryngeal cancers after inadequate CT results. The study comprised 45 patients investigated for primary laryngeal cancer or recurrence-residue in which CT was considered inadequate. A mass was found in 20 patients. Dynamic MRI and PET/CT were compared for diagnosis of mass, lymph node involvement, recurrence and residue. The dynamic curves formed in dynamic MRI were investigated for diagnostic contributions. The sensitivity and specificity of the dynamic MRI, for supraglottic, glottic and subglottic location, was 100%, 80%, and 92%; 100%, 85%, and 100%, respectively. In PET/CT the sensitivity and specificity were 100% for all of those localizations. For lymph node involvement, the sensitivity of dynamic MRI and PET/CT was 100%, the specificity was 100% and 93%, respectively. For recurrence-residue, the sensitivity and specificity of dynamic MRI were 86% and 67%, respectively, with 100% sensitivity and specificity in PET/CT. The sensitivity of type A curve for detection of malignancy was 40%, and specificity was 100%. When type A and B curves were included, the sensitivity was 100%. For patients investigated for laryngeal cancer in which CT is considered inadequate, dynamic MRI or PET/CT is useful.

[Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010].

PubMed

Bao, Ping-Ping; Li, Kai; Wu, Chun-Xiao; Huang, Zhe-Zhou; Wang, Chun-Fang; Xiang, Yong-Mei; Peng, Peng; Gong, Yang-Ming; Xiao, Xian-Min; Zheng, Ying

2013-04-01

To examine the recent incidences and trends of childhood malignant solid tumors in Shanghai. Data from the population-based Shanghai Cancer Registry and related retrospective survey were used to analyze the patterns of incidence and trends of malignant solid tumors diagnosed between 2002 and 2010 in children aged 0-14 years. The distributions of incidences were described according to gender, age and cancer types which were classified according to International Classification of Childhood Cancer (ICCC). Annual age-standardized rates (ASRs) were adjusted by the world standard population. Approximate confidence intervals for standardized rate ratios (SRR) based Poisson distribution test-based methods were used to assess changes in incidence over the period 2002 - 2006 and 2007 - 2010. (1)A total of 868 cases of childhood malignant solid tumors were diagnosed in Shanghai during 2002 - 2010, accounting for 65.8% of all childhood cancers. The ASR of 2002 - 2010 was 80.2 per million for all solid tumors. (2) The ASR was higher in boys (86.3 per million) than in girls (73.8 per million) with SRR 1.2 (95%CI 1.0 - 1.3). Incidence rate was the highest in the first five years of life with 93.4 per million. The age-specific incidence rates in 5 - 9 and 10 - 14 age groups were 65.2 and 79.3 per million, respectively. (3) CNS tumors, lymphomas, germ cell tumors, neuroblastoma, and soft tissue sarcomas were the top 5 most common solid tumors in children, with the incidence rate of 23.8, 11.0, 7.8, 7.7 and 6.8 per million, respectively. The patterns of subgroups varied in different age groups. Blastomas, such as neuroblastoma, retinoblastoma, were more common in the children aged 0 - 4 years, whereas epithelial carcinomas and bone tumors developed more frequently in elder children aged 10 - 14 years. (4) Compared with the ASR in 2002 - 2006, the ASR for both genders in 2007 - 2010 had no substantial changes (78.7 per million in 2002 - 2006 and 82.9 per million in 2007 - 2010). However, among boys, the incidence rate in 2007 - 2010 was significantly higher than that in 2002 - 2006 with SRR 1.2 (95%CI: 1.0 - 1.4). For specific subgroups of cancer, there were no substantial changes. Some cautions should be taken when interpreting results involving a small number of cases per year and those with wide 95% confidence intervals. The incidence rate of pediatric malignant solid tumors among males was higher than females during 2002 - 2010, and it differed among different age groups with the highest in the first five years of life. CNS tumor was the most common type of solid tumors in children. This was a unique characteristics comparing with adult reflected in disease spectrum and age of onset. The patterns of incidence and its trends for childhood malignant solid tumors in Shanghai could provide a basis for etiologic research and preventive interventions. The findings also suggest an urgent need for longer population-based surveillance to verify the pattern and changing trends.

Breast MRI background parenchymal enhancement (BPE) correlates with the risk of breast cancer.

PubMed

Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe; Moschetta, Marco

2016-02-01

To investigate whether background parenchymal enhancement (BPE) and breast cancer would correlate searching for any significant difference of BPE pattern distribution in case of benign or malignant lesions. 386 patients, including 180 pre-menopausal (group 1) and 206 post-menopausal (group 2), underwent MR examination. Two radiologists evaluated MR images classifying normal BPE as minimal, mild, moderate or marked. The two groups of patients were subdivided into 3 categories based on MRI findings (negative, benign and malignant lesions). The distribution of BPE patterns within the two groups and within the three MR categories was calculated. The χ2 test was used to evaluate BPE type distribution in the three patient categories and any statistically significant correlation of BPE with lesion type was calculated. The Student t test was applied to search for any statistically significant difference between BPE type rates in group 1 and 2. The χ2 test demonstrated a statistically significant difference in the distribution of BPE types in negative patients and benign lesions as compared with malignant ones (p<0.05). A significantly higher prevalence of moderate and marked BPE was found among malignant lesions (group 1: 32% and 42%, respectively; group 2: 31% and 46%, respectively) while a predominance of minimal and mild BPE among negative patients (group 1: 60% and 36%, respectively; group 2: 68% and 32%, respectively) and benign lesions (group 1: 54% and 38%, respectively; group 2: 75% and 17%, respectively) was found. The Student t test did not show a statistically significant difference between BPE type rates in group 1 and 2 (p>0.05). Normal BPE could correlate with the risk of breast cancer being such BPE patterns as moderate and marked associated with patients with malignant lesions in both pre and post-menopausal women. Copyright © 2015 Elsevier Inc. All rights reserved.

Management of ampullary neoplasms: A tailored approach between endoscopy and surgery

PubMed Central

Panzeri, Francesca; Crippa, Stefano; Castelli, Paola; Aleotti, Francesca; Pucci, Alessandro; Partelli, Stefano; Zamboni, Giuseppe; Falconi, Massimo

2015-01-01

Ampullary neoplasms, although rare, present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region. No specific guidelines about their management are available, and they are often assimilated either to biliary tract or to pancreatic carcinomas. Due to their location, they tend to become symptomatic at an earlier stage compared to pancreatic malignancies. This behaviour results in a higher resectability rate at diagnosis. From a pathological point of view they arise in a zone of transition between two different epithelia, and, according to their origin, may be divided into pancreatobiliary or intestinal type. This classification has a substantial impact on prognosis. In most cases, pancreaticoduodenectomy represents the treatment of choice when there is an overt or highly suspicious malignant behaviour. The rate of potentially curative resection is as high as 90% and in high-volume centres an acceptable rate of complications is reported. In selected situations less invasive approaches, such as ampullectomy, have been advocated, although there are some concerns mainly because of a higher recurrence rate associated with limited resections for invasive carcinomas. Importantly, these methods have the drawback of not including an appropriate lymphadenectomy, while nodal involvement has been shown to be frequently present also in apparently low-risk carcinomas. Endoscopic ampullectomy is now the procedure of choice in case of low up to high-grade dysplasia providing a proper assessment of the T status by endoscopic ultrasound. In the present paper the evidence currently available is reviewed, with the aim of offering an updated framework for diagnosis and management of this specific type of disease. PMID:26185369

Climatic Factors and Epidemiologic Characteristics of Head and Neck Skin Malignancies in Osijek Baranja County, Croatia.

PubMed

Orkić, Želimir; Puntarić, Dinko; Vidosavljević, Domagoj; Puntarić, Ida; Puntarić, Eda; Gvozdić, Vlatka; Mayer, Dijana; Vidosavljević, Marina; Vranješ, Andrijana Muller

2015-12-01

The aim of this study was to investigate and compare the incidence and epidemiological characteristics of head and/or neck skin malignancies in Osijek-Baranja County, Croatia, and to connect them with relative climatic indicators such as the number and intensity of sunny and cloudy days over a longer period of time. The study included patients from Osijek Baranja County with confirmed pathohistological diagnosis of the head and/or neck malignancies from January 1, 2004 to December 31, 2012. The patients were analyzed according to gender, age, residence, occupation, type and location of the neoplasm, and hair and eye colour. The analysis of climatic elements (mean monthly and annual cloudiness values, mean monthly and annual sum values of sunny days) for a period of 50 years (1961-2011) based on the data of the Croatian Meteorological and Hydrological Service for the investigated area was performed. The study included a total of 2,952 patients: 1,487 (50.4%) males and 1,465 (49.6%) females, representing the estimated annual incidence of 104/100,000. The mean age was 72 years. The patients were mostly from rural areas, 1,952 (66.2%); 2,137 (72.4%) worked outdoors: 907 farmers (42.4%) and 889 construction workers (41.6%). Given the type of neoplasm, the most common was a basal cell cancer (BCC) in 2,160 patients (73.2%). Malignant melanoma was found in 93 patients (3.1%). The most common localizations were face (839 cases, 28.7%) and nose (643 cases, 22.0%). Males had a significantly higher number of planocellular malignancies--341 (56.6%) than females--262 (43.4%) (p=0.005). The median age of the patients was 67 years. There were no significant differences in types of malignancies, place of residence, workplace, or occupation (with respect to working outdoors or indoors). It has been shown that the ears and lips are significantly more affected by squamous cell malignancies (p=0.039 and p<0.001) compared to the neck, eye and head with malignant melanoma (p=0.004, p<0.001, and p=0.026) and the nose where basal cell neoplasms (p=0.002) prevail. There were no significant differences in the type and frequency of malignant neoplasms in relation to hair and eye colour of the patients. The last 50 years in Osijek-Baranja County have seen a declining trend in the number of cloudy days and upward trend in the mean annual sum of sunny days. When compared, the increase in sunny days results in a higher number of patients suffering from malignant melanoma (ρ=0.695, p=0.038). It is obvious that malignant neoplasms of the skin, head and neck occur after decades of exposure, and as a cumulative effect of exposure to risk factors. A direct exposure to sun seems to play an important role, especially with regard to melanoma. Nevertheless, further research is needed. Copyright© by the National Institute of Public Health, Prague 2015.

Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions

PubMed Central

Roca, Elisa; Lacroix, Romaric; Judicone, Coralie; Laroumagne, Sophie; Robert, Stéphane; Cointe, Sylvie; Muller, Alexandre; Kaspi, Elise; Roll, Patrice; Brisson, Alain R.; Tantucci, Claudio

2016-01-01

Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign (n = 14) and malignant (n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions. PMID:26689993

Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions.

PubMed

Roca, Elisa; Lacroix, Romaric; Judicone, Coralie; Laroumagne, Sophie; Robert, Stéphane; Cointe, Sylvie; Muller, Alexandre; Kaspi, Elise; Roll, Patrice; Brisson, Alain R; Tantucci, Claudio; Astoul, Philippe; Dignat-George, Françoise

2016-01-19

Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign (n = 14) and malignant (n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions.

Type I insulin-like growth factor receptor signaling in hematological malignancies

PubMed Central

Vishwamitra, Deeksha; George, Suraj Konnath; Shi, Ping; Kaseb, Ahmed O.; Amin, Hesham M.

2017-01-01

The insulin-like growth factor (IGF) signaling system plays key roles in the establishment and progression of different types of cancer. In agreement with this idea, substantial evidence has shown that the type I IGF receptor (IGF-IR) and its primary ligand IGF-I are important for maintaining the survival of malignant cells of hematopoietic origin. In this review, we discuss current understanding of the role of IGF-IR signaling in cancer with a focus on the hematological neoplasms. We also address the emergence of IGF-IR as a potential therapeutic target for the treatment of different types of cancer including plasma cell myeloma, leukemia, and lymphoma. PMID:27661006

Reactive oxygen species modulator 1, a novel protein, combined with carcinoembryonic antigen in differentiating malignant from benign pleural effusion.

PubMed

Chen, Xianmeng; Zhang, Na; Dong, Jiahui; Sun, Gengyun

2017-05-01

The differential diagnosis of malignant pleural effusion and benign pleural effusion remains a clinical problem. Reactive oxygen species modulator 1 is a novel protein overexpressed in various human tumors. The objective of this study was to evaluate the diagnostic value of joint detection of reactive oxygen species modulator 1 and carcinoembryonic antigen in the differential diagnosis of malignant pleural effusion and benign pleural effusion. One hundred two consecutive patients with pleural effusion (including 52 malignant pleural effusion and 50 benign pleural effusion) were registered in this study. Levels of reactive oxygen species modulator 1 and carcinoembryonic antigen were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Results showed that the concentrations of reactive oxygen species modulator 1 both in pleural fluid and serum of patients with malignant pleural effusion were significantly higher than those of benign pleural effusion (both p < 0.05). The diagnostic sensitivity and specificity of pleural fluid reactive oxygen species modulator 1 were 61.54% and 82.00%, respectively, with the optimized cutoff value of 589.70 pg/mL. However, the diagnostic sensitivity and specificity of serum reactive oxygen species modulator 1 were only 41.38% and 86.21%, respectively, with the cutoff value of 27.22 ng/mL, indicating that serum reactive oxygen species modulator 1 may not be a good option in the differential diagnosis of malignant pleural effusion and benign pleural effusion. The sensitivity and specificity of pleural fluid carcinoembryonic antigen were 69.23% and 88.00%, respectively, at the cutoff value of 3.05 ng/mL, while serum carcinoembryonic antigen were 80.77% and 72.00% at the cutoff value of 2.60 ng/mL. The sensitivity could be raised to 88.17% in parallel detection of plural fluid reactive oxygen species modulator 1 and carcinoembryonic antigen concentration, and the specificity could be improved to 97.84% in serial detection.

Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

PubMed

Tsai, Hsin-Lin; Chang, Jei-Wen; Wu, Tsai-Hun; King, Kuang-Liang; Yang, Ling-Yu; Chan, Yu-Jiun; Yang, An-Hang; Chang, Fu-Pang; Pan, Chin-Chen; Yang, Wu-Chang; Loong, Che-Chuan

2014-07-15

To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

Laser induced autofluorescence for diagnosis of non-melanoma skin cancer

NASA Astrophysics Data System (ADS)

Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Merlemis, N.; Kalatzis, I.; Sianoudis, I. A.; Batsi, O.; Christofidou, E.; Stratigos, A. J.; Katsambas, A. D.; Antoniou, Ch.

2015-01-01

Non melanoma skin cancer is one of the most frequent malignant tumors among humans. A non-invasive technique, with high sensitivity and high specificity, would be the most suitable method for basal cell carcinoma (BCC) or other malignancies diagnostics, instead of the well established biopsy and histopathology examination. In the last decades, a non-invasive, spectroscopic diagnostic method was introduced, the laser induced fluorescence (LIF), which could generate an image contrast between different states of skin tissue. The noninvasiveness consists in that this biophotonic method do not require tissue sample excision, what is necessary in histopathology characterization and biochemical analysis of the skin tissue samples, which is worldwide used as an evaluation gold standard. The object of this study is to establish the possibilities of a relatively portable system for laser induced skin autofluorescence to differentiate malignant from nonmalignant skin lesions. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a Nd:YAG-3ω laser (λ=355 nm, 6 ns), used as an excitation source for the autofluorescence measurements. A portable fiber-based spectrometer was used to record fluorescence spectra of the sites of interest. The ex vivo results, obtained with this spectroscopic technique, were correlated with the histopathology results. After the analysis of the fluorescence spectra of almost 60 skin tissue areas, we developed an algorithm to distinguish different types of malignant lesions, including inflammatory areas. Optimization of the data analysis and potential use of LIF spectroscopy with 355 nm Nd:YAG laser excitation of tissue autofluorescence for clinical applications are discussed.

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

PubMed Central

Bagdonaite, Ieva; Wandall, Hans H.; Litvinov, Ivan V.; Nastasi, Claudia; Becker, Jürgen C.; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M.; Zhang, Qian; Wasik, Mariusz A.; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-01-01

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22ΔN), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22ΔN mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22ΔN (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22ΔN and CD22wt in these cells. In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients. PMID:25957418

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients.

PubMed

Bagdonaite, Ieva; Wandall, Hans H; Litvinov, Ivan V; Nastasi, Claudia; Becker, Jürgen C; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M; Zhang, Qian; Wasik, Mariusz A; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-06-10

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22∆N), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22∆N mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22∆N (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22∆N and CD22wt in these cells.In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients.

Rationale and Design of a Phase 1 Clinical Trial to Evaluate HSV G207 Alone or with a Single Radiation Dose in Children with Progressive or Recurrent Malignant Supratentorial Brain Tumors.

PubMed

Waters, Alicia M; Johnston, James M; Reddy, Alyssa T; Fiveash, John; Madan-Swain, Avi; Kachurak, Kara; Bag, Asim K; Gillespie, G Yancey; Markert, James M; Friedman, Gregory K

2017-03-01

Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors. G207 is a genetically engineered HSV-1 lacking genes essential for replication in normal brain cells. Safety has been established in preclinical investigations involving intracranial inoculation in the highly HSV-sensitive owl monkey (Aotus nancymai), and in three adult phase 1 trials in recurrent/progressive high-grade gliomas. No dose-limiting toxicities were seen in the adult studies and a maximum tolerated dose was not reached. Approximately half of the 35 treated adults had radiographic or neuropathologic evidence of response at a minimum of one time point. Preclinical studies in pediatric brain tumor models indicate that a variety of pediatric tumor types are highly sensitive to killing by G207. This clinical protocol outlines a first in human children study of intratumoral inoculation of an oncolytic virus via catheters placed directly into recurrent or progressive supratentorial malignant tumors.

A systematic review of automated melanoma detection in dermatoscopic images and its ground truth data

NASA Astrophysics Data System (ADS)

Ali, Abder-Rahman A.; Deserno, Thomas M.

2012-02-01

Malignant melanoma is the third most frequent type of skin cancer and one of the most malignant tumors, accounting for 79% of skin cancer deaths. Melanoma is highly curable if diagnosed early and treated properly as survival rate varies between 15% and 65% from early to terminal stages, respectively. So far, melanoma diagnosis is depending subjectively on the dermatologist's expertise. Computer-aided diagnosis (CAD) systems based on epiluminescense light microscopy can provide an objective second opinion on pigmented skin lesions (PSL). This work systematically analyzes the evidence of the effectiveness of automated melanoma detection in images from a dermatoscopic device. Automated CAD applications were analyzed to estimate their diagnostic outcome. Searching online databases for publication dates between 1985 and 2011, a total of 182 studies on dermatoscopic CAD were found. With respect to the systematic selection criterions, 9 studies were included, published between 2002 and 2011. Those studies formed databases of 14,421 dermatoscopic images including both malignant "melanoma" and benign "nevus", with 8,110 images being available ranging in resolution from 150 x 150 to 1568 x 1045 pixels. Maximum and minimum of sensitivity and specificity are 100.0% and 80.0% as well as 98.14% and 61.6%, respectively. Area under the receiver operator characteristics (AUC) and pooled sensitivity, specificity and diagnostics odds ratio are respectively 0.87, 0.90, 0.81, and 15.89. So, although that automated melanoma detection showed good accuracy in terms of sensitivity, specificity, and AUC, but diagnostic performance in terms of DOR was found to be poor. This might be due to the lack of dermatoscopic image resources (ground truth) that are needed for comprehensive assessment of diagnostic performance. In future work, we aim at testing this hypothesis by joining dermatoscopic images into a unified database that serves as a standard reference for dermatology related research in PSL classification.

Association between simian virus 40 and non-Hodgkin lymphoma

NASA Technical Reports Server (NTRS)

Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

2002-01-01

BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

Extranodal nasal-type NK/T-cell lymphoma of the palate and paranasal sinuses

PubMed Central

Nikolaos, Nikitakis; Grigorios, Polyzois; Konstantinos, Katoumas; Savvas, Titsinides; Vassiliki, Zolota; Alexandra, Sklavounou; Theodoros, Papadas

2012-01-01

Summary Background: Extranodal nasal-type natural killer (NK)/T-cell lymphoma represents a rare entity, typically originating in the nasal cavity, palate or midfacial region. Signs and symptoms include non-specific rhinitis and/or sinusitis, nasal obstruction, epistaxis, facial swelling and development of deep necrotic ulceration in the midline of the palate, causing an oronasal defect. Differential diagnosis includes fungal infections, Wegener’s granulomatosis, tertiary syphilis, other non-Hodgkin’s lymphomas and malignant epithelial midline tumors. Case Report: We present a case of a 40-year-old man complaining of headache, facial pain, nasal congestion and fever. Examination revealed a large deep necrotic ulcer in the middle of the palate, presenting as an oronasal defect. Endoscopic rhinoscopy revealed crusts in the nasal cavities, moderate perforation of the nasal septum cartilage and contraction of the middle and inferior conchae. Computer tomography showed occupation of the maxillary sinuses, ethmoidal cells and sphenoidal sinus by a hyperdense soft tissue mass. Laboratory investigation revealed increased erythrocyte sedimentation rate. A wide excision of the lesion was performed. Histopathological and immunohistochemical evaluation established the diagnosis of extranodal nasal-type NK/T-cell lymphoma. The patient was treated with CHOP chemotherapy, involved-field radiotherapy and autologous bone marrow transplantation. A removable partial denture with obturator was fabricated and inserted to relieve problems caused by the oronasal defect. Conclusions: Extranodal nasal-type NK/T-cell lymphoma is a very aggressive, rapidly progressing malignant neoplasm with a poor prognosis, which can be improved by early diagnosis and combined treatment. PMID:23569495

Detection and typing of human papillomaviruses (HPV) in malignant, dysplastic, nondysplastic and normal oral epithelium by nested polymerase chain reaction, immunohistochemistry and transitional electron microscopy in patients of northern Greece.

PubMed

Blioumi, E; Chatzidimitriou, D; Pazartzi, Ch; Katopodi, Th; Tzimagiorgis, G; Emmanouil-Nikoloussi, E-N; Markopoulos, A; Kalekou, C; Lazaridis, N; Diza, E; Antoniades, D

2014-09-01

To evaluate the role of HPV in oral carcinogenesis, we examined the prevalence of HPV in malignant, potentially malignant and normal oral epithelium and studied the relation of HPV prevalence with other factors obtained from the patient's records. Our material consisted of 291 tissue specimens from 258 individuals. From every individual formalin fixed and paraffin embedded tissues were examined by nested Polymerase Chain Reaction (NPCR) for the detection of HPV DNA and by immunohistochemistry (IHC) for the in situ detection of HPV L1 protein. Positive PCR products were sequenced in order to type HPVs. Also 33 fresh tissues were obtained, fixed and used to detect HPV particles by transitional electron microscopy (TEM). HPV was detected in 32.9% of the tissue specimens by NPCR, in 4.7% by immunohistochemistry and in 28.1% by TEM. In detail, by nested PCR HPV L1 DNA was detected in 40% of normal tissues, 40% of fibromas, 35.8% of non-dysplastic leukoplakias, 31.6% of dysplastic leukoplakias and 22.2% of oral squamous cell carcinomas. The HPV viral load of 96.5% of the samples was very low (1 viral copy per 10(2)-10(4) cells). HPV16 prevails in all histological groups in 89-100%. We conclude that HPV does not seem, from the specific sample examined, to play a substantial role in oral carcinogenesis. However, it cannot be excluded that HPV could be involved in oral carcinogenesis only in cases with high viral load or at early stages of carcinogenesis possibly through the hit-and-run mechanism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adding the power of iodinated contrast media to the credibility of mammography in breast cancer diagnosis

PubMed Central

Tsigginou, Alexandra; Chalazonitis, Athanasios; Feida, Eleni; Vlachos, Dimitrios Efthymios; Zagouri, Flora; Rellias, Ioannis; Dimitrakakis, Constantine

2016-01-01

Dual-energy contrast-enhanced spectral mammography (CESM) represents a relatively new diagnostic tool adjunct to mammography. The aim of this study was to strengthen the breast imaging-reporting and data system (BIRADS) classification score in order to improve early breast cancer diagnosis. For this reason, we propose a sum score, termed malignancy potential score (MPS), incorporating the standard BIRADS score and our proposed CESM score. From September 2014 to September 2015, 216 females (age range, 26–85 years; mean age 54.6 years) underwent CESM evaluation of mammographic findings that were primarily assessed as BIRADS 2–5. 10 of these patients had bilateral findings; a total of 226 lesions were examined. High-energy image evaluation was based on the intensity of contrast enhancement of the lesion compared with background enhancement, categorized as Type -1, 0, 1 or 2 enhancement. Histopathology reports were compared with imaging assessment. 98 of 226 lesions were malignant and 128 of 226 lesions were benign. The area under the curve was 0.843, 0.888 and 0.917 for mammographic BIRADS score, CESM score and MPS, respectively, with p-value < 0.05. The sensitivity, specificity and accuracy rates were 91.83, 80.47 and 85.40%, respectively, when a best MPS cut-off point of 4 was used. The malignancy potential score (MPS) has higher diagnostic performance than digital mammography or CESM alone. MPS empowers the credibility of the digital mammography BIRADS score and our proposed type of enhancement in dual-energy CESM and is a diagnostic tool that increases the accuracy rate in early breast cancer diagnosis. PMID:27452266

High-level expression of podoplanin in benign and malignant soft tissue tumors: immunohistochemical and quantitative real-time RT-PCR analysis.

PubMed

Xu, Yongjun; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tetsuo; Ariizumi, Takashi; Li, Guidong; Umezu, Hajime; Endo, Naoto

2011-03-01

Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells. D2-40 is a commercially available mouse monoclonal antibody which binds to an epitope on human podoplanin. D2-40 immunoreactivity is therefore highly sensitive and specific for lymphatic endothelium. Recent investigations have shown widespread applications of immunohistochemical staining with D2-40 in evaluating podoplanin expression as an immunohistochemical marker for diagnosis and prognosis in various tumors. To determine whether the podoplanin (D2-40) antibody may be useful for the diagnosis of soft tissue tumors, 125 cases, including 4 kinds of benign tumors, 15 kinds of malignant tumors and 3 kinds of tumor-like lesions were immunostained using the D2-40 antibody. Total RNA was extracted from frozen tumor tissue obtained from 41 corresponding soft tissue tumor patients and 12 kinds of soft tissue tumor cell lines. Quantitative real-time PCR reactions were performed. Immunohistochemical and quantitative real-time RT-PCR analyses demonstrated the expression of the podoplanin protein and mRNA in the majority of benign and malignant soft tissue tumors and tumor-like lesions examined, with the exception of alveolar soft part sarcoma, embryonal and alveolar rhabdomyosarcoma, extraskeletal Ewing's sarcoma/peripheral primitive neuro-ectodermal tumor and lipoma, which were completely negative for podoplanin. Since it is widely and highly expressed in nearly all kinds of soft tissue tumors, especially in spindle cell sarcoma, myxoid type soft tissue tumors and soft tissue tumors of the nervous system, podoplanin is considered to have little value in the differential diagnosis of soft tissue tumors.

Landscape of DNA Virus Associations across Human Malignant Cancers: Analysis of 3,775 Cases Using RNA-Seq

PubMed Central

Tannir, Nizar M.; Williams, Michelle D.; Chen, Yunxin; Yao, Hui; Zhang, Jianping; Thompson, Erika J.; Meric-Bernstam, Funda; Medeiros, L. Jeffrey; Weinstein, John N.

2013-01-01

Elucidation of tumor-DNA virus associations in many cancer types has enhanced our knowledge of fundamental oncogenesis mechanisms and provided a basis for cancer prevention initiatives. RNA-Seq is a novel tool to comprehensively assess such associations. We interrogated RNA-Seq data from 3,775 malignant neoplasms in The Cancer Genome Atlas database for the presence of viral sequences. Viral integration sites were also detected in expressed transcripts using a novel approach. The detection capacity of RNA-Seq was compared to available clinical laboratory data. Human papillomavirus (HPV) transcripts were detected using RNA-Seq analysis in head-and-neck squamous cell carcinoma, uterine endometrioid carcinoma, and squamous cell carcinoma of the lung. Detection of HPV by RNA-Seq correlated with detection by in situ hybridization and immunohistochemistry in squamous cell carcinoma tumors of the head and neck. Hepatitis B virus and Epstein-Barr virus (EBV) were detected using RNA-Seq in hepatocellular carcinoma and gastric carcinoma tumors, respectively. Integration sites of viral genes and oncogenes were detected in cancers harboring HPV or hepatitis B virus but not in EBV-positive gastric carcinoma. Integration sites of expressed viral transcripts frequently involved known coding areas of the host genome. No DNA virus transcripts were detected in acute myeloid leukemia, cutaneous melanoma, low- and high-grade gliomas of the brain, and adenocarcinomas of the breast, colon and rectum, lung, prostate, ovary, kidney, and thyroid. In conclusion, this study provides a large-scale overview of the landscape of DNA viruses in human malignant cancers. While further validation is necessary for specific cancer types, our findings highlight the utility of RNA-Seq in detecting tumor-associated DNA viruses and identifying viral integration sites that may unravel novel mechanisms of cancer pathogenesis. PMID:23740984

Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers.

PubMed

Ma, Xuefei; Zhang, Wei; Zhang, Rong; Li, Jingming; Li, Shufen; Ma, Yunlin; Jin, Wen; Wang, Kankan

2018-05-26

Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.

New players for advanced prostate cancer and the rationalisation of insulin-sensitising medication.

PubMed

Gunter, Jennifer H; Sarkar, Phoebe L; Lubik, Amy A; Nelson, Colleen C

2013-01-01

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of "old players" for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer.

Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia type 1

PubMed Central

Circelli, Luisa; Ramundo, Valeria; Marotta, Vincenzo; Sciammarella, Concetta; Marciello, Francesca; Del Prete, Michela; Sabatino, Lina; Pasquali, Daniela; Izzo, Francesco; Scala, Stefania; Colao, Annamaria; Faggiano, Antongiulio; Colantuoni, Vittorio

2015-01-01

CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype–phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1. PMID:25824098

Fidelity of DNA Replication in Normal and Malignant Human Breast Cells

DTIC Science & Technology

1998-07-01

synthesome has been extensively demonstrated to carry out full length DNA replication in vitro, and to accurately depict the DNA replication process as it...occurs in the intact cell. By examining the fidelity of the DNA replication process carried out by the DNA synthesome from a number of breast cell types...we have demonstrated for the first time, that the cellular DNA replication machinery of malignant human breast cells is significantly more error-prone than that of non- malignant human breast cells.

Role of exponential apparent diffusion coefficient in characterizing breast lesions by 3.0 Tesla diffusion-weighted magnetic resonance imaging

PubMed Central

Kothari, Shweta; Singh, Archana; Das, Utpalendu; Sarkar, Diptendra K; Datta, Chhanda; Hazra, Avijit

2017-01-01

Objective: To evaluate the role of exponential apparent diffusion coefficient (ADC) as a tool for differentiating benign and malignant breast lesions. Patients and Methods: This prospective observational study included 88 breast lesions in 77 patients (between 18 and 85 years of age) who underwent 3T breast magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) using b-values of 0 and 800 s/mm2 before biopsy. Mean exponential ADC and ADC of benign and malignant lesions obtained from DWI were compared. Receiver operating characteristics (ROC) curve analysis was undertaken to identify any cut-off for exponential ADC and ADC to predict malignancy. P value of <0.05 was considered statistically significant. Histopathology was taken as the gold standard. Results: According to histopathology, 65 lesions were malignant and 23 were benign. The mean ADC and exponential ADC values of malignant lesions were 0.9526 ± 0.203 × 10−3 mm2/s and 0.4774 ± 0.071, respectively, and for benign lesions were 1.48 ± 0.4903 × 10−3 mm2/s and 0.317 ± 0.1152, respectively. For both the parameters, differences were highly significant (P < 0.001). Cut-off value of ≤0.0011 mm2/s (P < 0.0001) for ADC provided 92.3% sensitivity and 73.9% specificity, whereas with an exponential ADC cut-off value of >0.4 (P < 0.0001) for malignant lesions, 93.9% sensitivity and 82.6% specificity was obtained. The performance of ADC and exponential ADC in distinguishing benign and malignant breast lesions based on respective cut-offs was comparable (P = 0.109). Conclusion: Exponential ADC can be used as a quantitative adjunct tool for characterizing breast lesions with comparable sensitivity and specificity as that of ADC. PMID:28744085

Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

ClinicalTrials.gov

2017-06-27

Adult Malignant Mesenchymoma; Adult Rhabdomyosarcoma; Childhood Alveolar Rhabdomyosarcoma; Childhood Botryoid-Type Embryonal Rhabdomyosarcoma; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Mesenchymoma; Non-Metastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

Nationwide population-based study reveals increased malignancy risk in taiwanese liver transplant recipients.

PubMed

Tsai, Yung Fong; Chen, Hsiu Pin; Liu, Fu Chao; Liu, Shih Hao; Chen, Chun Yu; Cheng, Chih Wen; Lin, Jr-Rung

2016-12-13

Post-transplant malignancy is a major cause of late mortality for liver transplant recipients (LTRs). This nationwide population-based cohort study investigated the cancer type, incidence, and risk factors associated with post-transplant malignancies in 2938 Taiwanese LTRs who underwent transplantation between 1998 and 2012. Data from the National Health Insurance Research Database were extracted on the basis of the International Classification of Disease, Ninth Revision, Clinical Modification codes. Among these patients, 284 post-transplant malignancies were diagnosed. These included 99 de novo malignancies among 98 patients, yielding a standardized incidence ratio of 2.17 (95% CI, 1.76 to 2.64) compared to the general population. The most common malignancies were infection related liver cancer (19.39%), oropharyngeal cancer (19.39%), non-Hodgkin's lymphoma (9.18%), and esophageal cancer (5.10%), as well as non-infection-related prostate cancer (6.12%). Patients with recurrent malignancies had the highest mortality. Furthermore, 186 recurrent malignancies relapsed, and the commonly affected organs were the liver (83.33%), lung (4.84%), bone and bone marrow (4.30%), and intrahepatic bile ducts (2.69%). Old age, the male sex, liver cirrhosis, hepatitis B, peptic ulcer, diabetes mellitus, and pre-existing cancer were all risk factors associated with post-transplant malignancies. Recipients with biliary atresia or urea cycle metabolism disorders were protected from post-transplant malignancies. Our data revealed a significantly increased risk of malignancies in Taiwanese LTRs and suggest implementation of a careful malignancy-surveillance program and immunosuppression-minimizing strategy for high-risk patients.

Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.

PubMed

Thokala, Radhika; Olivares, Simon; Mi, Tiejuan; Maiti, Sourindra; Deniger, Drew; Huls, Helen; Torikai, Hiroki; Singh, Harjeet; Champlin, Richard E; Laskowski, Tamara; McNamara, George; Cooper, Laurence J N

2016-01-01

Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.

Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion

PubMed Central

Lee, Seung Hyeun; Park, Myung Jae; Choi, Sue In; Lee, Eun Joo; Lee, Sang Yeub; In, Kwang Ho

2017-01-01

Abstract Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (n = 53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (n = 91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3 ng/mL, which was significantly higher than that in benign pleural effusions (P < 0.001). The optimal cutoff value of Romo1 to discriminate lung cancer-associated malignant effusion from benign effusions was 67.0 ng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750–0.886), which was significantly better than that of cytokeratin 19 fragments (P < 0.001). Pleural fluid Romo1 could discriminate lung cancer from benign diseases with considerable sensitivity and specificity. Our findings suggest a diagnostic potential of Romo1 for lung cancer-associated malignant effusion. PMID:28121949

Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies.

PubMed

Živković, Nevenka Piskač; Petrovečki, Mladen; Lončarić, Čedna Tomasović; Nikolić, Igor; Waeg, Georg; Jaganjac, Morana; Žarković, Kamelija; Žarković, Neven

2017-04-01

The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue. Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts. Both the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors. Both PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Utility of 18F-fluorodeoxyglucose-positron emission tomography in the differential diagnosis of benign and malignant gynaecological tumours.

PubMed

Takagi, Hiroaki; Sakamoto, Jinichi; Osaka, Yasuhiro; Shibata, Takeo; Fujita, Satoko; Sasagawa, Toshiyuki

2018-02-05

Positron emission tomography/computed tomography (PET/CT) involving 18F-fluorodeoxyglucose (FDG) is widely used for systemic cancer and recurrence diagnosis. However, the differential diagnosis of benign and malignant gynaecological tumours according to FDG accumulation is unclear. This study aimed to investigate the intensity of FDG uptake/metabolic activity for the differential diagnosis of benign and malignant gynaecological tumours. This study included seven patients with physiological phenomena, 34 with benign tumours, 13 with borderline malignant tumours and 119 with malignant tumours who underwent 18F-FDG PET/CT. We assessed the maximum standardized uptake value (SUVmax) and determined its utility in the diagnosis of benign and malignant tumours using a receiver operating characteristic (ROC) curve analysis. Among the 63 patients with ovarian tumours, the mean SUVmax of 22 patients with benign ovarian tumours was 2.48 and the mean SUVmax of 41 patients with malignant ovarian tumours was 10.98 (P < 0.001). In the ROC curve analysis, the area under the curve (AUC) was 0.977, with a 95% confidence interval of 0.947-1.000. With a cut-off value of 3.97 for the optimal SUVmax, the sensitivity and specificity were 95.1% and 86.4%, respectively. In addition, the AUC was 0.911 (95% CI: 0.768-1.000) for the assessment of uterine myomas and sarcomas. With a cut-off value of 10.62 for the optimal SUVmax, the sensitivity and specificity were 91.7% and 86.7% respectively. The SUVmax value helps differentiate benign and malignant ovarian tumours, as well as uterine myomas and uterine sarcomas. © 2018 The Royal Australian and New Zealand College of Radiologists.

Young investigator challenge: The utility of GATA3 immunohistochemistry in the evaluation of metastatic breast carcinomas in malignant effusions.

PubMed

Lew, Madelyn; Pang, Judy C; Jing, Xin; Fields, Kristina L; Roh, Michael H

2015-10-01

It is not uncommon to encounter challenges in the immunohistochemical confirmation of metastatic breast cancer given the limited sensitivities of mammaglobin and gross cystic disease fluid protein 15 (GCDFP-15/BRST-2) and the significant proportion of triple-negative breast carcinomas (ie, tumors that are negative for estrogen receptor [ER], and progesterone receptor [PgR], and human epidermal growth factor 2 [HER2]). GATA binding protein 3 (GATA3) has emerged as a potentially useful immunohistochemical adjunct during the evaluation of metastatic breast carcinomas in cytology specimens. The objective of the current study was to examine GATA3 expression in the context of malignant effusions secondary to both mammary and extramammary malignancies. In total, 306 malignant effusions (from 62 metastatic breast carcinomas and 244 extramammary malignancies) were examined using GATA3 immunohistochemistry. Effusions with metastatic breast carcinoma were also examined using immunohistochemistry for additional breast markers (ER, PgR, HER2, mammaglobin, and GCDFP-15/BRST-2). GATA3 immunohistochemistry highlighted the tumor cells in 58 of the 62 samples (93.5%) from patients with metastatic breast carcinoma, which was higher than the observed sensitivity of immunohistochemistry for ER (63.8%), PgR (41.4%), HER2 (15.5%), mammaglobin (22.4%), and GCDFP-15/BRST-2 (5.2%). GATA3 expression also was observed in a subset of malignant effusions secondary to extramammary primaries, specifically, in 28 of 244 specimens (11.5%). GATA3 is a highly sensitive marker for the detection of metastatic breast carcinomas in effusion specimens. However, this marker is not entirely specific for malignancies of breast origin. Thus, GATA3 should be used in conjunction with additional immunohistochemical markers during the cytologic evaluation of malignant effusions. © 2015 American Cancer Society.

HMB-45 and Melan-A are useful in the differential diagnosis between granular cell tumor and malignant melanoma.

PubMed

Gleason, Briana C; Nascimento, Alessandra F

2007-02-01

Granular cell tumors (GCTs), especially if atypical or malignant, may share cytomorphologic and architectural features with malignant melanoma, when the latter shows granular cell change. In many cases, these neoplasms can be differentiated from each other on histologic grounds, but distinction may sometimes be challenging. By immunohistochemistry, both tumors are strongly positive for S-100 protein and frequently express other nonspecific markers such as CD68, NSE, and NKIC3. In the current study, we reviewed 60 cases of conventional cutaneous, mucosal, and visceral GCT and studied the use of immunoperoxidase staining for the differential diagnosis between malignant melanoma and GCT. Immunohistochemical stains for S-100 protein, A, HMB-45, and microphthalmia transcription factor (MITF) were performed in all cases. All of the tumors were positive for S-100 protein. MITF immunostaining was diffusely positive in 53 (88%) cases, focally positive in three (5%) cases, and negative in four (7%). Fifty-seven (95%) tumors were negative for Melan-A, one case was focally positive, and two cases showed rare positive tumor cells. None of the tumors expressed HMB-45. In conclusion, GCT and malignant melanoma can be reliably differentiated on the basis of immunohistochemical stains in the majority of cases. Although not always positive in malignant melanoma, in this context, HMB-45 expression seems to be 100% specific for the diagnosis of melanoma. Melan-A is slightly less specific, with rare cases of GCT showing focal positivity. MITF is not useful in this differential-93% of the GCTs in our series showed nuclear reactivity for this marker. The latter finding highlights the limited specificity of this antibody in the diagnosis of melanocytic tumors.

Ultrasound-based logistic regression model LR2 versus magnetic resonance imaging for discriminating between benign and malignant adnexal masses: a prospective study.

PubMed

Shimada, Kanane; Matsumoto, Koji; Mimura, Takashi; Ishikawa, Tetsuya; Munechika, Jiro; Ohgiya, Yoshimitsu; Kushima, Miki; Hirose, Yusuke; Asami, Yuka; Iitsuka, Chiaki; Miyamoto, Shingo; Onuki, Mamiko; Tsunoda, Hajime; Matsuoka, Ryu; Ichizuka, Kiyotake; Sekizawa, Akihiko

2018-06-01

The diagnostic performances of the International Ovarian Tumor Analysis (IOTA) ultrasound-based logistic regression model (LR2) and magnetic resonance imaging (MRI) in discriminating between benign and malignant adnexal masses have not been directly compared in a single study. Using the IOTA LR2 model and subjective interpretation of MRI findings by experienced radiologists, 265 consecutive patients with adnexal masses were preoperatively evaluated in two hospitals between February 2014 and December 2015. Definitive histological diagnosis of excised tissues was used as a gold standard. From the 265 study subjects, 54 (20.4%) tumors were histologically diagnosed as malignant (including 11 borderline and 3 metastatic tumors). Preoperative diagnoses of malignant tumors showed 91.7% total agreement between IOTA LR2 and MRI, with a kappa value of 0.77 [95% confidence interval (CI), 0.68-0.86]. Sensitivity of IOTA LR2 (0.94, 95% CI, 0.85-0.98) for predicting malignant tumors was similar to that of MRI (0.96, 95% CI, 0.87-0.99; P = 0.99), whereas specificity of IOTA LR2 (0.98, 95% CI, 0.95-0.99) was significantly higher than that of MRI (0.91, 95% CI, 0.87-0.95; P = 0.002). Combined IOTA LR2 and MRI results gave the greatest sensitivity (1.00, 95% CI, 0.93-1.00) and had similar specificity (0.91, 95% CI, 0.86-0.94) to MRI. The IOTA LR2 model had a similar sensitivity to MRI for discriminating between benign and malignant tumors and a higher specificity compared with MRI. Our findings suggest that the IOTA LR2 model, either alone or in conjunction with MRI, should be included in preoperative evaluation of adnexal masses.

Synthesis and evaluation of ¹²³/¹³¹I-Iochlonicotinamide as a novel SPECT probe for malignant melanoma.

PubMed

Chang, Chih-Chao; Chang, Chih-Hsien; Shen, Chih-Chieh; Chen, Chuan-Lin; Liu, Ren-Shyan; Lin, Ming-Hsien; Wang, Hsin-Ell

2015-05-01

Malignant melanoma expresses a highly aggressive metastasis. Early diagnosis of malignant melanoma is important for patient survival. Radiolabeled benzamides and nicotinamides have been reported to be attractive candidates for malignant melanoma diagnosis as they bind to melanin, a characteristic substance that displays in malignant melanoma, and show high tumor accumulation and retention. Herein, we designed and synthesized a novel (123/131)I-labeled nicotinamide derivative that specifically binds to melanin. (123/131)I-Iochlonicotinamide was prepared with good radiochemical yield (50-70%, decay corrected) and high specific radioactivity (50-80 GBq/μmol). (131)I-Iochlonicotinamide exhibited good in vitro stability (radiochemical purity >95% after a 24-h incubation) in human serum. High uptake of (123/131)I-Iochlonicotinamide in B16F0 melanoma cells compared to that in A375 amelanotic cells demonstrated its selective binding to melanin. Intravenous administration of (123/131)I-Iochlonicotinamide in a melanoma-bearing mouse model revealed high uptake in melanotic melanoma and high tumor-to-muscle ratio. MicroSPECT scan of (123/131)I-Iochlonicotinamide injected mice also displayed high contrast tumor imaging as compared with normal organs. The radiation-absorbed dose projection for the administration of (131)I-Iochlonicotinamide to human was based on the results of biodistribution study. The effective dose appears to be approximately 0.44 mSv/MBq(-1). The specific binding of (123/131)I-Iochlonicotinamide to melanin along with a prolonged tumor retention and acceptable projected human dosimetry suggest that it may be a promising theranostic agent for treating malignant melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children.

PubMed

Sawada, Akihisa; Inoue, Masami; Kondo, Osamu; Yamada-Nakata, Kayo; Ishihara, Takashi; Kuwae, Yuko; Nishikawa, Masanori; Ammori, Yasuhiro; Tsuboi, Akihiro; Oji, Yusuke; Koyama-Sato, Maho; Oka, Yoshihiro; Yasui, Masahiro; Sugiyama, Haruo; Kawa, Keisei

2016-02-01

Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times. Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned. © 2015 Wiley Periodicals, Inc.

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents

PubMed Central

Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

2013-01-01

Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date. PMID:23459471

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents.

PubMed

Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

2013-01-01

Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.

Malignant tumors as cause of disability at the Instituto Mexicano del Seguro Social

PubMed

Zitle-García, Edgar Jesús; Sauceda-Valenzuela, Alma Lucila; Ascencio-Montiel, Iván de Jesús; García-Paredes, Jesús

2018-01-01

Cancer represents an important issue in health, with the economic impact that it takes. The aim of this paper is to analyze the epidemiological characteristics of a population with social security who was diagnosed with some type of cancer and required a disability pension. Observational study, retrolective cohort type, carried out at the Instituto Mexicano del Seguro Social (IMSS) with IMSS beneficiaries ruled with a state of disability due to malignancy during the period 2006 to 2012. 13 633 cases were studied, observing an increasing behavior among the years mentioned. The age average of the rightful claimants ruled was 47.75 years; the main causes of disability due to malignant tumors were breast, colon and brain cancer. The definitive opinions represented the 49.66%, which are likely to generate a constituent amount for the IMSS. It is important to have data of the survival in relation to the most frequent malignant tumors, which can provide information about the severity and prognosis of these diseases. The results obtained lead to discuss the effectiveness of programs established on the prevention and early detection of non-communicable diseases, mainly in breast cancer, since the impact that has this type of suffering may involve a major financial problem for the IMSS because of the payment of constituent amounts.

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets

PubMed Central

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-01-01

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are—for the time being—not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells. PMID:28703782

Understanding the Role of Non-Coding RNAs in Bladder Cancer: From Dark Matter to Valuable Therapeutic Targets.

PubMed

Pop-Bica, Cecilia; Gulei, Diana; Cojocneanu-Petric, Roxana; Braicu, Cornelia; Petrut, Bogdan; Berindan-Neagoe, Ioana

2017-07-13

The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival. The role of non-coding RNAs in bladder cancer emerged in the last decade, revealing that microRNAs (miRNAs) may act as tumor suppressor genes, respectively oncogenes, but also as biomarkers for early diagnosis. Regarding other types of non-coding RNAs, especially long non-coding RNAs (lncRNAs) which are extensively reviewed in this article, their exact roles in tumorigenesis are-for the time being-not as evident as in the case of miRNAs, but, still, clearly suggested. Therefore, this review covers the non-coding RNA expression profile of bladder cancer patients and their validated target genes in bladder cancer cell lines, with repercussions on processes such as proliferation, invasiveness, apoptosis, cell cycle arrest, and other molecular pathways which are specific for the malignant transformation of cells.

Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells.

PubMed

Mayevska, Oksana; Chen, Oleh; Karatsai, Olena; Bobak, Yaroslav; Barska, Maryna; Lyniv, Liliana; Pavlyk, Iuliia; Rzhepetskyy, Yuriy; Igumentseva, Natalia; Redowicz, Maria Jolanta; Stasyk, Oleh

2017-06-15

Anticancer therapy based on recombinant arginine-degrading enzymes has been proposed for the treatment of several types of malignant cells deficient in arginine biosynthesis. One of the predicted side effects of such therapy is restricted bioavailability of nitric oxide as arginine catabolic product. Prolonged NO limitation may lead to unwanted disturbances in NO-dependent vasodilation, cardiovascular and immune systems. This problem can be overcome by co-supplementation with exogenous NO donor. However, NO may potentially counteract anticancer effects of therapy based on arginine deprivation. In this study, we evaluate for the first time the effects of an exogenous NO donor, sodium nitroprusside, on viability and metastatic properties of two human melanoma cell lines SK-MEL-28 and WM793 under arginine-deprived conditions. It was revealed that NO did not rescue melanoma cells from specific effects evoked by arginine deprivation, namely decreased viability and induction of apoptosis, dramatically reduced motility, invasiveness and clonogenic potential. Moreover, sodium nitroprusside co-treatment augmented several of these antineoplastic effects. We report that a combination of NO-donor and arginine deprivation strongly and specifically impaired metastatic behavior of melanoma cells. Thus, sodium nitroprusside can be considered as an adjuvant for the more efficient treatment of malignant melanoma and possibly other tumors with arginine-degrading enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis

PubMed Central

Chi, Zhixia; Du, Shou-Hui; Chen, Can; Tay, Johan C.K.; Toh, Han Chong; Connolly, John E.; Xu, Xue Hu; Wang, Shu

2017-01-01

The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells. A single intraperitoneal injection of the CART cells eradicated established ovarian xenografts and resulted in significantly prolonged animal survival. Since EpCAM is also expressed on normal epithelium, anti-EpCAM CART cells were generated by mRNA electroporation that display a controlled cytolytic activity with a limited CAR expression duration. Multiple repeated infusions of these RNA CAR-modified T cells delayed disease progression in immunodeficient mice bearing well-established peritoneal ovarian and colorectal xenografts. Thus, our study demonstrates the effectiveness of using anti-EpCAM CAR-expressing T cells for local treatment of PC in mice. The possibility of using this approach for clinical treatment of EpCAM-positive gastrointestinal and gynecological malignancies warrants further validation. PMID:28088790

Statistical Methods for Identifying Sequence Motifs Affecting Point Mutations

PubMed Central

Zhu, Yicheng; Neeman, Teresa; Yap, Von Bing; Huttley, Gavin A.

2017-01-01

Mutation processes differ between types of point mutation, genomic locations, cells, and biological species. For some point mutations, specific neighboring bases are known to be mechanistically influential. Beyond these cases, numerous questions remain unresolved, including: what are the sequence motifs that affect point mutations? How large are the motifs? Are they strand symmetric? And, do they vary between samples? We present new log-linear models that allow explicit examination of these questions, along with sequence logo style visualization to enable identifying specific motifs. We demonstrate the performance of these methods by analyzing mutation processes in human germline and malignant melanoma. We recapitulate the known CpG effect, and identify novel motifs, including a highly significant motif associated with A→G mutations. We show that major effects of neighbors on germline mutation lie within ±2 of the mutating base. Models are also presented for contrasting the entire mutation spectra (the distribution of the different point mutations). We show the spectra vary significantly between autosomes and X-chromosome, with a difference in T→C transition dominating. Analyses of malignant melanoma confirmed reported characteristic features of this cancer, including statistically significant strand asymmetry, and markedly different neighboring influences. The methods we present are made freely available as a Python library https://bitbucket.org/pycogent3/mutationmotif. PMID:27974498

Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

PubMed Central

Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

2015-01-01

The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer. PMID:25609959

Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells.

PubMed

Park, Jae H; Brentjens, Renier J

2010-04-01

Chemotherapy-resistant B-cell hematologic malignancies may be cured with allogeneic hematopoietic stem cell transplantation (HSCT), demonstrating the potential susceptibility of these tumors to donor T-cell mediated immune responses. However, high rates of transplant-related morbidity and mortality limit this approach. For this reason, there is an urgent need for less-toxic forms of immune-based cellular therapy to treat these malignancies. Adoptive transfer of autologous T cells genetically modified to express chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens represents an attractive means of overcoming the limitations of conventional HSCT. To this end, investigators have generated CARs targeted to various antigens expressed by B-cell malignancies, optimized the design of these CARs to enhance receptor mediated T cell signaling, and demonstrated significant anti-tumor efficacy of the resulting CAR modified T cells both in vitro and in vivo mouse tumor models. These encouraging preclinical data have justified the translation of this approach to the clinical setting with currently 12 open clinical trials and one completed clinical trial treating various B-cell malignancies utilizing CAR modified T cells targeted to either the CD19 or CD20 B-cell specific antigens.

Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

PubMed

Kikushige, Yoshikane; Miyamoto, Toshihiro

2015-11-01

Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions.

PubMed

Saigal, Sonal; Bhargava, Ankur; Mehra, S K; Dakwala, Falguni

2011-07-01

The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia.

Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions

PubMed Central

Saigal, Sonal; Bhargava, Ankur; Mehra, S. K.; Dakwala, Falguni

2011-01-01

Background and Objective: The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. Materials and Methods: Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. Results: In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. Conclusion: The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia. PMID:22090762

Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors: A review

PubMed Central

Cháirez-Ramírez, MH; Moreno-Jiménez, MR; González-Laredo, RF; Gallegos-Infante, JA; Rocha-Guzmán, Nuria Elizabeth

2016-01-01

In recent times, a great deal of interest has been motivated on plant derived compounds known as nutraceuticals. These compounds exert important beneficial activities that improve people's health status when are consumed regularly, and now they appear as a viable option to explore their possible therapeutic effects against diseases like cancer. Particularly, lupane-type triterpenes have shown great ability to modulate multiple cancer-related signaling pathways and processes, including NF-κB, Wnt/β-catenin, PI3K/Akt, apoptosis, and many other routes related to proliferation or cell death, which are uncontrolled in malignant tumors. These investigations have promoted in vitro and in vivo studies, searching their mechanisms of action; although more research is still needed to prove its potential in human clinical trials. This review focuses on the ability of betulin, betulinic acid and lupeol to show benefits against the most common types of malignant tumors, which are considered a major global threat for public health. PMID:28337107

Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

PubMed Central

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

2012-01-01

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

Non-epithelial malignancies and metastatic tumours of the breast

PubMed Central

O'Donnell, Mark E; McCavert, Mark; Carson, Jim; Mullan, Fred J; Whiteside, Michael W; Garstin, W Ian

2009-01-01

Introduction Non-epithelial breast malignancies include primary lymphomas, sarcomas, haematological malignancies, melanomas as well as secondary metastases to the breast. They account for less than 1% of all breast tumours. The demographics and clinical features are similar to epithelial breast cancers but the prognosis and management options are often very different. Most reported series are small with limited follow-up. The main aim of this study was to review our experience for these malignancies and to compare this with the published literature. Methods A 14-year retrospective review of all breast resection specimens was completed in the Antrim Area Hospital Cancer Unit. Clinical records of patients diagnosed with non-epithelial breast malignancies were then reviewed for data regarding patient demographics, clinical presentation, pre-operative investigations, operative findings and outcome. Pathology reports were examined carefully for tumour type, location and for evidence of lymphovascular spread. This data was compared with the available literature. Results Nineteen (F = 16) patients were found to have non-epithelial breast malignancies between April 1994 and August 2007. Mean age was 61.6 years (range 25–86). 17 patients (89.5%) presented with a palpable lump, mastalgia or skin change, while 2 (10.5%) patients' tumours were detected through screening. The histological types of non-epithelial malignancies were as follows: lymphoma (n = 8; M = 1 and F = 7, mean age: 68.5 range 52–86), sarcoma (n = 5; M = 1 and F = 4, mean age 56.4 range 29–69), malignant melanoma (n = 3; M = 1 and F = 2, mean age 54.3 range 25–70), multiple myeloma (n = 1; F, 71), metastatic renal cell carcinoma (n = 1; F, 63) and metastatic carcinoid tumour (n = 1; F, 52). The mean follow-up was 1541 days (32–4589 days). Nine patients were alive at the end of follow-up. Only 1 of 11 deaths was not directly related to the malignancy. The average time from surgery to death was 798.5 days (range 32–3248 days). Conclusion Non-epithelial breast malignancies are rare cancers with significant mortality rates. Correct diagnosis and avoidance of inappropriate therapies requires a comprehensive triple assessment and a multidisciplinary management approach. PMID:19568446

Women with peritoneal carcinomatosis of unknown origin: Efficacy of image-guided biopsy to determine site-specific diagnosis.

PubMed

Hewitt, M J; Anderson, K; Hall, G D; Weston, M; Hutson, R; Wilkinson, N; Perren, T J; Lane, G; Spencer, J A

2007-01-01

To evaluate the use of image-guided biopsy (IGB) in routine clinical practice to obtain site-specific diagnoses in women presenting with peritoneal carcinomatosis (PC). Retrospective case study. Tertiary referral centre. A total of 149 consecutive women with PC who underwent IGB. Biopsy was performed in women considered unsuitable for primary surgery because of poor performance status or disease unlikely to be optimally debulked, with a prior history of malignancy or where there was clinicoradiological uncertainty about primary tumour site. Standard haematoxylin-eosin histological analysis was supplemented with immunohistochemistry. The rate of site-specific diagnosis. A total of 149 women underwent IGB using computed tomography or ultrasound over a 6-year period. The only complication was one rectus sheath haematoma. In 138 (93%) women, a site-specific cancer diagnosis was made on the IGB (including 111 müllerian tract, 8 gastrointestinal tract, 4 breast and 3 lymphoma); in ten women, a repeat biopsy was necessary, giving an overall failure rate of 7%. In a further six women, malignancy was confirmed but a site-specific diagnosis could not be made, and in four women, biopsy showed benign tissue. A site-specific diagnosis was obtained in 29 of the 32 women (94%) with previous malignancy, of which 18/32 (56%) showed a new primary cancer. IGB is a safe and accurate technique for providing site-specific diagnoses in women with PC in routine clinical practice, including those with a previous relevant malignancy. IGB can replace laparoscopic or open biopsy in defining primary therapeutic options. The data would suggest that the biopsy should be performed with ultrasound where feasible.

Passive antibody-mediated immunotherapy for the treatment of malignant gliomas.

PubMed

Mitra, Siddhartha; Li, Gordon; Harsh, Griffith R

2010-01-01

Despite advances in understanding the molecular mechanisms of brain cancer, the outcome of patients with malignant gliomas treated according to the current standard of care remains poor. Novel therapies are needed, and immunotherapy has emerged with great promise. The diffuse infiltration of malignant gliomas is a major challenge to effective treatment; immunotherapy has the advantage of accessing the entire brain with specificity for tumor cells. Therapeutic immune approaches include cytokine therapy, passive immunotherapy, and active immunotherapy. Cytokine therapy involves the administration of immunomodulatory cytokines to activate the immune system. Active immunotherapy is the generation or augmentation of an immune response, typically by vaccination against tumor antigens. Passive immunotherapy connotes either adoptive therapy, in which tumor-specific immune cells are expanded ex vivo and reintroduced into the patient, or passive antibody-mediated therapy. In this article, the authors discuss the preclinical and clinical studies that have used passive antibody-mediated immunotherapy, otherwise known as serotherapy, for the treatment of malignant gliomas.

Differentiation between benign and malignant palatal tumors using conventional MRI: a retrospective analysis of 130 cases.

PubMed

Zheng, Yingyan; Xiao, Zebin; Zhang, Hua; She, Dejun; Lin, Xuehua; Lin, Yu; Cao, Dairong

2018-04-01

To evaluate the discriminative value of conventional magnetic resonance imaging between benign and malignant palatal tumors. Conventional magnetic resonance imaging features of 130 patients with palatal tumors confirmed by histopathologic examination were retrospectively reviewed. Clinical data and imaging findings were assessed between benign and malignant tumors and between benign and low-grade malignant salivary gland tumors. The variables that were significant in differentiating benign from malignant lesions were further identified using logistic regression analysis. Moreover, imaging features of each common palatal histologic entity were statistically analyzed with the rest of the tumors to define their typical imaging features. Older age, partially defined and ill-defined margins, and absence of a capsule were highly suggestive of malignant palatal tumors, especially ill-defined margins (β = 6.400). The precision in determining malignant palatal tumors achieved a sensitivity of 92.8% and a specificity of 85.6%. In addition, irregular shape, ill-defined margins, lack of a capsule, perineural spread, and invasion of surrounding structures were more often associated with low-grade malignant salivary gland tumors. Conventional magnetic resonance imaging is useful for differentiating benign from malignant palatal tumors as well as benign salivary gland tumors from low-grade salivary gland malignancies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Improved Performance in Differentiating Benign from Malignant Sinonasal Tumors Using Diffusion-weighted Combined with Dynamic Contrast-enhanced Magnetic Resonance Imaging

PubMed Central

Wang, Xin-Yan; Yan, Fei; Hao, Hui; Wu, Jian-Xing; Chen, Qing-Hua; Xian, Jun-Fang

2015-01-01

Background: Differentiating benign from malignant sinonsal lesions is essential for treatment planning as well as determining the patient's prognosis, but the differentiation is often difficult in clinical practice. The study aimed to determine whether the combination of diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can improve the performance in differentiating benign from malignant sinonasal tumors. Methods: This retrospective study included 197 consecutive patients with sinonasal tumors (116 malignant tumors and 81 benign tumors). All patients underwent both DW and DCE-MRI in a 3-T magnetic resonance scanner. Two different settings of b values (0,700 and 0,1000 s/mm2) and two different strategies of region of interest (ROI) including whole slice (WS) and partial slice (PS) were used to calculate apparent diffusion coefficients (ADCs). A DW parameter with WS ADCsb0,1000 and two DCE-MRI parameters (time intensity curve [TIC] and time to peak enhancement [Tpeak]) were finally combined to use in differentiating the benign from the malignant tumors in this study. Results: The mean ADCs of malignant sinonasal tumors (WS ADCsb0,1000 = 1.084 × 10−3 mm2/s) were significantly lower than those of benign tumors (WS ADCsb0,1000 = 1.617 × 10−3 mm2/s, P < 0.001). The accuracy using WS ADCsb0,1000 alone was 83.7% in differentiating the benign from the malignant tumors (85.3% sensitivity, 81.2% specificity, 86.4% positive predictive value [PPV], and 79.5% negative predictive value [NPV]). The accuracy using DCE with Tpeak and TIC alone was 72.1% (69.1% sensitivity, 74.1% specificity, 77.5% PPV, and 65.1% NPV). Using DW-MRI parameter was superior than using DCE parameters in differentiation between benign and malignant sinonasal tumors (P < 0.001). The accuracy was 87.3% (90.5% sensitivity, 82.7% specificity, 88.2% PPV, and 85.9% NPV) using DW-MRI combined with DCE-MRI, which was superior than that using DCE-MRI alone or using DW-MRI alone (both P < 0.001) in differentiating the benign from the malignant tumors. Conclusions: Diffusion-weighted combined with DCE-MRI can improve imaging performance in differentiating benign from malignant sinonasal tumors, which has the potential to improve diagnostic accuracy and to provide added value in the management for these tumors. PMID:25698188

Immunologic Endocrine Disorders

PubMed Central

Michels, Aaron W.; Eisenbarth, George S.

2010-01-01

Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

Rap G protein signal in normal and disordered lymphohematopoiesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minato, Nagahiro, E-mail: minato@imm.med.kyoto-u.ac.jp

2013-09-10

Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the developmentmore » and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy.« less

Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies.

PubMed

Aghebati-Maleki, Leili; Younesi, Vahid; Baradaran, Behzad; Abdolalizadeh, Jalal; Motallebnezhad, Morteza; Nickho, Hamid; Shanehbandi, Dariush; Majidi, Jafar; Yousefi, Mehdi

2017-04-01

Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules. In the present study, scFvs against a specific peptide from the extracellular domain of ROR1 were selected using phage display technology. The selected scFvs were further characterized using polyclonal and monoclonal phage enzyme-linked immunosorbent assay (ELISA), soluble monoclonal ELISA, colony PCR, and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies were also evaluated in lymphoma and myeloma cancer cell lines using MTT and annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the ROR1 peptide. Colony PCR confirmed the presence of full-length V H and Vκ inserts. The percentages of cell growth after 24 h of treatment of cells with individual scFv revealed that the scFv significantly inhibited the growth of the RPMI8226 and chronic lymphocytic leukemia (CLL) cells in comparison with the untreated cells ( p < 0.05). Interestingly, 24-h treatment with specific scFv induced apoptosis cell death in the RPMI8226 and CLL cells. Taken together, our results demonstrate that targeting of ROR1 using peptide-specific scFv can be an effective immunotherapy strategy in hematological malignancies.

The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.

PubMed

Remenschneider, Aaron K; Dilger, Amanda E; Wang, Yingbing; Palmer, Edwin L; Scott, James A; Emerick, Kevin S

2015-04-01

Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. Blinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. A consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. Ninety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. SPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Does Lesion Size Affect the Value of Shear Wave Elastography for Differentiating Between Benign and Malignant Thyroid Nodules?

PubMed

Wang, Fen; Chang, Cai; Chen, Min; Gao, Yi; Chen, Ya-Ling; Zhou, Shi-Chong; Li, Jia-Wei; Zhi, Wen-Xiang

2018-03-01

We aimed to investigate the diagnostic performance of shear wave elastography (SWE) combined with conventional ultrasonography (US) for differentiating between benign and malignant thyroid nodules of different sizes. A total of 445 thyroid nodules from 445 patients were divided into 3 groups based on diameter (group 1, ≤ 10 mm; group 2, 10-20 mm; and group 3, > 20 mm). The mean elasticity index of the whole lesion was automatically calculated, and the threshold for differentiation between benign and malignant nodules was constructed by a receiver operating characteristic curve analysis. Diagnostic performances of conventional US and SWE were compared by using pathologic results as reference standards. The mean elasticity was significantly higher in malignant versus benign nodules for all size groups. The differences in mean elasticity in the size groups were not statistically significant for malignant or benign nodules. The specificity of US combined with SWE for group 1 was significantly higher than that for groups 2 and 3 (77.8% versus 62.9% and 53.3%; P < .05), and compared with group 1, the sensitivity was significantly higher for groups 2 and 3 (92.4% and 94.3% versus 80.7%; P < .05). When SWE was added, the specificity increased and the sensitivity and diagnostic accuracy decreased for group 1, and the sensitivity increased and the specificity decreased for groups 2 and 3; however, the differences were not significant. Combined with SWE, US yielded higher specificity for nodules of 10 mm and smaller and higher sensitivity for nodules larger than 10 mm. © 2017 by the American Institute of Ultrasound in Medicine.

Quantitative Shear Wave Velocity Measurement on Acoustic Radiation Force Impulse Elastography for Differential Diagnosis between Benign and Malignant Thyroid Nodules: A Meta-analysis.

PubMed

Liu, Bo-Ji; Li, Dan-Dan; Xu, Hui-Xiong; Guo, Le-Hang; Zhang, Yi-Feng; Xu, Jun-Mei; Liu, Chang; Liu, Lin-Na; Li, Xiao-Long; Xu, Xiao-Hong; Qu, Shen; Xing, Mingzhao

2015-12-01

The aim of this study was to evaluate the diagnostic performance of quantitative shear wave velocity (SWV) measurement on acoustic radiation force impulse (ARFI) elastography for differentiation between benign and malignant thyroid nodules using meta-analysis. The databases of PubMed and the Web of Science were searched. Studies published in English on assessment of the sensitivity and specificity of ARFI elastography for the differentiation of thyroid nodules were collected. The quantitative measurement of ARFI elastography was evaluated by SWV (m/s). Meta-Disc Version 1.4 software was used to describe and calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curves. We analyzed a total of 13 studies, which included 1,854 thyroid nodules (including 1,339 benign nodules and 515 malignant nodules) from 1,641 patients. The summary sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules by SWV were 0.81 (95% confidence interval [CI]: 0.77-0.84) and 0.84 (95% CI: 0.81-0.86), respectively. The pooled positive and negative likelihood ratios were 5.21 (95% CI: 3.56-7.62) and 0.23 (95% CI: 0.17-0.32), respectively. The pooled diagnostic odds ratio was 27.53 (95% CI: 14.58-52.01), and the area under the summary receiver operating characteristic curve was 0.91 (Q* = 0.84). In conclusion, SWV measurement on ARFI elastography has high sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules and can be used in combination with conventional ultrasound. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Malignancy Detection on Mammography Using Dual Deep Convolutional Neural Networks and Genetically Discovered False Color Input Enhancement.

PubMed

Teare, Philip; Fishman, Michael; Benzaquen, Oshra; Toledano, Eyal; Elnekave, Eldad

2017-08-01

Breast cancer is the most prevalent malignancy in the US and the third highest cause of cancer-related mortality worldwide. Regular mammography screening has been attributed with doubling the rate of early cancer detection over the past three decades, yet estimates of mammographic accuracy in the hands of experienced radiologists remain suboptimal with sensitivity ranging from 62 to 87% and specificity from 75 to 91%. Advances in machine learning (ML) in recent years have demonstrated capabilities of image analysis which often surpass those of human observers. Here we present two novel techniques to address inherent challenges in the application of ML to the domain of mammography. We describe the use of genetic search of image enhancement methods, leading us to the use of a novel form of false color enhancement through contrast limited adaptive histogram equalization (CLAHE), as a method to optimize mammographic feature representation. We also utilize dual deep convolutional neural networks at different scales, for classification of full mammogram images and derivative patches combined with a random forest gating network as a novel architectural solution capable of discerning malignancy with a specificity of 0.91 and a specificity of 0.80. To our knowledge, this represents the first automatic stand-alone mammography malignancy detection algorithm with sensitivity and specificity performance similar to that of expert radiologists.

Use of shear wave elastography to differentiate benign and malignant breast lesions

PubMed Central

Olgun, Deniz Çebi; Korkmazer, Bora; Kılıç, Fahrettin; Dikici, Atilla Süleyman; Velidedeoğlu, Mehmet; Aydoğan, Fatih; Kantarcı, Fatih; Yılmaz, Mehmet Halit

2014-01-01

PURPOSE We aimed to determine the correlations between the elasticity values of solid breast masses and histopathological findings to define cutoff elasticity values differentiating malignant from benign lesions. MATERIALS and METHODS A total of 115 solid breast lesions of 109 consecutive patients were evaluated prospectively using shear wave elastography (SWE). Two orthogonal elastographic images of each lesion were obtained. Minimum, mean, and maximum elasticity values were calculated in regions of interest placed over the stiffest areas on the two images; we also calculated mass/fat elasticity ratios. Correlation of elastographic measurements with histopathological results were studied. RESULTS Eighty-three benign and thirty-two malignant lesions were histopathologically diagnosed. The minimum, mean, and maximum elasticity values, and the mass/fat elasticity ratios of malignant lesions, were significantly higher than those of benign lesions. The cutoff value was 45.7 kPa for mean elasticity (sensitivity, 96%; specificity, 95%), 54.3 kPa for maximum elasticity (sensitivity, 95%; specificity, 94%), 37.1 kPa for minimum elasticity (sensitivity, 96%; specificity, 95%), and 4.6 for the mass/fat elasticity ratio (sensitivity, 97%; specificity, 95%). CONCLUSION SWE yields additional valuable quantitative data to ultrasonographic examination on solid breast lesions. SWE may serve as a complementary tool for diagnosis of breast lesions. Long-term clinical studies are required to accurately select lesions requiring biopsy. PMID:24509183

Elastography in the differential diagnosis of thyroid nodules in Hashimoto thyroiditis.

PubMed

Şahin, Mustafa; Çakal, Erman; Özbek, Mustafa; Güngünes, Aşkin; Arslan, Müyesser Sayki; Akkaymak, Esra Tutal; Uçan, Bekir; Ünsal, Ilknur Öztürk; Bozkurt, Nujen Çolak; Delibaşi, Tuncay

2014-08-01

Elastography is a method which assesses the risk of the malignancy and provides information about the degree of hardness in tissue. Hashimoto's thyroiditis, autoimmune lymphocytic infiltration and fibrosis, is considered to be a very common disease that is able to change the hardness of the tissue. The diagnostic value of elastography of this group of patients has not previously been reported. In our study, we aimed to determine the diagnostic value of elastography in 283 patients (255 female, 28 male) with Hashimoto's thyroiditis. Elastography score and index were measured with real-time ultrasound elastography (Hitachi(®) EUB 7000 HV machine with using 13 MHz linear transducer). The outcome of this measure shows that malignant nodules were with higher elastography scores (ES) and strain indexes (SI) values. ES ≥3 were observed in 16/20 malignant and 130/263 benign nodules, respectively. The area under the curve (AUC) for the elasto score (AUC) was 0.72 (p = 0.001), and AUC for the strain index was 0.77 (p < 0.0001). Accordingly, our study suggests that strain index reflects malignancy better than the elasto score. We conclude that elastography score is ≥3 providing 80 % sensitivity and 50 %, six specificity for diagnosing malignancy. For strain index, we found that 2.45 (72.2 % sensitivity and 70 % specificity) is a cut-off point. We have detected a lower cut-off point for SI in Hashimoto patients although sensitivity and specificity decreases in Hashimoto in this population.

Diagnostic Performance of SRU and ATA Thyroid Nodule Classification Algorithms as Tested With a 1 Million Virtual Thyroid Nodule Model.

PubMed

Boehnke, Mitchell; Patel, Nayana; McKinney, Kristin; Clark, Toshimasa

The Society of Radiologists in Ultrasound (SRU 2005) and American Thyroid Association (ATA 2009 and ATA 2015) have published algorithms regarding thyroid nodule management. Kwak et al. and other groups have described models that estimate thyroid nodules' malignancy risk. The aim of our study is to use Kwak's model to evaluate the tradeoffs of both sensitivity and specificity of SRU 2005, ATA 2009 and ATA 2015 management algorithms. 1,000,000 thyroid nodules were modeled in MATLAB. Ultrasound characteristics were modeled after published data. Malignancy risk was estimated per Kwak's model and assigned as a binary variable. All nodules were then assessed using the published management algorithms. With the malignancy variable as condition positivity and algorithms' recommendation for FNA as test positivity, diagnostic performance was calculated. Modeled nodule characteristics mimic those of Kwak et al. 12.8% nodules were assigned as malignant (malignancy risk range of 2.0-98%). FNA was recommended for 41% of nodules by SRU 2005, 66% by ATA 2009, and 82% by ATA 2015. Sensitivity and specificity is significantly different (< 0.0001): 49% and 60% for SRU; 81% and 36% for ATA 2009; and 95% and 20% for ATA 2015. SRU 2005, ATA 2009 and ATA 2015 algorithms are used routinely in clinical practice to determine whether thyroid nodule biopsy is indicated. We demonstrate significant differences in these algorithms' diagnostic performance, which result in a compromise between sensitivity and specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentiation of benign from malignant solid breast masses: comparison of two-dimensional and three-dimensional shear-wave elastography.

PubMed

Lee, Su Hyun; Chang, Jung Min; Kim, Won Hwa; Bae, Min Sun; Cho, Nariya; Yi, Ann; Koo, Hye Ryoung; Kim, Seung Ja; Kim, Jin You; Moon, Woo Kyung

2013-04-01

To prospectively compare the diagnostic performances of two-dimensional (2D) and three-dimensional (3D) shear-wave elastography (SWE) for differentiating benign from malignant breast masses. B-mode ultrasound and SWE were performed for 134 consecutive women with 144 breast masses before biopsy. Quantitative elasticity values (maximum and mean elasticity in the stiffest portion of mass, Emax and Emean; lesion-to-fat elasticity ratio, Erat) were measured with both 2D and 3D SWE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity of B-mode, 2D, 3D SWE and combined data of B-mode and SWE were compared. Sixty-seven of the 144 breast masses (47 %) were malignant. Overall, higher elasticity values of 3D SWE than 2D SWE were noted for both benign and malignant masses. The AUC for 2D and 3D SWE were not significantly different: Emean, 0.938 vs 0.928; Emax, 0.939 vs 0.930; Erat, 0.907 vs 0.871. Either 2D or 3D SWE significantly improved the specificity of B-mode ultrasound from 29.9 % (23 of 77) up to 71.4 % (55 of 77) and 63.6 % (49 of 77) without a significant change in sensitivity. Two-dimensional and 3D SWE performed equally in distinguishing benign from malignant masses and both techniques improved the specificity of B-mode ultrasound.

Primary B cell lymphoma of the tongue base: a case report

PubMed Central

Bechir, Achour; Asma, Achour; Haifa, Regaieg; Nesrine, Abdessayed; Yosra, Ben Youssef; Badreddine, Sriha; Abderrahim, Khelif

2016-01-01

Primary non-Hodgkin’s lymphoma’s of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution. PMID:28292136

Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs

PubMed Central

Jima, Dereje D.; Zhang, Jenny; Jacobs, Cassandra; Richards, Kristy L.; Dunphy, Cherie H.; Choi, William W. L.; Yan Au, Wing; Srivastava, Gopesh; Czader, Magdalena B.; Rizzieri, David A.; Lagoo, Anand S.; Lugar, Patricia L.; Mann, Karen P.; Flowers, Christopher R.; Bernal-Mizrachi, Leon; Naresh, Kikkeri N.; Evens, Andrew M.; Gordon, Leo I.; Luftig, Micah; Friedman, Daphne R.; Weinberg, J. Brice; Thompson, Michael A.; Gill, Javed I.; Liu, Qingquan; How, Tam; Grubor, Vladimir; Gao, Yuan; Patel, Amee; Wu, Han; Zhu, Jun; Blobe, Gerard C.; Lipsky, Peter E.; Chadburn, Amy

2010-01-01

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions. PMID:20733160

Conventional versus pigtail chest tube-are they similar for treatment of malignant pleural effusions?

PubMed

Mendes, Maria Aurora; China Pereira, Nuno; Ribeiro, Carla; Vanzeller, Manuela; Shiang, Teresa; Gaio, Rita; Campainha, Sérgio

2018-08-01

The optimal chest tube type and size for drainage and chemical pleurodesis of malignant pleural effusions remains controversial. This retrospective study was conducted to compare the efficacy of conventional versus pigtail chest tube in the treatment of malignant pleural effusions. Patients submitted to chest tube drainage and slurry talc pleurodesis due to malignant pleural effusion in our pulmonology ward from 2012 to 2016 were eligible. According to the type of chest tube, they were divided into two groups: group I-conventional chest tube and group II-pigtail chest tube. Number of deaths, recurrence of malignant pleural effusion, and timelines associated with the procedures were reviewed and compared between groups. Out of the 61 included patients, 46 (75.4%) were included in group I and 15 (24.6%) in group II. Only one patient had pigtail chest tube obstruction, with posterior insertion of conventional chest tube. Death during hospital stay and up to 3 months, recurrence at 4 weeks, total duration of hospital stay, time from chest tube insertion to pleurodesis, and time from chest tube insertion to removal were not significantly different between the two groups (all p > 0.05). These findings suggest that pigtail chest tube can be an alternative on palliation, with no compromise in pleurodesis performance.

Malignant changes developing from odontogenic cysts: A systematic review.

PubMed

Borrás-Ferreres, Jordi; Sánchez-Torres, Alba; Gay-Escoda, Cosme

2016-12-01

The aim of this study was to systematically review scientific literature in orderto describe the characteristics and prognosis of malignant entities developing from odontogenic cysts. A search in Pubmed (MEDLINE) and Cochrane databases was conducted. The inclusion criteria were articles published in English related to the malignisation of odontogenic cysts in humans. The exclusion criteria were articles that do not specify the type of odontogenic cyst, malignisation of parakeratinised keratocysts, the presence of an ameloblastic carcinoma and metastasis from distant primary tumours. The selected articles were classified according to Strength of Recommendation Taxonomy criteria. Statistical analysis of the data was carried out using statistical package software SPSS version 22.0. From the 1,237 articles initially obtained, the authors included 3 case series and 45 case reports in the end. Descriptive analysis showed that men have a disposition for malignisation from odontogenic cysts and they frequently appear at the posterior mandible, with pain and swelling being the most frequent signs and symptoms. Follicular cysts were the entities that underwent the most malignant changes with well differentiated squamous cell carcinomas being the most prevalent type of malignancy. The real prognosis of this malignancy is not known because of the heterogeneity of available studies. Key words: Odontogenic cysts, squamous cell carcinoma, neoplastic cell transformation, oral cancer.

Computed Tomography Features of Benign and Malignant Calcified Thyroid Nodules: A Single-Center Study.

PubMed

Kim, Donghyun; Kim, Dong Wook; Heo, Young Jin; Baek, Jin Wook; Lee, Yoo Jin; Park, Young Mi; Baek, Hye Jin; Jung, Soo Jin

No previous studies have investigated thyroid calcification on computed tomography (CT) quantitatively by using Hounsfield unit (HU) values. This study aimed to analyze quantitative HU values of thyroid calcification on preoperative neck CT and to assess the characteristics of benign and malignant calcified thyroid nodules (CTNs). Two hundred twenty patients who underwent neck CT before thyroid surgery from January 2015 to June 2016 were included. On soft-tissue window CT images, CTNs with calcified components of 3 mm or larger in minimum diameter were included in this study. The HU values and types of CTNs were determined and analyzed. Of 61 CTNs in 49 patients, there were 42 malignant nodules and 19 benign nodules. The mean largest diameter of the calcified component was 5.3 (2.5) mm (range, 3.1-17.1 mm). A statistically significant difference was observed in the HU values of calcified portions between benign and malignant CTNs, whereas there was no significant difference in patient age or sex or in the size, location, or type of each CTN. Of the 8 CTNs with pure calcification, 3 exhibited a honeycomb pattern on bone window CT images, and these 3 CTNs were all diagnosed as papillary thyroid carcinoma on histopathological examination. Hounsfield unit values of CTNs may be helpful for differentiating malignancy from benignity.

Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation.

PubMed

Tran, Van; Little, Mark P

2017-11-01

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and non-malignant, show downward curvature in the dose response, and for most endpoints this is statistically significant (p < 0.05). Associated with this, the low-dose extrapolation factor associated with neutron exposure is generally statistically significantly less than 1 for most malignant and non-malignant endpoints, with central estimates mostly in the range 0.1-0.9. In contrast to the situation at higher dose rates, there are statistically non-significant decreases of risk per unit dose at gamma dose rates of less than or equal to 5 mGy/h for most malignant endpoints, and generally non-significant increases in risk per unit dose at gamma dose rates ≤5 mGy/h for most non-malignant endpoints. Associated with this, the dose-rate extrapolation factor, the ratio of high dose-rate to low dose-rate (≤5 mGy/h) gamma dose response slopes, for many tumour sites is in the range 1.2-2.3, albeit not statistically significantly elevated from 1, while for most non-malignant endpoints the gamma dose-rate extrapolation factor is less than 1, with most estimates in the range 0.2-0.8. After neutron exposure there are non-significant indications of lower risk per unit dose at dose rates ≤5 mGy/h compared to higher dose rates for most malignant endpoints, and for all tumours (p = 0.001), and respiratory tumours (p = 0.007) this reduction is conventionally statistically significant; for most non-malignant outcomes risks per unit dose non-significantly increase at lower dose rates. Associated with this, the neutron dose-rate extrapolation factor is less than 1 for most malignant and non-malignant endpoints, in many cases statistically significantly so, with central estimates mostly in the range 0.0-0.2.

Impression cytology diagnosis of ulcerative eyelid malignancy.

PubMed

Sen, S; Lyngdoh, A D; Pushker, N; Meel, R; Bajaj, M S; Chawla, B

2015-02-01

The utility of impression cytology in ocular diseases has predominantly been restricted to the diagnosis of dry eye, limbal stem cell deficiency and conjunctival neoplasias. Its role in malignant eyelid lesions remains largely unexplored. Although scrape cytology is more popular for cutaneous lesions, impression cytology, being non-traumatic, has an advantage in small and delicate areas such as the eyelid. The present study has been designed to evaluate its role in the diagnosis and management of malignant eyelid lesions. Thirty-two histopathologically proven malignant eyelid lesions diagnosed over a 2-year period, including 13 basal cell carcinomas, 11 sebaceous carcinomas, four squamous cell carcinomas, two malignant melanomas and two poorly differentiated carcinomas, formed the study group. The results of impression cytology were compared with those of histopathology in the study group and with an age- and sex-matched group of benign cases as controls. The sensitivity of impression cytology was 84% (27/32) for the diagnosis of malignancy and 28% (9/32) for categorization of the type of malignancy. Impression cytology is a simple, useful, non-invasive technique for the detection of malignant ulcerative eyelid lesions. It is especially useful as a follow-up technique for the detection of recurrences. © 2014 John Wiley & Sons Ltd.

[About the signs of malignant pheochromocytoma].

PubMed

Simonenko, V B; Makanin, M A; Dulin, P A; Vasilchenko, M I; Lesovik, V S

2012-01-01

Morphological criteria for malignant pheochromocytoma remain to be developed According to the WHO recommendations, the sole absolute criteria is the presence of metastases in the organs normally containing no chromaffin tissue. Such signs as cellular and nuclear polymorphism, mytotic activity, vascular invasion, capsular ingrowth are not sufficient to describe a pheochromocytoma as malignant. It is equally dfficult to differentiate between malignant and benign tumours based on histological data since histologically mature neoplasms can produce metastases. Based on the results of original studies, the authors believe that such histological features as vascular and capsular invasion do not necessarily suggest unfavourable prognosis. Therefore, the conclusion of malignancy based on such features can not be regarded as absolute. Probably such neoplasms should be called "pheochromocytomas with morphological signs of malignant growths". They should be referred to the tumours with uncertain malignancy potential based on the known discrepancy between morphological structure and biological activity of neoplasms. Comparative studies of clinical and morphological features of pheochromocytomas showed that their histological type (alveolar; solid, dyscomplexed, trabecular) and morphological signs of malignant growth influence both the clinical picture and arterial hypertension. There are no significant relationship between the above morphological signs, timour mass and clinical manifestations of pheochromocytomas.

Risk of skin cancer in multiple myeloma patients: a retrospective cohort study.

PubMed

Robinson, Austin A; Wang, James; Vardanyan, Suzie; Madden, Erik K; Hebroni, Frank; Udd, Kyle A; Spektor, Tanya M; Nosrati, Jason D; Kitto, Alex Z; Zahab, Michael; Cheema, Simrin; Fors, Darron H; Norberg, Adam; Diehl, Joseph; Waterman, Gabriel N; Swift, Regina A; Crowley, John; Berenson, James R

2016-11-01

Immunosuppressed patients are known to have an increased incidence of skin cancer. Patients with multiple myeloma (MM) show impaired immune function. In the past, because of poor survival, the incidence of specific secondary primary malignancies such as skin cancer among these patients was difficult to establish. With more effective MM therapies that have emerged in recent years, these patients are living markedly longer, and therefore, it becomes of increasing importance to determine whether their risk of developing other medical problems such as skin cancer is increased. We performed a retrospective cohort study of 205 myeloma patients and 193 age-, race-, and gender-matched control subjects to assess the incidence of skin cancers among patients with MM and determine the specific types of and risk factors for skin cancer. We found that there is an increased occurrence of skin cancer among patients with MM compared to control subjects (26.8% vs. 16.1% in controls; P = 0.009). Among specific types of skin cancer, the proportion of patients with squamous cell carcinoma (SCC) was higher than controls (P = 0.016). In addition to MM diagnosis, older age and Caucasian ethnicity were predictors of skin cancer of any type. Furthermore, older age was also a predictor of SCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intracranial solitary fibrous tumors/hemangiopericytomas: first report of malignant progression.

PubMed

Apra, Caroline; Mokhtari, Karima; Cornu, Philippe; Peyre, Matthieu; Kalamarides, Michel

2018-06-01

OBJECTIVE Meningeal solitary fibrous tumors/hemangiopericytomas (MSFTs/HPCs) are rare intracranial tumors resembling meningiomas. Their classification was redefined in 2016 by the World Health Organization (WHO) as benign Grade I fibrohyaline type, intermediate Grade II hypercellular type, and malignant highly mitotic Grade III. This grouping is based on common histological features and identification of a common NAB2-STAT6 fusion. METHODS The authors retrospectively identified 49 cases of MSFT/HPC. Clinical data were obtained from the medical records, and all cases were analyzed according to this new 2016 WHO grading classification in order to identify malignant transformations. RESULTS Recurrent surgery was performed in 18 (37%) of 49 patients. Malignant progression was identified in 5 (28%) of these 18 cases, with 3 Grade I and 2 Grade II tumors progressing to Grade III, 3-13 years after the initial surgery. Of 31 Grade III tumors treated in this case series, 16% (5/31) were proved to be malignant progressions from lower-grade tumors. CONCLUSIONS Low-grade MSFTs/HPCs can transform into higher grades as shown in this first report of such progression. This is a decisive argument in favor of a common identity for MSFT and meningeal HPC. High-grade MSFTs/HPCs tend to recur more often and be associated with reduced overall survival. Malignant progression could be one mechanism explaining some recurrences or metastases, and justifying long-term follow-up, even for patients with Grade I tumors.

Malignant tumors associated with ovarian mature teratoma: A single institution experience.

PubMed

Trabzonlu, Levent; Durmaz, Guray; Vural, Cigdem; Muezzinoglu, Bahar; Corakci, Aydin

2017-05-01

The aims of this study are to present demographical features of cases diagnosed with malignant tumor associated with ovarian mature teratoma and to analyze histopathological features and clinical follow up of these tumors. Single-institution retrospective charts were reviewed to identify all cases of ovarian mature teratoma diagnosed from 1998 to 2015. Clinicopathological parameters that were analyzed include age, tumor size, tumor stage, histological type, laterality, IOC diagnosis and whether or not patient has received adjuvant chemotherapy. A total of 218 ovarian mature teratoma cases were identified during the study period. Of the 218 ovarian mature teratoma specimens, eight (3.7%) exhibited malignant tumors. The average age for cases of malignancy associated with ovarian mature teratoma was 44.6 years. The average size of tumors was 10.36cm. On final pathology, histological types of tumors were as follows: two cases each of squamous cell carcinoma and papillary thyroid carcinoma; one case each of mucinous adenocarcinoma, metastatic adenocarcinoma, sebaceous carcinoma and oligodendroglioma. Only one patient with Stage IIB tumor died of disease. One patient was alive with metastatic disease two months after initial diagnosis. Mean and median follow-up times were 64.1 and 49 months, respectively. An ovarian mass that has characteristics of a teratoma in a postmenopausal patient should alert for malignancy -regardless of tumor size. IOC is a valuable tool for the detection of malignancy and should be requested to determine the modality of surgical approach. Copyright © 2017 Elsevier GmbH. All rights reserved.

Multivariate evaluation of Thyroid Imaging Reporting and Data System (TI-RADS) in diagnosis malignant thyroid nodule: application to PCA and PLS-DA analysis.

PubMed

Zhang, Tan; Li, Fangxuan; Mu, Jiali; Liu, Juntian; Zhang, Sheng

2017-06-01

To explore the significance of ultrasonic features in differential diagnosis of thyroid nodules via combining the thyroid imaging reporting and data system (TI-RADS) and multivariate statistical analysis. Patients who received surgical treatment and was diagnosed with single thyroid nodule by postoperative pathology and preoperative ultrasound were enrolled in this study. Multivariate analysis was applied to assess the significant ultrasonic features which correlated with identifying benign or malignance and grading the TI-RADS classification of thyroid nodule. There were significant differences in the nodule size, aspect ratio, internal, echogenicity, boundary, presence or absence of calcifications, calcification type and CDFI between benign and malignant thyroid nodules. Multivariate analysis showed clear-cut distinction both between benign and malignance and among different TI-RADS categories of malignancy nodules. The shape and calcification of the nodule were important factors for distinguish the benign and malignance. Height of the nodule, aspect and calcification was important factors for grading TI-RADS categories of malignancy thyroid nodules. Ill-defined boundary, irregular shape and presence of calcification related with highly malignant risk for thyroid nodule. The larger height and aspect and presence of calcification related with higher TI-RADS classification of malignancy thyroid nodule.

[Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

PubMed

Shen, Si; Shen, Junwei; Zhu, Liang; Wu, Chaoqun; Li, Dongliang; Yu, Hongyu; Qiu, Yuanyuan; Zhou, Yi

2015-11-01

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

[Search for non-relative donor by the Russian register of bone marrow donors].

PubMed

Zaretskaia, Iu M; Khamaganova, E G; Aleshchenko, S M; Murashova, L A

2002-01-01

To select maximally HLA compatible donor for hematological patients who need transplantation of bone marrow from non-relative donor. 75 patients with hematological malignancy were observed. All of them have indications to non-relative transplantation of the bone marrow. Methods of polymerase chain reaction with sequence-specific primers and classic microlymphocytotoxic test were used. Typing of HLA antigens of class I and alleles of class II loci enabled search for non-relative donor for transplantation of bone marrow in accordance with the requirements of the European Federation of Immunogenetics. Most of the patients (86.6%) had at least one potential HLA-A, -B, -DR compatible donor. Half of the patients had potential donors typed at the allele level by class II loci. This diminishes time of HLA compatible donor selection. DNA typing enables the search for the non-relative donors meeting modern requirements. This allowed 5 non-relative bone marrow transplantations.

A rapid and convenient method for detecting a broad spectrum of malignant cells from malignant pleuroperitoneal effusion of patients using a multifunctional NIR heptamethine dye.

PubMed

Tian, Ying; Sun, Jing; Yan, Huaijiang; Teng, Zhaogang; Zeng, Leyong; Liu, Ying; Li, Yanjun; Wang, Jiandong; Wang, Shouju; Lu, Guangming

2015-02-07

Detection of malignant cells from malignant effusion is crucial to establish or adjust therapies of patients with cancer. The conventional qualitative detection in malignant pleuroperitoneal effusion is cytological analysis, which is time-consuming and complicated. Therefore, a faster and more convenient detection strategy is urgently needed. In this study, we report a rapid method to detect malignant cells from malignant pleuroperitoneal effusion (hydrothorax and ascites) of patients using IR-808, a tumor-targeted near-infrared (NIR) fluorescent heptamethine dye (tNRI dye), which exhibited superior labeling efficacy without specific conjugation to biomarkers. The targeted imaging performance toward malignant cells using IR-808 was confirmed by comparing with normal cells, and the fluorescence stability assay of IR-808 in malignant effusion was performed from 1 h to 48 h. In order to save time and dose, the incubation time and concentration were optimized to 10 min and 5 μM, which were used to detect malignant cells from 28 clinical samples of malignant pleuroperitoneal effusion. The results revealed that IR-808 could be internalized selectively by malignant cells of samples, and these malignant cells could be easily distinguished from normal cells under a fluorescence microscope. The positive rates between cytological analysis and the IR-808 staining method were 86% (24/28) and 79% (22/28), respectively. An excellent concordance level (Kappa = 0.752, P < 0.001) was observed between the two methods. Our results indicated that IR-808, a new NIR fluorescent heptamethine dye with unique optical imaging and tumor targeting properties, could provide a fast and simple way to detect a broad spectrum of malignant cells from malignant pleuroperitoneal effusion in patients.

Non-malignant pathological results on transthoracic CT guided core-needle biopsy: when is benign really benign?

PubMed

Rui, Y; Han, M; Zhou, W; He, Q; Li, H; Li, P; Zhang, F; Shi, Y; Su, X

2018-06-06

To determine true negatives and characterise the variables associated with false-negative results when interpreting non-malignant results of computed tomography (CT)-guided lung biopsy. Nine hundred and fifty patients with initial non-malignant findings on their first transthoracic CT-guided core-needle biopsy (TTNB) were included in the study. Initial biopsy results were compared to definitive diagnoses established later. The negative predictive value (NPV) of non-malignant diseases upon initial TTNB was 83.6%. When the biopsy results indicated specific infection or benign tumour (n=225, 26.1%), they all were confirmed true negative for malignancy later. Only one inconclusive "granuloma" diagnosis was false negative. All 141 patients (141/861, 16.4%) who were false negative for malignancy were from the "infection not otherwise specified (NOS)", "inflammatory diseases", or "inconclusive" groups. Age (p=0.002), cancer history (p<0.001), target size (p=0.003), and pneumothorax during lung biopsy (p=0.003) were found to be significant predictors of false-negative results; 47.6% (410/861) of patients underwent additional invasive examinations to reach a final diagnosis. Ultimately, 52.7% (216/410) were successfully diagnosed. Specific infection, benign tumour, and granulomatous inflammation of first TTNBs were mostly true negative. Older age, history of cancer, larger target size, and pneumothorax were highly predictive of false-negative results for malignancies. In such cases, additional invasive examinations were frequently necessary to obtain final diagnoses. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The role of pleural fluid MAGE RT-nested PCR in the diagnosis of malignant pleural effusion.

PubMed

Jeon, Eun Ju; Park, Hye Kyeong; Jeon, Kyeongman; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung; Ki, Chang-Seok; Kim, Jong-Won; Shim, Young Mog; Um, Sang-Won

2012-11-01

  Melanoma antigen (MAGE) genes are expressed in tumor cells, the testis and the placenta. The purpose of this prospective study was to investigate the sensitivity, specificity, and accuracy of the carcinoembryonic antigen (CEA), MAGE reverse transcriptase-nested polymerase chain reaction (RT-nested PCR), and cytology of pleural fluid in the diagnosis of malignant pleural effusion.   Patients in whom unilateral pleural effusion was identified on chest radiography from January to December 2009 were included in the study. MAGE genes were analyzed by RT-nested PCR using MAGE A1-6 common primers.   Of 81 enrolled patients, 46 were diagnosed as malignant pleural effusion, and 24 were diagnosed as benign pleural effusion. The diagnoses of 11 patients were not confirmed in this study. The diagnostic sensitivity, specificity, and accuracy of MAGE RT-nested PCR were 61.4%, 95.7%, and 73.1%, respectively. The diagnostic sensitivities of cytology and CEA (>5 ng/mL) were 61.4% and 75.0%, respectively. Among 17 patients with negative cytology who had malignant pleural effusion, 12 and 10 patients were positive for CEA (>5.0 ng/mL) and MAGE RT-nested PCR, respectively. However, of five patients with malignant pleural effusion that was not recognized by cytology and CEA, MAGE RT-nested PCR correctly predicted a malignant etiology in only one additional patient (20%).   MAGE RT-nested PCR seems to add little on the combination of conventional methods in the diagnosis of malignant effusion. © 2012 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty. Ltd.

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

PubMed

Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

2012-06-01

To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

Unexpected metastatic pheochromocytoma - an unusual presentation.

PubMed

Birrenbach, Tanja; Stanga, Zeno; Cottagnoud, Philippe; Stucki, Armin

2008-01-01

The classic triad of pheochromocytoma consists of episodic headache, sweating, and tachycardia. General clinicians should be aware, however, that this rare entity might present with a wide spectrum of clinical symptoms. We recently observed a noteworthy case of malignant pheochromocytoma where there was a lack of specific symptoms despite an advanced tumor stage. Malignancy is an important cause of mortality. Reliable diagnosis of malignancy depends upon evidence of local invasion, distant metastases, or recurrence. As in our case, new scintigraphic methods, such as 111-In-pentetreotide scintigraphy (Octreoscan), may occasionally reveal 123-I-metaiodobenzylguanidine-negative distant metastases and help to establish an early diagnosis of malignancy. Tumor size, and perhaps even biochemical profile, may be factors increasing the likelihood of a malignant process and may contribute to early identification of patients at risk.

Apolipoprotein concentrations are elevated in malignant ovarian cyst fluids suggesting that lipoprotein metabolism is dysregulated in epithelial ovarian cancer.

PubMed

Podzielinski, Iwona; Saunders, Brook A; Kimbler, Kimberly D; Branscum, Adam J; Fung, Eric T; DePriest, Paul D; van Nagell, John R; Ueland, Frederick R; Baron, Andre T

2013-05-01

SELDI-TOF MS analysis of ovarian cyst fluids revealed that peaks m/z 8696 and 8825 discriminate malignant, borderline, and benign tumors. These peaks correspond to isoforms of apoA2. ELISA demonstrates that apoA1, A2, B, C2, C3, and E cyst fluid concentrations are uncorrelated and higher in malignant ovarian tumors, but only apoA2, apoE, and age are independent classifiers of malignant ovarian tumors, yielding 55.1% sensitivity, 95% specificity, and 88.1% accuracy to discern malignant from benign and borderline tumors. These data suggest that lipoprotein metabolism is dysregulated in ovarian cancer and that apoA2 and apoE warrant further investigation as ovarian tumor biomarkers.

Possible relevance of tumor-related genes mutation to malignant transformation of endometriosis.

PubMed

Ma, X; Hui, Y; Lin, L; Wu, Y; Zhang, X; Qin, X

2016-01-01

Despite studies have suggested that endometriosis has malignant potential, the molecular mechanism underlying the malignant transformation of endometriosis is poorly understood so far. Endometriosis-associated ovarian cancer (EAOC) or ovarian cancer arising from endometriosis (OCEM) may provide an ideal model for genetic studies. To investigate the genetic alterations during transformation of ovarian endometriosis into cancer, the authors analysed mutations of tumour-related genes (PTEN and p53) in EAOC cases (n=23, group 1), including 19 cases which were detected co-existence of endometriosis and cancer and four cases which fulfilled the histological criteria in malignant transformation of endometriosis (OCEMs), and in atypical hyperplasia ovarian endometriosis (aEMs) (n = 10, group 2), as well as in solitary ovarian endometriosis (EMs) (n = 20, group 3), simultaneously, to study the correlation of the two genes in the development and progression of the ovarian endometriosis malignancy. Each paraffin block was sliced into serial ten-µm-thick sections. Extracted DNA was amplified by nested PCR. Mutations of PTEN and p53 were examined by bidirectional DNA sequencing. It was acknowledged by experiments that the PTEN and p53 mutation frequency in EAOCs were significantly higher than that in aEMs and EMs. There was significant difference to compare EAOCs with EMs (p < 0.01, p < 0.05), and converse to compare with aEMs (p > 0.05), respectively. No definite involvement between the frequency of PTEN and p53 mutations in EAOCs and age difference, histological type, clinical stage, pathological grade, and whether accompanied by metastasis (p > 0.05); however, a decreasing trend of PTEN mutation with the increased age, decreased clinical stage and pathological grade, and when accompanied by metastasis was detected. Adversely, an increasing trend of p53 mutation was represented. In EAOCs group, the authors detected eight PTEN and four p53 mutation events, respectively. Moreover, one case occurred PTEN and p53 mutation simultaneously. With 23 EAOCs, two cases which fulfilled the histological criteria in malignant transformation of endometriosis, which may be a specific entity distinct from non-endometriosis-associated ovarian cancer, the authors named them the OCEMs, occurred PTEN or p53 mutation, respectively. The present study suggested that the mutation and functional incapacitation of certain tumor-related genes may be involved in malignant transformation of endometriosis. PTEN mutation is the pristine event, but p53 mutation is the late.

Combination of radiological and gray level co-occurrence matrix textural features used to distinguish solitary pulmonary nodules by computed tomography.

PubMed

Wu, Haifeng; Sun, Tao; Wang, Jingjing; Li, Xia; Wang, Wei; Huo, Da; Lv, Pingxin; He, Wen; Wang, Keyang; Guo, Xiuhua

2013-08-01

The objective of this study was to investigate the method of the combination of radiological and textural features for the differentiation of malignant from benign solitary pulmonary nodules by computed tomography. Features including 13 gray level co-occurrence matrix textural features and 12 radiological features were extracted from 2,117 CT slices, which came from 202 (116 malignant and 86 benign) patients. Lasso-type regularization to a nonlinear regression model was applied to select predictive features and a BP artificial neural network was used to build the diagnostic model. Eight radiological and two textural features were obtained after the Lasso-type regularization procedure. Twelve radiological features alone could reach an area under the ROC curve (AUC) of 0.84 in differentiating between malignant and benign lesions. The 10 selected characters improved the AUC to 0.91. The evaluation results showed that the method of selecting radiological and textural features appears to yield more effective in the distinction of malignant from benign solitary pulmonary nodules by computed tomography.

Diagnostic implications of a small-voxel reconstruction for loco-regional lymph node characterization in breast cancer patients using FDG-PET/CT.

PubMed

Koopman, Daniëlle; van Dalen, Jorn A; Arkies, Hester; Oostdijk, Ad H J; Francken, Anne Brecht; Bart, Jos; Slump, Cornelis H; Knollema, Siert; Jager, Pieter L

2018-01-16

We evaluated the diagnostic implications of a small-voxel reconstruction for lymph node characterization in breast cancer patients, using state-of-the-art FDG-PET/CT. We included 69 FDG-PET/CT scans from breast cancer patients. PET data were reconstructed using standard 4 × 4 × 4 mm 3 and small 2 × 2 × 2 mm 3 voxels. Two hundred thirty loco-regional lymph nodes were included, of which 209 nodes were visualised on PET/CT. All nodes were visually scored as benign or malignant, and SUV max and TB ratio (=SUV max /SUV background ) were measured. Final diagnosis was based on histological or imaging information. We determined the accuracy, sensitivity and specificity for both reconstruction methods and calculated optimal cut-off values to distinguish benign from malignant nodes. Sixty-one benign and 169 malignant lymph nodes were included. Visual evaluation accuracy was 73% (sensitivity 67%, specificity 89%) on standard-voxel images and 77% (sensitivity 78%, specificity 74%) on small-voxel images (p = 0.13). Across malignant nodes visualised on PET/CT, the small-voxel score was more often correct compared with the standard-voxel score (89 vs. 76%, p <  0.001). In benign nodes, the standard-voxel score was more often correct (89 vs. 74%, p = 0.04). Quantitative data were based on the 61 benign and 148 malignant lymph nodes visualised on PET/CT. SUVs and TB ratio were on average 3.0 and 1.6 times higher in malignant nodes compared to those in benign nodes (p <  0.001), on standard- and small-voxel PET images respectively. Small-voxel PET showed average increases in SUV max and TB ratio of typically 40% over standard-voxel PET. The optimal SUV max cut-off using standard-voxels was 1.8 (sensitivity 81%, specificity 95%, accuracy 85%) while for small-voxels, the optimal SUV max cut-off was 2.6 (sensitivity 78%, specificity 98%, accuracy 84%). Differences in accuracy were non-significant. Small-voxel PET/CT improves the sensitivity of visual lymph node characterization and provides a higher detection rate of malignant lymph nodes. However, small-voxel PET/CT also introduced more false-positive results in benign nodes. Across all nodes, differences in accuracy were non-significant. Quantitatively, small-voxel images require higher cut-off values. Readers have to adapt their reference standards.

Profiling of zinc altered gene expression in human prostate normal versus cancer cells: a time course study

PubMed Central

Lin, Shu-fei; Wei, Hua; Maeder, Dennis; Franklin, Renty B.; Feng, Pei

2010-01-01

We have demonstrated that zinc exposure induces apoptosis in human prostate cancer cells (PC-3) and benign hyperplasia cells (BPH), but not in normal prostate cells (HPR-1). However, the mechanisms underlying the effects of zinc on prostate cancer cell growth and zinc homeostasis remain unclear. To explore the zinc effect on gene expression profiles in normal (HPR-1) and malignant prostate cells (PC-3), we conducted a time course study of Zn treatment with microarray analysis. Microarray data were evaluated and profiled using computational approach for the primary and secondary data analyses. Final analyses were focused on the genes: 1. highly sensitive to zinc, 2. associated with zinc homeostasis, i.e. metallothioneins (MTs), solute zinc carriers (ZIPs) and zinc exporters (ZnTs), 3. relevant to several oncogenic pathways. Zinc-mediated mRNA levels of MT isotypes were further validated by semi-quantitative RT-PCR. Results showed that zinc effect on genome-wide expression patterns was cell type specific, and zinc appeared to have mainly down-regulatory effects on thousands of genes (1,953 in HPR-1; 3,534 in PC-3) with a threshold of ±2.5-fold, while fewer genes were up-regulated (872 in HPR-1; 571 in PC-3). The patterns of zinc effect on functional MT genes’ expression provided evidence for the cell-type dependent zinc accumulation and zinc-induced apoptosis in prostate cells. In PC-3 cells, zinc significantly up-regulated the expression of MT-1 isotypes -J and -M, denoted previously as “non-functional” MT genes, and now a depictive molecular structure of MT-1J was proposed. Examination of genes involved in oncogenic pathways indicated that certain genes, e.g. Fos, Akt1, Jak3 and PI3K were highly regulated by zinc with cell type specificity. This work provided an extensive database on zinc related prostate cancer research. The strategy of data analysis was devoted to find genes highly sensitive to Zn, and the genes associated with zinc accumulation and zinc-induced apoptosis. The results indicate that zinc regulation of gene expression is cell-type specific, and MT genes play important roles in prostate malignancy. PMID:19071009

Correlation between fertility drugs use and malignant melanoma incidence: the state of the art.

PubMed

Tomao, Federica; Papa, Anselmo; Lo Russo, Giuseppe; Zuber, Sara; Spinelli, Gian Paolo; Rossi, Luigi; Caruso, Davide; Prinzi, Natalie; Stati, Valeria; Benedetti Panici, Pierluigi; Tomao, Silverio

2014-09-01

The relationship between fertility, reproductive hormones, and risk of malignant melanoma has acquired much interest in recent years. Melanocytes are hormonally responsive cells, and some in vitro studies demonstrated that estrogen hormones stimulate the growth of melanocytes. Moreover, estrogen receptors have been identified in melanoma cells, as well as in melanocytic nevi and in normal skin. Some evidences suggest a possible link between fertility treatments and the increased risk of malignant melanoma. This article addresses this association through a scrupulous search of the literature published thus far. The aim of this review is to determine the incidence of malignant melanoma in women treated with fertility drugs and to examine if the exposure to fertility treatments really increases the risk of malignant melanoma. In particular, our analysis focused on the different types of drugs and different treatment schedules used. Finally, this study provides additional insights regarding the long-term relationships between fertility drugs and the risk of malignant melanoma.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of primary cardiac malignant fibrous histiocytoma.

PubMed

Gok, Gulay; Elsayed, Mahmoud; Thind, Munveer; Uygur, Begum; Abtahi, Firoozeh; Chahwala, Jugal R; Yıldırımtürk, Özlem; Kayacıoğlu, İlyas; Pehlivanoğlu, Seçkin; Nanda, Navin C

2015-07-01

We describe a case of primary cardiac malignant fibrous histiocytoma where live/real time three-dimensional transesophageal echocardiography added incremental value to the two-dimensional modalities. Specifically, the three-dimensional technique allowed us to delineate the true extent and infiltration of the tumor, to identify characteristics of the tumor mass suggestive of its malignant nature, and to quantitatively assess the total tumor burden. © 2015, Wiley Periodicals, Inc.

Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pecoraro, G.; Morgan, D.; Defendi, V.

1989-01-01

The human papillomaviruses (HPVs) are associated with specific benign and malignant lesions of the skin and mucosal epithelia. Cloned viral DNAs from HPV types 6b, 16, and 18 associated with different pathological manifestations of genital neoplasia in vivo were introduced into primary human cervical epithelial cells by electroporation. Cells transfected with HPV16 or HPV18 DNA acquired indefinite lifespans, distinct morphological alterations, and anchorage-independent growth (HPV18), and contain integrated transcriptionally active viral genomes. HPV6b or plasmid electroporated cells senesced at low passage. The alterations in growth and differentiation of the cells appear to reflect the progressive oncogenic processes that result inmore » cervical carcinoma in vivo.« less

Updated epidemiological study of workers at two California petroleum refineries, 1950–95

PubMed Central

Satin, K; Bailey, W; Newton, K; Ross, A; Wong, O

2002-01-01

Objectives: To further assess the potential role of occupational exposures on mortality, a second update of a cohort study of workers at two petroleum refineries in California was undertaken. Methods: Mortality analyses were based on standardised mortality ratios (SMRs) and 95% confidence intervals (95% CIs) using the general population of California as a reference. Additional analyses of lymphatic and haematopoietic cancer deaths and diseases related to asbestos were undertaken. Results: The update consisted of 18 512 employees, who contributed 456 425 person-years of observation between 1950 and 1995. Both overall mortality and total cancer mortality were significantly lower than expected, as were several site specific cancers and non-malignant diseases. In particular, no significant increases were reported for leukaemia cell types or non-Hodgkin's lymphoma. Mortality excess from multiple myeloma was marginally significant. The excess was confined to employees enrolled before 1949. Furthermore, there was no significant upward trend based on duration of employment, which argues against a causal interpretation relative to employment or exposures at the refineries. No increase was found for diseases related to asbestos: pulmonary fibrosis; lung cancer; or malignant mesothelioma. There was no significant increase in mortality from any other cancers or non-malignant diseases. Conclusion: This second update provides additional reassurance that employment at these two refineries is not associated with increased risk of mortality. PMID:11934952

Physical Labeling of Papillomavirus-Infected, Immortal, and Cancerous Cervical Epithelial Cells Reveal Surface Changes at Immortal Stage

PubMed Central

Iyer, K. Swaminathan; Gaikwad, R. M.; Woodworth, C. D.; Volkov, D. O.

2013-01-01

A significant change of surface features of malignant cervical epithelial cells compared to normal cells has been previously reported. Here, we are studying the question at which progressive stage leading to cervical cancer the surface alteration happens. A non-traditional method to identify malignant cervical epithelial cells in vitro, which is based on physical (in contrast to specific biochemical) labelling of cells with fluorescent silica micron-size beads, is used here to examine cells at progressive stages leading to cervical cancer which include normal epithelial cells, cells infected with human papillomavirus type-16 (HPV-16), cells immortalized by HPV-16, and carcinoma cells. The study shows a statistically significant (at p <0.01) difference between both immortal and cancer cells and a group consisting of normal and infected. There is no significant difference between normal and infected cells. Immortal cells demonstrate the signal which is closer to cancer cells than to either normal or infected cells. This implies that the cell surface, surface cellular brush changes substantially when cells become immortal. Physical labeling of the cell surface represents a substantial departure from the traditional biochemical labeling methods. The results presented show the potential significance of physical properties of the cell surface for development of clinical methods for early detection of cervical cancer, even at the stage of immortalized, pre-malignant cells. PMID:22351422

Advancing the Capabilities of an Authentic Ex Vivo Model of Primary Human Prostate Cancer

DTIC Science & Technology

2014-10-01

maintained the PTEN expression of the native tissues after 5 days in culture. Prostate-specific membrane antigen ( PSMA ) was detected in benign and malignant...room temperature 1 h room temperature 30 min room temperature Abcam, Cambridge, MA, USA p63 SMA CD68 PSMA Mouse monoclonal Mouse monoclonal Mouse...Prostate-specific membrane antigen ( PSMA ) was detected in benign and malignant glands as expected in both native tissue and in TSCs after 5 days.47

An unusual presentation of primary malignant B-cell-type dural lymphoma

PubMed Central

Low, Yin Yee Sharon; Lai, Siang Hui; Ng, Wai Hoe

2014-01-01

Primary malignant B-cell-type dural lymphoma is a rare subtype of primary central nervous system lymphoma (PCNSL). We herein report an unusual case of diffuse B-cell lymphoma that presents as a chronic subdural haematoma without extracranial involvement. The notable aspects of this case include the patient’s immunocompetence, a short clinical history of symptom onset, rapid neurological deterioration and a final diagnosis of high-grade PCNSL. This case highlights the challenges neurosurgeons face, especially in the emergency setting, when the disease manifests in varied presentations. PMID:25631982

Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver.

PubMed

Tokgoz, Ozlem; Unlu, Ebru; Unal, Ilker; Serifoglu, Ismail; Oz, Ilker; Aktas, Elif; Caglar, Emrah

2016-03-01

To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the "cut-off" ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782±0.53×10(-3) mm(2)/s) and hemangiomas (2.705±0.63×10(-3) mm(2)/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the "cut-off" ADC value of 1.800×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the "cut-off" value of 1.858×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the "cut-off" value of 1.800×10(-3) mm(2)/s had a sensitivity of 96.1% and a specificity of 90.0%. DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure.

Pathogenic role for macrophage migration inhibitory factor in glioblastoma and its targeting with specific inhibitors as novel tailored therapeutic approach

PubMed Central

Mangano, Katia; Mazzon, Emanuela; Basile, Maria Sofia; Di Marco, Roberto; Bramanti, Placido; Mammana, Santa; Petralia, Maria Cristina; Fagone, Paolo; Nicoletti, Ferdinando

2018-01-01

Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine expressed by a variety of cell types. Although MIF has been primarily studied for its role in the pathogenesis of autoimmune diseases, it has also been shown to promote tumorigenesis and it is over expressed in various malignant tumors. MIF is able to induce angiogenesis, cell cycle progression, and to block apoptosis. As tailored therapeutic approaches for the inhibition of endogenous MIF are being developed, it is important to evaluate the role of MIF in individual neoplastic conditions that may benefit from specific MIF inhibitors. Along with this line, in this paper, we have reviewed the evidence of the involvement of MIF in the etiopathogenesis and progression of glioblastoma and the preclinical data suggesting the possible use of specific MIF inhibition as a potential novel therapeutic strategy for brain tumors. PMID:29707160

Reliability of IOTA score and ADNEX model in the screening of ovarian malignancy in postmenopausal women.

PubMed

Nohuz, Erdogan; De Simone, Luisa; Chêne, Gautier

2018-04-28

The IOTA (International Ovarian Tumor Analysis) group has developed the ADNEX (Assessment of Different NEoplasias in the adneXa) model to predict the risk that an ovarian mass is benign, borderline or malignant. This study aimed to test reliability of these risks prediction models to improve the performance of pelvic ultrasound and discriminate between benign and malignant cysts. Postmenopausal women with an adnexal mass (including ovarian, para-ovarian and tubal) and who underwent a standardized ultrasound examination before surgery were included. Prospectively and retrospectively collected data and ultrasound appearances of the tumors were described using the terms and definitions of the IOTA group and tested in accordance with the ADNEX model and were compared to the final histological diagnosis. Of the 107 menopausal patients recruited between 2011 and 2016, 14 were excluded (incomplete inclusion criteria). Thus, 93 patients constituted a cohort in whom 89 had benign cysts (83 ovarian and 6 tubal or para-ovarian cysts), 1 had border line tumor and 3 had invasive ovarian cancers (1 at first stage, 1 at advanced stage and 1 metastatic tumor in the ovary). The overall prevalence of malignancy was 4.3%. Every benign ovarian cyst was classified as probably benign by IOTA score which showed also a high specificity with the totality of probably malignant lesion proved malignant by histological exam. The limit of this score was the important rate of not classified or undetermined cysts. However, the malignancy risks calculated by ADNEX model allowed identifying the totality of malignancy. Thus, the combination of the two methods of analysis showed a sensitivity and specificity rates of respectively 100% and 98%. Evaluation of malignancy risks by these 2 tests highlighted a negative predictive value of 100% (there was no case of false negative) and a positive predictive value of 80%. On the basis of our findings, the IOTA classification and the ADNEX multimodal algorithm used as risks prediction models can improve the performance of pelvic ultrasound and discriminate between benign and malignant cysts in postmenopausal women, especially for undetermined lesions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance

PubMed Central

Nazarian, Javad; Ghanem, Anthony; Vukmanovic, Stanislav; Sandler, Anthony D.

2018-01-01

Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic profiles of the two phenotypic cell populations were compared to each other to determine the differential protein expression and molecular pathways of interest. We report exclusive or significant up-regulation of tumorigenic pathways expressed by the AI tumorspheres compared to the AD cancer cells. These pathways govern metastatic potential, enhanced malignancy and epithelial to mesenchymal transition. Furthermore, radio-therapy induced significant up-regulation of specific tumorigenic and proliferative proteins, namely survivin, CDC2 and the enzyme Poly [ADP-ribose] polymerase 1. Bio-functional characteristics of the AI tumorspheres were resistant to sutent inhibition of receptor tyrosine kinases (RTKs) as well as to 2.5 Gy radio-therapy as assessed by cell survival, proliferation, apoptosis and migration. Interestingly, PDGF-BB stimulation of the PDGFRβ led to transactivation of EGFR and VEGFR in AI tumorspheres more potently than in AD cells. Sutent inhibition of PDGFRβ abrogated this transactivation in both cell types. In addition, 48 h sutent treatment significantly down-regulated the protein expression of PDGFRβ, MYCN, SOX2 and Survivin in the AI tumorspheres and inhibited tumorsphere self-renewal. Radio-sensitivity in AI tumorspheres was enhanced when sutent treatment was combined with survivin knock-down. We conclude that AI tumorspheres have a differential protein expression compared to AD cancer cells that contribute to their malignant phenotype and radio-resistance. Specific targeting of both cellular phenotypes is needed to improve outcomes in neuroblastoma patients. PMID:29298329

Long-Term Outcomes Among Adult Survivors of Childhood Central Nervous System Malignancies in the Childhood Cancer Survivor Study

PubMed Central

Liu, Qi; Yasui, Yutaka; Huang, Sujuan; Ness, Kirsten K.; Leisenring, Wendy; Hudson, Melissa M.; Donaldson, Sarah S.; King, Allison A.; Stovall, Marilyn; Krull, Kevin R.; Robison, Leslie L.; Packer, Roger J.

2009-01-01

Background Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups. Methods We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided. Results Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage. Conclusions Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines. PMID:19535780

Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance.

PubMed

Abou-Antoun, Tamara J; Nazarian, Javad; Ghanem, Anthony; Vukmanovic, Stanislav; Sandler, Anthony D

2018-01-01

Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic profiles of the two phenotypic cell populations were compared to each other to determine the differential protein expression and molecular pathways of interest. We report exclusive or significant up-regulation of tumorigenic pathways expressed by the AI tumorspheres compared to the AD cancer cells. These pathways govern metastatic potential, enhanced malignancy and epithelial to mesenchymal transition. Furthermore, radio-therapy induced significant up-regulation of specific tumorigenic and proliferative proteins, namely survivin, CDC2 and the enzyme Poly [ADP-ribose] polymerase 1. Bio-functional characteristics of the AI tumorspheres were resistant to sutent inhibition of receptor tyrosine kinases (RTKs) as well as to 2.5 Gy radio-therapy as assessed by cell survival, proliferation, apoptosis and migration. Interestingly, PDGF-BB stimulation of the PDGFRβ led to transactivation of EGFR and VEGFR in AI tumorspheres more potently than in AD cells. Sutent inhibition of PDGFRβ abrogated this transactivation in both cell types. In addition, 48 h sutent treatment significantly down-regulated the protein expression of PDGFRβ, MYCN, SOX2 and Survivin in the AI tumorspheres and inhibited tumorsphere self-renewal. Radio-sensitivity in AI tumorspheres was enhanced when sutent treatment was combined with survivin knock-down. We conclude that AI tumorspheres have a differential protein expression compared to AD cancer cells that contribute to their malignant phenotype and radio-resistance. Specific targeting of both cellular phenotypes is needed to improve outcomes in neuroblastoma patients.

Adenocarcinoma arising from intracranial recurrent mature teratoma and featuring mutated KRAS and wild-type BRAF genes.

PubMed

Kim, Eun Soo; Kwon, Mi Jung; Song, Joon Ho; Kim, Dong Hoon; Park, Hye-Rim

2015-02-01

Malignant transformation or recurrence of intracranial mature teratoma is an extremely rare occurrence, compared to the usual ovarian counterpart. Previously, yolk sac tumor elements have been considered to be selective progenitors of enteric-type adenocarcinoma arising from intracranial germ cell tumors. However, the present case demonstrates the occurrence of enteric-type adenocarcinoma in recurrent intracranial mature cystic teratoma 12 years after gross total removal, a case of which has not previously been documented in the literature. The 11.5-cm long, dura mater-based tumor on the right fronto-temporal lobe displaced the brain; however, the patient had no neurologic symptoms or discomfort other than pus-like discharge on the scalp. Microscopic examinations revealed a small focus of adenocarcinoma and dysplastic colonic mucosa in the mature cystic teratoma. No immature elements were seen. The cystic wall was almost denuded and showed an exuberant xanthogranulomatous reaction with foreign-body type giant cells engulfing keratin materials and cholesterol clefts, suggesting that chronic inflammation due to repeated cyst wall rupture and the previous resection may contribute to malignant transformation. The adenocarcinoma showed strong immunohistochemical expression of CK20 and p53, but CK7 in patches. The molecular profile of the adenocarcinoma showed a mutation in KRAS and wild-type BRAF, which might be associated with malignant transformation of intracranial mature teratomas. In conclusion, the intracranial mature teratomas should require long-term follow-up, and clinicians, radiologists and pathologists should be aware of the potential for malignant progression of recurrent intracranial mature cystic teratoma despite gross total resection and no neurologic symptoms. © 2014 Japanese Society of Neuropathology.

A Druggable TCF4 and BRD4 dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm

PubMed Central

Ceribelli, Michele; Hou, Zhiying Esther; Kelly, Priscilla N.; Huang, Da Wei; Wright, George; Ganapathi, Karthik; Evbuomwan, Moses O.; Pittaluga, Stefania; Shaffer, Arthur L.; Marcucci, Guido; Forman, Stephen J.; Xiao, Wenming; Guha, Rajarshi; Zhang, Xiaohu; Ferrer, Marc; Chaperot, Laurence; Plumas, Joel; Jaffe, Elaine S.; Thomas, Craig J.; Reizis, Boris; Staudt, Louis M.

2016-01-01

SUMMARY Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNA interference screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETi’s) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers. BETi’s retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy. PMID:27846392

Preoperative discrimination between malignant and benign adnexal masses with transvaginal ultrasonography and colour blood flow imaging.

PubMed

Sawicki, W; Spiewankiewicz, B; Cendrowski, K; Stelmachów, J

2001-01-01

Ovarian cancer is one of the causes of death in women, and in about 70% of cases is recognized only in advanced stages. This study was undertaken to evaluate distinctive values of transvaginal and color Doppler ultrasonography in differentiating malignant and benign adnexal masses through analysis of ultrasonic morphological features of malignancy and estimation of location and intensification of angiogenesis as well as values of resistance of flow in examined masses. 329 women with malignant and benign adnexal masses underwent ultrasonographic and colour Doppler examination 1-5 days before surgery (laparotomy, laparoscopy) thus allowing histological verification of diagnosis. The ultrasonographic structure was assessed using a morphological scoring system devised by Sassone, Jain and Benacerraf. Regions showing vasculature, especially within septae and solid parts of tumours were examined by means of transvaginal colour Doppler. Location and intensification of angiogenesis as well as resistance index (RI) were investigated. Sensitivity, specificity, PPV and NPV of both techniques were assessed. Statistical analysis of obtained data were based on the Student's t test; p < 0.05 level was considered significant. Postoperatively 255 (77.5%) benign and 74 (22.5%) malignant tumours were seen. In the group of benign masses the average age of women was 42.6+/-12.3 and in the malignant it was 53.1+/-12.6 (p<0.0001). The transverse dimension of benign lesions was 77.2+/-19, whereas for malignant it was 107.0+/-31 (p<0.0001). Benign tumours in 63.0% were cystic, in 26.0% mixed cystic-solid and in 11.0% solid echostructures while in malignant they were respectively, 6.8%, 56.8% and 36.4% (p<0.0001). Doppler flow within the tumour was 74.5% in benign and 98.6% in malignant masses (p<0.0001). In benign lesions homogenous superficial or peripheral vasculature was visualized, and in the majority of cases (82.7%) it was of medium intensification. However in malignant central, peripheral or mixed vascularisation. in the majority intensified character was found. Average value of the resistance index in all benign masses amounted to 0.77+/-0.14, however in malignant it was 0.39+/-0.07 (p<0.0001). We contend that complete ultrasonographic estimation of ovarian neoplasms outside the qualification of structural details should include Doppler analysis of vasculature parameters. Most important is the qualification of resistance of flow, and location and intensification of vascularisation in examined masses which permit the differentiation of malignant and benign lesions. Preoperatively recognizing malignant processes with colour Doppler ultrasonography shows higher accuracy, specificity and PPV.

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival

PubMed Central

Kushchayev, Sergiy V; Sankar, Tejas; Eggink, Laura L; Kushchayeva, Yevgeniya S; Wiener, Philip C; Hoober, J Kenneth; Eschbacher, Jennifer; Liu, Ruolan; Shi, Fu-Dong; Abdelwahab, Mohammed G; Scheck, Adrienne C; Preul, Mark C

2012-01-01

Background A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR) exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated. Methods C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine) only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven). Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay. Results GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001) and tumor size was smaller (P < 0.02) in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005) and contralateral tumor-free hemisphere (P < 0.01) was associated with treatment. Conclusion Specific populations of monocyte-derived brain cells develop critical relationships with malignant gliomas. The biological effect of GCLRP in combination with radiation may be more successful because of the damage incurred by tumor cells by radiation and the enhanced or preserved presentation of tumor cell antigens by GCLRP-activated immune cells. Monocyte-derived brain cells may be important targets for creating effective immunological modalities such as employing the receptor system described in this study. PMID:23049281

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival.

PubMed

Kushchayev, Sergiy V; Sankar, Tejas; Eggink, Laura L; Kushchayeva, Yevgeniya S; Wiener, Philip C; Hoober, J Kenneth; Eschbacher, Jennifer; Liu, Ruolan; Shi, Fu-Dong; Abdelwahab, Mohammed G; Scheck, Adrienne C; Preul, Mark C

2012-01-01

A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR) exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated. C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine) only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven). Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay. GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001) and tumor size was smaller (P < 0.02) in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005) and contralateral tumor-free hemisphere (P < 0.01) was associated with treatment. Specific populations of monocyte-derived brain cells develop critical relationships with malignant gliomas. The biological effect of GCLRP in combination with radiation may be more successful because of the damage incurred by tumor cells by radiation and the enhanced or preserved presentation of tumor cell antigens by GCLRP-activated immune cells. Monocyte-derived brain cells may be important targets for creating effective immunological modalities such as employing the receptor system described in this study.

Expression of the pituitary tumor transforming gene (PTTG1) in pheochromocytoma as a potential marker for distinguishing benign versus malignant tumors.

PubMed

Haji Amousha, Mohamad Reza; Sabetkish, Nastaran; Sabet Kish, Nastaran; Heshmat, Ramin; Rajabiani, Afsaneh; Saffar, Hiva; Haghpanah, Vahid; Tavangar, Seyed Mohammad

2015-01-01

The Distinction between malignant and benign pheochromocytoma has always been a diagnostic challenge over the last decades. To date, the only reliable criterion is metastasis. The aim of the present study was to investigate the possible expression of pituitary-tumor transforming gene (PTTG1) and retinoblastoma (Rb) in benign and malignant pheochromocytoma. Paraffin blocks of 44 and 11 patients diagnosed with benign and malignant pheochromocytoma were collected. Parameters such as sex, age, tumor size, necrosis, and histological features were compared between the benign and malignant groups as well as immunohistochemical labeling using specific antibodies. PTTG1 showed negative expression in all (44) benign and 9 out of 11 (81.8%) malignant tumors with only 2 out of 11 (18.2%) malignant tumors showed positive reactivity for PTTG1 (P: 0.037) with spindle cell histological pattern in both of them (P: 0.013). Although Rb expression in malignant tumors (81.8%) was slightly more than the benign ones (52.3%), no statistically significant correlation was observed (P: 0.087). These results suggest that PTTG1 immunostaining may play a key role in distinguishing between benign and malignant phaeochromocytoma. However, larger studies are necessary to confirm the outcomes of the present study.

Update on non-acquired immunodeficiency syndrome-defining malignancies.

PubMed

Chiao, Elizabeth Y; Krown, Susan E

2003-09-01

Since the introduction of highly active antiretroviral therapy (HAART), the natural history of human immunodeficiency virus (HIV) infection has changed. Early in the acquired immunodeficiency syndrome (AIDS) epidemic, epidemiologic studies showed that HIV-infected patients were at higher risk for developing specific AIDS-defining malignancies. More recent studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. We review the most recent data regarding clinical presentation, pathology, and treatment outcomes for these non-AIDS-defining malignancies. Recent large cohort studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. Besides anal cancer and Hodgkin disease, the cohort studies have identified other malignancies that appear to occur at a higher rate in the HIV-infected population as compared with the general population. These malignancies include lung cancer, skin cancer, germ cell tumors, leiomyosarcomas, cancers of the head and neck, conjunctival cancer, multiple myeloma, and leukemias. As the epidemiology of non-AIDS-defining malignancies continues to evolve, it is unclear whether the appropriate treatments and outcomes for these or other malignancies are changed for HIV-infected patients treated with HAART.

Application values of 99mTc-methoxyisobutylisonitrile imaging for differentiating benign and malignant thymic masses.

PubMed

Lu, Chenghui; Wang, Xufu; Liu, Bin; Liu, Xinfeng; Wang, Guoming; Zhang, Qin

2017-08-01

The aim of the present study was to investigate the application value of 99m Tc-methoxyisobutylisonitrile (MIBI) imaging to differentiate between benign and malignant thymic masses. A total of 32 patients with space-occupying mediastinal masses were enrolled and early and delayed-phase images were collected following injection with the imaging agent. The tumor to background ratio (T/N) values at the different phases were also recorded. The sensitivity of the qualitative analysis to distinguish between benign and malignant thymic masses was 95.24%, with specificity as 90.91%. The T/N values in the early and delayed phases were not significantly different in the group with benign thymic masses, but demonstrated statistical significant differences in the groups with low- and intermediate-grade malignant thymic masses. The T/N values at the above early and delayed phase were significantly different between the benign and low-grade malignancy groups, as well as between low- and moderate-grade malignancy groups. Those between the benign and moderate-grade malignancy groups demonstrated no significant difference. 99m Tc-MIBI imaging was able to differentiate between benign and malignant thymic masses, and the simultaneous semi-quantitative analysis of the T/N values of the tumors may be able to initially determine the degree of malignancy of thymoma.

Modification of cytokine-induced killer cells with chimeric antigen receptors (CARs) enhances antitumor immunity to epidermal growth factor receptor (EGFR)-positive malignancies.

PubMed

Ren, Xuequn; Ma, Wanli; Lu, Hong; Yuan, Lei; An, Lei; Wang, Xicai; Cheng, Guanchang; Zuo, Shuguang

2015-12-01

Epidermal growth factor receptor (EGFR, ErbB1, Her-1) is a cell surface molecule overexpressing in a variety of human malignancies and, thus, is an excellent target for immunotherapy. Immunotherapy targeting EGFR-overexpressing malignancies using genetically modified immune effector cells is a novel and promising approach. In the present study, we have developed an adoptive cellular immunotherapy strategy based on the chimeric antigen receptor (CAR)-modified cytokine-induced killer (CAR-CIK) cells specific for the tumor cells expressing EGFR. To generate CAR-CIK cells, a lentiviral vector coding the EGFR-specific CAR was constructed and transduced into the CIK cells. The CAR-CIK cells showed significantly enhanced cytotoxicity and increased production of cytokines IFN-γ and IL-2 when co-cultured with EGFR-positive cancer cells. In tumor xenografts, adoptive immunotherapy of CAR-CIK cells could inhibit tumor growth and prolong the survival of EGFR-overexpressing human tumor xenografts. Moreover, tumor growth inhibition and prolonged survival in mice with EGFR(+) human cancer were associated with the increased persistence of CAR-CIK cells in vivo. Our study indicates that modification with EGFR-specific CAR strongly enhances the antitumor activity of the CIK cells against EGFR-positive malignancies.

[Value of narrow band imaging endoscopy in detection of early laryngeal squamous cell carcinoma].

PubMed

Staníková, L; Kučová, H; Walderová, R; Zeleník, K; Šatanková, J; Komínek, P

2015-01-01

Narrow band imaging (NBI) is an endoscopic method using filtered wavelengths in detection of microvascular abnormalities associated with preneoplastic and neoplastic changes of the mucosa. The aim of the study is to evaluate the value of NBI endoscopy in the dia-gnosis of laryngeal precancerous and early stages of cancerous lesions and to investigate impact of NBI method in prehistological diagnostics in vivo. One hundred patients were enrolled in the study and their larynx was investigated using white light HD endoscopy and narrow band imaging between 6/ 2013- 10/ 2014. Indication criteria included chronic laryngitis, hoarseness for more than three weeks or macroscopic laryngeal lesion. Features of mucosal lesions were evaluated by white light endoscopy and afterwards were compared with intra-epithelial papillary capillary loop changes, viewed using NBI endoscopy. Suspicious lesions (leukoplakia, exophytic tumors, recurrent respiratory papillomatosis and/ or malignant type of vascular network by NBI endoscopy) were evaluated by histological analysis, results were compared with prehistological NBI dia-gnosis. Using NBI endoscopy, larger demarcation of pathological mucosal features than in white light visualization were recorded in 32/ 100 (32.0%) lesions, in 4/ 100 (4.0%) cases even new lesions were detected only by NBI endoscopy. 63/ 100 (63.0%) suspected lesions were evaluated histologically -  malign changes (carcinoma in situ or invasive carcinoma) were observed in 25/ 63 (39.7%). Prehistological diagnostics of malignant lesions using NBI endoscopy were in agreement with results of histological examination in 23/ 25 (92.0%) cases. The sensitivity of NBI in detecting malignant lesions was 89.3%, specificity of this method was 94.9%. NBI endoscopy is a promising optical technique enabling in vivo differentiation of superficial neoplastic lesions. These results suggest endoscopic NBI may be useful in the early detection of laryngeal cancer and precancerous lesions.

Novel multiplex bead-based assay for detection of IDH1 and IDH2 mutations in myeloid malignancies.

PubMed

Shivarov, Velizar; Ivanova, Milena; Hadjiev, Evgueniy; Naumova, Elissaveta

2013-01-01

Isocitrate dehydrogenase 1 and 2 (IDH) mutations are frequently found in various cancer types such as gliomas, chondrosarcomas and myeloid malignancies. Their molecular detection has recently gained wide recognition in the diagnosis and prognosis of these neoplasms. For that purpose various molecular approaches have been used but a universally accepted method is still lacking. In this study we aimed to develop a novel bead-based liquid assay using Locked nucleic acids (LNA)-modified oligonucleotide probes for multiplexed detection of the most frequent IDH1 (p.R132C, p.R132G, p.R132H, p.R132L, p.R132S) and IDH2 (p.R140Q, p.R172K) mutations. The method includes four steps: 1) PCR amplification of the targeted fragments with biotinylated primers; 2) Direct hybridization to barcoded microbeads with specific LNA-modified oligonucleotide probes; 3) Incubation with phycoerythrin coupled streptavidin; 4) Acquisition of fluorescent intensities of each set of beads on a flow platform (LuminexCorp., USA). We tested the performance of the assay on both artificial plasmid constructs and on clinical samples from 114 patients with known or suspected myeloid malignancies. The method appeared to be superior to direct sequencing having a much higher sensitivity of 2.5% mutant alleles. Applying this method to patients' samples we identified a total of 9 mutations (one IDH1 p.R132C, seven IDH2 p.R140Q and one IDH2 p.R172K). In conclusion, this method could be successfully implemented in the diagnostic work-up for various tumors known to harbor IDH1/2 mutations (e.g. myeloid malignancies, gliomas, etc.). International initiatives are needed to validate the different existing methods for detection of IDH1/2 mutations in clinical settings.

Diffuse malignant pleural mesothelioma in an urban hospital: Clinical spectrum and trend in incidence over time

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shepherd, K.E.; Oliver, L.C.; Kazemi, H.

1989-01-01

This retrospective analysis reviews the clinical experience of a major urban referral hospital with diffuse malignant pleural mesothelioma during the 14-year period from 1973 through 1986. Seventy-five cases of definite or equivocal mesothelioma were identified. There were four cases of primary malignant peritoneal mesothelioma, seven cases of benign fibrous mesothelioma, and 64 cases of diffuse malignant pleural mesothelioma. In 43 cases (67%) of diffuse malignant pleural mesothelioma, there was historic evidence of asbestos exposure. In 21 cases (33%), there was no known history of asbestos exposure. An increase in annual incidence of diffuse malignant pleural mesothelioma was observed over themore » study period, from three cases in 1973 to ten cases in 1986. Despite greater awareness of this disease, the diagnosis remains a difficult one to establish given the nonspecific symptoms, signs and radiographic appearance, variable histologic appearance, and poor diagnostic sensitivity and specificity of thoracentesis and closed pleural biopsy. Thoracotomy, thoracoscopy, and CT-guided needle biopsies gave higher yields and are the diagnostic measures of choice when diffuse malignant pleural mesothelioma is suspected.« less

Ewing's Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies.

PubMed

Wolpert, Fabian; Grotzer, Michael A; Niggli, Felix; Zimmermann, Dieter; Rushing, Elisabeth; Bode-Lesniewska, Beata

2016-01-01

Modern multimodal treatment has significantly increased survival for patients affected by hematologic malignancies, especially in childhood. Following remission, however, the risk of developing a further malignancy is an important issue. The long-term estimated risk of developing a sarcoma as a secondary malignancy is increased severalfold in comparison to the general population. Ewing's sarcoma family encompasses a group of highly aggressive, undifferentiated, intra- and extraosseous, mesenchymal tumors, caused by several types of translocations usually involving the EWSR1 gene. Translocation associated sarcomas, such as Ewing sarcoma, are only rarely encountered as therapy associated secondary tumors. We describe the clinical course and management of three patients from a single institution with Ewing's sarcoma that followed successfully treated lymphoblastic T-cell leukemia or non-Hodgkin lymphoma. The literature on secondary Ewing's sarcoma is summarized and possible pathogenic mechanisms are critically discussed.

Study of the expression of cathepsins in histological material from pancreatic lesions.

PubMed

Martínez, Juan F; Aparicio, José Ramón; Peiró, Gloria; Cabezas, Antonio; Roger, Manuela; Ruiz, Francisco; Compañy, Luís; Casellas, Juan Antonio

2016-12-01

To assess the expression levels of cathepsins in malignant and premalignant lesions. We retrospectively included patients who underwent pancreatic surgery on pancreatic solid or cystic masses. The expression of cathepsin H, L, B and S was determined in both types of samples. Lesions were divided into three categories: malignant (pancreatic adenocarcinoma and malignant mucinous neoplasms), premalignant (mucinous neoplasms) and benign (other lesions). Thirty-one surgical resection samples were studied. The expression of cathepsins was significantly higher in malignant lesions than in premalignant and benign lesions (H 75%, 27%, 37% p = 0.05; L 92%, 36%, 37% p = 0.011; B 83%, 36%, 62% p = 0.069; S 92%, 36%, 25% p = 0.004, respectively). Cathepsins are overexpressed in histological samples of malignant lesions compared to premalignant and benign lesions. However, the expression of cathepsins is similar in both premalignant and benign lesions.

[Anorectal Malignant Melanoma Is a Very Rare Disease and Has a Poor Prognosis].

PubMed

Yoshida, Yuta; Noura, Shingo; Matsumura, Tae; Hirota, Masaki; Shuto, Takashi; Muratsu, Arisa; Yasuyama, Harunobu; Takata, Akihiro; Koga, Chikato; Kameda, Chizu; Murakami, Masahiro; Kawabata, Ryohei; Shimizu, Junzo; Miwa, Hideaki; Hasegawa, Junichi

2017-11-01

We performed abdomino-perineal-resection(APR)on 2 cases of anorectal malignant melanoma. The first case was a 70- year-old woman suffering from bloody stool. Colonoscopy showed a black tumor in the rectum. Biopsy revealed a malignant melanoma. A CT scan showed multiple lung metastases and liver metastasis. She underwent surgery for the purpose of bleeding control, but died shortly thereafter because her liver and lung metastases had worsened. The second case was a 43- years-old man suffering from bloody stool. He had a black type 3 tumor in the rectum. A biopsy revealed malignant melanoma. A CT scan showed lateral lymph node swelling. He underwent APR with right side-lateral dissection. An established treatment for anorectal malignant melanoma has not been agreed upon and it is controversial. We experienced 2 cases that underwent surgery and we report them along with relevant information from the literature.

Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

PubMed Central

Liu, Shin-Yun; Shun, Chia-Tung; Hung, Kuan-Yu; Juan, Hsueh-Fen; Hsu, Chia-Lang; Huang, Min-Chuan; Lai, I-Rue

2016-01-01

Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression. PMID:26848976

Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy.

PubMed

Kong, Bo; Bruns, Philipp; Behler, Nora A; Chang, Ligong; Schlitter, Anna Melissa; Cao, Jing; Gewies, Andreas; Ruland, Jürgen; Fritzsche, Sina; Valkovskaya, Nataliya; Jian, Ziying; Regel, Ivonne; Raulefs, Susanne; Irmler, Martin; Beckers, Johannes; Friess, Helmut; Erkan, Mert; Mueller, Nikola S; Roth, Susanne; Hackert, Thilo; Esposito, Irene; Theis, Fabian J; Kleeff, Jörg; Michalski, Christoph W

2018-01-01

The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras G12D -driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hospital-based epidemiological and clinical characterisation of the malignant transformation of oral leukoplakia in a Chinese population.

PubMed

Lyu, Ming-Yue; Guo, Yu-Si; Li, Shuo; Yang, Di; Hua, Hong

2017-08-01

The aim of this review was to analyse, systematically, hospital-based epidemiological information concerning the malignant transformation rate (MTR) of oral leukoplakia (OL) in a Chinese population, as well as the associated risk factors. Four electronic databases were searched for studies dealing with OL and related risk factors, including age, gender, type of lesion, site, and smoking and drinking habits. The MTR of OL in the hospital-based Chinese population ranged from 4% to 13%, based on the studies analysed. Regarding risk factors, we found that female patients had a higher MTR than male patients, and that patients older than 50 years of age also had a higher MTR. Patients who smoked had a lower MTR, while alcohol consumption seemed to have no association with MTR. Malignant transformation occurred most commonly on the tongue. Regarding lesion type, non-homogeneous OL had a higher MTR, with the granular type having the highest MTR. Our results regarding the epidemiology of OL showed a similar trend to those reported in western populations and provided preliminary epidemiological information on the Chinese population. Our findings show that female gender, age >50 years and non-homogeneous OL are risk factors for malignant transformation. It is important to develop clinical strategies to educate, diagnose and treat patients with OL and to minimise the MTR of OL. © 2017 FDI World Dental Federation.

Diagnostic performance of different measurement methods for lung nodule enhancement at quantitative contrast-enhanced computed tomography

NASA Astrophysics Data System (ADS)

Wormanns, Dag; Klotz, Ernst; Dregger, Uwe; Beyer, Florian; Heindel, Walter

2004-05-01

Lack of angiogenesis virtually excludes malignancy of a pulmonary nodule; assessment with quantitative contrast-enhanced CT (QECT) requires a reliable enhancement measurement technique. Diagnostic performance of different measurement methods in the distinction between malignant and benign nodules was evaluated. QECT (unenhanced scan and 4 post-contrast scans) was performed in 48 pulmonary nodules (12 malignant, 12 benign, 24 indeterminate). Nodule enhancement was the difference between the highest nodule density at any post-contrast scan and the unenhanced scan. Enhancement was determined with: A) the standard 2D method; B) a 3D method consisting of segmentation, removal of peripheral structures and density averaging. Enhancement curves were evaluated for their plausibility using a predefined set of criteria. Sensitivity and specificity were 100% and 33% for the 2D method resp. 92% and 55% for the 3D method using a threshold of 20 HU. One malignant nodule did not show significant enhancement with method B due to adjacent atelectasis which disappeared within the few minutes of the QECT examination. Better discrimination between benign and malignant lesions was achieved with a slightly higher threshold than proposed in the literature. Application of plausibility criteria to the enhancement curves rendered less plausibility faults with the 3D method. A new 3D method for analysis of QECT scans yielded less artefacts and better specificity in the discrimination between benign and malignant pulmonary nodules when using an appropriate enhancement threshold. Nevertheless, QECT results must be interpreted with care.

Evaluation of minimal disseminated disease in cryopreserved ovarian tissue from bone and soft tissue sarcoma patients.

PubMed

Dolmans, M M; Iwahara, Y; Donnez, J; Soares, M; Vaerman, J L; Amorim, C A; Poirel, H

2016-10-01

What is the risk of finding malignant cells in cryopreserved ovarian tissue from sarcoma patients? Minimal disseminated disease (MDD) was not detected in frozen-thawed ovarian tissue from 26 patients by any of the sensitive methods applied. In case of leukemia, the risk of malignant cell transmission through the graft is well known and widely documented. However, for bone cancer, like Ewing sarcoma or osteosarcoma, only a small number of case reports, have been published. These cancers often affect prepubertal girls, in whom ovarian tissue cryopreservation and transplantation is the only option to preserve fertility. The presence of malignant cells in cryopreserved ovarian tissue from patients with bone/soft tissue sarcoma was investigated with disease-specific markers for each patient, using immunohistochemistry (IHC), FISH and real-time quantitative RT-PCR (qPCR), with the original tumor serving as a positive control. Forty-eight sarcoma patients were enrolled in the study, 12 of whom subsequently died. In each case, tissue from the primary tumor was investigated in order to identify markers (immunohistochemical and/or molecular) to analyze the ovarian tissue case by case. Ovarian tissue from osteosarcoma (n = 15), liposarcoma (n = 1) and undifferentiated sarcoma (n = 5) patients could not be evaluated, as no specific markers were detected by FISH or sensitive IHC in any of their primary tumoral tissue. One patient with Li-Fraumeni syndrome was also excluded from the study. IHC analyses were therefore performed on ovarian tissue from 26 patients and qPCR on 19. The primary tumors involved were Ewing sarcoma family of tumors (n = 14), rhabdomyosarcoma (n = 7), synovial sarcoma (n = 2), clear cell sarcoma (n = 2) and a malignant peripheral nerve sheath tumor (n = 1). MDD was not detected in any of the 26 analyzed samples using sensitive techniques in this largest reported series, even from patients who subsequently died and/or those who presented with metastasis (11/26), hence the most aggressive forms of bone cancer. Indeed, anti-CD99 IHC and PCR performed on patients presenting with Ewing sarcoma family of tumors (n = 14) was negative in all cases. In patients with soft tissue sarcoma (n = 12) primitive tumor markers were detected by IHC and were negative in ovarian tissue. PCR could only be performed in 6/12 of these patients, again proving negative. Cryopreserved ovarian fragments to be transplanted cannot be tested, so this analysis of malignant cells cannot guarantee that all cryopreserved fragments will not contain any disseminated disease. Moreover, molecular markers are not readily available for all types of tumors. These results are reassuring regarding the risk of malignant cells in the ovary for transplantation, as the study involves a large series including different types of sarcomas. We believe this will help clinicians in their patient counseling for fertility preservation and restoration. This work was supported by the Fonds National de la Recherche Scientifique de Belgique-FNRS under Grants Nos 7.4578.14 (Télévie to MS) and 5/4/150/5 to MMD. The authors declare no competing financial interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lysine-specific demethylase 1 (LSD1) destabilizes p62 and inhibits autophagy in gynecologic malignancies.

PubMed

Chao, Angel; Lin, Chiao-Yun; Chao, An-Ning; Tsai, Chia-Lung; Chen, Ming-Yu; Lee, Li-Yu; Chang, Ting-Chang; Wang, Tzu-Hao; Lai, Chyong-Huey; Wang, Hsin-Shih

2017-09-26

Lysine-specific demethylase 1 (LSD1) - also known as KDM1A - is the first identified histone demethylase. LSD1 is highly expressed in numerous human malignancies and has recently emerged as a target for anticancer drugs. Owing to the presence of several functional domains, we speculated that LSD1 could have additional functions other than histone demethylation. P62 - also termed sequestasome 1 (SQSTM1) - plays a key role in malignant transformation, apoptosis, and autophagy. Here, we show that a high LSD1 expression promotes tumorigenesis in gynecologic malignancies. Notably, LSD1 inhibition with either siRNA or pharmacological agents activates autophagy. Mechanistically, LSD1 decreases p62 protein stability in a demethylation-independent manner. Inhibition of LSD1 reduces both tumor growth and p62 protein degradation in vivo . The combination of LSD1 inhibition and p62 knockdown exerts additive anticancer effects. We conclude that LSD1 destabilizes p62 and inhibits autophagy in gynecologic cancers. LSD1 inhibition reduces malignant cell growth and activates autophagy. The combinations of LSD1 inhibition and autophagy blockade display additive inhibitory effect on cancer cell viability. A better understanding of the role played by p62 will shed more light on the anticancer effects of LSD1 inhibitors.

Evaluation of usefulness of fine-needle aspiration cytology in the diagnosis of tumours of the accessory parotid gland: a preliminary analysis of a case series in Japan.

PubMed

Iguchi, Hiroyoshi; Wada, Tadashi; Matsushita, Naoki; Oishi, Masahiro; Teranishi, Yuichi; Yamane, Hideo

2014-07-01

The accuracy and sensitivity of fine-needle aspiration cytology (FNAC) in this analysis were not satisfactory, and the false-negative rate seemed to be higher than for parotid tumours. The possibility of low-grade malignancy should be considered in the surgical treatment of accessory parotid gland (APG) tumours, even if the preoperative results of FNAC suggest that the tumour is benign. Little is known about the usefulness of FNAC in the preoperative evaluation of APG tumours, probably due to the paucity of APG tumour cases. We examined the usefulness of FNAC in the detection of malignant APG tumours. We conducted a retrospective analysis of 3 cases from our hospital, along with 18 previously reported Japanese cases. We compared the preoperative FNAC results with postoperative histopathological diagnoses of APG tumours and evaluated the accuracy, sensitivity, specificity and false-negative rates of FNAC in detecting malignant APG tumours. There were four false-negative cases (19.0%), three of mucoepidermoid carcinomas and one of malignant lymphoma. One false-positive result was noted in the case of a myoepithelioma, which was cytologically diagnosed as suspected adenoid cystic carcinoma. The accuracy, sensitivity and specificity of FNAC in detecting malignant tumours were 76.2%, 60.0% and 90.9%, respectively.

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi.

PubMed

Clarke, Loren E; Flake, Darl D; Busam, Klaus; Cockerell, Clay; Helm, Klaus; McNiff, Jennifer; Reed, Jon; Tschen, Jaime; Kim, Jinah; Barnhill, Raymond; Elenitsas, Rosalie; Prieto, Victor G; Nelson, Jonathan; Kimbrell, Hillary; Kolquist, Kathryn A; Brown, Krystal L; Warf, M Bryan; Roa, Benjamin B; Wenstrup, Richard J

2017-02-15

Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617-628. © 2016 American Cancer Society. © 2016 Myriad Genetics, Inc. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Radiotherapy for non-malignant disorders: state of the art and update of the evidence-based practice guidelines

PubMed Central

Micke, O; Muecke, R

2015-01-01

Every year in Germany about 50,000 patients are referred and treated by radiotherapy (RT) for “non-malignant disorders”. This highly successful treatment is applied only for specific indications such as preservation or recovery of the quality of life by means of pain reduction or resolution and/or an improvement of formerly impaired physical body function owing to specific disease-related symptoms. Since 1995, German radiation oncologists have treated non-malignant disorders according to national consensus guidelines; these guidelines were updated and further developed over 3 years by implementation of a systematic consensus process to achieve national upgraded and accepted S2e clinical practice guidelines. Throughout this process, international standards of evaluation were implemented. This review summarizes most of the generally accepted indications for the application of RT for non-malignant diseases and presents the special treatment concepts. The following disease groups are addressed: painful degenerative skeletal disorders, hyperproliferative disorders and symptomatic functional disorders. These state of the art guidelines may serve as a platform for daily clinical work; they provide a new starting point for quality assessment, future clinical research, including the design of prospective clinical trials, and outcome research in the underrepresented and less appreciated field of RT for non-malignant disorders. PMID:25955230

Comparative study of three sonoelastographic scores for differentiation between benign and malignant cervical lymph nodes.

PubMed

Lenghel, Lavinia Manuela; Botar Jid, Carolina; Bolboaca, Sorana D; Ciortea, Cristiana; Vasilescu, Dan; Baciut, Grigore; Dudea, Sorin M

2015-06-01

The aim of the study was to explore the diagnostic value of three different sonoelastographic scoring systems (labeled S1-S3) for the differentiation between benign and malignant cervical lymph nodes. The authors propose a six pattern scoring system of the elastographic images with pattern 1 - representing purely soft nodes, pattern 2 - predominantly soft nodes, pattern 3 - predominantly soft nodes with focal had area, pattern 4 - predominantly hard node, pattern 5 - entirely hard node and pattern 6 - node with necrosis. The sonoelastographic images of 50 benign and 70 malignant lymph nodes were assessed. The area under the ROC curve (AUROC) for the differentiation between benign vs. malignant and benign vs. metastatic nodes were analyzed for the three scoring systems. When all the malignant lymph nodes were considered, the S1 score showed an AUROC=0.873 (95%CI [0.805-0.918], where CI=confidence interval; p<0.001), sensibility (Se)=58.57%, and specificity (Sp)=96%. For S2 score the AUROC was 0.890 (95%CI [0.824-0.933], p<0.001), Se=92.86%, and Sp=72%. For S3 score, the AUROC was 0.852 (95%CI [0.778-0.902], p<0.001), Se=64.29%, and Sp=94%). When lymphomatous nodes were excluded, for S1 the AUROC was 0.884 (95%CI [0.809-0.932], p<0.001), Se=64%, and Sp=96%. For S2 the AUROC was 0.894 (95%CI [0.818-0.939], p<0.001), Se=92%, and Sp=72%. For S3, the AUROC was 0.856 (95%CI [0.771-0.911], p<0.001), Se=66%, and Sp=94%. In the S3 scoring system, setting the benign vs. malignant cut off at pattern 3 increases the sensibility (41-65%) with minimal loss of specificity (96-94%). From the gray-scale and Doppler criteria, changes of the nodular margins and the presence of the vessels in the cortical part of the lymph node showed both very high sensibility and specificity, the others criteria taken into account had either very good sensibility with low specificity or high specificity and low sensibility. Our study suggests that there are no significant differences between the three scoring systems in terms of overall diagnostic value. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Identifying Thoracic Malignancies Through Pleural Fluid Biomarkers: A Predictive Multivariate Model.

PubMed

Porcel, José M; Esquerda, Aureli; Martínez-Alonso, Montserrat; Bielsa, Silvia; Salud, Antonieta

2016-03-01

The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural fluid samples are highly discriminative for signaling a malignant versus tuberculous effusion, or lung adenocarcinoma versus mesothelioma, respectively. Cathepsin-B could also be helpful in establishing the presence of a lymphomatous effusion versus that of TB, if the patient's age is simultaneously taken into consideration.

[Rapidly progressive pulmonary malignant perivascular epithelioid cell tumor: a case report and literature review].

PubMed

Shi, X Y; Long, F; Liang, B; Su, L L; Li, H C; Jiang, S J

2016-10-12

Objective: To analyze the pathogenesis, clinical features, diagnosis and differential diagnosis of primary perivascular epithelioid cell tumor(PEComa). Methods: The clinical features, auxiliary examinations and diagnosis of a case with rapidly progressive pulmonary malignant PEComa were reported and the related literatures were reviewed.The literature review was carried out respectively in Wanfang Data, CNKI and PubMed from Jan. 1975 to Jul. 2015 with "pulmonary malignant perivascular epithelioid cell tumor" and "PEComa" being the search terms. Results: A 50 year-old female patient was admitted to the hospital on September 4, 2014 because of cough and dyspnea for 60 days, hemoptysis for 40 days and fever for 7 days.Chest CT scan showed diffuse small nodules with infiltrative border and multiple pure and mixed ground-glass opacity. Transbronchial lung biopsy (TBLB) was performed and the pathological study confirmed the diagnosis of primary pulmonary malignant PEComa. The patient declined further specific therapy, but followed by rapidly progressive respiratory failure, and died two weeks after the diagnosis. A total of 8 literatures were retrieved from Wanfang Data, CNKI and PubMed and all of them were case reports.There were 3 male and 5 female patients, aging from 50 to 79 years.Radiographically, the previously reported cases presented as round and well-circumscribed masses with or without multiple nodules in both lungs. The symptoms had no specificity. Conclusions: Pulmonary malignant PEComa is a rare disease.It is easily misdiagnosed because of non-specific clinical and imaging manifestations.The final diagnosis depends on pathological biopsy.TBLB is an effective diagnostic method.

Serum total prostate-specific antigen values in men with symptomatic prostate enlargement in Nigeria: role in clinical decision-making.

PubMed

Nnabugwu, Ikenna I; Ugwumba, Fred O; Enivwenae, Oghenekaro A; Udeh, Emeka I; Otene, Chris O; Nnabugwu, Chinwe A

2015-01-01

Prostatic enlargement is a common cause of bladder outlet obstruction in men in Nigeria. Malignant enlargements must be differentiated from benign enlargements for adequate treatment of each patient. High serum total prostate-specific antigen (tPSA) levels suggest malignancy, but some of the biopsies done due to a serum tPSA value >4 ng/mL would be negative for malignancy because of the low specificity of tPSA for prostate cancer. This study aims to compare the histologic findings of all prostate specimens obtained from core needle biopsy, open simple prostatectomy, and transurethral resection of the prostate with the respective serum tPSA values in an attempt to decipher the role of serum tPSA in the management of these patients. The case notes of patients attended to from April 2009 to March 2012 were analyzed. Essentially, the age of the patient, findings on digital rectal examination, abdominopelvic ultrasonography report on the prostate, serum tPSA, and histology reports from biopsy or prostatectomy specimens as indicated were extracted for analysis. The relationship between age, findings on digital rectal examination, serum tPSA, abdominopelvic ultrasonography report, and histology are compared. A statistically significant relationship existed between a malignant histology and age 65 years and older, suspicious findings on digital rectal examination, suspicious ultrasonography findings, and serum tPSA >10 ng/mL, but not tPSA >4 ng/mL. In Nigerian patients with symptomatic prostate enlargement, serum tPSA should be seen as a continuum with increasing risk of prostate malignancy.

A near-infrared Fourier transform Raman spectroscopy of epidermal keratinocytes: changes in the protein?DNA structure following malignant transformation

NASA Astrophysics Data System (ADS)

Gao, Xiaoling; Butler, Ian S.; Kremer, Richard

2005-01-01

We report here the use of near-infrared (NIR) Fourier transform (FT) Raman spectroscopy to analyze normal human epidermal keratinocytes prior to and following malignant transformation. Our analysis indicates specific Raman spectral differences between immortalized (HPK1A) and malignant ras transformed (HPK1A- ras) cells. In addition, striking spectral differences are seen in the DNA isolated from these cells and particularly in the 843/810 cm -1 ratio with values of 1.6 ± 0.13 in HPK1A cells and 0.68 ± 0.09 in HPK1A- ras cells (mean ± S.D., n = 12, P < 0.001) indicating specific alterations in the backbone conformation markers following malignant transformation. Subsequently, we analysed the effect of a strong inhibitor of keratinocyte growth, the Vitamin D analog EB1089, on the Raman spectra of intact cells and on the 843/810 cm -1 ratio in the DNA isolated from both cell lines. Specific changes were observed in intact cells in the 1300-750 cm -1 region. Furthermore, the 843/810cm -1 ratio of isolated DNA from HPK1A cells was not affected by EB1089 but significantly increased in DNA isolated from HPK1A-ras cells so much that it became closer to the value observed for HPK1A cells (1.07 ± 0.10). Our data suggest that Raman analysis of DNA and in particular the 843/810cm -1 ratio can provide useful indices of malignant transformation and efficacy of anticancer agents.

Temporary use of silicone stents for severe airway stenosis in untreated malignant lymphoma.

PubMed

Oki, Masahide; Saka, Hideo

2013-01-01

Airway stenting has become a popular method for palliation of airway stenosis; however, little has been reported about their use for patients with malignant lymphoma that occasionally causes a life-threatening condition. The aim of the study was to evaluate the efficacy and safety of airway stenting in chemoradiotherapy naive patients with severe airway stenosis due to malignant lymphoma. Patients who underwent airway stent placement from April 2007 to July 2011 in a single center were retrospectively reviewed. All stenting procedures were performed using rigid and flexible bronchoscopes under general anesthesia. We performed 174 airway stenting procedures (silicone stents in 154 procedures and metallic in 20 procedures) for 150 patients during the study period. Of the patients, 7 had untreated malignant lymphomas (4 diffuse large B-cell lymphomas, 2 lymphoblastic lymphomas, 1 mucosa-associated lymphoid tissue lymphoma). All patients underwent stenting using the silicone Y-stent (6 on the main carina and 1 on the primary right carina). Dyspnea was relieved immediately in 6 of 7 patients including the mechanically ventilated patient. Stents could be removed in all patients (median 90 d after stenting; range, 32 to 245 d) because of the tumor response to tumor-specific therapy. One granuloma formation and 1 mucus retention triggered the decision to remove the stents. Airway stenting using silicone stents is safe and effective in palliation of airway stenosis in patients with untreated malignant lymphoma, and permits postprocedural tumor-specific therapy. The response to tumor-specific therapy can be expected, and so removable stents should be selected.

Schneiderian papillomas: Comparative review of exophytic, oncocytic, and inverted types

PubMed Central

Vira, Darshni; Suh, Jeffrey D.; Bhuta, Sunita; Wang, Marilene B.

2013-01-01

Background: Sinonasal papillomas are benign epithelial neoplasms arising from Schneiderian mucosa. The three subtypes, exophytic, oncocytic, and inverted (inverted papilloma [IP]), should be distinguished from one another histopathologically. This study (1) highlights the histopathological and clinical differences between the Schneiderian papilloma subtypes and (2) identifies clinical features that potentially predict papilloma subtypes. Methods: A retrospective review was performed of patients with Schneiderian papillomas over an 11-year period. Results: Seventy patients with sinonasal papillomas who underwent sinus surgery were identified. There were 50 (71%) male and 20 (29%) female subjects diagnosed at an average age of 53 years (range, 13–80 years). Exophytic (n = 25), oncocytic (n = 9), and IP (n = 37) were identified. IP was associated with transformation into squamous cell carcinoma in three (8%) cases and dysplasia in three (8%) cases. Neither oncocytic nor exophytic subtypes were associated with dysplasia or malignancy. On multivariate analysis of potential predictors of papilloma subtype, history of chronic rhinosinusitis (CRS) and location of papilloma were significantly associated with papilloma subtype. Using classification and regression tree model, papilloma subtypes can be predicted based on presence or absence of CRS and papilloma location with nominal 82.4% accuracy. Conclusion: The inverted and exophytic type are the most common sinonasal papillomas, with the inverted type having an 8% rate of malignant transformation in this study. In contrast, the oncocytic type was not associated with dysplasia or malignancy in our series despite reports in the literature indicating malignant potential. History of CRS and papilloma location can provide clues to the histological subtype, which is important for surgical planning and patient counseling. PMID:23883810

Dynamic MR imaging of soft tissue tumors with assessment of the rate and character of lesion enhancement.

PubMed

Tacikowska, Małgorzata

2002-02-01

The aim of this study was to analyze the diagnostic usefulness of dynamic MRI with determination of the coefficient of enhancement rate and the character of tumor enhancement, and to assess both parameters in the differentiation of malignant lesions. The material consisted of 45 patients (30 sarcomas, 15 non-malignant lesions), age 16-64 years. MRI was done using an Elscint 2T unit, gradient echo techniques, apex angle 80 degrees. The repetition time (TR) was 80-200 ms, the echo time (TE) was 2-6 ms, 1 excitation; the acquisition time (TA) was 70-80 ms. The coefficient of tissue enhancement rate was calculated in the region of interest, and expressed as percent per second (erc%/s). The limit value of erc%/s was determined. The sensitivity and specificity of MRI were calculated in the differentiation of malignant tumors. The method of contrast filling of the tumors was assessed in successive phases after administration of gadolinium Gd-DTPA. Dynamic MRI with determination of the index of tumor enhancement rate is highly sensitive (93%) and specific (73%) in the differentiation of malignant and benign lesions. The usefulness of the assessment of tumor enhancement character was not confirmed, since the sensitivity and specificity were 73% and 33%. Dynamic MRI with determination of erc%/s and tumor enhancement character is highly sensitive (93%) and specific (87%). Dynamic MRI with determination of erc%/s and tumor enhancement character is the best method for differential diagnosis.

Efficacy and safety of limited endoscopic sphincterotomy before self-expandable metal stent insertion for malignant biliary obstruction

PubMed Central

Nam, Hyeong Seok; Kang, Dae Hwan; Kim, Hyung Wook; Choi, Cheol Woong; Park, Su Bum; Kim, Su Jin; Ryu, Dae Gon

2017-01-01

AIM To evaluate the safety and efficacy of limited endoscopic sphincterotomy (ES) before placement of self-expandable metal stent (SEMS). METHODS This was a retrospective analysis of 244 consecutive patients with unresectable malignant biliary obstruction, who underwent placement of SEMSs following limited ES from December 2008 to February 2015. The diagnosis of malignant biliary obstruction and assessment of patient eligibility for the study was established by a combination of clinical findings, laboratory investigations, imaging and pathological results. All patients were monitored in the hospital for at least 24 h following endoscopic retrograde cholangio pancreatography (ERCP). The incidence of immediate or early post-ERCP complications such as post-ERCP pancreatitis (PEP) and bleeding related to limited ES were considered as primary outcomes. Also, characteristics and complications according to the cancer type were classified. RESULTS Among the 244 patients included, the underlying diagnosis was cholangiocarcinoma in 118 patients, pancreatic cancer in 79, and non-pancreatic or non-biliary malignancies in the remaining 47 patients. Early post-ERCP complications occurred in 9 patients (3.7%), with PEP in 7 patients (2.9%; mild, 6; moderate, 1) and mild bleeding in 2 patients (0.8%). There was no significant association between the incidence of post-ERCP complications and the type of malignancy (cholangiocarcinoma vs pancreatic cancer vs others, P = 0.696) or the type of SEMS used (uncovered vs covered, P = 1.000). Patients who had more than one SEMS placed at the first instance were at a significantly higher risk of post-ERCP complications (one SEMS vs two SEMS, P = 0.031). No other factors were predictive of post-ERCP complications. CONCLUSION Limited ES is feasible and safe, and effectively facilitates the placement of SEMS, without any significant risk of PEP or severe bleeding. PMID:28321164

Efficacy and safety of limited endoscopic sphincterotomy before self-expandable metal stent insertion for malignant biliary obstruction.

PubMed

Nam, Hyeong Seok; Kang, Dae Hwan; Kim, Hyung Wook; Choi, Cheol Woong; Park, Su Bum; Kim, Su Jin; Ryu, Dae Gon

2017-03-07

To evaluate the safety and efficacy of limited endoscopic sphincterotomy (ES) before placement of self-expandable metal stent (SEMS). This was a retrospective analysis of 244 consecutive patients with unresectable malignant biliary obstruction, who underwent placement of SEMSs following limited ES from December 2008 to February 2015. The diagnosis of malignant biliary obstruction and assessment of patient eligibility for the study was established by a combination of clinical findings, laboratory investigations, imaging and pathological results. All patients were monitored in the hospital for at least 24 h following endoscopic retrograde cholangio pancreatography (ERCP). The incidence of immediate or early post-ERCP complications such as post-ERCP pancreatitis (PEP) and bleeding related to limited ES were considered as primary outcomes. Also, characteristics and complications according to the cancer type were classified. Among the 244 patients included, the underlying diagnosis was cholangiocarcinoma in 118 patients, pancreatic cancer in 79, and non-pancreatic or non-biliary malignancies in the remaining 47 patients. Early post-ERCP complications occurred in 9 patients (3.7%), with PEP in 7 patients (2.9%; mild, 6; moderate, 1) and mild bleeding in 2 patients (0.8%). There was no significant association between the incidence of post-ERCP complications and the type of malignancy (cholangiocarcinoma vs pancreatic cancer vs others, P = 0.696) or the type of SEMS used (uncovered vs covered, P = 1.000). Patients who had more than one SEMS placed at the first instance were at a significantly higher risk of post-ERCP complications (one SEMS vs two SEMS, P = 0.031). No other factors were predictive of post-ERCP complications. Limited ES is feasible and safe, and effectively facilitates the placement of SEMS, without any significant risk of PEP or severe bleeding.

Efficiency of the Bethesda System for Thyroid Cytopathology.

PubMed

Mora-Guzmán, Ismael; Muñoz de Nova, José Luis; Marín-Campos, Cristina; Jiménez-Heffernan, José Antonio; Cuesta Pérez, Juan Julián; Lahera Vargas, Marcos; Torres Mínguez, Emma; Martín-Pérez, Elena

2018-03-28

Fine-needle aspiration biopsies are a key tool for preoperative assessment of thyroid nodules, and the Bethesda system is the preferred method to report cytological analysis. The purpose of this study is to assess the efficiency of the Bethesda system to identify the malignancy risk of thyroid nodules. Patients who underwent thyroid surgery between June 2010 and June 2017 were included. Samples were classified into 6categories according to rates of malignancy associated with each diagnostic category. In order to investigate the correlation between categories, a statistical analysis compared the categories with pathology reports. Diagnostic indicators were calculated as a screening test (categories IV, V, VI as true-positive) and as a method to identify malignancy (V, VI as true-positive). In a series of 522 patients, we found 184 (35.2%) malignant tumours, papillary carcinoma being the most prevalent with 155 cases (84.2%). Malignant rates for diagnostic categories were: I, 0%; II, 1.5%; III, 6.4%; IV, 31%; V, 86.5%; VI, 100%. A robust correlation was identified between categories on statistical analysis. For the «screening test» analysis, sensitivity was 98.9%, specificity 84.4%, positive predictive value 69.6%, negative predictive value 99.5%, and diagnostic accuracy 88.2%. Analysing the accuracy to detect malignancy, values were: sensitivity 98.6%, specificity 97.6%, positive predictive value 93.5%, negative predictive value 99.5%, diagnostic accuracy 97.9%. The Bethesda system is a clear and reliable approach to report thyroid cytology and therefore is an effective tool to identify malignancy risk and guide clinical management. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

1H-MRS evaluation of breast lesions by using total choline signal-to-noise ratio as an indicator of malignancy: a meta-analysis.

PubMed

Wang, Xin; Wang, Xiang Jiang; Song, Hui Sheng; Chen, Long Hua

2015-05-01

The aim of this study was to evaluate the diagnostic performance of the use of total choline signal-to-noise ratio (tCho SNR) criteria in MRS studies for benign/malignant discrimination of focal breast lesions. We conducted (1) a meta-analysis based on 10 studies including 480 malignant breast lesions and 312 benign breast lesions and (2) a subgroup meta-analysis of tCho SNR ≥ 2 as cutoff for malignancy based on 7 studies including 371 malignant breast lesions and 239 benign breast lesions. (1) The pooled sensitivity and specificity of proton MRS with tCho SNR were 0.74 (95 % CI 0.69-0.77) and 0.76 (95 % CI 0.71-0.81), respectively. The PLR and NLR were 3.67 (95 % CI 2.30-5.83) and 0.25 (95 % CI 0.14-0.42), respectively. From the fitted SROC, the AUC and Q* index were 0.89 and 0.82. Publication bias was present (t = 2.46, P = 0.039). (2) Meta-regression analysis suggested that neither threshold effect nor evaluated covariates including strength of field, pulse sequence, TR and TE were sources of heterogeneity (all P value >0.05). (3) Subgroup meta-analysis: The pooled sensitivity and specificity were 0.79 and 0.72, respectively. The PLR and NLR were 3.49 and 0.20, respectively. The AUC and Q* index were 0.92 and 0.85. The use of tCho SNR criteria in MRS studies was helpful for differentiation between malignant and benign breast lesions. However, pooled diagnostic measures might be overestimated due to publication bias. A tCho SNR ≥ 2 as cutoff for malignancy resulted in higher diagnostic accuracy.

Sperm associated antigen 9 (SPAG9) expression and humoral response in benign and malignant salivary gland tumors

PubMed Central

Agarwal, Sumit; Parashar, Deepak; Gupta, Namita; Jagadish, Nirmala; Thakar, Alok; Suri, Vaishali; Kumar, Rajive; Gupta, Anju; Ansari, Abdul S; Lohiya, Nirmal Kumar; Suri, Anil

2015-01-01

Salivary gland cancers are highly aggressive epithelial tumor associated with metastatic potential and high mortality. The tumors are biologically diverse and are of various histotypes. Besides, the detection and diagnosis is a major problem of salivary gland cancer for available treatment modalities. In the present study, we have investigated the association of sperm associated antigen 9 (SPAG9) expression with salivary gland tumor (SGT). Clinical specimens of benign (n = 16) and malignant tumors (n = 86) were examined for the SPAG9 expression. In addition, the sera and adjacent non-cancerous tissues (n = 72) from available patients were obtained. Our in situ RNA hybridization and immunohistochemistry (IHC) analysis revealed significant difference (p = 0.0001) in SPAG9 gene and protein expression in benign (63%) and malignant tumor (84%) specimens. Further, significant association was also observed between SPAG9 expression and malignant tumors (P = 0.05). A cut-off value of >10% cells expressing SPAG9 protein designated as positive in IHC, predicted presence of malignant SGT with 83.72% sensitivity, 100% specificity, 100% PPV and 83.72% NPV. Humoral response against SPAG9 protein was generated in 68% of SGT patients. A cut-off value of 0.212 OD for anti-SPAG9 antibodies in ELISA predicted presence of malignant SGT with 69.23% sensitivity, 100% specificity, 100% PPV and 78.94% NPV. Collectively, our data suggests that the majority of SGT show significant difference and association among benign and malignant tumors for SPAG9 gene and protein expression and also exhibit humoral response against SPAG9 protein. Hence, SPAG9 may be developed as a biomarker for detection and diagnosis of salivary gland tumors. PMID:25941602

Systemic Sclerosis and Malignancy: A Review of Current Data

PubMed Central

Zeineddine, Nabil; Khoury, Lara El; Mosak, Joseph

2016-01-01

Systemic sclerosis (SSc) is associated with increased risk of malignancy. The organ systems most commonly affected are the lungs, the breasts and the hematological system. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. The incidence of malignancies in SSc patients is variable from one report to another, but most importantly, questions regarding the role of immunosuppressive therapies and the effect of autoantibodies have weak or sometimes contradictory answers in most of the currently available literature and physicians have no available guidelines to screen their SSc patients for malignancies. The lack of a concretely defined high-risk profile and the absence of malignancy screening guidelines tailored for SSc patients raise the importance of the need for more studies on the association of SSc and cancer and should incite rheumatology colleges to develop specific recommendations for the clinician to follow while approaching patients with SSc. PMID:27540435

Malignant central airway obstruction

PubMed Central

Mudambi, Lakshmi; Miller, Russell

2017-01-01

This review comprehensively describes recent advances in the management of malignant central airway obstruction (CAO). Malignant CAO can be a dramatic and devastating manifestation of primary lung cancer or metastatic disease. A variety of diagnostic modalities are available to provide valuable information to plan a therapeutic intervention. Clinical heterogeneity in the presentation of malignant CAO provides opportunities to adapt and utilize endoscopic technology and tools in many ways. Mechanical debulking, thermal tools, cryotherapy and airway stents are methods and instruments used to rapidly restore airway patency. Delayed bronchoscopic methods, such as photodynamic therapy (PDT) and brachytherapy can also be utilized in specific non-emergent situations to establish airway patency. Although data regarding the success and complications of therapeutic interventions are retrospective and characterized by clinical and outcome measure variability, the symptoms of malignant CAO can often be successfully palliated. Assessment of risks and benefits of interventions in each individual patient during the decision-making process forms the critical foundation of the management of malignant CAO. PMID:29214067

Solitary pulmonary nodule evaluation in regions endemic for infectious diseases: Do regional variations impact the effectiveness of fluorodeoxyglucose positron emission tomography/computed tomography.

PubMed

Purandare, N C; Pramesh, C S; Agarwal, J P; Agrawal, A; Shah, S; Prabhash, K; Karimundackal, G; Jiwnani, S; Tandon, S; Rangarajan, V

2017-01-01

Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a preferred imaging modality for the evaluation of solitary pulmonary nodule (SPN), particularly in the developed world. Since FDG can concentrate in infective/inflammatory lesions, the diagnostic utility of FDG-PET can be questioned, particularly in regions endemic for infectious decisions. To evaluate the accuracy of FDG-PET/CT in evaluation of SPNs in a population endemic for infectious disease and to assess if regional variations have an impact on its effectiveness. All patients who underwent an FDG/PET-CT with a clinico-radiological diagnosis of SPN categorized as indeterminate were included. Based on a maximum standardized uptake values (SUVmax) cut-off of 2.5, lesions were classified as benign (<2.5) or malignant (>2.5) and compared with gold standard histopathology. The diagnostic accuracy of PET-CT to detect malignancy was calculated. On the basis of final histopathology, lesions were grouped as (a) malignant nodules (b) infective/granulomatous nodules with a specific diagnosis and (c) nonspecific inflammatory nodules. The SUVmaxbetween these groups was compared using nonparametric statistical tests. A total of 191 patients (129 males, 62 females) with a median age of 64 years (range: 36-83) were included. Totally, 144 nodules (75.3%) were malignant and 47 were benign (24.7%). Adenocarcinoma (n = 84) was the most common malignancy. Tuberculosis (n = 16) and nonspecific infections (n = 24) were the two most common benign pathologies. There was a significant overlap in the metabolic uptake of malignant (median SUVmax-11.2, range: 3.3-34.6) and tuberculous nodules (median SUVmax-10.3, range: 2.7-22.5) with no statistically difference between their SUVmaxvalues (P = 0.43). The false-positive rate was 65.2% and the false-negative rate was 5.5%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT for detecting malignancy were 94.4%, 34.7%, 81.9%, 66.6%, and 79.5%, respectively. Though FDG-PET scans show a very high sensitivity for malignant nodules, it has a high false-positive rate and reduced specificity when characterizing SPNs in an infectious endemic region. Physicians must be aware of this limitation in the workup of lung nodules, and regional variations must be considered before further management decisions are taken.

Epstein-Barr virus strains and variations: Geographic or disease-specific variants?

PubMed

Neves, Marco; Marinho-Dias, Joana; Ribeiro, Joana; Sousa, Hugo

2017-03-01

The Epstein-Barr Virus (EBV) is associated with the development of several diseases, including infectious mononucleosis (IM), Burkitt's Lymphoma (BL), Nasopharyngeal Carcinoma, and other neoplasias. The publication of EBV genome 1984 led to several studies regarding the identification of different viral strains. Currently, EBV is divided into EBV type 1 (B95-8 strain) and EBV type 2 (AG876 strain), also known as type A and type B, which have been distinguished based upon genetic differences in the Epstein-Barr nuclear antigens (EBNAs) sequence. Several other EBV strains have been described in the past 10 years considering variations on EBV genome, and many have attempted to clarify if these variations are ethnic or geographically correlated, or if they are disease related. Indeed, there is an increasing interest to describe possible specific disease associations, with emphasis on different malignancies. These studies aim to clarify if these variations are ethnic or geographically correlated, or if they are disease related, thus being important to characterize the epidemiologic genetic distribution of EBV strains on our population. Here, we review the current knowledge on the different EBV strains and variants and its association with different diseases. J. Med. Virol. 89:373-387, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity.

PubMed

Prendergast, Jillian M; Galvao da Silva, Ana Paula; Eavarone, David A; Ghaderi, Darius; Zhang, Mai; Brady, Dane; Wicks, Joan; DeSander, Julie; Behrens, Jeff; Rueda, Bo R

Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug conjugates (ADCs). These ADCs demonstrated in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in STn-expressing tumor xenograft cancer models with no evidence of overt toxicity.

Mathematical modeling of the malignancy of cancer using graph evolution.

PubMed

Gunduz-Demir, Cigdem

2007-10-01

We report a novel computational method based on graph evolution process to model the malignancy of brain cancer called glioma. In this work, we analyze the phases that a graph passes through during its evolution and demonstrate strong relation between the malignancy of cancer and the phase of its graph. From the photomicrographs of tissues, which are diagnosed as normal, low-grade cancerous and high-grade cancerous, we construct cell-graphs based on the locations of cells; we probabilistically generate an edge between every pair of cells depending on the Euclidean distance between them. For a cell-graph, we extract connectivity information including the properties of its connected components in order to analyze the phase of the cell-graph. Working with brain tissue samples surgically removed from 12 patients, we demonstrate that cell-graphs generated for different tissue types evolve differently and that they exhibit different phase properties, which distinguish a tissue type from another.

Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT

PubMed Central

Dong, Aisheng; Wang, Yang; Lu, Jianping; Zuo, Changjing

2016-01-01

Abstract Interpretation of 18F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging. PMID:26975010