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  1. Endogenous and exogenous fluorescence of gastrointestinal tumors: initial clinical observations

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    Borisova, Ekaterina; Plamenova, Lilia; Keremedchiev, Momchil; Vladimirov, Borislav; Avramov, Latchezar

    2013-03-01

    The limitations of standard endoscopy for detection and evaluation of cancerous changes in gastrointestinal tract (GIT) are significant challenge and initiate development of new diagnostic modalities. Therefore many spectral and optical techniques are applied recently into the clinical practice for obtaining qualitatively and quantitatively new data from gastrointestinal neoplasia with different level of clinical applicability and diagnostic success. One of the most promising approaches is fluorescence detection using naturally existing fluorescent molecules or added fluorescent markers. Deltaaminolevulinic acid / protoporphyrin IX is applied for exogenous fluorescent tumor detection in the upper part of gastrointestinal tract. The 5-ALA is administered per os six hours before measurements at dose 20mg/kg weight. Highpower light-emitting diode at 405 nm is used as a source and the excitation light is passed through the light-guide of standard video-endoscopic system to obtain 2-D visualization. Both kinds of spectra - autofluorescence signals and protoporphyrin IX signal are recorded and stored using a fiber-optic microspectrometer, as in endoscopy instrumental channel a fiber is applied to return information about fluorescence signals. In such way 1-D detection and 2-D visualization of the lesions' fluorescence are received. The results from in vivo detection show significant differentiation between normal and abnormal tissues in 1-D spectroscopic regime, but only moderate discrimination in 2-D imaging.

  2. [Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

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    Lyu, J M; Xiong, H C; Wu, B; Zhou, X Q; Hu, J

    2018-02-23

    Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

  3. Laparoscopic microwave thermosphere ablation of malignant liver tumors: an initial clinical evaluation.

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    Berber, Eren

    2016-02-01

    Microwave ablation (MWA) has been recently recognized as a technology to overcome the limitations of radiofrequency ablation. The aim of the current study was to evaluate the safety and efficacy of a new 2.45-GHz thermosphere MWA system in the treatment of malignant liver tumors. This was a prospective IRB-approved study of 18 patients with malignant liver tumors treated with MWA within a 3-month time period. Tumor sizes and response to MWA were obtained from triphasic liver CT scans done before and after MWA. The ablation zones were assessed for complete tumor response and spherical geometry. There were a total of 18 patients with an average of three tumors measuring 1.4 cm (range 0.2-4). Ablations were performed laparoscopically in all, but three patients who underwent combined liver resection. A single ablation was created in 72% and overlapping ablations in 28% of lesions. Total ablation time per patient was 15.6 ± 1.9 min. There was no morbidity or mortality. At 2-week CT scans, there was 100% tumor destruction, with no residual lesions. Roundness indices A, B and transverse were 1.1, 0.9 and 0.9, respectively, confirming the spherical nature of ablation zones. To the best of our knowledge, this is the first report of a new thermosphere MWA technology in the laparoscopic treatment of malignant liver tumors. The results demonstrate the safety of the technology, with satisfactory spherical ablation zones seen on post-procedural CT scans.

  4. Initial assessment of tumor tracking with a gimbaled linac system in clinical circumstances: A patient simulation study

    International Nuclear Information System (INIS)

    Depuydt, Tom; Poels, Kenneth; Verellen, Dirk; Engels, Benedikt; Collen, Christine; Haverbeke, Chloe; Gevaert, Thierry; Buls, Nico; Van Gompel, Gert; Reynders, Truus; Duchateau, Michael; Tournel, Koen; Boussaer, Marlies; Steenbeke, Femke; Vandenbroucke, Frederik; De Ridder, Mark

    2013-01-01

    Purpose: To have an initial assessment of the Vero Dynamic Tracking workflow in clinical circumstances and quantify the performance of the tracking system, a simulation study was set up on 5 lung and liver patients. Methods and materials: The preparatory steps of a tumor tracking treatment, based on fiducial markers implanted in the tumor, were executed allowing pursuit of the tumor with the gimbaled linac and monitoring X-rays acquisition, however, without activating the 6 MV beam. Data were acquired on workflow time-efficiency, tracking accuracy and imaging exposure. Results: The average time between the patient entering the treatment room and the first treatment field was about 9 min. The time for building the correlation model was 3.2 min. Tracking errors of 0.55 and 0.95 mm (1σ) were observed in PAN/TILT direction and a 2D range of 3.08 mm. A skin dose was determined of 0.08 mGy/image, with a source-to-skin distance of 900 mm and kV exposure of 1 mAs. On average 1.8 mGy/min kV skin dose was observed for 1 Hz monitoring. Conclusion: The Vero tracking solution proved to be fully functional and showed performance comparable with other real-time tracking systems

  5. EPID-based in vivo dosimetry for stereotactic body radiotherapy of non-small cell lung tumors: Initial clinical experience.

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    Consorti, R; Fidanzio, A; Brainovich, V; Mangiacotti, F; De Spirito, M; Mirri, M A; Petrucci, A

    2017-10-01

    EPID-based in vivo dosimetry (IVD) has been implemented for stereotactic body radiotherapy treatments of non-small cell lung cancer to check both isocenter dose and the treatment reproducibility comparing EPID portal images. 15 patients with lung tumors of small dimensions and treated with volumetric modulated arc therapy were enrolled for this initial experience. IVD tests supplied ratios R between in vivo reconstructed and planned isocenter doses. Moreover a γ-like analysis between daily EPID portal images and a reference one, in terms of percentage of points with γ-value smaller than 1, P γlevels of 5% for R ratio, P γlevel, and an average P γ90%. Paradigmatic discrepancies were observed in three patients: a set-up error and a patient morphological change were identified thanks to CBCT image analysis whereas the third discrepancy was not fully justified. This procedure can provide improved patient safety as well as a first step to integrate IVD and CBCT dose recalculation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  6. Image-guided radiofrequency ablation of Bosniak category III or IV cystic renal tumors: initial clinical experience

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    Park, Byung Kwan; Kim, Chan Kyo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea); Lee, Hyun Moo [Sungkyunkwan University School of Medicine, Department of Urology, Samsung Medical Center, Seoul (Korea)

    2008-07-15

    The purpose of this study was to assess the efficacy of image-guided radiofrequency (RF) ablation of cystic renal tumors. Between November 2005 and August 2007, computed tomography (CT) or ultrasound-guided RF ablation was performed in nine patients with 14 Bosniak category III (n = 5) or IV (n = 9) cystic renal tumors using an internally cooled RF ablation system. We evaluated the number of sessions, cycles and duration of energy application, treatment results, lesion size change, and complications. Together the cystic renal tumors required 15 sessions and 23 cycles of energy application. The duration of energy application per one tumor ablation ranged from 1 to 12 min (mean 6 min). The last follow-up CT indicated complete coagulation of 14/14 (100%) lesions. None of these tumors had recurred within 1-19 months (mean 8 months). The maximum diameter of the cystic renal tumors was significantly reduced from 2.5 {+-} 0.6 cm before ablation to 1.7 {+-} 0.7 cm at the last follow-up CT (P < 0.01). Complications were pneumothorax (n = 2), inguinal paresthesia (n = 1), and arteriovenous fistula (n = 1). Image-guided RF ablation is an effective treatment for Bosniak category III or IV cystic renal tumors, which might need relatively shorter duration of energy application than purely solid renal tumors of the same size. (orig.)

  7. Image-guided radiofrequency ablation of Bosniak category III or IV cystic renal tumors: initial clinical experience

    International Nuclear Information System (INIS)

    Park, Byung Kwan; Kim, Chan Kyo; Lee, Hyun Moo

    2008-01-01

    The purpose of this study was to assess the efficacy of image-guided radiofrequency (RF) ablation of cystic renal tumors. Between November 2005 and August 2007, computed tomography (CT) or ultrasound-guided RF ablation was performed in nine patients with 14 Bosniak category III (n = 5) or IV (n = 9) cystic renal tumors using an internally cooled RF ablation system. We evaluated the number of sessions, cycles and duration of energy application, treatment results, lesion size change, and complications. Together the cystic renal tumors required 15 sessions and 23 cycles of energy application. The duration of energy application per one tumor ablation ranged from 1 to 12 min (mean 6 min). The last follow-up CT indicated complete coagulation of 14/14 (100%) lesions. None of these tumors had recurred within 1-19 months (mean 8 months). The maximum diameter of the cystic renal tumors was significantly reduced from 2.5 ± 0.6 cm before ablation to 1.7 ± 0.7 cm at the last follow-up CT (P < 0.01). Complications were pneumothorax (n = 2), inguinal paresthesia (n = 1), and arteriovenous fistula (n = 1). Image-guided RF ablation is an effective treatment for Bosniak category III or IV cystic renal tumors, which might need relatively shorter duration of energy application than purely solid renal tumors of the same size. (orig.)

  8. Tumor markers in clinical oncology

    International Nuclear Information System (INIS)

    Novakovic, S.

    2004-01-01

    The subtle differences between normal and tumor cells are exploited in the detection and treatment of cancer. These differences are designated as tumor markers and can be either qualitative or quantitative in their nature. That means that both the structures that are produced by tumor cells as well as the structures that are produced in excessive amounts by host tissues under the influence of tumor cells can function as tumor markers. Speaking in general, the tumor markers are the specific molecules appearing in the blood or tissues and the occurrence of which is associated with cancer. According to their application, tumor markers can be roughly divided as markers in clinical oncology and markers in pathology. In this review, only tumor markers in clinical oncology are going to be discussed. Current tumor markers in clinical oncology include (i) oncofetal antigens, (ii) placental proteins, (iii) hormones, (iv) enzymes, (v) tumor-associated antigens, (vi) special serum proteins, (vii) catecholamine metabolites, and (viii) miscellaneous markers. As to the literature, an ideal tumor marker should fulfil certain criteria - when using it as a test for detection of cancer disease: (1) positive results should occur in the early stages of the disease, (2) positive results should occur only in the patients with a specific type of malignancy, (3) positive results should occur in all patients with the same malignancy, (4) the measured values should correlate with the stage of the disease, (5) the measured values should correlate to the response to treatment, (6) the marker should be easy to measure. Most tumor markers available today meet several, but not all criteria. As a consequence of that, some criteria were chosen for the validation and proper selection of the most appropriate marker in a particular malignancy, and these are: (1) markers' sensitivity, (2) specificity, and (3) predictive values. Sensitivity expresses the mean probability of determining an elevated tumor

  9. Initiation of universal tumor screening for Lynch syndrome in colorectal cancer patients as a model for the implementation of genetic information into clinical oncology practice.

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    Cohen, Stacey A; Laurino, Mercy; Bowen, Deborah J; Upton, Melissa P; Pritchard, Colin; Hisama, Fuki; Jarvik, Gail; Fichera, Alessandro; Sjoding, Britta; Bennett, Robin L; Naylor, Lorraine; Jacobson, Angela; Burke, Wylie; Grady, William M

    2016-02-01

    Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but the implementation can be complex. This article describes the evaluation, process development, and initiation of Lynch syndrome UTS at a tertiary referral cancer center. A multidisciplinary team developed the new process design. Issues in 5 themes were noted: timing, funding, second-opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process-improvement development. The issues related to testing were addressed individually for the successful implementation of UTS at the institutional level. In the conventional-care period, 9 of 30 cases (30%) received Lynch syndrome screening, and 4 cases were referred to medical genetics. During the 6 months following the implementation of UTS, 32 of 44 patients (73%) received Lynch syndrome screening. The 13 unscreened patients all had identified reasons for nonscreening (eg, financial limitations). Ten patients were referred to medical genetics, which identified no new cases of Lynch syndrome, but a low-risk adenomatous polyposis coli (APC) variant was detected in 1 individual. The implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. This experience with the assessment and management of issues relevant to the successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, and this is highly relevant in the current era of rapidly evolving genomic technology. © 2015 American Cancer Society.

  10. Mesenchymal stem cells cancel azoxymethane-induced tumor initiation.

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    Nasuno, Masanao; Arimura, Yoshiaki; Nagaishi, Kanna; Isshiki, Hiroyuki; Onodera, Kei; Nakagaki, Suguru; Watanabe, Shuhei; Idogawa, Masashi; Yamashita, Kentaro; Naishiro, Yasuyoshi; Adachi, Yasushi; Suzuki, Hiromu; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

    2014-04-01

    The role of mesenchymal stem cells (MSCs) in tumorigenesis remains controversial. Therefore, our goal was to determine whether exogenous MSCs possess intrinsic antineoplastic or proneoplastic properties in azoxymethane (AOM)-induced carcinogenesis. Three in vivo models were studied: an AOM/dextran sulfate sodium colitis-associated carcinoma model, an aberrant crypt foci model, and a model to assess the acute apoptotic response of a genotoxic carcinogen (AARGC). We also performed in vitro coculture experiments. As a result, we found that MSCs partially canceled AOM-induced tumor initiation but not tumor promotion. Moreover, MSCs inhibited the AARGC in colonic epithelial cells because of the removal of O(6)-methylguanine (O(6) MeG) adducts through O(6) MeG-DNA methyltransferase activation. Furthermore, MSCs broadly affected the cell-cycle machinery, potentially leading to G1 arrest in vivo. Coculture of IEC-6 rat intestinal cells with MSCs not only arrested the cell cycle at the G1 phase, but also induced apoptosis. The anti-carcinogenetic properties of MSCs in vitro required transforming growth factor (TGF)-β signaling because such properties were completely abrogated by absorption of TGF-β under indirect coculture conditions. MSCs inhibited AOM-induced tumor initiation by preventing the initiating cells from sustaining DNA insults and subsequently inducing G1 arrest in the initiated cells that escaped from the AARGC. Furthermore, tumor initiation perturbed by MSCs might potentially dysregulate WNT and TGF-β-Smad signaling pathways in subsequent tumorigenesis. Obtaining a better understanding of MSC functions in colon carcinogenesis is essential before commencing the broader clinical application of promising MSC-based therapies for cancer-prone patients with inflammatory bowel disease. © AlphaMed Press.

  11. Targeting sarcoma tumor-initiating cells through differentiation therapy

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    Dan Han

    2017-05-01

    Full Text Available Human leukocyte antigen class I (HLA-I down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.

  12. Initiative action of tumor-associated macrophage during tumor metastasis

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    Saroj Singh

    2017-06-01

    In this review article, we present an overview of mechanisms responsible for TAMs recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. We describe the interplay between Th17 cells and other immune cells in the tumor microenvironment, and we assess both the potential antitumorigenic and pro-tumorigenic activities of Th17 cells and their associated cytokines. Understanding the nature of Th17 cell responses in the tumor microenvironment will be important for the design of more efficacious cancer immunotherapies. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

  13. Circulating tumor cells: clinical validity and utility.

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    Cabel, Luc; Proudhon, Charlotte; Gortais, Hugo; Loirat, Delphine; Coussy, Florence; Pierga, Jean-Yves; Bidard, François-Clément

    2017-06-01

    Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

  14. The problem: Tumor radioresistance in clinical radiotherapy

    International Nuclear Information System (INIS)

    Peters, L.J.; Withers, H.R.; Thames, H.D.; Fletcher, G.H.; M.D. Anderson Hospital and Tumor Inst., Houston, TX)

    1983-01-01

    Tumor radioresistance in clinical radiotherapy implies failure to achieve local-regional disease control with radiation doses producing an acceptable degree of morbidity. Such radioresistance may be due to many different causes (biological and technical) which are reviewed in terms of possible remedial actions. Dose-response relationships for human cancers suggest that, in many sites, tumors are heterogeneous with respect to their cure-limiting characteristics. The case is developed that unless the predominant cure-limiting factor can be predicted, little benefit may be seen in trials of new treatment strategies using heterogeneous tumor populations. The fundamental problem of clinical radioresistance is therefore perceived as the inability to identify predictively its cause in the individual patient

  15. Clinical Presentation and Diagnosis of Neuroendocrine Tumors.

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    Vinik, Aaron I; Chaya, Celine

    2016-02-01

    Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

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    Ganapati V Hegde

    Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

  17. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

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    Yonatan Y Mahller

    Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

  18. Testicular tumors - clinical aspects and therapy

    International Nuclear Information System (INIS)

    Hirschmann, K.E.

    1981-01-01

    In this study the author reports about classification, clinical experience, therapy and therapeutic results of testicular tumors on the basis of results given in literature and of own investigations performed at the Clinic and Policlinic for Radiotherapy at Wuerzburg. In total, 97 patients with testicular tumors were examined and their cases analysed. These patients had received radiotherapy between January 1, 1962 and December 31, 1979. The difficulties with the intended classification of testicular tumors and the advantages and disadvantages of the individual nomenclatures are described. Consideration of the affected age-groups showed that this disease concerns mainly younger males with a high life expectancy. The study depicts the relatively discrete symptoms and signs and the difficulties connected with clinical diagnosis. A more generous indication for the exposition of the testicles is demanded. Also the lymphatic drainage of the testicular region, the resulting paths of metastatic spread and the difficulties connected with the lymphographic detection of metastases are described. There are three therapeutic measures: surgical intervention, radiotherapy and cytostatic treatment. With seminomas mandatory semitestectomy and radiotherapy will suffice; with other affections than seminomas, semitestectomy shall be followed by a combined therapy comprising removal of lymphatic nodes and cytostatic treatment and not so much radiotherapy. The results of treatment given in literature are compared with the own results. This comparison revealed good success with treatment of seminomas. With non-seminomal affections exclusive radiotherapy appears to be insufficient. Therefore a combined therapy is postulated, which must be rendered possible by a good interdisciplinary cooperation of pathologists, urologists and radiologists. (orig.) [de

  19. Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

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    Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

  20. Pyrrolizidine Alkaloids: Metabolic Activation Pathways Leading to Liver Tumor Initiation.

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    Fu, Peter P

    2017-01-17

    Pyrrolizidine alkaloids (PAs) and PA N-oxides are a class of phytochemical carcinogens contained in over 6000 plant species spread around the world. It has been estimated that approximately half of the 660 PAs and PA N-oxides that have been characterized are cytotoxic, genotoxic, and tumorigenic. It was recently determined that a genotoxic mechanism of liver tumor initiation mediated by PA-derived DNA adducts is a common metabolic activation pathway of a number of PAs. We proposed this set of PA-derived DNA adducts could be a common biological biomarker of PA exposure and a potential biomarker of PA-induced liver tumor formation. We have also found that several reactive secondary pyrrolic metabolites can dissociate and interconvert to other secondary pyrrolic metabolites, resulting in the formation of the same exogenous DNA adducts. This present perspective reports the current progress on these new findings and proposes future research needed for obtaining a greater understanding of the role of this activation pathway and validating the use of this set of PA-derived DNA adducts as a biological biomarker of PA-induced liver tumor initiation.

  1. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

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    Testa, Ugo; Pelosi, Elvira; Castelli, Germana

    2018-04-13

    Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

  2. Imaging of tumor viability in lung cancer. Initial results using 23Na-MRI

    International Nuclear Information System (INIS)

    Henzler, T.; Apfaltrer, P.; Haneder, S.; Schoenberg, S.O.; Fink, C.; Konstandin, S.; Schad, L.; Schmid-Bindert, G.; Manegold, C.; Wenz, F.

    2012-01-01

    23 Na-MRI has been proposed as a potential imaging biomarker for the assessment of tumor viability and the evaluation of therapy response but has not yet been evaluated in patients with lung cancer. We aimed to assess the feasibility of 23 Na-MRI in patients with lung cancer. Three patients with stage IV adenocarcinoma of the lung were examined on a clinical 3 Tesla MRI system (Magnetom TimTrio, Siemens Healthcare, Erlangen, Germany). Feasibility of 23 Na-MRI images was proven by comparison and fusion of 23 Na-MRI with 1 H-MR, CT and FDG-PET-CT images. 23 Na signal intensities (SI) of tumor and cerebrospinal fluid (CSF) of the spinal canal were measured and the SI ratio in tumor and CSF was calculated. One chemonaive patient was examined before and after the initiation of combination therapy (Carboplatin, Gemcitabin, Cetuximab). All 23 Na-MRI examinations were successfully completed and were of diagnostic quality. Fusion of 23 Na-MRI images with 1 H-MRI, CT and FDG-PET-CT was feasible in all patients and showed differences in solid and necrotic tumor areas. The mean tumor SI and the tumor/CSF SI ratio were 13.3 ± 1.8 x 103 and 0.83 ± 0.14, respectively. In necrotic tumors, as suggested by central non-FDG-avid areas, the mean tumor SI and the tumor/CSF ratio were 19.4 x 103 and 1.10, respectively. 23 Na-MRI is feasible in patients with lung cancer and could provide valuable functional molecular information regarding tumor viability, and potentially treatment response. (orig.)

  3. Ovarian tumor-initiating cells display a flexible metabolism

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    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  4. Ovarian tumor-initiating cells display a flexible metabolism

    International Nuclear Information System (INIS)

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-01-01

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L FFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

  5. Breast tomosynthesis in clinical practice: initial results

    International Nuclear Information System (INIS)

    Teertstra, Hendrik J.; Loo, Claudette E.; Bosch, Maurice A.A.J. van den; Muller, Sara H.; Gilhuijs, Kenneth G.A.; Tinteren, Harm van; Rutgers, Emiel J.T.

    2010-01-01

    The purpose of this study was to assess the potential value of tomosynthesis in women with an abnormal screening mammogram or with clinical symptoms. Mammography and tomosynthesis investigations of 513 woman with an abnormal screening mammogram or with clinical symptoms were prospectively classified according to the ACR BI-RADS criteria. Sensitivity and specificity of both techniques for the detection of cancer were calculated. In 112 newly detected cancers, tomosynthesis and mammography were each false-negative in 8 cases (7%). In the false-negative mammography cases, the tumor was detected with ultrasound (n=4), MRI (n=2), by recall after breast tomosynthesis interpretation (n=1), and after prophylactic mastectomy (n=1). Combining the results of mammography and tomosynthesis detected 109 cancers. Therefore in three patients, both mammography and tomosynthesis missed the carcinoma. The sensitivity of both techniques for the detection of breast cancer was 92.9%, and the specificity of mammography and tomosynthesis was 86.1 and 84.4%, respectively. Tomosynthesis can be used as an additional technique to mammography in patients referred with an abnormal screening mammogram or with clinical symptoms. Additional lesions detected by tomosynthesis, however, are also likely to be detected by other techniques used in the clinical work-up of these patients. (orig.)

  6. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-01-01

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  7. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  8. The clinical factors associated with benign renal tumors

    International Nuclear Information System (INIS)

    Yamashita, Ryo; Nakamura, Masafumi; Matsuzaki, Masato; Matsui, Takashi; Yamaguchi, Raizo; Niwakawa, Masashi; Tobisu, Kenichi; Asakura, Koiku; Ito, Ichiro

    2009-01-01

    In this study, we sought to define the incidence of benign renal tumors in our institute and to clarify the clinical factors associated with benign renal tumors, in order to assist in forming preoperative differential diagnoses. From October 2002 to July 2007, we performed 157 nephrectomies in patients preoperatively diagnosed with renal cell carcinoma. We chose 81 tumors, all of which were less than 5 cm, for further study. We reviewed double-phase helical CT imaging retrospectively, specifically focusing on attenuation patterns and homogeneity. We also compared clinical factors, including age, sex and tumor size, between the benign and malignant renal tumors. The patient's median age was 67 years (mean age, 63 years), and the median tumor diameter was 3.0 cm (mean, 3.2 cm). Benign renal tumors were found in 10 (12%) of the 81 tumors; these included seven cases of oncocytoma and three cases of angiomyolipoma with minimal fat. Several factors were significant clinical determinants of differentiation between benign and malignant renal tumors: homogeneity in CT, female gender, and small tumor size all predominated in cases of benign tumors. Attenuation pattern in CT, however, was not a significant factor (p=0.344). When a patient, especially a female, presents with a small and homogeneous renal tumor, careful consideration should be given to the possibility of a benign process, which needs further consideration before performing excessive surgery. (author)

  9. Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): Report of the Clinical Spectrum of 3 Cases.

    Science.gov (United States)

    Singh, Arun D; Soto, Hansell; Bellerive, Claudine; Biscotti, Charles V

    2017-09-01

    To report 3 cases providing insight into clinical progression of reactive retinal astrocytic tumor. The clinical, imaging, and when available, the cytologic features of 3 cases of reactive retinal astrocytic tumor (focal nodular gliosis) were reviewed. A 6-year-old female, a 49-year-old man, and a 39-year-old man each developed a white retinal mass associated with laser photocoagulation, lattice degeneration, and treatment of a presumed vascular tumor, respectively. All tumors were white, circumscribed retinal masses that tended to be associated with exudation and either initially or eventually minimal vascularity. Reactive retinal astrocytic tumor can be observed in response to a degenerative, inflammatory, or ischemic retinal insult. Such tumors may progress after therapeutic intervention.

  10. A Giant Heart Tumor in Neonate with Clinical Signs of Pierre - Robin Syndrome

    Science.gov (United States)

    Bejiqi, Ramush; Retkoceri, Ragip; Xhema-Bejiqi, Hana; Bejiqi, Rinor; Maloku, Arlinda

    2017-01-01

    Introduction: Pierre Robin syndrome is a congenital condition of facial abnormalities in humans. The three main features are: cleft palate, retrognathia and glossoptosis. Rarely heart tumors are associated with syndromes, mostly are isolated. Case report: In this presentation we describe a 3-weeks-old girl with Pierre-Robin syndrome and giant left ventricle tumor, diagnosed initially by transthoracic echocardiography. The purpose of this report is to review the literature on the fetuses and neonates with cardiac tumors in an attempt to determine the various ways which cardiac tumors differ clinically and morphologically in this age group. PMID:28790548

  11. Role of stem cells in tumor initiation, metastasis formation and their use in cancer therapy

    International Nuclear Information System (INIS)

    Altaner, C.; Altanerova, V.

    2010-01-01

    This review considers recent advances in the stem cell field focusing on the challenges and opportunities for their use in clinical practice. Various kinds of stem cells and their roles in the human organism are in the review described. Attention is given to the role of mesenchymal stem cells as a potential tool in regenerative medicine. The origin and consequences of existence of tumor-initiating cells known as cancer stem cells is discussed also in context of metastasis formation. It seems that tumor-initiating cells might be responsible for resistance to many conventional cancer therapies, which might explain the limitations of these therapeutic modalities. Furthermore, the review focuses to tumor homing property of adult mesenchymal (stromal) stem cells. The feasibility of mesenchymal stem cells isolation from human adipose tissue, their genetic modifications with suicide genes together with ability to find tumor in the organism make them an attractive vehicle for cancer therapy without systemic toxicity. Published achievements from our laboratory in stem cell-based gene cancer therapy are shortly summarized. Generally, it is believed that the stem cell therapies might be ideal future treatment modality for inherited, degenerative diseases and in curing human malignancies as well. (author)

  12. Percutaneous fiducial marker placement prior to stereotactic body radiotherapy for malignant liver tumors: an initial experience

    International Nuclear Information System (INIS)

    Ohta, Kengo; Shimohira, Masashi; Murai, Taro; Nishimura, Junichi; Iwata, Hiromitsu; Ogino, Hiroyuki; Hashizume, Takuya; Shibamoto, Yuta

    2016-01-01

    The aim of this study was to describe our initial experience with a gold flexible linear fiducial marker and to evaluate the safety and technical and clinical efficacy of stereotactic body radiotherapy using this marker for malignant liver tumors. Between July 2012 and February 2015, 18 patients underwent percutaneous fiducial marker placement before stereotactic body radiotherapy for malignant liver tumors. We evaluated the technical and clinical success rates of the procedure and the associated complications. Technical success was defined as successful placement of the fiducial marker at the target site, and clinical success was defined as the completion of stereotactic body radiotherapy without the marker dropping out of position. All 18 fiducial markers were placed successfully, so the technical success rate was 100% (18/18). All 18 patients were able to undergo stereotactic body radiotherapy without marker migration. Thus, the clinical success rate was 100% (18/18). Slight pneumothorax occurred as a minor complication in one case. No major complications such as coil migration or bleeding were observed. The examined percutaneous fiducial marker was safely placed in the liver and appeared to be useful for stereotactic body radiotherapy for malignant liver tumors

  13. Rectal prolapse as initial clinical manifestation of colon cancer.

    Science.gov (United States)

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  14. CLINICAL ASPECTS OF TRANSMISSIBLE VENEREAL TUMOR

    Directory of Open Access Journals (Sweden)

    A. C. Sá

    2016-07-01

    Full Text Available The transmissible venereal tumor is among the main diseases that affect domestic animals of the Canidae family. Abandoned animals are the main transmitters of the disease, which is highly contagious; most of the injuries are commonly found on animals genital organs and faces. This is a tumor without any involvement with an infectious agent, tumor cells are transferred from a sick animal to a healthy animal through natural breeding or direct contact of the lesions with other body parts. The disease has no predisposition for breeding, sex and species, therefore possibly affecting all canids although there are more reports on stray animals.The TVT lesions have cauliflower appearance and may be pedunculated, papillary or multilobulated, with hemorrhagic and crumbly aspect. The tumor can have benign or malignant potential, being the second most frequently commonly reported, wherein according to its potential raise the difficulty of the treatment or not.

  15. [Initiation, promotion, initiation experiments with radon and cigarette smoke: Lung tumors in rats]. Progress report

    International Nuclear Information System (INIS)

    Moolgavkar, S.H.

    1994-01-01

    During the past several years, the authors have made considerable progress in modeling carcinogenesis in general, and in modeling radiation carcinogenesis, in particular. They present an overview of their progress in developing stochastic carcinogenesis models and applying them to experimental and epidemiologic data sets. Traditionally, cancer models have been used for the analysis of incidence (or prevalence) data in epidemiology and time to tumor data in experimental studies. The relevant quantities for the analysis of these data are the hazard function and the probability of tumor. The derivation of these quantities is briefly described here. More recently, the authors began to use these models for the analysis of data on intermediate lesions on the pathway to cancer. Such data are available in experimental carcinogenesis studies, in particular in initiation and promotion studies on the mouse skin and the rat liver. If however, quantitative information on intermediate lesions on the pathway to lung cancer were to be come available at some future date, the methods that they have developed for the analysis of initiation-promotion experiments could easily be applied to the analysis of these lesions. The mathematical derivations here are couched in terms of a particular two-mutation model of carcinogenesis. Extension to models postulating more than two mutations is not always straightforward

  16. Fatal tumors: prenatal ultrasonographic findings and clinical characteristics

    International Nuclear Information System (INIS)

    Cho, Jeong Yeon; Lee, Young Ho

    2014-01-01

    The incidence of fetal tumors has been increased due to generalization of prenatal evaluation and improvement of imaging techniques. The early detection of a fetal tumor and understanding of its imaging features are very important for fetal, maternal, and neonatal care. Ultrasonography is usually used for the detection and differential diagnosis of fetal tumors, and magnetic resonance imaging is increasingly being used as a complementary study. Many fetal tumors have different clinical and imaging features compared with pediatric tumors. Although several fetal tumors may mimic other common anomalies, some specific imaging features may carry early accurate diagnosis of fetal tumors, which may alter the prenatal management of a pregnancy and the mode of delivery, and facilitate immediate postnatal treatment.

  17. Fatal tumors: prenatal ultrasonographic findings and clinical characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jeong Yeon [Dept. of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Young Ho [Dept. of Radiology, Cheil General Hospital and Women' s Healthcare Center, Kwandong University College of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    The incidence of fetal tumors has been increased due to generalization of prenatal evaluation and improvement of imaging techniques. The early detection of a fetal tumor and understanding of its imaging features are very important for fetal, maternal, and neonatal care. Ultrasonography is usually used for the detection and differential diagnosis of fetal tumors, and magnetic resonance imaging is increasingly being used as a complementary study. Many fetal tumors have different clinical and imaging features compared with pediatric tumors. Although several fetal tumors may mimic other common anomalies, some specific imaging features may carry early accurate diagnosis of fetal tumors, which may alter the prenatal management of a pregnancy and the mode of delivery, and facilitate immediate postnatal treatment.

  18. Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

    Directory of Open Access Journals (Sweden)

    George D. Cresswell

    2016-07-01

    Full Text Available The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT; current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.

  19. MR imaging-guided percutaneous cryotherapy for lung tumors: initial experience.

    Science.gov (United States)

    Liu, Shangang; Ren, Ruimei; Liu, Ming; Lv, Yubo; Li, Bin; Li, Chengli

    2014-09-01

    To evaluate prospectively the initial clinical experience of magnetic resonance (MR) imaging-guided percutaneous cryotherapy of lung tumors. MR imaging-guided percutaneous cryotherapy was performed in 21 patients with biopsy-proven lung tumors (12 men, 9 women; age range, 39-79 y). Follow-up consisted of contrast-enhanced chest computed tomography (CT) scan performed at 3-month intervals to assess tumor control; CT scanning was carried out for 12 months or until death. Cryotherapy procedures were successfully completed in all 21 patients. Pneumothorax occurred in 7 (33.3%) of 21 patients. Chest tube placement was required in one (4.8%) case. Hemoptysis was exhibited by 11 (52.4%) patients, and pleural effusion occurred in 6 (28.6%) patients. Other complications were observed in 14 (66.7%) patients. The mean follow-up period was 10.5 months (range, 9-12 mo) in patients who died. At month 12 of follow-up, 7 (33.3%) patients had a complete response to therapy, and 10 (47.6%) patients showed a partial response. In addition, two patients had stable disease, and two patients developed progressive disease; one patient developed a tumor in the liver, and the other developed a tumor in the brain. The 1-year local control rate was 81%, and 1-year survival rate was 90.5%. MR imaging-guided percutaneous cryotherapy appears feasible, effective, and minimally invasive for lung tumors. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

  20. Desmoid tumors: clinical features and treatment options: a case ...

    African Journals Online (AJOL)

    Desmoid tumors: clinical features and treatment options: a case report and a review of literature. Amel Achour Jenayah, Hajer Bettaieb, Sarra Saoudi, Anissa Gharsa, Ezzeddine Sfar, Fethia Boudaya, Dalenda Chelli ...

  1. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    2011-01-01

    Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

  2. Clinical implications of heterogeneity of tumor response to radiation therapy

    International Nuclear Information System (INIS)

    Suit, H.; Skates, S.; Taghian, A.; Okunieff, P.; Efird, J.T.

    1992-01-01

    Heterogeneity of response of tumor tissue to radiation clearly exists. Major parameters include histopathologic type, size (number of tumor rescue units (TRUs)), hemoglobin concentration, cell proliferation kinetics and immune rejection reaction by host. Further, normal and presumably tumor tissue response is altered in certain genetic diseases, e.g. ataxia telangiectasia. Any assessment of response of tumor tissue to a new treatment method or the testing of a new clinical response predictor is optimally based upon a narrow strata, viz., uniform with respect to known parameters of response, e.g. size, histological type. Even among tumors of such a clinical defined narrow strata, there will be residual heterogeneity with respect to inherent cellular radiation sensitivity, distributions of pO 2 , (SH), cell proliferation, etc. (author). 39 refs., 7 figs., 3 tabs

  3. Harnessing naturally occurring tumor immunity: a clinical vaccine trial in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Mayu O Frank

    2010-09-01

    Full Text Available Studies of patients with paraneoplastic neurologic disorders (PND have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC vaccine.We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002, decrease in prostate specific antigen (PSA slope (p = 0.016, and a two-fold increase in PSA doubling time (p = 0.003 were identified when we compared data before and after vaccination.An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine.ClinicalTrials.gov NCT00289341.

  4. Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

    Science.gov (United States)

    Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

    2016-01-01

    Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

  5. Endocrine tumor of the digestive tract - clinical case study

    International Nuclear Information System (INIS)

    Szwedziak, K.; Olejniczak, W.; Brichkovkiy, V.

    2008-01-01

    Introduction: Endocrine tumors of the digestive tract (ETDT) are neoplasms which stem from the APUD (amine precursors uptake and decarboxylation) cells. There are neuroendocrine pancreatic and gastroenteral carcinoid tumors which stand for 2% of digestive tract tumors, 0,5% of all human malignant neoplasms. All of them have secretion granulations in the cytoplasm. That is why a number of immune histochemic techniques is used in search for biogenic amines and hormones such as gastrin, CCK, GIP, VIP, motilin, glucagon, GRP, PP, GHRH and the others. In the majority of cases neuroendocrine tumors of the rectum are described as dysfunctional, which means that specific clinical symptoms are not connected with their hormonal overproduction. Material and methods: We describe a case of fifty seven years old male patient admitted to the Department of General and Transplant Surgery for the diagnosis and treatment of the rectal tumor. Per rectum examination revealed hard tumor. The pathologic examination of the biopsy taken from the lesion and CT scanning confirmed the presence of endocrine tumor of the digestive tract. Results: Anterior resection of the rectum was performed, the postoperative course was uneventful. At present patient is subjected to complementary treatment with the use of somatostatin analogue of the prolonged action. Conclusion: The endocrine tumors of the rectum are extremely rare, they occur in this localization in 0,26-0,52 out of 100.000 all rectal tumors. Diagnosis is usually made upon the microscopic examination and the immune histochemic reactions. (author)

  6. Clinical results of BNCT for malignant brain tumors in children

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Kageji, Teruyoshi; Mizobuchi, Yoshifumi; Kumada, Hiroaki; Nakagawa, Yoshiaki

    2009-01-01

    It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

  7. Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston MA, 02215 (United States); Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States); Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States)

    2017-03-15

    Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

  8. Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

    International Nuclear Information System (INIS)

    Nishino, Mizuki; Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra; Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto; Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin

    2017-01-01

    Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

  9. Assessing the clinical significance of tumor markers in common neoplasms.

    Science.gov (United States)

    Beketic-Oreskovic, Lidija; Maric, Petra; Ozretic, Petar; Oreskovic, Darko; Ajdukovic, Mia; Levanat, Sonja

    2012-06-01

    The term tumor markers include a spectrum of molecules and substances with widely divergent characteristics whose presence in the significant amount can be related to the malignant disease. An ideal tumor marker should have high specificity and sensitivity, which would allow its use in early diagnosis and prognosis of malignant disease, as well as in prediction of therapeutic response and follow-up of the patients. Numerous biochemical entities have emerged as potentially valuable tumor markers so far, but only few markers showed to be of considerable clinical reliability and have been accepted into standard clinical practice. Recent development of genomics and proteomics has enabled the examination of many new potential tumor markers. Scientific studies on discovery, development, and application of tumor markers have been proceeding quite rapidly providing great opportunities for improving the management of cancer patients. This review is focusing on the clinical usefulness of various tumor markers already in clinical practice as well as certain potential markers, giving a brief description of their prognostic and predictive significance in most common malignancies.

  10. Circulating tumor cell isolation and diagnostics: toward routine clinical use

    NARCIS (Netherlands)

    Stolpe, van de A.; Pantel, K.; Sleijfer, S.; Terstappen, L.W.; Toonder, den J.M.J.

    2011-01-01

    From February 7–11, 2011, the multidisciplinary Lorentz Workshop Circulating Tumor Cell (CTC) Isolation and Diagnostics: Toward Routine Clinical Use was held in Leiden (The Netherlands) to discuss progress and define challenges and potential solutions for development of clinically useful circulating

  11. Clinical application and research of tumor markers in colorectal cancer

    International Nuclear Information System (INIS)

    Chen Yumei

    2005-01-01

    Colorectal cancer is one of the most common malignant tumors. There are many tumor markers for detecting colorectal cancer, some of which have been widely used in clinical area. However, still lack an ideal tumor marker of colorectal cancer. In this review, we simply characterized some common tumor markers including carcinoembryonic antigen, CA19-9, CA50, CA242 etc and their dignostic value. And here we discussed some combined detecting procedures which improve diagnostic accuracy of colorectal cancer. In addition, with the development of the biomoleculer technique, some newly discovered tumor markers and genetic marekers have gained great progress in the research of colorectal cancer, and will become a promissing technique in the diagnosis of colorectal cancer. (authors)

  12. Initial treatment results using cyberknife for head and neck tumor

    International Nuclear Information System (INIS)

    Himei, Kengo; Katsui, Kuniaki; Yoshida, Atsushi; Takemoto, Mitsuhiro; Kobayashi, Mitsuru; Kuroda, Masahiro; Hiraki, Yoshio

    2002-01-01

    The CyberKnife, a medical device for stereotactic radiotherapy, is composed of a combination of a robot manipulator and LINAC. For the treatment of head and neck tumors, this system has been applied. Between June 2000 and January 2001, 18 patients with head and neck tumor were treated with this system because of tumor recurrence, difficulty in surgery or additional increase after external radiotherapy. The median age was 64 years. Primary lesions were skull base (4), nasopharynx (3), paranasal sinus (3), nasal cavity (2), lacrimal gland (1), oropharynx (1), oral floor (1), and buccul mucosa (1), metastatic lymph nodes were found in three. The prescribed dose was 12-38 Gy as for marginal dose. The response rate (CR+PR) was 44.4% and local control rate (CR+PR+NC) was 77.8%. The adverse effects were assessed by the NCI-CTC Version 2.0 and observed grade 3 in two cases. Our early experience indicates that this system could to be feasible for the treatment of locally advanced or recurrent head and neck tumor, and for the reduction of adverse effect and maintenance of useful QOL of patients. (author)

  13. Clinical studies of 57Co-BLM for tumor detection

    International Nuclear Information System (INIS)

    Lee, Jhin Oh; Ryu, Yong Wun; Kim, Jang Hee

    1986-12-01

    Investigation with 57 Co-Bleomycin in patients with the various cancers and in tumor bearing animals are described. In the patients, 57 Co-Bleomycin appears to be one of the useful tumor-seeking radiopharmaceuticals, and worth applicable to clinical uses. Labelled yield of 57 Co-Bleo. was about 97% by thin layer chromatography. The pyrogen free tests were performed to meet U.S.P. critical ranges. In clinical studies with 57 Co-Bleo, 4 cases out of 5 patients with lung cancer, 2 cases among 3 thyroid cancer patients, and all 3 hepatoma patients showed positive tumor scans. The patients with stomach cancer, and the esophageal cancer showed false negative scintigraphy. A case with pulmonary tuberculosis showed a positive scan while liver abscess showed a negative picture. The merits of 57 Co-Bleomycin scintigraphy seems to be its relatively high affinity to tumors and low radiation hazard in spite of long physical half life. (Author)

  14. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer.

    Science.gov (United States)

    Riva, Francesca; Dronov, Oleksii I; Khomenko, Dmytro I; Huguet, Florence; Louvet, Christophe; Mariani, Pascale; Stern, Marc-Henri; Lantz, Olivier; Proudhon, Charlotte; Pierga, Jean-Yves; Bidard, Francois-Clement

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. Prospective Clinical Study of Precision Oncology in Solid Tumors.

    Science.gov (United States)

    Sohal, Davendra P S; Rini, Brian I; Khorana, Alok A; Dreicer, Robert; Abraham, Jame; Procop, Gary W; Saunthararajah, Yogen; Pennell, Nathan A; Stevenson, James P; Pelley, Robert; Estfan, Bassam; Shepard, Dale; Funchain, Pauline; Elson, Paul; Adelstein, David J; Bolwell, Brian J

    2015-11-09

    Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Maxillary brown tumor as initial presentation of parathyroid adenoma: A case report

    Directory of Open Access Journals (Sweden)

    Hon-Ke Sia

    2012-07-01

    Full Text Available Brown tumor is a rare late-stage skeletal change caused by long-term stimulation of excess parathyroid hormone. It is not neoplastic, but a reparative cellular process. Common sites of brown tumor are the ribs, clavicle, long bones and pelvic girdle. Solitary maxillary brown tumor as initial presentation of primary hyperparathyroidism is rare; it is often accompanied by brown tumors of the other facial bones. Here, we present the first case of solitary maxillary brown tumor in a 29-year-old ethnic Chinese woman with initial presentation of a large tumor filling the left maxillary sinus. Underlying long-standing primary hyperparathyroidism caused by a large parathyroid adenoma was finally diagnosed. Brown tumor tends to be misdiagnosed as malignancy, and delayed diagnosis of the underlying hyperparathyroidism is common. Our case validates the suggestion that young women have a higher probability of brown tumor. Biopsy of the suspicious bone tumor and blood tests for calcium and parathyroid hormone level are crucial and essential to reach the correct diagnosis. Most brown tumors show spontaneous regression after parathyroidectomy. However, direct excision of the brown tumor may be indicated to avoid the risk of facial deformity and orbital compression at a special anatomical site, as in our case.

  17. Brown tumors of the anterior skull base as the initial manifestation of true normocalcemic primary hyperparathyroidism: report of three cases and review of the literature.

    Science.gov (United States)

    Khalatbari, Mahmoud Reza; Hamidi, Mehrdokht; Moharamzad, Yashar; Setayesh, Ali; Amirjamshidi, Abbas

    2013-01-01

    Brown tumor is a bone lesion secondary to hyperparathyroidism of various etiologies. Skeletal involvement in primary hyperparathyroidism secondary to parathyroid adenoma is very uncommon and brown tumor has become extremely a rare clinical entity. Hyperparathyroidism is usually associated with high levels of serum calcium. Brown tumor as the only and initial symptom of normocalcemic primary hyperparathyroidism is extremely rare. Moreover, involvement of the skull base and the orbit is exceedingly rare. The authors would report three cases of brown tumor of the anterior skull base that were associated with true normocalcemic primary hyperparathyroidism. Clinical manifestations, neuroimaging findings, pathological findings, diagnosis and treatment of the patients are discussed and the relevant literature is reviewed.

  18. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  19. Tumor initiating cells in malignant gliomas: biology and implications for therapy.

    Science.gov (United States)

    Hadjipanayis, Costas G; Van Meir, Erwin G

    2009-04-01

    A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas.

  20. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.

    Science.gov (United States)

    Lammers, Twan; Kiessling, Fabian; Hennink, Wim E; Storm, Gert

    2012-07-20

    Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells, active drug targeting to endothelial cells and triggered drug delivery. Significant progress has been made in this area of research both at the preclinical and at the clinical level, and a number of (primarily passively tumor-targeted) nanomedicine formulations have been approved for clinical use. Significant progress has also been made with regard to better understanding the (patho-) physiological principles of drug targeting to tumors. This has led to the identification of several important pitfalls in tumor-targeted drug delivery, including I) overinterpretation of the EPR effect; II) poor tumor and tissue penetration of nanomedicines; III) misunderstanding of the potential usefulness of active drug targeting; IV) irrational formulation design, based on materials which are too complex and not broadly applicable; V) insufficient incorporation of nanomedicine formulations in clinically relevant combination regimens; VI) negligence of the notion that the highest medical need relates to metastasis, and not to solid tumor treatment; VII) insufficient integration of non-invasive imaging techniques and theranostics, which could be used to personalize nanomedicine-based therapeutic interventions; and VIII) lack of (efficacy analyses in) proper animal models, which are physiologically more relevant and more predictive for the clinical situation. These insights strongly suggest that besides making ever more nanomedicine formulations, future efforts should also address some of the conceptual drawbacks of drug targeting to tumors, and that strategies should be developed to overcome these shortcomings. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

    International Nuclear Information System (INIS)

    Vordermark, D.; Brown, J.M.

    2003-01-01

    Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1α responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1α overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a benefit from specific hypoxia

  2. Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics

    International Nuclear Information System (INIS)

    Dang, Hien; Ding, Wei; Emerson, Dow; Rountree, C Bart

    2011-01-01

    Tumor initiating stem-like cells (TISCs) are a subset of neoplastic cells that possess distinct survival mechanisms and self-renewal characteristics crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by TGFβ has been recently linked to the acquisition of TISC characteristics in breast cancer. In HCC, a TISC and EMT phenotype correlates with a worse prognosis. In this work, our aim is to elucidate the underlying mechanism by which cells acquire tumor initiating characteristics after EMT. Gene and protein expression assays and Nanog-promoter luciferase reporter were utilized in epithelial and mesenchymal phenotype liver cancer cell lines. EMT was analyzed with migration/invasion assays. TISC characteristics were analyzed with tumor-sphere self-renewal and chemotherapy resistance assays. In vivo tumor assay was performed to investigate the role of Snail1 in tumor initiation. TGFβ induced EMT in epithelial cells through the up-regulation of Snail1 in Smad-dependent signaling. Mesenchymal liver cancer post-EMT demonstrates TISC characteristics such as tumor-sphere formation but are not resistant to cytotoxic therapy. The inhibition of Snail1 in mesenchymal cells results in decreased Nanog promoter luciferase activity and loss of self-renewal characteristics in vitro. These changes confirm the direct role of Snail1 in some TISC traits. In vivo, the down-regulation of Snail1 reduced tumor growth but was not sufficient to eliminate tumor initiation. In summary, TGFβ induces EMT and TISC characteristics through Snail1 and Nanog up-regulation. In mesenchymal cells post-EMT, Snail1 directly regulates Nanog expression, and loss of Snail1 regulates tumor growth without affecting tumor initiation

  3. Metastatic neuroendocrine tumor with initial presentation of orbital apex syndrome

    Directory of Open Access Journals (Sweden)

    Yen-Yu Huang

    2017-03-01

    Full Text Available The possible etiologies of orbital apex syndrome range from inflammatory, infectious, neoplastic, iatrogenic/traumatic, to vascular processes. In patients without obvious infection or systemic cancer history, judicious use of corticosteroids is a reasonable strategy. We describe a 64-year-old man who presented with orbital apex syndrome and had progressed to total visual loss in three days after admission. Radiological imaging and pathological studies were consistent with a neuroendocrine tumor with multiple metastases. We recommend that a biopsy-proven specimen is warranted in patient with orbital apex syndrome even without a cancer history.

  4. Targeting Tumor Oct4 to Deplete Prostate Tumor and Metastasis Initiating Cells

    Science.gov (United States)

    2017-12-01

    is associated with androgen receptor (AR). We detected Oct4 protein expression in prostate cancer cells as well as in tumor tissue specimens...unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Identification of genes driving prostate carcinogenesis will lead to new cancer treatment. The human...a pseudogene of embryonic Oct4 (POU5F1). A recent study found that tumor Oct4 found in prostate cancer cells is due to the gene expression of POU5F1B

  5. What is the microscopic tumor extent beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers?

    International Nuclear Information System (INIS)

    Choo, Richard; Woo, Tony; Assaad, Dalal; Antonyshyn, Oleh; Barnes, Elizabeth A.; McKenzie, David; Fialkov, Jeffrey; Breen, Dale; Mamedov, Alexander

    2005-01-01

    Purpose: To quantify the microscopic tumor extension beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers. Methods and Materials: A prospective, single arm, study. Preoperatively, a radiation oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental marks in four directions from the delineated border. Under local anesthesia, the lesion was excised, and resection margins were assessed microscopically by frozen section. Once resection margins were clear, the microscopic tumor extent was calculated using the presurgical incremental markings as references. A potential relationship between the distance of microscopic tumor extension and other variables was analyzed. Results: A total of 71 lesions in 64 consecutive patients, selected for surgical excision with frozen-section-assisted assessment of resection margins, were accrued. The distance of microscopic tumor extension beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.2 mm. A margin of 10 mm was required to provide a 95% chance of obtaining clear resection margins. The microscopic tumor extent was positively correlated with the size of gross lesion, but not with other variables. Conclusions: The distance of microscopic tumor extension beyond a gross nonmelanoma skin cancer was variable, with a mean of 5.2 mm. Such information is critical for the proper radiation planning of skin cancer therapy

  6. What is the microscopic tumor extent beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers?

    Science.gov (United States)

    Choo, Richard; Woo, Tony; Assaad, Dalal; Antonyshyn, Oleh; Barnes, Elizabeth A; McKenzie, David; Fialkov, Jeffrey; Breen, Dale; Mamedov, Alexander

    2005-07-15

    To quantify the microscopic tumor extension beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers. A prospective, single arm, study. Preoperatively, a radiation oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental marks in four directions from the delineated border. Under local anesthesia, the lesion was excised, and resection margins were assessed microscopically by frozen section. Once resection margins were clear, the microscopic tumor extent was calculated using the presurgical incremental markings as references. A potential relationship between the distance of microscopic tumor extension and other variables was analyzed. A total of 71 lesions in 64 consecutive patients, selected for surgical excision with frozen-section-assisted assessment of resection margins, were accrued. The distance of microscopic tumor extension beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.2 mm. A margin of 10 mm was required to provide a 95% chance of obtaining clear resection margins. The microscopic tumor extent was positively correlated with the size of gross lesion, but not with other variables. The distance of microscopic tumor extension beyond a gross nonmelanoma skin cancer was variable, with a mean of 5.2 mm. Such information is critical for the proper radiation planning of skin cancer therapy.

  7. Benign fatty tumors: classification, clinical course, imaging appearance, and treatment

    International Nuclear Information System (INIS)

    Bancroft, Laura W.; Kransdorf, Mark J.; Peterson, Jeffrey J.; O'Connor, Mary I.

    2006-01-01

    Lipoma is the most common soft-tissue tumor, with a wide spectrum of clinical presentations and imaging appearances. Several subtypes are described, ranging from lesions entirely composed of mature adipose tissue to tumors intimately associated with nonadipose tissue, to those composed of brown fat. The imaging appearance of these fatty masses is frequently sufficiently characteristic to allow a specific diagnosis. However, in other cases, although a specific diagnosis is not achievable, a meaningful limited differential diagnosis can be established. The purpose of this manuscript is to review the spectrum of benign fatty tumors highlighting the current classification system, clinical presentation and behavior, spectrum of imaging appearances, and treatment. The imaging review emphasizes computed tomography (CT) scanning and magnetic resonance (MR) imaging, differentiating radiologic features. (orig.)

  8. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    Directory of Open Access Journals (Sweden)

    Scott Okuno

    2011-08-01

    Full Text Available Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

  9. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    International Nuclear Information System (INIS)

    Joglekar, Siddharth B.; Rose, Peter S.; Sim, Franklin; Okuno, Scott; Petersen, Ivy

    2011-01-01

    Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation

  10. Primary hyperparathyroidism, adrenal tumors and neuroendocrine tumors of the pancreas - clinical diagnosis and imaging requirements

    International Nuclear Information System (INIS)

    Auernhammer, C.J.; Engelhardt, D.; Goeke, B.

    2003-01-01

    Diseases of the parathyroids, the adrenals and of neuroendocrine tumors of the pancreas are primarily diagnosed by clinical and endocrinological evaluation.The requirements concerning various imaging techniques and their relative importance in localization strategies of the different tumors are complex. Current literature search, using PubMed. Evaluation of primary hyperparathyroidism requires bone densitometry by DXA and search for nephrolithiasis by ultrasound or native CT examination.While ultrasound of the thyroid and parathyroids seems useful before any parathyroid surgery,more extensive preoperative localization strategies (sestamibi scintigraphy, MRI) should be restricted to minimal invasive parathyroid surgery or re-operations.For adrenal tumors CT and MRI are of similar diagnostic value. Imaging of pheochromocytomas should be completed by MIBG scintigraphy. Each adrenal incidentaloma requires an endocrinological work-up.A fine-needle aspiration or core needle biopsy of an adrenal tumor is rarely indicated.Before adrenal biopsy a pheochromocytoma has to be excluded.Successful localization strategies for neuroendocrine tumors of the pancreas include somatostatin receptor scintigraphy, endoscopic ultrasound and MRI.Discussion Specific localization strategies have been established for the aforementioned tumors.The continuous progress of different imaging techniques requires a regular reevaluation of these localization strategies. (orig.) [de

  11. Radiotherapy for pediatric brain tumors: Standard of care, current clinical trials, and new directions

    International Nuclear Information System (INIS)

    Kun, Larry E.

    1996-01-01

    Objectives: To review the clinical characteristics of childhood brain tumors, including neurologic signs, neuroimaging and neuropathology. To critically assess indications for therapy relevant to presenting characteristics, age, and disease status. To discuss current management strategies including neurosurgery, radiation therapy, and chemotherapy. To analyze current clinical trials and future directions of clinical research. Brain tumors account for 20% of neoplastic diseases in children. The most common tumors include astrocytoma and malignant gliomas, medulloblastoma and supratentorial PNET's, ependymoma, craniopharyngioma, and intracranial germ cell tumors. Tumor type and clinical course are often correlated with age at presentation and anatomic site. The clinical characteristics and disease extent largely determine the relative merits of available 'standard' and investigational therapeutic approaches. Treatment outcome, including disease control and functional integrity, is dependent upon age at presentation, tumor type, and disease extent. An understanding of the clinical, neuroimaging, and histologic characteristics as they relate to decisions regarding therapy is critical to the radiation oncologist. Appropriate radiation therapy is central to curative therapy for a majority of pediatric brain tumor presentations. Technical advances in neurosurgery provide greater safety for 'gross total resection' in a majority of hemispheric astrocytomas and medulloblastomas. The relative roles of 'standard' radiation therapy and evolving chemotherapy for centrally located astrocytomas (e.g., diencephalic, optic pathway) need to be analyzed in the context of initial and overall disease control, neurotoxicities, and potential modifications in the risk:benefit ratio apparent in the introduction of precision radiation techniques. Modifications in radiation delivery are fundamental to current investigations in medulloblastoma; the rationale for contemporary and projected

  12. Studies on the tumor initiation/promotion potential of six middle distillates (MDs) in mouse skin.

    Science.gov (United States)

    Jungen, H; Mellert, W; Wenzel-Hartung, R

    1995-08-01

    Six middle distillates (MDs) were tested for tumor initiating/promoting activity after application to the skin of 30 male CD-1 (ICR) BR mice per group. As the control, 7,12-dimethylbenz[a]-anthracene (DMBA) was used for initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) for promotion. For assessing the tumor-initiating activity, 50 microliters of neat MDs was administered for 5 days with subsequent TPA promotion. In the promotion bioassay, after DMBA initiation 50 microliters of the neat MDs was administered twice weekly until Week 28. For the examination of complete carcinogenic activity, one MD was given without DMBA initiation. Hyperkeratosis, hyperplasia, and dermal inflammation, occurring during the initiation with the MDs, were completely reversible during the 2-week treatment-free period after initiation. Similar skin findings were observed during promotion with the MDs. Regarding the number of affected animals and the severity of the response, TPA was more irritating than the MDs. The initiation study revealed skin tumors for the DMBA/TPA control (30/30), MD 57,389 (14/30), MD 57,396 (5/30), MD 57,383 (4/30) and MD 57,324 (2/30). The promotion study revealed tumor induction by MDs 57,389 (9/30), 57,324 (1/30), 57,393 (1/30), and 57,396 (1/30). Two of 30 animals treated with MD 57,389 developed tumors without DMBA initiation thus indicating that it also is a complete carcinogen. MD 57,399 caused neither initiating nor promoting effects. The tumors observed were diagnosed histopathologically predominantly as squamous cell papillomas.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Non tumoral intracranial expansive processes: clinical tomographic correlation

    International Nuclear Information System (INIS)

    Campos, P.; Herrera, G.; Valneica, F.

    1991-01-01

    Presentation of clinical-tomographic correlation in 111 cases of non tumoral intracranial expansive processes seen between 1984-1988 in the Hospital Cayetano Heredia (Lima, Peru). Emphasis is given fundamentally to: the importance of establishing the organicity of partial and late epilepsy; the high incidence rate of inflammatory infectious processes with CNS compromise in under developing countries; the necessity of making public the importance of two parasitic diseases in the differential diagnosis of non tumoral intracranial expansive processes: free living amebiasis, and toxoplasmosis (especially in association with AIDS). (author)

  14. Overview on Clinical Relevance of Intra-Tumor Heterogeneity.

    Science.gov (United States)

    Stanta, Giorgio; Bonin, Serena

    2018-01-01

    Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH) is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

  15. Overview on Clinical Relevance of Intra-Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Giorgio Stanta

    2018-04-01

    Full Text Available Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

  16. Clinical and Treatment Features of Orbital Neurogenic Tumors

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    Pınar Bingöl Kızıltunç

    2013-10-01

    Full Text Available Purpose: To evaluate the clinical and treatment features of orbital neurogenic tumors. Material and Method: The records of 35 patients with orbital neurogenic tumors who were diagnosed and treated at Ankara University Faculty of Medicine, Department of Ophthalmology, between 1998 and 2011 were evaluated retrospectively. Results: Orbitotomy via a cutaneous approach was performed in 21 (60% cases and orbitotomy via a transconjunctival approach was performed in 7 (20% cases. Three (8% cases had been operated at different centers. Four (12% cases were diagnosed clinically. Total excisional biopsy was performed in 11 (31.4% cases, subtotal excisional biopsy was performed in 7 (20%, and incisional biopsy was performed in 10 (28.6% cases. 14 (40% 35 cases were diagnosed as meningioma, 12 (34% as peripheral nerve sheath tumor, and 9 (26% cases were diagnosed as optic nerve glioma. Six (43% meningioma cases were optic nerve sheath meningioma, 5 (36% were sphenoid wing meningioma, 2 (14% were ectopic meningioma, and 1 (7% was perisellar meningioma. Six (50% of peripheral nerve sheath tumors were schwannoma, 2 (16% were solitary neurofibroma, 4 (34% were plexiform neurofibroma. External beam radiotherapy was performed in 15 (42.8% cases, cyberknife radiosurgery in 1 (2.8% , chemotherapy in 1 (2.8%, and enucleation ( because of neovascular glaucoma and vitreous hemorrhage was performed in 1 (2.8% case. Discussion: The most common orbital neurogenic tumors are meningioma, peripheral nerve sheath tumor, and optic nerve glioma. For meningioma and glioma, external beam radiotherapy is required; for schwannoma and solitary neurofibroma, total excisional biopsy is the preferred treatment. The success of visual and anatomic results are high after treatment. (Turk J Ophthalmol 2013; 43: 335-9

  17. Imaging Reporters for Proteasome Activity Identify Tumor- and Metastasis-Initiating Cells

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    Amanda C. Stacer

    2015-08-01

    Full Text Available Tumor-initiating cells, also designated as cancer stem cells, are proposed to constitute a subpopulation of malignant cells central to tumorigenesis, metastasis, and treatment resistance. We analyzed the activity of the proteasome, the primary organelle for targeted protein degradation, as a marker of tumor- and metastasis-initiating cells. Using human and mouse breast cancer cells expressing a validated fluorescent reporter, we found a small subpopulation of cells with low proteasome activity that divided asymmetrically to produce daughter cells with low or high proteasome activity. Breast cancer cells with low proteasome activity had greater local tumor formation and metastasis in immunocompromised and immunocompetent mice. To allow flexible labeling of cells, we also developed a new proteasome substrate based on HaloTag technology. Patient-derived glioblastoma cells with low proteasome activity measured by the HaloTag reporter show key phenotypes associated with tumor-initiating cells, including expression of a stem cell transcription factor, reconstitution of the original starting population, and enhanced neurosphere formation. We also show that patient-derived glioblastoma cells with low proteasome activity have higher frequency of tumor formation in mouse xenografts. These studies support proteasome function as a tool to investigate tumor- and metastasis-initiating cancer cells and a potential biomarker for outcomes in patients with several different cancers.

  18. Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

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    Vordermark, D. [Dept. of Radiation Oncology, Univ. of Wuerzburg (Germany); Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States); Brown, J.M. [Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States)

    2003-12-01

    Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1{alpha} responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1{alpha} overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a

  19. Clinical study on brain tumors in the aged

    International Nuclear Information System (INIS)

    Teramoto, Akira; Manaka, Shinya; Takakura, Kintomo

    1981-01-01

    In order to investigate the clinical features and the prognosis of brain tumors in the aged, 132 cases over 60 years of age were studied from the consecutive series of 1,793 brain tumors in the University of Tokyo Hospital (1963 - 1979). The incidence of brain tumors in the aged was 7.4% on the whole, while it showed a significant increase from 4.8% (1960's) to 11.5% (the later half of 1970's). Histologically, meningiomas were the most common tumors (26%), followed by neurinomas (17%), pituitary adenomas (16%) and metastatic tumors (15%). Malignant gliomas were found more frequently than benign ones. There were more meningiomas as age advanced. The proportion and the number of meningioma cases has obviously increased in recent years when CT scanners became available. Symptoms of intracranial hypertention were found less frequently in aged patients although they were still common in cases of glioblastomas. The duration from onset to surgery was relatively long, especially in cases of neurinomas and pituitary adenomas. Two cases of astrocytomas belonged to the category of silent gliomas. Overall operative mortality rate was 10.6%, while it showed a marked decrease to 4.7% in the 1970's. Five-year survival rates were as follows: meningiomas (58%), pituitary adenomas (70%), neurinomas (80%), glioblastomas (20%) and astrocytomas (25%). As for functional prognoses, 30% of the patients showed poor states on ADL, mostly because of residual psychic disorders. (author)

  20. Toward a science of tumor forecasting for clinical oncology.

    Science.gov (United States)

    Yankeelov, Thomas E; Quaranta, Vito; Evans, Katherine J; Rericha, Erin C

    2015-03-15

    We propose that the quantitative cancer biology community makes a concerted effort to apply lessons from weather forecasting to develop an analogous methodology for predicting and evaluating tumor growth and treatment response. Currently, the time course of tumor response is not predicted; instead, response is only assessed post hoc by physical examination or imaging methods. This fundamental practice within clinical oncology limits optimization of a treatment regimen for an individual patient, as well as to determine in real time whether the choice was in fact appropriate. This is especially frustrating at a time when a panoply of molecularly targeted therapies is available, and precision genetic or proteomic analyses of tumors are an established reality. By learning from the methods of weather and climate modeling, we submit that the forecasting power of biophysical and biomathematical modeling can be harnessed to hasten the arrival of a field of predictive oncology. With a successful methodology toward tumor forecasting, it should be possible to integrate large tumor-specific datasets of varied types and effectively defeat one cancer patient at a time. ©2015 American Association for Cancer Research.

  1. Clinical Efficacy of Various Diagnostic Tests for Small Bowel Tumors and Clinical Features of Tumors Missed by Capsule Endoscopy

    Directory of Open Access Journals (Sweden)

    Jung Wan Han

    2015-01-01

    Full Text Available Background. We aimed to evaluate the efficacy of various diagnostic tools such as computerized tomography (CT, small bowel follow-through (SBFT, and capsule endoscopy (CE in diagnosing small bowel tumors (SBTs. Additionally, we aimed to evaluate the clinical features of SBTs missed by CE. Methods. We retrospectively studied 79 patients with histologically proven SBT. Clinical data were analyzed with particular attention to the efficacy of CT, SBFT, and CE in detecting SBT preoperatively. We also analyzed the clinical features of SBTs missed by CE. Results. The most common symptoms of SBT were bleeding (43% and abdominal pain (13.9%. Diagnostic yields were as follows: CT detected 55.8% of proven SBTs; SBFT, 46.1%; and CE, 83.3%. The sensitivity for detecting SBTs was 40.4% for CT, 43.9% for SBFT, and 79.6% for CE. Two patients with nondiagnostic but suspicious findings on CE and seven patients with negative findings on CE were eventually found to have SBT. These nine patients were eventually diagnosed with gastrointestinal stromal tumor (4, small polyps (3, inflammatory fibroid polyp (1, and adenocarcinoma (1. These tumors were located in the proximal jejunum (5, middle jejunum (1, distal jejunum (1, and proximal ileum (1. Conclusion. CE is more efficacious than CT or SBFT for detecting SBTs. However, significant tumors may go undetected with CE, particularly when located in the proximal jejunum.

  2. Initial clinical experience with the heartstring

    International Nuclear Information System (INIS)

    Kazui, Toshinobu; Doi, Hirosato; Suzuki, Masato; Okamoto, Takashi; Koshima, Ryuji; Sugiki, Kenji; Ohno, Takemi

    2006-01-01

    The Heartstring is one of the devices that enable proximal anastomosis without clamping the aorta. We have applied the device not only to low-risk patients with normal aortas but also to high-risk patients with diseased aortas. The purpose of this study was to investigate the initial outcomes of using this device. The Heartstring was used on 87 patients between January and December 2004. The patients comprised 62 men and 25 women 48-86 years old (mean 68.4±8.4 years). The ascending aorta was evaluated by computed tomography (CT) scanning before surgery. If a patient's aorta was severely calcified, epiaortic echocardiography was performed. The aortas were ranked into four grades, and the preoperative patient's status were evaluated by the EuroSCORE. Angiography was performed on the third postoperative day. CT scanning revealed that 74 patients had no calcification in the ascending aorta, 10 patients had scattered calcification, and 3 patients had plate-like calcification. The EuroSCORE was 6.86±1.03. We performed 93 proximal anastomoses and 149 distal anastomoses. The average distal anastomosis was 1.6±0.6 sites per graft. Of the distal anastomoses, 74.2% were to the circumflex artery territory. Postoperative coronary angiography revealed that all grafts were patent. The Heartstring facilitates safe proximal anastomosis, even in high-risk patients. Their short-term outcome was good. The device assists in bypassing circumflex artery territory. Long-term follow-up is necessary. (author)

  3. An inhibitor of K+ channels modulates human endometrial tumor-initiating cells

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    Leslie Kimberly K

    2011-08-01

    Full Text Available Abstract Background Many potassium ion (K+ channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC, are critical to cancer progression. Results A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA, was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.

  4. Malignant fatty tumors: classification, clinical course, imaging appearance and treatment

    International Nuclear Information System (INIS)

    Peterson, J.J.; Kransdorf, M.J.; Bancroft, L.W.; O'Connor, M.I.

    2003-01-01

    Liposarcoma is a relatively common soft tissue malignancy with a wide spectrum of clinical presentations and imaging appearances. Several subtypes are described, ranging from lesions nearly entirely composed of mature adipose tissue, to tumors with very sparse adipose elements. The imaging appearance of these fatty masses is frequently sufficiently characteristic to allow a specific diagnosis, while in other cases, although a specific diagnosis is not achievable, a meaningful limited differential diagnosis can be established. The purpose of this paper is to review the spectrum of malignant fatty tumors, highlighting the current classification system, clinical presentation and behavior, treatment and spectrum of imaging appearances. The imaging review will emphasize CT scanning and MR imaging, and will stress differentiating radiologic features. (orig.)

  5. Radiotherapy for pediatric brain tumors: Standard of care, current clinical trials and new directions

    International Nuclear Information System (INIS)

    Kun, Larry E.

    1997-01-01

    Objectives: To review the clinical characteristics of childhood brain tumors, including neurologic signs, neuroimaging and neuropathology. To critically assess indications for therapy relevant to presenting characteristics, age, and disease status. To discuss current management strategies including neurosurgery, radiation therapy, and chemotherapy. To analyze current clinical trials and future directions of clinical research. Brain tumors account for 20% of neoplastic diseases in children. The most common tumors include astrocytoma and malignant gliomas, medulloblastoma and supratentorial PNET's, ependymoma, craniopharyngioma, and intracranial germ cell tumors. The clinical characteristics and disease extent largely determine the relative merits of available 'standard' and investigational therapeutic approaches. Treatment outcome, including disease control and functional integrity, is dependent upon tumor type and site, age at presentation, and disease extent. An understanding of the clinical, neuroimaging, and histologic characteristics as they relate to decisions regarding therapy is critical to the radiation oncologist. Appropriate radiation therapy is central to curative therapy for a majority of pediatric brain tumor presentations. Technical advances in neurosurgery provide greater safety for 'gross total resection' in a majority of hemispheric astrocytomas and medulloblastomas. The relative roles of radiation therapy and chemotherapy for centrally located astrocytomas (e.g., diencephalic, optic pathway) need to be analyzed in the context of initial and overall disease control, neurotoxicities, and potential modifications in the risk:benefit ratio apparent in the introduction of 3-dimensional radiation techniques. Modifications in radiation delivery are important components of current investigations in medulloblastoma; the rationale for contemporary cooperative group trials will be presented as well as the background data re surgical, radiotherapeutic, and

  6. Tumor-initiating CD49f cells are a hallmark of chemoresistant triple negative breast cancer.

    Science.gov (United States)

    Gomez-Miragaya, Jorge; González-Suárez, Eva

    2017-01-01

    Taxanes are mainstay treatment of triple negative breast cancer (TNBC) patients but resistance often develops. Using TNBC patient-derived orthoxenografts (PDX) we have recently discovered that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands in tumors that have acquired resistance. Importantly, sensitivity to taxanes is recovered after long-term drug interruption. The characterization of this chemoresistant CD49f+ cells provides a unique opportunity to identify novel targets for the treatment of chemoresistant TNBC.

  7. Tumor scintigraphy by the method for subtracting the initial image with technetium-99m labeled antibody

    International Nuclear Information System (INIS)

    Karube, Yoshiharu; Katsuno, Kentaro; Ito, Sanae; Matsunaga, Kazuhisa; Takata, Jiro; Kuroki, Masahide; Murakami, Masaaki; Matsuoka, Yuji

    1999-01-01

    The method for subtracting the initial image from the localization image was evaluated for radioimmunoscintigraphy of tumors with technetium-99m (Tc-99m) labeled antibodies. Monoclonal antibodies were parental mouse and mouse-human chimeric antibodies to carcinoembryonic antigen (CEA), designated F11-39 and ChF11-39, respectively, both of which have been found to discriminate CEA in tumor tissues from the CEA-related antigens. After reduction of the intrinsic disulfide bonds, these antibodies were labeled with Tc-99m. In vivo studies were performed on athymic nude mice bearing the human CEA-producing gastric carcinoma xenografts. Though biodistribution results showed selective and progressive accumulation of Tc-99m labeled antibodies at the tumor site, high radioactivity in blood was inappropriate for scintigraphic visualization of the tumors within a few hours. We examined the subtraction of the initial Tc-99m image from the Tc-99m localization image after a few hours. Subtracted images of the same count reflected the in vivo behavior of the Tc-99m radioactivity. The subtracted scintigrams revealed excellent tumor images with no significant extrarenal background. Visualization of the tumor site was dependent on antigen-specific binding and nonspecific exudation. These results demonstrate that a method of subtraction of the initial image may serve as a potentially useful diagnostic method for an abnormal site for agents with a low pharmacokinetic value. (author)

  8. Gastric stromal tumors: clinical presentations diagnosis and outcome

    International Nuclear Information System (INIS)

    Hussain, D.; Zafar, H.; Raja, A.J.

    2006-01-01

    To determine the clinical presentations, of gastric stromal tumors with diagnostic methods, pathology and outcome after surgery. All patients of age 14 years and above, diagnosed histopathologically to have gastric stromal tumors were included. The data of these patients was collected retrospectively from January 1988 to December 1998, and prospectively from January 1999 to December 2002. All the patients were studied as a single group. There were 11 patients. Their mean age was 54 years, with 8 males and 3 females. Five patients presented with upper gastrointestinal bleeding, and 4 with lower gastrointestinal bleeding. Eight patients had pain in epigastrium and 2 had vomiting. Upper gastrointestinal endoscopy was done in all patients, and ultrasound was done in 4 patients. CT scan was done in 7 patients. Preoperative diagnosis could be made in 6 patients. Only one patient had liver metastasis. Wedge resection was performed in 5 proximal gastrectomy with gastroesophageal anastomosis in 3, and partial gastrectomy with gastrojejunostomy in another 3 patients. The mean tumor size was 8.0 centimeters. Two patients had benign, 2 had intermediate and 7 had malignant tumors. The mean duration of followup was 41 months. Follow-up was completed in 8 patients, out of whom 6 were alive, and 2 patients expired due to other causes at the time of completion of this study. (author)

  9. Cauda equina syndrome as the initial presenting clinical feature of medulloblastoma: a case report

    Directory of Open Access Journals (Sweden)

    Al-Otaibi Faisal

    2012-05-01

    Full Text Available Abstract Introduction Medulloblastoma is one of the most common pediatric brain malignancies. The usual presenting clinical features are related to posterior fossa syndrome or/and hydrocephalus. Cauda equina syndrome is a very rare presentation for this disease. Case presentation We describe the case of a three-year-old boy with cauda equina syndrome as the initial presenting clinical feature for medulloblastoma. He was initially diagnosed as having a spinal tumor by magnetic resonance imaging scan. Subsequently, a cranial magnetic resonance imaging scan revealed a posterior fossa tumor with features of dissemination. He had substantial improvement after treatment. This case report is complemented by a literature review related to this unusual presentation. Conclusions Medulloblastoma primarily presenting with cauda equina syndrome is very rare. However, spinal drop metastasis should be considered in the pediatric age group to avoid suboptimal management.

  10. Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

    International Nuclear Information System (INIS)

    Fangusaro, Jason

    2012-01-01

    High grade gliomas (HGG) are one of the most common central nervous system (CNS) tumors encountered in adults, but they only represent approximately 8–12% of all pediatric CNS tumors. Historically, pediatric HGG were thought to be similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR) when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic, and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes, and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

  11. Pediatric High Grade Glioma: a Review and Update on Tumor Clinical Characteristics and Biology

    Energy Technology Data Exchange (ETDEWEB)

    Fangusaro, Jason, E-mail: jfangusaro@luriechildrens.org [Pediatric Neuro-Oncology, The Ann & Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL (United States)

    2012-08-24

    High grade gliomas (HGG) are one of the most common central nervous system (CNS) tumors encountered in adults, but they only represent approximately 8–12% of all pediatric CNS tumors. Historically, pediatric HGG were thought to be similar to adult HGG since they appear histologically identical; however, molecular, genetic, and biologic data reveal that they are distinct. Similar to adults, pediatric HGG are very aggressive and malignant lesions with few patients achieving long-term survival despite a variety of therapies. Initial treatment strategies typically consist of a gross total resection (GTR) when feasible followed by focal radiotherapy combined with chemotherapy. Over the last few decades, a wealth of data has emerged from basic science and pre-clinical animal models helping to better define the common biologic, genetic, and molecular make-up of these tumors. These data have not only provided a better understanding of tumor biology, but they have also provided new areas of research targeting molecular and genetic pathways with the potential for novel treatment strategies and improved patient outcomes. Here we provide a review of pediatric non-brainstem HGG, including epidemiology, presentation, histology, imaging characteristics, treatments, survival outcomes, and an overview of both basic and translational research. An understanding of all relevant pre-clinical tumor models, including their strengths and pitfalls is essential in realizing improved patient outcomes in this population.

  12. Albumin-bound paclitaxel in solid tumors: clinical development and future directions.

    Science.gov (United States)

    Kundranda, Madappa N; Niu, Jiaxin

    2015-01-01

    Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.

  13. BMI-1 targeting interferes with patient-derived tumor-initiating cell survival and tumor growth in prostate cancer

    Science.gov (United States)

    Yusuff, Shamila; Davis, Stephani; Flaherty, Kathleen; Huselid, Eric; Patrizii, Michele; Jones, Daniel; Cao, Liangxian; Sydorenko, Nadiya; Moon, Young-Choon; Zhong, Hua; Medina, Daniel J.; Kerrigan, John; Stein, Mark N.; Kim, Isaac Y.; Davis, Thomas W.; DiPaola, Robert S.; Bertino, Joseph R.; Sabaawy, Hatem E.

    2016-01-01

    Purpose Current prostate cancer (PCa) management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy-resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TICs-tailored therapies appears to be a promising approach. Experimental design We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient derived prostate cancer cells and xenograft models to characterize the effects of pharmacological inhibitors of BMI-1. Results We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacological inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor (AR)-directed therapies, without toxic effects on normal tissues. Conclusions Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective PCa treatment. PMID:27307599

  14. Canonical and Non-Canonical NF-κB Signaling Promotes Breast Cancer Tumor-Initiating Cells

    Science.gov (United States)

    Kendellen, Megan F.; Bradford, Jennifer W.; Lawrence, Cortney L.; Clark, Kelly S.; Baldwin, Albert S.

    2014-01-01

    Tumor-initiating cells (TICs) are a sub-population of cells that exhibit a robust ability to self-renew and contribute to the formation of primary tumors, the relapse of previously treated tumors, and the development of metastases. TICs have been identified in various tumors, including those of the breast, and are particularly enriched in the basal-like and claudin-low subtypes of breast cancer. The signaling pathways that contribute to the function and maintenance of TICs are under intense study. We explored the potential involvement of the NF-κB family of transcription factors in TICs in cell lines that are representative of basal-like and claudin-low breast cancer. NF-κB was found to be activated in breast cancer cells that form tumorspheres efficiently. Moreover, both canonical and non-canonical NF-κB signaling is required for these cells to self-renew in vitro and to form xenograft tumors efficiently in vivo using limiting dilutions of cells. Consistent with this, canonical and non-canonical NF-κB signaling is activated in TICs isolated from breast cancer cell lines. Experimental results indicate that NF-κB promotes the function of TICs by stimulating epithelial-to-mesenchymal transition (EMT) and by upregulating the expression of the inflammatory cytokines IL-1β and IL-6. The results suggest the use of NF-κB inhibitors for clinical therapy of certain breast cancers. PMID:23474754

  15. Evaluation of esophageal peristalsis in patients with esophageal tumors. Initial experience with cine MR imaging

    International Nuclear Information System (INIS)

    Koyama, Takashi; Kobayashi, Ari; Hiraga, Akira; Umeoka, Shigeaki; Saga, Tsuneo; Watanabe, Go; Tamai, Ken; Shimada, Yutaka; Togashi, Kaori

    2005-01-01

    We evaluated esophageal peristalsis in patients with esophageal tumors by cine MR using steady-state free precession (SSFP) sequence and correlated the alteration of the esophageal peristalsis with clinical symptoms and tumor stages. Thirteen patients with pathologically proven esophageal tumors, including 12 esophageal cancers and one submucosal leiomyoma, underwent cine MRI using true fast imaging with steady precession (trueFISP) sequence, which is one SSFP sequence, after contrast-enhanced MR scanning for clinical purposes. A total of 120 serial images were obtained within 60 s through the plane along the long axis of the esophagus while patients chewed gum. The serial trueFISP images were evaluated for the presence, frequency, speed of progression, and passage of peristalsis through the tumor. The data from cine MRI were compared with clinical symptoms and tumor stages. Peristalsis was clearly identified in all patients. Seven patients with complete interruption of peristalsis had dysphagia; one with partially impaired peristalsis could intake solid foods with discomfort; and two with partially impaired peristalsis and three with preserved peristalsis remained asymptomatic. Patients with complete or partial interruption of peristalsis had Stage T3 or T4 esophageal cancer. In conclusion, trueFISP cine MR imaging enables direct visualization of esophageal peristalsis in relation to esophageal tumors. Complete interruption of peristalsis causes dysphagia, whereas partial interruption of and preserved peristalsis usually do not cause digestive problems. Interruption of peristalsis may indicate impaired muscle function caused by invasion of advanced esophageal cancers. (author)

  16. [Support Team for Investigator-Initiated Clinical Research].

    Science.gov (United States)

    Fujii, Hisako

    2017-07-01

    Investigator-initiated clinical research is that in which investigators plan and carry out their own clinical research in academia. For large-scale clinical research, a team should be organized and implemented. This team should include investigators and supporting staff, who will promote smooth research performance by fulfilling their respective roles. The supporting staff should include project managers, administrative personnel, billing personnel, data managers, and clinical research coordinators. In this article, I will present the current status of clinical research support and introduce the research organization of the Dominantly Inherited Alzheimer Network (DIAN) study, an investigator-initiated international clinical research study, with particular emphasis on the role of the project management staff and clinical research coordinators.

  17. Impact of initial tumor volume on radiotherapy outcome in patients with T2 glottic cancer

    International Nuclear Information System (INIS)

    Rutkowski, T.

    2014-01-01

    The aim of this study was to quantify the impact of initial tumor volume (TV) on radiotherapy (RT) outcome in patients with T2 glottic cancer. Initial TV was calculated for 115 consecutive patients with T2 glottic cancer who had been treated with definitive RT alone at a single institution. The results showed strong correlations of TV with 3-year local tumor control (LTC) and disease-free survival (DFS). For TV ≤ 0.7 cm 3 , 3-year LTC was 83 %; for TV 0.7-3.6 cm 3 this was 70 % and for TV 3.6-17 cm 3 44 %. Analysis of total dose vs. initial TV showed that larger T2 glottic tumors with a TV of around 5 cm 3 (2-2.5 cm in diameter with 10 10 cancer cells) need an extra 6.5 Gy to achieve similar 3-year LTC rates as for small tumors with a TV of 0.5 cm 3 (∝1 cm in diameter with 10 9 cancer cells). Although classification of tumors according to TV cannot replace TNM staging in daily practice, it could represent a valuable numerical supplement for planning the optimal dose fractionation scheme for individual patients. (orig.)

  18. Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

    Science.gov (United States)

    Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

    2015-02-01

    Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have

  19. FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells.

    Directory of Open Access Journals (Sweden)

    Sungeun Kim

    Full Text Available Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic potential, self-renewal, heterogeneous differentiation, and bipotency. Gene expression analysis and immunostaining of TICs and non-TICs revealed that FGFR2 was preferentially expressed in TICs. Loss of FGFR2 impaired self-renewal of TICs, thus resulting in marked decreases in the TIC population and tumorigenic potential. Restoration of FGFR2 rescued the defects in TIC pool maintenance, bipotency, and breast tumor growth driven by FGFR2 knockdown. In addition, pharmacological inhibition of FGFR2 kinase activity led to a decrease in the TIC population which resulted in suppression of breast tumor growth. Moreover, human breast TICs isolated from patient tumor samples were found enriched in a FGFR2+ population that was sufficient to initiate tumor growth. Our data suggest that FGFR2 is essential in sustaining the breast TIC pool through promotion of self-renewal and maintenance of bipotent TICs, and raise the possibility of FGFR2 inhibition as a strategy for anti-cancer therapy by eradicating breast TICs.

  20. CD200-expressing human basal cell carcinoma cells initiate tumor growth.

    Science.gov (United States)

    Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

    2013-01-22

    Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

  1. A Targetable EGFR-Dependent Tumor-Initiating Program in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Paul Savage

    2017-10-01

    Full Text Available Summary: Therapies targeting epidermal growth factor receptor (EGFR have variable and unpredictable responses in breast cancer. Screening triple-negative breast cancer (TNBC patient-derived xenografts (PDXs, we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing of 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated EGFR expression was significantly enriched in a mesenchymal/stem-like cellular cluster. Sorted EGFRhi subpopulations exhibited enhanced stem-like features, including ALDH activity, sphere-forming efficiency, and tumorigenic and metastatic potential. EGFRhi cells gave rise to EGFRhi and EGFRlo cells in primary and metastatic tumors, demonstrating an EGFR-dependent expansion and hierarchical state transition. Similar tumorigenic EGFRhi subpopulations were identified in independent PDXs, where heterogeneous EGFR expression correlated with gefitinib sensitivity. This provides new understanding for an EGFR-dependent hierarchy in TNBC and for patient stratification for therapeutic intervention. : Savage et al. demonstrate that sensitivity to EGFR inhibitor, gefitinib, in triple-negative breast cancer is paradoxically associated with EGFR heterogeneity. Using single-cell RNA sequencing in conjunction with functional assays, they identify TNBC tumors in which EGFR expression identifies cells with tumor-initiating capacity whose proliferative expansion is sensitive to EGFR inhibition. Keywords: breast cancer, tumor heterogeneity, patient-derived xenograft, single-cell RNA sequencing, EGFR inhibition, therapeutic response, tumor-initiating cell, cell hierarchy, BRCA1 mutation

  2. Tumor Suppressor Gene-Based Nanotherapy: From Test Tube to the Clinic

    Directory of Open Access Journals (Sweden)

    Manish Shanker

    2011-01-01

    Full Text Available Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

  3. Tumor suppressor gene-based nanotherapy: from test tube to the clinic.

    Science.gov (United States)

    Shanker, Manish; Jin, Jiankang; Branch, Cynthia D; Miyamoto, Shinya; Grimm, Elizabeth A; Roth, Jack A; Ramesh, Rajagopal

    2011-01-01

    Cancer is a major health problem in the world. Advances made in cancer therapy have improved the survival of patients in certain types of cancer. However, the overall five-year survival has not significantly improved in the majority of cancer types. Major challenges encountered in having effective cancer therapy are development of drug resistance by the tumor cells, nonspecific cytotoxicity, and inability to affect metastatic tumors by the chemodrugs. Overcoming these challenges requires development and testing of novel therapies. One attractive cancer therapeutic approach is cancer gene therapy. Several laboratories including the authors' laboratory have been investigating nonviral formulations for delivering therapeutic genes as a mode for effective cancer therapy. In this paper the authors will summarize their experience in the development and testing of a cationic lipid-based nanocarrier formulation and the results from their preclinical studies leading to a Phase I clinical trial for nonsmall cell lung cancer. Their nanocarrier formulation containing therapeutic genes such as tumor suppressor genes when administered intravenously effectively controls metastatic tumor growth. Additional Phase I clinical trials based on the results of their nanocarrier formulation have been initiated or proposed for treatment of cancer of the breast, ovary, pancreas, and metastatic melanoma, and will be discussed.

  4. Clinical considerations for neutron capture therapy of brain tumors

    International Nuclear Information System (INIS)

    Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr.

    1990-01-01

    The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the US in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should not be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam cases gamma rays to be generated when it interacts with tissue, they think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue

  5. Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Kim

    2018-02-01

    Full Text Available PURPOSE: Phyllodes tumors (PTs of the breast are rare, accounting for less than 1% of all breast tumors. Among PTs, malignant PTs (MPTs have malignant characteristics and distant metastases occur in about 20% to 30% of MPTs. However, there is no effective treatment for MPTs with distant metastasis, resulting in an abject prognosis. We performed targeted deep sequencing on PTs to identify the associations between genetic alterations and clinical prognosis. METHODS: We performed targeted deep sequencing to evaluate the genetic characteristics of PTs and analyzed the relationships between clinical and genetic characteristics. RESULTS: A total of 17 PTs were collected between 2001 and 2012. Histologic review was performed by pathologists. The samples included three benign PTs, one borderline PT, and 13 MPTs. The most frequently detected genetic alteration occurred in the TERT promoter region (70.6%, followed by MED12 (64.7%. EGFR amplification and TP53 alteration were detected in four MPTs without genetic alterations in MED12 and TERT promoter regions. Genetic alterations of RARA and ZNF703 were repeatedly found in PTs with local recurrence, and genetic alterations of SETD2, BRCA2, and TSC1 were detected in PTs with distant metastasis. Especially, MPT harboring PTEN and RB1 copy number deletion showed rapid disease progression. CONCLUSIONS: In this study, we provide genetic characterization and potential therapeutic target for this rare, potentially lethal disease. Further large-scale comprehensive genetic study and functional validation are warranted.

  6. Clinical application of positron emission tomography imaging in urologic tumors

    International Nuclear Information System (INIS)

    Tang Ganghua; Wu Guangyuan

    2007-01-01

    Positron emission tomography (PET) is an advanced noninvasive molecular imaging modality that is being investigated for use in the differentiation, diagnosis, and guiding therapy ora variety of cancer types. FDG PET has the unique clinical value in the differentiation, diagnosis, and monitoring therapy of prostate, such as bladder, renal, and testicle cancer. However, high false-positive and false-negative findings are observed in the detection of these tumors with FDG PET. 11 C-Choline (CH) and 11 C-acetate (AC) can overcome the pitfall of FDG, and appear to be more successful than FGD in imaging prostate cancer and bladder cancer. The short half-life of 11 C prevents the widespread use of CH and AC and 18 F-fluorocholine (FCH) and 18 F-fluoroacetate (FAC) seem to be potential tracers. Potential clinical value of the new PET tracers, such as 3'-deoxy-3'- 18 F-fluorothymidine (FLT), 18 F-fluorodihydrotestosterone (FDHT), and 9-(4- 18 F-3-hydroxymethylbutyl)-guanine( 18 F-FHBG) in the detection of urologic tumors, can deserve further study. (authors)

  7. Prospective Evaluation of Changes in Tumor Size and Tumor Metabolism in Patients with Advanced Gastric Cancer Undergoing Chemotherapy: Association and Clinical Implication.

    Science.gov (United States)

    Park, Seongyeol; Ha, Seunggyun; Kwon, Hyun Woo; Kim, Woo Hyoung; Kim, Tae-Yong; Oh, Do-Youn; Cheon, Gi Jeong; Bang, Yung-Jue

    2017-06-01

    A change in tumor size is a well-validated and commonly used value for evaluating response to chemotherapy in cancer. Metabolic changes induced by chemotherapy are related to prognosis in several tumor types. However, the clinical implication of metabolic changes in patients with advanced gastric cancer (AGC) undergoing chemotherapy remains unclear. We aimed to evaluate response of tumor size and metabolism in AGC during chemotherapy and to reveal the relationship between them in view of their impact on patient survival. Methods: We prospectively enrolled patients with AGC before the initiation of first-line palliative chemotherapy. Using baseline and follow-up contrast-enhanced CT and 18 F-FDG PET, we assessed the tumor diameter, SUV max , and total lesion glycolysis in each lesion and their changes during chemotherapy at the same time. We included all lesions with the maximal longest diameters over 1 cm on CT, and each lesion was evaluated by matched 18 F-FDG PET. We analyzed the association between changes in tumor metabolism and tumor size and performed outcome analysis on overall survival (OS) and progression-free survival (PFS). Results: Seventy-four patients were enrolled, and the number of all lesions included in this study was 620. Compared with adenocarcinomas, poorly cohesive carcinomas demonstrated lower SUV max irrespective of tumor size ( P chemotherapy had a linear correlation with the changes in tumor size of each lesion, and a 30% tumor size reduction was associated with a 50% SUV max reduction ( P chemotherapy correlated with changes in tumor size in AGC. Considering both changes in metabolism and size could help predict a more accurate prognosis for AGC patients undergoing chemotherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  8. Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

    2018-03-01

    This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62-92 GyE 10 . Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

  9. Tumor immunotherapy : clinics of cytokines and monoclonal antibodies

    NARCIS (Netherlands)

    Nieken, Judith

    1999-01-01

    Tumor immunotherapy is defines as treatment that induces anti-tumor responses via the modulation of both cellular and homoral components of the host immune system. Its concept is based on hte assumption that tumor cells express unique protiens, so-calles tumor antigens, that can be identified as

  10. Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans

    Czech Academy of Sciences Publication Activity Database

    Stapelberg, M.; Zobalová, Renata; Nguyen, M.N.; Walker, T.; Stantic, M.; Goodwin, J.; Pasdar, E.A.; Thai, T.; Prokopová, Kateřina; Yan, B.; Hall, S.; de Pennington, N.; Thomas, S.R.; Grant, G.; Štursa, Jan; Bajziková, Martina; Meedeniya, A.C.B.; Truksa, Jaroslav; Ralph, S. J.; Ansorge, O.; Dong, L.-F.; Neužil, Jiří

    2014-01-01

    Roč. 67, FEB (2014), s. 41-50 ISSN 0891-5849 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP305/12/1708 Institutional support: RVO:86652036 ; RVO:61388963 Keywords : IDO * Tumor-initiating cells * Mitocans * Mitochondrially targeted vitamin E succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.736, year: 2014

  11. Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

    International Nuclear Information System (INIS)

    Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

    1989-01-01

    The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors

  12. Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

    Energy Technology Data Exchange (ETDEWEB)

    Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

    1989-05-01

    The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors.

  13. Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

    2010-01-01

    Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

  14. The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

    Science.gov (United States)

    Walsh, Joseph C.; Lebedev, Artem; Aten, Edward; Madsen, Kathleen; Marciano, Liane

    2014-01-01

    I. Introduction II. The Clinical Importance of Tumor Hypoxia A. Pathophysiology of hypoxia B. Hypoxia's negative impact on the effectiveness of curative treatment 1. Hypoxic tumors accumulate and propagate cancer stem cells 2. Hypoxia reduces the effectiveness of radiotherapy 3. Hypoxia increases metastasis risk and reduces the effectiveness of surgery 4. Hypoxic tumors are resistant to the effects of chemotherapy and chemoradiation C. Hypoxia is prognostic for poor patient outcomes III. Diagnosis of Tumor Hypoxia A. Direct methods 1. Oxygen electrode—direct pO2 measurement most used in cancer research 2. Phosphorescence quenching—alternative direct pO2 measurement 3. Electron paramagnetic resonance 4. 19F-magnetic resonance spectroscopy 5. Overhauser-enhanced MRI B. Endogenous markers of hypoxia 1. Hypoxia-inducible factor-1α 2. Carbonic anhydrase IX 3. Glucose transporter 1 4. Osteopontin 5. A combined IHC panel of protein markers for hypoxia 6. Comet assay C. Physiologic methods 1. Near-infrared spectroscopy/tomography—widely used for pulse oximetry 2. Photoacoustic tomography 3. Contrast-enhanced color duplex sonography 4. MRI-based measurements 5. Blood oxygen level-dependent MRI 6. Pimonidazole 7. EF5 (pentafluorinated etanidazole) 8. Hypoxia PET imaging—physiologic hypoxia measurement providing tomographic information a. 18F-fluoromisonidazole b. 18F-fluoroazomycinarabinofuranoside c. 18F-EF5 (pentafluorinated etanidazole) d. 18F-flortanidazole e. Copper (II) (diacetyl-bis (N4-methylthiosemicarbazone)) f. 18F-FDG imaging of hypoxia IV. Modifying Hypoxia to Improve Therapeutic Outcomes A. Use of hypoxia information in radiation therapy planning B. Use of hypoxia assessment for selection of patients responsive to nimorazole C. Use of hypoxia assessment for selection of patients responsive to tirapazamine D. Use of hypoxia assessment for selection of patients

  15. Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

    Directory of Open Access Journals (Sweden)

    Nina P Connolly

    Full Text Available Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS virus / tumor virus receptor-A (tv-a transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

  16. Clinical significance of serum thymosin α1 assay in tumor patients

    International Nuclear Information System (INIS)

    Wang Jiamin; Lv Ming'en; Zhao Xiaojuan; Gao Weiqiang; Bai Xia; Wang Zhaoyue

    2003-01-01

    Objective: To investigate the clinical significance of thymosin α1(Tα1) measurement in evaluating clinical status of patients with solid malignant tumors. Methods: Tα1 levels in serum of 50 normal adults, 20 patients with benign tumors and 63 patients with malignant tumors were measured by enzyme linked immunosorbent assay (ELISA). The association of Tα1 level with tumor invasion, metastasis and its alteration after different treatment in patients with malignant tumors were also studied. Results: The serum Tα1 level was 0.69±0.35 μg/L in normal adults, 0.96±0.37 μg/L in patients with benign tumors and 1.46±0.90 μg/L in patients with malignant tumors. In comparison it was both increased between patients with benign and malignant tumors and the normal adults (P<0.01 and P<0.001). And its increasing extent in malignant tumors was much greater than that in benign tumors (P<0.05). The serum Tα1 level in patients with malignant tumors was correlated with tumor invasion, metastasis and different treatment intervention. Conclusions: Our findings suggest that the serum Tα1 level be increased in tumor patients, and that it may be used as a new tumor marker in clinic

  17. Salivary gland tumors in Uganda: clinical pathological study ...

    African Journals Online (AJOL)

    African Health Sciences ... salivary gland tumors as defined by WHO classification (1991), is accepted world-wide but little is available in the literature ... Objective: To outline the clinicopathological features of salivary gland tumors in Uganda.

  18. PDT for malignant tumors: a clinical analysis of 152 cases

    Science.gov (United States)

    Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

    1993-03-01

    Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

  19. Phyllodes tumor: clinical, radiological and pathological correlation in 50 cases; Tumor filodes: correlacion clinica, radiologica y anatomopatologica en 50 casos

    Energy Technology Data Exchange (ETDEWEB)

    Higueras, A.; Alvarez, M.; Jimenez, A.; Garcia Revillo, J.; Cano, A. [Hospital Universitario Reina Sofia. Cordoba (Spain)

    2000-07-01

    To review the radiological features of the phyllodes tumor, correlating them with the clinical presentation, histological type and response to treatment. Fifty phyllodes tumors in 29 patients aged 16 to 59 years (mean: 41 years) were analyzed retrospectively. The series included 12 cases of recurrence, 1 of bilateral tumor and 6 of multiple tumor. Forty-five lesions were studied by mammography and 36 by ultrasound. Clinically guided fine-needle aspiration cytology was performed in 8 cases. The pathological diagnosis was obtained by means of surgical biopsy in every case (31 benign and 19 malignant). Twenty-four patients underwent postoperative clinical and radiological follow-up for a mean period of 32 months. Mammography revealed the presence of a nodule or mass in 42 cases, asymmetrical density in two and a generalized increase in density in one: Multifocal lesions were detected in six cases. The size varied widely, with masses measuring >5 cm showing a greater probability of malignancy (p<0.01). Calcifications were observed in 13% of the cases. Ultrasound revealed the presence of heterogeneous, hypoechoic nodules, with cystic areas in five tumors, all of which were malignant (p<0.01). Local recurrence was detected in 31% of the cases and bone metastases in one. The phyllodes tumor is an uncommon fibroepithelial tumor that has a potential for recurrence and distant metastasis. Mammographic and ultrasound features are similar to those of the fibroadenoma, a lesion with which it is occasionally associated. Multiple lesions are not infrequent and it can present with calcifications. The presence of cystic areas and a tumor size of >5 cm are the only radiological findings that are statistically associated with malignancy. The recurrence rate is greater in malignant tumors than in benign lesions, especially in patients treated by tumor resection. (Author) 28 refs.

  20. Giant phyllodes tumor of the breast: a clinical observation

    Directory of Open Access Journals (Sweden)

    A. A. Volchenko

    2012-01-01

    Full Text Available The paper describes a case of giant phyllodes tumor of the breast. Phyllodes tumor is a rare type of fibroepithelial tumor composed of epithelial and connective tissue with the predominant development of a connective tissue component. Surgery is the only radical treatment.

  1. Giant phyllodes tumor of the breast: a clinical observation

    OpenAIRE

    A. A. Volchenko; D. D. Pak; F. N. Usov; E. Yu. Fetisova

    2012-01-01

    The paper describes a case of giant phyllodes tumor of the breast. Phyllodes tumor is a rare type of fibroepithelial tumor composed of epithelial and connective tissue with the predominant development of a connective tissue component. Surgery is the only radical treatment.

  2. Clinically Meaningful Use of Blood Tumor Markers in Oncology.

    Science.gov (United States)

    Holdenrieder, Stefan; Pagliaro, Lance; Morgenstern, David; Dayyani, Farshid

    2016-01-01

    Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.

  3. Clinically Meaningful Use of Blood Tumor Markers in Oncology

    Directory of Open Access Journals (Sweden)

    Stefan Holdenrieder

    2016-01-01

    Full Text Available Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.

  4. Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

    Science.gov (United States)

    Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

    2017-06-15

    Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Implementation of a quality improvement initiative in Belgian diabetic foot clinics: feasibility and initial results.

    Science.gov (United States)

    Doggen, Kris; Van Acker, Kristien; Beele, Hilde; Dumont, Isabelle; Félix, Patricia; Lauwers, Patrick; Lavens, Astrid; Matricali, Giovanni A; Randon, Caren; Weber, Eric; Van Casteren, Viviane; Nobels, Frank

    2014-07-01

    This article aims to describe the implementation and initial results of an audit-feedback quality improvement initiative in Belgian diabetic foot clinics. Using self-developed software and questionnaires, diabetic foot clinics collected data in 2005, 2008 and 2011, covering characteristics, history and ulcer severity, management and outcome of the first 52 patients presenting with a Wagner grade ≥ 2 diabetic foot ulcer or acute neuropathic osteoarthropathy that year. Quality improvement was encouraged by meetings and by anonymous benchmarking of diabetic foot clinics. The first audit-feedback cycle was a pilot study. Subsequent audits, with a modified methodology, had increasing rates of participation and data completeness. Over 85% of diabetic foot clinics participated and 3372 unique patients were sampled between 2005 and 2011 (3312 with a diabetic foot ulcer and 111 with acute neuropathic osteoarthropathy). Median age was 70 years, median diabetes duration was 14 years and 64% were men. Of all diabetic foot ulcers, 51% were plantar and 29% were both ischaemic and deeply infected. Ulcer healing rate at 6 months significantly increased from 49% to 54% between 2008 and 2011. Management of diabetic foot ulcers varied between diabetic foot clinics: 88% of plantar mid-foot ulcers were off-loaded (P10-P90: 64-100%), and 42% of ischaemic limbs were revascularized (P10-P90: 22-69%) in 2011. A unique, nationwide quality improvement initiative was established among diabetic foot clinics, covering ulcer healing, lower limb amputation and many other aspects of diabetic foot care. Data completeness increased, thanks in part to questionnaire revision. Benchmarking remains challenging, given the many possible indicators and limited sample size. The optimized questionnaire allows future quality of care monitoring in diabetic foot clinics. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Diagnosis and prognosis of brain tumors in clinical trials

    OpenAIRE

    Gorlia, Thierry

    2013-01-01

    textabstractAccording to the Central Brain Registry Of The United States (CBTRUS) statistical report (February 2012) the incidence rate of all primary non malignant and malignant brain and central nervous system tumors is 19.89 cases per 100.000 (11.58 for non-malignant tumors and 7.31 for malignant tumors). Malignant brain tumors account for only 1% to 2% of all adult cancers. As a comparison, in 2012, the incidence of women breast cancer was 121.2 (per 100.000). Tumors of neuroepithelial ti...

  7. Endocrine Tumors Causing Arterial Hypertension: Pathophysiological Mechanisms and Clinical Implications.

    Science.gov (United States)

    Buonacera, Agata; Stancanelli, Benedetta; Malatino, Lorenzo

    2017-09-01

    Some tumors are a relatively rare and amendable cause of hypertension, often associated with a higher cardiovascular morbidity and mortality, as compared with that of both general population and patients with essential hypertension. This worse prognosis is not entirely related to blood pressure increase, because the release of substances from the tumor can directly influence blood pressure behavior. Diagnostic approach is challenging and needs a deep knowledge of the different neuro-hormonal and genetic mechanisms determining blood pressure increase. Surgical tumor removal can, but not always, cause blood pressure normalization, depending on how early was tumor detection, since a long-standing history of hypertension is often associated with a much weaker effect on blood pressure. Moreover, target organ damage can be affected by the substances themselves released by the tumors as well as by tumor removal. In this review we consider the phenotype and genetic features of patients with tumor-induced hypertension and focus on their diagnostic work-up.

  8. Targeting cytokine signaling checkpoint CIS activates NK cells to protect from tumor initiation and metastasis

    Science.gov (United States)

    Putz, Eva M.; Guillerey, Camille; Kos, Kevin; Stannard, Kimberley; Miles, Kim; Delconte, Rebecca B.; Nicholson, Sandra E.; Huntington, Nicholas D.; Smyth, Mark J.

    2017-01-01

    ABSTRACT The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy. PMID:28344878

  9. Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Joseph G Skeate

    Full Text Available Nano-Pulse Stimulation (NPS is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.

  10. Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response.

    Science.gov (United States)

    Skeate, Joseph G; Da Silva, Diane M; Chavez-Juan, Elena; Anand, Snjezana; Nuccitelli, Richard; Kast, W Martin

    2018-01-01

    Nano-Pulse Stimulation (NPS) is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16)-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS) to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s) associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence.

  11. In Vivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors

    Directory of Open Access Journals (Sweden)

    Nabendu Pore

    2015-06-01

    Full Text Available Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up-regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX, monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model.

  12. Apparent diffusion coefficients of breast tumors. Clinical application

    International Nuclear Information System (INIS)

    Hatakenaka, Masamitsu; Soeda, Hiroyasu; Yabuuchi, Hidetake; Matsuo, Yoshio; Kamitani, Takeshi; Oda, Yoshinao; Tsuneyoshi, Masazumi; Honda, Hiroshi

    2008-01-01

    The purpose of this study was to evaluate the usefulness of apparent diffusion coefficient (ADC) for the differential diagnosis of breast tumors and to determine the relation between ADC and tumor cellularity. One hundred and thirty-six female patients (age range, 17-83 years; average age, 51.7 years) with 140 histologically proven breast tumors underwent diffusion-weighted magnetic resonance (MR) imaging (DWI) using the spin-echo echo-planar technique, and the ADCs of the tumors were calculated using 3 different b values, 0, 500, and 1000 s/mm 2 . The diagnoses consisted of fibroadenoma (FA, n=16), invasive ductal carcinoma, not otherwise specified (IDC, n=117), medullary carcinoma (ME, n=3) and mucinous carcinoma (MU, n=4). Tumor cellularity was calculated from surgical specimens. The ADCs of breast tumors and cellularity were compared between different histological types by analysis of variance and Scheffe's post hoc test. The correlation between tumor cellularity and ADC was analyzed by Pearson correlation test. Significant differences were observed in ADCs between FA and all types of cancers (P 2 =0.451). The ADC may potentially help in differentiating benign and malignant breast tumors. Tumor ADC correlates inversely with tumor cellularity. (author)

  13. Initial Readability Assessment of Clinical Trial Eligibility Criteria

    Science.gov (United States)

    Kang, Tian; Elhadad, Noémie; Weng, Chunhua

    2015-01-01

    Various search engines are available to clinical trial seekers. However, it remains unknown how comprehensible clinical trial eligibility criteria used for recruitment are to a lay audience. This study initially investigated this problem. Readability of eligibility criteria was assessed according to (i) shallow and lexical characteristics through the use of an established, generic readability metric; (ii) syntactic characteristics through natural language processing techniques; and (iii) health terminological characteristics through an automated comparison to technical and lay health texts. We further stratified clinical trials according to various study characteristics (e.g., source country or study type) to understand potential factors influencing readability. Mainly caused by frequent use of technical jargons, a college reading level was found to be necessary to understand eligibility criteria text, a level much higher than the average literacy level of the general American population. The use of technical jargons should be minimized to simplify eligibility criteria text. PMID:26958204

  14. Cholangiocarcinoma stem-like subset shapes tumor-initiating niche by educating associated macrophages

    DEFF Research Database (Denmark)

    Raggi, Chiara; Correnti, Margherita; Sica, Antonio

    2017-01-01

    BACKGROUND AND AIMS: Therapeutically challenging subset, termed cancer stem cells (CSCs) are responsible for cholangiocarcinoma (CCA) clinical severity. Presence of tumor-associated macrophages (TAMs) has prognostic significance in CCA and other malignancies. Thus, we hypothesized that CSCs may......-activator. Gene expression profile of CCA-SPH activated MØ (SPH MØ) revealed unique molecular TAM-like features confirmed by high invasion capacity. Also, freshly isolated MØs from CCA-resections recapitulated similar molecular phenotype of in vitro educated-MØs. Consistently with invasive features, largest CD163...... providing a rationale for a synergistic therapeutic strategy for CCA-disease. LAY SUMMARY: Immune plasticity represents an important hallmark of tumor outcome. Since cancer stem cells are able to manipulate stromal cells to their needs, a better definition of key deregulated immune subtype responsible...

  15. Influence of clinical and tumoral factors on the inter-fractions bones displacements during the treatment of gastric or esophagus cancers by external irradiation

    International Nuclear Information System (INIS)

    Quivrin, M.; Peignaux, K.; Truc, G.; Blanchard, N.; Ligey-Bartolomeu, A.; Maingon, P.; Crehange, G.; Liegard, M.; Bonnetain, F.; Petitfils, A.

    2009-01-01

    Purpose: to evaluate the influence of clinical and tumoral characteristics on the inter fractions bones displacements during the irradiation of eso gastric cancers. Conclusion: the local control of irradiated esophagus and gastric cancers stay not satisfying and could be improved by the individual adjustment of peritumoral margins in function of clinical and tumoral characteristics as age, sex, average weight at the beginning of the treatment, the index of the initial average body mass. (N.C.)

  16. Clinical evaluation of scintigraphy for malignant tumors in children

    International Nuclear Information System (INIS)

    Ishii, Katsumi; Aso, Koichi; Yamada, Nobuaki; Horiike, Shigeharu; Matsubayashi, Takashi

    1982-01-01

    X-ray study, Computed tomography, Echography and Scintigraphy are chosen to draw visual images of malignant tumors in children. To obtain higher diagnostic sensitivity, we recommend that 67-Ga-scintigraphy and other different scitigraphy for organs are performed on each child suspected of having malignant tumor. 67-Ga does not have accurate sensitivity for neuroblastoma, but bone scintigraphy with 99m-Tc-labelled phosphate complexes detects neuroblastoma as a positive image. 67-Ga scintigraphy and other different radiopharmaceutical scintigraphy should be used for primary visualization and control of malignant tumor in children. Serial scintigraphy at proper intervals are very effective to detect local recurrence and metastasis of malignant tumors. (author)

  17. Renal Tumor Anatomic Complexity: Clinical Implications for Urologists.

    Science.gov (United States)

    Joshi, Shreyas S; Uzzo, Robert G

    2017-05-01

    Anatomic tumor complexity can be objectively measured and reported using nephrometry. Various scoring systems have been developed in an attempt to correlate tumor complexity with intraoperative and postoperative outcomes. Nephrometry may also predict tumor biology in a noninvasive, reproducible manner. Other scoring systems can help predict surgical complexity and the likelihood of complications, independent of tumor characteristics. The accumulated data in this new field provide provocative evidence that objectifying anatomic complexity can consolidate reporting mechanisms and improve metrics of comparisons. Further prospective validation is needed to understand the full descriptive and predictive ability of the various nephrometry scores. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Upregulation of mitochondrial NAD+ levels impairs the clonogenicity of SSEA1+ glioblastoma tumor-initiating cells.

    Science.gov (United States)

    Son, Myung Jin; Ryu, Jae-Sung; Kim, Jae Yun; Kwon, Youjeong; Chung, Kyung-Sook; Mun, Seon Ju; Cho, Yee Sook

    2017-06-09

    Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD + ) metabolism. However, the functional role of NAD + metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD + levels affect the characteristics of glioma-driven SSEA1 + TICs, including clonogenic growth potential. An increase in the mitochondrial NAD + levels by the overexpression of the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) significantly suppressed the sphere-forming ability and induced differentiation of TICs, suggesting a loss of the characteristics of TICs. In addition, increased SIRT3 activity and reduced lactate production, which are mainly observed in healthy and young cells, appeared following NNT-overexpressed TICs. Moreover, in vivo tumorigenic potential was substantially abolished by NNT overexpression. Conversely, the short interfering RNA-mediated knockdown of NNT facilitated the maintenance of TIC characteristics, as evidenced by the increased numbers of large tumor spheres and in vivo tumorigenic potential. Our results demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD + levels and SIRT3 activity could be a promising strategy for abolishing the development of TICs as a new therapeutic approach to treating aging-associated tumors.

  19. Conservative management of pineal tumors - Mayo clinic experience

    International Nuclear Information System (INIS)

    Laws, E.R.; Abay, E.O.; Forbes, G.S.; Grado, G.L.; Bruckman, J.E.; Scott, M.

    1984-01-01

    The typical pineal tumor occurs in an adolescent boy with subacute increased intracranial pressure and Parinaud's syndrome. Diagnosis is confirmed by CT scanning, and long-term survival usually following shunting and radiation therapy. Direct surgical methods for successful treatment of suitable pineal tumors have evolved and may be utilized with relatively low risk in appropriate cases

  20. Diagnosis and prognosis of brain tumors in clinical trials

    NARCIS (Netherlands)

    T.S. Gorlia (Thierry)

    2013-01-01

    textabstractAccording to the Central Brain Registry Of The United States (CBTRUS) statistical report (February 2012) the incidence rate of all primary non malignant and malignant brain and central nervous system tumors is 19.89 cases per 100.000 (11.58 for non-malignant tumors and 7.31 for malignant

  1. Brown tumor of secondary hyperparathyroidism: surgical approach and clinical outcome.

    Science.gov (United States)

    Queiroz, Isaac Vieira; Queiroz, Samara Pereira; Medeiros, Rui; Ribeiro, Rodolfo Bonfim; Crusoé-Rebello, Iêda Margarida; Leão, Jair Carneiro

    2016-12-01

    Secondary hyperparathyroidism is a frequent complication of chronic renal failure. The brown tumor is an unusual presentation of fibrous osteitis that represents a serious complication of renal osteodystrophy, affecting predominantly the hands, feet, skull, and facial bones. The aim of this paper is to describe the case of a 53-year-old female patient, with renal failure who has been on dialysis for 6 years and developed severe secondary hyperparathyroidism and brown tumor of the maxilla and mandible, confirmed by incisional biopsy. Parathyroidectomy was indicated as a result of rapid growth of the tumor and the maintenance of laboratory findings. Despite the normalization of serum parathyroid hormone and alkaline phosphatase, tumor regression was slow and patient's important functional and esthetic deficits persisted. Excision of the mandible tumor was conservative. Osteoplasty was recommended because during a 5-year follow-up there was regression of the lesion, decreased pain, bleeding, and tooth mobility.

  2. Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2013-10-01

    According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

  3. A clinical and radiological objective tumor response with somatostatin analogs (SSA in well-differentiated neuroendocrine metastatic tumor of the ileum: a case report

    Directory of Open Access Journals (Sweden)

    De Divitiis C

    2015-03-01

    Full Text Available Chiara De Divitiis,1 Claudia von Arx,2 Roberto Carbone,3 Fabiana Tatangelo,4 Elena di Girolamo,5 Giovanni Maria Romano,1 Alessandro Ottaiano,1 Elisabetta de Lutio di Castelguidone,3 Rosario Vincenzo Iaffaioli,1 Salvatore Tafuto1 On behalf of the European Neuroendocrine Tumor Society (ENETS Center of Excellence Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy 1Department of Abdominal Oncology, National Cancer Institute “Fondazione G. Pascale”, Naples, Italy; 2Department of Clinical Medicine and Surgery, “Federico II” University, Naples, Italy; 3Department of Radiology, 4Department of Pathology, 5Department of Endoscopy, National Cancer Institute “Fondazione G Pascale”, Naples, Italy Abstract: Somatostatin analogs (SSAs are typically used to treat the symptoms caused by neuroendocrine tumors (NETs, but they are not used as the primary treatment to induce tumor shrinkage. We report a case of a 63-year-old woman with a symptomatic metastatic NET of the ileum. Complete symptomatic response was achieved after 1 month of treatment with SSAs. In addition, there was an objective response in the liver, with the disappearance of secondary lesions noted on computed tomography scan after 3 months of octreotide treatment. Our experience suggests that SSAs could be useful for downstaging and/or downsizing well-differentiated NETs, and they could allow surgery to be performed. Such presurgery therapy could be a promising tool in the management of patients with initially inoperable NETs. Keywords: neuroendocrine tumor, somatostatin analogs, octreotide, metastatic tumor of the ileum, radiological tumor response

  4. Giant cell tumor of the bone: aggressive case initially treated with denosumab and intralesional surgery

    Energy Technology Data Exchange (ETDEWEB)

    Von Borstel, Donald; Strle, Nicholas A. [Oklahoma State University Medical Center, Department of Radiology, Tulsa, OK (United States); Taguibao, Roberto A. [University of California, Irvine, UCI Medical Center, Department of Pathology, Orange, CA (United States); Burns, Joseph E. [University of California, Irvine, UCI Medical Center, Department of Radiological Sciences, Orange, CA (United States)

    2017-04-15

    Giant cell tumor of the bone (GCTB) is a locally aggressive benign tumor, which has historically been treated with wide surgical excision. We report a case of a 29-year-old male with histology-proven GCTB of the distal ulna. The initial imaging study was a contrast-enhanced magnetic resonance imaging (MRI) examination of the left wrist, which was from an outside facility performed before presenting to our institution. On the initial MRI, the lesion had homogenous T2-hyperintense and T1-hypointense signal with expansive remodeling of the osseous contour. A radiographic study performed upon presentation to our institution 1 month later showed progression of the lesion with atypical imaging characteristics. After confirming the diagnosis, denosumab therapy was implemented allowing for reconstitution of bone and intralesional treatment. The patient was treated with five doses of denosumab over the duration of 7 weeks. Therapeutic changes of the GCTB were evaluated by radiography and a post-treatment MRI. This MRI was interpreted as suspicious for worsening disease due to the imaging appearance of intralesional signal heterogeneity, increased perilesional fluid-like signal, and circumferential cortical irregularity. However, on subsequent intralesional curettage and bone autografting 6 weeks later, no giant cells were seen on the specimen. Thus, the appearance on the MRI, rather than representing a manifestation of lesion aggressiveness or a non-responding tumor, conversely represented the imaging appearance of a positive response to denosumab therapy. On follow-up evaluation, 5 months after intralesional treatment, the patient had recurrent disease and is now scheduled for wide-excision with joint prosthesis. (orig.)

  5. Advance MRI for pediatric brain tumors with emphasis on clinical benefits

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo; Ra, Young Shin [Asan Medical Center, University of Ulsan College of Medicine, Seoul(Korea, Republic of)

    2017-01-15

    Conventional anatomic brain MRI is often limited in evaluating pediatric brain tumors, the most common solid tumors and a leading cause of death in children. Advanced brain MRI techniques have great potential to improve diagnostic performance in children with brain tumors and overcome diagnostic pitfalls resulting from diverse tumor pathologies as well as nonspecific or overlapped imaging findings. Advanced MRI techniques used for evaluating pediatric brain tumors include diffusion-weighted imaging, diffusion tensor imaging, functional MRI, perfusion imaging, spectroscopy, susceptibility-weighted imaging, and chemical exchange saturation transfer imaging. Because pediatric brain tumors differ from adult counterparts in various aspects, MRI protocols should be designed to achieve maximal clinical benefits in pediatric brain tumors. In this study, we review advanced MRI techniques and interpretation algorithms for pediatric brain tumors.

  6. CT assessment of the correlation between clinical examination and bone involvement in oral malignant tumors

    International Nuclear Information System (INIS)

    Albuquerque, Marco Antonio Portela; Oliveira, Ilka Regina Souza; Cavalcanti, Marcelo Gusmao Paraiso; Kuruoshi, Marcia Etsuko

    2009-01-01

    Oral cancers have a tendency to invade the surrounding bone structures, and this has a direct influence on the treatment management and on outcomes. The objective of this study was to correlate the clinical parameters (location, clinical presentation and TNM staging) of oral malignant tumors that can be associated with a potential of bone invasion and determine the accuracy of clinical examination to predict bone involvement, using computed tomography (CT). Twenty five patients, with oral malignant tumors were submitted to clinical and CT examinations. CT was considered the standard parameter to evaluate the presence of bone involvement. Clinical assessment of location, presentation form and TNM staging of the tumors were then compared to the CT findings in predicting bone involvement. Bone involvement was observed in 68% of the cases. It was predicted that tumors located in the retromolar trigone and hard palate, with a clinical aspect of infiltrative ulcer or nodule and classified in stage IV had a high potential to cause bone involvement. The clinical examination assessment of these tumors showed to be a valuable tool to predict bone invasion, with high sensitivity (82%) and specificity (87.5%), based on the results found in the CT images. No statistical significance was found between the CT and clinical examinations regarding bone involvement. The identification of some clinical parameters such as location, clinical presentation, and TNM stage, associated with a detailed clinical examination, was considered a valuable tool for the assessment of bone destruction by oral malignant tumors. (author)

  7. CLINICAL VALUE OF CHROMOGRANIN A IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS

    Directory of Open Access Journals (Sweden)

    N. V. Lyubimova

    2015-01-01

    Full Text Available Background: Neuroendocrine tumors (NET is a heterogeneous group of neoplasms characterized by hypersecretion of biologically active sub- stances that manifests by specific syndromes and determines the clinical course of the disease. The most common NET types are those of gastrointestinal tract. The obligatory biochemical marker used in the examination of NET patients is chromogranin A (CgA.Aim: Evaluation of the CgA value for diagnostics and monitoring of gastrointestinal NETs.Materials and methods: A comparative study of plasma CgA levels was performed in 146 patients with gastroenteropancreatic neuroendocrine tu- mors and 66 healthy individuals using the enzyme immunoassay “Chromogranin A ELISA kit” (Dako A/S, Denmark.Results: CgA levels were significantly higher in patients with NETs of all localizations, such as pancreas, stomach, gut, small and large bowel, than in the healthy subjects (р < 0.000001. In NET patients, CgA secretion was highly variable, with the highest value in the group of patients with gastric NETs (102000 U/l. The highest CgA medians were detected in patients with small intestinal (183.9 U/l, colon (148.4 U/l and pancreatic (135.9 U/l NETs. There was an association between CgA secretion and extension or activity of NETs, with the highest median values in patients with hepatic metastases (395 U/l and those with carcinoid syndrome (352 U/l. The clinical significance of CgA as a NET marker was assessed using the cut-off value of 33 U/l, calculated according to the results in the control group. Overall diagnostic sensitivity of CgA in NET patients was high (85.8% with a specificity of 98.5%. Conclusion: The results obtained confirm a high sensitivity of CgA as a NET marker whose determination helps to improve accuracy of diagnostics and to assess NET prevalence.

  8. Patient engagement in clinical trials: The Clinical Trials Transformation Initiative's leadership from theory to practical implementation.

    Science.gov (United States)

    Patrick-Lake, Bray

    2018-02-01

    Patient engagement is an increasingly important aspect of successful clinical trials. Over the past decade, as patient group involvement in clinical trials has continued to increase and diversify, the Clinical Trials Transformation Initiative has not only recognized the crucial role patients play in improving the clinical trial enterprise but also made a deep commitment to help grow and shape the emerging field of patient engagement. This article describes the evolution of patient engagement including the origins of the patient engagement movement; barriers to successful engagement and remaining challenges to full and valuable collaboration between patient groups and trial sponsors; and Clinical Trials Transformation Initiative's role in influencing the field through organizational practices, formal project work and resulting recommendations, and external advocacy efforts.

  9. SU-E-J-181: Magnetic Resonance Image-Guided Radiation Therapy Workflow: Initial Clinical Experience

    International Nuclear Information System (INIS)

    Green, O; Kashani, R; Santanam, L; Wooten, H; Li, H; Rodriguez, V; Hu, Y; Mutic, S; Hand, T; Victoria, J; Steele, C

    2014-01-01

    Purpose: The aims of this work are to describe the workflow and initial clinical experience treating patients with an MRI-guided radiotherapy (MRIGRT) system. Methods: Patient treatments with a novel MR-IGRT system started at our institution in mid-January. The system consists of an on-board 0.35-T MRI, with IMRT-capable delivery via doubly-focused MLCs on three 60 Co heads. In addition to volumetric MR-imaging, real-time planar imaging is performed during treatment. So far, eleven patients started treatment (six finished), ranging from bladder to lung SBRT. While the system is capable of online adaptive radiotherapy and gating, a conventional workflow was used to start, consisting of volumetric imaging for patient setup using visible tumor, evaluation of tumor motion outside of PTV on cine images, and real-time imaging. Workflow times were collected and evaluated to increase efficiency and evaluate feasibility of adding the adaptive and gating features while maintaining a reasonable patient throughput. Results: For the first month, physicians attended every fraction to provide guidance on identifying the tumor and an acceptable level of positioning and anatomical deviation. Average total treatment times (including setup) were reduced from 55 to 45 min after physician presence was no longer required and the therapists had learned to align patients based on soft-tissue imaging. Presently, the source strengths were at half maximum (7.7K Ci each), therefore beam-on times will be reduced after source replacement. Current patient load is 10 per day, with increase to 25 anticipated in the near future. Conclusion: On-board, real-time MRI-guided RT has been incorporated into clinical use. Treatment times were kept to reasonable lengths while including volumetric imaging, previews of tumor movement, and physician evaluation. Workflow and timing is being continuously evaluated to increase efficiency. In near future, adaptive and gating capabilities of the system will be

  10. Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

    International Nuclear Information System (INIS)

    Sabharwal, Rohan; Vladica, Philip

    2006-01-01

    Purpose. To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality. Methods. Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. With the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter. Results. Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 ± 10.43 years. Mean tumor size was 1.95 ± 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications. Conclusions. Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors

  11. Initial clinical test of a breast-PET scanner

    International Nuclear Information System (INIS)

    Raylman, Raymond R.; Koren, Courtney; Schreiman, Judith S.; Majewski, Stan; Marano, Gary D.; Abraham, Jame; Kurian, Sobha; Hazard, Hannah; Filburn, Shannon

    2011-01-01

    The goal of this initial clinical study was to test a new positron emission/tomography imager and biopsy system (PEM/PET) in a small group of selected subjects to assess its clinical imaging capabilities. Specifically, the main task of this study is to determine whether the new system can successfully be used to produce images of known breast cancer and compare them to those acquired by standard techniques. The PEM/PET system consists of two pairs of rotating radiation detectors located beneath a patient table. The scanner has a spatial resolution of ∼2 mm in all three dimensions. The subjects consisted of five patients diagnosed with locally advanced breast cancer ranging in age from 40 to 55 years old scheduled for pre-treatment, conventional whole body PET imaging with F-18 Fluorodeoxyglucose (FDG). The primary lesions were at least 2 cm in diameter. The images from the PEM/PET system demonstrated that this system is capable of identifying some lesions not visible in standard mammograms. Furthermore, while the relatively large lesions imaged in this study where all visualised by a standard whole body PET/CT scanner, some of the morphology of the tumours (ductal infiltration, for example) was better defined with the PEM/PET system. Significantly, these images were obtained immediately following a standard whole body PET scan. The initial testing of the new PEM/PET system demonstrated that the new system is capable of producing good quality breast-PET images compared standard methods.

  12. Initial Clinical Experience Using the Amplatzer Vascular Plug

    International Nuclear Information System (INIS)

    Tuite, David J.; Kessel, David O.; Nicholson, Anthony A.; Patel, Jai V.; McPherson, Simon J.; Shaw, David R.

    2007-01-01

    Background and purpose. The Amplatzer Vascular Plug (AVP) is a self-expanding nitinol wire mesh vascular embolization device derived from the Amplatz septal occluder. We assessed the results of vascular embolization obtained using the AVP. Methods. A retrospective review was carried out of 23 consecutive cases of vascular embolization using the AVP in a variety of different clinical settings. The AVP was chosen to have a diameter approximately 30-50% greater than the target vessel. The device was delivered via an appropriately sized guide catheter and was released when satisfactorily positioned. Additional embolic agents were used in some cases. Results. All target vessels were successfully occluded with no device malpositioning or malfunction. In 14 (61%) patients the AVP was the sole embolic material. In the remaining patients additional agents were used, particularly in preoperative embolization of highly vascular renal tumors. The AVP does not cause instantaneous thrombosis and in high-flow situations thrombosis typically takes up to 15 min. Conclusion. The AVP is a safe, effective embolization device that provides a useful adjunct to the therapeutic armamentarium. It is particularly suited to the treatment of short high-flow vessels where coil migration and catheter dislodgment might occur. In the majority of cases no additional embolic agents are necessary but it may take up to 15 min for complete thrombosis to occur

  13. Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation.

    Science.gov (United States)

    Morenas-Rodríguez, Estrella; Sala, Isabel; Subirana, Andrea; Pascual-Goñi, Elba; Sánchez-Saudinós, MaBelén; Alcolea, Daniel; Illán-Gala, Ignacio; Carmona-Iragui, María; Ribosa-Nogué, Roser; Camacho, Valle; Blesa, Rafael; Fortea, Juan; Lleó, Alberto

    2018-06-04

    Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p clinical DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.

  14. Limited resection for duodenal gastrointestinal stromal tumors: Surgical management and clinical outcome

    Science.gov (United States)

    Hoeppner, Jens; Kulemann, Birte; Marjanovic, Goran; Bronsert, Peter; Hopt, Ulrich Theodor

    2013-01-01

    AIM: To analyze our experience in patients with duodenal gastrointestinal stromal tumors (GIST) and review the appropriate surgical approach. METHODS: We retrospectively reviewed the medical records of all patients with duodenal GIST surgically treated at our medical institution between 2002 and 2011. Patient files, operative reports, radiological charts and pathology were analyzed. For surgical therapy open and laparoscopic wedge resections and segmental resections were performed for limited resection (LR). For extended resection pancreatoduodenectomy was performed. Age, gender, clinical symptoms of the tumor, anatomical localization, tumor size, mitotic count, type of resection resectional status, neoadjuvant therapy, adjuvant therapy, risk classification and follow-up details were investigated in this retrospective study. RESULTS: Nine patients (5 males/4 females) with a median age of 58 years were surgically treated. The median follow-up period was 45 mo (range 6-111 mo). The initial symptom in 6 of 9 patients was gastrointestinal bleeding (67%). Tumors were found in all four parts of the duodenum, but were predominantly located in the first and second part of the duodenum with each 3 of 9 patients (33%). Two patients received neoadjuvant medical treatment with 400 mg imatinib per day for 12 wk before resection. In one patient, the GIST resection was done by pancreatoduodenectomy. The 8 LRs included a segmental resection of pars 4 of the duodenum, 5 wedge resections with primary closure and a wedge resection with luminal closure by Roux-Y duodeno-jejunostomy. One of these LRs was done minimally invasive; seven were done in open fashion. The median diameter of the tumors was 54 mm (14-110 mm). Using the Fletcher classification scheme, 3/9 (33%) tumors had high risk, 1/9 (11%) had intermediate risk, 4/9 (44%) had low risk, and 1/9 (11%) had very low risk for aggressive behaviour. Seven resections showed microscopically negative transsection margins (R0), two

  15. Initial clinical results of linac-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Shrieve, Dennis C.; Alexander, Eben; Kaiser, Ursula B.; Richardson, Gary E.; Black, Peter McL.; Loeffler, Jay S.

    1998-01-01

    Purpose: To retrospectively evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor and hormonal control and adverse effects of the treatment. Subjects and Methods: Forty-eight patients with pituitary adenoma who underwent SRS or SRT between September 1989 and September 1995 were analyzed. Of these, 18 received SRS and 30 received SRT. The median tumor volumes were 1.9 cm 3 for SRS and 5.7 cm 3 for SRT. Eleven of the SRS and 18 of the SRT patients were hormonally active at the time of the initial diagnosis. Four of the SRS and none of the SRT patients had a history of prior radiation therapy. Both SRS and SRT were performed using a dedicated stereotactic 6-MV linear accelerator (LINAC). The dose and normalization used for the SRS varied from 1000 cGy at 85% of the isodose line to 1500 cGy at 65% of the isodose line. For SRT patients, a total dose of 4500 cGy at 90% or 95% of the isodose line was delivered in 25 fractions of 180 cGy daily doses. Results: Disease control--The three year tumor control rate was 91.1% (100% for SRS and 85.3% for SRT). Normalization of the hormonal abnormality was achieved in 47% of the 48 patients (33% for SRS and 54% for SRT). The average time required for normalization was 8.5 months for SRS and 18 months for SRT. Adverse effects--The 3-year rate of freedom from central nervous system adverse effects was 89.7% (72.2% for SRS and 100% for SRT). Three patients who received SRS for a tumor in the cavernous sinus developed a ring enhancement in the temporal lobe as shown by follow-up magnetic resonance imaging. Two of these cases were irreversible and were considered to be radiation necrosis. None of the 48 patients developed new neurocognitive or visual disorders attributable to the irradiation. The incidence of endocrinological adverse effects were similar in the two groups, resulting in 3-year rates of freedom from newly

  16. Targeting tumor-initiating cells: Eliminating anabolic cancer stem cells with inhibitors of protein synthesis or by mimicking caloric restriction

    Science.gov (United States)

    Lamb, Rebecca; Harrison, Hannah; Smith, Duncan L.; Townsend, Paul A.; Jackson, Thomas; Ozsvari, Bela; Martinez-Outschoorn, Ubaldo E.; Pestell, Richard G.; Howell, Anthony; Lisanti, Michael P.; Sotgia, Federica

    2015-01-01

    We have used an unbiased proteomic profiling strategy to identify new potential therapeutic targets in tumor-initiating cells (TICs), a.k.a., cancer stem cells (CSCs). Towards this end, the proteomes of mammospheres from two breast cancer cell lines were directly compared to attached monolayer cells. This allowed us to identify proteins that were highly over-expressed in CSCs and/or progenitor cells. We focused on ribosomal proteins and protein folding chaperones, since they were markedly over-expressed in mammospheres. Overall, we identified >80 molecules specifically associated with protein synthesis that were commonly upregulated in mammospheres. Most of these proteins were also transcriptionally upregulated in human breast cancer cells in vivo, providing evidence for their potential clinical relevance. As such, increased mRNA translation could provide a novel mechanism for enhancing the proliferative clonal expansion of TICs. The proteomic findings were functionally validated using known inhibitors of protein synthesis, via three independent approaches. For example, puromycin (which mimics the structure of tRNAs and competitively inhibits protein synthesis) preferentially targeted CSCs in both mammospheres and monolayer cultures, and was ~10-fold more potent for eradicating TICs, than “bulk” cancer cells. In addition, rapamycin, which inhibits mTOR and hence protein synthesis, was very effective at reducing mammosphere formation, at nanomolar concentrations. Finally, mammosphere formation was also markedly inhibited by methionine restriction, which mimics the positive effects of caloric restriction in cultured cells. Remarkably, mammosphere formation was >18-fold more sensitive to methionine restriction and replacement, as directly compared to monolayer cell proliferation. Methionine is absolutely required for protein synthesis, since every protein sequence starts with a methionine residue. Thus, the proliferation and survival of CSCs is very sensitive to

  17. Full structure assignments of pyrrolizidine alkaloid DNA adducts and mechanism of tumor initiation.

    Science.gov (United States)

    Zhao, Yuewei; Xia, Qingsu; Gamboa da Costa, Gonçalo; Yu, Hongtao; Cai, Lining; Fu, Peter P

    2012-09-17

    Pyrrolizidine alkaloid-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids are among the first chemical carcinogens identified in plants. Previously, we determined that metabolism of pyrrolizidine alkaloids in vivo and in vitro generated a common set of DNA adducts that are responsible for tumor induction. Using LC-ESI/MS/MS analysis, we previously determined that four DNA adducts (DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4) were formed in rats dosed with riddelliine, a tumorigenic pyrrolizidine alkaloid. Because of the lack of an adequate amount of authentic standards, the structures of DHP-dA-3 and DHP-dA-4 were not elucidated, and the structural assignment for DHP-dG-4 warranted further validation. In this study, we developed an improved synthetic methodology for these DNA adducts, enabling their full structural elucidation by mass spectrometry and NMR spectroscopy. We determined that DHP-dA-3 and DHP-dA-4 are a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl) dehydrosupinidine, while DHP-dG-4 is 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine, an epimer of DHP-dG-3. With the structures of these DNA adducts unequivocally elucidated, we conclude that cellular DNA preferentially binds dehydropyrrolizidine alkaloid, for example, dehydroriddelliine, at the C9 position of the necine base, rather than at the C7 position. We also determined that DHP-dA-3 and DHP-dA-4, as well as DHP-dG-3 and DHP-dG-4, are interconvertible. This study represents the first report with detailed structural assignments of the DNA adducts that are responsible for pyrrolizidine alkaloid tumor induction on the molecular level. A mechanism of tumor initiation by pyrrolizidine alkaloids is consequently fully determined.

  18. Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer.

    Science.gov (United States)

    Giessler, Klara M; Kleinheinz, Kortine; Huebschmann, Daniel; Balasubramanian, Gnana Prakash; Dubash, Taronish D; Dieter, Sebastian M; Siegl, Christine; Herbst, Friederike; Weber, Sarah; Hoffmann, Christopher M; Fronza, Raffaele; Buchhalter, Ivo; Paramasivam, Nagarajan; Eils, Roland; Schmidt, Manfred; von Kalle, Christof; Schneider, Martin; Ulrich, Alexis; Scholl, Claudia; Fröhling, Stefan; Weichert, Wilko; Brors, Benedikt; Schlesner, Matthias; Ball, Claudia R; Glimm, Hanno

    2017-07-03

    A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences. © 2017 Giessler et al.

  19. Microarray analysis in clinical oncology: pre-clinical optimization using needle core biopsies from xenograft tumors

    International Nuclear Information System (INIS)

    Goley, Elizabeth M; Anderson, Soni J; Ménard, Cynthia; Chuang, Eric; Lü, Xing; Tofilon, Philip J; Camphausen, Kevin

    2004-01-01

    DNA microarray profiling performed on clinical tissue specimens can potentially provide significant information regarding human cancer biology. Biopsy cores, the typical source of human tumor tissue, however, generally provide very small amounts of RNA (0.3–15 μg). RNA amplification is a common method used to increase the amount of material available for hybridization experiments. Using human xenograft tissue, we sought to address the following three questions: 1) is amplified RNA representative of the original RNA profile? 2) what is the minimum amount of total RNA required to perform a representative amplification? 3) are the direct and indirect methods of labeling the hybridization probe equivalent? Total RNA was extracted from human xenograft tissue and amplified using a linear amplification process. RNA was labeled and hybridized, and the resulting images yielded data that was extracted into two categories using the mAdb system: 'all genes' and 'outliers'. Scatter plots were generated for each slide and Pearson Coefficients of correlation were obtained. Results show that the amplification of 5 μg of total RNA yields a Pearson Correlation Coefficient of 0.752 (N = 6,987 genes) between the amplified and total RNA samples. We subsequently determined that amplification of 0.5 μg of total RNA generated a similar Pearson Correlation Coefficient as compared to the corresponding original RNA sample. Similarly, sixty-nine percent of total RNA outliers were detected with 5 μg of amplified starting RNA, and 55% of outliers were detected with 0.5 μg of starting RNA. However, amplification of 0.05 μg of starting RNA resulted in a loss of fidelity (Pearson Coefficient 0.669 between amplified and original samples, 44% outlier concordance). In these studies the direct or indirect methods of probe labeling yielded similar results. Finally, we examined whether RNA obtained from needle core biopsies of human tumor xenografts, amplified and indirectly

  20. Clinical features analysis of elderly patients with malignant tumor before dying

    International Nuclear Information System (INIS)

    Tang Haiying

    2010-01-01

    Objective: To analyse the clinical features of elderly patients with malignant tumor before death. Method: Fifty-two elderly patients with malignant tumor were retrospectively analyzed respectively from sputum culture and plasma FIB, D-dimer, albumin, hemoglobin aspects. Result: Results of sputum cultures showed the percentage of gram-negative bacteria was 56. 6%, gram-positive bacteria was 24. 5% and fungus was 18. 8%. The level of plasma FIB and D-dimer in the tumor group significantly higher than those in the control (P < 0. 05). The level of plasma albumin and hemoglobin in the tumor group were significantly lower than those in the control (P < 0. 01). Conclusion: Elderly patients with malignant tumor has obvious clinical features before death. Understanding them has important significance for guidelines of clinical treatment and judgement of prognosis. (authors)

  1. Clinical results of radiation therapy for thymic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Fushiki, Masato

    1991-12-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author).

  2. Clinical results of radiation therapy for thymic tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki; Takahashi, Masaji; Fushiki, Masato.

    1991-01-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author)

  3. Clinical course of non-operated patients with spinal cord tumor

    International Nuclear Information System (INIS)

    Kamata, Michihiro; Kinouchi, Junnosuke; Maruiwa, Hirofumi; Nakamura, Masaya; Matsumoto, Morio; Chiba, Kazuhiro; Toyama, Yoshiaki

    2003-01-01

    The clinical course of spinal cord tumors in 24 non-operated patients who were followed by MRI for more than 1 year was investigated retrospectively. Only 7 patients were positive in neurological symptoms. 7 patients had multiple tumors, and the histopathologic diagnosis in 16 patients was neurinoma. The MRI findings changed in 4 patients, and follow-up MR images showed rapid growth of 2 neurinomas. The clinical manifestations did not change in 17 patients, but they improved in 3 patients whose symptoms were not caused by tumors and improved after temporary worsening caused by tumor growth in 2 patients. They worsened in 2 patients with intramedullary tumors associated with neurological symptoms. The diameter of the spinal cord of the patients with intramedullary tumors increased, making the spinal cord susceptible to both anterior and posterior compression. Finally, the clinical course of the patients with spinal cord tumors did not deteriorate rapidly, except in the patients with intramedullary tumor associated with neurological manifestations. We concluded that when spinal cord tumors that are asymptomatic or associated with minor symptoms are diagnosed as neurinoma or neurofibroma based on the MRI findings, early surgery should not be performed and followed by meticulous follow-up. (author)

  4. Endobronchial carcinoid tumor: Radiological findings of a clinical case

    Directory of Open Access Journals (Sweden)

    Rodolfo Mendes Queiroz

    Full Text Available Summary We describe the case of a female patient, 21 years old, complaining of dyspnea attacks and wheezing 2 years ago. Chest radiography showed volume loss in the left lower lobe and ipsilateral retrocardiac triangular basal opacity. CT scan showed an extensive solid mass with apex protruding into the left main and lower lobar bronchi, causing distal atelectasis. Histopathological and immunohistochemical study of transbronchial biopsy of the lesion revealed a typical carcinoid tumor, confirmed after tumor resection with total left pneumectomy.

  5. Clinical trial aims to study immunotherapy for central nervous system tumors | Center for Cancer Research

    Science.gov (United States)

    A new clinical trial aims to determine whether nivolumab, an immune checkpoint inhibitor, can improve control of cancer for patients with several types of tumors of the central nervous system (CNS). The CNS is composed of the brain and spinal cord and the cause of most CNS tumors in adults is unknown. Learn more...

  6. Radiofrequency ablation of liver tumors (II): clinical application and outcomes.

    Science.gov (United States)

    Vanagas, Tomas; Gulbinas, Antanas; Pundzius, Juozas; Barauskas, Giedrius

    2010-01-01

    Radiofrequency ablation is one of the alternatives in the management of liver tumors, especially in patients who are not candidates for surgery. The aim of this article is to review applicability of radiofrequency ablation achieving complete tumor destruction, utility of imaging techniques for patients' follow-up, indications for local ablative procedures, procedure-associated morbidity and mortality, and long-term results in patients with different tumors. The success of local thermal ablation consists in creating adequate volumes of tissue destruction with adequate "clear margin," depending on improved delivery of radiofrequency energy and modulated tissue biophysiology. Different volumes of coagulation necrosis are achieved applying different types of electrodes, pulsing energy sources, utilizing sophisticated ablation schemes. Some additional methods are used to increase the overall deposition of energy through alterations in tissue electrical conductivity, to improve heat retention within the tissue, and to modulate tolerance of tumor tissue to hyperthermia. Contrast-enhanced computed tomography, magnetic resonance imaging, ultrasound or positron emission tomography are applied to control the effectiveness of radiofrequency ablation. The long-term results of radiofrequency ablation are controversial.

  7. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress

    NARCIS (Netherlands)

    Lammers, Twan Gerardus Gertudis Maria; Kiessling, F.; Hennink, W.E.; Storm, Gerrit

    2012-01-01

    Abstract Many different systems and strategies have been evaluated for drug targeting to tumors over the years. Routinely used systems include liposomes, polymers, micelles, nanoparticles and antibodies, and examples of strategies are passive drug targeting, active drug targeting to cancer cells,

  8. Parents' perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative.

    Science.gov (United States)

    Greenberg, Rachel G; Gamel, Breck; Bloom, Diane; Bradley, John; Jafri, Hasan S; Hinton, Denise; Nambiar, Sumathi; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

    2018-03-01

    Enrollment of children into pediatric clinical trials remains challenging. More effective strategies to improve recruitment of children into trials are needed. This study used in-depth qualitative interviews with parents who were approached to enroll their children in a clinical trial in order to gain an understanding of the barriers to pediatric clinical trial participation. Twenty-four parents whose children had been offered the opportunity to participate in a clinical trial were interviewed: 19 whose children had participated in at least 1 clinical trial and 5 who had declined participation in any trial. Each study aspect, from the initial explanation of the study to the end of the study, can affect the willingness of parents to consent to the proposed study and future studies. Establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents' decisions. In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials.

  9. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.

    2007-01-01

    ) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. Cell lines isolated from MMTV-cyclin D1-Cdk2 (MMTV-D1K2) tumors exhibit Rb and p130 hyperphosphorylation and up-regulation of the protein products of E2F-dependent genes. These results suggest that cyclin D1/Cdk2 complexes may...... sites. Together, these results suggest that deregulation of the Cdk/Rb/E2F axis reprograms mammary epithelial cells to initiate a paracrine loop with tumor-associated fibroblasts involving TGF beta and HGF, resulting in desmoplasia. The MMTV-DIK2 mice should provide a useful model system...

  10. Allogeneic tumor cell vaccines: the promise and limitations in clinical trials.

    Science.gov (United States)

    Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

    2014-01-01

    The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies.

  11. Clinical experience in humans with radiolabeled antibody for tumor detection

    International Nuclear Information System (INIS)

    Morrison, R.T.; Lyster, D.M.; Szasz, I.; Alcorn, L.N.; Huckell, V.F.; Rhodes, B.; Breslow, K.; Burchiel, S.

    1982-01-01

    I-131 and Tc-99m labeled polyclonal or monoclonal antibody and fragments of antibody, specific to human chorionic gonadotropin (hCG) or to a melanoma cell surface antigen (MCSA) were injected into proven cancer patients. Using standard homeostasis parameters, and scanning techniques, the safety and efficacy of each antibody was evaluated. Antibody fragments were expected to clear faster from the circulation allowing for earlier imaging and a better target-to-non-target ratio. The technetium label may perturb the antiboby's kinetics so that clearance is more rapid for both whole antibody and fragments. After a statistical evaluation of all parameters measured pre and post injection it was concluded that no acute toxicity reactions were present in any patient studied. Scan results were not acceptable for a tumor detecting procedure used in routine practice. Tumor upake was seen in less than 10% of scans

  12. Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

    DEFF Research Database (Denmark)

    Antonovic, Laura; Lindblom, Emely; Dasu, Alexandru

    2014-01-01

    , using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER...... was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related...... to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high...

  13. Clinically Meaningful Use of Blood Tumor Markers in Oncology

    OpenAIRE

    Holdenrieder, Stefan; Pagliaro, Lance; Morgenstern, David; Dayyani, Farshid

    2016-01-01

    Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. H...

  14. Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes

    Directory of Open Access Journals (Sweden)

    Deep Dutta

    2013-01-01

    Full Text Available Primitive neuroectodermal tumor (PNET of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm on computed tomography (CT was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen, vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE. This is the first report of adrenal peripheral PNET (pPNET from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.

  15. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Malgorzata Banys

    2014-01-01

    Full Text Available Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  16. Clinical impact of anatomo-functional evaluation of brain function during brain tumor surgery

    International Nuclear Information System (INIS)

    Mikuni, Nobuhiro; Kikuchi, Takayuki; Matsumoto, Atsushi; Yokoyama, Yohei; Takahashi, Jun; Hashimoto, Nobuo

    2009-01-01

    To attempt to improve surgical outcome of brain surgery, clinical significance of anatomo-functional evaluation of brain function during resection of brain tumors was assessed. Seventy four patients with glioma located near eloquent areas underwent surgery while awake. Intraoperative tractography-integrated functional neuronavigation and cortical/subcortical electrical stimulation were correlated with clinical symptoms during and after resection of tumors. Cortical functional areas were safely removed with negative electric stimulation and eloquent cortices could be removed in some circumstances. Subcortical functional mapping was difficult except for motor function. Studying cortical functional compensation allows more extensive removal of brain tumors located in the eloquent areas. (author)

  17. Detecting somatostatin receptor in breast tumor tissue and its clinical significance

    International Nuclear Information System (INIS)

    Zhang Yongjian; Yu Xian; Lin Wei; Ding Xuan; Huang Shizhang; Lu Guangming

    2002-01-01

    The authors observe the difference of somatostatin receptor (SSR) between benign and malignant breast tumor and the relation between SSR and estrogen receptor (ER) or progesterone receptor (PR) in breast tumor tissue, and to predict the clinical value of detecting breast tumor by SSR receptor imaging. These tissues excised from operation in breast tumor were divided into 4 groups: breast malignant tumor group (BMTG) and its control group (C1G), breast benign tumor group (BBTG) and its control group (C2G). SSR was detected by radioligand binding assay (RBA) and ER, PR by LsAB method in these groups. Results is: (1) The SSR express quantity is 108.6 +- 67.3 fmol/mg pr, 37.2 +- 9.6 fmol/mg pr, 43.4 +- 12.6 fmol/mg pr 33.9 +- 10.2 fmol/mg pr respectively in BMTG, C1G, BBTG, C2G. The SSR of BMTG is the most among these groups, the difference is obvious, P 0.05); (2) The correlation coefficient of SSR and ER is 0.859, SSR and PR is 0.750. Most breast tumor tissues express high density SSR, the authors suppose that malignant tumor can been distinguished from benign tumor preliminarily by SSR receptor imaging. There is a good correlation between SSR and ER, PR, detecting SSR may predict the quality of tumor and the prognosis of the patient

  18. Intra-tumor heterogeneity in head and neck cancer and its clinical implications

    Directory of Open Access Journals (Sweden)

    Edmund A. Mroz

    2016-06-01

    Full Text Available The presence of heritable differences among cancer cells within a tumor, called intra-tumor genetic heterogeneity, has long been suspected of playing a role in poor responses to therapy. Research over the past decade has documented the existence of such heterogeneity within tumors of individual patients and documented its potential clinical significance. The research methods for identifying this heterogeneity were not, however, readily adaptable to widespread clinical application. After a brief review of this background, we describe the development of a measure of intra-tumor genetic heterogeneity, based on whole-exome sequencing of individual tumor samples, that could be applied to biopsy specimens in a clinical setting. This measure has now been used in head and neck squamous cell carcinoma (HNSCC to document, for the first time, a relation of high intra-tumor genetic heterogeneity to shorter overall survival in a large, multi-institutional study. The implications of heterogeneity for research and clinical care thus now need to be addressed. Keywords: Head and neck squamous cell carcinoma, Intra-tumor genetic heterogeneity, Next-generation sequencing, Targeted therapy

  19. Parents' perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative

    Directory of Open Access Journals (Sweden)

    Rachel G. Greenberg

    2018-03-01

    In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials.

  20. Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

    Science.gov (United States)

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-10-01

    Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

  1. NMR imaging of bladder tumors in males. Preliminary clinical experience

    International Nuclear Information System (INIS)

    Sigal, R.; Rein, A.J.J.T.; Atlan, H.; Lanir, A.; Kedar, S.; Segal, S.

    1985-01-01

    Nuclear magnetic resonance (NMR) of the normal and pathologic bladder was performed in 10 male subjects: 5 normal volunteers, 4 with bladder primary carcinoma, 1 with bladder metastasis. All scanning was done using a superconductive magnet operating at 0.5 T. Spin echo was used as pulse sequence. The diagnosis was confirmed in all cases by NMR imaging. The ability of the technique to provide images in axial, sagital and coronal planes allowed a precise assessment of the morphology and the size of the tumors. The lack of hazards and the quality of images may promote NMR imaging to a prominent role in the diagnosis of human bladder cancer [fr

  2. Clinical and pathological analysis of benign brain tumors resected after Gamma Knife surgery.

    Science.gov (United States)

    Liu, Ali; Wang, Jun-Mei; Li, Gui-Lin; Sun, Yi-Lin; Sun, Shi-Bin; Luo, Bin; Wang, Mei-Hua

    2014-12-01

    The goal of this study was to assess the clinical and pathological features of benign brain tumors that had been treated with Gamma Knife surgery (GKS) followed by resection. In this retrospective chart review, the authors identified 61 patients with intracranial benign tumors who had undergone neurosurgical intervention after GKS. Of these 61 patients, 27 were male and 34 were female; mean age was 49.1 years (range 19-73 years). There were 24 meningiomas, 18 schwannomas, 14 pituitary adenomas, 3 hemangioblastomas, and 2 craniopharyngiomas. The interval between GKS and craniotomy was 2-168 months, with a median of 24 months; for 7 patients, the interval was 10 years or longer. For 21 patients, a craniotomy was performed before and after GKS; in 9 patients, pathological specimens were obtained before and after GKS. A total of 29 patients underwent GKS at the Beijing Tiantan Hospital. All specimens obtained by surgical intervention underwent histopathological examination. Most patients underwent craniotomy because of tumor recurrence and/or exacerbation of clinical signs and symptoms. Neuroimaging analyses indicated tumor growth in 42 patients, hydrocephalus in 10 patients with vestibular schwannoma, cystic formation with mass effect in 7 patients, and tumor hemorrhage in 13 patients, of whom 10 had pituitary adenoma. Pathological examination demonstrated that, regardless of the type of tumor, GKS mainly induced coagulative necrosis of tumor parenchyma and stroma with some apoptosis and, ultimately, scar formation. In addition, irradiation induced vasculature stenosis and occlusion and tumor degeneration as a result of reduced blood supply. GKS-induced vasculature reaction was rarely observed in patients with pituitary adenoma. Pathological analysis of tumor specimens obtained before and after GKS did not indicate increased tumor proliferation after GKS. Radiosurgery is effective for intracranial benign tumors of small size and deep location and for tumor recurrence

  3. Pathological characteristics and clinical specifications in gastroenteropancreatic neuroendocrine tumors: a study of 68 cases.

    Science.gov (United States)

    Stoica-Mustafa, Elena; Pechianu, C; Iorgescu, Andreea; Hortopan, Monica; Dima, Simona Olimpia; Tomulescu, V; Dumitraşcu, T; Ungureanu, C; Andronesi, D; Popescu, I; Herlea, V

    2012-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of tumors, having their origin in cells of diffuse endocrine system, with particular clinical course, diagnosis and treatment. In our study, were included 68 patients with neuroendocrine digestive tumors admitted, diagnosed and treated in Fundeni Clinical Institute, Bucharest, in the last ten years--2000-2010 (retrospective study). Thirty-three (49%) patients were males, 35 (51%) females, and the main age was 58.9 years. In 62 (90.3%) cases was possible to find the primary tumor. The examined tumors had different localizations: pancreas--32 (47.04%) cases (head--17 (24.99%) cases, and body and tail--15 (22.05%) cases), stomach--7 (10.29%) cases, small intestine--7 (10.29%) cases, 6 (8.82%) cases--unknown primary site (diagnosis was established on metastases), right colon--6 (8.82%) cases, liver--6 (8.82%) cases, rectum--2 (2.94%) cases, and retroperitoneum--2 (2.94%) cases. Microscopic examination revealed 59 (86.8%) malignant tumors and 9 (13.2%) benign tumors. Using WHO 2000 Classification, 28 cases of malignant tumors were well-differentiated neuroendocrine carcinomas, and 31 cases were poor differentiated neuroendocrine carcinomas. From malignant cases, 25 (42.3%) have distant metastases and 15 (25.9%) lymph node metastases. Cases of gastroenteropancreatic neuroendocrine tumors included in our study had clinical and histopathological features in correspondence with data from literature--slight predominance in women, predominance in 5th and 6th decades of life, the most frequent localizations were at pancreatic level--both head and body and tail, but the rarest were in colon and retroperitoneum. Most of the cases studied, were malignant tumors, from these more than a half were poor differentiated, and a quarter of them having lymph node or distant metastases.

  4. Maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Beckett, M.

    1987-01-01

    We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .1 24 hrs following treatment with 7 Gy in plateau phase cultures is associated with tumor cell types (melanoma, osteosarcoma) with a high probability of radiotherapy failure or tumor cells derived from patients who actually failed radiotherapy. Therefore, total cellular recovery following radiation may be an important determinant of radiocurability. Accurate assays of radiotherapy outcome may need to account for all these radiobiological parameters

  5. Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Garfield, Susan H.; Thorgeirsson, Snorri S.; Avital, Itzhak

    2012-01-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  6. The clinical pathological features, diagnosis, treatment and prognosis of small intestine primary malignant tumors.

    Science.gov (United States)

    Guo, Xiaochuan; Mao, Zhiyuan; Su, Dan; Jiang, Zhaocai; Bai, Li

    2014-04-01

    The aim of the study was to describe and analyze the clinicopathological features and diagnosis of Chinese patients with small intestine primary malignant tumors and to explore the best therapy to small bowel adenocarcinoma (SBA). More than 26,000 patients with digestive tract malignant tumors received treatment in PLA hospital from 2000 to 2011, and among them, there were 887 patients who had small intestine primary malignant tumors, and 666 of 887 patients had the completed basic clinical documents. We retrospectively analyzed the correlation between clinical and pathological features of the 666 patients and analyzed the survival and prognosis of 173 SBA patients with follow-up data. Both the number of patients with primary malignant tumors of the small intestine and the number of patients who received chemotherapy showed an increasing trend. The ratio of male to female was 1.58:1. The male patients significantly exceed the female patients with tumors of non-ampullary duodenum, jejunum and duodenal ampulla; and most of the patients are over 60 years of age. For patients burdened with either of the pathological types of tumors, the males exceeded the females, but there was no significant difference. Abdominal pain was the main clinical manifestation for patients with tumors of non-ampullary duodenum, jejunum and ileum, and the most common clinical manifestations were jaundice and abdominal pain for patients with ampullary duodenal tumors, adenocarcinoma, neuroendocrine tumors and sarcoma. In addition, patients with stromal tumors were prone to gastrointestinal bleeding. Gastrointestinal endoscopy was the most common examinational procedure. Patients under 60 years of age were prone to surgery and chemotherapy after surgery, and patients over 60 years of age were prone to supportive treatment and chemotherapy without surgery. The medium overall survival of patients who received surgery without chemotherapy, chemotherapy after surgery, chemotherapy without surgery

  7. A Giant Heart Tumor in Neonate with Clinical Signs of Pierre - Robin Syndrome

    OpenAIRE

    Bejiqi, Ramush; Retkoceri, Ragip; Xhema-Bejiqi, Hana; Bejiqi, Rinor; Maloku, Arlinda

    2017-01-01

    Introduction: Pierre Robin syndrome is a congenital condition of facial abnormalities in humans. The three main features are: cleft palate, retrognathia and glossoptosis. Rarely heart tumors are associated with syndromes, mostly are isolated. Case report: In this presentation we describe a 3-weeks-old girl with Pierre-Robin syndrome and giant left ventricle tumor, diagnosed initially by transthoracic echocardiography. The purpose of this report is to review the literature on the fetuses and n...

  8. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice

    DEFF Research Database (Denmark)

    Sturgeon, Catharine M; Hoffman, Barry R; Chan, Daniel W

    2008-01-01

    BACKGROUND: This report presents updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines summarizing quality requirements for the use of tumor markers. METHODS: One subcommittee developed guidelines for analytical quality relevant to serum and tissue-based tumor...... questions to ensure selection of the appropriate test, adherence to good clinical and laboratory practices (e.g., minimization of the risk of incorrect patient and/or specimen identification, tube type, or timing), use of internationally standardized and well-characterized methods, careful adherence...... records. Also mandatory is extensive validation encompassing all stages of analysis before introduction of new technologies such as microarrays and mass spectrometry. Provision of high-quality tumor marker services is facilitated by dialogue involving researchers, diagnostic companies, clinical...

  9. Radiotherapy for pediatric brain tumors: Standards of care, current clinical trials, and new directions

    International Nuclear Information System (INIS)

    Goldwein, Joel W.

    1995-01-01

    The objectives of the course are to evaluate the role of radiation therapy in the treatment of pediatric brain tumors. Areas where the role is evolving will be identified, and the results of clinical trials which been mounted to clarify radiotherapy's role will be reviewed. Brain tumors are the second most common malignancy of childhood after leukemias and lymphomas. However, they remain the most common group of childhood tumors to require radiation therapy. Therefore, a thorough understanding of these tumors, and the appropriate role of surgery, radiation and chemotherapy is critical. Issues surrounding the management of sequelae are no less important. The role of radiotherapy for the treatment of these tumors is far different from that for adults. These differences relate to the profound potential for sequelae from therapy, the higher overall cure rates, and the utility of multimodality therapies. In addition, the rarity of childhood brain tumors compared with adults' makes them more difficult to study. In this session, the following issues will be reviewed; 1. Incidence of pediatric brain tumors, 2. General issues regarding symptoms, diagnosis, diagnostic tests and evaluation, 3. Importance of a team approach, 4. General issues regarding treatment sequelae, 5. Specific tumor types/entities; a. Cerebellar Astrocytomas b. Benign and malignant Gliomas including brainstem and chiasmatic lesions c. Primitive Neuroectodermal Tumors (PNET) and Medulloblastoma d. Ependymomas e. Craniopharyngiomas f. Germ cell tumors g. Miscellaneous and rare pediatric brain tumors 6. Management of sequelae 7. New and future directions a. Treatment of infants b. The expanding role of chemotherapy c. Advances in radiotherapy. The attendees will complete the course with a better understanding of the role that radiation therapy plays in the treatment of pediatric brain tumors. They will be knowledgeable in the foundation for that role, and the changes which are likely to take place in the

  10. [Clinical evaluation of female pelvic tumors : Application fields of integrated PET/MRI].

    Science.gov (United States)

    Grueneisen, J; Umutlu, L

    2016-07-01

    Integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) scanning has recently become established in clinical imaging. Various studies have demonstrated the great potential of this new hybrid imaging procedure for applications in the field of oncology and the diagnostics of inflammatory processes. With initial studies demonstrating the feasibility and high diagnostic potential of PET/MRI comparable to PET-computed tomography (CT), the focus of future studies should be on the identification of application fields with a potential diagnostic benefit of PET/MRI over other established diagnostic tools. Both MRI and PET/CT are widely used in the diagnostic algorithms for malignancies of the female pelvis. A simultaneous acquisition of PET and MRI data within a single examination provides complementary information which can be used for a more comprehensive evaluation of the primary tumor as well as for whole body staging. Therefore, the aim of this article is to outline potential clinical applications of integrated PET/MRI for the diagnostic work-up of primary or recurrent gynecological neoplasms of the female pelvis.

  11. The functions and clinical applications of tumor-derived exosomes

    Science.gov (United States)

    Shao, Yingkuan; Shen, Yanwei; Chen, Ting; Xu, Fei; Chen, Xuewen; Zheng, Shu

    2016-01-01

    Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm. They can be secreted by all cell types and transfer information in the form of their contents, which include proteins, lipids and nucleic acids, to other cells throughout the body. They have roles in normal physiological processes as well as in disease development. Here, we review recent findings regarding tumor-derived exosomes, including methods for their extraction and preservation. We also describe the actions of exosomes in tumorigenesis. The exosomal antigen-presenting effect during antitumor immune responses and its suppressive function in immune tolerance are discussed. Finally, we describe the potential application of exosomes to cancer therapy and liquid biopsy. PMID:27517627

  12. 'A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies'

    International Nuclear Information System (INIS)

    Marsden, Carolyn G; Wright, Mary Jo; Carrier, Latonya; Moroz, Krzysztof; Pochampally, Radhika; Rowan, Brian G

    2012-01-01

    The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis. Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC). Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor α (ERα)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 × 10 3 cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples. Tumorspheres isolated under defined culture

  13. Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Hamid R. Mirzaei

    2017-12-01

    Full Text Available Adoptive cellular immunotherapy (ACT employing engineered T lymphocytes expressing chimeric antigen receptors (CARs has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

  14. Clinical Evaluation of 57Co-labelled Bleomycin for Tumor Localization

    International Nuclear Information System (INIS)

    Ryu, Yong Wun; Kim, Jang Hee; Lee, Jhin Oh

    1987-01-01

    Investigation with 57 Co-Bleomycin in patients with the various cancers and in tumor bearing animals are described. In the patients, 57 Co-Bleomycin appears to be one of the useful tumor- seeking radiopharmaceuticals, and worth applicable to clinical uses. Labelled yield of 57 Co-Bleo was about 97% by thin layer chromatography. The pyrogen free tests were performed to meet U.S.P. critical ranges. In clinical studies with 57 Co-Bleo, 4 cases out of 5 patients with lung cancer, 2 cases among 3 thyroid cancer patients, and all 3 hepatoma patients showed positive tumor scans. The patients with stomach cancer, and the esophageal cancer showed false negative scintigraphy. A case with pulmonary tuberculosis showed a positive scan while liver abscess showed a negative picture. The merits of 57 Co-Bleomycin scintigraphy seems to be its relatively high affinity to tumors and low radiation hazard in spite of long physical half life.

  15. Clinical features and treatment outcomes of vasoproliferative tumors in Indian participants

    Directory of Open Access Journals (Sweden)

    Jaydeep Avinash Walinjkar

    2018-01-01

    Full Text Available Purpose: The aim of the study was to describe the clinical features and treatment outcomes of vasoproliferative tumors (VPT in Indian participants. Methods: This study design was a retrospective case series in a tertiary eye care center. Case records of patients diagnosed with VPT from 2011 to 2015 were reviewed, and their demographic details, clinical presentation, and treatment outcomes were documented. Baseline and follow-up visual acuity and tumor dimensions were statistically compared by applying paired t-test. Statistical analysis used SPSS version 14. Results: Twenty-two tumors from 19 eyes of 17 patients were included. Mean age at presentation was 43.5 years (range: 15–68 years. Mean presenting best-corrected visual acuity (BCVA was + 1.10 logMAR. Sixty-eight percent eyes had secondary tumors. Most common association of secondary VPT was Coats disease followed by retinal vasculitis, polypoidal choroidal vasculopathy, familial exudative vitreoretinopathy, and traumatic chorioretinopathy. Ten tumors (45% involved the inferior quadrant. Tumor-associated features were intra/subretinal exudates, vitritis, subretinal fluid, vitreous hemorrhage, preretinal fibrosis, epiretinal membrane, and subretinal blood. Treatment included cryotherapy, intravitreal or oral steroids, laser photocoagulation, cryotherapy with encirclage, cryotherapy with anti-vascular endothelial growth factor, and observation. Complications included tumor recurrence, retinal detachment, raised intraocular pressure, neovascularization of iris, and cataract. Ninety-five percent VPT regressed at mean 21 months (Median: 17 months; Range: 3–64 months. Mean final BCVA was + 1.21 logMAR. Conclusion: VPTs are commonly unilateral, unifocal, and located anterior to equator in inferior fundus. Secondary tumors are more common than primary tumors. Treatment achieves tumor regression in majority of cases.

  16. Some epidemiological and clinical characteristics of solid malignant tumors in children from Las Tunas

    Directory of Open Access Journals (Sweden)

    Silvio Laffita Estévez

    2015-11-01

    Full Text Available Background: cancer has kept up as the second cause of death in Las Tunas pediatric population.Objective: to characterize clinical and epidemiological variables of the cases diagnosed with solid malignant tumors in children seen and treated in the onco-pediatric consultation of “Mártires de Las Tunas” Pediatric Hospital from 2010 to 2014.Methods: a descriptive and retrospective study was carried out in 62 patients with solid malignant tumors in the pediatric population of Las Tunas province, from January, 2010 to December, 2014. The variables considered were: presumptive diagnosis, age, family history of tumors, clinical signs of alarm related to the tumor at the moment of diagnosis and investigations to confirm the diagnosis.  Results: non-Hodgkin lymphoma was the most frequently diagnosed tumor, with a 19, 35% of the patients. The most affected age group was between 11 and 14 years old, with a 33, 87%. The 16, 13% of the patients had family history of solid malignant tumors. The most frequent form of presentation was the abdominal tumor, with 29, 03 %. Abdominal ultrasound and computerized axial tomography were the most used complementary diagnostic means, both in the 17, 74% of the patients. Biopsy was used to confirm the 96, 77% of the cases.Conclusions: the clinical and epidemiological variables were characterized in pediatric patients diagnosed with solid malignant tumors in Las Tunas. Children between 11 and 14 years old and family history of malignant tumors were the most significant findings.

  17. A novel clinically translatable fluorescent nanoparticle for targeted molecular imaging of tumors in living subjects.

    Science.gov (United States)

    Gao, Jinhao; Chen, Kai; Luong, Richard; Bouley, Donna M; Mao, Hua; Qiao, Tiecheng; Gambhir, Sanjiv S; Cheng, Zhen

    2012-01-11

    The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD(2) to integrin α(v)β(3)-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future. © 2011 American Chemical Society

  18. Which drug or drug delivery system can change clinical practice for brain tumor therapy?

    OpenAIRE

    Siegal, Tali

    2013-01-01

    The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanis...

  19. PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

    Science.gov (United States)

    Li, Jiarong; Karaplis, Andrew C.; Huang, Dao C.; Siegel, Peter M.; Camirand, Anne; Yang, Xian Fang; Muller, William J.; Kremer, Richard

    2011-01-01

    Parathyroid hormone–related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer — it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention. PMID:22056386

  20. Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations.

    Science.gov (United States)

    Tamborero, David; Rubio-Perez, Carlota; Deu-Pons, Jordi; Schroeder, Michael P; Vivancos, Ana; Rovira, Ana; Tusquets, Ignasi; Albanell, Joan; Rodon, Jordi; Tabernero, Josep; de Torres, Carmen; Dienstmann, Rodrigo; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria

    2018-03-28

    While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Here we present the Cancer Genome Interpreter, a versatile platform that automates the interpretation of newly sequenced cancer genomes, annotating the potential of alterations detected in tumors to act as drivers and their possible effect on treatment response. The results are organized in different levels of evidence according to current knowledge, which we envision can support a broad range of oncology use cases. The resource is publicly available at http://www.cancergenomeinterpreter.org .

  1. Rare cancers in children - The EXPeRT Initiative: a report from the European Cooperative Study Group on Pediatric Rare Tumors.

    Science.gov (United States)

    Bisogno, G; Ferrari, A; Bien, E; Brecht, I B; Brennan, B; Cecchetto, G; Godzinski, J; Orbach, D; Reguerre, Y; Stachowicz-Stencel, T; Schneider, D T

    2012-10-01

    The low incidence and the heterogeneity of very rare tumors (VRTs) demand for international cooperation. In 2008, EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) was founded by national groups from Italy, France, United Kingdom, Poland and Germany. The first aims of EXPeRT were to agree on a uniform definition of VRTs and to develop the currently most relevant scientific questions. Current initiatives include international data exchange, retrospective and prospective studies of specific entities, and the development of harmonized and internationally recognized guidelines. Moreover, EXPeRT established a network for expert consultation to assist in clinical decision in VRTs. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling

    Directory of Open Access Journals (Sweden)

    Eunice Yuen Ting Lau

    2016-05-01

    Full Text Available Like normal stem cells, tumor-initiating cells (T-ICs are regulated extrinsically within the tumor microenvironment. Because HCC develops primarily in the context of cirrhosis, in which there is an enrichment of activated fibroblasts, we hypothesized that cancer-associated fibroblasts (CAFs would regulate liver T-ICs. We found that the presence of α-SMA(+ CAFs correlates with poor clinical outcome. CAF-derived HGF regulates liver T-ICs via activation of FRA1 in an Erk1,2-dependent manner. Further functional analysis identifies HEY1 as a direct downstream effector of FRA1. Using the STAM NASH-HCC mouse model, we find that HGF-induced FRA1 activation is associated with the fibrosis-dependent development of HCC. Thus, targeting the CAF-derived, HGF-mediated c-Met/FRA1/HEY1 cascade may be a therapeutic strategy for the treatment of HCC.

  3. Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

    Science.gov (United States)

    Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N

    2018-03-01

    Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. {sup 18}F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xiaoyuan; Park, Ryan; Shahinian, Anthony H.; Tohme, Michel; Khankaldyyan, Vazgen; Bozorgzadeh, Mohammed H.; Bading, James R.; Moats, Rex; Laug, Walter E.; Conti, Peter S. E-mail: pconti@usc.edu

    2004-02-01

    Brain tumors are highly angiogenesis dependent. The cell adhesion receptor integrin {alpha}{sub v}{beta}{sub 3} is overexpressed in glioma and activated endothelial cells and plays an important role in brain tumor growth, spread and angiogenesis. Suitably labeled {alpha}{sub v}{beta}{sub 3}-integrin antagonists may therefore be useful for imaging brain tumor associated angiogenesis. Cyclic RGD peptide c(RGDyK) was labeled with {sup 18}F via N-succinimidyl-4-[{sup 18}F]fluorobenzoate through the side-chain {epsilon}-amino group of the lysine residue. The radiotracer was evaluated in vivo for its tumor targeting efficacy and pharmacokinetics in subcutaneously implanted U87MG and orthotopically implanted U251T glioblastoma nude mouse models by means of microPET, quantitative autoradiography and direct tissue sampling. The N-4-[{sup 18}F]fluorobenzoyl-RGD ([{sup 18}F]FB-RGD) was produced in less than 2 h with 20-25% decay-corrected yields and specific activity of 230 GBq/{mu}mol at end of synthesis. The tracer showed very rapid blood clearance and both hepatobiliary and renal excretion. Tumor-to-muscle uptake ratio at 30 min was approximately 5 in the subcutaneous U87MG tumor model. MicroPET imaging with the orthotopic U251T brain tumor model revealed very high tumor-to-brain ratio, with virtually no uptake in the normal brain. Successful blocking of tumor uptake of [{sup 18}F]FB-RGD in the presence of excess amount of c(RGDyK) revealed receptor specific activity accumulation. Hence, N-4-[{sup 18}F]fluorobenzoyl labeled cyclic RGD peptide [{sup 18}F]FB-RGD is a potential tracer for imaging {alpha}{sub v}{beta}{sub 3}-integrin positive tumors in brain and other anatomic locations.

  5. [A clinical trial of neutron capture therapy for brain tumors

    International Nuclear Information System (INIS)

    Zamenhof, R.G.

    1990-01-01

    This document briefly describes recent advances in the author's laboratory. Topics described include neutron beam design, high- resolution autoradiography, boronated phenylalanine (BPA) distribution and survival studies in glioma bearing mice, computer- aided treatment planning, prompt gamma boron 10 analysis facility at MITI-II, non-rodent BPA toxicity studies, and preparations for clinical studies

  6. Heidelberg Ion Therapy Center (HIT): Initial clinical experience in the first 80 patients

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E. (Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)), E-mail: Stephanie.Combs@med.uni-heidelberg.de; Ellerbrock, Malte; Haberer, Thomas (Heidelberger Ionenstrahl Therapiezentrum (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg (Germany)) (and others)

    2010-10-15

    The Heidelberg Ion Therapy Center (HIT) started clinical operation in November 2009. In this report we present the first 80 patients treated with proton and carbon ion radiotherapy and describe patient selection, treatment planning and daily treatment for different indications. Patients and methods. Between November 15, 2009 and April 15, 2010, 80 patients were treated at the Heidelberg Ion Therapy Center (HIT) with carbon ion and proton radiotherapy. Main treated indications consisted of skull base chordoma (n = 9) and chondrosarcoma (n = 18), malignant salivary gland tumors (n=29), chordomas of the sacrum (n = 5), low grade glioma (n=3), primary and recurrent malignant astrocytoma and glioblastoma (n=7) and well as osteosarcoma (n = 3). Of these patients, four pediatric patients aged under 18 years were treated. Results. All patients were treated using the intensity-modulated rasterscanning technique. Seventy-six patients were treated with carbon ions (95%), and four patients were treated with protons. In all patients x-ray imaging was performed prior to each fraction. Treatment concepts were based on the initial experiences with carbon ion therapy at the Gesellschaft fuer Schwerionenforschung (GSI) including carbon-only treatments and carbon-boost treatments with photon-IMRT. The average time per fraction in the treatment room per patient was 29 minutes; for irradiation only, the mean time including all patients was 16 minutes. Position verification was performed prior to every treatment fraction with orthogonal x-ray imaging. Conclusion. Particle therapy could be included successfully into the clinical routine at the Dept. of Radiation Oncology in Heidelberg. Numerous clinical trials will subsequently be initiated to precisely define the role of proton and carbon ion radiotherapy in radiation oncology.

  7. Neurotrophin Signaling via TrkB and TrkC Receptors Promotes the Growth of Brain Tumor-initiating Cells*

    Science.gov (United States)

    Lawn, Samuel; Krishna, Niveditha; Pisklakova, Alexandra; Qu, Xiaotao; Fenstermacher, David A.; Fournier, Michelle; Vrionis, Frank D.; Tran, Nam; Chan, Jennifer A.; Kenchappa, Rajappa S.; Forsyth, Peter A.

    2015-01-01

    Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma. PMID:25538243

  8. Fractionated stereotactic radiation therapy for intracranial benign tumor : preliminary results of clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Yong; Ahn, Yong Chan; Huh, Seung Jae [Samsung Medical Center, Syungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)] (and others)

    1998-06-01

    With the development of stereotactic immobilization systems capable of reliable serial repositioning, fractionated stereotactic radiation therapy(FSRT) offers the potential for an improved treatment outcome by excellent dose delivery, and dose distribution characteristics with the favorable radio-biological properties of fractionated irradiation. We describe our initial experience using FSRT for the treatment of intracranial benign tumor. Between August 1995 and December 1996, 15 patients(7 males and 8 females aged 6-70 years) were treated with FSRT. The patients had the following diagnosis : pituitary adenoma(10) including one patient who previously had received radiotherapy, craniopharyngioma(2), acoustic neurinoma(1), meningioma(2). Using the Gill-Thomas-Cos-man relocatable head frame and multiple non-coplanar therapy, the daily dose of 2Gy was irradiated at 90% to 100% isodose surface of the isocenter. The collimator sizes ranged from 26mm to 70mm. In all patients except one follow-up lost, disease was well-controlled. Acute complication was negligible and no patient experienced cranial nerve neuropathies and radiation necrosis. In overall patient setup with scalp measurements, reproducibility was found to have mean of 1.1{+-}0.6mm from the baseline reading. Relocatable stereotactic system for FSRT is highly reproducible and comfortable. Although the follow-up period was relatively short, FSRT is considered to be a safe an effective radiation technique as the treatment of intracranial tumor. But the fractionation schedule(fraction size, overall treatment time and total dose) still remains to be solved by further clinical trials.

  9. Clinical and experimental studies on unilateral exophthalmos caused by intraorbital tumors

    International Nuclear Information System (INIS)

    Senoo, Kanehito

    1989-01-01

    Twenty eight patients with histologically confirmed intraorbital mass received transcranial surgery. According to the origin of mass, the patients were classified as having primary (15), secondary (4), metastatic (4), or pseudo-tumor (4) masses. Localization of intracranial masses fell into four types: the upper-lateral, medial, retrobulbar-apex, and diffuse types. The most common initial symptoms for the upper-lateral type and for the retrobulbar-apex type were exophtalmos and visual disturbance, respectively. Cranial X-rays and CT revealed bone destruction or proliferation and abnormal calcification in 57% of the patients. CAG revealed tumor stains in 18%. CT revealed the position and involvement of intraorbital mass. The ratio of the intraorbital mass to the orbital cavity area (the M/OC ratio) was calculated at the level of the optic nerve on CT scans. The M/OC ratio was correlated with the degree of impaired visual acuity. When it exceeded 50%, visual function was considerably disturbed. CT failed to discriminate between optic sheath meningioma and pyocele. The success rate of transcranial surgery, as evaluated by visual function recovery rate, was 46%. According to types, it was as high as 70% for the medial type. In an attempt to assess a correlation between the degree of exophthalmos and localization or volume of intraorbital mass, an experiment was made with a dry human skull, silicone rubber eye balls, gelatine and silicone balloons. When a mass more than 3 cm 3 in volume was in the lateral or medial part of the orbit, the rate of pressure increased. When it was in the apex part, the pressure gradually increased. These findings were in accordance with clinical findings. (N.K.) 73 refs

  10. An overview of clinical governance policies, practices and initiatives.

    Science.gov (United States)

    Braithwaite, Jeffrey; Travaglia, Joanne F

    2008-02-01

    To map the emergence of, and define, clinical governance; to discuss current best practices, and to explore the implications of these for boards of directors and executives wishing to promote a clinical governance approach in their health services. Review and analysis of the published and grey literature on clinical governance from 1966 to 2006. Medline and CINAHL databases, key journals and websites were systematically searched. Central issues were identified in the literature as key to effective clinical governance. These include: ensuring that links are made between health services' clinical and corporate governance; the use of clinical governance to promote quality and safety through a focus on quality assurance and continuous improvement; the creation of clinical governance structures to improve safety and quality and manage risk and performance; the development of strategies to ensure the effective exchange of data, knowledge and expertise; and the sponsoring of a patient-centred approach to service delivery. A comprehensive approach to clinical governance necessarily includes the active participation of boards and executives in sponsoring and promoting clinical governance as a quality and safety strategy. Although this is still a relatively recent development, the signs are promising.

  11. Anti-tumor effect of a recombinant plasmid expressing human interleukin-12: an initial research

    International Nuclear Information System (INIS)

    Zheng Chuansheng; Xia Xiangwen; Feng Gansheng; Li Xin; Liang Huimin; Liang Bin

    2010-01-01

    Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CI I L- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CI I L-12) to liver cancer cell HepG 2 in vitro, and detect reproductive activity of the cell using MTT and the activity of expressing vascular endothelial growth factor(VEGF) using semiquantitative PCR. And then, we deliver the gene to rabbit liver tumor tissue intraarterial and combine with chemoembolization to observe the anti- tumor effect to VX 2 tumor in vivo. Results: There are no statistical difference compared With control group in activity of reproductive and expressing VEGF in vitro. In vivo, tumor growth rate significantly reduce in gene therapy combined with chemoembolization group. Conclusion: Recombinant gene (pEGFP-Cl I L-12) exhibit significant anti-tumor effect in vivo but not in vitro, perhaps the anti-tumor effect is associated with an indirect pathway instead of a direct pathway. (authors)

  12. Ovarian tumors: pathogenia, clinical pattern, echographic and histopathological diagnosis

    International Nuclear Information System (INIS)

    Pons Porrata, Laura Maria; Garcia Gomez, Odalis; Salmon Cruzata, Acelia

    2012-01-01

    Two case reports of young patients, who were treated in the Otolaryngology Department from 'Dr. Joaquin Castillo Duany' Teaching Clinical Surgical Hospital in Santiago de Cuba are presented. One of the cases presented nasal obstruction, rhinorrhoea and facial pain, for 7 months; the other one presented an increase of volume in the right ocular globe. In both, the results of the biopsy confirmed the diagnosis of differentiated nasosinusal epidermoid carcinoma

  13. Adenomatoid tumor of the adrenal gland in young woman: from clinical and radiological to pathological study

    Directory of Open Access Journals (Sweden)

    Brankica Krstevska

    2016-12-01

    Full Text Available Adenomatoid tumors are neoplasms of mesothelial origin, usually occurring in the male and female genital tracts. Extragenital localization sites such as adrenal glands are rare but have been reported. When found in the adrenals, they represent great clinical, radiological and pathological diagnostic challenge, with wide range of differential diagnoses to be considered. We present a case of a 30 years old female, with incidental ultrasound finding of unilateral tumor in the right adrenal gland. Multi slices CT scan was of value in localizing this tumor, but not in the precise diagnosis. The tumor ranged from 5.6 cm to 6.4 cm in greatest diameter. Clinical and hormonal examinations excluded Sy. Cushing, M. Conn and pheochromocytoma. The patient underwent laparoscopic right adrenalectomy. A large tumor (d: 8×7×3 cm was removed showing no infiltration of the adrenal cortex or medulla, or extra-adrenal extension into the periadrenal adipose tissue. Histological examination showed numerous cystic spaces lined by flattened cubical epithelial cells. The small cystic spaces were separated by edematous fibrovascular stroma with rare epithelial cells with vacuolated cytoplasm. Immunohistochemical staining was positive with vimentin (+, S100 (+, MCA mesothelial Ag (+, CD 68 (+ and negative with acitin (-, CK7 (-, CD3 (-. Adenomatoid tumor is a rare benign neoplasm that should be added in the differential diagnosis of any adrenal tumor occurring in adrenal gland. The histological and immunohistochemical profiles of this adrenal adenomatoid tumor are very supportive in reaching the diagnosis of this benign tumor of a mesothelial cell origin, helping to avoid invasive treatment.

  14. Video-Assisted Thoracoscopic Surgery in Patients With Clinically Resectable Lung Tumors

    Directory of Open Access Journals (Sweden)

    H. Sakai

    1996-01-01

    Full Text Available To investigate the feasibility of thoracoscopic resection, a pilot study was performed in patients with clinically resectable lung tumors. In 40 patients, Video-assisted thoracic surgery (VATS was performed because of suspicion of malignancy. There were 29 men and 11 women with a median age of 54.8 years (range 18 to 78. Preoperative indications were suspected lung cancer and tumor in 27 patients, assessment of tumor resectability in 7 patients, and probability of metastatic tumors in 6 patients. The final diagnoses in the 27 patients with suspected lung cancer were 12 primary lung cancers, 6 lung metastases, and 9 benign lesions. The success rates for VATS (no conversion to thoracotomy were 1 of 12 (8.3% for resectable stage I lung cancer, 8 of 12 (66.7% for metastatic tumors, and 9 of 9 (100% for benign tumors. With VATS, 6 of 7 patients (85.7%, possible stage III non-small cell lung cancer, an explorative thoracotomy with was avoided, significantly reducing morbidity. The reasons for conversion to thoracotomy were 1 oncological (N2 lymph node dissection and prevention of tumor spillage and 2 technical (inability to locate the nodule, central localization, no anatomical fissure, or poor lung function requiring full lung ventilation. The ultimate diagnoses were 19 lung cancers, 12 metastatic lung tumors, and 9 benign lung tumors. Our data show the limitations of VATS for malignant tumors in general use. These findings, together with the fact that experience in performing thoracoscopic procedures demonstrates a learning curve, may limit the use of thoracoscopic resection as a routine surgical procedure, especially when strict oncological rules are respected.

  15. MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kazuyo [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Kuroda, Takafumi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Takaya, Akari; Kubo, Terufumi; Kanaseki, Takayuki; Tsukahara, Tomohide [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hasegawa, Tadashi [Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Saito, Tsuyoshi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Sato, Noriyuki [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Torigoe, Toshihiko, E-mail: torigoe@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan)

    2016-04-15

    Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

  16. [Clinical experience in facial nerve tumors: a review of 27 cases].

    Science.gov (United States)

    Zhang, Fan; Wang, Yucheng; Dai, Chunfu; Chi, Fanglu; Zhou, Liang; Chen, Bing; Li, Huawei

    2010-01-01

    To analyze the clinical manifestations and the diagnosis of the facial nerve tumor according to the clinical information, and evaluate the different surgical approaches depending on tumor location. Twenty-seven cases of facial nerve tumors with general clinical informations available from 1999.9 to 2006.12 in the Shanghai EENT Hospital were reviewed retrospectively. Twenty (74.1%) schwannomas, 4 (14.8%) neurofibromas ,and 3 (11.1%) hemangiomas were identified with histopathology postoperatively. During the course of the disease, 23 patients (85.2%) suffered facial paralysis, both hearing loss and tinnitus affected 11 (40.7%) cases, 5 (18.5%) manifested infra-auricular mass and the others showed some of otalgia or vertigo or ear fullness or facial numbness/twitches. CT or/and MRI results in 24 cases indicated that the tumors originated from the facial nerve. Intra-operative findings showed that 24 (88.9%) cases involved no less than 2 segments of the facial nerve, of these 24 cases 87.5% (21/24) involved the mastoid portion, 70.8% (17/24) involved the tympanic portion, 62.5% (15/24) involved the geniculate ganglion, only 4.2% (1/24) involved the internal acoustic canal (IAC), and 3 cases (11.1%) had only one segments involved. In all of these 27 cases, the tumors were completely excised, of which 13 were resected followed by an immediate facial nerve reconstruction, including 11 sural nerve cable graft, 1 facial nerve end-to-end anastomosis and 1 hypoglossal-facial nerve end-to-end anastomosis. Tumors were removed with preservation of facial nerve continuity in 2 cases. Facial nerve tumor is a rare and benign lesion, and has numerous clinical manifestations. CT and MRI can help surgeons to make a right diagnosis preoperatively. When and how to give the patients an operation depends on the patients individually.

  17. A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor.

    Science.gov (United States)

    Gadd, Samantha; Huff, Vicki; Walz, Amy L; Ooms, Ariadne H A G; Armstrong, Amy E; Gerhard, Daniela S; Smith, Malcolm A; Auvil, Jaime M Guidry; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Hermida, Leandro C; Davidsen, Tanja; Gesuwan, Patee; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J; Moore, Richard A; Marra, Marco A; Dome, Jeffrey S; Mullighan, Charles G; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Ross, Nicole; Gastier-Foster, Julie M; Arold, Stefan T; Perlman, Elizabeth J

    2017-10-01

    We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.

  18. A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor

    KAUST Repository

    Gadd, Samantha

    2017-08-21

    We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.

  19. Telomerase activity is not enough for tumor initiation in human cells

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... signaling factors associated with both acute and chronic .... be associated with a worse prognosis in pancreatic ductal adenocarcinoma, whereas undetectable expression of this molecule showed an intermediate risk of tumor-.

  20. A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor

    KAUST Repository

    Gadd, Samantha; Huff, Vicki; Walz, Amy L; Ooms, Ariadne H A G; Armstrong, Amy E; Gerhard, Daniela S; Smith, Malcolm A; Auvil, Jaime M Guidry; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Hermida, Leandro C; Davidsen, Tanja; Gesuwan, Patee; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J; Moore, Richard A; Marra, Marco A; Dome, Jeffrey S; Mullighan, Charles G; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Ross, Nicole; Gastier-Foster, Julie M; Arold, Stefan T.; Perlman, Elizabeth J

    2017-01-01

    We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.

  1. [Coexistence of two germinal cell tumors, seminomatous and nonseminomatous, with an uncommon clinical presentation].

    Science.gov (United States)

    Soriano Sarrió, Pilar; Chirivella, Isabel; Navarro Fos, Samuel

    2008-06-01

    The existence of non seminomatous mixed germ cell tumors of the testis is a frequent event in urologic oncology. Nevertheless, the presence of both components, seminomatous and non seminomatous, in a germ cell tumor is unusual. We present a case of pure classic seminoma of the testis with a lymph node metastasis of pure embryonal carcinoma, with confirmatory immuohistochemical study and clinical outcome of the patient. A 34-year-old man presented with 3 cm supraclavicular tumor. CT scan also revealed multiple metastases in lymph nodes, liver, kidney and left adrenal gland. Tumor markers were negative and the biopsy performed discovered a lymph node metastasis of embryonal carcinoma of probable testicular origin. Ultrasound revealed a 6 mm hypoechoic nodule in the right testis. Orchyectomy was performed and pathologic analysis demonstrated a tumor, 1 cm of diameter, histopathologically compatible with classical seminoma with pagetoid extension to rete testis. Albuginea and spermatic cord did not present neoplastic involvement. Currently the patient is being treated with chemotherapy. The interest of the case is to remark an unusual aggressive clinical presentation as well as to perform a bibliographic review with emphasis in the theories regarding heterogeneous differentiation and spontaneous regression of germ cell tumors of the testis.

  2. Clinical efficacy and safety of surface imaging guided radiosurgery (SIG-RS) in the treatment of benign skull base tumors.

    Science.gov (United States)

    Lau, Steven K M; Patel, Kunal; Kim, Teddy; Knipprath, Erik; Kim, Gwe-Ya; Cerviño, Laura I; Lawson, Joshua D; Murphy, Kevin T; Sanghvi, Parag; Carter, Bob S; Chen, Clark C

    2017-04-01

    Frameless, surface imaging guided radiosurgery (SIG-RS) is a novel platform for stereotactic radiosurgery (SRS) wherein patient positioning is monitored in real-time through infra-red camera tracking of facial topography. Here we describe our initial clinical experience with SIG-RS for the treatment of benign neoplasms of the skull base. We identified 48 patients with benign skull base tumors consecutively treated with SIG-RS at a single institution between 2009 and 2011. Patients were diagnosed with meningioma (n = 22), vestibular schwannoma (n = 20), or nonfunctional pituitary adenoma (n = 6). Local control and treatment-related toxicity were retrospectively assessed. Median follow-up was 65 months (range 61-72 months). Prescription doses were 12-13 Gy in a single fraction (n = 18), 8 Gy × 3 fractions (n = 6), and 5 Gy × 5 fractions (n = 24). Actuarial tumor control rate at 5 years was 98%. No grade ≥3 treatment-related toxicity was observed. Grade ≤2 toxicity was associated with symptomatic lesions (p = 0.049) and single fraction treatment (p = 0.005). SIG-RS for benign skull base tumors produces clinical outcomes comparable to conventional frame-based SRS techniques while enhancing patient comfort.

  3. A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion.

    Science.gov (United States)

    Shelton, Laura M; Mukherjee, Purna; Huysentruyt, Leanne C; Urits, Ivan; Rosenberg, Joshua A; Seyfried, Thomas N

    2010-09-01

    Glioblastoma multiforme (GBM) is a rapidly progressive disease of morbidity and mortality and is the most common form of primary brain cancer in adults. Lack of appropriate in vivo models has been a major roadblock to developing effective therapies for GBM. A new highly invasive in vivo GBM model is described that was derived from a spontaneous brain tumor (VM-M3) in the VM mouse strain. Highly invasive tumor cells could be identified histologically on the hemisphere contralateral to the hemisphere implanted with tumor cells or tissue. Tumor cells were highly expressive for the chemokine receptor CXCR4 and the proliferation marker Ki-67 and could be identified invading through the pia mater, the vascular system, the ventricular system, around neurons, and over white matter tracts including the corpus callosum. In addition, the brain tumor cells were labeled with the firefly luciferase gene, allowing for non-invasive detection and quantitation through bioluminescent imaging. The VM-M3 tumor has a short incubation time with mortality occurring in 100% of the animals within approximately 15 days. The VM-M3 brain tumor model therefore can be used in a pre-clinical setting for the rapid evaluation of novel anti-invasive therapies.

  4. Clinical experiences with a chemical radioprotector in tumor radiotherapy: WR-2721

    International Nuclear Information System (INIS)

    Tanaka, Y.

    1984-01-01

    Since cysteine was found to protect lethally irradiated rats, sulfhydryl compounds that provide protection of laboratory animals against lethal doses of ionizing radiations have also been given much attention. The SH compounds have been the most extensively investigated, and β-aminoethylisothiouronium (AET) and cysteamine have been selected as being representative of those drugs that are highly protective. However, clinical application is limited, as the toxicity of these compounds is high. In a series of experiments to reevaluate radioprotective agents with low toxicity, the authors found that 2-mercaptopropionylglycine (MPG) and adrenochrome monoguangylhydrazone methanesulfonate (AMM) have a potent radioprotector effect in a dose far below their toxic doses in both mice and humans. Recently, the development of effective thiophosphate derivatives of cysteamine, namely WR-2721 [S-2-(3-amino-propylaminoethyl)phosphorothioate] by the U.S. Army Medical Research and Development Commands, led to a reevaluation of these compounds and their potential in radiotherapy. Initial investigations indicated that WR-2721 provided a considerable degree of radioprotection to normal tissues. This compound provided excellent protection for normal tissues (DMF = 2-2.5) but little protection for the transplanted tumor. Thus this drug may have a differential protection in vivo and may be useful for improving the therapeutic ratio in cancer radiotherapy. The results of animal and chemical experiments in Japan are summarized herein

  5. A Practical Approach to Tumor Heterogeneity in Clinical Research and Diagnostics.

    Science.gov (United States)

    Stanta, Giorgio; Bonin, Serena

    2018-01-01

    This Pathobiology issue tries to better define the complex phenomenon of intratumor heterogeneity (ITH), mostly from a practical point of view. This topic has been chosen because ITH is a central issue in tumor development and has to be investigated directly in patient tissue and immediately applied in the treatment of the presenting patient. Different types of ITH should be considered: clonal genetic and epigenetic evolution, morphological heterogeneity, and tumor sampling, heterogeneity resulting from microenvironmental autocrine and paracrine interaction, and stochastic plasticity related to different functional cell efficiencies. For a higher level of reproducibility in clinical research and diagnostics, it is necessary to establish standardized analytical methods, including microdissection. In situ techniques can be pivotal to explore tumor microenvironment and can be improved with associated digital analysis. Liquid biopsies for plasma DNA analysis are at present the best method to study recurrent tumors with treatment adaptation, and widespread clinical use could be beneficial. The different types of tumor genomic instabilities could have pragmatic applications to rank ITH for clinical applications: treatment approaches differ in patients with a high nucleotide mutation rate and patients with high copy number alterations. © 2017 S. Karger AG, Basel.

  6. Hsp90 as a Gatekeeper of Tumor Angiogenesis: Clinical Promise and Potential Pitfalls

    Directory of Open Access Journals (Sweden)

    J. E. Bohonowych

    2010-01-01

    Full Text Available Tumor vascularization is an essential modulator of early tumor growth, progression, and therapeutic outcome. Although antiangiogenic treatments appear promising, intrinsic and acquired tumor resistance contributes to treatment failure. Clinical inhibition of the molecular chaperone heat shock protein 90 (Hsp90 provides an opportunity to target multiple aspects of this signaling resiliency, which may elicit more robust and enduring tumor repression relative to effects elicited by specifically targeted agents. This review highlights several primary effectors of angiogenesis modulated by Hsp90 and describes the clinical challenges posed by the redundant circuitry of these pathways. The four main topics addressed include (1 Hsp90-mediated regulation of HIF/VEGF signaling, (2 chaperone-dependent regulation of HIF-independent VEGF-mediated angiogenesis, (3 Hsp90-dependent targeting of key proangiogenic receptor tyrosine kinases and modulation of drug resistance, and (4 consideration of factors such as tumor microenvironment that pose several challenges for the clinical efficacy of anti-angiogenic therapy and Hsp90-targeted strategies.

  7. Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, Yoshinori; Shiomi, Susumu; Sasaki, Nobumitsu; Jomura, Hisato; Nishiguchi, Shuhei; Seki, Shuichi; Kawabe, Joji; Ochi, Hironobu [Osaka City Univ. (Japan). Medical School

    2000-04-01

    We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma. FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV. The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the {alpha}-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC. (author)

  8. The clinical usefulness of initial serum procalcitonin as an ...

    African Journals Online (AJOL)

    The serum levels of WBC counts and C‑reactive protein in the aggravation group were elevated. However, the median value (interquartile range) of procalcitonin was relatively increased at 2.28 (0.41–7.84 ng/ml), demonstrating a significant difference. Conclusions: In conclusion, initial serum levels of procalcitonin might be ...

  9. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

    Science.gov (United States)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-08-06

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed.

  10. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

    International Nuclear Information System (INIS)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed

  11. Tumor-infiltrating CD8+ lymphocytes effect on clinical outcome of muco-cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Mahtab Rahbar

    2015-01-01

    Full Text Available Background: Recent data have changed our views of prognostic factors in cutaneous melanoma, while some newer methods have yielded better prognostic information. Tumor-infiltrating lymphocytes are believed to represent the immune reaction/response to melanoma cells which is often found in melanocytic cancer. Aim and Objective: We carried out an analysis, aiming to establish pooled estimates for clinical outcomes based on the presence of CD8+ T cell in melanocytic cancer. Materials and Methods: We have included 42 patients with primary cutaneous melanocytic cancer without preoperative treatments in our study. We next analyzed the proliferative activity of CD8+ T cells that infiltrated in tumor cell nests. The intratumoral and adjacent to invasive margin of tumor CD+ T-cell infiltration were analyzed which could also reflect antitumor immunity. Results: The total number of CD8+ cells especially adjacent to invasive margin of tumor was positively correlated with anatomical tumor thickness (P < .001 and not correlated with patient′s age and sex. The stage of tumor which is related to vascular-neural invasion, regional lymph nodes involvement and tumor thickness shows positive correlation with CD8+ infiltration in tumor (P < .004, P < .005, P < .001, respectively. Acral melanoma shows more CD8 lymphocytes infiltration and also recurrence rate of tumor (P < .005. Conclusion: We believe that CD8+ T-cell infiltration in primary cutaneous melanocytic cancer represents the immune reaction/response to melanoma which could be an important new therapy for melanoma although more research is needed on this treatment modality.

  12. Clinical audit in dentistry: From a concept to an initiation.

    Science.gov (United States)

    Malleshi, Suchetha N; Joshi, Mahasweta; Nair, Soumya K; Ashraf, Irshad

    2012-11-01

    Clinical audit is a quality improvement process that aims to improve patient care through a systematic review of care against explicit criteria. It is a cyclic and multidisciplinary process which involves a series of steps from planning the audit through measuring the performance to implementing and sustaining the change. Although audit contains some facets of research, it is essential to understand the difference between the two. Auditing can be done right from the record maintaining, diagnosis and treatment and postoperative evaluation and follow-up. The immense potential of clinical audit can be utilized only when open-mindedness and innovativeness are encouraged and evidence-based work culture is cultivated.

  13. Clinical, ultrasonographic, and laboratory findings in 12 llamas and 12 alpacas with malignant round cell tumors

    Science.gov (United States)

    Martin, Jeanne M.; Valentine, Beth A.; Cebra, Christopher K.

    2010-01-01

    Clinical signs, duration of illness, clinicopathologic findings, and ultrasonographic findings were evaluated in 12 llamas and 12 alpacas with malignant round cell tumors (MRCT). All but 1 animal died or was euthanized. Common clinical findings were anorexia, recumbency or weakness, and weight loss or poor growth. Peripheral lymphadenomegaly occurred in only 7 animals and was detected more often at necropsy than during physical examination. Common clinicopathologic abnormalities were hypoalbuminemia, acidosis, azotemia, anemia, hyperglycemia, and neutrophilia. Ultrasonography detected tumors in 4/6 animals. Cytologic evaluation of fluid or tissue aspirates or histopathology of biopsy tissue was diagnostic in 5/6 cases. A clinical course of 2 wk or less prior to death or euthanasia was more common in animals ≤ 2 y of age (9/11) than in older animals (6/13). Regular examination of camelids to include clinical pathology and evaluation of peripheral lymph nodes may result in early detection of MCRT. PMID:21358931

  14. Clinical and Pathologic Findings of Spitz Nevi and Atypical Spitz Tumors with ALK Fusions

    Science.gov (United States)

    Busam, Klaus J; Kutzner, Heinz; Cerroni, Lorenzo; Wiesner, Thomas

    2016-01-01

    Spitz tumors represent a group of melanocytic neoplasms that typically affects young individuals. Microscopically the lesions are composed of cytologically distinct spindle and epithelioid melanocytes, with a range in the architectural display or the cells, their nuclear features, and secondary epidermal or stromal changes. Recently, kinase fusions have been documented in a subset of Spitz tumors, but there is limited information on the clinical and pathologic features associated with those lesions. Here, we report a series of 17 patients (9 male, 8 female) with spitzoid neoplasms showing ALK fusions (5 Spitz nevi and 12 atypical Spitz tumors). The patients’ ages ranged from 2 years to 35 years (mean = 17; median = 16). Most lesions were located on the lower extremities and presented clinically as polypoid nodules. All tumors were compound melanocytic proliferations with a predominant intradermal growth. Tumor thickness ranged from 1.1 to 6 mm (mean = 2.9 mm; median = 2.5 mm). The most characteristic histopathologic feature of the tumors (seen in all but two lesions) was a plexiform dermal growth of intersecting fascicles of fusiform melanocytes. All but two tumors were amelanotic. All tumors were strongly immunoreactive for ALK. The ALK rearrangements were confirmed in all cases by fluorescence in situ hybridization (FISH) and the fusion partner was determined by quantitative polymerase chain reaction as TPM3 (tropomyosin 3) in 11 cases and DCTN1 (dynactin 1) in 6 cases. None of the eight tumors, which were analyzed by FISH for copy number changes of 6p, 6q, 9p, or 11q met criteria for melanoma. Two patients underwent a sentinel lymph node biopsy, and in both cases melanocytes nests were found in the subcapsular sinus of the node. Array comparative genomic hybridization of these two tumors revealed no chromosomal gains or losses. In conclusion, our study revealed that Spitz nevi/tumors with ALK rearrangement show a characteristic plexiform morphology and that

  15. Non-invasive pre-clinical MR imaging of prostate tumor hypoxia for radiation therapy prognosis

    Directory of Open Access Journals (Sweden)

    Derek White

    2014-03-01

    patient stratification for clinical implementation.------------------------------Cite this article as: White DA, Mason RP. Non-invasive pre-clinical MR imaging of prostate tumor hypoxia for radiation therapy prognosis. Int J Cancer Ther Oncol 2014; 2(2:020243. DOI: 10.14319/ijcto.0202.43

  16. Radiosensitivity of lymph node metastases versus initial subcutaneous tumors in nude mice

    International Nuclear Information System (INIS)

    Guichard, M.; Courdi, A.; Fertil, B.; Malaise, E.P.

    1979-01-01

    The in vivo and in vitro radiosensitivity of EMT6 tumor cells growing subcutaneously and metastasizing to the regional lymph nodes has been studied in congenitally athymic nude mice. The fraction of hypoxic cells was determined using an in vitro colony method to assay cell survival after irradiation of both air-breathing and nitrogen-asphyxiated animals. In air-breathing animals, lymph node metastases contained a significantly higher fraction of hypoxic cells than subcutaneous tumors of the same size (61 and 36% respectively). Survival curves did not differ under hypoxic conditions (nitrogen-asphyxiated animals). Likewise, survival curves of cells extracted from tumors at both sites and irradiated in vitro were identical

  17. Modeling tumor control probability for spatially inhomogeneous risk of failure based on clinical outcome data

    DEFF Research Database (Denmark)

    Lühr, Armin; Löck, Steffen; Jakobi, Annika

    2017-01-01

    PURPOSE: Objectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation. METHODS AND ...

  18. Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Gehl, Julie

    2011-01-01

    and genes to intracranial tumors in humans, and demonstrate a method to optimize the design (i.e. geometry) of the electrode device prototype to improve both clinical performance and geometrical tolerance (robustness). We have employed a semiempirical objective function based on constraints similar to those...... sensitive to random geometrical deviations. The method is readily applicable to other electrode configurations....

  19. Clinical validation of synthetic brain MRI in children: initial experience

    International Nuclear Information System (INIS)

    West, Hollie; Leach, James L.; Jones, Blaise V.; Care, Marguerite; Radhakrishnan, Rupa; Merrow, Arnold C.; Alvarado, Enrique; Serai, Suraj D.

    2017-01-01

    The purpose of this study was to determine the diagnostic accuracy of synthetic MR sequences generated through post-acquisition processing of a single sequence measuring inherent R1, R2, and PD tissue properties compared with sequences acquired conventionally as part of a routine clinical pediatric brain MR exam. Thirty-two patients underwent routine clinical brain MRI with conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1, T2, and T2 fluid attenuation inversion recovery or proton density-weighted sequences were made to match the comparable clinical sequences. Two exams for each patient were de-identified. Four blinded reviewers reviewed eight patients and were asked to generate clinical reports on each exam (synthetic or conventional) at two different time points separated by a mean of 33 days. Exams were rated for overall and specific finding agreement (synthetic/conventional and compared to gold standard consensus review by two senior reviewers with knowledge of clinical report), quality, and diagnostic confidence. Overall agreement between conventional and synthetic exams was 97%. Agreement with consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There were no significant differences in sensitivity, specificity, or accuracy for specific imaging findings involving the ventricles, CSF, brain parenchyma, or vasculature between synthetic or conventional exams (p > 0.05). No significant difference in exam quality, diagnostic confidence, or noise/artifacts was noted comparing studies with synthetic or conventional sequences. Diagnostic accuracy and quality of synthetically generated sequences are comparable to conventionally acquired sequences as part of a standard pediatric brain exam. Further confirmation in a larger study is warranted. (orig.)

  20. Clinical validation of synthetic brain MRI in children: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    West, Hollie; Leach, James L.; Jones, Blaise V.; Care, Marguerite; Radhakrishnan, Rupa; Merrow, Arnold C.; Alvarado, Enrique; Serai, Suraj D. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

    2017-01-15

    The purpose of this study was to determine the diagnostic accuracy of synthetic MR sequences generated through post-acquisition processing of a single sequence measuring inherent R1, R2, and PD tissue properties compared with sequences acquired conventionally as part of a routine clinical pediatric brain MR exam. Thirty-two patients underwent routine clinical brain MRI with conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1, T2, and T2 fluid attenuation inversion recovery or proton density-weighted sequences were made to match the comparable clinical sequences. Two exams for each patient were de-identified. Four blinded reviewers reviewed eight patients and were asked to generate clinical reports on each exam (synthetic or conventional) at two different time points separated by a mean of 33 days. Exams were rated for overall and specific finding agreement (synthetic/conventional and compared to gold standard consensus review by two senior reviewers with knowledge of clinical report), quality, and diagnostic confidence. Overall agreement between conventional and synthetic exams was 97%. Agreement with consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There were no significant differences in sensitivity, specificity, or accuracy for specific imaging findings involving the ventricles, CSF, brain parenchyma, or vasculature between synthetic or conventional exams (p > 0.05). No significant difference in exam quality, diagnostic confidence, or noise/artifacts was noted comparing studies with synthetic or conventional sequences. Diagnostic accuracy and quality of synthetically generated sequences are comparable to conventionally acquired sequences as part of a standard pediatric brain exam. Further confirmation in a larger study is warranted. (orig.)

  1. Fibulectomy for primary proximal fibular bone tumors: A functional and clinical outcome in 46 patients

    Directory of Open Access Journals (Sweden)

    Zile Singh Kundu

    2018-01-01

    Full Text Available Background: Primary benign and malignant tumors of the proximal fibula are not very common. Upper fibula being an expendable bone; the majority of the primary bone tumors at this site are usually treated with en bloc proximal fibulectomy. There is scarce literature on functional results, difficulties faced during dissection when to preserve or sacrifice common peroneal nerve and importance of lateral collateral ligament repair after proximal fibulectomy. The present study attempts at assessing these variables. Materials and Methods: This retrospective study included 46 patients; 30 males and 16 females with age ranging from 12 to 44 years (average: 26 years operated between 2003 and 2014. There were 34 benign and 12 malignant tumors. All were treated with proximal en bloc fibulectomy as indicated and decided by the operating surgeon keeping in view its extent on magnetic resonance imaging. Peroneal nerve sacrifice or preservation was decided as per the type (benign/malignant, its involvement by the tumor and the extent of the tumor. In 14 (for 12 malignant and two benign giant cell tumors [GCTs] patients, the peroneal nerve required resection for the margins. Partial upper tibial resection was performed in cases of malignant tumors and three GCTs. The followup ranged between 24 and 120 months (median: 48 months. Results: Patients with peroneal nerve resection had inferior functional outcome than those without peroneal nerve resection. There was no higher risk of tibia fracture in patients with partial tibial resection. Lateral collateral reconstruction yielded better results and should be performed in all cases. Functional outcome was significantly better in patients with benign tumors than in patients with malignant tumors as these required neither resection of the peroneal nerve nor large amount of muscle excision. The functional results were evaluated using Musculoskeletal Tumor Society (MSTS score, and clinical outcomes were evaluated using

  2. Tumor-mimicking primary angiitis of the central nervous system: initial and follow-up MR features

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Youkyung; Kim, Ji-hoon; Kim, Eunhee; Yim, Yoo Jeong; Sohn, Chul-Ho [Department of Radiology, Seoul National University Hospital, Seoul (Korea); Park, Sung-Hye [Seoul National University, Department of Pathology, School of Medicine, Seoul (Korea); Chang, Kee-Hyun [Department of Radiology, Seoul National University Hospital, Seoul (Korea); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea); Seoul National University Medical Research Center, Neuroscience Research Institute, Seoul (Korea)

    2009-10-15

    Primary angiitis of the central nervous system (PACNS) is an extremely rare vasculitis of unknown etiology. The purpose of this study was to describe the initial and follow-up magnetic resonance (MR) imaging features of the tumor-mimicking PACNS. We retrospectively reviewed a total of 21 initial and follow-up brain MR images obtained in four patients with biopsy-proven PACNS mimicking brain tumor on MR images during the periods from 1 to 8.1 years. In the initial study, diffusion-weighted imaging (DWI; n=4), MR angiogram (n=4), conventional catheter angiogram (n=3), perfusion MR (n=1), and computed tomography (n=1) and proton MR spectroscopy (MRS; n=2) were included. The lesions of the brain were qualitatively assessed in terms of location, number, size, shape, signal intensity, absence or presence of hemorrhage, enhancement pattern, and changes on the follow-up studies. Initially, the lesion manifested as single suprasellar (n=1) and frontal hemispheric (n=1) mass and as multiple-enhancing lesions in the unilateral supratentorial hemisphere (n=2). A patient showed steno-occlusive lesions in the internal carotid and middle cerebral arteries. DWI, perfusion imaging, and MRS revealed inconsistent findings among the patients. On the follow-up studies, a patient had two relapses but there was either significant decrease in size and extent or disappearance of the lesions with immunosuppressive therapy in all patients. Tumor-mimicking PACNS shows variable features on initial MR images but shows good responses to appropriate immunosuppressive therapy on follow-up MR images. (orig.)

  3. Tumor-mimicking primary angiitis of the central nervous system: initial and follow-up MR features

    International Nuclear Information System (INIS)

    Lee, Youkyung; Kim, Ji-hoon; Kim, Eunhee; Yim, Yoo Jeong; Sohn, Chul-Ho; Park, Sung-Hye; Chang, Kee-Hyun

    2009-01-01

    Primary angiitis of the central nervous system (PACNS) is an extremely rare vasculitis of unknown etiology. The purpose of this study was to describe the initial and follow-up magnetic resonance (MR) imaging features of the tumor-mimicking PACNS. We retrospectively reviewed a total of 21 initial and follow-up brain MR images obtained in four patients with biopsy-proven PACNS mimicking brain tumor on MR images during the periods from 1 to 8.1 years. In the initial study, diffusion-weighted imaging (DWI; n=4), MR angiogram (n=4), conventional catheter angiogram (n=3), perfusion MR (n=1), and computed tomography (n=1) and proton MR spectroscopy (MRS; n=2) were included. The lesions of the brain were qualitatively assessed in terms of location, number, size, shape, signal intensity, absence or presence of hemorrhage, enhancement pattern, and changes on the follow-up studies. Initially, the lesion manifested as single suprasellar (n=1) and frontal hemispheric (n=1) mass and as multiple-enhancing lesions in the unilateral supratentorial hemisphere (n=2). A patient showed steno-occlusive lesions in the internal carotid and middle cerebral arteries. DWI, perfusion imaging, and MRS revealed inconsistent findings among the patients. On the follow-up studies, a patient had two relapses but there was either significant decrease in size and extent or disappearance of the lesions with immunosuppressive therapy in all patients. Tumor-mimicking PACNS shows variable features on initial MR images but shows good responses to appropriate immunosuppressive therapy on follow-up MR images. (orig.)

  4. CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

    Directory of Open Access Journals (Sweden)

    I. A. Dzhanyan

    2015-01-01

    Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N.  Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013  were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.

  5. Simple and complex dysembryoplastic neuroepithelial tumors (DNT) variants: clinical profile, MRI, and histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Alexandre R.; Clusmann, Hans; Lehe, Marec von; Schramm, Johannes [University of Bonn Medical Center, Department of Neurosurgery, Bonn (Germany); Niehusmann, Pitt; Becker, Albert J. [University of Bonn Medical Center, Department of Neuropathology, Bonn (Germany); Urbach, Horst [University of Bonn Medical Center, Department of Radiology, Bonn (Germany)

    2009-07-15

    Dysembryoplastic neuroepithelial tumors (DNTs) are long-term epilepsy associated tumors subdivided into simple and complex variants. The purpose of this study was to relate different DNT components identified on magnetic resonance imaging (MRI) to histopathological features and to test the hypothesis that glial nodules as a histopathological feature of complex variants induce an occasional glioma misdiagnosis. Clinical, MRI, and histopathologic features of DNTs operated between 1988 and 2008 were reviewed. From a total of 61 DNTs, 48 simple and 13 complex variants were identified. Multiple or single pseudocysts in a cortical/subcortical location with small cysts sometimes separated from the tumor represented the glioneuronal element and were found in all DNTs. FLAIR hyperintense tissue was found between pseudocysts but - in neocortical DNTs - also circumscript in deeper tumor parts. Calcification and hemorrhages in this location occurred in four of 13 complex variants, and one of these patients was also the only one with tumor growth. Patients with complex variants had earlier seizure onset, and complex variants were more often located outside the temporal lobe. Although complex variants represented a higher diagnostic challenge, misdiagnoses also occurred in simple variants. One of five of DNTs showed contrast enhancement, which varied on follow-up studies with enhancing parts becoming nonenhancing and vice versa. The glioneuronal element is readily identifiable on MRI and should be considered to support the DNT diagnosis. Complex DNT variants have a different clinical profile and a more variable histopathological and MRI appearance; however, misdiagnoses occasionally also occur in simple variants. (orig.)

  6. Clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy for lung tumors.

    Science.gov (United States)

    Asai, Kaori; Nakamura, Katsumasa; Shioyama, Yoshiyuki; Sasaki, Tomonari; Matsuo, Yoshio; Ohga, Saiji; Yoshitake, Tadamasa; Terashima, Kotaro; Shinoto, Makoto; Matsumoto, Keiji; Hirata, Hidenari; Honda, Hiroshi

    2015-12-01

    We retrospectively investigated the clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy (SBRT) for lung tumors. Between April 2003 and July 2012, 473 patients with lung tumors were treated with SBRT. We identified 12 patients (2.5 %) with pneumothorax caused by SBRT, and evaluated the clinical features of pneumothorax. All of the tumors were primary lung cancers. The severity of radiation pneumonitis was grade 1 in 10 patients and grade 2 in two patients. Nine patients had emphysema. The planning target volume and pleura overlapped in 11 patients, and the tumors were attached to the pleura in 7 patients. Rib fractures were observed in three patients before or at the same time as the diagnosis of pneumothorax. The median time to onset of pneumothorax after SBRT was 18.5 months (4-84 months). The severity of pneumothorax was grade 1 in 11 patients and grade 3 in one patient. Although pneumothorax was a relatively rare late adverse effect after SBRT, some patients demonstrated pneumothorax after SBRT for peripheral lung tumors. Although most pneumothorax was generally tolerable and self-limiting, careful follow-up is needed.

  7. Clinical audit in dentistry: From a concept to an initiation

    Directory of Open Access Journals (Sweden)

    Suchetha N Malleshi

    2012-01-01

    Full Text Available Clinical audit is a quality improvement process that aims to improve patient care through a systematic review of care against explicit criteria. It is a cyclic and multidisciplinary process which involves a series of steps from planning the audit through measuring the performance to implementing and sustaining the change. Although audit contains some facets of research, it is essential to understand the difference between the two. Auditing can be done right from the record maintaining, diagnosis and treatment and postoperative evaluation and follow-up. The immense potential of clinical audit can be utilized only when open-mindedness and innovativeness are encouraged and evidence-based work culture is cultivated.

  8. Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

    Directory of Open Access Journals (Sweden)

    Prat Frederic

    2008-06-01

    Full Text Available Abstract Background Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap. Methods Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm2 for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to in vivo studies on pig esophagi. Results Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases. Conclusion This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.

  9. Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract.

    Science.gov (United States)

    Xiao, Changji; Zhao, Jing; Guo, Peng; Wang, Dan; Zhao, Dachun; Ren, Tong; Yang, Jiaxin; Shen, Keng; Lang, Jinghe; Xiang, Yang; Cui, Quancai

    2014-03-01

    The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract. From April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital. The location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence. Primitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.

  10. [Stumbling-blocks: initiating a psychosomatic pain clinic].

    Science.gov (United States)

    Heger, S; Lieberz, K

    2000-12-01

    Despite psychosocial factors playing an important role in the course of chronic pain disorder, there is a noticeable imbalance between demand and availability of psychosomatic care for these patients. This led us to establish a psychosomatic pain clinic within the framework of our outpatient clinic at the Department of Psychosomatic Medicine and Psychotherapy at the Central Institute of Mental Health, Mannheim, Germany. A recent study aimed at the evaluation of sociodemographic variables, state of chronification, symptom load and psychiatric comorbidity. Additionally we wanted to determine whether existing conditions at our hospital can be considered suitable for those patients. During the clinic's first year we assessed 40 consecutive patients based on a psychosomatic interview as well as a set of psychometric questionnaires (BDI, STAI, SCL-90-R). To detect differences between pain patients and psychotherapy inpatients, we compared the two groups in terms of sociodemographic variables and symptom load. Most pain patients were in advanced states of chronification, showing extensive psychiatric comorbidity, particularly anxiety and depressive syndromes. Drug addiction was found more infrequently. Use of the before mentioned questionnaires prevented us from underestimating existing anxiety syndromes. Pain patients differed substantially from psychotherapy inpatients in terms of age, education, family status and symptom load. Our examination routine effectively demonstrated the special needs of chronic pain patients. As there is significant demand for psychosomatic intervention in those patients, earlier referral appears highly desirable. As pain patients differ also greatly from the remaining hospital population, specialized therapeutic concepts must be developed.

  11. Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells.

    Science.gov (United States)

    Lawn, Samuel; Krishna, Niveditha; Pisklakova, Alexandra; Qu, Xiaotao; Fenstermacher, David A; Fournier, Michelle; Vrionis, Frank D; Tran, Nam; Chan, Jennifer A; Kenchappa, Rajappa S; Forsyth, Peter A

    2015-02-06

    Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice

    DEFF Research Database (Denmark)

    Kragh, M; Spang-Thomsen, M; Kristjansen, P E

    1999-01-01

    , 11, or 15 days after inoculation. The time from inoculation until initiation of exponential tumor growth was determined along with the post-therapeutic growth delay and the initial tumor doubling time (TD) for each individual tumor (n=103) on the basis of tumor volume growth curves. We found that: i......) the onset of growth of U87 xenografts was effectively inhibited by concurrent treatment with TNP-470 beyond the first three days after inoculation, ii) this effect was fully reversible upon termination of therapy, and iii) the post-therapeutic growth delay was independent of the accumulated dose...

  13. Initial clinical results of linac stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for pituitary adenomas

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Shrieve, Dennis C.; Alexander, Eben; Kaiser, Ursula B.; Richardson, Gary E.; McL Black, Peter; Loeffler, Jay S.

    1997-01-01

    Purpose: To evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor control and toxicity of the treatment, thus evaluate the feasibility of these technique for the treatment of pituitary adenomas. Subjects and Methods: 48 patients with either inoperable, recurrent or residual pituitary adenoma who underwent either SRS or SRT at the Brigham and Women's Hospital between 9/89 and 9/95 were analyzed. Of these, 18 received treatment with SRS, and 30 received SRT. SRS was contraindicated for the patients in whom the minimal distance of the target and optic chiasm or optic nerve was less than 5 mm. Patient characteristics were similar in the two groups, with the exception of tumor volume and previous irradiation. Median tumor volumes were 1.8 cm 3 and 7.7 cm 3 for SRS and SRT, respectively. Three of the SRS and none of the SRT patients had a history of previous external radiation therapy. Both SRS and SRT were performed by the use of dedicated stereotactic 6-MV linear accelerator with a treatment plan designed using a dedicated software. Doses were prescribed to the isodose distribution that covered the identified target. Dose and normalization used for SRS varied from 1000 cGy at 85 % isodose line to 1800 cGy at 80 % isodose line. For SRT patients, total dose of 4500 cGy was normalized at 90 or 95 % isodose line and this was delivered in 25 fractions of 180 cGy daily dose. Results: Local control: There was 1 case of local failure in each of SRS and SRT series (median follow up 42.5 months and 22 month, respectively). CNS adverse effects: There were 3 SRS cases in whom a ring enhancement in the temporal lobe was observed in follow-up MRI. (median follow up 32 months). Of these, one resolved spontaneously, whereas the other 2 lesion persisted and considered to be radiation necrosis. None of them required surgical intervention to date. These were observed in the

  14. Simultaneous 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic neuroendocrine tumors: initial results.

    Science.gov (United States)

    Beiderwellen, Karsten J; Poeppel, Thorsten D; Hartung-Knemeyer, Verena; Buchbender, Christian; Kuehl, Hilmar; Bockisch, Andreas; Lauenstein, Thomas C

    2013-05-01

    The aim of this pilot study was to demonstrate the potential of simultaneously acquired 68-Gallium-DOTA-D-Phe1-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison with 68Ga-DOTATOC PET/computed tomography (PET/CT) in patients with known gastroenteropancreatic neuroendocrine tumors (NETs). Eight patients (4 women and 4 men; mean [SD] age, 54 [17] years; median, 55 years; range 25-74 years) with histopathologically confirmed NET and scheduled 68Ga-DOTATOC PET/CT were prospectively enrolled for an additional integrated PET/MRI scan. Positron emission tomography/computed tomography was performed using a triple-phase contrast-enhanced full-dose protocol. Positron emission tomography/magnetic resonance imaging encompassed a diagnostic, contrast-enhanced whole-body MRI protocol. Two readers separately analyzed the PET/CT and PET/MRI data sets including their subscans in random order regarding lesion localization, count, and characterization on a 4-point ordinal scale (0, not visible; 1, benign; 2, indeterminate; and 3, malignant). In addition, each lesion was rated in consensus on a binary scale (allowing for benign/malignant only). Clinical imaging, existing prior examinations, and histopathology (if available) served as the standard of reference. In PET-positive lesions, the standardized uptake value (SUV max) was measured in consensus. A descriptive, case-oriented data analysis was performed, including determination of frequencies and percentages in detection of malignant, benign, and indeterminate lesions in connection to their localization. In addition, percentages in detection by a singular modality (such as PET, CT, or MRI) were calculated. Interobserver variability was calculated (Cohen's κ). The SUVs in the lesions in PET/CT and PET/MRI were measured, and the correlation coefficient (Pearson, 2-tailed) was calculated. According to the reference standard, 5 of the 8 patients had malignant NET lesions at

  15. Digital breast tomosynthesis (DBT): initial experience in a clinical setting

    International Nuclear Information System (INIS)

    Skaane, Per; Gullien, Randi; Eben, Ellen B.; Haakenaasen, Unni; Naess Jebsen, Ingvild; Krager, Mona; Bjoerndal, Hilde; Ekseth, Ulrika; Jahr, Gunnar

    2012-01-01

    Background: Digital breast tomosynthesis (DBT) is a promising new technology. Some experimental clinical studies have shown positive results, but the future role and indications of this new technique, whether in a screening or clinical setting, need to be evaluated. Purpose: To compare digital mammography and DBT in a side-by-side feature analysis for cancer conspicuity, and to assess whether there is a potential additional value of DBT to standard state-of-the-art conventional imaging work-up with respect to detection of additional malignancies. Material and Methods: The study had ethics committee approval. A total of 129 women underwent 2D digital mammography including supplementary cone-down and magnification views and breast ultrasonography if indicated, as well as digital breast tomosynthesis. The indication for conventional imaging in the clinical setting included a palpable lump in 30 (23%), abnormal mammographic screening findings in 54 (42%), and surveillance in 45 (35%) of the women. The women were examined according to present guidelines, including spot-magnification views, ultrasonography, and needle biopsies, if indicated. The DBT examinations were interpreted several weeks after the conventional imaging without knowledge of the conventional imaging findings. In a later session, three radiologists performed a side-by-side feature analysis for cancer conspicuity in a sample of 50 cases. Results: State-of-the-art conventional imaging resulted in needle biopsy of 45 breasts, of which 20 lesions were benign and a total of 25 cancers were diagnosed. The remaining 84 women were dismissed with a normal/definitely benign finding and without indication for needle biopsy. The subsequent DBT interpretation found suspicious findings in four of these 84 women, and these four women had to be called back for repeated work-up with knowledge of the tomosynthesis findings. These delayed work-ups resulted in two cancers (increasing the cancer detection by 8%) and two

  16. Radiologic and clinical observation of tuberculous cavity in initial treatment

    International Nuclear Information System (INIS)

    Huh, Jin Do

    1986-01-01

    Tuberculous cavity is important in diagnosis and observation in the course of pulmonary tuberculosis. Author analyzed the radiologic findings of cavity and average months of negative conversion in AFB culture in 89 cases of initial treatment. The results were as follows: 1. The more number of cavities, the longer period in negative conversion of AFB culture. 2. No relation between sums of diameter and thickness of cavity and average months of negative conversion in AFB culture. 3. In the cases of cavity with air-fluid level took longer period in negative conversion og AFB culture than those of cavity without air-fluid level, significantly. 4. No relation between radiologic findings of cavity and results of chemotherapy for pulmonary tuberculosis.

  17. Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

    Science.gov (United States)

    Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

    2015-10-13

    Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

  18. Initial experience with golimumab in clinical practice for ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Luisa Castro-Laria

    Full Text Available Background: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis. Purpose: To research the effectiveness and safety of golimumab in patients with ulcerative colitis in clinical practice. Methods: Retrospective study of the effectiveness and safety of golimumab in patients with ulcerative colitis. All patients received golimumab 200 mg subcutaneously at week 0, and golimumab 100 mg subcutaneously at week 2. After the induction treatment, each patient received 50 mg sc. every 4 weeks in patients with body weight less than 80 kg, and 100 mg every 4 weeks in patients with body weight greater than or equal to 80 kg. Results: Study of a group of 23 ulcerative colitis patients, 7 of whom were naive to any anti-TNF therapy, and 16 patients who had previously been treated with an anti-TNF agent other than golimumab (non-naive patients. The average treatment time with golimumab was 14.3 weeks. Globally, withdrawal of corticosteroids was observed in 74% of cases. Clinical response was observed in 85.5% of patients who had not received biological treatment previously, and in patients who had previously received biological treatment the response rate was 75%. Conclusions: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients. It is also a safe therapy, given that there were no adverse effects in the patients studied.

  19. Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening.

    Science.gov (United States)

    Christensen, Anne G; Ehmsen, Sidse; Terp, Mikkel G; Batra, Richa; Alcaraz, Nicolas; Baumbach, Jan; Noer, Julie B; Moreira, José; Leth-Larsen, Rikke; Larsen, Martin R; Ditzel, Henrik J

    2017-08-01

    A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics. Within these pairs, one, but not the other, resulted in tumors in immunodeficient NOD/Shi-scid/IL-2 Rγ null mice and efficiently formed mammospheres. Quantitative proteomics and phosphoproteomics were used to map signaling pathways associated with the tumor-initiating ability. Signaling associated with apoptosis was suppressed in tumor-initiating versus nontumorigenic counterparts with pro-apoptotic proteins, such as Bcl2-associated agonist of cell death (BAD), FAS-associated death domain protein (FADD), and myeloid differentiation primary response protein (MYD88), downregulated in tumor-initiating epithelial-like cells. Functional studies confirmed significantly lower apoptosis in tumor-initiating versus nontumorigenic cells. Moreover, central pathways, including β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related signaling, exhibited increased activation in the tumor-initiating cells. To evaluate the CSC model as a tool for drug screening, we assessed the effect of separately blocking NF-κB and Wnt/β-catenin signaling and found markedly reduced mammosphere formation, particularly for tumor-initiating cells. Similar reduction was also observed using patient-derived primary cancer cells. Furthermore, blocking NF-κB signaling in mice transplanted with tumor-initiating cells significantly reduced tumor outgrowth. Our study demonstrates that suppressed apoptosis, activation

  20. Aminopeptidase A initiates tumorigenesis and enhances tumor cell stemness via TWIST1 upregulation in colorectal cancer

    OpenAIRE

    Chuang, Hui-Yu; Jiang, Jeng-Kae; Yang, Muh-Hwa; Wang, Hsei-Wei; Li, Ming-Chun; Tsai, Chan-Yen; Jhang, Yau-Yun; Huang, Jason C.

    2017-01-01

    Metastasis accounts for the high mortality rate associated with colorectal cancer (CRC), but metastasis regulators are not fully understood. To identify a novel gene involved in tumor metastasis, we used oligonucleotide microarrays, transcriptome distance analyses, and machine learning algorithms to determine links between primary and metastatic colorectal cancers. Aminopeptidase A (APA; also known as ENPEP) was selected as our focus because its relationship with colorectal cancer requires cl...

  1. Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

    Science.gov (United States)

    Chua, Chee Wai; Epsi, Nusrat J; Leung, Eva Y; Xuan, Shouhong; Lei, Ming; Li, Bo I; Bergren, Sarah K; Hibshoosh, Hanina; Mitrofanova, Antonina

    2018-01-01

    Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer. PMID:29334357

  2. Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic Tumor (PHAT).

    Science.gov (United States)

    Scalici Gesolfo, Cristina; Serretta, Vincenzo; Di Maida, Fabrizio; Giannone, Giulio; Barresi, Elisabetta; Franco, Vito; Montironi, Rodolfo

    2017-02-01

    Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion characterized by slow growth, infiltrative behavior and high rate of local recurrences. Only one case has been described in retroperitoneum, at renal hilum, but not involving pelvis or parenchyma. Here we present the first case of PHAT arising in the renal parenchyma. A nodular lesion in right kidney lower pole was diagnosed to a 61 year old woman. The patient underwent right nephrectomy. Microscopically, the lesion showed solid and pseudo-cystic components with hemorrhagic areas characterized by aggregates of ectatic blood vessels. Pleomorphic cells were characterized by large eosinophilic cytoplasm with irregular and hyperchromatic nuclei. Immunohistochemistry was performed and the lesion was classified as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT). Due to the clinical behavior of this tumor, in spite of its benign nature, review of the surgical margins and close follow up after partial nephrectomy are mandatory. Copyright © 2016. Published by Elsevier GmbH.

  3. Neuroendocrine tumors: a review of the clinical aspects, diagnosis and treatment

    International Nuclear Information System (INIS)

    Rodriguez Fernandez, Lisbet; Hernandez Yero, Arturo; Pina Rivera, Yordanka; Yanes Quesada, Marelys

    2008-01-01

    The study of neuroendocrine tumors has been object of interests by medical science. Different methods have been developed for their diagnosis, treatment and prognosis, each of them with its advantages and inconveniences. The published results are based on the experience of other countries, and it would be very useful to apply them in our country to get closer to the real incidence of these tumors in our environment and to have an adequate treatment of the patients affected with this disease. The objective of this paper is to offer a view of the current trends as regards the clinical aspects, the diagnosis and treatment of the neuroendocrine tumors that serves as a working tool for medical practice and for the teaching activity of the physicians related to this topic

  4. Matrix Metalloproteinase-9/Neutrophil Gelatinase-Associated Lipocalin Complex Activity in Human Glioma Samples Predicts Tumor Presence and Clinical Prognosis

    Directory of Open Access Journals (Sweden)

    Ming-Fa Liu

    2015-01-01

    Full Text Available Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL complex activity is elevated in brain tumors and may serve as a molecular marker for brain tumors. However, the relationship between MMP-9/NGAL activity in brain tumors and patient prognosis and treatment response remains unclear. Here, we compared the clinical characteristics of glioma patients with the MMP-9/NGAL activity measured in their respective tumor and urine samples. Using gelatin zymography assays, we found that MMP-9/NGAL activity was significantly increased in tumor tissues (TT and preoperative urine samples (Preop-1d urine. Activity was reduced by seven days after surgery (Postop-1w urine and elevated again in cases of tumor recurrence. The MMP-9/NGAL status correlated well with MRI-based tumor assessments. These findings suggest that MMP-9/NGAL activity could be a novel marker to detect gliomas and predict the clinical outcome of patients.

  5. To Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

    Science.gov (United States)

    2018-04-23

    Neuroblastoma; Rhabdomyosarcoma; Ewing's Sarcoma; Ewing's Tumor; Sarcoma, Ewing's; Sarcomas, Epitheliod; Sarcoma, Soft Tissue; Sarcoma, Spindle Cell; Melanoma; Malignant Melanoma; Clinical Oncology; Oncology, Medical; Pediatrics, Osteosarcoma; Osteogenic Sarcoma; Osteosarcoma Tumor; Sarcoma, Osteogenic; Tumors; Cancer; Neoplasia; Neoplasm; Histiocytoma; Fibrosarcoma; Dermatofibrosarcoma

  6. Clinical application of preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta in the resection of sacral tumors

    International Nuclear Information System (INIS)

    Chen Wenhua; Wang Qi; He Zhongming; Zhou Jian; Wang Yimin; Wang Jie

    2012-01-01

    Objective: To investigate the clinical application of preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta in performing the surgical resection of sacral tumors. Methods: Conventional surgical excision of sacral tumors was employed in 24 patients with sacral tumors (control group), while preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta was carried out in 32 patients with sacral tumors (study group). The operation time, blood loss during the surgery and the one-year recurrence rate of both groups were documented, and the results were statistically analyzed. Results: Angiography showed that in the study group the sacral tumors were supplied by several vessels, and these feeding arteries were occluded separately. The tumors were successfully removed in all patients with the help of intraoperative balloon occlusion of the abdominal aorta. During the surgery, the surgical area was clearly exposed and the blood loss wa remarkably reduced. After the surgery, no ectopic vascular embolization, renal ischemia, limb ischemia or other complications occurred. Statistically significant difference in the operation time, blood loss during the surgery and the one-year recurrence rate existed between the two groups (P<0.05). Conclusion: Preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta can effectively shorten the operation time, reduce the blood loss during the surgery and provide a clear surgical field, and thus the surgical safety can be significantly ensured. (authors)

  7. Circulating tumor cells and their relationship with clinical and morphological characteristics of colorectal cancer

    Directory of Open Access Journals (Sweden)

    O I Kit

    2018-02-01

    Full Text Available Aim. To investigate the dependence of the number of circulating tumor cells in peripheral blood of colorectal cancer patients on the clinical and morphological characteristics of underlying disease. Methods. 91 patients with verified metastatic colorectal cancer Т3-4N1-2М1 were included in the study. The average age of the patients was 61.5±1.7 years. The patients were divided into the study group (laparoscopic surgical treatment, n=44 and control group (open surgical intervention, n=47. The number of circulating tumor cells was determined in CellSearch™ system in the peripheral blood drawn before the intervention. The study of the association of attributes by constructing contingency tables consisted in calculating Pearson’s contingency coefficient c2 with Mantel-Haenszel correction for likelihood (nonparametric correction, estimating statistical significance of contingency and analyzing the tightness of the association by A. Chuprov’s mutual contingency coefficient. Results. We found contingency of the number of circulating tumor cells with clinical and morphological parameters of patients with colorectal cancer. The relationship between potential risk factors and increase of the number of circulating tumor cells in the peripheral blood was observed in all colorectal cancer patients, regardless of the surgical intervention method. The most pronounced association of the number of circulating tumor cells in the peripheral blood of metastatic colorectal cancer patients before surgery according to the mutual contingency coefficient (K was shown to be with present distant metastases (status M1b; K=0.63, p=0.0001 and stage T4 (K=0.56, p=0.0009. Conclusion. The obtained results emphasize the important predictive significance of the circulating tumor cells level in peripheral blood for assessment of the potential for colorectal cancer progression.

  8. Clinical usefulness of endoscopic ultrasonography for the evaluation of ulcerative colitis-associated tumors

    Science.gov (United States)

    Kobayashi, Kiyonori; Kawagishi, Kana; Ooka, Shouhei; Yokoyama, Kaoru; Sada, Miwa; Koizumi, Wasaburo

    2015-01-01

    AIM: To evaluate the clinical usefulness of endoscopic ultrasonography (EUS) for the diagnosis of the invasion depth of ulcerative colitis-associated tumors. METHODS: The study group comprised 13 patients with 16 ulcerative colitis (UC)-associated tumors for which the depth of invasion was preoperatively estimated by EUS. The lesions were then resected endoscopically or by surgical colectomy and were examined histopathologically. The mean age of the subjects was 48.2 ± 17.1 years, and the mean duration of UC was 15.8 ± 8.3 years. Two lesions were treated by endoscopic resection and the other 14 lesions by surgical colectomy. The depth of invasion of UC-associated tumors was estimated by EUS using an ultrasonic probe and was evaluated on the basis of the deepest layer with narrowing or rupture of the colonic wall. RESULTS: The diagnosis of UC-associated tumors by EUS was carcinoma for 13 lesions and dysplasia for 3 lesions. The invasion depth of the carcinomas was intramucosal for 8 lesions, submucosal for 2, the muscularis propria for 2, and subserosal for 1. Eleven (69%) of the 16 lesions arose in the rectum. The macroscopic appearance was the laterally spreading tumor-non-granular type for 4 lesions, sessile type for 4, laterally spreading tumor-granular type for 3, semi-pedunculated type (Isp) for 2, type 1 for 2, and type 3 for 1. The depth of invasion was correctly estimated by EUS for 15 lesions (94%) but was misdiagnosed as intramucosal for 1 carcinoma with high-grade submucosal invasion. The 2 lesions treated by endoscopic resection were intramucosal carcinoma and dysplasia, and both were diagnosed as intramucosal lesions by EUS. CONCLUSION: EUS provides a good estimation of the invasion depth of UC-associated tumors and may thus facilitate the selection of treatment. PMID:25759538

  9. Advancing Medication Reconciliation in an Outpatient Internal Medicine Clinic through a Pharmacist-Led Educational Initiative

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    Sarah M. Westberg, Pharm.D.

    2010-01-01

    Full Text Available Objectives: To develop and deliver an effective pharmacist-led educational initiative to clinic staff to advance medication reconciliation in the electronic medical record of an outpatient internal medicine clinic.Methods: An educational initiative designed to improve the ability of nursing staff in medication reconciliation was launched in the outpatient internal medicine clinic of a regional healthcare system. The education was provided by the pharmacist to clinic nursing staff, including registered nurses, licensed practical nurses, and certified medical assistants. The impact of this training was measured through pre-initiation and post-implementation surveys, competency assessments and an audit. Results: The educational initiative was successfully designed and delivered to clinic nursing staff. Assessment of the initiative found that all nursing staff completing competency assessments successfully passed. Pre-initiation- and post-implementation- survey responses on the self-assessed ability to gather and document accurate medication lists did not show significant changes. Informal observations in the clinic indicated that this initiative changed the culture of the clinic, creating increased awareness of the importance of accurate medications and increased emphasis on medication reconciliation.Conclusions: The expertise of pharmacists can be utilized to educate nursing staff on the skills and abilities necessary to gather and document accurate medication lists. This study did not find measurable changes in the accuracy of medication lists in this clinic. Future research is needed to determine the best methods to train health professionals in medication reconciliation to ensure accurate medication lists in the outpatient setting.

  10. Evolution of modern nuclear medicine tumor-imaging diagnostics in clinical oncology

    International Nuclear Information System (INIS)

    Piperkova, E.

    2000-01-01

    The evolution of current nuclear medicine diagnostic is closely related to the technical progress in imaging equipment development, and application of radiopharmaceuticals (Rphs) with a different tumor-uptake mechanism. It is the aim of the study to present groups of tumor-imaging Rphs differing by tumor uptake mechanisms, used in clinical oncology. The obtained results are described, and compared with the ones reported by other researchers. Sensitivity and specificity of Rphs for cardio-scintigraphy with 99m Tc - MIBI and 201 Tl are relatively high, amounting to 93.7% and 60% respectively, in the various tumors. These indicators depend on the stage, location, histopathology, level of malignancy and biological activity of the neoplasm. 99m Tc - MIBI scintigraphy is endowed with considerable diagnostic potential for assaying multiple drug resistance (MDR), and is also a good criterion for its elimination following anti-MDR therapy. The obtained results show that radioimmunoscintigraphy (RIS) using different radiolabeled monoclonal antibodies (MoAb) have high sensitivity and specificity respectively: 86% and 80% in ovarian carcinoma with B72.3 antiTAG; 68.6% and 92.5% in colorectal carcinoma with B73.2 antiTAG, antiCEA, antiCA 19-9; 92% and 83% in breast cancer with antiCEA, 86.8% and 67-69% in malignant melanoma with 225.28s. Receptor scintigraphy may reach up to 86% sensitivity and 100% specificity in tumors saturated with somatostatin receptors. Positron emission tomography (PET) with 18F-FDG enhances the metabolic activity of tumor cells, and attains tumor-detecting rate amounting to 97%. Tumor imaging evolution characterized by the introduction and practical implementation of different Rphs, visualizing the functional and biochemical activity of tumor cells in the primary neoplasm, sentinel lymph nodes and distant metastases. radiolabelling of a variety of new biochemical substances, including DNA and RNA, drugs and lysosomes contributes to a successful imaging

  11. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma.

    Science.gov (United States)

    Chen, Jian; Yang, Wei-Jun; Sun, Hai-Jian; Yang, Xia; Wu, Yu-Zhang

    2016-08-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma.

  12. Preliminary clinical results of locoregional hyperthermia for primary and secondary bone tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, J.L.; Nagata, Yasushi; Kanamori, Shuichi; Mitsumori, Michihide; Okuno, Yoshishige; Horii, Naotoshi; Nishimura, Yasumasa; Masunaga, Shinitiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-03-01

    Nineteen primary and secondary bone tumors in 16 patients were treated with hyperthermia plus radiotherapy and/or chemotherapy between 1982 and 1997 at Kyoto University Hospital. The thermometric and clinical results were analyzed retrospectively. In 55 of 86 hyperthermia sessions, the intratumor temperature was measured using a thermometer. Of the 19 tumors, 16 (84%) received heat treatment 4-7 times, and 3 (16%) received 1 or 2 treatments of hyperthermia. The mean maximum, mean minimum and average intratumor temperatures were 42.9, 40.4 and 41.6 deg C, respectively, and 12 (67%) reached a tumor maximum temperature above 42.5 deg C. The durations that intratumor points exceeded 42, 41 and 40 deg C were 27, 34 and 38 min, respectively. The local tumor response to treatment was assessed using X-ray computed tomography. The local response rate was 16% and the local pain relief rate was 63%. The 1-year cumulative survival rate was 60%. Our preliminary results indicated that thermoradiotherapy and thermochemotherapy are clinicaly feasible and potentially beneficial in the management of locally advanced bone tumors. (author)

  13. Gastric Collision Tumors: An Insight into Their Origin and Clinical Significance

    Directory of Open Access Journals (Sweden)

    Adamantios Michalinos

    2015-01-01

    Full Text Available Collision tumors are rare neoplasms displaying two distinct cell populations developing in juxtaposition to one another without areas of intermingling. They are rare entities with only 63 cases described in English literature. Tumors encountered are gastric adenocarcinomas colliding with lymphomas, gastrointestinal stromal tumors, squamous cell carcinomas, and neuroendocrine tumors. Their cell origin is obsolete by the time of diagnosis. Different tumorigenesis theories have been suggested to explain their behavior, yet none has managed to provide satisfactory explanation for all cases. Clinically they are indistinguishable from the dominant tumor. Lack of data does not allow detailed assessment of their behavior yet they seem aggressive neoplasms with dismal prognosis. The majority of cases have been diagnosed postoperatively during histologic examination of specimens. There are no guidelines or concrete evidence to support best way of adjuvant or other types of treatment. However, these rare neoplasms might help in unlocking secrets of cancer behavior including tumorigenesis, differentiation, and adhesion and thus clinicians should be aware of their existence.

  14. Photodynamic therapy (PDT) of malignant tumors by photosensitzer photosens: results of 45 clinical cases

    Science.gov (United States)

    Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Aristarkhova, E. I.; Filonenko, E. V.; Belous, T. A.; Vorozhtsov, Georgy N.; Zharkova, Natalia N.; Smirnov, V. V.; Zhitkova, Margarita B.

    1996-01-01

    Photosensitizer Photosens is a mixture of sulphonated Al-phthalocyanines with a different number of substituents per phthalocyanine molecule. In the beginning of 1994, this photosensitizer was approved for clinical trials. Since that time till May 1995, 45 patients with 120 tumors were treated by PDT-Photosens. The main tumor localizations were lung (5/6), head and neck (4/4), esophagus (8/8), stomach (2/2), vulva (2/2), bladder (1/1), breast cancer (3/3), skin (basalioma, melanoma, sarcoma Kaposi, mts breast cancer) (20 patients/94 tumors). The lesions were photoirradiated 48-72 h after intravenous injection of Photosens in doses from 0.5 to 2.0 mg/kg b.w. (1.0 mg/kg b.w., on average). PDT was performed by laser power density from 20 to 1400 mW/sq cm (300 mW/sq.cm, on average), energy density varying from 15 to 200 J/sq cm (100 J/sq.cm, on average). The therapeutical effect of PDT was evaluated histologically, endoscopically, roentgenologically and sonographically 3 - 4 weeks after the treatment. Complete regression of tumors was reached in 56%, significant remission was reached in 34%, and partial remission was observed in 10% of cases. The follow-up of patients with complete tumor regression was to 15 months.

  15. Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model.

    Science.gov (United States)

    Pishali Bejestani, Elham; Cartellieri, Marc; Bergmann, Ralf; Ehninger, Armin; Loff, Simon; Kramer, Michael; Spehr, Johannes; Dietrich, Antje; Feldmann, Anja; Albert, Susann; Wermke, Martin; Baumann, Michael; Krause, Mechthild; Bornhäuser, Martin; Ehninger, Gerhard; Bachmann, Michael; von Bonin, Malte

    2017-01-01

    The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model. In addition, we analyzed phenotypic and functional changes of cancer cells and UniCAR-T cells in association with the administration of the targeting module to reveal potential immunoevasive mechanisms. Most notably, UniCAR-T cell activation induced upregulation of immune-inhibitory molecules such as programmed death ligands. In conclusion, this work illustrates that the UniCAR platform mediates potent anti-tumor activity in a relevant in vitro and in vivo solid tumor model.

  16. Clinical Significances of Serum Vitamin B12, Folate and Ferritin Levels in Patients with Malignant Tumors

    International Nuclear Information System (INIS)

    Monn, Youn Sung; Soung, In Whan; Kim, Sam Yong; Ro, Heung Kyu; Lee, Bok Hee

    1987-01-01

    In order to evaluate the clinical significances of the serum vitamin B 12 , folate and ferritin levels in patients with malignant tumors, the levels were measured in 10 normal control subjects, 70 patients with malignant tumors, 7 patients with liver cirrhosis and 25 patients with other benign diseases. The results are as follows: 1) In normal control subjects, mean serum values for vitamin B 12 , folate and ferritin level were 588.80±131.58 pg/ml, 5.59±1.52 ng/ml and 89.22±42.78 ng/ml retrospectively. 2) There was no significant difference in serum levels between patients with benign diseases and normal control subjects. 3) The serum vitamin B 12 and ferritin levels in patients with liver cirrhosis were significantly higher than in normal control, and the serum folate levels in these patients were lower than in normal control subjects. 4) The serum vitamin B 12 and ferritin levels in patients with malignant tumors were significantly higher than in normal control subjects, and the serum folate levels in these patients were significantly lower than in normal control subjects. The above results suggest that the serum vitamin B 12 and ferritin may be useful as tumor markers in patients with malignant tumors.

  17. Initial Clinical Evaluation of the Modular Prosthetic Limb

    Directory of Open Access Journals (Sweden)

    Briana N. Perry

    2018-03-01

    Full Text Available The Modular Prosthetic Limb (MPL was examined for its feasibility and usability as an advanced, dexterous upper extremity prosthesis with surface electromyography (sEMG control in with two individuals with below-elbow amputations. Compared to currently marketed prostheses, the MPL has a greater number of sequential and simultaneous degrees of motion, as well as wrist modularity, haptic feedback, and individual digit control. The MPL was successfully fit to a 33-year-old with a trans-radial amputation (TR01 and a 30-year-old with a wrist disarticulation amputation (TR02. To preserve anatomical limb length, we adjusted the powered degrees of freedom of wrist motion between users. Motor training began with practicing sEMG and pattern recognition control within the virtual integration environment (VIE. Prosthetic training sessions then allowed participants to complete a variety of activities of daily living with the MPL. Training and Motion Control Accuracy scores quantified their ability to consistently train and execute unique muscle-to-motion contraction patterns. Each user also completed one prosthetic functional metric—the Southampton Hand Assessment Procedure (SHAP for TR01 and the Jebsen-Taylor Hand Function Test (JHFT for TR02. Haptic feedback capabilities were integrated for TR01. TR01 achieved 95% accuracy at 84% of his VIE sessions. He demonstrated improved scores over a year of prosthetic training sessions, ultimately achieving simultaneous control of 13 of the 17 (76% attempted motions. His performance on the SHAP improved from baseline to final assessment with an increase in number of tasks achieved. TR01 also used vibrotactile sensors to successfully discriminate between hard and soft objects being grasped by the MPL hand. TR02 demonstrated 95% accuracy at 79% of his VIE sessions. He demonstrated improved scores over months of prosthetic training sessions, however there was a significant drop in scores initially following a mid

  18. Clinical Evaluation of {sup 57}Co-labelled Bleomycin for Tumor Localization

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Yong Wun; Kim, Jang Hee; Lee, Jhin Oh [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1987-03-15

    Investigation with {sup 57}Co-Bleomycin in patients with the various cancers and in tumor bearing animals are described. In the patients, {sup 57}Co-Bleomycin appears to be one of the useful tumor- seeking radiopharmaceuticals, and worth applicable to clinical uses. Labelled yield of {sup 57}Co-Bleo was about 97% by thin layer chromatography. The pyrogen free tests were performed to meet U.S.P. critical ranges. In clinical studies with {sup 57}Co-Bleo, 4 cases out of 5 patients with lung cancer, 2 cases among 3 thyroid cancer patients, and all 3 hepatoma patients showed positive tumor scans. The patients with stomach cancer, and the esophageal cancer showed false negative scintigraphy. A case with pulmonary tuberculosis showed a positive scan while liver abscess showed a negative picture. The merits of {sup 57}Co-Bleomycin scintigraphy seems to be its relatively high affinity to tumors and low radiation hazard in spite of long physical half life.

  19. CD133+ brain tumor-initiating cells are dependent on STAT3 signaling to drive medulloblastoma recurrence.

    Science.gov (United States)

    Garg, N; Bakhshinyan, D; Venugopal, C; Mahendram, S; Rosa, D A; Vijayakumar, T; Manoranjan, B; Hallett, R; McFarlane, N; Delaney, K H; Kwiecien, J M; Arpin, C C; Lai, P-S; Gómez-Biagi, R F; Ali, A M; de Araujo, E D; Ajani, O A; Hassell, J A; Gunning, P T; Singh, S K

    2017-02-02

    Medulloblastoma (MB), the most common malignant paediatric brain tumor, is currently treated using a combination of surgery, craniospinal radiotherapy and chemotherapy. Owing to MB stem cells (MBSCs), a subset of MB patients remains untreatable despite standard therapy. CD133 is used to identify MBSCs although its functional role in tumorigenesis has yet to be determined. In this work, we showed enrichment of CD133 in Group 3 MB is associated with increased rate of metastasis and poor clinical outcome. The signal transducers and activators of transcription-3 (STAT3) pathway are selectively activated in CD133 + MBSCs and promote tumorigenesis through regulation of c-MYC, a key genetic driver of Group 3 MB. We screened compound libraries for STAT3 inhibitors and treatment with the selected STAT3 inhibitors resulted in tumor size reduction in vivo. We propose that inhibition of STAT3 signaling in MBSCs may represent a potential therapeutic strategy to treat patients with recurrent MB.

  20. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

    Science.gov (United States)

    Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

    2007-04-01

    Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

  1. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

    International Nuclear Information System (INIS)

    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo; Ki, Chang Seok

    2012-01-01

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  2. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo [Dept. of Radiology, Dong-A University Medicine Center, Dong-A University College of Medicine, Busan (Korea, Republic of); Ki, Chang Seok [Dept. of Radiology, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  3. Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism

    Czech Academy of Sciences Publication Activity Database

    Rychtarčíková, Zuzana; Lettlová, Sandra; Tomkova, Veronika; Korenková, Vlasta; Langerová, Lucie; Simonova, Ekaterina; Zjablovskaja, Polina; Alberich-Jorda, Meritxell; Neužil, Jiří; Truksa, Jaroslav

    2017-01-01

    Roč. 8, č. 4 (2017), s. 6376-6398 ISSN 1949-2553 R&D Projects: GA ČR GA13-28830S; GA ČR GA15-03796S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:68378050 Keywords : tumor-initiating cells * breast cancer * iron metabolism Subject RIV: FD - Oncology ; Hematology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Cell biology; Cell biology (UMG-J) Impact factor: 5.168, year: 2016

  4. Considerations in the development of circulating tumor cell technology for clinical use

    Directory of Open Access Journals (Sweden)

    Parkinson David R

    2012-07-01

    Full Text Available Abstract This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development–analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA and the US National Cancer Institute (NCI.

  5. Clinical and pathological characteristics of primitive neuroectodermal tumor of the cerebral

    International Nuclear Information System (INIS)

    Fu Jun; Zhou Youxin; Xu Feng; Ye Ming; Zhou Dai; Bao Yaodong; Kang Suya

    2004-01-01

    Objective: To study the features of the cerebral primitive neuroectodermal tumor (PNET) in the clinical manifestation and in the histogenesis, morphology. Methods: Seven cases of cerebral PNET was analyzed with their clinical manifestations, histologic and immunohistochemical results. Results: Five patients of this group were children or young adults. Seven tumors were composed of primitive cells with focal evidence of glial or neuronal differentiation. Five out seven expressed NSE, one out seven expressed Syn, two out seven expressed CD99 and only one case expressed Vimentin, None expressed GFAP and S-100. CT findings were a homogeneous high density or heterogeneous mass. MR findings were high signal intensity both on T1 and T2 images. Conclusion: To diagnose the cerebral PNET depends on pathology and cerebral PNET have poor prognosis

  6. Inflammatory pseudo tumor (pseudo sarcoma) of the urinary bladder: clinical aspects and computed tomography images

    International Nuclear Information System (INIS)

    Romero, A.; Bueno, A.; Trigo, J.E.; Torres, A.

    1998-01-01

    Inflammatory pseudo tumor (pseudosarcoma) of the urinary bladder is an uncommon lesion with benign histopathological features. It consists of large cell proliferation, spindle-cell morphology (myofibroblasts) deriving from the bladder sub mucosa. It can present in patients of either sex and of any age; on occasion, it has been related to a history of surgery or previous bladder injury. Both the clinical and radiological features are nonspecific in that they do not differentiate this lesion from malignant disease; its diagnosis can only be definitively established by histopathological study. We present a case of inflammatory bladder pseudo tumor in a young girl, describing the clinical and radiological features of this lesion, which only rarely has been dealt with in the literature, particularly that concerning radiology. (Author) 13 refs

  7. A realistic closed-form radiobiological model of clinical tumor-control data incorporating intertumor heterogeneity

    International Nuclear Information System (INIS)

    Roberts, Stephen A.; Hendry, Jolyon H.

    1998-01-01

    Purpose: To investigate the role of intertumor heterogeneity in clinical tumor control datasets and the relationship to in vitro measurements of tumor biopsy samples. Specifically, to develop a modified linear-quadratic (LQ) model incorporating such heterogeneity that it is practical to fit to clinical tumor-control datasets. Methods and Materials: We developed a modified version of the linear-quadratic (LQ) model for tumor control, incorporating a (lagged) time factor to allow for tumor cell repopulation. We explicitly took into account the interpatient heterogeneity in clonogen number, radiosensitivity, and repopulation rate. Using this model, we could generate realistic TCP curves using parameter estimates consistent with those reported from in vitro studies, subject to the inclusion of a radiosensitivity (or dose)-modifying factor. We then demonstrated that the model was dominated by the heterogeneity in α (tumor radiosensitivity) and derived an approximate simplified model incorporating this heterogeneity. This simplified model is expressible in a compact closed form, which it is practical to fit to clinical datasets. Using two previously analysed datasets, we fit the model using direct maximum-likelihood techniques and obtained parameter estimates that were, again, consistent with the experimental data on the radiosensitivity of primary human tumor cells. This heterogeneity model includes the same number of adjustable parameters as the standard LQ model. Results: The modified model provides parameter estimates that can easily be reconciled with the in vitro measurements. The simplified (approximate) form of the heterogeneity model is a compact, closed-form probit function that can readily be fitted to clinical series by conventional maximum-likelihood methodology. This heterogeneity model provides a slightly better fit to the datasets than the conventional LQ model, with the same numbers of fitted parameters. The parameter estimates of the clinically

  8. Stereotactic Ablative Radiation Therapy for Subcentimeter Lung Tumors: Clinical, Dosimetric, and Image Guidance Considerations

    International Nuclear Information System (INIS)

    Louie, Alexander V.; Senan, Suresh; Dahele, Max; Slotman, Ben J.; Verbakel, Wilko F.A.R.

    2014-01-01

    Purpose: Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials: We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results: Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions: Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize

  9. Using tumor phenotype, histological tumor distribution, and mammographic appearance to explain the survival differences between screen-detected and clinically detected breast cancers.

    Science.gov (United States)

    Chuang, Shu-Lin; Chen, Sam Li-Sheng; Yu, Cheng-Ping; Chang, King-Jen; Yen, Amy Ming-Fang; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Tabár, László; Stephen, Duffy W; Smith, Robert A; Chen, Hsiu-Hsi

    2014-08-01

    In the era of mass screening for breast cancer with mammography, it has been noted that conventional tumor attributes and mammographic appearance are insufficient to account for the better prognosis of screen-detected tumors. Such prognostication may require additional updated pathological information regarding tumor phenotype (e.g., basal status) and histological tumor distribution (focality). We investigated this hypothesis using a Bayesian approach to analyze breast cancer data from Dalarna County, Sweden. We used data for tumors diagnosed in the Swedish Two-County Trial and early service screening period, 1977-1995, and from the mature service screening period, 1996-1998. In the early period of mammographic screening (1977-1995), the crude hazard ratio (HR) of breast cancer death for screen-detected cases compared with symptomatic ones was 0.22 (95% CI: 0.17-0.29) compared with 0.53 (95% CI: 0.34-0.76) when adjusted for conventional tumor attributes only. Using the data from the mature service screening period, 1996-1998, the HR was 0.23 (95% CI: 0.08-0.44) unadjusted and 0.71 (95% CI: 0.26-1.47) after adjustment for tumor phenotype, mammographic appearance, histological tumor distribution, and conventional tumor attributes. The area under the ROC curve (AUC) for the prediction of breast cancer deaths using these variables without the detection mode was 0.82, only slightly less than that observed when additionally including the detection mode (AUC=0.83). Using Freedman statistics, conventional tumor attributes and mammographic appearances explained 58% (95% CI: 57.5-58.6%) of the difference of breast cancer survival between the screen-detected and the clinically detected breast cancers, whereas the corresponding figure was increased to 77% (95% CI: 75.6-77.6%) when adding the two information on tumor phenotype and histological tumor distribution. The results indicated that conventional tumor attributes and mammographic appearance are not sufficient to be

  10. Clinical Evaluation and Cost-Effectiveness Analysis of Serum Tumor Markers in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2013-01-01

    Full Text Available The detection of serum tumor markers is valuable for the early diagnosis of lung cancer. Tumor markers are frequently used for the management of cancer patients. However, single markers are less efficient but marker combinations increase the cost, which is troublesome for clinics. To find an optimal serum marker combination panel that benefits the patients and the medical management system as well, four routine lung cancer serum markers (SCCA, NSE, CEA, and CYFRA21-1 were evaluated individually and in combination. Meanwhile, the costs and effects of these markers in clinical practice in China were assessed by cost-effectiveness analysis. As expected, combinations of these tumor markers improved their sensitivity for lung cancer and different combination panels had their own usefulness. NSE + CEA + CYFRA21-1 was the optimal combination panel with highest Youden’s index (0.64, higher sensitivity (75.76%, and specificity (88.57%, which can aid the clinical diagnosis of lung cancer. Nevertheless, the most cost-effective combination was SCCA + CEA, which can be used to screen the high-risk group.

  11. Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

    Science.gov (United States)

    Horta, Rodrigo S; Lavalle, Gleidice E; Monteiro, Lidianne N; Souza, Mayara C C; Cassali, Geovanni D; Araújo, Roberto B

    2018-03-01

    Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, r P = -0.610), history of tumor recurrence ( P < .0001, r P = -0.550), Patnaik ( P < .0001, r P = -0.380) and Kiupel grades ( P < .0001, r P = -0.500), predominant organization of neoplastic cells ( P < .0001, r P = -0.452), mitotic count ( P < .0001, r P = -0.325), Ki-67 labeling index ( P < .0001, r P = -0.414), KITr pattern ( P = .02, r P = 0.207), and c-KIT mutational status ( P < .0001, r P = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

  12. Autofluorescence lifetime imaging during transoral robotic surgery: a clinical validation study of tumor detection (Conference Presentation)

    Science.gov (United States)

    Lagarto, João. L.; Phipps, Jennifer E.; Unger, Jakob; Faller, Leta M.; Gorpas, Dimitris; Ma, Dinglong M.; Bec, Julien; Moore, Michael G.; Bewley, Arnaud F.; Yankelevich, Diego R.; Sorger, Jonathan M.; Farwell, Gregory D.; Marcu, Laura

    2017-02-01

    Autofluorescence lifetime spectroscopy is a promising non-invasive label-free tool for characterization of biological tissues and shows potential to report structural and biochemical alterations in tissue owing to pathological transformations. In particular, when combined with fiber-optic based instruments, autofluorescence lifetime measurements can enhance intraoperative diagnosis and provide guidance in surgical procedures. We investigate the potential of a fiber-optic based multi-spectral time-resolved fluorescence spectroscopy instrument to characterize the autofluorescence fingerprint associated with histologic, morphologic and metabolic changes in tissue that can provide real-time contrast between healthy and tumor regions in vivo and guide clinicians during resection of diseased areas during transoral robotic surgery. To provide immediate feedback to the surgeons, we employ tracking of an aiming beam that co-registers our point measurements with the robot camera images and allows visualization of the surgical area augmented with autofluorescence lifetime data in the surgeon's console in real-time. For each patient, autofluorescence lifetime measurements were acquired from normal, diseased and surgically altered tissue, both in vivo (pre- and post-resection) and ex vivo. Initial results indicate tumor and normal regions can be distinguished based on changes in lifetime parameters measured in vivo, when the tumor is located superficially. In particular, results show that autofluorescence lifetime of tumor is shorter than that of normal tissue (p robot assisted cancer removal interventions.

  13. Analysis of angiogenic factors and cyclooxygenase-2 expression in cartilaginous tumors: clinical and histological correlation

    Directory of Open Access Journals (Sweden)

    Francisco Fontes Cintra

    2011-01-01

    Full Text Available OBJECTIVES: To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis. INTRODUCTION: For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course-as monitored by sequential imaging techniques-even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of proangiogenic factors. METHODS: In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase- 2 expression. RESULTS: The significant variables that were associated with poor outcome were 1 higher-grade chondrosarcomas, 2 tumors that developed in flat bones, and 3 over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields. Moreover, CD34 expression (measured using the Chalkley method revealed significantly higher microvessel density in flat bone chondrosarcomas. DISCUSSION: Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain-at least in part-the more aggressive biological course that is taken by these tumors. CONCLUSIONS

  14. Survival analysis of female dogs with mammary tumors after mastectomy: epidemiological, clinical and morphological aspects

    Directory of Open Access Journals (Sweden)

    Maria Luíza de M. Dias

    2016-03-01

    Full Text Available Abstract: Mammary gland tumors are the most common type of tumors in bitches but research on survival time after diagnosis is scarce. The purpose of this study was to investigate the relationship between survival time after mastectomy and a number of clinical and morphological variables. Data was collected retrospectively on bitches with mammary tumors seen at the Small Animal Surgery Clinic Service at the University of Brasília. All subjects had undergone mastectomy. Survival analysis was conducted using Cox's proportional hazard method. Of the 139 subjects analyzed, 68 died and 71 survived until the end of the study (64 months. Mean age was 11.76 years (SD=2.71, 53.84% were small dogs. 76.92% of the tumors were malignant, and 65.73% had both thoracic and inguinal glands affected. Survival time in months was associated with age (hazard rate ratios [HRR] =1.23, p-value =1.4x10-4, animal size (HRR between giant and small animals =2.61, p-value =0.02, nodule size (HRR =1.09, p-value =0.03, histological type (HRR between solid carcinoma and carcinoma in a mixed tumor =2.40, p-value =0.02, time between diagnosis and surgery (TDS, with HRR =1.21, p-value =2.7x10-15, and the interaction TDS*follow-up time (HRR =0.98, p-value =1.6x10-11. The present study is one of the few on the subject matter. Several important covariates were evaluated and age, animal size, nodule size, histological type, TDS and TDS*follow up time were identified as significantly associated to survival time.

  15. Tumor initiating cells and chemoresistance: which is the best strategy to target colon cancer stem cells?

    Science.gov (United States)

    Paldino, Emanuela; Tesori, Valentina; Casalbore, Patrizia; Gasbarrini, Antonio; Puglisi, Maria Ausiliatrice

    2014-01-01

    There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called "cancer stem cells" (CSCs). In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.

  16. Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses

    Directory of Open Access Journals (Sweden)

    Aaberg Jr TM

    2014-12-01

    Full Text Available Thomas M Aaberg Jr,1 Robert W Cook,2 Kristen Oelschlager,2 Derek Maetzold,2 P Kumar Rao,3 John O Mason III41Michigan State University Medical School and Retina Specialists of Michigan, Grand Rapids, MI, 2Castle Biosciences, Friendswood, TX, 3Washington University School of Medicine in St Louis, St Louis, MO, 4Retina Consultants of Alabama and University of Alabama Birmingham, Birmingham, AL, USA Objective: Assess current clinical practices for uveal melanoma (UM and the impact of molecular prognostic testing on treatment decisions.Design: Cross-sectional survey and sequential medical records review.Participants: Ophthalmologists who treat UM.Methods: (A Medical records review of all Medicare beneficiaries tested by UM gene expression profile in 2012, conducted under an institutional review board-approved protocol. (B 109 ophthalmologists specializing in the treatment of UM were invited to participate in 24-question survey in 2012; 72 were invited to participate in a 23-question survey in 2014.Main outcome measures: Responses analyzed by descriptive statistics, frequency analyses (percentages, Tukey, histograms, and Fisher’s exact test. Descriptive presentation of essay answers.Results: The review of Medicare medical records included 191 evaluable patients, 88 (46% with documented medical treatment actions or institutional policies related to surveillance plans. Of these 88, all gene expression profiling (GEP Class 1 UM patients were treated with low-intensity surveillance. All GEP Class 2 UM patients were treated with high-intensity surveillance (P<0.0001 versus Class 1. There were 36 (19% with information concerning referrals after initial diagnosis. Of these 36, all 23 Class 2 patients were referred to medical oncology; however, none of the 13 Class 1 patients were referred (P<0.0001 versus Class 1. Only Class 2 patients were recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with an annual median of 35 new UM

  17. Differential tumor biology effects of double-initiation in a mouse skin chemical carcinogenesis model comparing wild type versus protein kinase Cepsilon overexpression mice.

    Science.gov (United States)

    Li, Yafan; Wheeler, Deric L; Ananthaswamy, Honnavara N; Verma, Ajit K; Oberley, Terry D

    2007-12-01

    Our previous studies showed that protein kinase Cepsilon (PKCepsilon) verexpression in mouse skin resulted in metastatic squamous cell carcinoma (SCC) elicited by single 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion in the absence of preceding papilloma formation as is typically observed in wild type mice. The present study demonstrates that double-DMBA initiation modulates tumor incidence, multiplicity, and latency period in both wild type and PKCepsilon overexpression transgenic (PKCepsilon-Tg) mice. After 17 weeks (wks) of tumor promotion, a reduction in papilloma multiplicity was observed in double- versus single-DMBA initiated wild type mice. Papilloma multiplicity was inversely correlated with cell death indices of interfollicular keratinocytes, indicating decreased papilloma formation was caused by increased cell death and suggesting the origin of papillomas is in interfollicular epidermis. Double-initiated PKCepsilon-Tg mice had accelerated carcinoma formation and cancer incidence in comparison to single-initiated PKCepsilon-Tg mice. Morphologic analysis of mouse skin following double initiation and tumor promotion showed a similar if not identical series of events to those previously observed following single initiation and tumor promotion: putative preneoplastic cells were observed arising from hyperplastic hair follicles (HFs) with subsequent cancer cell infiltration into the dermis. Single-initiated PKCepsilon-Tg mice exhibited increased mitosis in epidermal cells of HFs during tumor promotion.

  18. Characterization and propagation of tumor initiating cells derived from colorectal liver metastases: trials, tribulations and a cautionary note.

    Directory of Open Access Journals (Sweden)

    Mark I James

    Full Text Available Tumor initiating cells (TIC are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment. Tumor initiating cells from liver metastases were characterised using combinations of EPCAM, Aldehyde dehydrogenase activity, CD133 and CD26. CD133 expression was significantly lower in patients who had received chemotherapy, but this was accounted for by a decrease observed in the male patient cohort only. ALDHhigh populations were rare (0.4 and 0.3% for EPCAM+/ALDHhigh/CD133- and EPCAM+/ALDHhigh/CD133+ populations respectively and below the limits of detection in 28% of samples. Spheroid outgrowth of metastatic tumor cells across all samples could not be readily achieved using standard spheroid-formation techniques, thus requiring further method validation to reliably propagate cells from the majority of tissues. Spheroid formation was not enhanced using additional growth factors or fibroblast co-culture, but once cells were passaged through NOD-SCID mice, spheroid formation was observed in 82% samples, accompanied by a significant increase in CD26. Order of spheroid forming ability was ALDHhigh>CD133>CD26. Samples sorted by these markers each had the ability to reform ALDHhigh, CD133 and CD26 positive populations to a similar extent, suggestive of a high degree of plasticity for each population. Ex vivo TIC models are increasingly being utilised to assess efficacy of therapeutic interventions. It is therefore essential that such investigations use well-characterised models that are able to sustain TIC populations across a large patient cohort in order that the inherent

  19. Macro- and microadenoma of thyrotropin secreting pituitary tumors--two clinical cases.

    Science.gov (United States)

    Hubalewska-Hola, Alicja; Fröss, Katarzyna; Kostecka-Matyja, Marta; Sowa-Staszczak, Anna; Szybiński, Zbigniew; Huszno, Bohdan; Ptak, Marzena

    2003-01-01

    Thyrotropin secreting adenoma, thyrotropinoma (TSH-oma), is a rare cause of hyperthyroidism--called secondary hyperthyroidism. The hormonal profile in pituitary hyperthyroidism is characterized by a nonsuppressed TSH in the presence of high levels of free thyroid hormones (fT4, fT3) reflecting an abnormal feedback. The diagnosis of TSH-oma is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. Two cases of TSH-secreting adenoma were detected in Chair and Department of Endocrinology, Collegium Medicum of the Jagiellonian University in Krakow for the last twenty years. Case 1: 49 year old woman was admitted to the Clinic of Endocrinology in 1999 with recurring hyperthyroidism treated with surgical thyroid ablation in 1992 and thyreostatics for the previous nine years. On admission to the Clinic her thyroid panel presented with elevated free hormone levels (mainly fT3-14.8 pmol/l) and not suppressed TSH-0.7 mIU/l suggesting central hyperthyroidism. MRI scan of the pituitary gland revealed microadenoma of 5 mm in diameter. She was qualified to transsphenoidal resection of the tumor. Histopathology revealed acidophilic adenoma with positive TSH staining. Thyroid hormones 8 days after the operation suggested full effectiveness of the surgery. Case 2: 65 year old man treated for one year with L-Thyroxin because of elevated TSH (60 mIU/l) and then with thyreostatics for elevated fT3 and fT4 was admitted to the Clinic of Endocrinology in 2000 with suspected thyrotropinoma. On admission to the Clinic thyroid panel suggested hyperthyroidism with fT4-40 pmol/l, FT3-11.2 pmol/l without suppression of TSH 2.2 mIU/l. MRI scan revealed a pituitary tumor 20 x 18 x 20 mm, compressing the optic chiasm. He was administered octreotide as a preparation for the operation. The patient underwent trans-sphenoidal resection of the adenoma

  20. Postoperative intraspinal subdural collections after pediatric posterior fossa tumor resection: incidence, imaging, and clinical features.

    Science.gov (United States)

    Harreld, J H; Mohammed, N; Goldsberry, G; Li, X; Li, Y; Boop, F; Patay, Z

    2015-05-01

    Postoperative intraspinal subdural collections in children after posterior fossa tumor resection may temporarily hinder metastasis detection by MR imaging or CSF analysis, potentially impacting therapy. We investigated the incidence, imaging and clinical features, predisposing factors, and time course of these collections after posterior fossa tumor resection. Retrospective review of postoperative spine MRI in 243 children (5.5 ± 4.6 years of age) from our clinical data base postresection of posterior fossa tumors from October 1994 to August 2010 yielded 37 (6.0 ± 4.8 years of age) subjects positive for postoperative intraspinal subdural collections. Their extent and signal properties were recorded for postoperative (37/37), preoperative (15/37), and follow-up spine (35/37) MRI. Risk factors were compared with age-matched internal controls (n = 37, 5.9 ± 4.5 years of age). Associations of histology, hydrocephalus and cerebellar tonsillar herniation, and postoperative intracranial subdural collections with postoperative intraspinal subdural collections were assessed by the Fisher exact test or χ(2) test. The association between preoperative tumor volume and postoperative intraspinal subdural collections was assessed by the Wilcoxon rank sum test. The overall incidence of postoperative intraspinal subdural collections was 37/243 (15.2%), greatest ≤7 days postoperatively (36%); 97% were seen 0-41 days postoperatively (12.9 ± 11.0 days). They were T2 hyperintense and isointense to CSF on T1WI, homogeneously enhanced, and resolved on follow-up MR imaging (35/35). None were symptomatic. They were associated with intracranial subdural collections (P = .0011) and preoperative tonsillar herniation (P = .0228). Postoperative intraspinal subdural collections are infrequent and clinically silent, resolve spontaneously, and have a distinctive appearance. Preoperative tonsillar herniation appears to be a predisposing factor. In this series, repeat MR imaging by 4 weeks

  1. Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors.

    Science.gov (United States)

    Roy, Laurent-Olivier; Poirier, Marie-Belle; Fortin, David

    2018-04-08

    Glioblastoma (GBM) represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-β). We hypothesized that TGF-β gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-β₁ and -β₂ expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan-Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS). In GBM, TGF-β₁ and -β₂ levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and multivariate analyses revealed that high to moderate expressions of TGF-β₁ significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-β₁ is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β₂. We believe our study is the first to unveil a significant relationship between TGF-β₁ expression and OS or PFS in newly diagnosed GBM. TGF-β₁ could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.

  2. Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors

    Directory of Open Access Journals (Sweden)

    Laurent-Olivier Roy

    2018-04-01

    Full Text Available Glioblastoma (GBM represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-β. We hypothesized that TGF-β gene expression could correlate with overall survival (OS and serve as a prognostic biomarker. TGF-β1 and -β2 expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan–Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS. In GBM, TGF-β1 and -β2 levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan–Meier and multivariate analyses revealed that high to moderate expressions of TGF-β1 significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-β1 is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-β2. We believe our study is the first to unveil a significant relationship between TGF-β1 expression and OS or PFS in newly diagnosed GBM. TGF-β1 could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.

  3. A clinical audit of provider-initiated HIV counselling and testing in a ...

    African Journals Online (AJOL)

    Background. Early initiation of antiretroviral therapy reduces transmission of HIV and prolongs life. Expansion of HIV testing is therefore pivotal in overcoming the HIV pandemic. Provider-initiated counselling and testing (PICT) at first clinical contact is one way of increasing the number of individuals tested. Our impression is ...

  4. Tumor Initiating Cells and Chemoresistance: Which Is the Best Strategy to Target Colon Cancer Stem Cells?

    Directory of Open Access Journals (Sweden)

    Emanuela Paldino

    2014-01-01

    Full Text Available There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called “cancer stem cells” (CSCs. In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.

  5. Clinical use of serum TRA-1-60 as tumor marker in patients with germ cell cancer

    DEFF Research Database (Denmark)

    Lajer, Henrik; Daugaard, Gedske; Andersson, Anna-Maria

    2002-01-01

    TRA-1-60 antigen has been related to the presence of embryonal germ cell carcinoma (EC) and carcinoma in situ. Our study further investigated the clinical efficacy of TRA-1-60 as a serum tumor marker for germ cell cancer in the testis. Three groups of patients with germ cell tumors were included:...

  6. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  7. p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells.

    Science.gov (United States)

    Forsyth, Peter A; Krishna, Niveditha; Lawn, Samuel; Valadez, J Gerardo; Qu, Xiaotao; Fenstermacher, David A; Fournier, Michelle; Potthast, Lisa; Chinnaiyan, Prakash; Gibney, Geoffrey T; Zeinieh, Michele; Barker, Philip A; Carter, Bruce D; Cooper, Michael K; Kenchappa, Rajappa S

    2014-03-21

    Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target.

  8. Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring.

    Science.gov (United States)

    Chang, Yi; Tolani, Bhairavi; Nie, Xiuhong; Zhi, Xiuyi; Hu, Mu; He, Biao

    2017-01-01

    Circulating cell-free DNA (cfDNA) released by tumor cells, termed ctDNA, closely reflects the heterogeneity of primary cancers and their metastases. As a noninvasive, real-time monitoring biomarker, ctDNA is a promising tool for detecting driver gene mutations, assessing tumor burden and acquired resistance, and early diagnosis. However, isolation and enrichment of cfDNA is a big challenge due to the high degree of DNA fragmentation and its relatively low abundance in the bloodstream. This review aims to provide insights into the recent technological advances in acquisition of optimal quality cfDNA, the use of preservatives, isolation methods, processing timelines, and detection techniques. It also describes clinical applications of ctDNA in cancer patient management.

  9. Clinical characteristics of elastofibroma dorsi incidentally detected on FDG-PET/CT for a thoracic tumor

    International Nuclear Information System (INIS)

    Kawasaki, Hidenori; Higa, Noboru; Yohena, Tomofumi

    2011-01-01

    When elastofibroma dorsi with FDG accumulation is found by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with a malignant tumor, its differentiation from a metastasis seems to be a difficult and critical problem. As there are few reports on FDG-PET for elastofibroma dorsi, we reviewed those cases of elastofibroma dorsi which were incidentally discovered on FDG-PET/CT. We retrospectively reviewed 306 patients who underwent FDG-PET/CT for the evaluation of a lung or mediastinal tumor, and in whom elastofibroma dorsi was detected, and analyzed their clinical characteristics. Elastofibroma dorsi was detected in 16 of the 306 cases (5.2%); 10 of whom were women and 6 were men. Age ranged from 55 to 82 years, with an average of 71.6 years. Woman were predominant among the patients with elastofibroma dorsi, compared with patients without a tumor (p=0.0177). Elderly patients were also predominant among the patients with elastofibroma dorsi, compared with patients without a tumor, but the difference was not significant (p=0.0587). The accumulation of FDG was observed in 8 of the 16 cases (15 of 31 tumors). The maximum standardized uptake values (SUVmax) ranged from 2.0 to 2.9, with an average of 2.3, among those cases in which the SUVmax was evaluated. Although elastofibroma is rare, it is important for physicians to know that some elastofibromas exhibit FDG accumulation on PET. This knowledge may help to prevent unnecessary biopsies or surgical interventions, and also prevent excessive anxiety in patients with elastofibroma dorsi. (author)

  10. Advancing Medication Reconciliation in an Outpatient Internal Medicine Clinic through a Pharmacist-Led Educational Initiative

    Directory of Open Access Journals (Sweden)

    Sarah M. Westberg

    2010-06-01

    Full Text Available Objectives: To develop and deliver an effective pharmacist-led educational initiative to clinic staff to advance medication reconciliation in the electronic medical record of an outpatient internal medicine clinic. Methods: An educational initiative designed to improve the ability of nursing staff in medication reconciliation was launched in the outpatient internal medicine clinic of a regional healthcare system. The education was provided by the pharmacist to clinic nursing staff, including registered nurses, licensed practical nurses, and certified medical assistants. The impact of this training was measured through pre-initiation and post-implementation surveys, competency assessments and an audit. Results: The educational initiative was successfully designed and delivered to clinic nursing staff. Assessment of the initiative found that all nursing staff completing competency assessments successfully passed. Pre-initiation- and post-implementation- survey responses on the self-assessed ability to gather and document accurate medication lists did not show significant changes. Informal observations in the clinic indicated that this initiative changed the culture of the clinic, creating increased awareness of the importance of accurate medications and increased emphasis on medication reconciliation. Conclusions: The expertise of pharmacists can be utilized to educate nursing staff on the skills and abilities necessary to gather and document accurate medication lists. This study did not find measurable changes in the accuracy of medication lists in this clinic. Future research is needed to determine the best methods to train health professionals in medication reconciliation to ensure accurate medication lists in the outpatient setting. Type: Original Research

  11. Mass Medication Clinic (MMC) Patient Medical Assistant (PMA) System Training Initiative

    Science.gov (United States)

    2007-06-01

    AD_________________ Award Number: W81XWH-06-2-0045 TITLE: Mass Medication Clinic (MMC) Patient ...SUBTITLE 5a. CONTRACT NUMBER Mass Medication Clinic (MMC) Patient Medical Assistant (PMA) System Training Initiative 5b. GRANT NUMBER W81XWH-06-2...sections will describe the events, results, and accomplishments of this study. With validation through this project the Patient Medical Assistant

  12. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li Xin

    2010-04-01

    Full Text Available Abstract Background The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1 in nasopharyngeal carcinoma (NPC and its correlation with clinicopathologic features, including patients' survival time. Methods Using real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated. Results The expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (P EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues (P EIF4G1 protein in tumors were positively correlated with tumor T classification (P = 0.039, lymph node involvement (N classification, P = 0.008, and the clinical stages (P = 0.003 of NPC patients. Patients with higher EIF4G1 expression had shorter overall survival time (P = 0.019. Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth. Conclusion Our data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.

  13. Circulating Tumor Cell Analysis: Technical and Statistical Considerations for Application to the Clinic

    Directory of Open Access Journals (Sweden)

    Alison L. Allan

    2010-01-01

    Full Text Available Solid cancers are a leading cause of death worldwide, primarily due to the failure of effective clinical detection and treatment of metastatic disease in distant sites. There is growing evidence that the presence of circulating tumor cells (CTCs in the blood of cancer patients may be an important indicator of the potential for metastatic disease and poor prognosis. Technological advances have now facilitated the enumeration and characterization of CTCs using methods such as PCR, flow cytometry, image-based immunologic approaches, immunomagnetic techniques, and microchip technology. However, the rare nature of these cells requires that very sensitive and robust detection/enumeration methods be developed and validated in order to implement CTC analysis for widespread use in the clinic. This review will focus on the important technical and statistical considerations that must be taken into account when designing and implementing CTC assays, as well as the subsequent interpretation of these results for the purposes of clinical decision making.

  14. Neuroendocrine tumors of colon and rectum: validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and European Neuroendocrine Tumor Society staging systems.

    Science.gov (United States)

    Shen, Chaoyong; Yin, Yuan; Chen, Huijiao; Tang, Sumin; Yin, Xiaonan; Zhou, Zongguang; Zhang, Bo; Chen, Zhixin

    2017-03-28

    This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression (P<0.05). Data from 192 consecutive patients histopathologically diagnosed with CRNETs and had undergone surgical resection from January 2009 to May 2016 in a single center were retrospectively analyzed. Findings suggest that the WHO classifications are superior over the ENETS classification system in predicting the prognosis of CRNETs. Additionally, the WHO classifications can be widely used in clinical practice.

  15. CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

    International Nuclear Information System (INIS)

    Seidel, Claudia; Dietrich, Antje; Wondrak, Marit; Kunz-Schughart, Leoni A.; Grade, Marian; Ried, Thomas

    2009-01-01

    The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133 + ) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133 + subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133 + cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133 + / CD133 - subpopulations

  16. On clinical usefulness of Tl-201 scintigraphy for the management of malignant soft tissue tumors

    International Nuclear Information System (INIS)

    Terui, Shoji; Terauchi, Takashi; Abe, Hiroyuki; Fukuma, Hisatoshi; Beppu, Yasuo; Chuman, Koichi; Yokoyama, Ryohei

    1994-01-01

    The purpose of this study was to investigate Tl-201 as a tumor scanning agent in patients with malignant soft tissue sarcomas and to establish the sensitivity of this type of scintigraphy concerning local recurrences or metastases that may remain clinically suspected. Seventy-eight patients with malignant soft tissue sarcomas and 22 with benign soft tissue tumors were studied. Of these 78 malignant soft tissue sarcomas patients, the sensitivity of Tl-201 (81.2%) was higher than that of Ga-67 (68.8%). Thirty-three out of 78 patients received a total of 95 consecutive scintigraphic follow-up examinations. Therapeutic effects was assessed by comparing the results of Tl-201 examinations with the clinical findings. Of these 33 patients, the therapeutic effects observed were as follows: complete remission 1, partial remission 8, progress of disease 1, and no remarkable change 23. Tl-201 scintigraphy has proved itself very useful not only in clinically detecting the malignant soft tissue sarcomas and in assessing therapeutic effects on these diseases, but also in assessing the follow-up patients with malignant soft tissue sarcomas. (author)

  17. Osteotoxicity after chronic dietary administration of 13-CIS-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion

    International Nuclear Information System (INIS)

    Forsyth, K.S.; Gensler, H.L.; Watson, R.R.

    1989-01-01

    In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-O-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU or retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP/g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion results in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased O-fold, 1.4-fold, and 3.6-fold. Bone deformities was augmented O-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium did not alter the bone toxicity of RP. 13-cis-retionic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidence by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osterotoxicities were similar in the mice fed diets supplemented with RP and CRA

  18. Clinical value of proton magnetic resonance spectroscopy for differentiating recurrent or residual brain tumor from delayed cerebral necrosis

    International Nuclear Information System (INIS)

    Taylor, June S.; Langston, James W.; Reddick, Wilburn E.; Kingsley, Peter B.; Ogg, Robert J.; Pui, Margaret H.; Kun, Larry E.; Jenkins, Jesse J.; Gang, Chen; Ochs, Judith J.; Sanford, Robert A.; Heideman, Richard L.

    1996-01-01

    Purpose: Delayed cerebral necrosis (DN) is a significant risk for brain tumor patients treated with high-dose irradiation. Although differentiating DN from tumor progression is an important clinical question, the distinction cannot be made reliably by conventional imaging techniques. We undertook a pilot study to assess the ability of proton magnetic resonance spectroscopy ( 1 H MRS) to differentiate prospectively between DN or recurrent/residual tumor in a series of children treated for primary brain tumors with high-dose irradiation. Methods and Materials: Twelve children (ages 3-16 years), who had clinical and MR imaging (MRI) changes that suggested a diagnosis of either DN or progressive/recurrent brain tumor, underwent localized 1 H MRS prior to planned biopsy, resection, or other confirmatory histological procedure. Prospective 1 H MRS interpretations were based on comparison of spectral peak patterns and quantitative peak area values from normalized spectra: a marked depression of the intracellular metabolite peaks from choline, creatine, and N-acetyl compounds was hypothesized to indicate DN, and median-to-high choline with easily visible creatine metabolite peaks was labeled progressive/recurrent tumor. Subsequent histological studies identified the brain lesion as DN or recurrent/residual tumor. Results: The patient series included five cases of DN and seven recurrent/residual tumor cases, based on histology. The MRS criteria prospectively identified five out of seven patients with active tumor, and four out of five patients with histologically proven DN correctly. Discriminant analysis suggested that the primary diagnostic information for differentiating DN from tumor lay in the normalized MRS peak areas for choline and creatine compounds. Conclusions: Magnetic resonance spectroscopy shows promising sensitivity and selectivity for differentiating DN from recurrent/progressive brain tumor. A novel diagnostic index based on peak areas for choline and

  19. Clinical manifestations and computed tomography of the pseudovascular form of metastatic brain tumor

    International Nuclear Information System (INIS)

    Kurimoto, Tadahisa; Mizuno, Makoto; Tani, Sadayasu; Miki, Kazuhito; Kawamura, Yasuo; Matsumura, Hiroshi

    1982-01-01

    Forty-two cases of metastatic brain tumor were subdivided into 3 groups (acute, subacute, and chronic) from their mode of the onset of symptoms and signs. The clinical symptoms and signs and the computed tomogram were all analyzed and compared with each other. The acute form was found in 14 cases (33%), of which 7% (3 cases) were seizures and 26% (11 cases) were acute neurological deficits, including hemorrhages from tumors (3 cases, 7%). There were no significant differences in their age, sex, or primary lesions. The characteristic course of the acute form, other than seizure and hemorrhage, involved acutely and progressively developing neurological symptoms, symptoms and signs of increased intracranial pressure were rare. In computed tomogram, the solitary metastasis in the parietal and occipital lesions was much more in the acute form than in other forms, and the perifocal low-density area showed a tendency to be larger than the other forms. In these cases, acute symptoms and signs appeared to occur easily when perifocal edema was joined in the above locations. The pathogenesis of acute neurological symptoms and signs other than seizure and hemorrhage is unclear. We suggest that the location of a tumor and peritumoral edema be important factors in causing acute symptoms and signs, but, in addition to that, abrupt hemodynamic changes in the peritumoral edema may also be of importance. (J.P.N.)

  20. Clinical evaluation of tumor scintigraphy with /sup 57/Co-bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, K; Kawahira, K; Nakayama, C; Kamoi, I; Matsuura, K [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-06-01

    Of 84 patients to whom tumor scintigraphy with /sup 57/Co-bleomycin was performed, 76 patients were clinically evaluated. 47 per cent of the patients with malignant tumor were positive, and 3 of 10 patients with benign diseases showed positive picture. The positive rate was examined according to diseases, and 65.4% was found to be positive in primary lung cancer and 50% in malignant lymphoma. As positive rate was relatively low and count efficiency was also low in spite of the accumulation in the lesion in the scintigraphy with /sup 57/Co-bleomycin, the examination took long time and there was a difficulty in the management of urine excretions. It was therefore, inferior to that with /sup 67/Ga-citrate which was widely utilized at present. However, /sup 57/Co-bleomycin distributed in the bones in a small amount and the radioactivity level in the blood was low, so that it was considered to be effective to the diagnosis of tumors localized in the regions that were not above the bones. This point should be investigated as a future program.

  1. Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

    Directory of Open Access Journals (Sweden)

    Sarah Phillips

    2014-05-01

    Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

  2. Loss of p19(Arf facilitates the angiogenic switch and tumor initiation in a multi-stage cancer model via p53-dependent and independent mechanisms.

    Directory of Open Access Journals (Sweden)

    Danielle B Ulanet

    2010-08-01

    Full Text Available The Arf tumor suppressor acts as a sensor of oncogenic signals, countering aberrant proliferation in large part via activation of the p53 transcriptional program, though a number of p53-independent functions have been described. Mounting evidence suggests that, in addition to promoting tumorigenesis via disruptions in the homeostatic balance between cell proliferation and apoptosis of overt cancer cells, genetic alterations leading to tumor suppressor loss of function or oncogene gain of function can also incite tumor development via effects on the tumor microenvironment. In a transgenic mouse model of multi-stage pancreatic neuroendocrine carcinogenesis (PNET driven by inhibition of the canonical p53 and Rb tumor suppressors with SV40 large T-antigen (Tag, stochastic progression to tumors is limited in part by a requirement for initiation of an angiogenic switch. Despite inhibition of p53 by Tag in this mouse PNET model, concomitant disruption of Arf via genetic knockout resulted in a significantly accelerated pathway to tumor formation that was surprisingly not driven by alterations in tumor cell proliferation or apoptosis, but rather via earlier activation of the angiogenic switch. In the setting of a constitutional p53 gene knockout, loss of Arf also accelerated tumor development, albeit to a lesser degree. These findings demonstrate that Arf loss of function can promote tumorigenesis via facilitating angiogenesis, at least in part, through p53-independent mechanisms.

  3. Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial.

    Science.gov (United States)

    Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

    2017-09-01

    Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than

  4. Pan coast tumor. Literature review and report of a clinical case

    International Nuclear Information System (INIS)

    Vázquez, A.; Terzieff, V.

    2004-01-01

    A purpose of diagnosis and treatment of 29-year or carrier Pancoast Tumor perform the review of the literature and communicate said case. Material and Methods: We reviewed ten years of literature on the subject, aspects diagnoses, statistical and treatments. Results: pancoast tumor described in 1924 by this author, was reported for the first time in 1838 by Edwin Hare In our Ricaldoni what described at the beginning of last century. Lung tumor origin, located in the upper lobe with infiltration of adjacent structures characterized in the same by infiltration of the first rib, brachial plexus, cervical, and sympathetic system with its peculiar clinical presentation. Is between 1.2 and 5 % Of total CBP in different series for NPC tumors. It is preferred and recommended study by MRI, and eventually transmural puncture mediastinoscopy since N2 lymph node infiltration is worse prognosis than N3. treatment of it has evolved into the Qt-Rt induction prior to surgery, when it is possible to do. He still is in search of drugs and doses more efficient and optimal heating technique. In relation to surgery preferred techniques using block. Discussion: Based on the search for the best treatment, it is directly linked to the study and after staging the patient highlighting the value of preoperative MRI. The platinum-based induction and phasing Rt dose is discussed prioritizing reach 60 Gy or more. We report a case of a 29 years carrier of this disease in stage T4N3M1 in metastatic debut with his bad foreseeable development

  5. Clinical PET of Neuroendocrine Tumors Using 64Cu-DOTATATE: First-in-Humans Study

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Knigge, Ulrich Peter; Mortensen, Jann

    2012-01-01

    MBq of 64Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq). Conclusion: This first-in-humans study supports the clinical use of 64Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when...... administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical...... performance of 64Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3...

  6. Cervix cancer: clinical aspects of tumoral control and radiotherapy treatment time

    International Nuclear Information System (INIS)

    Petitto, J.V.

    1994-01-01

    The author analyzed 35 patients with recurrence or residual tumor at the end of the radiotherapy program. These patients were selected out of a group of 338 patients cervix cancer who had also undergone on the same radiotherapy program. Those patients were compared with control group of 30 patients without clinical evidence of the disease, from the same group of 338 patients. It has studied the clinical results considering the total radiotherapy time to developed the radiation program and factors that could modify the time for a longer program, and also modify the final survival results. No significant difference was shown in this study, but it should be taken in consideration the total radiotherapy time, because this is a factor that could change the final results if the time would be longer than what was shown in this work. (author). 26 refs, 10 tabs

  7. DIAGNOSTIC VALUE OF THE DEJA VU PHENOMENON IN THE CLINICAL PICTURE OF GLIAL BRAIN TUMORS

    Directory of Open Access Journals (Sweden)

    Pavel Nikolaevich Vlasov

    2009-01-01

    This investigation was undertaken to study the implication of the DV phenomenon in the clinical picture of glial brain tumors (GBT. One hundred and sixty-one subjects (mean age 29,2±6,4 years; males 47%, including 129 healthy individuals and 32 patients with GBT, were examined. In the clinical picture of GBT with seizures, DV is a common symptom that is encountered in the involvement of predominantly the right temporal lobe and accompanied by generalized convulsive attacks and olfactory hallucinations. DV in GBT occurs more than once daily; its duration is a few (as many as 5 minutes; DV is characterized by a negative emotional tinge and attended by fear

  8. Clinical pharmacokinetics and effects of vincristine sulfate in dogs with transmissible venereal tumor (TVT).

    Science.gov (United States)

    Hantrakul, Supannika; Klangkaew, Narumol; Kunakornsawat, Sunee; Tansatit, Tawewan; Poapolathep, Ammart; Kumagai, Susumu; Poapolathep, Saranya

    2014-12-01

    This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m(2) of body surface area. Blood samples were collected starting from 5 min to 48 hr after drug administration. The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model. The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively. Tumor regression was determined at weekly interval by a physical examination and histopathological analysis. In our study, three to eight administrations of vincristine at a dose of 0.7 mg/m(2) were able to induce a complete tumor regression without any evidence of gross lesion of disease. Therefore, this investigation provides the pharmacokinetic characteristics of vincristine in dogs with TVT, which may be used as an integration tool to gain a better understanding of the disposition properties of the drug and the correlation of these properties with the drug's clinical effects. In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.

  9. Clinical and ultrasonographic features of male breast tumors: A retrospective analysis.

    Science.gov (United States)

    Yuan, Wei-Hsin; Li, Anna Fen-Yau; Chou, Yi-Hong; Hsu, Hui-Chen; Chen, Ying-Yuan

    2018-01-01

    The purpose of this study was to determine clinical and ultrasonographic characteristics of male breast tumors. The medical records of male patients with breast lesions were retrieved from an electronic medical record database and a pathology database and retrospectively reviewed. A total of 112 men (125 breast masses) with preoperative breast ultrasonography (US) were included (median age, 59.50 years; age range, 15-96 years). Data extracted included patient age, if the lesions were bilateral, palpable, and tender, and the presence of nipple discharge. Breast lesion features on static US images were reviewed by three experienced radiologists without knowledge of physical examination or pathology results, original breast US image interpretations, or surgical outcomes. The US features were documented according to the BI-RADS (Breast Imaging-Reporting and Data System) US lexicons. A forth radiologist compiled the data for analysis. Of the 125 breast masses, palpable tender lumps and bilateral synchronous masses were more likely to be benign than malignant (both, 100% vs 0%, P nipples were common in malignant lesions (P nipple, irregular shape, the presence of an echogenic halo, predominantly internal vascularity, and rich color flow signal on color Doppler ultrasound were significantly related to malignancy (all, P < 0.05). An echogenic halo and the presence of rich color flow signal were independent predictors of malignancy. Specific clinical and US characteristics of male breast tumors may help guide treatment, and determine if surgery or conservative treatment is preferable.

  10. Clinical study of combined radio-thermotherapy for radioresistant tumors, 1

    International Nuclear Information System (INIS)

    Hiraoka, Masahiro; Ri, Nariyoshi; Ono, Kouji; Nishidai, Takehiro; Takahashi, Masaji

    1981-01-01

    Seventeen cases of superficial malignant tumors considered to be refractory to conventional treatment modalities were treated by thermotherapy in combination with radiation. Heat was generated by a microwave apparatus of 2450MHz. Fourteen cases which received complete thermotherapy were analysed and the following results were obtained. 1. Intratumor temperature of over 41 0 C was obtained in all cases and temperature of over 42.5 0 C was achieved in ten cases (71%). 2. In five out of fourteen cases, both intratumor and adjacent normal tissue temperatures were measured and intratumor temperature was approximately 1 0 C higher on the average than normal tissue temperature. 3. Phantom and clinical examinations demonstrated that effective heating depth obtained by this apparatus was approximately 3 cm from the surface. 4. Of eleven cases who hadn't received any radiotherapy, five cases showed complete regression (46%), three cases partial regression (27%) and no regression was observed in three cases (27%). Of three cases who had received full course of radiotherapy, two cases showed partial regression (67%) and one demonstrated no regression (33%). It was concluded that this heating unit was applicable to the thermotherapy for superficial malignant tumors. Radiosensitizing effect of heat was suggested, however more clinical experiences are needed to evaluate the definite usefulness of this treatment. (author)

  11. Clinical Trials of Immunogene Therapy for Spontaneous Tumors in Companion Animals

    Directory of Open Access Journals (Sweden)

    Gerardo Claudio Glikin

    2014-01-01

    Full Text Available Despite the important progress obtained in the treatment of some pets’ malignancies, new treatments need to be developed. Being critical in cancer control and progression, the immune system’s appropriate modulation may provide effective therapeutic options. In this review we summarize the outcomes of published immunogene therapy veterinary clinical trials reported by many research centers. A variety of tumors such as canine melanoma, soft tissue sarcomas, osteosarcoma and lymphoma, feline fibrosarcoma, and equine melanoma were subjected to different treatment approaches. Both viral and mainly nonviral vectors were used to deliver gene products as cytokines, xenogeneic tumor associated antigens, specific ligands, and proapoptotic regulatory factors. In some cases autologous, allogenic, or xenogeneic transgenic cytokine producing cells were assayed. In general terms, minor or no adverse collateral effects appeared during this kind of therapies and treated patients usually displayed a better course of the disease (longer survival, delayed or suppressed recurrence or metastatic spread, and improvement of the quality of life. This suggests the utility of these methodologies as standard adjuvant treatments. The encouraging outcomes obtained in companion animals support their ready application in veterinary clinical oncology and serve as preclinical proof of concept and safety assay for future human gene therapy trials.

  12. Imaging and Clinical Data of Placental Site Trophoblastic Tumor: A Case Report

    International Nuclear Information System (INIS)

    Niknejadi, Maryam; Ahmadi, Firoozeh; Akhbari, Farnaz

    2016-01-01

    Placental site trophoblastic tumor (PSTT) is a very rare variant of gestational trophoblastic tumor. It can occur after normal termination of pregnancy or spontaneous abortion and ectopic or molar pregnancy. There is a wide range of clinical manifestations from a benign condition to an aggressive disease with fatal outcome. One of the most important characteristics of PSTT, unlike other forms of gestational trophoblastic diseases (GTD) is the presence of low beta-subunit of human chorionic gonadotropin (β-hCG) levels because it is a neoplastic proliferation of intermediate trophoblastic cells. However, human placental lactogen (hPL) is increased on histologic section and in the serum of patients too. We present a case of PSTT and discuss the differential diagnosis in order to further familiarize physicians with the diagnosis and treatment of this disease. It has a varied clinical spectrum and usually presents with irregular vaginal bleeding or amenorrhea. Diagnosis is confirmed by dilatation and curettage (D and C) and hysterectomy. Because chemotherapy is not effective, surgery is the cornerstone of treatment. This case is presented because it is a rare neoplasm with different treatments and it should be differentiated from molar pregnancy

  13. Overexpression of matrix metalloproteinase-7 and -9 in NSCLC tumor and stromal cells: correlation with a favorable clinical outcome.

    Science.gov (United States)

    Stenvold, Helge; Donnem, Tom; Andersen, Sigve; Al-Saad, Samer; Al-Shibli, Khalid; Busund, Lill-Tove; Bremnes, Roy M

    2012-02-01

    Matrix metalloproteinases (MMPs) are considered important players in angiogenesis and cancer progression. Several drugs developed for targeting MMPs have until now been without clinical efficacy. As both malignant cells and cells of the surrounding stroma contribute to tumor growth, we have explored the impact of MMP-2, -7 and -9 expression in both the tumor and stromal compartment of non-small-cell lung cancers (NSCLC). From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). Immunohistochemistry was used to detect the expression of MMP-2, -7 and -9 in tumor and stromal cells. In univariate analyses, high tumor cell MMP-7 expression (P=0.029) and high stromal MMP-9 expression (P=0.001) were positive prognostic factors. In the multivariate analysis, high tumor cell MMP-7 expression (HR 1.58, CI 1.08-2.32, P=0.020) and high stromal MMP-9 expression (HR 1.92, CI 1.25-2.96, P=0.003) were independent positive prognostic factors for disease-specific survival. High levels of MMP-7 in tumor cells and high levels of MMP-9 in tumor associated stroma were independent positive prognostic factors in NSCLC patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Acute Appendicitis as the Initial Clinical Presentation of Primary HIV-1 Infection

    DEFF Research Database (Denmark)

    Schleimann, Mariane H; Leth, Steffen; Krarup, Astrid R

    2018-01-01

    We report a case of an adolescent who presented at our emergency department with acute abdominal pain. While the initial diagnosis was acute appendicitis, a secondary and coincidental diagnosis of primary HIV-1 infection was made. Concurrent and subsequent clinical and molecular biology findings ...... form the basis of our argument that primary HIV-1 infection was the cause of acute appendicitis in this individual.......We report a case of an adolescent who presented at our emergency department with acute abdominal pain. While the initial diagnosis was acute appendicitis, a secondary and coincidental diagnosis of primary HIV-1 infection was made. Concurrent and subsequent clinical and molecular biology findings...

  15. Tumor hypoxia at the micro-regional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers

    International Nuclear Information System (INIS)

    Bussink, Johan; Kaanders, Johannes H.A.M.; Kogel, Albert J. van der

    2003-01-01

    Background and purpose: Tumor oxygenation is recognized as an important determinant of the outcome of radiotherapy and possibly also of other treatment modalities in a number of tumor types and in particular in squamous cell carcinomas. The hypoxic status of various solid tumors has been related to a poor prognosis due to tumor progression towards a more malignant phenotype, with increased metastatic potential, and an increased resistance to treatment. It has been demonstrated in head and neck cancer that hypoxic radioresistance can be successfully counteracted by hypoxia modifying approaches. The microregional distribution and the level of tumor hypoxia depend on oxygen consumption and temporal and spatial variations in blood supply. It is unclear if severely hypoxic cells can resume clonogenicity when O 2 and nutrients become available again as a result of (treatment related) changes in the tumor microenvironment. Non-terminally differentiated hypoxic cells that are capable of proliferation are important for outcome because of their resistance to radiotherapy and possibly other cytotoxic treatments. Various exogenous and endogenous markers for hypoxia are currently available and can be studied in relation to each other, the tumor architecture and the tumor microenvironment. Use of nitroimidazole markers with immunohistochemical detection allows studying tumor cell hypoxia at the microscopic level. Co-registration with other microenvironmental parameters, such as vascular architecture (vascular density), blood perfusion, tumor cell proliferation and apoptosis, offers the possibility to obtain a comprehensive functional image of tumor patho-physiology and to study the effects of different modalities of cancer treatment. Conclusion: A number of functional microregional parameters have emerged that are good candidates for future use as indicators of tumor aggressiveness and treatment response. The key question is whether these parameters can be used as tools for

  16. N-glycan signatures identified in tumor interstitial fluid and serum of breast cancer patients - association with tumor biology and clinical outcome.

    Science.gov (United States)

    Terkelsen, Thilde; Haakensen, Vilde D; Saldova, Radka; Gromov, Pavel; Hansen, Merete Kjaer; Stöckmann, Henning; Lingjaerde, Ole Christian; Børresen-Dale, Anne-Lise; Papaleo, Elena; Helland, Åslaug; Rudd, Pauline M; Gromova, Irina

    2018-04-26

    Particular N-glycan structures are known to be associated with breast malignancies by coordinating various regulatory events within the tumor and corresponding microenvironment, thus implying that N-glycan patterns may be used for cancer stratification and as predictive or prognostic biomarkers. However, the association between N-glycans secreted by breast tumor and corresponding clinical relevance remain to be elucidated. We profiled N-glycans by HILIC UPLC across a discovery dataset composed of tumor interstitial fluids (TIF, n=85), paired normal interstitial fluids (NIF, n=54) and serum samples (n=28) followed by independent evaluation, with the ultimate goal of identifying tumor-related N-glycan patterns in blood of breast cancer patients. The segregation of N-linked oligosaccharides revealed 33 compositions, which exhibited differential abundances between TIF and NIF. TIFs were depleted of bisecting N-glycans, which are known to play essential roles in tumor suppression. An increased level of simple high mannose N-glycans in TIF strongly correlated with the presence of tumor infiltrating lymphocytes within tumor. At the same time, a low level of highly complex N-glycans in TIF inversely correlated with the presence of infiltrating lymphocytes within tumor. Survival analysis showed that patients exhibiting increased TIF abundance of GP24 had better outcomes, whereas low levels of GP10, GP23, GP38, and coreF were associated with poor prognosis. Levels of GP1, GP8, GP9, GP14, GP23, GP28, GP37, GP38, and coreF were significantly correlated between TIF and paired serum samples. Cross-validation analysis using an independent serum dataset supported the observed correlation between TIF and serum, for five out of nine N-glycan groups: GP8, GP9, GP14, GP23, and coreF. Collectively, our results imply that profiling of N-glycans from proximal breast tumor fluids is a promising strategy for determining tumor-derived glyco-signature(s) in the blood. N-glycans structures

  17. The protons of space and brain tumors: I. Clinical and dosimetric considerations

    International Nuclear Information System (INIS)

    Dalrymple, G.V.; Nagle, W.A.; Moss, A.J.; Cavin, L.A.; Broadwater, J.R.; McGuire, E.L.; Eason, C.S.

    1989-01-01

    Almost 25 years ago a large group of Rhesus monkeys were irradiated with protons (32--2300 MeV). The experiments were designed: (1) To estimate the RBE of protons, per se, and (2) To provide some estimate of the hazards of the radiation environment of space. The initial results showed the RBE to be about 1.0 for acute radiation effects (mortality, hematologic changes, etc). The colony has been maintained at Brooks AFB, TX since irradiation. The survivors of 55 MeV proton irradiation have developed a very high incidence of Glioblastoma multiforme, a highly malignant primary brain tumor. These tumors appeared 1--20 yrs after surface doses of 400--800 rads. Reconstruction of the dosimetry suggests that some areas within the brain may have received doses of 1500--2500 rads. More than 30 radiation induced Glioblastomas have been reported in human patients who had received therapeutic head irradiation. The radiation doses required to induce Glioblastoma were of the same order of magnitude as required to induce Glioblastoma in the Rhesus monkey

  18. Clinical analysis of four serum tumor markers in 458 patients with ovarian tumors: diagnostic value of the combined use of HE4, CA125, CA19-9, and CEA in ovarian tumors

    Directory of Open Access Journals (Sweden)

    Chen F

    2018-05-01

    Full Text Available Fawen Chen,1,2 Jing Shen,3 Jianwei Wang,1 Pengwei Cai,1 Yi Huang3 1Department of Clinical Laboratory, Fujian Provincial Hospital South Branch, 2Department of Blood Transfusion, 3Department of Clinical Laboratory, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou, People’s Republic of China Purpose: To investigate the diagnostic values of human epididymis protein 4 (HE4, carbohydrate antigen 125 (CA125, carbohydrate antigen 19-9 (CA19-9, and carcinoembryonic antigen (CEA for ovarian tumors. Methods: The participants were divided into three groups: 386 healthy women (control group, 262 patients with benign ovarian tumors (the benign group, and 196 patients with malignant pelvic tumors (the malignant group. The serum levels of HE4, CA125, CA19-9, and CEA were analyzed by electrochemiluminescent immunoassay. Results: It showed that serum levels of HE4, CA125, CA19-9, and CEA of patients with ­malignant ovarian tumors were significantly higher than those in the control group and benign group (P<0.01. HE4 had a high specificity (96.56% in malignant ovarian tumors. The tumor markers HE4, CA125, CA19-9, and CEA had a sensitivity of 63.78%, 62.75%, 35.71%, and 38.78%, respectively. The combined use of two or more tumor markers (parallel test had a higher diagnostic sensitivity but lower specificity than a single tumor marker. The combined efficiency of HE4 and CA125 was the highest, with a sensitivity and specificity of 80.10% and 69.08%, respectively. HE4 and CA125 combined with the Risk of Ovarian Malignancy Algorithm provided an efficient means of screening and diagnosis of ovarian malignancies. The diagnostic sensitivity increased to 88.52% when three or four tumor markers were used but showed no significant difference compared with the combination of HE4 and CA125 (P>0.05. Conclusion: The combination of three or four tumor markers did not improve the diagnostic efficacy when compared with the combination

  19. CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

    Directory of Open Access Journals (Sweden)

    Mihalescu-Maingot Maria

    2010-02-01

    Full Text Available Abstract Background Tumor initiating cells (TICs provide a new paradigm for developing original therapeutic strategies. Methods We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. Results A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs. Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Conclusions Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

  20. CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

    International Nuclear Information System (INIS)

    Patru, Cristina; Berhneim, Alain; Mihalescu-Maingot, Maria; Haiech, Jacques; Bièche, Ivan; Moura-Neto, Vivaldo; Daumas-Duport, Catherine; Junier, Marie-Pierre; Chneiweiss, Hervé; Romao, Luciana; Varlet, Pascale; Coulombel, Laure; Raponi, Eric; Cadusseau, Josette; Renault-Mihara, François; Thirant, Cécile; Leonard, Nadine

    2010-01-01

    Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies. We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies

  1. Clinical characteristics, surgical and neuropsychological outcomes in drug resistant tumoral temporal lobe epilepsy.

    Science.gov (United States)

    Ravat, Sangeeta; Iyer, Vivek; Muzumdar, Dattatraya; Shah, Urvashi; Pradhan, Pranjali; Jain, Neeraj; Godge, Yogesh

    2016-12-01

    Glioneuronal tumors are found in nearly one third patients who undergo surgery for pharmacoresistant epilepsy with temporal lobe being the most common location. Few studies, however have concentrated on the neurological and neuropsychological outcomes after surgery, hitherto none from India. We studied 34 patients with temporal lobe tumors and drug resistant epilepsy. These patients underwent anterior temporal lobectomy or lesionectomy based on the involvement of the hippocampus and mesial temporal structures. The clinical history, EEG, neuropsychology profile and MRI were compared. Seizure outcome was categorized using Engel's classification. At a mean follow up of 62 months, 85.29% of the patients were seizure free (Engel's Class I). All 8 patients with intraoperative electrocorticography (ECoG) guided resection were seizure free. Presence of a residual lesion was significantly associated with persistence of seizures post surgery (p = 0.002). Group analysis revealed no significant shifts in IQ and memory scores postoperatively. There was a significant improvement in the quality of life scores (total and across all subdomains) in all patients (p temporal lobe tumors and refractory epilepsy offers complete seizure freedom in majority. Complete surgical excision of the epileptogenic zone is of paramount importance in achieving seizure freedom. Intraoperative electrocorticography (EcoG) is a useful adjunct to ensure complete removal of epileptogenic zone, thus achieving optimal seizure freedom. There is a significant improvement in the quality of life scores (p < 0.001) with no negative impact of surgery on memory and intelligence. Even the patients who are not seizure free can achieve worthwhile improvement post surgery. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  2. Overexpression of Pokemon in non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results.

    Science.gov (United States)

    Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-Li; Zhang, Jian; Fu, Kai

    2008-10-01

    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor alternative reading frame (ARF), exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in non-small cell lung cancer and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Observe the expression of Pokemon in NSCLC and investigate its mechanism and clinical significance. Determine the expression of Pokemon in human NSCLC cell lines as well as 55 cases of NSCLC tumor tissues, tumor adjacent tissues and surrounding tissues by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and analyze the relationship between Pokemon expression in NSCLC tumor tissues and clinicopathological features. Determine 62 NSCLC tumor tissues (5 years ago) and p14(ARF) expression with immunohistochemical technique, discuss the correlation between them and assess the effect of Pokemon on prognosis of patients with lung cancer. Pokemon mRNA and protein took on high expression in lung cancer cell lines, and the expression difference between cancer tissues, tumor adjacent tissues and surrounding tissues had statistical significance (PPokemon expression and p14(ARF) expression were negatively correlated (r=-0.287). The expression of Pokemon was determined not to be associated with the patient's sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (PPokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). There was high expression of Pokemon in NSCLC

  3. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  4. Glomus tumors in neurofibromatosis type 1: genetic, functional and clinical evidence of a novel association

    OpenAIRE

    Brems, Hilde; Park, Caroline; Maertens, Ophélia; Pemov, Alexander; Messiaen, Ludwine; Upadhyaya, Meena; Claes, Kathleen; Beert, Eline; Peeters, Kristel; Mautner, Victor; Sloan, Jennifer L.; Yao, Lawrence; Lee, Chyi-Chia Richard; Sciot, Raf; Smet, Luc De

    2009-01-01

    Neurofibromatosis type 1 (NF1) is a common disorder that arises secondary to mutations in the tumor suppressor gene NF1. Glomus tumors are small, benign but painful tumors that originate from the glomus body, a thermoregulatory shunt concentrated in the fingers and toes. We report eleven individuals with NF1 who harbored 20 glomus tumors of the fingers and one in the toe; five individuals had multiple glomus tumors. We hypothesized that bi-allelic inactivation of NF1 underlies the pathogenesi...

  5. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters

    NARCIS (Netherlands)

    Jonsson, Michele; Fusco, Jennifer S.; Cole, Stephen R.; Thomas, James C.; Porter, Kholoud; Kaufman, Jay S.; Davidian, Marie; White, Alice D.; Hartmann, Katherine E.; Eron, Joseph J.; del Amo, Julia; Meyer, Laurence; Bucher, Heiner C.; Chene, Geneviève; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Babiker, Abdel; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kaldor, John; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Pedersen, Court; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Hamouda, Osamah; Geskus, Ronald; van der Helm, Jannie; Schuitemaker, Hanneke

    2011-01-01

    To estimate the clinical benefit of highly active antiretroviral therapy (HAART) initiation vs deferral in a given month in patients with CD4 cell counts less than 800/μL. In this observational cohort study of human immunodeficiency virus type 1 seroconverters from CASCADE (Concerted Action on

  6. p75 Neurotrophin Receptor Cleavage by α- and γ-Secretases Is Required for Neurotrophin-mediated Proliferation of Brain Tumor-initiating Cells*

    Science.gov (United States)

    Forsyth, Peter A.; Krishna, Niveditha; Lawn, Samuel; Valadez, J. Gerardo; Qu, Xiaotao; Fenstermacher, David A.; Fournier, Michelle; Potthast, Lisa; Chinnaiyan, Prakash; Gibney, Geoffrey T.; Zeinieh, Michele; Barker, Philip A.; Carter, Bruce D.; Cooper, Michael K.; Kenchappa, Rajappa S.

    2014-01-01

    Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target. PMID:24519935

  7. A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics.

    Science.gov (United States)

    van den Bent, Martin J; Weller, Michael; Wen, Patrick Y; Kros, Johan M; Aldape, Ken; Chang, Susan

    2017-05-01

    The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classification, which is now for adult diffuse glioma centered around isocitrate dehydrogenase (IDH) and 1p/19q diagnostics. This revised classification is reviewed with a focus on adult brain tumors, and includes a recommendation of genes of which routine testing is clinically useful. Apart from assessment of IDH mutational status including sequencing of R132H-immunohistochemistry negative cases and testing for 1p/19q, several other markers can be considered for routine testing, including assessment of copy number alterations of chromosome 7 and 10 and of TERT promoter, BRAF, and H3F3A mutations. For "glioblastoma, IDH mutated" the term "astrocytoma grade IV" could be considered. It should be considered to treat IDH wild-type grades II and III diffuse glioma with polysomy of chromosome 7 and loss of 10q as glioblastoma. New developments must be more quickly translated into further revised diagnostic categories. Quality control and rapid integration of molecular findings into the final diagnosis and the communication of the final diagnosis to clinicians require systematic attention. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

  9. Quality of clinical brain tumor MR spectra judged by humans and machine learning tools.

    Science.gov (United States)

    Kyathanahally, Sreenath P; Mocioiu, Victor; Pedrosa de Barros, Nuno; Slotboom, Johannes; Wright, Alan J; Julià-Sapé, Margarida; Arús, Carles; Kreis, Roland

    2018-05-01

    To investigate and compare human judgment and machine learning tools for quality assessment of clinical MR spectra of brain tumors. A very large set of 2574 single voxel spectra with short and long echo time from the eTUMOUR and INTERPRET databases were used for this analysis. Original human quality ratings from these studies as well as new human guidelines were used to train different machine learning algorithms for automatic quality control (AQC) based on various feature extraction methods and classification tools. The performance was compared with variance in human judgment. AQC built using the RUSBoost classifier that combats imbalanced training data performed best. When furnished with a large range of spectral and derived features where the most crucial ones had been selected by the TreeBagger algorithm it showed better specificity (98%) in judging spectra from an independent test-set than previously published methods. Optimal performance was reached with a virtual three-class ranking system. Our results suggest that feature space should be relatively large for the case of MR tumor spectra and that three-class labels may be beneficial for AQC. The best AQC algorithm showed a performance in rejecting spectra that was comparable to that of a panel of human expert spectroscopists. Magn Reson Med 79:2500-2510, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  10. Clinical trials of a new chlorin photosensitizer for photodynamic therapy of malignant tumors

    Science.gov (United States)

    Privalov, Valeriy A.; Lappa, Alexander V.; Seliverstov, Oleg V.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.; Kochneva, Elena V.; Evnevich, Michail V.; Anikina, Alla S.; Reshetnicov, Andrey V.; Zalevsky, Igor D.; Kemov, Yuriy V.

    2002-06-01

    Photodynamic therapy (PDT) was performed with a new photosensitizer, a water soluble form of chlorins (Radachlorin, Russia) possessing an absorption peak around 662 nm. As light source there was used the diode laser (ML-662-SP, Russia) with 662 nm wavelength and 2.5 W optical power. The sensitizer had passed broad pre-clinical in vitro and in vivo studies, which showed safety and efficiency of it. PDT was applied to 51 patients with basal cell cancer of the skin (about 60% of all cases), breast cancer, lip cancer, melanoma, cancer of esophagus, stomach, and rectum, cancer and leucoplacia of vulva, malignant ganglioneuroma, sarcoma of soft tissue, cancer and reticular sarcoma of thyroid gland, cancer of ductus choledochus. Most of non-basalioma patients had either forth stage or recurrence of disease. The sensitizer was injected intravenously or applied externally (Radachlorin gel). There were used surface, endoscopic, and interstitial ways of irradiation. Full tumor regression with excellent cosmetic effect was reached in 100% cases of 1-3 stage basal cell cancer patients treated with intravenous Radachlorin injection. In most other (non-basalioma) cases significant regression of tumors and improvement of life quality of patients (recanalization and regain of conductivity) was obtained.

  11. Treatment patterns and clinical characteristics prior to initiating depot typical antipsychotics for nonadherent schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Montgomery William

    2009-07-01

    Full Text Available Abstract Background Nonadherence with antipsychotic medication is an important clinical and economic problem in the treatment of schizophrenia. This study identified treatment patterns and clinical characteristics that immediately precede the initiation of depot typical antipsychotics in the usual treatment of schizophrenia patients with a recent history of nonadherence with oral antipsychotic regimens. Methods Data were drawn from a large, multisite, 3-year prospective noninterventional observational study of persons treated for schizophrenia in the United States, which was conducted between 7/1997 and 9/2003. The analytical sample included patients who, in the 6 months prior to enrollment, were considered nonadherent with oral antipsychotics and were not treated with depot antipsychotics (N = 314. Patients who were subsequently initiated on typical depots during the 3-year follow-up were compared with patients who continued therapy with only oral antipsychotic agents. Group comparisons were made on patient baseline characteristics and precedent variables that were assessed 1 to 6 months prior to depot initiation. Patient assessments were made at predetermined intervals throughout the 3-year study using standard psychiatric measures, a patient-reported questionnaire, and medical record information. Results A small proportion of patients (12.4% who were recently nonadherent with oral antipsychotics were subsequently initiated on depot therapy during the 3-year study. Compared to patients treated with only oral antipsychotics, those subsequently initiated on a depot were significantly more likely to be hospitalized at depot initiation or the previous 30 days, to have recent involvement with the criminal justice system (arrests, recent illicit drug use, recent switching or augmentation of oral antipsychotics, and recent treatment with oral typical antipsychotics. Conclusion Despite prior nonadherence with oral antipsychotic medication, only a

  12. Initiation of antiretroviral therapy at rural primary health care clinics in KwaZulu Natal

    Directory of Open Access Journals (Sweden)

    Hilda Ganesen-Moothusamy

    2013-05-01

    Full Text Available South Africa bears the greatest burden of HIV infection globally with the most infected people living in KwaZulu-Natal (KZN. Decentralised medical care for HIV positive patients and antiretroviral therapy (ART delivery to primary health care facilities were proposed nationally to achieve adequate ART coverage for patients in need of treatment. This study described the HIV positive patients who accessed medical care and were initiated on ART at two existing government Primary Health Care (PHC clinics with no added donor support, in Ilembe, KZN. This was an observational descriptive study of ART initiation from 01 April 2008 to 30 April 2009. Data were collected from clinical records kept on site. HIV Testing and the pre-ART programmes which consisted of medical care prior to ART initiation are briefly described. Socio-economic, demographic and clinical characteristics of patients who were initiated on ART were sampled and described. A minority (2.95% of the study population tested for HIV of which 36.0%tested positive. Majority (60.0% of patients who joined the pre-ART programme care did not return. The ART sample consisted of 375 patients of whom 65.0%were women, 85.9%were unmarried, 61.6%were unemployed and 50.4%had a secondary level of education. Tuberculosis (TB prevalence and incidence at ART initiation were 22.1%and 14.7%respectively. The prevalence of Syphilis and Hepatitis B co-infections were 13.1%and 8.6 %respectively. Two thirds of female patients (66.4% received a Pap smear result of which the majority (62.3% were abnormal. Uptake for HIV testing followed by relevant CD4 testing was poor. High TB, Hepatitis B and Syphilis co-infection was noted amongst patients initiated on ART. Cervical cancer screening must be intensified. Although ART initiation with no added external resources was successful, record keeping was suboptimal.

  13. Evaluation of clinical value of combined tumor markers detection in diagnosis of lung cancer

    International Nuclear Information System (INIS)

    Zhang Guangming; Deng Shouzhen; Wang Yun; Xu Lianqin; He Wanting; Gao Quan; Lin Xiangtong

    2002-01-01

    To evaluate clinical value of single or combined tumor marker detection CY21-1, CEA, CA15-3 and SCC in the diagnosis of lung cancer. There was retrospective analysis of 87 lung cancer inpatients, all of them was confirmed by pathology. Results showed: (1) Sensitivity of CY21-1, CEA, CA15-3 and SCC by single detection in diagnosing lung cancer was 59.8%, 39.1%, 44.8%, 18.4%, respectively. (2) Sensitivity of group I (CY21-1 + CEA) was 78.2%; sensitivity of group II (CY21-1 + CEA + CA15-3) was 88.5%; sensitivity of group III (CY21-1 + CEA + CA15-3 + SCC) was the same as group II. In the diagnosis of lung cancer, the combined detection with CY21-1, CEA, CA15-3 was an ideal selective combination

  14. Techniques for heating eccentrically located tumors with the BSD annular phased array system (APAS): Clinical experience

    International Nuclear Information System (INIS)

    Samulski, T.V.; Kapp, D.S.; Bagshaw, M.A.; Fessenden, P.; Lee, E.R.; Lohrbach, A.W.

    1985-01-01

    The authors are currently investigating the potential for treatment optimization with the BSD APAS in tumors which are eccentrically located within the lower abdomen and pelvis. Attempts have been made to manipulate electric field (E-field) distribution during treatments through frequency changes and partial array activation (driving less than all four quadrants). Field shifts are qualitatively documented using the manufacturer's supplied diode array probes located at the patient/bolus interface in anterior, posterior and bilateral positions. Preliminary findings indicate that the internal E-field distributions can be manipulated to result in better treatment tolerance and better temperature distributions in selected target volumes. Phantom and clinical data are presented demonstrating the utility of these approaches

  15. ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor initiating cell state

    Science.gov (United States)

    Chudnovsky, Yakov; Kim, Dohoon; Zheng, Siyuan; Whyte, Warren A.; Bansal, Mukesh; Bray, Mark-Anthony; Gopal, Shuba; Theisen, Matthew A.; Bilodeau, Steve; Thiru, Prathapan; Muffat, Julien; Yilmaz, Omer H.; Mitalipova, Maya; Woolard, Kevin; Lee, Jeongwu; Nishimura, Riko; Sakata, Nobuo; Fine, Howard A.; Carpenter, Anne E.; Silver, Serena J.; Verhaak, Roel G. W.; Califano, Andrea; Young, Richard A.; Ligon, Keith L.; Mellinghoff, Ingo K.; Root, David E.; Sabatini, David M.; Hahn, William C.; Chheda, Milan G.

    2014-01-01

    Summary Glioblastomas (GBM) harbor subpopulations of therapy-resistant tumor initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC maintenance and identified ZFHX4, a 397-kDa transcription factor. ZFHX4 is required to maintain TIC-associated and normal human neural precursor cell phenotypes in vitro, suggesting that ZFHX4 regulates differentiation, and its suppression increases glioma-free survival in intracranial xenografts. ZFHX4 interacts with CHD4, a core member of the NuRD (nucleosome remodeling and deacetylase) complex. ZFHX4 and CHD4 bind to overlapping sets of genomic loci and control similar gene expression programs. Using expression data derived from GBM patients, we found that ZFHX4 significantly affects CHD4-mediated gene expression perturbations, which defines ZFHX4 as a master regulator of CHD4. These observations define ZFHX4 as a regulatory factor that links the chromatin remodeling NuRD complex and the GBM TIC state. PMID:24440720

  16. Clinical Implementation of Intrafraction Cone Beam Computed Tomography Imaging During Lung Tumor Stereotactic Ablative Radiation Therapy

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    Li, Ruijiang; Han, Bin; Meng, Bowen [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Maxim, Peter G.; Xing, Lei; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: Diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

    2013-12-01

    Purpose: To develop and clinically evaluate a volumetric imaging technique for assessing intrafraction geometric and dosimetric accuracy of stereotactic ablative radiation therapy (SABR). Methods and Materials: Twenty patients received SABR for lung tumors using volumetric modulated arc therapy (VMAT). At the beginning of each fraction, pretreatment cone beam computed tomography (CBCT) was used to align the soft-tissue tumor position with that in the planning CT. Concurrent with dose delivery, we acquired fluoroscopic radiograph projections during VMAT using the Varian on-board imaging system. Those kilovolt projections acquired during millivolt beam-on were automatically extracted, and intrafraction CBCT images were reconstructed using the filtered backprojection technique. We determined the time-averaged target shift during VMAT by calculating the center of mass of the tumor target in the intrafraction CBCT relative to the planning CT. To estimate the dosimetric impact of the target shift during treatment, we recalculated the dose to the GTV after shifting the entire patient anatomy according to the time-averaged target shift determined earlier. Results: The mean target shift from intrafraction CBCT to planning CT was 1.6, 1.0, and 1.5 mm; the 95th percentile shift was 5.2, 3.1, 3.6 mm; and the maximum shift was 5.7, 3.6, and 4.9 mm along the anterior-posterior, left-right, and superior-inferior directions. Thus, the time-averaged intrafraction gross tumor volume (GTV) position was always within the planning target volume. We observed some degree of target blurring in the intrafraction CBCT, indicating imperfect breath-hold reproducibility or residual motion of the GTV during treatment. By our estimated dose recalculation, the GTV was consistently covered by the prescription dose (PD), that is, V100% above 0.97 for all patients, and minimum dose to GTV >100% PD for 18 patients and >95% PD for all patients. Conclusions: Intrafraction CBCT during VMAT can provide

  17. Intensity-Modulated Radiation Therapy in Oropharyngeal Carcinoma: Effect of Tumor Volume on Clinical Outcomes

    International Nuclear Information System (INIS)

    Lok, Benjamin H.; Setton, Jeremy; Caria, Nicola; Romanyshyn, Jonathan; Wolden, Suzanne L.; Zelefsky, Michael J.; Park, Jeffery; Rowan, Nicholas; Sherman, Eric J.; Fury, Matthew G.; Ho, Alan; Pfister, David G.; Wong, Richard J.; Shah, Jatin P.; Kraus, Dennis H.; Zhang, Zhigang; Schupak, Karen D.; Gelblum, Daphna Y.; Rao, Shyam D.; Lee, Nancy Y.

    2012-01-01

    Purpose: To analyze the effect of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) on treatment outcomes in patients treated with definitive intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC). Methods and Materials: Between September 1998 and April 2009, a total of 442 patients with squamous cell carcinoma of the oropharynx were treated with IMRT with curative intent at our center. Thirty patients treated postoperatively and 2 additional patients who started treatment more than 6 months after diagnosis were excluded. A total of 340 patients with restorable treatment plans were included in this present study. The majority of the patients underwent concurrent platinum-based chemotherapy. The pGTV and nGTV were calculated using the original clinical treatment plans. Cox proportional hazards models and log-rank tests were used to evaluate the correlation between tumor volumes and overall survival (OS), and competing risks analysis tools were used to evaluate the correlation between local failure (LF), regional failure (RF), distant metastatic failure (DMF) vs. tumor volumes with death as a competing risk. Results: Median follow-up among surviving patients was 34 months (range, 5-67). The 2-year cumulative incidence of LF, RF and DF in this cohort of patients was 6.1%, 5.2%, and 12.2%, respectively. The 2-year OS rate was 88.6%. Univariate analysis determined pGTV and T-stage correlated with LF (p < 0.0001 and p = 0.004, respectively), whereas nGTV was not associated with RF. On multivariate analysis, pGTV and N-stage were independent risk factors for overall survival (p = 0.0003 and p = 0.0073, respectively) and distant control (p = 0.0008 and p = 0.002, respectively). Conclusions: In this cohort of patients with OPC treated with IMRT, pGTV was found to be associated with overall survival, local failure, and distant metastatic failure.

  18. Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.

    Science.gov (United States)

    Brems, Hilde; Park, Caroline; Maertens, Ophélia; Pemov, Alexander; Messiaen, Ludwine; Messia, Ludwine; Upadhyaya, Meena; Claes, Kathleen; Beert, Eline; Peeters, Kristel; Mautner, Victor; Sloan, Jennifer L; Yao, Lawrence; Lee, Chyi-Chia Richard; Sciot, Raf; De Smet, Luc; Legius, Eric; Stewart, Douglas R

    2009-09-15

    Neurofibromatosis type 1 (NF1) is a common disorder that arises secondary to mutations in the tumor suppressor gene NF1. Glomus tumors are small, benign but painful tumors that originate from the glomus body, a thermoregulatory shunt concentrated in the fingers and toes. We report 11 individuals with NF1 who harbored 20 glomus tumors of the fingers and 1 in the toe; 5 individuals had multiple glomus tumors. We hypothesized that biallelic inactivation of NF1 underlies the pathogenesis of these tumors. In 12 NF1-associated glomus tumors, we used cell culture and laser capture microdissection to isolate DNA. We also analyzed two sporadic (not NF1-associated) glomus tumors. Genetic analysis showed germ line and somatic NF1 mutations in seven tumors. RAS mitogen-activated protein kinase hyperactivation was observed in cultured NF1(-/-) glomus cells, reflecting a lack of inhibition of the pathway by functional neurofibromin, the protein product of NF1. No abnormalities in NF1 or RAS mitogen-activated protein kinase activation were found in sporadic glomus tumors. By comparative genomic hybridization, we observed amplification of the 3'-end of CRTAC1 and a deletion of the 5'-end of WASF1 in two NF1-associated glomus tumors. For the first time, we show that loss of neurofibromin function is crucial in the pathogenesis of glomus tumors in NF1. Glomus tumors of the fingers or toes should be considered as part of the tumor spectrum of NF1.

  19. Clinical manifestations of testicular adrenal rest tumor in males with congenital adrenal hyperplasia

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    Min Kyung Yu

    2015-09-01

    Full Text Available PurposeIn male patients with congenital adrenal hyperplasia (CAH, the presence of testicular adrenal rest tumors (TARTs have been reported, however their prevalence and clinical manifestations are not well known. Untreated TARTs may lead to testicular structural damage and infertility. This study was conducted to investigate the prevalence of TARTs in male patients with CAH, and characterize the manifestations to identify contributing factors to TART.MethodsAmong 102 CAH patients aged 0-30 years, 24 male patients have been regularly followed up in our outpatient clinic at Severance Children's Hospital from January 2000 to December 2014. In order to reveiw the characteristics of TART patients, we calculated the mean levels of hormones during the 5 years before the time of investigation. Five patients underwent follow-up scrotal ultrasonography (US after adjusting the dosage of glucocorticoids.ResultsTARTs were detected in 8 of the 13 patients (61.5%. The median age of TARTs diagnosis was 20.2 years with the youngest case being 15.5 years old. The mean serum level of adrenocorticotropic hormone (ACTH was higher in the TARTs patient group compared to the non-TARTs group (P<0.05. The tumor size decreased in 3 cases, slightly increased in 1 case, and had no change in another case.ConclusionThe serum ACTH level might be associated with the growth promoting factor for TARTs, but the exact mechanism has not been clearly identified. Screening for TARTs using US is important in male patients with CAH for early-detection and prevention of ongoing complications, such as infertility.

  20. CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

    Science.gov (United States)

    Shmelkov, Sergey V.; Butler, Jason M.; Hooper, Andrea T.; Hormigo, Adilia; Kushner, Jared; Milde, Till; St. Clair, Ryan; Baljevic, Muhamed; White, Ian; Jin, David K.; Chadburn, Amy; Murphy, Andrew J.; Valenzuela, David M.; Gale, Nicholas W.; Thurston, Gavin; Yancopoulos, George D.; D’Angelica, Michael; Kemeny, Nancy; Lyden, David; Rafii, Shahin

    2008-01-01

    Colon cancer stem cells are believed to originate from a rare population of putative CD133+ intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133+ cancer cells are capable of tumor initiation. However, the precise contribution of CD133+ tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133lacZ/+), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10–/–CD133lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133– population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133+ and CD133– metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133– cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44+CD24–), whereas the CD133+ fraction is composed of CD44lowCD24+ cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic

  1. Vulvar and vaginal graft versus host disease: A healthcare clinic initiative

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    Naomi Van Dam

    2017-01-01

    Full Text Available Objective: In patients receiving bone marrow transplantation (BMT, their mucosa becomes altered and sclerotic changes in the female external genital organs occur. Although a few studies have specifically addressed vulvar and vaginal graft versus host disease (VVGvHD and its repercussions on the sexual health and quality of life of patients, VVGvHD can be overlooked by health practitioners. The objective of the study is to describe the initiation of a health care clinic specializing in VVGvHD in a general tertiary hospital. Methods: A VVGvHD clinic was founded as a part of BMT daycare in a joint initiative of the nursing staff and the medical director of the department and a gynecologist specializing in vulva and vaginal disease. Patients were assessed for vulvovaginal symptoms, such as dryness, burning, itching, pain to touch, pain during intercourse, and dysuria. These patients might be subsequently referred to the VVGvHD clinic according to their needs assessed by daycare nurses. Treatment guidelines were developed by the specialist gynecologist. Results: A total of 81 women aged 2–66 years (median age = 38 years visited the clinic from 2009 to 2015. Of these women, 70 received an allogeneic transplant and 11 underwent autologous transplantation before consultation in our clinic. VVGvHD was detected in 54% of the patients. Conclusions: The VVGvHD clinic was developed to fulfill the specific needs of female patients who underwent BMT. The pioneer clinic was founded as a joint effort of the multidisciplinary team. Evidence supporting the optimum treatment for this condition is insufficient. This was the main reason for performing this study to explore the clinic that was newly based in Israel. VVGvHD may be a fluctuating condition with frequent deterioration and improvement. Therefore, regular clinical examinations are necessary.

  2. Mel-18 controls the enrichment of tumor-initiating cells in SP fraction in mouse breast cancer.

    Science.gov (United States)

    Janakiraman, Harinarayanan; Nobukiyo, Asako; Inoue, Hiroko; Kanno, Masamoto

    2011-06-01

    Side population (SP) cell analysis has been used to identify and isolate a minor population of cells with stem cell properties in normal tissues and in many cancers including breast cancer cells. However, the molecular mechanisms that operate in tumor-initiating cells (TICs) in SP fraction remain unclear. The Polycomb group genes, including Bmi1 and Mel-18, have been implicated in the maintenance of hematopoietic stem cells (HSCs) and suggested to be oncogenic and tumor suppressive, respectively, in breast cancer. In this study, we determined the critical role of Mel-18 in the enrichment mechanisms of TICs with the SP phenotype in a mouse breast cancer cell line, MMK3, that was established from a breast cancer developed spontaneously in Mel-18+/- mice. The Mel-18 protein expression level significantly correlates to the percentage of SP fraction in the mouse breast cancer cell line MMK3 series. The comparison between MMK3V3 (V3) cells containing one copy of the Mel-18 gene and MMK3S2 (S2) cells having twice the amount of Mel-18 expression clearly demonstrates the above relationship. Similar results obtained with the percentage of ALDH+ cells in V3 and S2 further confirmed the correlation between protein expression level of Mel-18 and the TICs. More importantly, transplantation of SP and non-SP cells of V3 and S2 cells into the NOD/SCID mice clearly showed that the heterozygous level of Mel-18 leads to the disappearance of enrichment of TICs into SP fraction in vivo. Stem cell pathway focused gene expression profiling of V3 and S2 cells revealed that the genes Abcg2, Aldh1a1 and Dhh were highly down-regulated in V3 compared to S2. These results indicate that the precise Mel-18 expression level controls TIC enrichment mechanisms through the regulation of channel molecule of Abcg2 and functional TIC marker of Aldhlal. In conclusion, our findings revealed the significance of fine-tuning mechanisms for Mel-18 protein expression level in the maintenance of TIC into SP

  3. Sick leave and disability pension before and after initiation of antirheumatic therapies in clinical practice.

    Science.gov (United States)

    Neovius, M; Simard, J F; Klareskog, L; Askling, J

    2011-08-01

    To investigate sick leave and disability pension in rheumatoid arthritis (RA) in relation to the initiation of biological and non-biological antirheumatic therapies in clinical practice. Patients aged 19-60 years initiating non-biological mono (n=2796) or combination disease-modifying antirheumatic drug (DMARD) therapy (n=973), or biological agents (n=4787) were identified in the Swedish Rheumatology Quality Register between 1999 and 2007. Sick leave and disability pension data (1995-2010) were retrieved from national registers. During the year before the start of mono DMARD, combination DMARD and biological treatment, 10%, 12% and 43% of patients received disability pension benefits, respectively. The corresponding combined annual sick leave and disability pension days were 78 (54+25), 132 (105+27) and 190 (79+111). Irrespective of treatment type, initiators were characterised by a history of increasing sick leave and disability pension. Treatment start was associated with a break in this trajectory: sick leave decreased while disability pension increased, resulting in a net stabilisation of total days. Higher levels of days on sick leave and disability pension at treatment start were observed in patients initiating biologics in 1999 (236 days/year) compared with 2007 (150 days/year; ppension increased rapidly before the initiation of antirheumatic therapy, which was associated with a halt but not a reversal of this development. Work ability is a metric of importance for clinical practice, signalling large remaining needs in the RA population, and the need for intervention earlier in the disease process.

  4. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors.

    Science.gov (United States)

    Luke, Jason J; Lemons, Jeffrey M; Karrison, Theodore G; Pitroda, Sean P; Melotek, James M; Zha, Yuanyuan; Al-Hallaq, Hania A; Arina, Ainhoa; Khodarev, Nikolai N; Janisch, Linda; Chang, Paul; Patel, Jyoti D; Fleming, Gini F; Moroney, John; Sharma, Manish R; White, Julia R; Ratain, Mark J; Gajewski, Thomas F; Weichselbaum, Ralph R; Chmura, Steven J

    2018-02-13

    Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1-treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to evaluate the safety of pembrolizumab with multisite SBRT in patients with metastatic solid tumors. Patients and Methods Patients progressing on standard treatment received SBRT to two to four metastases. Not all metastases were targeted, and metastases > 65 mL were partially irradiated. SBRT dosing varied by site and ranged from 30 to 50 Gy in three to five fractions with predefined dose de-escalation if excess dose-limiting toxicities were observed. Pembrolizumab was initiated within 7 days after completion of SBRT. Pre- and post-SBRT biopsy specimens were analyzed in a subset of patients to quantify interferon-γ-induced gene expression. Results A total of 79 patients were enrolled; three patients did not receive any treatment and three patients only received SBRT. Patients included in the analysis were treated with SBRT and at least one cycle of pembrolizumab. Most (94.5%) of patients received SBRT to two metastases. Median follow-up for toxicity was 5.5 months (interquartile range, 3.3 to 8.1 months). Six patients experienced dose-limiting toxicities with no radiation dose reductions. In the 68 patients with imaging follow-up, the overall objective response rate was 13.2%. Median overall survival was 9.6 months (95% CI, 6.5 months to undetermined) and median progression-free survival was 3.1 months (95% CI, 2.9 to 3.4 months). Expression of interferon-γ-associated genes from post-SBRT tumor biopsy specimens significantly correlated with nonirradiated tumor response. Conclusion Multisite SBRT followed by pembrolizumab was well tolerated with acceptable toxicity. Additional studies exploring the clinical benefit and predictive biomarkers of combined

  5. Clinical mentorship of nurse initiated antiretroviral therapy in Khayelitsha, South Africa: a quality of care assessment.

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    Ann Green

    Full Text Available INTRODUCTION: To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontières (MSF implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses. METHODS: A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship. RESULTS: Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p = 0.03, assessing adherence (50% vs 78%, p<0.001 and WHO staging (63% vs 91%, p<0.001. Nurse ART initiation indicators were successfully completed at 95-100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin; STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects. CONCLUSIONS: Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a

  6. Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome

    International Nuclear Information System (INIS)

    Arpino, Grazia; Bardou, Valerie J; Clark, Gary M; Elledge, Richard M

    2004-01-01

    Invasive lobular carcinoma (ILC) comprises approximately 10% of breast cancers and appears to have a distinct biology. Because it is less common than infiltrating ductal carcinoma (IDC), few data have been reported that address the biologic features of ILC in the context of their clinical outcome. In the present study we undertook an extensive comparison of ILC and IDC using a large database to provide a more complete and reliable assessment of their biologic phenotypes and clinical behaviors. The clinical and biological features of 4140 patients with ILC were compared with those of 45,169 patients with IDC (not otherwise specified). The median follow-up period was 87 months. In comparison with IDC, ILC was significantly more likely to occur in older patients, to be larger in size, to be estrogen and progesterone receptor positive, to have lower S-phase fraction, to be diploid, and to be HER-2, p53, and epidermal growth factor receptor negative. It was more common for ILC than for IDC to metastasize to the gastrointestinal tract and ovary. The incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (20.9% versus 11.2%; P < 0.0001). Breast preservation was modestly less frequent in ILC patients than in IDC patients. The 5-year disease-free survival was 85.7% for ILC and 83.5% for IDC (P = 0.13). The 5-year overall survival was 85.6% for ILC and 84.1% for IDC (P = 0.64). Despite the fact that the biologic phenotype of ILC is quite favorable, these patients do not have better clinical outcomes than do patients with IDC. At present, management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology

  7. The importance of clinical information in patients with gastroenteropancreatic neuroendocrine tumor.

    Science.gov (United States)

    Kudo, Atsushi; Akashi, Takumi; Kumagai, Jiro; Ban, Daisuke; Inokuchi, Mikito; Kojima, Kazuyuki; Kawano, Tatsuyuki; Tanaka, Shinji; Arii, Shigeki

    2012-01-01

    The WHO 2010 grading system for gastroenteropancreatic neuroendocrine tumors(GEP-NETs) is used to evaluate the malignant potential without clinicopathological information. This study was conducted to examine whether the new index is superior to the previous WHO 2004 classification, e.g.for well-differentiated endocrine carcinoma (WEC),involving clinical information. Between 2000 and 2011, 77 patients with sporadic GEP-NETs were treated at our institution and statistically estimated risk factors for overall survival (OS) were evaluated. Cox proportional hazards regression analyses were performed to estimate risk factors for OS. Overall 1-, 3- and 5-year survival rates were 92.8%, 78.4% and 76.0%, respectively. Median OS was 551 days in WEC-patients (odds ratio (OR)for OS=13.1, 95% confidence interval (CI)=2.90-59.5;p=0.001). The median OS was 813 days in G3-patients as compared with 1885 days in G1/G2-patients(OR for OS= 2.64, p=0.002). Multivariate analyses according to baseline characteristics revealed WEC as independent risk factor (OR=9.06, p=0.01). WEC was the only predictor of prognosis with an area under the receiver operating characteristic curves of 0.78(p=0.001). Clinical information was the best predictor for the prognosis of NETs.

  8. A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes

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    Marie-Andrée Forget

    2017-08-01

    Full Text Available Following the clinical success achieved with the first generation of adoptive cell therapy (ACT utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs, the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.

  9. MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.

    Science.gov (United States)

    DuBois, Steven G; Mody, Rajen; Naranjo, Arlene; Van Ryn, Collin; Russ, Douglas; Oldridge, Derek; Kreissman, Susan; Baker, David L; Parisi, Marguerite; Shulkin, Barry L; Bai, Harrison; Diskin, Sharon J; Batra, Vandana; Maris, John M; Park, Julie R; Matthay, Katherine K; Yanik, Gregory

    2017-11-01

    Prior studies suggest that neuroblastomas that do not accumulate metaiodobenzylguanidine (MIBG) on diagnostic imaging (MIBG non-avid) may have more favorable features compared with MIBG avid tumors. We compared clinical features, biologic features, and clinical outcomes between patients with MIBG nonavid and MIBG avid neuroblastoma. Patients had metastatic high- or intermediate-risk neuroblastoma and were treated on Children's Oncology Group protocols A3973 or A3961. Comparisons of clinical and biologic features according to MIBG avidity were made with chi-squared or Fisher exact tests. Event-free (EFS) and overall (OS) survival compared using log-rank tests and modeled using Cox models. Thirty of 343 patients (8.7%) had MIBG nonavid disease. Patients with nonavid tumors were less likely to have adrenal primary tumors (34.5 vs. 57.2%; P = 0.019), bone metastases (36.7 vs. 61.7%; P = 0.008), or positive urine catecholamines (66.7 vs. 91.0%; P neuroblastoma have lower rates of adrenal primary tumors, bone metastasis, and catecholamine secretion. Despite being more likely to have MYCN-amplified tumors, these patients have superior outcomes compared with patients with MIBG avid disease. © 2017 Wiley Periodicals, Inc.

  10. Diagnostic Ability of Percutaneous Needle Biopsy Immediately After Radiofrequency Ablation for Malignant Lung Tumors: An Initial Experience

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    Hasegawa, Takaaki, E-mail: t-hasegawa@aichi-cc.jp [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kondo, Chiaki [Aichi Cancer Center Hospital, Department of Pathology and Molecular Diagnosis (Japan); Sato, Yozo; Inaba, Yoshitaka; Yamaura, Hidekazu; Kato, Mina; Murata, Shinichi; Onoda, Yui [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kuroda, Hiroaki; Sakao, Yukinori [Aichi Cancer Center Hospital, Department of Thoracic Surgery (Japan); Yatabe, Yasushi [Aichi Cancer Center Hospital, Department of Pathology and Molecular Diagnosis (Japan)

    2016-08-15

    PurposeTo evaluate the safety and diagnostic ability of percutaneous needle biopsy performed immediately after lung radiofrequency ablation (RFA).Materials and MethodsFrom May 2013 to April 2014, percutaneous needle biopsy was performed immediately after RFA for 3 patients (2 men and 1 woman, aged 57–76 years) who had lung tumors measuring 1.3–2.6 cm in diameter. All patients had prior history of malignancy, and all tumors were radiologically diagnosed as malignant. Obtained specimens were pathologically classified using standard hematoxylin and eosin staining.ResultsWe completed three planned sessions of RFA followed by percutaneous needle biopsy, all of which obtained tumor tissue that could be pathologically diagnosed. Two tumors were metastatic from renal clear cell carcinoma and rectal adenocarcinoma, respectively; one tumor was primary lung adenocarcinoma. There was no death or major complication related to the procedures. Although pneumothorax occurred in two patients, these resolved without the need for aspiration or chest tube placement. Tumor seeding was not observed, but 21 months after the procedure, one case developed local tumor progression that was treated by additional RFA.ConclusionPathologic diagnosis was possible by needle biopsy immediately after RFA for lung tumors. This technique may reduce the risks and efforts of performing biopsy and RFA on separate occasions.

  11. Clinical Response to Gefitinib Retreatment of Lung Adenocarcinoma Patients Who Benefited from An Initial Gefitinib Therapy: A Retrospective Analysis

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    Junling LI

    2012-01-01

    Full Text Available Background and objective Gefitinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI that has been widely used for the treatment of non-small cell lung cancer (NSCLC. It is most effective in women, as well as in patients who have never smoked, have pulmonary adenocarcinomas, or are of Asian origin. Several treatment options are available for NSCLC patients who responded to initial gefitinib therapy but demonstrated tumor progression, of which gefitinib readministration is the chosen therapeutic option. The present study aims to evaluate the efficacy and toxicity of gefitinib readministration. Methods The clinical data of 18 patients with NSCLC who had shown partial response (PR or achieved a stable disease (SD status after gefitinib administration and were retreated with gefitinib due to failure of the initial therapy were reviewed and retrospectively analyzed. Results Of the 18 patients studied, 1 (6% showed partial remission (PR, 11 (61% achieved SD, and 6 (33% experienced disease progression. The disease control rate was 67%, and the median progression-free survival was 5.16 months (range, 1 to 24.8 months. The median overall survival from the start of the gefitinib therapy was 39.4 months (range, 15.38 to 52.44 months. Moreover, the median overall survival from the beginning of the 2nd therapy was 12.41 months (range, 3.98 to 38.24 months. Mild toxicity was observed with the 2nd gefitinib therapy. Conclusion The results of the present study indicate that patients with NSCLC may still be expected to achieve prolonged survival through gefitinib readministration if they initially responded to gefitinib and underwent various subsequent treatments.

  12. Transgenic overexpression of NanogP8 in the mouse prostate is insufficient to initiate tumorigenesis but weakly promotes tumor development in the Hi-Myc mouse model.

    Science.gov (United States)

    Liu, Bigang; Gong, Shuai; Li, Qiuhui; Chen, Xin; Moore, John; Suraneni, Mahipal V; Badeaux, Mark D; Jeter, Collene R; Shen, Jianjun; Mehmood, Rashid; Fan, Qingxia; Tang, Dean G

    2017-08-08

    This project was undertaken to address a critical cancer biology question: Is overexpression of the pluripotency molecule Nanog sufficient to initiate tumor development in a somatic tissue? Nanog1 is critical for the self-renewal and pluripotency of ES cells, and its retrotransposed homolog, NanogP8 is preferentially expressed in somatic cancer cells. Our work has shown that shRNA-mediated knockdown of NanogP8 in prostate, breast, and colon cancer cells inhibits tumor regeneration whereas inducible overexpression of NanogP8 promotes cancer stem cell phenotypes and properties. To address the key unanswered question whether tissue-specific overexpression of NanogP8 is sufficient to promote tumor development in vivo , we generated a NanogP8 transgenic mouse model, in which the ARR 2 PB promoter was used to drive NanogP8 cDNA. Surprisingly, the ARR 2 PB-NanogP8 transgenic mice were viable, developed normally, and did not form spontaneous tumors in >2 years. Also, both wild type and ARR 2 PB-NanogP8 transgenic mice responded similarly to castration and regeneration and castrated ARR 2 PB-NanogP8 transgenic mice also did not develop tumors. By crossing the ARR 2 PB-NanogP8 transgenic mice with ARR 2 PB-Myc (i.e., Hi-Myc) mice, we found that the double transgenic (i.e., ARR 2 PB-NanogP8; Hi-Myc) mice showed similar tumor incidence and histology to the Hi-Myc mice. Interestingly, however, we observed white dots in the ventral lobes of the double transgenic prostates, which were characterized as overgrown ductules/buds featured by crowded atypical Nanog-expressing luminal cells. Taken together, our present work demonstrates that transgenic overexpression of NanogP8 in the mouse prostate is insufficient to initiate tumorigenesis but weakly promotes tumor development in the Hi-Myc mouse model.

  13. Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

    Directory of Open Access Journals (Sweden)

    Ines Herrmann

    2010-10-01

    Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

  14. Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Rapp, Stephen R; Case, L Doug; Peiffer, Ann; Naughton, Michelle M; Chan, Michael D; Stieber, Volker W; Moore, Dennis F; Falchuk, Steven C; Piephoff, James V; Edenfield, William J; Giguere, Jeffrey K; Loghin, Monica E; Shaw, Edward G

    2015-05-20

    Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments. © 2015 by American Society of Clinical Oncology.

  15. Challenges in the transition to clinical training in dentistry: An ADEE special interest group initial report.

    Science.gov (United States)

    Serrano, C M; Botelho, M G; Wesselink, P R; Vervoorn, J M

    2018-02-03

    Curricular integration in higher education has been widely supported in the educational literature. As a result, several health care and specifically dental curricula have evolved from compartmentalised disciplinary training to integrated modalities; however, in many courses, a pre-clinical-clinical watershed remains a barrier to integration in dental education. This article introduces a general description of the pre-clinical-clinical transition in dentistry according to the outcomes of the discussion held during the first working group session of the "Transition to Clinical Training" Special Interest Group during the 2016 annual meeting of the Association for Dental Education in Europe. An online questionnaire was made available before the meeting to survey the curricular characteristics of the participants' schools. During the meeting, a working session related to the pre-clinical-clinical transition occurred. Conclusions from the discussion are summarised in this article. Fourteen dental schools from 12 countries participated in the online survey. The included programmes had an average duration of 5.3 years (SD = 0.48), with high school or the local equivalent as the required entrance level for dentistry. The hybrid curriculum was the leading curriculum design (n = 9) followed by competence-based curricula (n = 3), with patient treatment as the core of clinical training in every included programme. The pre-clinical-clinical transition in dentistry is a recognisable matter in dental education that requires assessment and research to ease the management of a stage with relevant influence on educational outcomes. This article presents an initial framework for further research and educational intervention. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

    LENUS (Irish Health Repository)

    Mulsow, J

    2012-02-01

    Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

  17. Proton Radiotherapy for Pediatric Ewing’s Sarcoma: Initial Clinical Outcomes

    International Nuclear Information System (INIS)

    Rombi, Barbara; DeLaney, Thomas F.; MacDonald, Shannon M.; Huang, Mary S.; Ebb, David H.; Liebsch, Norbert J.; Raskin, Kevin A.; Yeap, Beow Y.; Marcus, Karen J.; Tarbell, Nancy J.; Yock, Torunn I.

    2012-01-01

    Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing’s sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA). Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing’s sarcoma who were treated with PT between April 2003 and April 2009. Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure. Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.

  18. Proton Radiotherapy for Pediatric Ewing's Sarcoma: Initial Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Rombi, Barbara [ATreP (Provincial Agency for Proton Therapy), Trento (Italy); DeLaney, Thomas F.; MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Huang, Mary S.; Ebb, David H. [Department of Pediatric Hematology and Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Liebsch, Norbert J. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Raskin, Kevin A. [Department of Orthopaedic Surgery, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Marcus, Karen J. [Division of Radiation Oncology, Children' s Hospital Boston, MA (United States); Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States)

    2012-03-01

    Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA). Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009. Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure. Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.

  19. Preclinical and clinical evaluation of O-[11C]methyl-L-tyrosine for tumor imaging by positron emission tomography

    International Nuclear Information System (INIS)

    Ishiwata, Kiichi; Tsukada, Hideo; Kubota, Kazuo; Nariai, Tadashi; Harada, Norihiro; Kawamura, Kazunori; Kimura, Yuichi; Oda, Keiichi; Iwata, Ren; Ishii, Kenji

    2005-01-01

    We performed preclinical and clinical studies of O-[ 11 C]methyl-L-tyrosine, a potential tracer for imaging amino acid transport of tumors by positron emission tomography (PET). Examinations of the radiation-absorbed dose by O-[ 11 C]methyl-L-tyrosine and the acute toxicity and mutagenicity of O-methyl-L-tyrosine showed suitability of the tracer for clinical use. The whole-body imaging of monkeys and healthy humans by PET showed low uptake of O-[ 11 C]methyl-L-tyrosine in all normal organs except for the urinary track and bladder, suggesting that the O-[ 11 C]methyl-L-tyrosine PET has the potential for tumor imaging in the whole-body. Finally, the brain tumor imaging was preliminarily demonstrated

  20. Clinical evaluation of high-resolution CT, 1. CT diagnosis of liver tumors and its limit

    Energy Technology Data Exchange (ETDEWEB)

    Araki, T [Tokyo Univ. (Japan). Faculty of Medicine

    1980-03-01

    To estimate diagnostic accuracy of CT in liver tumors, CT diagnosis in 120 patients with primary hepatocellular carcinoma was discussed. As a result, primary hepatocellular carcinoma less than 2 cm in diameter could not be visualized by CT. Even tumors between 4 and 8 cm in diameter showed false negative caused by isodense tumors on images of 4 patients. To improve the detectability of liver tumors by CT, the higher resolution of low contrast regions on images are required. As a method to improve qualitative diagnosis of liver tumors, rapid intravenous injection of contrast medium was performed on 42 patients with liver tumors, As a result, images reflecting vascularity of tumors were obtained, and the differential diagnosis was possible to some extent by observing the movement of the contrast. Especially, cavernous hemangioma could be distinguished from hepatocellular carcinoma, because cavernous hemangioma showed specific images and could be diagnosed accurately.

  1. SU-E-J-59: Feasibility of Markerless Tumor Tracking by Sequential Dual-Energy Fluoroscopy On a Clinical Tumor Tracking System

    Energy Technology Data Exchange (ETDEWEB)

    Dhont, J; Poels, K; Verellen, D; Tournel, K; Gevaert, T; Steenbeke, F; Burghelea, M; De Ridder, M [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Brussels (Belgium)

    2015-06-15

    Purpose: To evaluate the feasibility of markerless tumor tracking through the implementation of a novel dual-energy imaging approach into the clinical dynamic tracking (DT) workflow of the Vero SBRT system. Methods: Two sequential 20 s (11 Hz) fluoroscopy sequences were acquired at the start of one fraction for 7 patients treated for primary and metastatic lung cancer with DT on the Vero system. Sequences were acquired using 2 on-board kV imaging systems located at ±45° from the MV beam axis, at respectively 60 kVp (3.2 mAs) and 120 kVp (2.0 mAs). Offline, a normalized cross-correlation algorithm was applied to match the high (HE) and low energy (LE) images. Per breathing phase (inhale, exhale, maximum inhale and maximum exhale), the 5 best-matching HE and LE couples were extracted for DE subtraction. A contrast analysis according to gross tumor volume was conducted based on contrast-to-noise ratio (CNR). Improved tumor visibility was quantified using an improvement ratio. Results: Using the implanted fiducial as a benchmark, HE-LE sequence matching was effective for 13 out of 14 imaging angles. Overlying bony anatomy was removed on all DE images. With the exception of two imaging angles, the DE images showed no significantly improved tumor visibility compared to HE images, with an improvement ratio averaged over all patients of 1.46 ± 1.64. Qualitatively, it was observed that for those imaging angles that showed no significantly improved CNR, the tumor tissue could not be reliably visualized on neither HE nor DE images due to a total or partial overlap with other soft tissue. Conclusion: Dual-energy subtraction imaging by sequential orthogonal fluoroscopy was shown feasible by implementing an additional LE fluoroscopy sequence. However, for most imaging angles, DE images did not provide improved tumor visibility over single-energy images. Optimizing imaging angles is likely to improve tumor visibility and the efficacy of dual-energy imaging. This work was in

  2. Canolol inhibits gastric tumors initiation and progression through COX-2/PGE2 pathway in K19-C2mE transgenic mice.

    Directory of Open Access Journals (Sweden)

    Donghui Cao

    Full Text Available 4-Vinyl-2, 6-dimethoxyphenol (canolol is an antioxidant phenolic compound extracted from crude canola oil. In current research, K19-C2mE transgenic mice, developing hyperplastic tumors spontaneously in the glandular stomach, were used to study the mechanisms involved in the anti-inflammation and anti-tumor effects of canolol. Tg mice receiving canolol diet had a reduced tumor incidence, to 41.2%, compared with Non-treatment Tg mice, 77.8% of which had gastric tumor (P=0.002. Besides that, the mean tumor diameter was decreased from 6.5 mm to 4.5 mm (P<0.001 after canolol administration. COX-2/PGE2 pathway is known to play pivotal role in inflammation-induced gastric tumorigenesis. The neutrophils and lymphocytes infiltration was suppressed significantly, and the mRNA levels of the proinflammatory cytokines COX-2, IL-1β and IL-12b were also downregulated in gastric mucosa. Additionally, immunohistochemical analysis showed that COX-2, EP2, Gαs and β-catenin, key factors involving in PGE2 signal transduction, were positive staining with higher H scores in Non-treatment Tg mice, while the expressions were suppressed significantly by 0.1% canolol (P<0.001. In addition, tumor-suppressor miR-7 was reactivated after canolol administration, and COX-2 was showed to be a functional target of miR-7 to suppress the tumor progression. In conclusion, canolol could inhibit the gastritis-related tumor initiation and progression, and the suppression effect was correlated with the blocking up of canonical COX-2/PGE2 signaling pathway and might be regulated by miR-7.

  3. Properties of internalization factors contributing to the uptake of extracellular DNA into tumor-initiating stem cells of mouse Krebs-2 cell line.

    Science.gov (United States)

    Dolgova, Evgeniya V; Potter, Ekaterina A; Proskurina, Anastasiya S; Minkevich, Alexandra M; Chernych, Elena R; Ostanin, Alexandr A; Efremov, Yaroslav R; Bayborodin, Sergey I; Nikolin, Valeriy P; Popova, Nelly A; Kolchanov, Nikolay A; Bogachev, Sergey S

    2016-05-25

    Previously, we demonstrated that poorly differentiated cells of various origins, including tumor-initiating stem cells present in the ascites form of mouse cancer cell line Krebs-2, are capable of naturally internalizing both linear double-stranded DNA and circular plasmid DNA. The method of co-incubating Krebs-2 cells with extracellular plasmid DNA (pUC19) or TAMRA-5'-dUTP-labeled polymerase chain reaction (PCR) product was used. It was found that internalized plasmid DNA isolated from Krebs-2 can be transformed into competent Escherichia coli cells. Thus, the internalization processes taking place in the Krebs-2 cell subpopulation have been analyzed and compared, as assayed by E. coli colony formation assay (plasmid DNA) and cytofluorescence (TAMRA-DNA). We showed that extracellular DNA both in the form of plasmid DNA and a PCR product is internalized by the same subpopulation of Krebs-2 cells. We found that the saturation threshold for Krebs-2 ascites cells is 0.5 μg DNA/10(6) cells. Supercoiled plasmid DNA, human high-molecular weight DNA, and 500 bp PCR fragments are internalized into the Krebs-2 tumor-initiating stem cells via distinct, non-competing internalization pathways. Under our experimental conditions, each cell may harbor 340-2600 copies of intact plasmid material, or up to 3.097 ± 0.044×10(6) plasmid copies (intact or not), as detected by quantitative PCR. The internalization dynamics of extracellular DNA, copy number of the plasmids taken up by the cells, and competition between different types of double-stranded DNA upon internalization into tumor-initiating stem cells of mouse ascites Krebs-2 have been comprehensively analyzed. Investigation of the extracellular DNA internalization into tumor-initiating stem cells is an important part of understanding their properties and possible destruction mechanisms. For example, a TAMRA-labeled DNA probe may serve as an instrument to develop a target for the therapy of cancer, aiming at elimination of

  4. Clinical results of primary malignant musculoskeletal tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen.

    Science.gov (United States)

    Paholpak, Permsak; Sirichativapee, Winai; Wisanuyotin, Taweechok; Kosuwon, Weerachai; Jeeravipoolvarn, Polasak

    2015-06-01

    To evaluate the clinical results of primary malignant musculoskeletal tumors treated with wide resection and recycling autograft reconstruction using liquid nitrogen. We reviewed 12 patients who had a primary malignant bone and soft tissue tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen between March 2006 and March 2013. The results were judged by recurrence, functional status and complications. Functional status was assessed according to the Musculoskeletal Tumor Society Score (MSTSS). Clinical failure was defined as need for reoperation in order to change the type of reconstruction or to amputate, and the presence of local recurrence. The most common tumor was osteosarcoma (eight cases) followed by Ewing's sarcoma (two cases). The tibia was the most frequently involved skeletal site (six cases) followed by the femur (three cases). The median follow-up period was 32 months. In 12 patients, 7 were still alive without recurrence. There were 3 clinical failures: 1 local recurrence and 2 graft complications at 28, 51 and 20 months after reconstruction, respectively. The main complication was infection (three cases). All osteotomy sites were radiographic unions, and the union time was 8.2 ± 2.7 months. The mean ± SD MSTSS score was 79% ± 11%; excellent functional results were achieved in seven patients. Recycling autograft reconstruction using liquid nitrogen had favorable clinical outcomes in terms of functional status and local recurrence. This reconstruction method, therefore, represents a reasonable alternative for limb salvage surgery. © 2014 Wiley Publishing Asia Pty Ltd.

  5. Role of Mesenchymal Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases

    Science.gov (United States)

    2017-07-01

    Clinical Metastases PRINCIPAL INVESTIGATOR: Jeffrey Green CONTRACTING ORGANIZATION: The Geneva Foundation Tacoma, WA 98402 REPORT DATE: July 2017 TYPE...2016 - 14 June 2017 4. TITLE AND SUBTITLE Role of Mesenchymal-Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical ...and/or select agents. Nothing to report. 6. PRODUCTS: • publications, conference papers, and presentations ; Jennifer Zhu submitted an abstract and will

  6. Role of Mesenchymal-Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases

    Science.gov (United States)

    2017-07-01

    Clinical Metastases PRINCIPAL INVESTIGATOR: Rosandra Kaplan CONTRACTING ORGANIZATION: The Geneva Foundation Tacoma, WA 98402 REPORT DATE: July 2017...2017 4. TITLE AND SUBTITLE Role of Mesenchymal-Derived Stem Cells in Stimulating Dormant Tumor Cells to Proliferate and Form Clinical Metastases 5a...PRODUCTS:  publications, conference papers, and presentations ; Jennifer Zhu submitted an abstract and will present this work at the Annual

  7. SU-E-T-183: Clinical Quality Assurance Workflow for Dynamic Tumor Tracking Radiation Dose Delivery

    International Nuclear Information System (INIS)

    Mamalui-Hunter, M; Su, Z; Li, Z

    2015-01-01

    Purpose: One of the most important aspects of implementation of new treatment modalities is an ‘end-to-end’ verification of the treatment process. Radiation treatment based on dynamic tracking of a tumor is highly patient-specific, therefore, special attention should be paid to quality assurance of the treatment delivery. Our goal was to design the clinical workflow that ensures accurate delivery of the planned dose using the Dynamic Target Tracking option of VeroTM (BrainLab,MHI) linac. Methods: A patient simulation is designed to include a pre-treatment session to verify whether the system can reliably track the motion of the implanted marker and build the 4D model of the target motion. The external surrogate and target motion patterns are recorded in the ExactracTM log files. In this work, a spectrum of custom marker and external surrogate motion trajectories closely resembling the patient specific motion patterns was used. 1mm thick/11mm long VisicoilTM marker was placed 15 and 20mm from the center of the spherical tissue equivalent target (centroid to centroid distance) in the 4D motion phantom (CIRSTM). 3D conformal (3 mm block margin) SBRT plans were delivered to 2 moving targets in the phantom: 1) 20mm diameter target that allows ion chamber dose measurement and 2) 25mm target that allows using film to measure CAX dose (GafchromicTM EBT3 used). The measured dose was compared to the iPlanTM TPS results using MonteCarlo algorithm (1% variance, Dose-to-water). Results: On average, film shows 98.9% pass using gamma criterion for 2% and 2mm DTA, 94.3% match for 2% and 1 mm DTA, 98% pass for 1% and 2 mm DTA however only 88% points passing for 1% and 1 mm DTA. Ion chamber measurements agreed with the calculation within 1.5%. Conclusion: The clinical QA workflow was designed for SBRT delivery using real-time tumor tracking on VeroTM linac

  8. Designing a Clinical Data Warehouse Architecture to Support Quality Improvement Initiatives.

    Science.gov (United States)

    Chelico, John D; Wilcox, Adam B; Vawdrey, David K; Kuperman, Gilad J

    2016-01-01

    Clinical data warehouses, initially directed towards clinical research or financial analyses, are evolving to support quality improvement efforts, and must now address the quality improvement life cycle. In addition, data that are needed for quality improvement often do not reside in a single database, requiring easier methods to query data across multiple disparate sources. We created a virtual data warehouse at NewYork Presbyterian Hospital that allowed us to bring together data from several source systems throughout the organization. We also created a framework to match the maturity of a data request in the quality improvement life cycle to proper tools needed for each request. As projects progress in the Define, Measure, Analyze, Improve, Control stages of quality improvement, there is a proper matching of resources the data needs at each step. We describe the analysis and design creating a robust model for applying clinical data warehousing to quality improvement.

  9. Initiating antiretroviral therapy for HIV at a patient's first clinic visit: a cost-effectiveness analysis of the rapid initiation of treatment randomized controlled trial.

    Science.gov (United States)

    Long, Lawrence C; Maskew, Mhairi; Brennan, Alana T; Mongwenyana, Constance; Nyoni, Cynthia; Malete, Given; Sanne, Ian; Fox, Matthew P; Rosen, Sydney

    2017-07-17

    Determine the cost and cost-effectiveness of single-visit (same-day) antiretroviral treatment (ART) initiation compared to standard of care initiation. Cost-effectiveness analysis of individually randomized (1 : 1) pragmatic trial of single-visit initiation, which increased viral suppression at 10 months by 26% [relative risk (95% confidence interval) 1.26 (1.05-1.50)]. Primary health clinic in Johannesburg, South Africa. HIV positive, adult, nonpregnant patients not yet on ART or known to be eligible who presented at the clinic 8 May 2013 to 29 August 2014. Same-day ART initiation using point-of-care laboratory instruments and accelerated clinic procedures to allow treatment-eligible patients to receive antiretroviral medications at the same visit as testing HIV positive or having an eligible CD4 cell count. Comparison was to standard of care ART initiation, which typically required three to five additional clinic visits. Average cost per patient enrolled and per patient achieving the primary outcome of initiated 90 days or less and suppressed 10 months or less, and production cost per patient achieving primary outcome (all costs per primary outcome patients). The average cost per patient enrolled, per patient achieving the primary outcome, and production cost were $319, $487, and $738 in the standard arm and $451, $505, and $707 in the rapid arm. Same-day treatment initiation was more effective than standard initiation, more expensive per patient enrolled, and less expensive to produce a patient achieving the primary outcome. Omitting point-of-care laboratory tests at initiation and focusing on high-volume clinics have the potential to reduce costs substantially and should be evaluated in routine settings.

  10. Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases

    Science.gov (United States)

    Li, Yingmei; Pan, Wenying; Connolly, Ian D.; Reddy, Sunil; Nagpal, Seema

    2017-01-01

    Cerebral spinal fluid (CSF) from brain tumor patients contains tumor cellular and cell-free DNA (cfDNA), which provides a less-invasive and routinely accessible method to obtain tumor genomic information. In this report, we used droplet digital PCR to test mutant tumor DNA in CSF of a patient to monitor the treatment response of metastatic melanoma leptomeningeal disease (LMD). The primary melanoma was known to have a BRAFV600E mutation, and the patient was treated with whole brain radiotherapy and BRAF inhibitors. We collected 9 CSF samples over 6 months. The mutant cfDNA fraction gradually decreased from 53 % (time of diagnosis) to 0 (time of symptom alleviation) over the first 6 time points. Three months after clinical improvement, the patient returned with severe symptoms and the mutant cfDNA was again detected in CSF at high levels. The mutant DNA fraction corresponded well with the patient’s clinical response. We used whole exome sequencing to examine the mutation profiles of the LMD tumor DNA in CSF before therapeutic response and after disease relapse, and discovered a canonical cancer mutation PTENR130* at both time points. The cellular and cfDNA revealed similar mutation profiles, suggesting cfDNA is representative of LMD cells. This study demonstrates the potential of using cellular or cfDNA in CSF to monitor treatment response for LMD. PMID:26961773

  11. A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. | Office of Cancer Genomics

    Science.gov (United States)

    We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A.

  12. Adenosarcoma of the uterine body initially presenting as an interstitial small tumor of the uterus: a case report.

    Science.gov (United States)

    Miyata, H; Tsuji, N; Jimi, T; Butsuhara, Y; Terakawa, K; Nagano, T

    2014-01-01

    Adenosarcoma of the uterine body is a rare mixed tumor in which a benign epithelial component is mixed with a malignant stromal element. It has been considered that this tumor originates from the endometrium and its most common finding of imaging is a polypoid tumor occupying the uterine cavity. The authors herein present a case of 37-year-old female with a complaint of abnormal vaginal bleeding. At the first visit, transvaginal ultrasound and magnetic resonance imaging (MRI) showed a round mass with a diameter of one cm in the uterine wall. No malignant pathological finding was detected. The patient visited the authors again one year later, because of continuous bleeding. At that time, they found a polypoid tumor in the uterine cavity, which turned out to be adenosarcoma with sarcomatous overgrowth. The round mass in the uterus detected at first time seems to have been incipience of adenosarcoma. Prodromal sign of adenosarcoma has not been reported previously.

  13. Benign and malignant cartilage tumors of bone and joint: their anatomic and theoretical basis with an emphasis on radiology, pathology and clinical biology. II. Juxtacortical cartilage tumors

    International Nuclear Information System (INIS)

    Brien, E.W.; Mirra, J.M.; Luck, J.V. Jr.

    1999-01-01

    In part I, we reviewed the varied clinical presentations, pathogenesis, histologic findings, radiologic findings, and treatment of intramedullary cartilaginous lesions of bone. In this section, we will evaluate our cases and consultations of juxtacortical cartilaginous tumors. Radiographic differential diagnosis includes the numerous juxtacortical lesions particularly osteochondroma, parosteal chondroma, Trevor's disease, trauma (fracture and periostitis ossificans), and the low- and high-grade surface osteosarcomas. By emphasizing pathogenesis in conjunction with radiographic and histologic findings, pitfalls in diagnosis and subsequent treatment can be avoided in such cases. (orig.)

  14. Benign and malignant cartilage tumors of bone and joint: their anatomic and theoretical basis with an emphasis on radiology, pathology and clinical biology. II. Juxtacortical cartilage tumors

    Energy Technology Data Exchange (ETDEWEB)

    Brien, E.W. [Orthopaedic Oncology Service, Orthopaedic Hospital, Los Angeles, CA (United States)]|[Musculoskeletal Tumor Service, Orthopaedic Hospital, Los Angeles, CA (United States); Mirra, J.M.; Luck, J.V. Jr. [Orthopaedic Oncology Service, Orthopaedic Hospital, Los Angeles, CA (United States)

    1999-01-01

    In part I, we reviewed the varied clinical presentations, pathogenesis, histologic findings, radiologic findings, and treatment of intramedullary cartilaginous lesions of bone. In this section, we will evaluate our cases and consultations of juxtacortical cartilaginous tumors. Radiographic differential diagnosis includes the numerous juxtacortical lesions particularly osteochondroma, parosteal chondroma, Trevor`s disease, trauma (fracture and periostitis ossificans), and the low- and high-grade surface osteosarcomas. By emphasizing pathogenesis in conjunction with radiographic and histologic findings, pitfalls in diagnosis and subsequent treatment can be avoided in such cases. (orig.) With 32 figs., 2 tabs., 32 refs.

  15. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hamid Omid

    2011-11-01

    Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

  16. The relationship between radiological features and clinical manifestation and dental expenses of keratocystic odontogenic tumor

    International Nuclear Information System (INIS)

    Min, Jung Hyun; Huh, Kyung Heo; Heo, Min Suk; Choi, Soon Chul; Lee, Sam Sun; Bae, Kwang Hak; Choi, Jin Woo

    2013-01-01

    This study was performed to identify correlations between keratocystic odontogenic tumor (KCOT) data from CT sections, and data on the KCOT clinical manifestation and resulting dental expenses. Following local Institutional Review Board (IRB) approval, a seven-years of retrospective study was performed regarding patients with KCOTs treated at the Seoul National University Dental Hospital. A total of 180 KCOT were included in this study. The following information was collected: age, gender, location and size of the lesion, radiological features, surgical treatment provided and dental expenses. There was no significant association between the size of the KCOT and age, gender, and presenting preoperative symptoms. In both jaws, it was unusual to find KCOTs under 10 mm. The correlation between the number of teeth removed and the size of the KCOT in the tooth bearing area was statistically significant in the mandible, whereas in the maxilla, no significant relationship was found. Dental expenses compared with the size of the KCOT were found to be significant in both jaws. The size of KCOT was associated with a significant increase in dental expenses for both jaws and the number of teeth removed from the mandible. These findings emphasize the importance of routine examinations and early detection of lesions, which in turn helps preserving anatomical structures and reducing dental expenses.

  17. Using literature and data to learn Bayesian networks as clinical models of ovarian tumors.

    Science.gov (United States)

    Antal, Peter; Fannes, Geert; Timmerman, Dirk; Moreau, Yves; De Moor, Bart

    2004-03-01

    Thanks to its increasing availability, electronic literature has become a potential source of information for the development of complex Bayesian networks (BN), when human expertise is missing or data is scarce or contains much noise. This opportunity raises the question of how to integrate information from free-text resources with statistical data in learning Bayesian networks. Firstly, we report on the collection of prior information resources in the ovarian cancer domain, which includes "kernel" annotations of the domain variables. We introduce methods based on the annotations and literature to derive informative pairwise dependency measures, which are derived from the statistical cooccurrence of the names of the variables, from the similarity of the "kernel" descriptions of the variables and from a combined method. We perform wide-scale evaluation of these text-based dependency scores against an expert reference and against data scores (the mutual information (MI) and a Bayesian score). Next, we transform the text-based dependency measures into informative text-based priors for Bayesian network structures. Finally, we report the benefit of such informative text-based priors on the performance of a Bayesian network for the classification of ovarian tumors from clinical data.

  18. Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Hideyasu Tsumura

    2017-01-01

    Full Text Available Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR or low-dose-rate (LDR brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT. Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative and again immediately after the surgical manipulation (intraoperative. Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs using the CellSearch System. While no preoperative samples showed CTCs (0%, they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012. Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

  19. Clinical application of vacuum bag immobilization of the trunk in malignant tumor patients

    International Nuclear Information System (INIS)

    Su Jianxin; Wu Yuqi; Huang Jun; Lin Chengguang; Liu Hui; Huang Xiaoyan

    2005-01-01

    Objective: To evaluate the clinical application of vacuum bag immobilization of thorax and pelvis for patients with malignant tumors. Methods: Of 714 patients (fields) chosen randomly, 582(fields) were immobilized with vacuum bag, while the other 132 (fields) used only sand bags, tapes, and other simple immobilizing devices. The field movements were measured and compared before and after the setup, along with 56 patients immobilized twice with vacuum bag. Results: The variance of movement before and after the setup was 6.7% for patients with vacuum bag , while that was 26.5% for patients without the vacuum bag. It was even 32.1% for patients immobilized twice with vacuum bag. Conclusions: The variance of movement decreases significantly with vacuum bag immobilization. It should be used as frequently as possible. As the variance of movement rises obviously when vacuum bag is used twice, the semi-soft vacuum bag should be prepared afresh and checked under the simulator before the second use. (authors)

  20. The relationship between radiological features and clinical manifestation and dental expenses of keratocystic odontogenic tumor

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Hyun; Huh, Kyung Heo; Heo, Min Suk; Choi, Soon Chul; Lee, Sam Sun; Bae, Kwang Hak [Dept. of School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Choi, Jin Woo [Dept. of Oral and Maxillofacial Radiology, Dankook University College of Dentistry, Cheonan (Korea, Republic of)

    2013-06-15

    This study was performed to identify correlations between keratocystic odontogenic tumor (KCOT) data from CT sections, and data on the KCOT clinical manifestation and resulting dental expenses. Following local Institutional Review Board (IRB) approval, a seven-years of retrospective study was performed regarding patients with KCOTs treated at the Seoul National University Dental Hospital. A total of 180 KCOT were included in this study. The following information was collected: age, gender, location and size of the lesion, radiological features, surgical treatment provided and dental expenses. There was no significant association between the size of the KCOT and age, gender, and presenting preoperative symptoms. In both jaws, it was unusual to find KCOTs under 10 mm. The correlation between the number of teeth removed and the size of the KCOT in the tooth bearing area was statistically significant in the mandible, whereas in the maxilla, no significant relationship was found. Dental expenses compared with the size of the KCOT were found to be significant in both jaws. The size of KCOT was associated with a significant increase in dental expenses for both jaws and the number of teeth removed from the mandible. These findings emphasize the importance of routine examinations and early detection of lesions, which in turn helps preserving anatomical structures and reducing dental expenses.

  1. Variation of gross tumor volume and clinical target volume definition for lung cancer

    International Nuclear Information System (INIS)

    Liang Jun; Li Minghui; Chen Dongdu

    2011-01-01

    Objective: To study the variation of gross tumor volume (GTV) and clinical target volume (CTV) definition for lung cancer between different doctors. Methods: Ten lung cancer patients with PET-CT simulation were selected from January 2008 to December 2009.GTV and CTV of these patients were defined by four professors or associate professors of radiotherapy independently. Results: The mean ratios of largest to smallest GTV and CTV were 1.66 and 1.65, respectively. The mean coefficients of variation for GTV and CTV were 0.20 and 0.17, respectively. System errors of CTV definition in three dimension were less than 5 mm, which was the largest in inferior and superior (0.48 cm, 0.37 cm, 0.32 cm; F=0.40, 0.60, 0.15, P=0.755, 0.618, 0.928). Conclusions: The variation of GTV and CTV definition for lung cancer between different doctors exist. The mean ratios of largest to smallest GTV and CTV were less than 1.7. The variation was in hilar and mediastinum lymphanode regions. System error of CTV definition was the largest (<5 mm) in cranio-caudal direction. (authors)

  2. Clinical practice and outcomes in advanced gastrointestinal stromal tumor: Experience from an Indian tertiary care center

    Directory of Open Access Journals (Sweden)

    Subhadeep Bose

    2017-01-01

    Full Text Available Background: Management of advanced Gastrointestinal stromal tumors (GIST has been revolutionized with the use of Imatinib guided by mutation analysis. Data from India remains scarce. Materials and Methods: Patients with metastatic GIST who were treated at Department of Gastro-intestinal & Hepaticopancreaticobiliary Oncology Unit at Tata Memorial Hospital, Mumbai between December, 2004 and December 2015 were included in the analysis. Clinical and radiological data was retrieved from stored medical records and charts. Results: A total of 83 patients with metastatic GIST were available for analysis. Median age was 54 years with a 3:1 male predominance. Stomach was the most common site of primary with liver being the most common site of metastasis. c-Kit mutation analysis results were available for 44 patients with exon 11 mutant being the most common mutation. With a median follow up of 33 months, the 10 years estimated progression free and overall survival (OS was 18% and 51% respectively. Overall response rate to first line imatinib was 37.6% and estimated 3 years OS to first line therapy was significantly better for Exon 11 mutated patients (p=0.016. 34 patients received second line therapy in the form of either sunitinib, pazopanib or increased dose imatinib with a clinical benefit rate of 73.5%. C-Kit mutated patients had a better median OS compared to non mutated patients. Conclusions: GIST diagnosed and treated in the Indian subcontinent appears to show improved outcomes. The importance of c-Kit mutation analysis in determining the prognosis and outcomes of patients with advanced GIST is emphasized.

  3. Clinical characteristics and outcomes of placental site trophoblastic tumor: experience of single institution in Korea.

    Science.gov (United States)

    Lee, Hye-Joo; Shin, Wonkyo; Jang, Yun Jeong; Choi, Chel Hun; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

    2018-05-01

    Placental site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD) and the optimum management is still controversial. In this study, we analyzed the clinical features, treatment, and outcomes of 6 consecutive patients with PSTT treated in our institution. The electronic medical record database of Samsung Medical Center was screened to identify patients with PSTT from 1994 to 2017. Medical records for the details of each patient's clinical features and treatment were extracted and reviewed. This study was approved Institutional Review Board of our hospital. A total of 418 cases of GTD, 6 (1.4%) patients with PSTT were identified. The median age of the patients was 31 years. The antecedent pregnancy was term in all 5 cases with available antecedent pregnancy information and the median interval from pregnancy to diagnosis of PSTT was 8 months. The median titer of serum beta human chorionic gonadotropin (β-hCG) at diagnosis was 190.9 mIU/mL. Five (83.3%) patients presented with irregular vaginal bleeding and one (16.7%) had amenorrhea. All patients had disease confined to the uterus without metastasis at diagnosis and were successfully treated by hysterectomy alone. All of them were alive without disease during the follow-up period. In this study, we observed low level serum β-hCG titer and irregular vaginal bleeding with varying interval after antecedent term pregnancy were most common presenting features of PSTT. In addition, we demonstrated hysterectomy alone was successful for the treatment of stage I disease of PSTT.

  4. Atypical Uterine Smooth Muscle Tumors: A Retrospective Evaluation of Clinical and Pathologic Features.

    Science.gov (United States)

    Maltese, Giuseppa; Fontanella, Caterina; Lepori, Stefano; Scaffa, Cono; Fucà, Giovanni; Bogani, Giorgio; Provenzano, Salvatore; Carcangiu, Maria Luisa; Raspagliesi, Francesco; Lorusso, Domenica

    2018-01-01

    Clinical characteristics combined with new biomarkers help discriminate between atypical uterine smooth muscle tumors (AUSMT) and leiomyosarcomas (LMS). We retrospectively collected a series of leiomyomas (LM), AUSMT, and LMS. Estrogen receptors (ER), progesterone receptors (PR), p16, Ki-67, and p53 expression were assessed by immunohistochemistry. For AUSMT patients, immunohistochemistry evaluations were performed at the time of diagnosis and at recurrences. A total of 27 cases of AUSMT, 22 LM, and 31 LMS were identified. The expression of ER and PR decreased from LM to LMS (ER+: LM 95.5%, AUSMT 88.9%, LMS 41.9%, p < 0.001; PR+: LM 100%, AUSMT 88.9%, LMS 38.2%, p = 0.002). By contrast, p16 and p53 expression increased (p16+: LM 4.5%, AUSMT 40.7%, LMS 45.2%, p = 0.004; p53: LM 9.1%, AUSMT 33.3%, LMS 58.1%, p = 0.001). At a median follow-up of 33.47 months, 40.7% of patients with AUSMT experienced recurrent disease, 6 patients relapsed as AUSMT and 5 as LMS. In univariate analysis was observed that ER status (p = 0.027) and p53 expression (p = 0.015) predicted risk of relapse. Treatment of AUSMT should be centralized in dedicated centers. International collaborations are needed to optimize research strategy, which may lead to the identification of new useful biomarkers and to improvement in the clinical management of this rare disease. © 2017 S. Karger AG, Basel.

  5. A Miniaturized Chemical Proteomic Approach for Target Profiling of Clinical Kinase Inhibitors in Tumor Biopsies

    Science.gov (United States)

    Chamrád, Ivo; Rix, Uwe; Stukalov, Alexey; Gridling, Manuela; Parapatics, Katja; Müller, André C.; Altiok, Soner; Colinge, Jacques; Superti-Furga, Giulio; Haura, Eric B.; Bennett, Keiryn L.

    2014-01-01

    While targeted therapy based on the idea of attenuating the activity of a preselected, therapeutically relevant protein has become one of the major trends in modern cancer therapy, no truly specific targeted drug has been developed and most clinical agents have displayed a degree of polypharmacology. Therefore, the specificity of anticancer therapeutics has emerged as a highly important but severely underestimated issue. Chemical proteomics is a powerful technique combining postgenomic drug-affinity chromatography with high-end mass spectrometry analysis and bioinformatic data processing to assemble a target profile of a desired therapeutic molecule. Due to high demands on the starting material, however, chemical proteomic studies have been mostly limited to cancer cell lines. Herein, we report a down-scaling of the technique to enable the analysis of very low abundance samples, as those obtained from needle biopsies. By a systematic investigation of several important parameters in pull-downs with the multikinase inhibitor bosutinib, the standard experimental protocol was optimized to 100 µg protein input. At this level, more than 30 well-known targets were detected per single pull-down replicate with high reproducibility. Moreover, as presented by the comprehensive target profile obtained from miniaturized pull-downs with another clinical drug, dasatinib, the optimized protocol seems to be extendable to other drugs of interest. Sixty distinct human and murine targets were finally identified for bosutinib and dasatinib in chemical proteomic experiments utilizing core needle biopsy samples from xenotransplants derived from patient tumor tissue. Altogether, the developed methodology proves robust and generic and holds many promises for the field of personalized health care. PMID:23901793

  6. Brown tumor: clinical findings of secondary hyperparathyroidism in patients with renal osteodystrophy.

    Science.gov (United States)

    Silva, Mairaira Teles Leão E; Cedraz, Juliana Silva Barros; Pontes, Caetano Guilherme Carvalho; Trento, Cleverson Luciano; Brasileiro, Bernardo Ferreira; Piva, Marta Rabello; Pereira, Fabiano Alvim

    2017-01-01

    A brown tumor, or osteoclastoma, is a nonneoplastic bony lesion associated with hyperparathyroidism and directly related to increased levels of parathyroid hormone. These tumors result from excessive osteoclastic activity. This article presents 3 cases of brown tumor localized in facial bones. The lesions were the result of secondary hyperparathyroidism associated with chronic renal failure. The patients were two 42-year-old men and a 39-year-old woman. All patients had been treated systemically by hemodialysis for more than 10 years. This article highlights the importance of proper diagnosis and management of dental patients presenting with a brown tumor.

  7. Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells.

    Science.gov (United States)

    Brown, Christine E; Starr, Renate; Aguilar, Brenda; Shami, Andrew F; Martinez, Catalina; D'Apuzzo, Massimo; Barish, Michael E; Forman, Stephen J; Jensen, Michael C

    2012-04-15

    To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to target this therapeutically resistant glioma subpopulation. A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine(+) CTL-mediated killing in vitro and in vivo. We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2(pos) cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine(+) CTL were capable of efficient recognition and killing of both IL13Rα2(pos) GSCs and IL13Rα2(pos) differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine(+) CTL displayed robust antitumor activity against established IL13Rα2(pos) GSC TS-initiated orthotopic tumors in mice. Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine(+) CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations. ©2012 AACR.

  8. EDCTP regional networks of excellence: initial merits for planned clinical trials in Africa.

    Science.gov (United States)

    Miiro, George M; Oukem-Boyer, Odile Ouwe Missi; Sarr, Ousmane; Rahmani, Maerangis; Ntoumi, Francine; Dheda, Keertan; Pym, Alexander; Mboup, Souleymane; Kaleebu, Pontiano

    2013-03-22

    Achieving the Millennium Development Goals (MDGs) and combating hotspots with escalating but preventable communicable diseases remain major challenges in Africa. The European and Developing Countries Clinical Trials Partnership (EDCTP) intervened to combat poverty-related diseases including malaria, tuberculosis and HIV/AIDS, and to conduct multi-centre clinical trials and multi-disciplinary health research through an innovative model of regional Networks of Excellence (NoEs). We participated in a quasi-formative evaluation between October and December 2011 on the 4 regional-led research networks. These included the: Central Africa Network on Tuberculosis, HIV/AIDS and Malaria (CANTAM); East African Consortium for Clinical Research (EACCR); West African Network of Excellence for TB, AIDS and Malaria (WANETAM), and the Trials of Excellence for Southern Africa (TESA) launched between 2009 and 2010. We shared a participatory appraisal of field reports, progress reports and presentations from each network to jointly outline the initial experiences of the merits, outputs and lessons learnt. The self-regulating democratic networks, with 64 institutions in 21 African countries, have trained over 1, 000 African scientists, upgraded 36 sites for clinical trials, leveraged additional € 24 million and generated 38 peer-reviewed publications through networking and partnerships. The shared initial merits and lessons learnt portray in part the strengthened capacity of these networks for improved research coordination and conduct of planned multi-center clinical trials in Africa. Increased funding by African agencies, governments and international health partners will ensure sustainability of these networks for research capacity development and demonstrate their commitment to achieving the MDGs in Africa.

  9. Evaluation of endourological tools to improve the diagnosis and therapy of ureteral tumors – from model development to clinical application

    Directory of Open Access Journals (Sweden)

    Wagner D.

    2015-09-01

    Full Text Available Adequate diagnosis of upper urinary tract (UUT tumors is essential for successful local treatment. Organsparing approaches are technically difficult and require consistent further development. Appropriate models for investigating new diagnostic and therapeutic methods are not yet available. This study demonstrates the incorporation of a fresh sample model into five different test levels (I-V for improving the diagnosis and therapy of ureteral tumors. In these test levels, new diagnostic and ablation techniques are evaluated for feasibility, application safety, efficacy and accuracy. An assessment of their suitability for broad preclinical and clinical application also took economic aspects into account.

  10. A clinical trial comparing the responses of animal tumors receiving heat sensitizing drugs prior to whole body hyperthermia

    International Nuclear Information System (INIS)

    Klein, M.K.; Forsyth, K.; Dewhirst, M.W.; Fuller, D.J.M.

    1984-01-01

    Whole body hyperthermia (WBH) has rarely been found effective in inducing complete tumor responses. Recent in vitro studies showing that heat sensitizion is possible have renewed interest in this field. In this protocol, WBH is induced via a commercially available inductive device and maintained at 42 0 C for thirty minutes. The heat sensitizing drugs, difluoromethylornithine (DFMO) methylglyoxal bis (guanylhydrazone) (MGBG) are administered 48 hours before, in accordance with in vitro studies. Goals of the study include evaluation of normal tissue toxicity and tumor response. Two normal dogs were treated to study acute toxicities before inception of the clinical trial. The gastrointestinal and hematopoietic systems were used to monitor toxicities using systems review and serial bloodwork. These studies and preliminary clinical results of observed tumor regression in dogs with lymphomas are discussed. Consistent changes in all patients included elevations in liver enzymes, creatine phosphokinase (CPK), and white blood cell counts, as well as, decreases in platelet counts. All changes were transient and clinical signs were not associated with them. Tumor volume reductions from 25% to 74% have been documented

  11. [Predictive methods versus clinical titration for the initiation of lithium therapy. A systematic review].

    Science.gov (United States)

    Geeraerts, I; Sienaert, P

    2013-01-01

    When lithium is administered, the clinician needs to know when the lithium in the patient’s blood has reached a therapeutic level. At the initiation of treatment the level is usually achieved gradually through the application of the titration method. In order to increase the efficacy of this procedure several methods for dosing lithium and for predicting lithium levels have been developed. To conduct a systematic review of the publications relating to the various methods for dosing lithium or predicting lithium levels at the initiation of therapy. We searched Medline systematically for articles published in English, French or Dutch between 1966 and April 2012 which described or studied a method for dosing lithium or for predicting the lithium level reached following a specific dosage. We screened the reference lists of relevant articles in order to locate additional papers. We found 38 lithium prediction methods, in addition to the clinical titration method. These methods can be divided into two categories: the ‘a priori’ methods and the ‘test-dose’ methods, the latter requiring the administration of a test dose of lithium. The lithium prediction methods generally achieve a therapeutic blood level faster than the clinical titration method, but none of the methods achieves convincing results. On the basis of our review, we propose that the titration method should be used as the standard method in clinical practice.

  12. Clinical application of micro-implant anchorage in initial orthodontic retraction.

    Science.gov (United States)

    Wahabuddin, Shaji; Mascarenhas, Rohan; Iqbal, Mahamad; Husain, Akhter

    2015-02-01

    Micro-implant is a device that is temporarily fixed to bone for the purpose of enhancing orthodontic anchorage either by supporting the teeth of the reactive unit or by obviating the need for the reactive unit altogether, and which is subsequently removed after use. The purpose of this study was to evaluate the clinical efficiency of micro-implants in reinforcing anchorage during the initial retraction of anterior teeth, check the rate of initial retraction for 8 weeks, and assess the stability of micro-implants during this period. Eighteen micro-implants were placed (10 in the maxilla and 8 in the mandible) and immediately loaded with 200-250 g of force using 9-mm closed coil Nitinol springs. The amount of space closure was measured every 2 weeks until the eighth week. Cephalometric measurements were made at the end of the study to evaluate anchor loss, if any. Micro-implant stability was also assessed. The rate of initial retraction in the maxilla at the end of 8 weeks was 1.65 mm/quadrant and 1.51 mm/quadrant in the mandible. The amount of retraction on the left side of the arches was 1.66 mm/quadrant and 1.49 mm/quadrant on the right side. The average initial retraction for both arches per month was 0.78 mm. An anchor loss of 0.1 mm (0.06%) was observed in the maxilla while no mandibular anchor loss was recorded. The rate of initial retraction observed in the maxilla was more than that achieved in the mandible. Initial retraction was also more on the left side of the arches. There was no anchor loss in the mandible. The micro-implant-reinforced anchorage was helpful in minimizing anchor loss and accepted heavy traction forces but did not bring about a faster rate of retraction.

  13. Clinical relevance of F-18 FDG PET for imaging of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Adams, S.; Baum, R.P.; Hoer, G.

    2001-01-01

    Neuroendocrine tumors are characterized immunocytochemically by the expression of different peptides and biogenic amines. Hormones induce their biological action by binding to and stimulating specific membrane-associated receptors for e.g. somatostatin. The presence of somatostatin receptors (SR) has been described mainly in endocrine glands and the central nervous system. Interestingly, a large variety of human tumors, including gastroenteropancreatic (GEP) tumors and medullary thyroid carcinomas (MTC) also express a high density of SR and can be imaged with [ 111 In-DTPA-D-Phe 1 ]-pentetreotide. Cell proliferative activity is an important indicator of the growth of various malignant tumors associated with a poorer prognosis and Ki-67 expression. 18 F-FDG is a marker of tumor viability, based upon the increased glycolysis that is associated with malignancy as compared with normal tissue. SR-containing neuroendocrine tumors are well-differentiated and tend to grow slowly. Furthermore, these tumors demonstrate inverse relationship between in vivo SR expression, cell proliferation (low Ki-67 expression) and FDG uptake (normal biodistribution). In comparison, less differentiated tumors, e.g. atypical carcinoids or MTC with increasing CEA levels show mitotic activity (high levels of Ki-67 immunoreactivity and increased FDG uptake) and often lack of SR. In conclusion, SR scintigraphy has been shown to localize well-differentiated neuroendocrine tumors. In contrast, PET imaging is valuable for predicting malignancy only in less differentiated tumors with increased glucose metabolism. Therefore, an additional F-18 FDG PET should be performed if SR scintigraphy (GEP tumors) or combined imaging using [ 111 In-DTPA-D-Phe 1 ]-pentetreotide and 99m Tc(V)-DMSA (MTC) is negative. (orig.) [de

  14. Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

    International Nuclear Information System (INIS)

    Rossi, Sabrina; Toschi, Luca; Castello, Angelo; Grizzi, Fabio; Mansi, Luigi; Lopci, Egesta

    2017-01-01

    The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

  15. Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Sabrina; Toschi, Luca [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano (Italy); Castello, Angelo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Grizzi, Fabio [Humanitas Clinical and Research Hospital, Immunology and Inflammation, Rozzano (Italy); Mansi, Luigi [Seconda Universita di Napoli, Nuclear Medicine, Naples (Italy); Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano, MI (Italy)

    2017-12-15

    The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

  16. "Salvage microbiology": detection of bacteria directly from clinical specimens following initiation of antimicrobial treatment.

    Directory of Open Access Journals (Sweden)

    John J Farrell

    Full Text Available PCR coupled with electrospray ionization mass spectrometry (ESI-MS is a diagnostic approach that has demonstrated the capacity to detect pathogenic organisms from culture negative clinical samples after antibiotic treatment has been initiated. [1] We describe the application of PCR/ESI-MS for detection of bacteria in original patient specimens that were obtained after administration of antibiotic treatment in an open investigation analysis.We prospectively identified cases of suspected bacterial infection in which cultures were not obtained until after the initiation of antimicrobial treatment. PCR/ESI-MS was performed on 76 clinical specimens that were submitted for conventional microbiology testing from 47 patients receiving antimicrobial treatment.In our series, 72% (55/76 of cultures obtained following initiation of antimicrobial treatment were non-diagnostic (45 negative cultures; and 10 respiratory specimens with normal flora (5, yeast (4, or coagulase-negative staphylococcus (1. PCR/ESR-MS detected organisms in 83% (39/47 of cases and 76% (58/76 of the specimens. Bacterial pathogens were detected by PCR/ESI-MS in 60% (27/45 of the specimens in which cultures were negative. Notably, in two cases of relapse of prosthetic knee infections in patients on chronic suppressive antibiotics, the previous organism was not recovered in tissue cultures taken during extraction of the infected knee prostheses, but was detected by PCR/ESI-MS.Molecular methods that rely on nucleic acid amplification may offer a unique advantage in the detection of pathogens collected after initiation of antimicrobial treatment and may provide an opportunity to target antimicrobial therapy and "salvage" both individual treatment regimens as well as, in select cases, institutional antimicrobial stewardship efforts.

  17. Saudi Oncology Society clinical management guidelines for testicular germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mohammed Al Otaibi

    2011-01-01

    Full Text Available In this report, guidelines for the evaluation, medical and surgical management of transitional cell carcinoma of testicular germ cell tumors is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The recommendations are presented with supporting level of evidence.

  18. Clinical relevance of occult tumor cells in lymph nodes from gastric cancer patients.

    NARCIS (Netherlands)

    Doekhie, F.S.; Mesker, W.H.; Krieken, J.H.J.M. van; Kok, N.F.; Hartgrink, H.H.; Kranenbarg, E.K.; Putter, H.; Kuppen, P.J.; Tanke, H.J.; Tollenaar, R.A.E.M.; Velde, C.J. van de

    2005-01-01

    The current method for staging in gastric cancer is not sufficient as even after a complete primary tumor resection, patients with node-negative gastric cancer suffer from disease recurrence. In this study, the relation between disease recurrence and the presence of occult tumor cells (OTC) in lymph

  19. Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature.

    Science.gov (United States)

    Siegfried, Aurore; Cances, Claude; Denuelle, Marie; Loukh, Najat; Tauber, Maïté; Cavé, Hélène; Delisle, Marie-Bernadette

    2017-04-01

    Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. PET in tumor imaging: research only or a cost effective clinical tool?

    International Nuclear Information System (INIS)

    Wahl, R.L.

    1997-01-01

    PET imaging has for many years been a versatile tool for non-invasive imaging of neuro-physiology and, indeed, whole body physiology. Quantitative PET imaging of trace amounts of radioactivity is scientifically elegant and can be very complex. This lecture focuses on whether and where this test is clinically useful. Because of the research tradition, PET imaging has been perceived as an 'expensive' test, as it costs more per scan than CT and MRI scans at most institutions. Such a superficial analysis is incorrect, however, as it is increasingly recognized that imaging costs, which in some circumstances will be increased by the use of PET, are only a relatively small component of patient care costs. Thus, PET may raise imaging costs and the number of imaging procedures in some settings, though PET may reduce imaging test numbers in other settings. However, the analysis must focus on the total costs of patient management. Analyses focused on total patient care costs, including cost of hospitalization and cost surgery as well as imaging costs, have shown that PET can substantially reduce total patient care costs in several settings. This is achieved by providing a more accurate diagnosis, and thus having fewer instances of an incorrect diagnosis resulting in subsequent inappropriate surgery or investigations. Several institutions have shown scenarios in which PET for tumor imaging is cost effective. While the specific results of the analyses vary based on disease prevalence and cost input values for each procedure, as well as the projected performance of PET, the similar results showing total care cost savings in the management of several common cancers, strongly supports the rational for the use of PET in cancer management. In addition, promising clinical results are forthcoming in several other illnesses, suggesting PET will have broader utility than these uses, alone. Thus, while PET is an 'expensive' imaging procedure and has considerable utility as a research

  1. A Clinical Study of Serum Thyroglobulin Levels in Patients with Thyroid Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Choong Kyu; Yu, Byung Hee; Lee, Woo Hyung; Yoo, Hyung Joon; Lee, Chong Suk [National Medical Canter, Seoul (Korea, Republic of)

    1983-03-15

    Serum thyroglobulin (Tg) was measured by radioimmunoassay in 81 patients with thyroid tumor who were treated in the department of Internal medicine of National Medical Center from January, 1981 to June, 1982. The results were as follows: 1) The mean serum thyroglobulin level in thyroid tumor was significantly higher than normal subjects (p<0.001). 2) The mean serum thyroglobulin level in benign tumor was lower than malignant tumor (p<0.05). 3) The thyroid carcinoma with metastasis had significant high level of serum thyroglobulin than without metastasis (p<0.001). 4) The mean postoperative serum thyroglobulin level was significantly lower than preoperative level (p<0.001). Data from our study show that serum thyroglobulin determination is useful for assessing the presence of malignant thyroid tumor, metastasis and the extent of residual or recurrent thyroid cancer after surgery.

  2. A Clinical Study of Serum Thyroglobulin Levels in Patients with Thyroid Tumor

    International Nuclear Information System (INIS)

    Lee, Choong Kyu; Yu, Byung Hee; Lee, Woo Hyung; Yoo, Hyung Joon; Lee, Chong Suk

    1983-01-01

    Serum thyroglobulin (Tg) was measured by radioimmunoassay in 81 patients with thyroid tumor who were treated in the department of Internal medicine of National Medical Center from January, 1981 to June, 1982. The results were as follows: 1) The mean serum thyroglobulin level in thyroid tumor was significantly higher than normal subjects (p<0.001). 2) The mean serum thyroglobulin level in benign tumor was lower than malignant tumor (p<0.05). 3) The thyroid carcinoma with metastasis had significant high level of serum thyroglobulin than without metastasis (p<0.001). 4) The mean postoperative serum thyroglobulin level was significantly lower than preoperative level (p<0.001). Data from our study show that serum thyroglobulin determination is useful for assessing the presence of malignant thyroid tumor, metastasis and the extent of residual or recurrent thyroid cancer after surgery.

  3. A European multi-language initiative to make the general population aware of independent clinical research

    DEFF Research Database (Denmark)

    Mosconi, Paola; Antes, Gerd; Barbareschi, Giorgio

    2016-01-01

    2. An animated film about clinical trials, dubbed in the 23 official languages of the European Community, and an interactive tutorial 3. An inventory of resources, available in 23 languages, searchable by topic, author, and media type 4. Two educational games for young people, developed in six......BACKGROUND: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. METHODS: Participants in the ECRAN...... materials and tools, making them freely available under a Creative Commons licence. RESULTS: The principal communication materials developed were: 1. A website ( http://ecranproject.eu ) in six languages, including a Media centre section to help journalists to disseminate information about the ECRAN project...

  4. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  5. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome).

    Science.gov (United States)

    Buchanan, Daniel D; Rosty, Christophe; Clendenning, Mark; Spurdle, Amanda B; Win, Aung Ko

    2014-01-01

    Carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome). MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening) is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification) and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic

  6. Klf5 deletion promotes Pten deletion-initiated luminal-type mouse prostate tumors through multiple oncogenic signaling pathways.

    Science.gov (United States)

    Xing, Changsheng; Ci, Xinpei; Sun, Xiaodong; Fu, Xiaoying; Zhang, Zhiqian; Dong, Eric N; Hao, Zhao-Zhe; Dong, Jin-Tang

    2014-11-01

    Krüppel-like factor 5 (KLF5) regulates multiple biologic processes. Its function in tumorigenesis appears contradictory though, showing both tumor suppressor and tumor promoting activities. In this study, we examined whether and how Klf5 functions in prostatic tumorigenesis using mice with prostate-specific deletion of Klf5 and phosphatase and tensin homolog (Pten), both of which are frequently inactivated in human prostate cancer. Histologic analysis demonstrated that when one Pten allele was deleted, which causes mouse prostatic intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth, increased cell proliferation, and caused more severe morphologic and molecular alterations. Homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Pten deletion alone expanded basal cell population in a tumor as reported, Klf5 deletion in the Pten-null background clearly reduced basal cell population while expanding luminal cell population. Global gene expression profiling, pathway analysis, and experimental validation indicate that multiple mechanisms could mediate the tumor-promoting effect of Klf5 deletion, including the up-regulation of epidermal growth factor and its downstream signaling molecules AKT and ERK and the inactivation of the p15 cell cycle inhibitor. KLF5 also appears to cooperate with several transcription factors, including CREB1, Sp1, Myc, ER and AR, to regulate gene expression. These findings validate the tumor suppressor function of KLF5. They also yield a mouse model that shares two common genetic alterations with human prostate cancer-mutation/deletion of Pten and deletion of Klf5.

  7. Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties.

    Science.gov (United States)

    Kedia, George T; Uckert, Stefan; Assadi-Pour, Farhang; Kuczyk, Markus A; Albrecht, Knut

    2013-02-01

    Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. However, a significant number of patients remain dissatisfied with the available therapies due a lack of efficacy or discomfort arising from adverse events. Several new PDE5 inhibitors, among which are avanafil (TA-1790), lodenafil, mirodenafil, udenafil, SLX-2101, JNJ-10280205 and JNJ-10287069, have recently been approved and introduced into the market or are in the final stages of their clinical development. Avanafil (marketed in the US under the brand name STENDRA(™)) has been developed by VIVUS Inc. (Mountain View, CA, USA) and has recently received approval from the US Food and Drug Administration (FDA) for use in the treatment of male ED. The drug has demonstrated improved selectivity for PDE5, is rapidly absorbed after oral administration with a fast onset of action and a plasma half-life that is comparable to sildenfil and vardenafil. In phase II and phase III clinical trials that included a large number of patients, avanafil has been shown to be effective and well tolerated. Owing to its favorable pharmacodynamic and pharmacokinetic profile, avanafil is considered as a promising new option in the treatment of ED. The present article summarizes the initial data and clinical key properties of avanafil.

  8. Impact of the Pharmacy Practice Model Initiative on Clinical Pharmacy Specialist Practice.

    Science.gov (United States)

    Jacobi, Judith; Ray, Shaunta'; Danelich, Ilya; Dodds Ashley, Elizabeth; Eckel, Stephen; Guharoy, Roy; Militello, Michael; O'Donnell, Paul; Sam, Teena; Crist, Stephanie M; Smidt, Danielle

    2016-05-01

    This paper describes the goals of the American Society of Health-System Pharmacists' Pharmacy Practice Model Initiative (PPMI) and its recommendations for health-system pharmacy practice transformation to meet future patient care needs and elevate the role of pharmacists as patient care providers. PPMI envisions a future in which pharmacists have greater responsibility for medication-related outcomes and technicians assume greater responsibility for product-related activities. Although the PPMI recommendations have elevated the level of practice in many settings, they also potentially affect existing clinical pharmacists, in general, and clinical pharmacy specialists, in particular. Moreover, although more consistent patient care can be achieved with an expanded team of pharmacist providers, the role of clinical pharmacy specialists must not be diminished, especially in the care of complex patients and populations. Specialist practitioners with advanced training and credentials must be available to model and train pharmacists in generalist positions, residents, and students. Indeed, specialist practitioners are often the innovators and practice leaders. Negotiation between hospitals and pharmacy schools is needed to ensure a continuing role for academic clinical pharmacists and their contributions as educators and researchers. Lessons can be applied from disciplines such as nursing and medicine, which have developed new models of care involving effective collaboration between generalists and specialists. Several different pharmacy practice models have been described to meet the PPMI goals, based on available personnel and local goals. Studies measuring the impact of these new practice models are needed. © 2016 Pharmacotherapy Publications, Inc.

  9. Pseudoanaplastic tumors of bone

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Won-Jong [Uijongbu St. Mary Hospital, The Catholic University of Korea, Department of Orthopaedic Surgery, Gyunggido, 480-821 (Korea); Mirra, Joseph M. [Orthopaedic Hospital, Orthopedic Oncology, Los Angeles, California (United States)

    2004-11-01

    To discuss the concept of pseudoanaplastic tumors of bone, which pathologically show hyperchromatism and marked pleomorphism with quite enlarged, pleomorphic nuclei, but with no to extremely rare, typical mitoses, and to propose guidelines for their diagnosis. From a database of 4,262 bone tumors covering from 1971 to 2001, 15 cases of pseudoanaplastic bone tumors (0.35% of total) were retrieved for clinical, radiographic and pathologic review. Postoperative follow-up after surgical treatment was at least 3 years and a maximum of 7 years. There were eight male and seven female patients. Their ages ranged from 10 to 64 years with average of 29.7 years. Pathologic diagnoses of pseudoanaplastic variants of benign bone tumors included: osteoblastoma (4 cases), giant cell tumor (4 cases), chondromyxoid fibroma (3 cases), fibrous dysplasia (2 cases), fibrous cortical defect (1 case) and aneurysmal bone cyst (1 case). Radiography of all cases showed features of a benign bone lesion. Six cases, one case each of osteoblastoma, fibrous dysplasia, aneurysmal bone cyst, chondromyxoid fibroma, giant cell tumor and osteoblastoma, were initially misdiagnosed as osteosarcoma. The remaining cases were referred for a second opinion to rule out sarcoma. Despite the presence of significant cytologic aberrations, none of our cases showed malignant behavior following simple curettage or removal of bony lesions. Our observation justifies the concept of pseudoanaplasia in some benign bone tumors as in benign soft tissue tumors, especially in their late evolutionary stage when bizarre cytologic alterations strongly mimic a sarcoma. (orig.)

  10. Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management

    Directory of Open Access Journals (Sweden)

    Manuela Gaebler

    2017-09-01

    Full Text Available Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.

  11. Intensity-modulated radiation therapy (IMRT) for locally advanced paranasal sinus tumors: incorporating clinical decisions in the optimization process

    International Nuclear Information System (INIS)

    Tsien, Christina; Eisbruch, Avraham; McShan, Daniel; Kessler, Marc; Marsh, Robin C.; Fraass, Benedick

    2003-01-01

    Purpose: Intensity-modulated radiotherapy (IMRT) plans require decisions about priorities and tradeoffs among competing goals. This study evaluates the incorporation of various clinical decisions into the optimization system, using locally advanced paranasal sinus tumors as a model. Methods and Materials: Thirteen patients with locally advanced paranasal sinus tumors were retrospectively replanned using inverse planning. Two clinical decisions were assumed: (1) Spare both optic pathways (OP), or (2) Spare only the contralateral OP. In each case, adequate tumor coverage (treated to 70 Gy in 35 fractions) was required. Two beamlet IMRT plans were thus developed for each patient using a class solution cost function. By altering one key variable at a time, different levels of risk of OP toxicity and planning target volume (PTV) compromise were compared in a systematic manner. The resulting clinical tradeoffs were analyzed using dosimetric criteria, tumor control probability (TCP), equivalent uniform dose (EUD), and normal tissue complication probability. Results: Plan comparisons representing the two clinical decisions (sparing both OP and sparing only the contralateral OP), with respect to minimum dose, TCP, V 95 , and EUD, demonstrated small, yet statistically significant, differences. However, when individual cases were analyzed further, significant PTV underdosage (>5%) was present in most cases for plans sparing both OP. In 6/13 cases (46%), PTV underdosage was between 5% and 15%, and in 3 cases (23%) was greater than 15%. By comparison, adequate PTV coverage was present in 8/13 cases (62%) for plans sparing only the contralateral OP. Mean target EUD comparisons between the two plans (including 9 cases where a clinical tradeoff between PTV coverage and OP sparing was required) were similar: 68.6 Gy and 69.1 Gy, respectively (p=0.02). Mean TCP values for those 9 cases were 56.5 vs. 61.7, respectively (p=0.006). Conclusions: In IMRT plans for paranasal sinus tumors

  12. Initial Virologic Response and HIV Drug Resistance Among HIV-Infected Individuals Initiating First-line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India

    Science.gov (United States)

    Hingankar, Nitin K.; Thorat, Smita R.; Deshpande, Alaka; Rajasekaran, S.; Chandrasekar, C.; Kumar, Suria; Srikantiah, Padmini; Chaturbhuj, Devidas N.; Datkar, Sharda R.; Deshmukh, Pravin S.; Kulkarni, Smita S.; Sane, Suvarna; Reddy, D. C. S.; Garg, Renu; Jordan, Michael R.; Kabra, Sandhya; Paranjape, Ramesh S.

    2012-01-01

    Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART. PMID:22544202

  13. Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

    Science.gov (United States)

    McCabe, Martin G.; Bäcklund, L. Magnus; Leong, Hui Sun; Ichimura, Koichi; Collins, V. Peter

    2011-01-01

    Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies. PMID:21292688

  14. Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications.

    Science.gov (United States)

    Vaupel, Peter; Mayer, Arnulf

    2014-01-01

    Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development of aggressive phenotypes and treatment resistance. Based on underlying mechanisms and their duration, two main types of hypoxia have been identified, coexisting with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly caused by diffusion limitations due to enlarged diffusion distances and adverse diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh- vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or flow stop (e.g., due to disturbed Starling forces or intratumor solid stress). Acute hypoxia mainly results from transient disruptions in perfusion (e.g., vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or short-term contractions of the interstitial matrix. In each of these hypoxia subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient supply, waste removal, delivery of anticancer or diagnostic agents, and repair competence can be impaired or may not be affected. This detailed differentiation of tumor hypoxia may impact on our understanding of tumor biology and may aid in the development of novel treatment strategies, tumor detection by imaging and tumor targeting, and is thus of great clinical relevance.

  15. Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: Clinical outcome

    International Nuclear Information System (INIS)

    Voort van Zyp, Noelle C. van der; Prevost, Jean-Briac; Hoogeman, Mischa S.; Praag, John; Holt, Bronno van der; Levendag, Peter C.; Klaveren, Robertus J. van; Pattynama, Peter; Nuyttens, Joost J.

    2009-01-01

    Purpose: To report the clinical outcome of treatment using real-time tumor tracking for 70 patients with inoperable stage I non-small cell lung cancer (NSCLC). Materials and methods: Seventy inoperable patients with peripherally located early-stage NSCLC were treated with 45 or 60 Gy in three fractions using CyberKnife. Pathology was available in 51% of patients. Thirty-nine patients had a T1-tumor and 31 had a T2-tumor. Markers were placed using the vascular, percutaneous intra-, or extra-pulmonary approach, depending on the risk of pneumothorax. Results: The actuarial 2-year local control rate for patients treated with 60 Gy was 96%, compared to 78% for patients treated with a total dose of 45 Gy (p = 0.197). All local recurrences (n = 4) occurred in patients with T2-tumors. Overall survival for the whole group at two years was 62% and the cause specific survival was 85%. The median follow-up was 15 months. Grade 3 toxicity occurred in two patients (3%) after marker placement. Treatment-related late grade 3 toxicity occurred in 7 patients (10%). No grade ≥4 toxicity occurred. Conclusion: Excellent local control of 96% at 1- and 2-years was achieved using 60 Gy in three fractions for NSCLC patients treated with the real-time tumor tracking. Toxicity was low.

  16. Role of chemical carcinogens in epithelial and mesenchymal neoplasms with tumor initiation-promotion protocol and the effect of 13-cis retinoic acid in chemo prevention

    International Nuclear Information System (INIS)

    Bukhari, S.M.H.; Shahzad, S.Q.; Naeem, S.; Qureshi, G.R.; Naveed, I.A.

    2002-01-01

    Objective: To study the effects of chemical carcinogens on epithelial and mesenchymal tumorigenesis with tumor initiation-promotion protocol and the use of 13-cis retinoic acid as a chemo preventive agent. Design: It was an experimental study. Place and Duration of Study: The study was conducted at Postgraduate Medical Institute (PGML) Lahore for 20 weeks. Materials and Methods: Sixty albino rats were divided into six groups of ten of animals each. First group of animals (control) was not given carcinogens and 13-cis retinoic acid in second group DMBA was applied on the dorsal skin in repeated dos of 100 mu g/ml in acetone, twice a weak. In the third group DMBA was given 100 mu g/ml as single dose while TPA was given 10 mu g//ml in acetone, twice a weak after two weeks of DMBA applications. In fourth group only DMBA 100 mu g/ml in acetone was applied as a single dose. In fifth and sixth groups 13-cis retinoic acid was given topically before and after the application of DMBA and TPA. Results: First and fourth groups did not develop any tumor. In second groups 2 animals developed malignant fibrous histiocytoma, 4 squamous cell carcinoma while 1 dysphasia and 1 carcinoma in situ. Third group developed osteoma (3 animals), papilloma (3 animals, squamous cell carcinoma (01) and dysplasia (01). Conclusion: Our results showed that DMBA acts as tumor initiator while TPA as promoter. DMBA also produces tumors itself when given alone in repeated doses. The chemical carcinogens are not only a cause of epithelial carcinogenesis but also responsible for mesenchymal tumorigenesis. 13 cis retinoic acid was equally effective in both stages of tumorigenesis. It also prevents malignant conversion of chemically induced benign tumors. (author)

  17. Clinical Evaluation of a Fully-automatic Segmentation Method for Longitudinal Brain Tumor Volumetry

    Science.gov (United States)

    Meier, Raphael; Knecht, Urspeter; Loosli, Tina; Bauer, Stefan; Slotboom, Johannes; Wiest, Roland; Reyes, Mauricio

    2016-03-01

    Information about the size of a tumor and its temporal evolution is needed for diagnosis as well as treatment of brain tumor patients. The aim of the study was to investigate the potential of a fully-automatic segmentation method, called BraTumIA, for longitudinal brain tumor volumetry by comparing the automatically estimated volumes with ground truth data acquired via manual segmentation. Longitudinal Magnetic Resonance (MR) Imaging data of 14 patients with newly diagnosed glioblastoma encompassing 64 MR acquisitions, ranging from preoperative up to 12 month follow-up images, was analysed. Manual segmentation was performed by two human raters. Strong correlations (R = 0.83-0.96, p < 0.001) were observed between volumetric estimates of BraTumIA and of each of the human raters for the contrast-enhancing (CET) and non-enhancing T2-hyperintense tumor compartments (NCE-T2). A quantitative analysis of the inter-rater disagreement showed that the disagreement between BraTumIA and each of the human raters was comparable to the disagreement between the human raters. In summary, BraTumIA generated volumetric trend curves of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments comparable to estimates of human raters. These findings suggest the potential of automated longitudinal tumor segmentation to substitute manual volumetric follow-up of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments.

  18. Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis.

    Science.gov (United States)

    Thariani, Rahber; Henry, Norah Lynn; Ramsey, Scott D; Blough, David K; Barlow, Bill; Gralow, Julie R; Veenstra, David L

    2013-05-01

    Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors. We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation.

  19. Radiological diagnostics of skeletal tumors

    International Nuclear Information System (INIS)

    Uhl, M.; Herget, G.W.

    2008-01-01

    The book contains contributions concerning the following topics: 1. introduction and fundamentals: WHO classification of bone tumors, imaging diagnostics and their function; localization, typical clinical and radiological criteria, TNM classification and status classification, invasive tumor diagnostics; 2. specific tumor diagnostics: chondrogenic bone tumors, osseous tumors, connective tissue bony tumors, osteoclastoma, osteomyelogenic bone tumors, vascular bone tumors, neurogenic bone tumors, chordoma; adamantinoma of the long tubular bone; tumor-like lesions, bony metastases, bone granulomas, differential diagnostics: tumor-like lesions

  20. Understanding managerial behaviour during initial steps of a clinical information system adoption.

    Science.gov (United States)

    Rodríguez, Charo; Pozzebon, Marlei

    2011-06-17

    While the study of the information technology (IT) implementation process and its outcomes has received considerable attention, the examination of pre-adoption and pre-implementation stages of configurable IT uptake appear largely under-investigated. This paper explores managerial behaviour during the periods prior the effective implementation of a clinical information system (CIS) by two Canadian university multi-hospital centers. Adopting a structurationist theoretical stance and a case study research design, the processes by which CIS managers' patterns of discourse contribute to the configuration of the new technology in their respective organizational contexts were longitudinally examined over 33 months. Although managers seemed to be aware of the risks and organizational impact of the adoption of a new clinical information system, their decisions and actions over the periods examined appeared rather to be driven by financial constraints and power struggles between different groups involved in the process. Furthermore, they largely emphasized technological aspects of the implementation, with organizational dimensions being put aside. In view of these results, the notion of 'rhetorical ambivalence' is proposed. Results are further discussed in relation to the significance of initial decisions and actions for the subsequent implementation phases of the technology being configured. Theoretical and empirically grounded, the paper contributes to the underdeveloped body of literature on information system pre-implementation processes by revealing the crucial role played by managers during the initial phases of a CIS adoption.

  1. Diffusion-weighted magnetic resonance imaging for the initial characterization of non-fatty soft tissue tumors: correlation between T2 signal intensity and ADC values

    Energy Technology Data Exchange (ETDEWEB)

    Gondim Teixeira, Pedro Augusto [Service d' Imagerie Guilloz, CHU Nancy, Nancy (France); Universite de Lorraine, IADI, UMR S 947, Vandoeuvre-les-Nancy (France); Gay, Frederique; Blum, Alain [Service d' Imagerie Guilloz, CHU Nancy, Nancy (France); Chen, Bailiang; Felblinger, Jacques [Universite de Lorraine, IADI, UMR S 947, Vandoeuvre-les-Nancy (France); Zins, Marie [University Versailles St-Quentin, Versailles (France); Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Villejuif (France); Sirveaux, Francois [Centre Chirurgical Emile Galle, Service de Chirurgie Traumatologique et Orthopedique, Nancy (France)

    2016-02-15

    To evaluate the performance of quantitative diffusion-weighted imaging (DWI) correlated with T2 signal in differentiating non-fatty benign from malignant tumors. A total of 76 patients with a histologically confirmed non-fatty soft tissue tumors (46 benign and 30 malignant) were prospectively included in this ethics committee approved study. All patients signed an informed consent and underwent MRI with DWI with two b values (0 and 600). ADC values from the solid components of these tumors were obtained and were correlated with the lesion's signal intensity on T2-weighted fat-saturated sequences. ADC values were obtained from adjacent normal muscle to allow calculation of tumor/muscle ADC ratios. There were 58 hyperintense and 18 iso or hypointense lesions. All hypointense lesions were benign. The mean ADC values for benign and malignant tumors were 1.47 ± 0.54 x 10{sup -3} and 1.17 ± 0.38 x 10{sup -3} mm{sup 2}/s respectively (p < 0.005). The mean ADC ratio in benign iso or hypointense tumors was significantly lower than that of hyperintense ones (0.76 ± 0.21 versus 1.58 ± 0.82 - p < 0.0001). An ADC ratio lower than 0.915 was highly specific for malignancy (96.4 %), whereas an ADC ratio higher than 1.32 was highly sensitive for benign lesions (90 %). ADC analysis can be useful in the initial characterization of T2 hyperintense non-fatty soft tissue masses, although this technique alone is not likely to change patient management. (orig.)

  2. Monitoring of tumor microcirculation during fractionated radiotherapy in patients with rectal carcinomas: a clinical study using contrast enhanced MR imaging

    International Nuclear Information System (INIS)

    Vries, A. de; Judmaier, W.; Griebel, J.; Kremser, Ch.; Gneiting, T.; Peer, S.; Aichner, F.; Lukas, P.

    1996-01-01

    Purpose/Objective: Combined radio chemotherapy is a frequently used treatment scheme for malignant neoplasms. The purpose of using chemotherapeutics such as 5-FU during radiotherapy is to enhance the effectiveness of radiation. The effectiveness of this approach depends on the accumulation of the drugs within the tumor, which is governed by micro circulatory parameters. However, to date scheduling of chemotherapy application is based on empirical data. There is no clinical study available monitoring tumor microcirculation during fractionated radiotherapy. Contrast enhanced MR imaging in tumors provides not only a better understanding of tumor micro vascularity but is also a method to characterize the substance accumulation within the tumor matrix during radiotherapy. This could help to optimize the scheduling of chemotherapy application. Materials and Methods: Patients with clinical and histological proven rectal carcinoma underwent a preoperative combined radio chemotherapy up to a total dose of 39,4Gy, hyperfractionated with b.i.d., single dose 1,1Gy. The fields in box-technique included the rectal canal and adjacent lymph nodes. 5-FU (300mg/m 2 per treatment day) was given continuously parallel to irradiation. To evaluate the Gd-DTPA (Magnevist, Schering, Germany) concentration time curve after i.v. constant rate infusion (0,05 mmol/kg Gd-DTPA) we used an ultrafast T1-mapping sequence on a 1,5-T whole body imager (Magneton Vision, Siemens, Germany). The transaxial slice (thickness 5 mm) was chosen so that both tumor and arterial vessels could be clearly identified. Before, during and after the infusion 53 T1 maps were obtained within 40 min in intervals of 14s (35 scans) and 120s (15 scans). Assuming a linear relation between relaxation rate, R1=1/T1, and Gd-DTPA concentration, concentration time curves were evaluated for arterial blood and tumor. The patients underwent MR imaging before and in constant intervals during fractionated radiotherapy. As a first

  3. First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.

    Science.gov (United States)

    Schijns, Virgil E J C; Pretto, Chrystel; Devillers, Laurent; Pierre, Denis; Hofman, Florence M; Chen, Thomas C; Mespouille, Pascal; Hantos, Peter; Glorieux, Philippe; Bota, Daniela A; Stathopoulos, Apostolos

    2015-05-28

    Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine(®)), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Germ cell tumors in patients with disorders of sex development: Risk factors, initial developmental stages and targets for early diagnosis

    NARCIS (Netherlands)

    M.B.C.M. Cools (Martine)

    2006-01-01

    textabstractThis thesis describes the origin, identification and correct diagnosis of the earliest stages of malignant germ cell tumors, i.e. intra tubular germ cell neoplasia unclassified (ITGNU) and gonadoblastoma, in patients with disorders of sex development. Special attention is given to the

  5. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.

    2007-01-01

    Cyclin D1/cyclin-dependent kinase 2 (Cdk2) complexes are present at high frequency in human breast cancer cell lines, but the significance of this observation is unknown. This report shows that expression of a cyclin D1-Cdk2 fusion protein under the control of the mouse mammary tumor virus (MMITV...

  6. Differentiated thyroid cancer (papillary). Brain tumor metastasis as clinical onset. surgical treatment and "1"3"1I. 8 years disease-free

    International Nuclear Information System (INIS)

    Mena, D.; Pena, M.; Alvarez, L.; García del Rio, H.; Bruno, O.

    2015-01-01

    Introduction: The differentiated thyroid cancer is the most common endocrine neoplasia. The major manifestation belongs to the papillary variant (65-90%). The prognosis tends to be very favorable, with a mortality rate of 1.8 % and a disease-free rate up to 10 years of around 90-95 %. The distant metastasis in brain accounts for 0.1-5 %. There are no established protocols for the management of brain metastasis. Therapeutic options are: surgery, stereotactic radiotherapy / radiosurgery, and "1"3"1I. The successful management of this case is