Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling.

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Belharazem, Djeda; Grass, Albert; Paul, Cornelia; Vitacolonna, Mario; Schalke, Berthold; Rieker, Ralf J; Körner, Daniel; Jungebluth, Philipp; Simon-Keller, Katja; Hohenberger, Peter; Roessner, Eric M; Wiebe, Karsten; Gräter, Thomas; Kyriss, Thomas; Ott, German; Geserick, Peter; Leverkus, Martin; Ströbel, Philipp; Marx, Alexander

2017-10-27

The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1 high thymomas and TCs.

Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).

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Sergieva, Sonya; Robev, Bozhil; Dimcheva, Milena; Fakirova, Albena; Hristoskova, Radka

2016-01-01

Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

Optimal surgical approach to thymic malignancies: New trends challenging old dogmas.

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Ruffini, Enrico; Filosso, Pier Luigi; Guerrera, Francesco; Lausi, Paolo; Lyberis, Paraskevas; Oliaro, Alberto

2018-04-01

Until recently, the surgical approach to thymic tumors has remained basically unchanged. The collaborative effort led by ITMIG with the collaboration of regional and society-based interest groups (ESTS, JART) produced an enthusiastic surge of interest in testing the new technological advances in thoracic surgery and many historical dogmas in thymic surgery have been questioned and challenged. The present review addresses the new trends in the optimal surgical management of thymic tumors based on the review of the current literature. 1. Minimally-invasive techniques (MIT) including video-assisted thoracic surgery (VATS) and robotic-assisted thoracic Surgery (RATS) are now to be considered the standard of care in early-stage thymic tumors. MIT are no inferior to open approaches in terms of postoperative complications, loco-regional recurrence rates and survival. MIT are associated with a shorter length of stay, reduced intraoperative blood loss and better cosmetic results. 2. The adoption of the ITMIG/IASLC TNM staging system for thymic tumors requires a paradigm shift among thoracic surgeons to include regional lymphadenectomy according to the IASLC/ITMIG nodal map in the surgical management of thymic tumors. 3. A limited thymectomy instead of total thymectomy along with the removal of the thymic tumor in nonmyasthenic Stage I-II tumors has been proposed by some authors, although the results are not uniform. Until more mature data is available, adherence to the current guidelines recommending total thymectomy in addition to thymomectomy is always indicated. 4. In locally-advanced Stage IVa patients with pleural involvement, major pleural resections, including pleurectomy/decortication or extrapleural pneumonectomy are indicated, provided a complete resection of the pleural deposits is anticipated, usually in a multidisciplinary setting, with excellent long-term results. The incorporation of these new concepts and techniques in the surgical armamentarium of the

Thymic pathology and cardiac myxomas: Coincidence or a closer relationship?

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Moraitis, Sotirios D; Agrafiotis, Apostolos C; Pappas, Dimitrios; Pothitakis, Chrysovalantis; Stergianni, Maria; Koukis, Ioannis

2018-04-30

Myxomas are the most common benign cardiac tumors and are located more frequently in the left atrium. In the literature there are cases describing the coexistence of thymic tumors and cardiac myxomas. In the case reported herein, during the resection of a cardiac myxoma, an enlarged thymus gland was encountered and resected. The histological exam revealed a thymic hyperplasia. The aim of this case study is to assess the need of conducting further studies in order to identify a common histological pathway between thymic lesions and cardiac myxomas. The diagnosis of a cardiac myxoma could justify a further workup of the anterior mediastinum in order not to overlook a lesion of thymic origin.

Doubling time of thymic epithelial tumours on CT: correlation with histological subtype

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Choe, Jooae; Lee, Sang Min; Kim, Namkug; Do, Kyung-Hyun; Seo, Joon Beom [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Songpa-gu, Seoul (Korea, Republic of); Lim, Soyeoun [Ulsan University Hospital, Department of Radiology, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Choi, Se Hoon [University of Ulsan College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of)

2017-10-15

We retrospectively evaluated the doubling time (DT) of thymic epithelial tumours (TET) according to the histological subtype on CT. From January 2005 to June 2016, we enrolled 53 patients who had pathologically confirmed TET and at least two CT scans. Tumour size was measured using a two-dimensional method, and the DT was calculated. DTs were compared among histological subtypes, and factors associated with rapid tumour growth (DT <180 days) were assessed. In 42 of the 53 patients (79.2%) the tumours showed interval growth (>2 mm) during follow-up. The median DT for all tumours was 400 days (range 48-1,964 days). There were no significant differences in DT in relation to histological subtype (p = 0.177). When TETs were recategorized into three groups, i.e. low-risk thymomas (types A, AB, B1), high-risk thymomas (types B2, B3), and thymic carcinoma, DT was significantly different among the groups (median DT 436, 381 and 189 days, respectively; p = 0.031). Histological subtype (type B3 and thymic carcinoma) was the single independent predictor of rapid tumour growth. The majority of TETs grew during follow-up with variable and relatively slow growth rates. Histological features of aggressive behaviour significantly correlated with a decreased DT and rapid growth. circle The majority of thymic epithelial tumours grew during follow-up (79.2%, 42/53). (orig.)

Effect of Bcl11b genotypes and γ-radiation on the development of mouse thymic lymphomas

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Yoshikai, Yoshihiro; Sato, Toshihiro; Morita, Shinichi; Kohara, Yuki; Takagi, Ritsuo; Mishima, Yukio; Kominami, Ryo

2008-01-01

Bcl11b is a haploinsufficient tumor suppressor gene and expressed in many tissues such as thymus, brain and skin. Irradiated Bcl11b +/- heterozygous mice mostly develop thymic lymphomas, but the preference of Bcl11b inactivation for thymic lymphomas remains to be addressed. We produced Bcl11b +/- heterozygous and Bcl11b wild-type mice of p53 +/- background and compared their incidence of γ-ray induced thymic lymphomas. Majority of the tumors in p53 +/- mice were skin tumors, and only 5 (36%) of the 14 tumors were thymic lymphomas. In contrast, Bcl11b +/- p53 +/- doubly heterozygous mice developed thymic lymphomas at the frequency of 27 (79%) of the 34 tumors developed (P = 0.008). This indicates the preference of Bcl11b impairment for thymic lymphoma development. We also analyzed loss of the wild-type alleles in the 27 lymphomas, a predicted consequence given by γ-irradiation. However, the loss frequency was low, only six (22%) for Bcl11b and five (19%) for p53. The frequencies did not differ from those of spontaneously developed thymic lymphomas in the doubly heterozygous mice, though the latency of lymphoma development markedly differed between them. This suggests that the main contribution of irradiation at least in those mice is not for the tumor initiation by inducing allelic losses but probably for the promotion of thymic lymphoma development

Radiation carcinogenesis in mouse thymic lymphomas

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Kominami, Ryo; Niwa, Ohtsura

2006-01-01

Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

Mutational status of EGFR and KIT in thymoma and thymic carcinoma.

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Yoh, Kiyotaka; Nishiwaki, Yutaka; Ishii, Genichiro; Goto, Koichi; Kubota, Kaoru; Ohmatsu, Hironobu; Niho, Seiji; Nagai, Kanji; Saijo, Nagahiro

2008-12-01

This study was conducted to evaluate the prevalence of EGFR and KIT mutations in thymomas and thymic carcinomas as a means of exploring the potential for molecularly targeted therapy with tyrosine kinase inhibitors. Genomic DNA was isolated from 41 paraffin-embedded tumor samples obtained from 24 thymomas and 17 thymic carcinomas. EGFR exons 18, 19, and 21, and KIT exons 9, 11, 13, and 17, were analyzed for mutations by PCR and direct sequencing. Protein expression of EGFR and KIT was evaluated immunohistochemically. EGFR mutations were detected in 2 of 20 thymomas, but not in any of the thymic carcinomas. All of the EGFR mutations detected were missense mutations (L858R and G863D) in exon 21. EGFR protein was expressed in 71% of the thymomas and 53% of the thymic carcinomas. The mutational analysis of KIT revealed only a missense mutation (L576P) in exon 11 of one thymic carcinoma. KIT protein was expressed in 88% of the thymic carcinomas and 0% of the thymomas. The results of this study indicate that EGFR and KIT mutations in thymomas and thymic carcinomas are rare, but that many of the tumors express EGFR or KIT protein.

Intrapericardial primary thymic carcinoma in a 73-year-old man.

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Calderon, Ana Maria; Merchan, Juan Andres; Rozo, Juan Carlos; Guerrero, Cesar Ivan; Treistman, Bernardo; Sulak, Laura E; Cheong, Benjamin Y C; Rodríguez, German; Mesa, Andrés

2008-01-01

Thymic carcinoma is a rare, highly aggressive type of tumor that typically occurs in the anterior mediastinum. We describe the case of a 73-year-old man who presented with weakness, cough, dyspnea, anorexia, and weight loss. An echocardiogram showed an intrapericardial mass that occupied the space around the lateral walls of the left ventricle and distally compressed the right ventricle. Magnetic resonance imaging and a biopsy confirmed the presence of intrapericardial primary thymic carcinoma. The patient underwent surgical excision of the tumor and died of right ventricular rupture during the procedure. This case highlights the importance of considering thymic carcinoma whenever an otherwise unexplained intrapericardial mass is encountered.

Tumor carcinóide do timo - Caso clínico Thymic carcinoid - case report

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Lina Carvalho

2010-01-01

Full Text Available Os tumores neuroendócrinos primários representam cerca de 4% do total dos tumores do mediastino anterior, incluindo o timo, afectando mais homens que mulheres numa razão de 3:1 e apresentando uma maior incidência entre os 40 e os 60 anos. Antigamente classificados como timomas, desde 1972 são considerados um grupo distinto de neoplasias tímicas, podendo ser biologicamente activos, estando sobretudo associados à síndroma NEM-1 (19 a 25% dos doentes, sendo nestes casos mais agressivos. São descritos como tendo grande progressão local, recorrência e metástases em elevada percentagem de casos, o que determina um mau prognóstico. O estadiamento é o parâmetro mais importante para determinar a sobrevida. Tumores detectados em fase precoce e capsulados associam-se a um excelente prognóstico, enquanto em estádios avançados, localmente invasivos, têm prognóstico relativamente pobre. A remoção cirúrgica completa, para todos os tumores tímicos, é a base da terapêutica e o factor crítico para a sobrevivência a longo prazo, independentemente do tipo histológico. São uma causa de morte importante, nomeadamente os tumores associados a NEM-1 e síndroma de Cushing, e há autores que defendem a realização de timectomia profiláctica nestes doentes.Primary neuroendocrine tumours (carcinoid tumours account for about 4% of anterior mediastinal tumours concerning thymus localization. They appear to have a male predilection (3:1 ratio and occur mostly between 40 and 60 years of age. Classified primarily as thymomas, they have been considered a different group of thymic neoplasia since 1972. They can be biologically active, mostly associated with MEN-1 (19-25% of patients and more aggressive in these cases. As a locally invasive disease, with recurrence and metastasis in a high percentage of cases, it correlates with a poor prognosis. Staging is the most important determinant of survival. Encapsulated tumours diagnosed in early stages

Thymic enlargement in patients with hyperthyroidism

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Myung, Jae Sung; Goo, Jin Mo; Im, Jung Gi [College of medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, Mi Young [Sejong General Hospital, Seoul (Korea, Republic of); Park, Yang Hee [National Police Hospital, Seoul (Korea, Republic of)

2000-08-01

To evaluate the radiologic findings and clinical feasibility of thymic enlargement in patients with hyperthyroidism. Seven patients with hyperthyroidism and anterior mediastinal bulging revealed by chest radiography were evaluated. The CT findings were analyzed with regard to the shape of the anterior mediastinal mass, surrounding infiltration, and enlargement of mediastinal lymph nodes. Whether or not tumor markers (alpha-fetoprotein, beta-human chorionic gonadotrophin, and chorionic embryonic antigen) showed increased levels was determined, and the size and thickness of the anterior mediastinal mass were measured and compared with previously described age-matched thymus data. In addition, changes in the thyroid gland were evaluated. In all seven patients, anterior mediastinal masses were bi-lobed, with no surrounding infiltration or enlarged mediastinal lymph node, and tumor marker levels showed no increase. The masses were therefore considered to be thymus. In six patients, the size of the thymus exceeded two upper standard deviations of mean value and in one patient, it was smaller than this. In three patients, PCNB (percutaneous needle biopsy) revealed normal thymic tissue and in two, follow-up chest PA demonstrated no interval change. CT showed that in three patients, the thyroid glands were diffusely enlarged. In patients with hyperthyroidism, an anterior mediastinal mass seen on chest radiographs was due to thymic enlargement. The recognition of CT findings of thymic enlargement in such patients may avoid unnecessary biopsy. (author)

Preoperative CT prediction for Masaoka staging of thymic epithelial tumor

International Nuclear Information System (INIS)

Feng Zhan; Huang Zhen; Zhang Liang

2013-01-01

Objective: To discuss the value of CT prognosis on the Masaoka staging system of thymic epithelial tumors (TET) before surgical resection. Methods: The CT images of 102 patients with TET proved by surgery and pathology were reviewed retrospectively. The TET were reclassified according to Masaoka stage system. The size, homogeneity, sharp, contour, infiltration of surrounding tissue, and metastasis on CT were analyzed with Logistic analysis. The diagnostic value was also evaluated with a ROC curve. Results: Masaoka pathologic stages were stage Ⅰ for 36 (35.3 %), stage Ⅱ for 27 (26.5 %), stage Ⅲ for 30 (29.4 %), and stage Ⅳ for 9 (8.8 %). A multivariable Logistic regression model showed that TET with larger size of tumor (20/35, P = 0.0371, OR = 4.539), irregular or lobulated tumor contour (26/42, P = 0.0230, OR = 4.870), heterogeneous (21/33, P = 0.0154, OR = 6.020), infiltration of surrounding fat (25/32, P = 0.0019, OR = 14.005), and pleural seeding (11/11, P = 0.0032, OR = 36.153) were more likely to have stage Ⅲ or Ⅳ disease. The area under ROC curve was 0.940. Conclusions: The tumor CT imaging features can differentiate between stage Ⅰ, Ⅱ and stage Ⅲ, Ⅳ disease. This helps identified patients more likely to benefit from neoadjuvant therapy. (authors)

Minimally Invasive Surgery in Thymic Malignances

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Wentao FANG

2018-04-01

Full Text Available Surgery is the most important therapy for thymic malignances. The last decade has seen increasing adoption of minimally invasive surgery (MIS for thymectomy. MIS for early stage thymoma patients has been shown to yield similar oncological results while being helpful in minimize surgical trauma, improving postoperative recovery, and reduce incisional pain. Meanwhile, With the advance in surgical techniques, the patients with locally advanced thymic tumors, preoperative induction therapies or recurrent diseases, may also benefit from MIS in selected cases.

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

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Dhalapathy Sadacharan

2013-01-01

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

[Thymic carcinoma involving aortic arch; report of a case].

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Noriyuki, Toshio; Hamamoto, M; Takazawa, Y; Katoh, K; Hashimoto, M; Kuranishi, F; Nakahara, M; Fukuda, T; Ishizaki, Y; Okuda, H; Akimoto, E; Yonehara, S

2009-05-01

Adenocarcinoma of the thymus is a very rare malignant tumor. The standard treatment for advanced thymic carcinoma has not yet been established, and the prognosis is poor. We report a case of thymic carcinoma that involving the aortic arch and the innominate vein. A 78-year-old woman was admitted to our hospital complaining of hoarseness in April 2007. The computed tomography (CT) scan showed an anterior mediastinal tumor contiguous to the aortic arch and the innominate vein with swelling lymphnodes. Microspcopic examinations of specimens obtained by CT-guided needle biopsy revealed poorly differenciated adenocarcinoma. The carcinoembryonic antigen (CEA) level of serum elevated at 54.9 ng/ml. Thymic carcinoma was diagnosed. The chemoradiotherapy [concurrent, carboplatin (CBDCA) + paclitaxel(TXL)-->vinorelbine (NVB), 60 Gy] was performed, but the effect of the therapy was limited. The resection of the tumor with a part of aortic arch and other peripheral tissues was performed in Augast 2007. The postoperative course was uneventful and the CEA level of serum lowered to the normal. She was discharged 30 days after surgery.

Computed tomography of thymic abnormalities: review of 10 patients

International Nuclear Information System (INIS)

Marins, J.L.C.; Brito Pacheco, E.M. de; Cazerta, N.M.G.; Silva, M.J.G. da

1990-01-01

Chest radiographs and computed tomographic scans of the mediastinum were correlated with pathologic findings of the thymus following thymectomy in 10 patients with thymic disease. There were five patients with thymoma, four with thymic hiperplasia and one with benign thymic cyst. Computed tomography shoud be the imaging method of choice following plain chest radiographs when a suspect thymic abnormality requires further evaluation. Recognition of variations in the normal location, size, shape and density of the thymus prevents misinterpretation as abnormal mediastinal mass. Furthermore, knowledge of the normal computed tomography appearance has proved helpful in evaluating thymic abnormalities. (author)

Genetic Regulation of Development of Thymic Lymphomas Induced by N‐Propyl‐N‐nitrosourea in the Rat

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Fukami, Hiroko; Nishimura, Mayumi; Matsuyama, Mutsushi

1995-01-01

To clarify the linkage between Hbb and Tls‐1 (thymic lymphoma susceptible‐1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N‐propyl‐N‐nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls‐1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY × BUF) × WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls‐3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls‐3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls‐3 may not be identical with Tls‐1 and other genes known to be relevant to thymic tumors, but its relationship with Tls‐2 remains obscure. PMID:7559080

Isolated splenic metastasis from a thymic carcinoma: A case report.

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Chen, Dongmei; Meng, Xiangying; Zhao, Yaowei; Wu, Shikai

2016-09-01

Thymic carcinomas are rare tumors that arise in the anterior mediastinum. Most of these malignancies develop local metastases limited in the thorax. Splenic metastases from thymic carcinomas are extremely rare. Here we report a case of isolated splenic metastasis from a 38-year-old female patient with Stage IV thymic carcinoma, who was treated with chemoradiotherapy. At twenty-2 months follow-up, the patient was found to have an isolated spleen metastasis, which was treated by Cyberknife with a reduced size of the metastasis, representing a partial response. Although splenic metastasis is a rare phenomenon, physicians need to be aware of the possibility of such metastases.

Heat shock protein 90-sheltered overexpression of insulin-like growth factor 1 receptor contributes to malignancy of thymic epithelial tumors.

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Breinig, Marco; Mayer, Philipp; Harjung, Andreas; Goeppert, Benjamin; Malz, Mona; Penzel, Roland; Neumann, Olaf; Hartmann, Arndt; Dienemann, Hendrik; Giaccone, Giuseppe; Schirmacher, Peter; Kern, Michael André; Chiosis, Gabriela; Rieker, Ralf Joachim

2011-04-15

The underlying molecular mechanisms of thymic epithelial malignancies (TEMs) are poorly understood. Consequently, there is a lack of efficacious targeted therapies and patient prognosis remains dismal, particularly for advanced TEMs. We sought to investigate protumorigenic mechanism relevant to this understudied cancer. Recently established cell lines derived from thymic epithelial tumors were used as a model system. The antitumor activity of specific heat shock protein 90 (Hsp90) inhibitors was investigated by an analysis of cell viability, cell cycle, and apoptosis using MTT-assays and flow cytometry. Western blotting was used to investigate the altered expression of Hsp90 clients. Pharmacological inhibitors against select Hsp90 clients, as well as RNAi, were employed to test the relevance of each client independently. Tissue microarray analysis was performed to match the in vitro findings with observations obtained from patient-derived samples. Hsp90 inhibition significantly reduces cell viability of thymic carcinoma cells, induces cell cycle arrest and apoptosis, and blocks invasiveness. Hsp90 inhibition triggers the degradation of multiple oncogenic clients, for example insulin-like growth factor 1 receptor (IGF-1R), CDK4, and the inactivation of PI3K/Akt and RAF/Erk signaling. Mechanistically, the IGF/IGF-1R-signaling axis contributes to the establishment of the antiapoptotic phenotype of thymic cancer cells. Finally, IGF-1R is overexpressed in advanced TEMs. We have unraveled a novel protumorigenic mechanism in TEMs, namely Hsp90-capacitated overexpression of IGF-1R, which confers apoptosis evasion in malignant thymic epithelial cells. Our data indicate that Hsp90 inhibition, which simultaneously blocks multiple cancer hallmarks, represents a therapeutic strategy in TEMs that may merit evaluation in clinical trials. ©2011 AACR.

Anti-apoptotic signature in thymic squamous cell carcinomas – functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

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Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfried; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

2016-01-01

The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might ...

Sonographic measurement of thymic size in healthy Korean neonates

International Nuclear Information System (INIS)

Seo, Hyun Joo; Yoon, Dae Young; Han, Dae Hee; Han, Sang Wook; Kim, Ho Chul; Kim, Young Mook; Choi, Chul Soon; Bae, Sang Hoon

2001-01-01

To assess the variation in thymic size in healthy Korean neonates by sonography and to study the possible correlation to clinical variables. This study was made of 112 healthy Korean neonates (94 full-term and 18 preterm), at less than a week of age. The transverse diameter of the thymus was measured in a transverse scan and the largest sagittal area was assessed in a longitudinal scan. The thymic index was defined as the product of these two values. Then, this index was compared to clinical variables, such as sex, delivery method (spontaneous delivery vs cesarian section), body weight, height, body surface area, head circumference, chest circumference, gestational age, and maternal age in both full-term and preterm groups. The thymic index was 9.6 ± 3.1 (range 3.1-20.2) in full-term and 4.2 ± 2.4 (range 0.9-9.9) in preterm neonates, respectively. The thymic index was positively correlated to the body weight (R=0.550 in full-term, R=0.669 in preterm) and body surface area (R=0.540 in full-term, R=0.674 in preterm) in both full-term and preterm groups (p<0.01). There was no statistically significant correlation to sex, delivery method, height, head circumference, chest circumference, maternal age or gestational age. The thymic index in Healthy Korean neonates as measured by sonography is significantly correlated to the body weight and body surface area of the neonate.

Platinum-based chemotherapy with or without thoracic radiation therapy in patients with unresectable thymic carcinoma

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Nakamura, Yoichi; Kunitoh, Hideo; Kubota, Kaoru

2000-01-01

Thymic carcinoma is a rare mediastinal neoplasm with poor prognosis. Although the clinical benefit of chemotherapy for thymic carcinoma is controversial, cisplatin-based chemotherapy with or without radiation therapy is ordinarily adopted in advanced cases. We evaluated the clinical outcome of platinum-based chemotherapy with or without radiation therapy in unresectable thymic carcinoma patients. Ten patients with unresectable thymic carcinoma were treated with platinum-based chemotherapy with or without radiation therapy in the National Cancer Center Hospital between 1989 and 1998. We reviewed the histological type, treatment, response and survival of these patients. Four of the 10 patients responded to chemotherapy and both the median progression-free survival period and the median response duration were 6.0 months. The median survival time was 11.0 months. There was no relationship between histological classification and prognosis. Platinum-based chemotherapy with or without thoracic radiation is, regardless of tumor histology, marginally effective in advanced thymic carcinoma patients, giving only a modest tumor response rate and short response duration and survival. (author)

Anti-apoptotic signature in thymic squamous cell carcinomas - functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c

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Bei eHuang

2013-12-01

Full Text Available The molecular pathogenesis of thymomas and thymic carcinomas (TCs is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and thymic carcinomas, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCC with a custom made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

{sup 18}F-FDG uptake on PET in primary mediastinal non-thymic neoplasm: A clinicopathological study

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Kaira, Kyoichi, E-mail: kkaira1970@yahoo.co.jp [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Abe, Masato [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakagawa, Kazuo; Ohde, Yasuhisa; Okumura, Takehiro [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Takahashi, Toshiaki; Murakami, Haruyasu; Shukuya, Takehito; Kenmotsu, Hirotsugu; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Hayashi, Isamu [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Oriuchi, Noboru [Department of Diagnostic Radiology and Nuclear medicine, Gunma University Graduate School of Medicine, Showa-machi, Maebashi 371-8511, Gunma (Japan); Endo, Masahiro [Division of Diagnostic Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Kondo, Haruhiko [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakajima, Takashi [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan)

2012-09-15

Background: The usefulness of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) has been investigated in thymic epithelial tumors. However, little is known about PET imaging of {sup 18}F-FDG in primary non-thymic mediastinal neoplasms. The aim of this study is to explore the clinicopathological significance of {sup 18}F-FDG PET in primary mediastinal (non-thymic) neoplasms. Methods: Twenty-one patients with mediastinal neoplasms who underwent {sup 18}F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1α); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); Akt/mTOR signaling pathway (p-Akt and p-mTOR); cell cycle control (p53). Results: Seventeen of 21 patients were imaged on PET system using {sup 18}F-FDG, but 4 patients with a histology of cyst showed nothing abnormal in PET scans. The histology of the resected tumors was as follows: 6 schwannoma, 3 teratoma, 4 cyst, 3 sarcoma, 1 undifferentiated carcinoma, 1 seminoma, 1 mediastinal goiter, 1 ganglioneuroma, and 1 Hodgkin lymphoma. {sup 18}F-FDG uptake was significantly correlated with Glut1, HIF-1α, EGFR, p-Akt and p-S6K. These biomarkers were highly expressed in schwannoma, teratoma and high grade malignancies, whereas all patients with cyst and ganglioneuroma had no positive expression of these biomarkers. High uptake of {sup 18}F-FDG was significant associated with Glut1, VEGF, EGFR, p-Akt, p-S6K and tumor maximal size. Conclusion: The amount of {sup 18}F-FDG uptake in primary mediastinal non-thymic neoplasms is determined by the presence of glucose metabolism (Glut1), hypoxia (HIF-1α) and upstream components of HIF-1α (EGFR, p-Akt and p-S6K)

Spontaneous rupture of thymic neuroendocrine carcinoma: A case report

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Park, Chan Yeong; Lee, In Jae; Min, Soo Kee [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

2015-11-15

Thymic neuroendocrine carcinoma (NEC) is a rare neoplasm with tendencies of local invasion and metastasis. Usually, it is detected incidentally or by its symptoms caused by mass effect. Rupture of the tumor is extremely rare. In this study, we report a case of a ruptured thymic NEC that was combined with a potentially fatal hemorrhage. This lesion was manifested as a progressive bulging of the right cardiac border on serial chest radiographs, and on CT as a large anterior mediastinal mass with heterogeneous enhancement, internal necrosis, and hematoma.

Cystic thymic diseases: CT manifestations

International Nuclear Information System (INIS)

Song, Soon Young; Choi, Yo Won; Jeon, Eui Yong; Jeon, Seok Chol; Seo, Heung Suk; Hahm, Chang Kok

1995-01-01

To describe CT findings and differential points of cystic thymic lesions. We evaluated retrospectively total 19 masses with well marginated cystic lesions at thymic area on CT scans. They were 10 teratomas, 3 congenital thymic cysts, 2 multilocular thymic cysts(associated with thymoma and myasthenia gravis in each), 2 cysts Assciated with thymic Hodgkin's lymphomas an ectopic parathyroid cyst, and an infected thymic cyst. The radiological abnormalities evaluated were thickness of the wall, presence or abscene of septa, mural nodule, solid component, calcification and fat component. All three cases of congenital thymic cysts and an ectopic parathyroid cyst appeared as thin-walled unilocular cyst with homogeneous internal density and without identifiable solid component. In multilocular thymic cyst, there were thick wall and solid components(n =2), thick internal septa and calcifications(n = 1). The cysts of teratomas manifested thick walls(n = 9), internal septa(n = 4), calcifications(n = 6), fat components(n = 4), and solid components(n = 4). Cysts in Hodgkin's diseases appeared as multilocular or unilocular and had thick wall and septa without calcification. Infected thymic cyst presented with multilocular cystic mass with identifiable wall and septa, calcification, and solid components. The thymic diseases with cystic lesion include teratomas, congenital thymic cysts, multilocular thymic cysts, parathyroid cyst, and Hodgkin's disease. Congenital thymic cyst and ectopic parathyroid cyst are thin-walled unilocular cystic lesions. Cystic lesions associated with teratoma, Hodgkin's disease, and multilocular thymic cyst are thick-walled cystic lesions with or without solid component

Cystic thymic diseases: CT manifestations

Energy Technology Data Exchange (ETDEWEB)

Song, Soon Young; Choi, Yo Won; Jeon, Eui Yong; Jeon, Seok Chol; Seo, Heung Suk; Hahm, Chang Kok [School of Medicine, Hanyang University, Seoul (Korea, Republic of)

1995-09-15

To describe CT findings and differential points of cystic thymic lesions. We evaluated retrospectively total 19 masses with well marginated cystic lesions at thymic area on CT scans. They were 10 teratomas, 3 congenital thymic cysts, 2 multilocular thymic cysts(associated with thymoma and myasthenia gravis in each), 2 cysts Assciated with thymic Hodgkin's lymphomas an ectopic parathyroid cyst, and an infected thymic cyst. The radiological abnormalities evaluated were thickness of the wall, presence or abscene of septa, mural nodule, solid component, calcification and fat component. All three cases of congenital thymic cysts and an ectopic parathyroid cyst appeared as thin-walled unilocular cyst with homogeneous internal density and without identifiable solid component. In multilocular thymic cyst, there were thick wall and solid components(n =2), thick internal septa and calcifications(n = 1). The cysts of teratomas manifested thick walls(n = 9), internal septa(n = 4), calcifications(n = 6), fat components(n = 4), and solid components(n = 4). Cysts in Hodgkin's diseases appeared as multilocular or unilocular and had thick wall and septa without calcification. Infected thymic cyst presented with multilocular cystic mass with identifiable wall and septa, calcification, and solid components. The thymic diseases with cystic lesion include teratomas, congenital thymic cysts, multilocular thymic cysts, parathyroid cyst, and Hodgkin's disease. Congenital thymic cyst and ectopic parathyroid cyst are thin-walled unilocular cystic lesions. Cystic lesions associated with teratoma, Hodgkin's disease, and multilocular thymic cyst are thick-walled cystic lesions with or without solid component.

Analysis of the expression level and methylation of tumor protein p53, phosphatase and tensin homolog and mutS homolog 2 in N-methyl-N-nitrosourea-induced thymic lymphoma in C57BL/6 mice.

Science.gov (United States)

Huo, Xueyun; Li, Zhenkun; Zhang, Shuangyue; Li, Changlong; Guo, Meng; Lu, Jing; Lv, Jianyi; Du, Xiaoyan; Chen, Zhenwen

2017-10-01

Tumorigenesis is often caused by somatic mutation or epigenetic changes in genes that regulate aspects of cell death, proliferation and survival. Although the functions of multiple tumor suppressor genes have been well studied in isolation, how these genes cooperate during the progression of a single tumor remains unclear in numerous cases. The present study used N-methyl-N-nitrosourea (MNU), one of the most potent mutagenic nitrosourea compounds, to induce thymic lymphoma in C57BL/6J mice. Subsequently, the protein expression levels of phosphatase and tensin homolog (PTEN), transformation protein 53 and mutS homolog 2 (MSH2) were evaluated concomitantly in the thymus, liver, kidney and spleen of MNU-treated mice by western blotting. To determine whether changes in expression level were due to aberrant epigenetic regulation, the present study further examined the methylation status of each gene by MassARRAY analysis. During the tumorigenesis process of an MNU-induced single thymic lymphoma, the expression level of PTEN was revealed to be reduced in thymic lymphoma samples but not in normal or non-tumor thymus tissue samples. Furthermore, a marked reduction of P53 expression levels were demonstrated in thymic lymphomas and spleens with a metastatic tumor. Conversely, MSH2 upregulation was identified only in liver, kidney, and spleen samples that were infiltrated by thymic lymphoma cells. Furthermore, the present study revealed that a number of 5'-C-phosphate-G-3' sites located in the promoter of aberrantly expressed genes had significantly altered methylation statuses. These results improve the understanding of the course of mutagen-induced cancer, and highlight that epigenetic regulation may serve an important function in cancer.

Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns

DEFF Research Database (Denmark)

Birk, Nina Marie; Nissen, Thomas Nørrelykke; Zingmark, Vera

2017-01-01

Background: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size...... with a large thymic size at birth. Conclusion: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity...... in the newborn....

Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

International Nuclear Information System (INIS)

Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho

2005-01-01

This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II ∼ IV or WHO tumor type B2 ∼ C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; ρ = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; ρ = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; ρ = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; ρ = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated

Application values of 99mTc-methoxyisobutylisonitrile imaging for differentiating benign and malignant thymic masses.

Science.gov (United States)

Lu, Chenghui; Wang, Xufu; Liu, Bin; Liu, Xinfeng; Wang, Guoming; Zhang, Qin

2017-08-01

The aim of the present study was to investigate the application value of 99m Tc-methoxyisobutylisonitrile (MIBI) imaging to differentiate between benign and malignant thymic masses. A total of 32 patients with space-occupying mediastinal masses were enrolled and early and delayed-phase images were collected following injection with the imaging agent. The tumor to background ratio (T/N) values at the different phases were also recorded. The sensitivity of the qualitative analysis to distinguish between benign and malignant thymic masses was 95.24%, with specificity as 90.91%. The T/N values in the early and delayed phases were not significantly different in the group with benign thymic masses, but demonstrated statistical significant differences in the groups with low- and intermediate-grade malignant thymic masses. The T/N values at the above early and delayed phase were significantly different between the benign and low-grade malignancy groups, as well as between low- and moderate-grade malignancy groups. Those between the benign and moderate-grade malignancy groups demonstrated no significant difference. 99m Tc-MIBI imaging was able to differentiate between benign and malignant thymic masses, and the simultaneous semi-quantitative analysis of the T/N values of the tumors may be able to initially determine the degree of malignancy of thymoma.

Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns

DEFF Research Database (Denmark)

Birk, Nina Marie; Nissen, Thomas Nørrelykke; Zingmark, Vera

2017-01-01

BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size...... to age 3 mo were parent-reported. RESULTS: BCG vaccination did not affect thymic size at age 3 mo, measured as TI. At birth, the number of lymphocytes, CD4+ T cells, CD8+ T cells, and RTEs were positively associated with TI and TWI. Furthermore, a reduced risk of infections up to age 3 mo was associated...... with a large thymic size at birth. CONCLUSION: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity...

Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting.

Science.gov (United States)

Imbimbo, Martina; Maury, Jean-Michel; Garassino, Marina; Girard, Nicolas

2018-02-02

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Thymic Carcinoma Management Patterns among International Thymic Malignancy Interest Group (ITMIG) Physicians with Consensus from the Thymic Carcinoma Working Group.

Science.gov (United States)

Shepherd, Annemarie; Riely, Gregory; Detterbeck, Frank; Simone, Charles B; Ahmad, Usman; Huang, James; Korst, Robert; Rajan, Arun; Rimner, Andreas

2017-04-01

Thymic carcinomas are rare epithelial malignancies with limited data to guide management. To identify areas of agreement and variability in current clinical practice, a 16-question electronic survey was given to members of the International Thymic Malignancy Interest Group (ITMIG). Areas of controversy were discussed with the Thymic Carcinoma Working Group and consensus was achieved, as described. A total of 100 ITMIG members responded. There was general agreement regarding the role for multimodality therapy with definitive surgical resection in physically fit patients with advanced but resectable disease. Areas of controversy included the need for histologic confirmation before surgery, the role of adjuvant therapy, the optimal first-line chemotherapy regimen, and the recommended treatment course for marginally resectable disease with invasion into the great vessels, pericardium, and lungs. The results of the questionnaire provide a description of the management of thymic carcinoma by 100 ITMIG members with a specific interest or expertise in thymic malignancies. Although there was agreement in some areas, clinical practice appears to vary significantly. There is a great need for collaborative research to identify optimal evaluation and treatment strategies. Given the need for multimodality therapy in many cases, a multidisciplinary discussion of the management of patients with thymic carcinoma is critical. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Significance of thymic scintigraphy

International Nuclear Information System (INIS)

Baba, Hiromi; Oshiumi, Yoshihiko; Nakayama, Chikashi; Morita, Kazunori; Koga, Ichinari

1978-01-01

Thymic scintigraphy by 67 Ga-citrate and 75 Se-methionine was done on 6 cases of thymoma, and 5 cases of myasthenia gravis. Scan was positive on 5 of 6 cases of thymoma. All patients with malignant thymoma were positive. Among the 7 cases of myasthenia gravis, scintigrams revealed 2 thymomas and 1 hyperplasia on whom no thymic mass suspected. Thymic scintigraphy is useful examination when dealing with myasthenia gravis. (auth.)

Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies

International Nuclear Information System (INIS)

Gomez, Daniel R.; Komaki, Ritsuko

2012-01-01

For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use

Images in pediatrics: the thymic sail sign and thymic wave sign.

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Alves, Nuno D; Sousa, Marta

2013-01-01

The authors present a radiographic image portraying the "thymic sail sign" and the "thymic wave sign," both normal findings in infant radiographs and present a short description of these signs. These are distinguished from pathologic findings such as the "spinnaker-sail sign" in pneumomediastinum.

PPARgamma Deficiency Counteracts Thymic Senescence

Directory of Open Access Journals (Sweden)

David Ernszt

2017-11-01

Full Text Available Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma. This is supported by observations reporting that systemic PPARgamma activation accelerates thymic adipose involution. Therefore, we hypothesized that decreased PPARgamma activity could prevent thymic adipose involution, although it may trigger metabolic adverse effects. We have confirmed that both human and murine thymic sections show marked staining for PPARgamma at senior ages. We have also tested the thymic lobes of PPARgamma haplo-insufficient and null mice. Supporting our working hypothesis both adult PPARgamma haplo-insufficient and null mice show delayed thymic senescence by thymus histology, thymocyte mouse T-cell recombination excision circle qPCR and peripheral blood naive T-cell ratio by flow-cytometry. Delayed senescence showed dose–response with respect to PPARgamma deficiency. Functional immune parameters were also evaluated at senior ages in PPARgamma haplo-insufficient mice (null mice do not reach senior ages due to metabolic adverse affects. As expected, sustained and elevated T-cell production conferred oral tolerance and enhanced vaccination efficiency in senior PPARgamma haplo-insufficient, but not in senior wild-type littermates according to ELISA IgG measurements. Of note, humans also show increased oral intolerance issues and decreased protection by vaccines at senior ages. Moreover, PPARgamma haplo-insufficiency also exists in human known as a rare disease (FPLD3 causing metabolic adverse effects, similar to the mouse. When compared to age- and metabolic disorder-matched other patient samples (FPLD2 not affecting PPARgamma activity, FPLD3 patients showed increased human Trec (hTrec values by qPCR (within healthy human range suggesting delayed thymic senescence, in accordance with

Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas - Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c.

Science.gov (United States)

Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A; Rieker, Ralf J; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

2013-01-01

The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.

Thymic epithelial cells. I. Expression of strong suppressive (veto) activity in mouse thymic epithelial cell cultures

DEFF Research Database (Denmark)

Claesson, Mogens Helweg; Ropke, C

1990-01-01

We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level. It is conclu......We show that thymic epithelial cells grown under serum-free conditions in a chemically defined culture medium can act as veto cells in vitro. The veto activity of thymic epithelial cells results in inactivation of specific alloreactive cytotoxic T-cell precursors at the clonal level...

Inferior Vena Cava and Renal Vein Thrombosis Associated with Thymic Carcinoma

Directory of Open Access Journals (Sweden)

Vlad Teodor Berbecar

2017-01-01

Full Text Available Thymic tumors are rare mediastinal tumors that can present with a wide variety of symptoms. They can cause distant manifestations and are frequently associated with paraneoplastic syndromes. In our case, we describe the evolution of a 68-year-old male whose first manifestation was thrombosis of the inferior vena cava and renal veins. Thrombosis of large abdominal veins is rare, especially without being associated with any other comorbidity or risk factors.

Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas – Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c

Science.gov (United States)

Huang, Bei; Belharazem, Djeda; Li, Li; Kneitz, Susanne; Schnabel, Philipp A.; Rieker, Ralf J.; Körner, Daniel; Nix, Wilfred; Schalke, Berthold; Müller-Hermelink, Hans Konrad; Ott, German; Rosenwald, Andreas; Ströbel, Philipp; Marx, Alexander

2013-01-01

The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC. PMID:24427739

Computed tomography of thymic abnormalities

Energy Technology Data Exchange (ETDEWEB)

Schnyder, P.; Candardjis, G.

1987-05-01

Computed tomographic examinations of 38 patients with surgically and histologically proven diagnosis were reviewed. Twenty subjects (52%) had an invasive thymoma and 16% an hyperplastic thymus. Myasthenia gravis was present in 6 cases (16%) of thymic abnormalities, four (10,5%) with invasive thymoma and two (5%) with thymic hyperplasia. Graves' disease was also present in one case of thymic hyperplasia. We emphasize the contribution of CT to the diagnosis and the prognosis.

Computed tomography of thymic abnormalities

International Nuclear Information System (INIS)

Schnyder, P.; Candardjis, G.

1987-01-01

Computed tomographic examinations of 38 patients with surgically and histologically proven diagnosis were reviewed. Twenty subjects (52%) had an invasive thymoma and 16% an hyperplastic thymus. Myasthenia gravis was present in 6 cases (16%) of thymic abnormalities, four (10,5%) with invasive thymoma and two (5%) with thymic hyperplasia. Graves' disease was also present in one case of thymic hyperplasia. We emphasize the contribution of CT to the diagnosis and the prognosis. (orig.)

The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma

Energy Technology Data Exchange (ETDEWEB)

Janowski, M [Centre d' Etude de l' Energie Nucleaire, Mol (Belgium); Cox, R [Medical Research Council, Harwell (UK). Radiobiological Research Unit; Strauss, P G [GSF, Neuherberg (Germany, F.R.). Abt. fuer Molekulare Zellpathologie

1990-04-01

In mice, external X- or {gamma}-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking {alpha}-emitters may induce osteosarcomas, and to a lesser extent acute myeloid leukaemia. The paper reviews briefly some experimental data in respect to molecular mechanisms underlying these radio-carcinogenic processes. Thymic lymphomagenesis proceeds by an indirect mechanism in which recombinant proviruses could be involved. Myeloid leukaemogenesis is characterized by a very early putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumors often contain somatically acquired proviruses. (UK).

Flt3 ligand-receptor interaction is important for maintenance of early thymic progenitor numbers in steady-state thymopoiesis.

Science.gov (United States)

Kenins, Linda; Gill, Jason W; Holländer, Georg A; Wodnar-Filipowicz, Aleksandra

2010-01-01

T-cell production throughout life depends on efficient colonization and intrathymic expansion of BM-derived hematopoietic precursors. After irradiation-induced thymic damage, thymic recovery is facilitated by Flt3 ligand (FL), expressed by perivascular fibroblasts surrounding the thymic entry site of Flt3 receptor-positive progenitor cells. Whether intrathymic FL-Flt3 interactions play a role in steady-state replenishment of T cells remains unknown. Here, using competitive BM transplantation studies and fetal thymic organ cultures we demonstrated the continued numerical advantage of Flt3+ intrathymic T-cell precursors. Sub-kidney capsule thymic transplantation experiments, in which WT and FL-/- thymic lobes were grafted into FL-/- recipients, revealed that FL expression by the thymic microenvironment plays a role in steady-state thymopoiesis. The deficiency of the most immature thymic T-cell precursors correlated to upregulation of FL by thymic MTS15+ fibroblasts, suggesting that the number of Flt3+ progenitor cells may regulate the thymic expression of this cytokine. Together, these results show that FL expression by thymic stromal fibroblasts interacting with Flt3+ T-cell progenitors is important for the physiological maintenance of early T-cell development.

CT differentiation of invasive thymoma and thymic carcinoma

International Nuclear Information System (INIS)

Lee, Eun Jung; Jung, Gyoo Sik; Kim, Seong Min; Huh, Jin Do; Joh, Young Duk; Shin, Mi Jung; Kim, Jung Sik; Suh, Soo Jhi

1998-01-01

In order to determine the differential points between them, we analyzed the CT findings of invasive thymoma and thymic carcinoma. We retrospectively reviewed the CT scans of 14 patients with invasive thymoma and 15 with thymic carcinoma, confirmed by surgery(n=3D19) or percutaneous needle aspiration(n=3D10) between 1988 and 1996. CT findings were evaluated in each group for intrathoracic spread(posterior, direct posterior, and anterolateral), obliteration of the fat plane between the mass and vascular structures, vessel encasement, invasion of adjacent mediastinal structures, pleural implants, mediastinal nodes and distant metastasis. Direct posterior spread was more common in thymic carcinoma than invasive thymoma;it was seen in one case (7%) of invasive thymoma and 12(80%) of thymic carcinoma(p=3D0.00). Posterior spread was seen in six cases (43%) of in vasive thymoma and nine (60%) of thymic carcinoma. Anterolateral spread was seen only in two cases (13%) of thymic carcinoma. Obliteration of the fat plane was seen in nine cases (64%) of invasive thymoma and 14 (93%) of thymic carcinoma, while vessel encasement was seen in two cases (14%) of invasive thymoma and 13(87%) of thymic carcinoma(p=3D0.00). Invasion of adjacent structures was seen in two cases (14%) of invasive thymoma and eight (53%) of thymic carcinoma. Pleural implants were more common in invasive thymoma than thymic carcinoma, being seen in six cases (43%) of the former and one (7%) of the latter(p=3D0.04). Mediastinal lymphadenopathy was seen in three cases (21%) of invasive thymoma and ten (67%) of thymic carcinoma. Distant metastases were observed only in six cases (40%) of thymic carcinoma(p=3D0.02). Although differentiation between invasive thymoma and thymic carcinoma is difficult on the basis of CT findings, there are certain differential points. Thymic carcinomas showed a higher rate of direct posterior intrathoracic spread, vessel encasement, mediastinal nodes and distant metastases than

Gallium 67 uptake in thymic rebound

International Nuclear Information System (INIS)

Hurst, R.; Sabio, H.; Teates, C.D.

1988-01-01

We have reported a case of localized thymic enlargement and uptake of gallium 67 in a child who had received antineoplastic chemotherapy. The enlarged thymus showed normal histology, a picture consistent with thymic rebound after nonspecific stress. This case further demonstrates the need to consider thymic rebound as a cause of gallium 67 uptake in children with neoplastic diseases

Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

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Kong, Ling-Yan; Zhang, Wei; Zhou, Yue; Xu, Hai; Shi, Hai-Bin; Feng, Qing; Xu, Xiao-Quan; Yu, Tong-Fu

2018-04-01

To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADC HS-ROI ) and histogram-based approach. ADC histogram parameters included mean ADC (ADC mean ), median ADC (ADC median ), 10 and 90 percentile of ADC (ADC 10 and ADC 90 ), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADC mean , ADC median , ADC 10 , ADC 90 and ADC HS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC 10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

Apoptosis-promoted tumorigenesis: γ-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death

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Michalak, Ewa M.; Vandenberg, Cassandra J.; Delbridge, Alex R.D.; Wu, Li; Scott, Clare L.; Adams, Jerry M.; Strasser, Andreas

2010-01-01

Although tumor development requires impaired apoptosis, we describe a novel paradigm of apoptosis-dependent tumorigenesis. Because DNA damage triggers apoptosis through p53-mediated induction of BH3-only proteins Puma and Noxa, we explored their roles in γ-radiation-induced thymic lymphomagenesis. Surprisingly, whereas Noxa loss accelerated it, Puma loss ablated tumorigenesis. Tumor suppression by Puma deficiency reflected its protection of leukocytes from γ-irradiation-induced death, because...

Detection of chemotherapy-induced thymic changes in patients with metastasised testicular tumors by computed tomography

International Nuclear Information System (INIS)

Hendrickx, P.; Doehring, W.

1989-01-01

Serial thoracic CT scans of 100 patients suffering from testicular cancer revealed that the thymus appears to atrophy temporarily during administration of cytostatic agents. About two months after cessation of chemotherapy rebound enlargement of the thymus occurs and persists for about two years followed by a slow involution. Using a semiquantitative score system, thymic CT images of these patients were compared with that of 100 patients suffering from other malignancies, 100 patients without malignant disease and 52 patients with myasthenia gravis, taking into account the age-related changes of the size of the organ. Rebound thymic enlargement should not be misinterpreted as metastatic lymph nodes. (orig.) [de

Detection of chemotherapy-induced thymic changes in patients with metastasised testicular tumors by computed tomography

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Hendrickx, P.; Doehring, W.

1989-03-01

Serial thoracic CT scans of 100 patients suffering from testicular cancer revealed that the thymus appears to atrophy temporarily during administration of cytostatic agents. About two months after cessation of chemotherapy rebound enlargement of the thymus occurs and persists for about two years followed by a slow involution. Using a semiquantitative score system, thymic CT images of these patients were compared with that of 100 patients suffering from other malignancies, 100 patients without malignant disease and 52 patients with myasthenia gravis, taking into account the age-related changes of the size of the organ. Rebound thymic enlargement should not be misinterpreted as metastatic lymph nodes.

Massive thymic hemorrhage and hemothorax occurring in utero.

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Gargano, Giancarlo; Paltrinieri, Anna Lucia; Gallo, Claudio; Di Pancrazio, Luciana; Roversi, Maria Federica; Ferrari, Fabrizio

2015-11-14

Thymic enlargement is a common and physiological finding in children and neonates' X-rays, but it is usually asymptomatic. Occasionally it can cause respiratory distress. In most cases the aetiology of this expansion remains unclear and it is diagnosed as a thymic hyperplasia. True thymic hyperplasia is defined as a gland expansion, both in size and weight, while maintaining normal microscopic architecture. Often it is a diagnosis of exclusion and prognosis is good. Thymic haemorrhage is an unusual condition related to high foetal and neonatal mortality. We report a case of spontaneous massive thymic haemorrhage in a newborn developing at birth acute respiratory distress associated with severe bilateral haemothorax. Thymic enlargement was evident after pleural evacuation and confirmed by radiographic, Computed Tomography (CT) images and Magnetic Resonance Imaging (MRI) sequences. The spontaneous resolution of this enlargement seen with CT scan and MRI sequences suggested a thymic haemorrhage; surgery was not necessary. Thymic haemorrhage should be considered in newborn infants with pleural effusion, mediastinal space enlargement and Respiratory Distress.

nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma

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Go Makimoto

2014-01-01

Full Text Available We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

Inhibitory effects of a polypeptide thymic factor on the development of 7,12-dimethylbenz(a)anthragene-induced mammary adenocarcinoma in female rats

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Anisimov, V.N.; Danetskaya, E.V.; Morozov, V.G.; Khavinson, V.Kh.

1980-01-01

It has come to be recognized that tumor growth is accompanied by inhibition of cellular immunity and the function of the T lymphocytes. Restitution of T lymphocyte function by means of several pharmacologic agents such as levamisole, phenformin, or epithalamin (an epiphyseal factor) has, in a number of cases, been accompanied by growth inhibition of both spontaneous and induced tumors. In addition, the importance of the thymus in the regulation of T lymphocytes and in antitumor immunity has been recognized. Several indicators point to the fact that the thymus contains physiologically active substances which stimulate T cell-dependent immunity and prevent the occurrence of neoplasms. These considerations have led to attempts at isolation of active thymic factors and studies on their effects on the appearance and growth of tumors. Previously, a thymic factor - thymarin - had been isolated which imparted immunocompetence to the T lymphocytes. This factor differs from other thymic preparations, including thymosine, in terms of a number of physicochemical characteristics and is a polypeptide with a molecular weight of 5000. This study is concerned with its effects on tumor development - mammary gland adenocarcinoma induced in animals with a chemical carcinogen.

Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings

International Nuclear Information System (INIS)

Pirronti, T.; Rinaldi, P.; Marano, P.; Batocchi, A.P.; Evoli, A.; Di Schino, C.

2002-01-01

Purpose: To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG). Material and Methods: Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients. Results: CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR. Conclusion: In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up

Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings

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Pirronti, T.; Rinaldi, P.; Marano, P. [Univ. Cattolica del S. Cuore, Roma (Italy). Inst. of Radiology; Batocchi, A.P.; Evoli, A.; Di Schino, C. [Univ. Cattolica del S. Cuore, Roma (Italy). Inst. of Neurology

2002-07-01

Purpose: To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG). Material and Methods: Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients. Results: CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR. Conclusion: In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up.

Review of thymic pathology in 30 cats and 36 dogs.

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Day, M J

1997-09-01

Data are presented from 30 cats and 36 dogs in which thymic disease was recognised clinically or on postmortem examination. The diagnoses included thymic lymphoma (19 cats, 12 dogs), thymoma (five cats, 18 dogs), thymic branchial cyst formation or cystic change (one cat, four dogs), thymic hyperplasia (two cats), congenital hypoplasia (one cat, one dog), thymic haemorrhage (one cat, one dog) and thymic amyloidosis (one cat). Thymic lymphoma occurred in younger dogs and cats, and was recorded equally among domestic shorthaired and purebred (especially Siamese) cats. Eight cats with thymic lymphoma were tested for feline leukaemia virus and four were positive. Thymoma occurred more frequently in older cats and dogs, and in Labradors and German shepherd dogs. Thymic tumours were associated with paraneoplastic hypercalcaemia (six dogs), megaoesophagus (two dogs) or interface dermatitis with basement membrane immune complex deposition (one cat). Non-neoplastic thymic diseases were associated with myasthenia gravis (one cat), pemphigus foliaceus (one cat) and superficial necrolytic dermatitis (one cat).

Adjuvant Therapy for Thymic Carcinoma--A Decade of Experience in a Taiwan National Teaching Hospital.

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Yen-Han Tseng

Full Text Available Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma.To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014.Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS and overall survival (OS were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003. Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11. Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029. Among 30 patients (with stage I- IV carcinoma who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months than 2 patients who received adjuvant chemotherapy (5.9 months or 4 patients who received concurrent chemoradiotherapy (7.5 months after surgery (p = 0.003.Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.

Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

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Sojka, Dorothy K; Plougastel-Douglas, Beatrice; Yang, Liping; Pak-Wittel, Melissa A; Artyomov, Maxim N; Ivanova, Yulia; Zhong, Chao; Chase, Julie M; Rothman, Paul B; Yu, Jenny; Riley, Joan K; Zhu, Jinfang; Tian, Zhigang; Yokoyama, Wayne M

2014-01-01

Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001 PMID:24714492

Changes in protein expression in p53 deleted spontaneous thymic lymphomas

DEFF Research Database (Denmark)

Honoré, Bent; Vorum, Henrik; Pedersen, Anders Elm

2004-01-01

with the protein expression in p53+/+ and p53-/- thymocytes. Only a minority (13 proteins) of the quantitatively changed proteins were common for the two thymic lymphoma cell lines, suggesting that the p53 deficiency mainly results in genetic dysfunctions which are individual for a given tumor. Two of the detected...... structure containing motifs of the glyoxalase-bleomycin resistance protein family (MDR) as deduced from the cDNA....

The effect of age on thymic function

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Donald B. Palmer

2013-10-01

Full Text Available Age-related regression of the thymus is associated with a decline in naïve T cell output. This is thought to contribute to the reduction in T cell diversity seen in older individuals and linked with increased susceptibility to infection, autoimmune disease and cancer. Thymic involution is one of the most dramatic and ubiquitous changes seen in the ageing immune system, but the mechanisms which underlying this process are poorly understood. However, a picture is emerging, implicating the involvement of both extrinsic and intrinsic factors. In this review we assess the role of the thymic microenvironment as a potential target that regulates thymic involution, question whether thymocyte development in the aged thymus is functionally impaired and explore the kinetics of thymic involution.

Differentiating the grades of thymic epithelial tumor malignancy using textural features of intratumoral heterogeneity via (18)F-FDG PET/CT.

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Lee, Hyo Sang; Oh, Jungsu S; Park, Young Soo; Jang, Se Jin; Choi, Ik Soo; Ryu, Jin-Sook

2016-05-01

We aimed to explore the ability of textural heterogeneity indices determined by (18)F-FDG PET/CT for grading the malignancy of thymic epithelial tumors (TETs). We retrospectively enrolled 47 patients with pathologically proven TETs who underwent pre-treatment (18)F-FDG PET/CT. TETs were classified by pathological results into three subgroups with increasing grades of malignancy: low-risk thymoma (LRT; WHO classification A, AB and B1), high-risk thymoma (B2 and B3), and thymic carcinoma (TC). Using (18)F-FDG PET/CT, we obtained conventional imaging indices including SUVmax and 20 intratumoral heterogeneity indices: i.e., four local-scale indices derived from the neighborhood gray-tone difference matrix (NGTDM), eight regional-scale indices from the gray-level run-length matrix (GLRLM), and eight regional-scale indices from the gray-level size zone matrix (GLSZM). Area under the receiver operating characteristic curve (AUC) was used to demonstrate the abilities of the imaging indices for differentiating subgroups. Multivariable logistic regression analysis was performed to show the independent significance of the textural indices. Combined criteria using optimal cutoff values of the SUVmax and a best-performing heterogeneity index were applied to investigate whether they improved differentiation between the subgroups. Most of the GLRLM and GLSZM indices and the SUVmax showed good or fair discrimination (AUC >0.7) with best performance for some of the GLRLM indices and the SUVmax, whereas the NGTDM indices showed relatively inferior performance. The discriminative ability of some of the GLSZM indices was independent from that of SUVmax in multivariate analysis. Combined use of the SUVmax and a GLSZM index improved positive predictive values for LRT and TC. Texture analysis of (18)F-FDG PET/CT scans has the potential to differentiate between TET tumor grades; regional-scale indices from GLRLM and GLSZM perform better than local-scale indices from the NGTDM. The SUVmax

Micronodular thymic neoplasms: case series and literature review with emphasis on the spectrum of differentiation.

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Mneimneh, Wadad S; Gökmen-Polar, Yesim; Kesler, Kenneth A; Loehrer, Patrick J; Badve, Sunil

2015-11-01

We report nine cases of micronodular thymoma with lymphoid B-cell hyperplasia and one case of micronodular thymic carcinoma with lymphoid hyperplasia from our institution. For a better understanding of these rare tumors, clinical records, and histological features of these cases were reviewed, with detailed review of additional 64 literature cases of micronodular thymic neoplasms. The joint analysis identified 64 cases of micronodular thymoma with lymphoid B-cell hyperplasia and 9 cases of micronodular thymic carcinoma with lymphoid hyperplasia. Both groups revealed slight male predilection, with male:female ratio of 1.3:1 and 5:4, and occurred at >40 years of age, with a mean of 64 (41-83) and 62 (42-78) years, respectively. Myasthenia gravis was noted in 3/64 (5%) and 1/9 (11%) patients, respectively. Other systemic, disimmune, or hematologic disorders were noted in 6/64 (9%) and 1/9 (11%) patients, respectively. Components of conventional thymoma were reported in 11/64 (17%) micronodular thymomas with lymphoid B-cell hyperplasia, with transitional morphology between the two components in most of them. Cellular morphology was predominantly spindle in micronodular thymoma with lymphoid B-cell hyperplasia when specified (30/43), and epithelioid in micronodular thymic carcinoma with lymphoid hyperplasia (6/9), and cytological atypia was more encountered in the latter. Dedifferentiation/transformation from micronodular thymoma with lymphoid B-cell hyperplasia to micronodular thymic carcinoma with lymphoid hyperplasia seems to occur in a small subset of cases. Three cases of micronodular thymomas with lymphoid B-cell hyperplasia were described with co-existent low-grade B-cell lymphomas. Follow-up data were available for 30 micronodular thymomas with lymphoid B-cell hyperplasia and 6 micronodular thymic carcinomas with lymphoid hyperplasia, with a mean of 47 (0.2-180) months and 23 (3-39) months, respectively. Patients were alive without disease, except for five

Immunologic competence in adults following thymic irradiation in infancy

International Nuclear Information System (INIS)

Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

1977-01-01

Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis

Immunologic competence in adults following thymic irradiation in infancy

Energy Technology Data Exchange (ETDEWEB)

Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

1977-07-01

Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis.

Genetic analysis of radiation-induced mouse thymic lymphomas

International Nuclear Information System (INIS)

Kominami, R.; Wakabayashi, Y.; Niwa, O.

2003-01-01

Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

Unusual Thymic Hyperplasia Mimicking Lipomatous Tumor in an Eight-Year-Old Boy with Concomitant Pericardial Lipomatosis and Right Facial Hemihypertrophy

International Nuclear Information System (INIS)

Kim, Yoo Jin; Kim Woo Sun; Cheon, Jung Eun; Lim, Yun Jung; Kim, In One; Yeon, Kyung Mo; Jung, Kyeong Cheon; Byun, Sun Ju

2011-01-01

We report a case of thymic hyperplasia accompanied by pericardial lipomatosis and right facial hemihypertrophy in an 8-year-old boy. On imaging studies, the hyperplastic thymus had prominent curvilinear and nodular fatty areas simulating a fat-containing anterior mediastinal mass, which is an unusual finding in children. To our knowledge, this is the first report on a child with a combination of thymic hyperplasia, pericardial lipomatosis, and right facial hemihypertrophy. The radiologic findings are presented with a brief discussion.

Rag defects and thymic stroma: lessons from animal models

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Veronica eMarrella

2014-06-01

Full Text Available Thymocytes and thymic epithelial cells (TECs cross-talk is essential to support T-cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T (nTreg cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development (leading to Severe Combined Immune Deficiency, SCID or late stages in thymocyte maturation (resulting in combined immunodeficiency. Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS. In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells (DCs and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signalling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution.

Osseous oligometastases from thymic carcinoma: a case report suggesting the effectiveness of palliative-intent radiotherapy treatment

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Kashima J

2016-02-01

Full Text Available Jumpei Kashima,1 Hirotoshi Horio,1 Yusuke Okuma,1,2 Yukio Hosomi,1 Tsunekazu Hishima3 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; 2Division of Oncology, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan; 3Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan Background: Oligometastasis, a recently proposed concept, is defined as an intermediate state of cancer, between localized and systemic disease, that may be well controlled by local ablative treatment. Thymic carcinoma is a rare cancer with a poor prognosis. A definitive management approach has yet to be confirmed by a high level of evidence.Case presentation: We present the case of a 41-year-old female who underwent curative-intent surgery for a stage III squamous cell carcinoma of the thymus. Bone metastases were detected 1 year later by magnetic resonance imaging. These were treated with palliative-intent radiotherapy. Disease progression has not been observed in more than 15 years since the achievement of complete radiological remission.Conclusion: The treatment outcomes in this and other reported cases suggest that some patients with oligometastatic thymic carcinoma may achieve prolonged survival or even cure with low-dose radiotherapy delivered to the metastases. Keywords: oligometastasis, thymic carcinoma, thymic epithelial tumor, bone metastasis

Thymic hyperplasia in Graves′ disease

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Narendra Kotwal

2013-01-01

Full Text Available Graves′ disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. It is known to be associated with autoimmune conditions such as myasthenia gravis, Addison′s disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare autoimmune association of Graves′ disease with thymic hyperplasia which regressed after treatment with antithyroid drugs. Exact pathophysiology of thymic hyperplasia in Graves′ is not well understood; it is likely to be the result of rather than the cause of Graves′ disease.

Computer tomographic examination of the thymus

International Nuclear Information System (INIS)

Weiss, C.; Dinkel, E.; Wimmer, B.; Grosser, G.; Schildge, J.

1987-01-01

The diagnostic value of CT in follicular thymic hyperplasia and in thymomas in 8 patients with myasthenia gravis and in 12 patients without myasthenia gravis suffering from thymic tumors was evaluated by correlating CT-findings to surgical results and pathological-histological findings. Thymic size of the six patients with histologically proven follicular hyperplasia were scattered within the normal range, but half of them were at the upper limit. Thymic tumors were differentiated between invasive and non invasive tumors by CT staging. Solid tumors with different histology could not be further classified; the attenuation values ranging from 15-55 HU were the same in tumors, follicular hyperplasia and normal thymus. (orig.) [de

Computer tomographic examination of the thymus. Normal and pathological findings

Energy Technology Data Exchange (ETDEWEB)

Weiss, C.; Dinkel, E.; Wimmer, B.; Grosser, G.; Schildge, J.

1987-09-01

The diagnostic value of CT in follicular thymic hyperplasia and in thymomas in 8 patients with myasthenia gravis and in 12 patients without myasthenia gravis suffering from thymic tumors was evaluated by correlating CT-findings to surgical results and pathological-histological findings. Thymic size of the six patients with histologically proven follicular hyperplasia were scattered within the normal range, but half of them were at the upper limit. Thymic tumors were differentiated between invasive and non invasive tumors by CT staging. Solid tumors with different histology could not be further classified; the attenuation values ranging from 15-55 HU were the same in tumors, follicular hyperplasia and normal thymus.

Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

Science.gov (United States)

Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

2017-06-01

Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Chest roentgenographic findings of thymic size and shape in respiratory distress syndrome

International Nuclear Information System (INIS)

Oh, Young Ho; Yoon, Sung Do; Sung, Ki Yeal; Park, Seog Hee; Kim, Jong Woo; Bahk, Yong Whee

1984-01-01

Thymic size can be affected by both exogenous and endogenous glucocorticoids. Development of the respiratory distress syndrome (RDS) is influenced by adrenal cortical function. Thus, thymic size in RDS is considered to be enlarged due to decreased adrenal cortical function. To find whether the presence of RDS correlates with the thymus, the size and shape of the thymus were evaluated in the radiographs of premature infants with RDS, without RDS (control prematurity) and normal infants. The subjects were consisted of chest films of Korean premature infants, 120 with RDS, 60 without RDS, and 60 of normal infants taken at the Department of Radiology, Our Lady of Mercy Hospital during the period of 62 months since January 1978. Relative size of the thymus was determine by cardiothymic/thoracic ratio (CT /T ratio). Grading and location of the thymic prominence as well as incidence of the shape were examined. And all the relations among the radiographs of RDS, control prematurity and normal infants were analyzed. The results were as follows: 1. The CT/T ratio of premature infants with RDS was significantly greater than that of control prematurity and normal infants (P< 0.01). 2. The incidence of bilateral thymic prominence was more frequent in premature infant with RDS than in control prematurity and normal infants (P<0.05). 3. The frequency of thymic prominence was greater in the right than left side in all the three groups (P<0.05). 4. As in the shape of the thymus, a rounded type was most frequent, and a triangular type was least frequent in all three groups. 5. Incident of RDS was very low (9.8%) when the CT/T ratio is below 0.3 and it was very high (90.9%) when the CT/T ratio is above 0.49.

Immune activation is associated with decreased thymic function in ...

African Journals Online (AJOL)

Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

Thymic B cell development is controlled by the B potential of progenitors via both hematopoietic-intrinsic and thymic microenvironment-intrinsic regulatory mechanisms.

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Shiyun Xiao

Full Text Available Hematopoietic stem cells (HSCs derived from birth through adult possess differing differentiation potential for T or B cell fate in the thymus; neonatal bone marrow (BM cells also have a higher potential for B cell production in BM compared to adult HSCs. We hypothesized that this hematopoietic-intrinsic B potential might also regulate B cell development in the thymus during ontogeny.Foxn1lacZ mutant mice are a model in which down regulation of a thymic epithelial cell (TEC specific transcription factor beginning one week postnatal causes a dramatic reduction of thymocytes production. In this study, we found that while T cells were decreased, the frequency of thymic B cells was greatly increased in these mutants in the perinatal period. We used this model to characterize the mechanisms in the thymus controlling B cell development.Foxn1lacZ mutants, T cell committed intrathymic progenitors (DN1a,b were progressively reduced beginning one week after birth, while thymic B cells peaked at 3-4 weeks with pre-B-II progenitor phenotype, and originated in the thymus. Heterochronic chimeras showed that the capacity for thymic B cell production was due to a combination of higher B potential of neonatal HSCs, combined with a thymic microenvironment deficiency including reduction of DL4 and increase of IL-7 that promoted B cell fate.Our findings indicate that the capacity and time course for thymic B-cell production are primarily controlled by the hematopoietic-intrinsic potential for B cells themselves during ontogeny, but that signals from TECs microenvironment also influence the frequency and differentiation potential of B cell development in the thymus.

CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis

International Nuclear Information System (INIS)

Liu Fugeng; Wei Jiahu; Pan Jishu; Zhou Cheng; Chen Qihang; Yu Jingying; Wu Guogeng; Xu Xianhao

2006-01-01

Objective: To evaluate the CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis (MG). Methods: The CT findings of thymus area of 134 adult patients with lymphofollicular thymic hyperplasia in MG were reviewed, all of them with surgically and histologically proven diagnosis, and compared with the CT findings of 165 normal subjects. Results: In the group of patient, CT showed enlargement of thymus in 31 patients, 5 patients had nodule or mass ( 3 cm) and 9 patients (6.7%) had normal size thymus with soft-tissue density, it can considered with thymic hyperplasia. The spotty or streak shadow showed in other patients, though it could not be certain diagnosed as thymic hyperplasia, but could not be except it. The thymus area tissue complete replacement by fatty density were not found in patient group. The CT findings of patients had marked difference when compared with group of normal subjects (P<0.01), except the spotty or streak shadows. Conclusion: CT scan is an important method in diagnosing thymic lymphofollicular hyperplasia of MG in adult. (authors)

comparison of clinical features and CT findings between atypical thymoma and thymic carcinoma

International Nuclear Information System (INIS)

Wang Xiangyang; Tan Ye; Chen Juan; Wei Jiahu; Pan Jishun; Du Jun; Zhou Cheng

2011-01-01

Objective: To investigate the differences and the similarities of clinical presentations and CT features between type B3 thymoma (atypical thymoma) and type C thymoma (thymic carcinoma) in the WHO classification of thymic epithelial tumors. Methods: Complete CT findings of thirty cases of type B3 and seventeen cases of type C thymic epithelial tumors confirmed by histopathology according to WHO 2004 Classification System and clinical features including the prognosis of each case were reviewed retrospectively. Statistical analyses of the data for the age and the long diameter were performed with Independent-Samples t test between the two groups. Statistical analysis for gender, association with myasthenia gravis, method of the operation, contours, shapes, calcification,necrosis, enhancement pattern of the tumors on CT, presence of mediastinal lymphadenopathy, invasion of mediastinal fat, chest wall, pericardium, great vessel, pleural mediastinum, metastasis to the plural, pleural effusion, distant metastasis were performed with Fisher exact test. Kaplan-Meier method was employed for survival analysis. Results: Clinical data: the average age of type B3 group was significantly younger (t=-2.905, P=0.006). 90.0% (27/30) of patients in type B3 group were complicated by myasthenia gravis, while only 5.9% (1/17) of patients in type C group were complicated by myasthenia gravis. The difference between the two groups was statistically significant (P=0.000). The ratio of complete resection of type B3 group (80.0%) was significantly higher than that in type C group (P=0.001), 70.6% (12/17) of patients in type C group died within 2 years after surgical resection, while only 20.0% (6/30) of patients in type B3 group died within one to nine years after surgical resection. Three years' survival ratio of C group was 29.4%, and five years' survival ratio of C group was lower than 14.7%, which was significantly lower than B3 group five years' survival ratio was 94.7%), which was

Spleen and thymic sonography as estimator of the immune response in children with repeated infections

International Nuclear Information System (INIS)

Rabaza, Jesus; Fundora, Hermes; Rodriguez, Alexis; Hernandez, Maria de los Angeles

2010-01-01

The spleen is a secondary lymphoid organ. The spleen has many functions: IgM class antibody production and phagocytosis of encapsulated bacteria. We propose to measure the dimensions of the spleen in children with repeated infections, in order to describe them as a diagnosis marker and to explore the probable correlation between the thymic characteristics and the dimensions of the spleen. We study 81 patients that attended the consultation of Immunology from Aballi hospital with repeated infections and they were from 8 months to 9 years old. Children with nutritional value up to the third percentile and those taking steroids 45 days before the study were excluded. We measured the thymic and splenic areas by mediastinal and abdominal echography. The length, the splenic index and the weight are less in patients with repeated infections. These data were significant in 12 to 23 month of age group. The length and the splenic index were less in patients with depletion of thymic area. The sonographic evaluation of the spleen is very important in patients from 1 to 2 years old and in patients with thymic depletion, because they are on the age of vaccine administration according to the Cuban schedule and having affected a main organ for immune response might be a reason for them to show a deficient response and need special schedules

Antitumor action of 3-bromopyruvate implicates reorganized tumor growth regulatory components of tumor milieu, cell cycle arrest and induction of mitochondria-dependent tumor cell death.

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Yadav, Saveg; Kujur, Praveen Kumar; Pandey, Shrish Kumar; Goel, Yugal; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

2018-01-15

Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death. Further, the expression of cell survival regulatory molecules and hemodynamic characteristics of the tumor milieu were analysed to decipher mechanisms underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing hosts retarded tumor progression accompanied by induction of tumor cell death, cell cycle arrest, declined metabolism, inhibited mitochondrial membrane potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3-BP reconstituted the external milieu, in concurrence with deregulated glucose and pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T lymphocytes. Further, 3-BP administration altered the expression of key regulatory molecules involved in glucose uptake, intracellular pH and tumor cell survival. The outcomes of this study will help in optimizing the therapeutic application of 3-BP by targeting crucial tumor growth regulatory components of tumor milieu. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic value of plain chest roentgenogram and CT scan findings in four cases of massive thymic hyperplasia

International Nuclear Information System (INIS)

Kobayashi, T.; Hirabayashi, Y.; Kobayashi, Y.

1986-01-01

Massive thymic hyperplasia (MTH) is rare in the pediatric age group, especially in infants. However, because of a wide variation in size and weight of the thymus, an enlarged gland is often resected because of suspicion of a neoplasm or a cyst. Some cases of thymoma resembling pulmonary acute infection occur less frequently than MTH, but if respiratory problems are accompanied by a large thymus immediate diagnosis is often necessary to differentiate between these two conditions. Four infants (14 days to 4 months of age) with MTH were recently studied, all having an acute onset an of severe respiratory distress. The infants were referred to our center with a tentative diagnosis of thymic or other intrathoracic tumors. The following case reports illustrate our diagnostic approach to evaluate patients with symptoms suggesting MTH and the response to the ''steroid test''. (orig.)

A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing's syndrome.

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Trott, M J; Farah, G; Stokes, V J; Wang, L M; Grossman, A B

2016-01-01

We present a case of a young female patient with a rare cause of relapsing and remitting Cushing's syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing's syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms 'relapsing and remitting' in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing's syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking. Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing's syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient's symptoms is noteworthy, given the paucity of this finding among other published cases.

Ectopic Thymic Cyst of the Subglottis: Considerations for Diagnosis and Management.

Science.gov (United States)

Ahmad, Iram; Kirby, Patricia; Liming, Bryan

2018-03-01

To share the diagnostic and management challenges created by an extremely rare airway lesion-the subglottic ectopic thymic cyst. Case report and literature review. We review the presentation, management, and clinical course of an infant who presented with a subglottic mass that was histologically confirmed as a thymic cyst. A brief literature review supplements the case presentation Results: We present the third described case of an ectopic thymic cyst presenting as a subglottic mass. The differential diagnosis of subglottic masses in neonates consists primarily of subglottic hemangioma and mucous retention cysts. Otolaryngologists must be prepared for unexpected findings when dealing with critical airways. We compare the presentation and management of our patient with the 2 previously described cases. We propose an embryologic theory for the origin of these rare lesions. An ectopic thymic cyst is a rare and unexpected cause of neonatal stridor. Management of pediatric airway lesions must allow for unexpected findings at the time of diagnostic and therapeutic endoscopy. The appropriate management of subglottic thymic cysts is poorly defined, but close surveillance for recurrence is mandatory.

Radiation-induced quantitative alterations in prenatal thymic development in the beagle dog

International Nuclear Information System (INIS)

Miller, G.K.; Benjamin, S.A.

1985-01-01

Quantitative morphology of the canine fetal thymus was studied to evaluate the age-dependent radiosensitivity of the developing immune system. Pregnant beagle dams received abdominal 60 Co gamma exposures (200 R) or were sham irradiated at one of three ages in gestation, 30, 40, or 45 days. The mean calculated dose to each fetus was 1.5 Gray. One-half of the fetuses in each litter were harvested by hysterotomy at 5 days and one-half at 10 days post-irradiation (PI). The volumes of the thymic lobules and lobular cortices were significantly reduced at 5 and 10 days PI when compared with age-matched controls. Thymic cortical volumes in irradiated fetuses were reduced between 13 and 29% from control volumes by 5 days PI and 8 and 13% by 10 day PI. Thymic medullary volumes in irradiated fetuses were reduced 18 to 23% by 5 days PI and 27 to 54% by 10 days PI. The reductions in medullary volumes in fetuses irradiated at 35, 40, and 45 days of gestation and evaluated at 10 days PI were 54, 38, and 27%, respectively. Although injury to both thymic cortices and medullas was greater following exposures earlier in gestation, damage to medullas was relatively more severe than in cortices following exposure at any one age. The degree of reduction of medullary volume reflects thymic epithelial injury and is surprising since thymic epithelium is considered to be radioresistant in the adult. Such injury may have serious consequences postnatally as normal differentiation of T cell subpopulations is dependent upon the integrity of the thymic microenvironment. Damage to the thymic microenvironment could result in defects in immunologic regulation and in immune deficiencies

Direct analysis of thymic function in children with Down's syndrome

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Meschiari Liviana

2005-02-01

Full Text Available Abstract Background Down's syndrome (DS is characterized by several immunological defects, especially regarding T cell compartment. DS is considered the best example of accelerated ageing in humans. Direct observations of the thymus have shown that in DS this organ undergoes severe histological and morphological changes. However, no data on its capacity to generate T cells are present in the literature. Here, using a new technology based upon real time PCR, we have investigated the capacity of the thymus to produce and release newly generated T lymphocytes (the so called "recent thymic emigrants", RTE in children with DS. Methods We studied 8 children affected by DS, aged 2–7 years, compared with 8 age- and sex-matched healthy controls. Flow cytometry was used to determine different lymphocytes subsets. Real time PCR with the Taqman system was used to quantify the amount of RTE, i.e. peripheral blood lymphocytes that express the T cell receptor rearrangement excision circles (TREC. Results In comparison with control children, those with DS had a significant lower number of TREC+ peripheral blood cells. Moreover, in DS children but not in controls, a strong negative correlation between age and the levels of TREC+ cells was found. Conclusions The direct measure of thymic output indicates that the impairment of the organ results in a reduced production of newly generated T cells. This observation could suggest that cytokines able to modulate thymic function, such as interleukins, could be useful to improve the functionality of the organ and to treat the immunodeficiency present in DS subjects.

Thymic epithelial tumours: from basic principles to individualised treatment strategies

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Nicolas Girard

2013-03-01

Full Text Available Thymic epithelial tumours represent a wide range of anatomical, clinical, histological and molecular malignant entities that may be aggressive and difficult to treat. The histopathological classification distinguishes thymomas from thymic carcinomas. Thymomas may be associated with autoimmune disorders. The management of thymic epithelial tumours is a paradigm of co-operation between clinicians, surgeons and pathologists, from establishing the diagnosis to organising the multimodal therapeutic strategy. Surgery is the mainstay of the curative-intent treatment, as complete resection represents the most significantly favourable prognostic factor on overall survival. In case of invasion of intra-thoracic structures and/or dissemination to the pleura and the pericardium, precluding complete resection to be achieved, primary chemotherapy has been used to reduce the tumour burden, possibly allowing subsequent surgery and/or radiotherapy. Novel strategies are needed, especially for refractory, recurrent tumours and thymic carcinomas, which carry a poor prognosis. Personalised approaches are currently being developed, as potentially “druggable” molecular targets are emerging from recent integrated genomic analyses. Along with the large variety of questions relative to the treatment strategy, thymic epithelial tumours represent a model of therapeutic implementation and achievement in orphan thoracic oncology, showing how the advent of new results induces new questions, as well as diversifies further clinical research directions and international collaborative initiatives.

Thymic nurse cells and thymic repopulation after whole body sublethal irradiation in mice

International Nuclear Information System (INIS)

Houben-Defresne, M.P.; Varlet, A.; Boniver, J.

1984-01-01

Thymic Nurse Cells (TNCs) are lymphoepithelial complexes which are thought to play a role in the early stages of the intrathymic differentiation pathway. Their repopulation kinetics were analyzed in mice after sublethal whole-body irradiation. Changes of the number of TNCs per thymus were parallel with the evolution of the whole thymocyte population. Particularly, a first wave of TNCs restoration was followed by a secondary depletion and a final recovery. This suggests that TNCs restoration is related to the proliferating progeny of intrathymic radioresistant thymocytes. When normal bone marrow cells were grafted intravenously after irradiation, no secondary depletion was found. This pattern of restoration was obviously related to thymic repopulation by cells which were derived from the inoculated bone marrow. Homing studies with FITC labelled bone marrow cells showed that inoculated bone marrow cells did not penetrate TNCs early after irradiation. Later on, when immigrant cells started to proliferate, they were found preferentially within TNCs before spreading in the whole thymus. (Auth.)

LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

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Keitaro Hayashi

2016-11-01

Full Text Available L-type amino acid transporter 1 (LAT1, SLC7A5 incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

International Nuclear Information System (INIS)

Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

1983-01-01

The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

Fate of thymic radioactivity after local labeling with 125Iododeoxyuridine

International Nuclear Information System (INIS)

Laissue, J.A.; Chanana, A.D.; Cottier, H.; Cronkite, E.P.; Joel, D.D.

1976-01-01

The thymic cortex was locally labeled with 125 Iododeoxyuridine ( 125 IUdR) in young adult mice in an attempt to provide a simple quantitative assessment of the fate of cortical thymocytes. Similarly operated and nonoperated mice given 125 IUdR intravenously were used for comparison. Analogous experiments were performed in adrenalectomized animals. More than 90 percent of thymic activity present 1 day after labeling had been lost by day 8. That proportion of radioactivity contributed to a given organ by accumulation of labeled thymic migrants was estimated by comparison of values obtained after local labeling with those acquired after systemic labeling. Thymic cell accumulation was apparent in the intestine, spleen, mesenteric lymph node, and femurs of locally labeled mice; however, only a few percent of the total activity lost from the thymus was accounted for in these lymphoid organs. The pattern of fecal and urinary elimination of 125 I did not markedly differ in the various experimental groups, the bulk of the activity being recovered in the urine. The intestine could not be ruled out as a major site of thymocyte loss. Since significant radiation or pharmacologic toxicity was unlikely with the doses of 125 IUdR used, the data indicated that the vast majority of newly formed thymocytes dies after a short life and only a small fraction of thymic migrants is longer lived

Bioprocessing feasibility analysis. [thymic hormone bioassay and electrophoresis

Science.gov (United States)

1978-01-01

The biology and pathophysiology of the thymus gland is discussed and a clinical procedure for thymic hormone assay is described. The separation of null lymphocytes from mice spleens and the functional characteristics of the cells after storage and transportation were investigated to develop a clinical procedure for thymic hormone assay, and to determine whether a ground-based approach will provide the desired end-product in sufficient quantities, or whether the microgravity of space should be exploited for more economical preparation of the hormone.

Exploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium.

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Adrien De Voeght

Full Text Available Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease progression. The goal of this study was to explore the hypothesis of potential links between microbial translocation and thymic function in HIV-1 patients living in Belgium. The extent of microbial translocation was assessed through the measurement of soluble CD14 (sCD14. T-cell receptor excision circles (sjTRECs and dβTRECs were used as a measure of thymic function. Data were collected from 75 HIV-infected patients. Simple and complex linear regressions were done to analyze the link between these two processes. We found a statistically relevant negative correlation between thymopoiesis (sjTREC and sCD14 level (p = 0.004. These results suggest a link between thymic function failure, microbial translocation and innate immune activation.

The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis

International Nuclear Information System (INIS)

Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E.

1997-01-01

The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs

Thymic hyperplasia - clinical course and imaging diagnostic

International Nuclear Information System (INIS)

Drebov, R.; Panov, M.; Totev, M.; Deliverski, T.; Tcandev, I.; Velkovski, I.

2006-01-01

The real thymic hyperplasia is benign disease sometimes simulating malignant tumours. The aim of this study is to analyse the clinical symptoms of real thymic hyperplasia and the results from imaging diagnostic based on our clinical material. Clinical material include 27 children, aged from two months to 15 years, admitted in department of thoracic surgery, for a period of 20 years (1985 - 2004). We retrospectively analyze the clinical signs and results from X-ray investigation, CT (Siemens Somatom DRG and Philips Secura) and echocardiography (Acuson TX, 5 and 7 MHz). We discuss the diagnostic value of different methods as well as typical and atypical findings. (authors)

Malignant mast cell tumor of the thymus in an Royal College of Surgeons (RCS) rat.

Science.gov (United States)

Terayama, Yui; Matsuura, Tetsuro; Ozaki, Kiyokazu

2017-01-01

A 152-week-old male Royal College of Surgeons (RCS) rat kept as a non-treated animal in a long-term animal study presented with a soft mass in the anterior mediastinum, which adhered to the pleura of the lung. Histopathologically, the mass mainly consisted of round to short spindle-shaped tumor cells that had infiltrated through the hyperplastic thymic tissue. The tumor cells were arranged in loose to dense sheets. Nuclei were moderate in size and round to spindle-shaped, with small nucleoli. Almost all tumor cells exhibited abundant eosinophilic cytoplasm, including eosinophilic granules of a range of sizes. The granules of tumor cells exhibited metachromasia with toluidine blue stain and were positive for c-kit and mast cell protease II. These findings indicate that the tumor described here represents a rare case of spontaneous malignant mast cell tumor with thymic epithelial hyperplasia.

Effect of allogenic thymic cells on radioleukaemogenesis in AKR-T1ALD mice

International Nuclear Information System (INIS)

Legrand, E.; Sankar-Mistry, P.; Kressmann, M.C.

1975-01-01

When AKR mice are irradiated with a sub-lethal dose (4 times 175 R), thymic lymphosarcomas (L.S.) occur earlier than in controls. This accelerated leukaemogenesis is not inhibited by syngenic restoration with bone marrows cells (BM). Using the AKR/T1ALD substrain which bears 38 chromosomes with 1 metacentric markers, it has been shown that AKR radio-chimaeras restored by T1ALD BM developed two kinds of L.S.: early (radiation-induced) L.S. originating mainly from host cells surviving irradiation and late L.S. from donor cells. The experiments were to investigate the potential influence of normal allogenic thymic cells, with or without syngenic B.M., on the incidence, latency and origin of LS appearing in irradiated AKR recipients. Adding C3H allogenic thymic cells to syngenic B.M. increases the percentage of early L.S. whose latencies are unchanged. Besides, when C3H thymic cells are injected to irradiated controls without syngenic B.M. cells, L.S. are seen to occur significantly earlier than in just the irradiated animals alone. In radio-chimaeras restored by allogenic thymic cells and syngenic B.M., except in one case, all the L.S. were seen to originate from B.M. cells. The interpretation of these results depends on the possible role of allogenic thymic cells on host cells surviving the irradiation, or the exogeneous B.M. In the first case, allogenic thymocytes could induce a graft versus host reaction increasing the post-irradiation depletion of lymphoid system and hastening thymic endoregeneration which is supposed to be the first step towards leukaemogenesis. The second hypothesis, which seems the most likely, would be that C1H thymic cells could selectively act on host cells surviving irradiation and enhance the differenciation of haemopoietic precursors at the expense of the lymphoid cells [fr

Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

DEFF Research Database (Denmark)

Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette

2002-01-01

) repertoire were determined. The study demonstrated no correlation between the 2 scanning methods (r = 0.201, p = 0.358 in patients and r = 0.457, p = 0.184 in controls). Among the patients, no association was found between the sonographically estimated thymic size and immunological parameters such as CD4...... count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating...

Clinical analysis of thymic regrowth following chemotherapy in children and adolescents with malignant lymphoma

International Nuclear Information System (INIS)

Zhen Zijun; Sun Xiaofei; Xia Yi; Ling Jiayu; Cai Yue; Wang Juan; Guan Zhongzhen

2010-01-01

Thymic regrowth following chemotherapy has typical clinical and imaging manifestations that can be used to diagnose it prior to pathological diagnosis. We investigated methods for diagnosing thymic regrowth following chemotherapy with non-invasive methods. Our study included 26 children and adolescents with thymic regrowth following chemotherapy for malignant lymphoma. Computed tomography scans were routinely performed for follow-up observations. After the emergence of new mediastinal masses, patients either underwent Fluorine-18 fluorodeoxyglucose-positron emission tomography scans to identify the characteristics of the mass, or were closely followed up. Thymic regrowth occurred 1-12 months after the last chemotherapy (mean, 4 months). Computed tomography mostly revealed diffusely enlarged thymic parenchymatous tissues that maintained normal thymic morphology. Computed tomography values were 36.72±9.48 Hu and increased by 5.56±2.62 Hu in contrast enhancement. The mean volume of the mass was 19.2 cm 3 . Twenty patients underwent positron emission tomography; among them, five (25%) showed no intake of Fluorine-18 fluorodeoxyglucose in the anterior mediastinal mass, and 15 (75%) showed radioactivity distribution in the mass with a mean standardized uptake value of 2.7; the shape was regular and radioactivity distribution was uniform. The mean follow-up duration was 40 months and all patients achieved disease-free survival. In the absence of pathological diagnosis, thymic regrowth following chemotherapy can be diagnosed by clinical features combined with characteristic manifestations in computed tomography and positron emission tomography scans. (author)

Cyclosporine promotes the induction of thymic lymphomas in C57BL/6 mice initiated by a single dose of γ-radiation

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Yabu, Koji; Warty, V.S.; Gorelik, E.; Shinozuka, Hisashi

1991-01-01

We previously demonstrated that a single dose of γ-radiation (350 rads) was able to induce thymic lymphomas in C57BL mice when followed by promoting treatment with oral cyclosporine (CsA), a non-genotoxic immunosuppressant. We have now tested the efficacy of various doses of γ-radiation as an initiator of CsA promotion of the induction of thymic lymphomas in male C57BL mice. The effects of oral CsA on the splenic natural killer (NK) cell activity of non-irradiated and irradiated (400 rads, 1X) mice were tested by the standard 51 Cr release assays against YAC-1 cells. The cumulative incidence of thymic lymphomas induced by a single dose of γ-radiation at 100, 200, 400 and 600 rads were 10, 25, 63 and 75% respectively, after 42 weeks of CsA promotion. The splenic NK cell activity in non-irradiated mice given CsA for 4 weeks was twice as high as that in the control mice. CsA inhibited poly I:C-induced augmentation of the splenic NK cell activity. In mice given a single dose (400 rads) of γ-radiation and CsA for 4 weeks, a similar but reduced enhancement of the splenic NK cell activity as seen in non-irradiated mice was observed. These results indicate that the efficacy of CsA promotion in the induction of thymic lymphomas is dependent on the initiating doses of γ-radiation, and that CsA enhances host splenic NK cell activity during the early stage of tumor promotion. (author)

Evidence That Androgens Modulate Human Thymic T Cell Output

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Olsen, Nancy J.; Kovacs, William J.

2010-01-01

Background The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Methods Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs). Cells bearing T cell receptor excision circles (TRECs) were quantitated using real-time PCR amplification of DNA isolated from PBMCs from normal men and from hypogonadal men before and after testosterone replacement therapy. Results CD4+CD45+ (“naïve”) T cells comprised 10.5% of lymphocytes in normal males; this proportion was greatly increased in two hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after one month and to 12.51% after 7 months of normalized androgen levels. In two hypogonadal patients TREC levels fell by 83% and 78% after androgen replacement therapy. Conclusions Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement. PMID:21218609

Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis

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Wendland, Kerstin; Niss, Kristoffer; Kotarsky, Knut

2018-01-01

Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis. In the abse......Despite the essential role of thymic epithelial cells (TEC) in T cell development, the signals regulating TEC differentiation and homeostasis remain incompletely understood. In this study, we show a key in vivo role for the vitamin A metabolite, retinoic acid (RA), in TEC homeostasis...

Antiretroviral therapy increases thymic output in children with HIV

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Schou Sandgaard, Katrine; Lewis, Joanna; Adams, Stuart

2014-01-01

OBJECTIVE: Disease progression and response to antiretroviral therapy (ART) in HIV-infected children is different to that of adults. Immune reconstitution in adults is mainly from memory T cells, whereas in children it occurs predominantly from the naive T-cell pool. It is unclear however what...... with a recently described mathematical model to give explicit measures of thymic output. RESULTS: We found that age-adjusted thymic output is reduced in untreated children with HIV, which increases significantly with length of time on ART. CONCLUSION: Our results suggest that a highly active thymus in early...

Association between thymic function and allogeneic hematopoietic stem cell transplantation outcome: results of a pediatric study.

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Saglio, Francesco; Cena, Silvia; Berger, Massimo; Quarello, Paola; Boccasavia, Viola; Ferrando, Federica; Pittana, Laura; Bruno, Benedetto; Fagioli, Franca

2015-06-01

Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Modification of radiation-induced murine thymic lymphoma incidence by curcumin

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Dange, P.S.; Yadav, H.D.; Kumar, Vimalesh; Bhilwade, H.N.; Pandey, B.N.; Sarma, H.D.

2017-01-01

Curcumin is a known antioxidant, preventing radiation damage including carcinogenesis. However, concentration and feeding schedule of curcumin in modification of radiation induced thymic lymphoma incidence in vivo model has not been studied. We report here modification of incidence of γ-radiation-induced thymic lymphoma in mice fed with different doses of curcumin (0.05 to 1 %) in diet. Results: Female Swiss mice (6-8 weeks) fed with normal diet and exposed to 3 Gy whole body "6"0Co γ-irradiation (WBI) showed 85 % incidence of thymic lymphoma (TL) at 120 days post-irradiation. A concentration of 1 % curcumin was found the most effective in TL incidence prevention than other fed concentrations. The TL incidence was remarkably reduced when curcumin was fed to the mice before than after the radiation exposure. These results suggest modification of TL incidence by curcumin in irradiated mice involving DNA damage and apoptotic death mechanisms

Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

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Wertheimer, Tobias; Velardi, Enrico; Tsai, Jennifer; Cooper, Kirsten; Xiao, Shiyun; Kloss, Christopher C.; Ottmüller, Katja J.; Mokhtari, Zeinab; Brede, Christian; deRoos, Paul; Kinsella, Sinéad; Palikuqi, Brisa; Ginsberg, Michael; Young, Lauren F.; Kreines, Fabiana; Lieberman, Sophia R.; Lazrak, Amina; Guo, Peipei; Malard, Florent; Smith, Odette M.; Shono, Yusuke; Jenq, Robert R.; Hanash, Alan M.; Nolan, Daniel J.; Butler, Jason M.; Beilhack, Andreas; Manley, Nancy R.; Rafii, Shahin; Dudakov, Jarrod A; van den Brink, Marcel RM

2018-01-01

The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. Here we show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration, via their production of BMP4. ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signalling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance and regeneration; and its downstream targets such as Dll4, itself a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity. PMID:29330161

Studies on radiation-induced thymic lymphomagenesis in B10 strain mice

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Muto, Masahiro

1989-01-01

Using B10.Thy 1 congenic strain mice, we reexamined the earlier results by Kaplan and others that lymphomas could develop from lymphocytes present in the nonirradiated parental thymuses grafted into thymectomized, fractionally irradiated H-2 semiincompatible recipient mice. The results indicated that 37 out of 91 thymectomized and irradiated B10.Thy 1.2 mice developed lymphomas of which 75 % were shown to have originated from grafted thymuses. The evidence was not obtained that supported the involvement of endogenous MuLV or some kind of transmissible agents during thymic lymphomagenesis. We found, with intrathymic injection assay, that 'preneoplastic' cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment first appeared in the thymuses about 4-8 days after irradiation. These thymic prelymphoma cells 'thymus-dependent' preneoplastic cells were detected in 26.1 % of the test donor thymuses when examined at 14 days and in more than 63 % 21 and 31 days after irradiation. It was found that lymphomagenic irradiation resulted in the anomalous appearance of CD4 + and/or CD8 + thymocytes bearing IL-2 receptor (IL-2R) which were different from normal thymocyte subpopulations. Thymic prelymphoma cells existed mainly in CD4 - CD8 - and CD4 - CD8 + thymocyted subpopulations and also in CD4 + CD8 + subpopulation. T cell lymphomas derived from CD4 - CD8 - prelymphoma cells had mainly CD4 - CD8 - or CD4 - CD8 + phenotypes. T cell lymphomas developed from CD4 - CD8 + prelymphoma cells mainly expressed CD4 - CD8 + or CD4 + CD8 + phenotype. T cell lymphomas originated from CD4 + CD8 + prelymphoma cells were mainly CD4 + CD8 + but some CD4 - CD8 + or CD4 + CD8 - cells were also present. These T cell lymphomas expressed IL-2R on various levels. The development of thymic prelymphoma cells is discussed in view of thymocyte differentiation. (J.P.N)

Thyroid and thymic exeresis in surgery of hyperparathyroidism.

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Diaconescu, Mr; Glod, M; Costea, I; Grigorovici, M; Diaconescu, S

2014-01-01

Owing to close anatomical and embryological connexions between the thyroid, parathyroids and thymus,manifold coexisting pathology can be identified during the surgery of hyperparathyroidism (Hp). In this retrospective study we report the incidence, clinical forms, histology and management of thyroid and thymic synchronous lesions encountered in as eries of 82 consecutive patients with various types of Hp operated on in the last three decades. Demography, clinical records, biochemical data, imaging procedures, pathology reports and surgical protocols were revised. Between 1984-2013, 82 cases of Hp, 20 primary and 62 renal (27 secondary and 35 tertiary), 57 women and 25 males (sex ratio: 2.3 1) of 15-72 (mean 46.5) years, under went surgery in our clinic. Concomitant thyroid exereses were performed in 32 patients (2 subtotal thyroidectomies, 12 lobectomies, 8 atypical resections and 10 diagnosis biopsies), foruni- or bilateral (multi)nodular goiters or different €œminutelesions. Pathology showed 11 colloid goiters, 3 follicular adenomas,5 nodular hyperplasias and 6 thyroiditis cases, 3 papillary microcarcinomas and 4 specimens with normal thyroid tissue.Excision of the fibrofatty retromanubrial tissue in total parathyroidectomies for renal Hp (19 cases) revealed one nonmyastenicthymoma, one thymic cyst and thymic remnants in 6 patients.Morbidity in these extended operations was not significantly increased, comparing to the parathyroid exploration alone. Meticulous pre- and intraoperative evaluation in all cases of Hp enables the actual shift from bilateral neck exploration to minimally invasive surgery,increasing however the potential risk of missing thyroid or thymic coexistent significant lesions. The surgeon dedicated to this pathology must be aware of the possibility of encountering such synchronous association and make generous efforts to wards their complete cure in a single operation. Celsius.

T-lymphocyte subsets, thymic size and breastfeeding in infancy

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Jeppesen, Dorthe Lisbeth; Hasselbalch, Helle; Lisse, Ida M

2004-01-01

We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4......+ and CD8+ cells. Two different populations of infants between birth and 1 year of age were examined. Study Group I: infants with a variable duration of breastfeeding. Study Group II: long-term breastfed infants. In both groups a correlation was found between CD8+ cells and the thymic index at 10 months...... to 10 months of age; and a positive correlation between the number of breastfeedings per day at 8 months of age, and an increase in CD4+ cells from 8 to 10 months of age (p Breastfeeding might have both a current and long...

Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

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Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

1985-01-01

The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

A mechanism misregulating p27 in tumors discovered in a functional genomic screen.

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Carrie M Garrett-Engele

2007-12-01

Full Text Available The cyclin-dependent kinase inhibitor p27(KIP1 is a tumor suppressor gene in mice, and loss of p27 protein is a negative prognostic indicator in human cancers. Unlike other tumor suppressors, the p27 gene is rarely mutated in tumors. Therefore misregulation of p27, rather than loss of the gene, is responsible for tumor-associated decreases in p27 protein levels. We performed a functional genomic screen in p27(+/- mice to identify genes that regulate p27 during lymphomagenesis. This study demonstrated that decreased p27 expression in tumors resulted from altered transcription of the p27 gene, and the retroviral tagging strategy enabled us to pinpoint relevant transcription factors. inhibitor of DNA binding 3 (Id3 was isolated and validated as a transcriptional repressor of p27. We further demonstrated that p27 was a downstream target of Id3 in src-family kinase Lck-driven thymic lymphomagenesis and that p27 was an essential regulator of Lck-dependent thymic maturation during normal T-cell development. Thus, we have identified and characterized transcriptional repression of p27 by Id3 as a new mechanism decreasing p27 protein in tumors.

Development of Thymic Epithelial Cells

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Ulyanchenko, Svetlana; Vaidya, Harsh J.; O'Neill, Kathy E.

2016-01-01

The thymus is the primary lymphoid organ in which the T cell repertoire is generated. The complex cellularity of this organ is uniquely designed to facilitate T cell development: defects in thymus development or function can cause immunodeficiencies ranging from the absence of T cell-mediated imm......The thymus is the primary lymphoid organ in which the T cell repertoire is generated. The complex cellularity of this organ is uniquely designed to facilitate T cell development: defects in thymus development or function can cause immunodeficiencies ranging from the absence of T cell......-mediated immunity to broad-spectrum autoimmune disease. Peak thymus size and output occurs early in life, after which the thymus undergoes a natural process of involution. This results in the progressive loss of functional thymus tissue and correspondingly in decreased production of new naïve T cells with age...... - contributing to the diminished capacity of the aged immune system to adequately respond to new antigenic challenge. Age-related thymic involutions, together with the thymic involutions associated with cytotoxic therapies (e.g., radio- or chemotherapy), have raised interest in development of clinically useful...

Frequent silencing of RASSF1A by DNA methylation in thymic neuroendocrine tumours.

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Kajiura, Koichiro; Takizawa, Hiromitsu; Morimoto, Yuki; Masuda, Kiyoshi; Tsuboi, Mitsuhiro; Kishibuchi, Reina; Wusiman, Nuliamina; Sawada, Toru; Kawakita, Naoya; Toba, Hiroaki; Yoshida, Mitsuteru; Kawakami, Yukikiyo; Naruto, Takuya; Imoto, Issei; Tangoku, Akira; Kondo, Kazuya

2017-09-01

Aberrant methylation of promoter CpG islands (CGIs) of tumour suppressor genes is a common epigenetic mechanism underlying cancer pathogenesis. The methylation patterns of thymic tumours have not been studied in detail since such tumours are rare. Herein, we sought to identify genes that could serve as epigenetic targets for thymic neuroendocrine tumour (NET) therapy. Genome-wide screening for aberrantly methylated CGIs was performed in three NET samples, seven thymic carcinoma (TC) samples, and eight type-B3 thymoma samples. The methylation status of thymic epithelial tumours (TETs) samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. We identified a CGI on a novel gene, RASSF1A, which was strongly hypermethylated in NET, but not in thymic carcinoma or B3 thymoma. RASSF1A was identified as a candidate gene statistically and bibliographically, as it showed frequent CGI hypermethylation in NET by genome-wide screening. Pyrosequencing confirmed significant hypermethylation of a RASSF1A CGI in NET. Low-grade NET tissue was more strongly methylated than high-grade NET. Quantitative PCR and immunohistochemical staining revealed that RASSF1A mRNA and protein expression levels were negatively regulated by DNA methylation. RASSF1A is a tumour suppressor gene epigenetically dysregulated in NET. Aberrant methylation of RASSF1A has been reported in various tumours, but this is the first report of RASSF1A hypermethylation in TETs. RASSF1A may represent an epigenetic therapeutic target in thymic NET. Copyright © 2017 Elsevier B.V. All rights reserved.

Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

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Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

1995-01-01

, the rank-order correlation coefficient between the single dose hypoxic versus fractionated dose TCD50s under hypoxic or aerobic conditions was 1.0. For all 5 tumors examined, a trend for rank correlation was observed between the single dose and the fractionated dose TCD50s performed under normal or clamp hypoxic conditions (r=0.7, p=0.16 in both cases). The linear correlation coefficients were 0.83, p=0.08 and 0.72, p=0.17, respectively. Failure to attain a rank correlation of 1.0 was due to one tumor exhibiting an insignificant fractionation effect. The rank correlation between the TCD50s for fractionated treatments under normal versus the extrapolated TCD50s under clamp hypoxic conditions was 1.00; the linear correlation coefficient was 0.97 (p=0.01). Conclusions: In the tumor models examined, factors controlling the single fraction tumor control dose, also impact the response to fractionated treatments. These results suggest that laboratory estimates of intrinsic radiosensitivity and tumor clonogen number at the onset of treatment, will be of use in predicting radiocurability for fractionated treatments, as has been observed for single dose treatments

A rear case of multilocular thymic cyst with follicular lymphoid hyperplasia; Radiologic and histopathologic features

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Kim, Jin Suk; Cha, Eun Jung [Konyang University Hospital, Daejeon (Korea, Republic of)

2016-06-15

Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.

Elevation of oleate-activated phospholipase D activity during thymic atrophy

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Lee, Youngkyun; Song, Soo-Mee; Park, Heung Soon; Kim, Sungyeol; Koh, Eun-Hee; Choi, Myung Sun; Choi, Myung-Un

2002-01-01

Various phospholipases are thought to be associated with the in vitro apoptosis of thymocytes. In the present study, the in vivo phospholipase D (PLD) activity of rat thymus was studied after whole-body X-irradiation or injection of dexamethasone (DEX). Using exogenous [14C]dipalmitoyl phosphatidylcholine (PC) as the substrate, an elevation of oleate-activated PLD activity was observed during thymic atrophy. The activity increases were sevenfold at 48 hr after 5-Gy irradiation and fourfold at 72 hr after injection of 5 mg/kg DEX. The elevation of PLD activity appeared to parallel extensive thymus shrinkage. An increased level of thymic phosphatidic acid (PA), the presumed physiological product of PLD action on PC, was also detected. By comparing the acyl chains of PA with those of other phospholipids, PA appeared to originate from PC. To assess the role of PLD during thymic atrophy, thymocytes and stromal cells were isolated. Although thymocytes themselves exhibited significant PLD activation, the major elevation in PLD activity (greater than fourfold) was found in isolated stromal cells. PLD was also activated during in vitro phagocytosis of apoptotic thymocytes by the macrophage-like cell line P388D1. This in vitro phagocytosis was significantly inhibited by PLD action blockers, such as 2,3-diphosphoglycerate and 1-butanol. These observations strongly suggest that the alteration of oleate-activated PLD activity is part of an in vivo event in the progression of thymic atrophy, including phagocytic clearance of apoptotic thymocytes. PMID:12460188

Endometrial cancer: correlation of apparent diffusion coefficient (ADC) with tumor cellularity and tumor grade.

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Kishimoto, Keiko; Tajima, Shinya; Maeda, Ichiro; Takagi, Masayuki; Ueno, Takahiko; Suzuki, Nao; Nakajima, Yasuo

2016-08-01

Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD. © The Foundation Acta Radiologica 2015.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumor types are associated with increased TERT expression and telomerase activation

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Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Liang, Junbo; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Wang, Si-Zhen; Jiao, Yu-Chen; Yan, Hai; Tao, Hou-Quan

2015-01-01

Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets. PMID:25843513

Common pediatric cerebellar tumors: correlation between cell densities and apparent diffusion coefficient metrics.

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Koral, Korgün; Mathis, Derek; Gimi, Barjor; Gargan, Lynn; Weprin, Bradley; Bowers, Daniel C; Margraf, Linda

2013-08-01

To test whether there is correlation between cell densities and apparent diffusion coefficient (ADC) metrics of common pediatric cerebellar tumors. This study was reviewed for issues of patient safety and confidentiality and was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and was compliant with HIPAA. The need for informed consent was waived. Ninety-five patients who had preoperative magnetic resonance imaging and surgical pathologic findings available between January 2003 and June 2011 were included. There were 37 pilocytic astrocytomas, 34 medulloblastomas (23 classic, eight desmoplastic-nodular, two large cell, one anaplastic), 17 ependymomas (13 World Health Organization [WHO] grade II, four WHO grade III), and seven atypical teratoid rhabdoid tumors. ADCs of solid tumor components and normal cerebellum were measured. Tumor-to-normal brain ADC ratios (hereafter, ADC ratio) were calculated. The medulloblastomas and ependymomas were subcategorized according to the latest WHO classification, and tumor cellularity was calculated. Correlation was sought between cell densities and mean tumor ADCs, minimum tumor ADCs, and ADC ratio. When all tumors were considered together, negative correlation was found between cellularity and mean tumor ADCs (ρ = -0.737, P correlation between cellularity and ADC ratio. Negative correlation was found between cellularity and minimum tumor ADC in atypical teratoid rhabdoid tumors (ρ = -0.786, P correlation was found between cellularity and mean tumor ADC and ADC ratio. There was no correlation between the ADC metrics and cellularity of the pilocytic astrocytomas, medulloblastomas, and ependymomas. Negative correlation was found between cellularity and ADC metrics of common pediatric cerebellar tumors. Although ADC metrics are useful in the preoperative diagnosis of common pediatric cerebellar tumors and this utility is generally attributed to differences in cellularity of tumors

Acute respiratory failure revealing a multilocular thymic cyst in an infant: a case report.

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Asma, Bouziri; Ammar, Khaldi; Khaled, Menif; Najoua, Guandoura; Nejla, Ben Jaballah

2009-11-30

Multilocular thymic cysts are rare benign lesions of the neck and mediastinum that can occur at any age. In children, multilocular thymic cysts are usually symptomatic after the age of 2 years and produce few symptoms. We present an unusual case of a multilocular thymic cyst diagnosed in a 3-month-old girl and causing severe respiratory failure. A 3 month-old-girl, with a medical history of dyspnea and wheezing since the age of 20 days, presented in our pediatric intensive care unit for acute respiratory failure requiring mechanical ventilation. The chest radiograph showed thoracic distension without any other abnormalities. The diagnosis of severe asthma was initially suspected and the patient was treated by intravenous corticosteroids and continuous perfusion of salbutamol without any improvement. A chest tomography scan was performed and demonstrated an anterior mediastinal multiseptated cystic mass extending from the inferior face of the thyroid gland to the left cardiophrenic angle. Sternotomy and excision biopsy were planned urgently. The cystic mass was excised completely. The histopathological examination confirmed the diagnosis of a multilocular thymic cyst. The particularities of our observation are the occurrence of a multilocular thymic cyst in a young infant and its presentation by a severe acute respiratory failure mimicking asthma.

Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

International Nuclear Information System (INIS)

Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y.; Yan, Mingshan

2009-01-01

Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

PICTORIAL ESSAY Thymic masses: A radiological review

African Journals Online (AJOL)

On chest X-ray, thymic abnormalities typically manifest as focal or diffuse ... Department of Radiodiagnosis and Imaging, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India. Corresponding author: B ... are considered of primary mediastinal origin if there is neither a detectable gonadal primary nor.

Audiovisual biofeedback improves the correlation between internal/external surrogate motion and lung tumor motion.

Science.gov (United States)

Lee, Danny; Greer, Peter B; Paganelli, Chiara; Ludbrook, Joanna Jane; Kim, Taeho; Keall, Paul

2018-03-01

Breathing management can reduce breath-to-breath (intrafraction) and day-by-day (interfraction) variability in breathing motion while utilizing the respiratory motion of internal and external surrogates for respiratory guidance. Audiovisual (AV) biofeedback, an interactive personalized breathing motion management system, has been developed to improve reproducibility of intra- and interfraction breathing motion. However, the assumption of the correlation of respiratory motion between surrogates and tumors is not always verified during medical imaging and radiation treatment. Therefore, the aim of the study was to test the hypothesis that the correlation of respiratory motion between surrogates and tumors is the same under free breathing without guidance (FB) and with AV biofeedback guidance for voluntary motion management. For 13 lung cancer patients receiving radiotherapy, 2D coronal and sagittal cine-MR images were acquired across two MRI sessions (pre- and mid-treatment) with two breathing conditions: (a) FB and (b) AV biofeedback, totaling 88 patient measurements. Simultaneously, the external respiratory motion of the abdomen was measured. The internal respiratory motion of the diaphragm and lung tumor was retrospectively measured from 2D coronal and sagittal cine-MR images. The correlation of respiratory motion between surrogates and tumors was calculated using Pearson's correlation coefficient for: (a) abdomen to tumor (abdomen-tumor) and (b) diaphragm to tumor (diaphragm-tumor). The correlations were compared between FB and AV biofeedback using several metrics: abdomen-tumor and diaphragm-tumor correlations with/without ≥5 mm tumor motion range and with/without adjusting for phase shifts between the signals. Compared to FB, AV biofeedback improved abdomen-tumor correlation by 11% (p = 0.12) from 0.53 to 0.59 and diaphragm-tumor correlation by 13% (p = 0.02) from 0.55 to 0.62. Compared to FB, AV biofeedback improved abdomen-tumor correlation by 17% (p = 0

The IASLC/ITMIG Thymic Epithelial Tumors Staging Project

DEFF Research Database (Denmark)

Kondo, Kazuya; Van Schil, Paul; Detterbeck, Frank C

2014-01-01

Stage classification is an important underpinning of management of patients with cancer, and rests on a combination of three components: T for tumor extent, N for nodal involvement, and M for more distant metastases. This article details an initiative to develop proposals for the first official...

[Impact of thymic function in age-related immune deterioration].

Science.gov (United States)

Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

2013-01-01

Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

Interaction between thymic cells and hemopoietic stem cells. Enhanced repopulation of the irradiated thymus

International Nuclear Information System (INIS)

Daculsi, Richard; Legrand, Elisabeth; Duplan, J.-F.

1977-01-01

In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells [fr

Lymphocyte depletion in thymic nurse cells: a tool to identify in situ lympho-epithelial complexes having thymic nurse cell characteristics

NARCIS (Netherlands)

Leene, W.; de Waal Malefijt, R.; Roholl, P. J.; Hoeben, K. A.

1988-01-01

In situ pre-existing complexes of epithelial cells and thymocytes having thymic nurse cell characteristics were visualized in the murine thymus cortex using dexamethasone as a potent killer of cortisone-sensitive thymocytes. The degradation and subsequent depletion of cortisone-sensitive thymocytes

Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling (Review).

Science.gov (United States)

Yan, Fenggen; Mo, Xiumei; Liu, Junfeng; Ye, Siqi; Zeng, Xing; Chen, Dacan

2017-11-01

The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress‑mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.

Tumor segmentation of whole-body magnetic resonance imaging in neurofibromatosis type 1 patients: tumor burden correlates

Energy Technology Data Exchange (ETDEWEB)

Heffler, Michael A.; Xi, Yin; Chhabra, Avneesh [University of Texas Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Le, Lu Q. [University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, TX (United States)

2017-01-15

Segmentation of whole-body MRI (WBMRI) to assess the feasibility, quantitate the total tumor volume (tumor burden) in patients with neurofibromatosis type 1 (NF1) and examine associations with demographic, disease-related and anthropomorphic features. A consecutive series of patients with NF1 underwent WBMRI and were reviewed for tumors. Tumors were segmented using a semiautomated software-based tool. Tumors were classified as superficial or deep and discrete or plexiform. Segmentation times were recorded. Segmentation yielded the quantity and tumor burden of superficial, internal and plexiform tumors. Correlations between segmentation data and demographic, disease-related and anthropomorphic features were examined. Fifteen patients were evaluated (42.3 ± 13.6 years, 10 female, 5 male). Segmentation times were a median of 30 min and yielded 2,328 tumors (1,582 superficial, 746 internal and 23 plexiform). One tumor was malignant. Tumor counts ranged from 14 to 397. Tumor burden ranged from 6.95 cm3 to 571 cm3. Individual tumor volume ranged from 0.0120 cm3 to 298 cm3. Significant correlation was found between the total volume of superficial tumors and height (ρ = 0.5966, p < 0.02). Male patients had higher overall tumor burdens (p < 0.05) and higher superficial tumor burden (p < 0.03). Patients with negative family history had more tumors (p < 0.05). Segmentation of WBMRI in patients with NF1 is feasible and elucidates meaningful relationships among disease phenotype, anthropomorphic and demographic features. (orig.)

Tumor segmentation of whole-body magnetic resonance imaging in neurofibromatosis type 1 patients: tumor burden correlates

International Nuclear Information System (INIS)

Heffler, Michael A.; Xi, Yin; Chhabra, Avneesh; Le, Lu Q.

2017-01-01

Segmentation of whole-body MRI (WBMRI) to assess the feasibility, quantitate the total tumor volume (tumor burden) in patients with neurofibromatosis type 1 (NF1) and examine associations with demographic, disease-related and anthropomorphic features. A consecutive series of patients with NF1 underwent WBMRI and were reviewed for tumors. Tumors were segmented using a semiautomated software-based tool. Tumors were classified as superficial or deep and discrete or plexiform. Segmentation times were recorded. Segmentation yielded the quantity and tumor burden of superficial, internal and plexiform tumors. Correlations between segmentation data and demographic, disease-related and anthropomorphic features were examined. Fifteen patients were evaluated (42.3 ± 13.6 years, 10 female, 5 male). Segmentation times were a median of 30 min and yielded 2,328 tumors (1,582 superficial, 746 internal and 23 plexiform). One tumor was malignant. Tumor counts ranged from 14 to 397. Tumor burden ranged from 6.95 cm3 to 571 cm3. Individual tumor volume ranged from 0.0120 cm3 to 298 cm3. Significant correlation was found between the total volume of superficial tumors and height (ρ = 0.5966, p < 0.02). Male patients had higher overall tumor burdens (p < 0.05) and higher superficial tumor burden (p < 0.03). Patients with negative family history had more tumors (p < 0.05). Segmentation of WBMRI in patients with NF1 is feasible and elucidates meaningful relationships among disease phenotype, anthropomorphic and demographic features. (orig.)

Volume-based quantification using dual-energy computed tomography in the differentiation of thymic epithelial tumours: an initial experience

Energy Technology Data Exchange (ETDEWEB)

Chang, Suyon; Hur, Jin; Im, Dong Jin; Suh, Young Joo; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Choi, Byoung Wook [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Han, Kyunghwa [Yonsei University College of Medicine, Yonsei Biomedical Research Institute, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Kim, Dae Joon; Lee, Chang Young [Yonsei University College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of); Shin, Ha Young [Yonsei University College of Medicine, Department of Neurology, Seoul (Korea, Republic of)

2017-05-15

To investigate the diagnostic value of dual-energy computed tomography (DECT) in differentiating between low- and high-risk thymomas and thymic carcinomas. Our institutional review board approved this study, and patients provided informed consent. We prospectively enrolled 37 patients (20 males, mean age: 55.6 years) with thymic epithelial tumour. All patients underwent DECT. For quantitative analysis, two reviewers measured the following tumour parameters: CT attenuation value in contrast Hounsfield units (CHU), iodine-related HU and iodine concentration (mg/ml). Pathological results confirmed the final diagnosis. Of the 37 thymic tumours, 23 (62.2 %) were low-risk thymomas, five (13.5 %) were high-risk thymomas and nine (24.3 %) were thymic carcinomas. According to quantitative analysis, iodine-related HU and iodine concentration were significantly different among low-risk thymomas, high-risk thymomas and thymic carcinomas (median: 29.78 HU vs. 14.55 HU vs. 19.95 HU, p = 0.001 and 1.92 mg/ml vs. 0.99 mg/ml vs. 1.18 mg/ml, p < 0.001, respectively). DECT using a quantitative analytical method based on iodine concentration measurement can be used to differentiate among thymic epithelial tumours using single-phase scanning. (orig.)

Effects of whole-body irradiation on neonatally thymectomized mice. Incidence of benign and malignant tumors

International Nuclear Information System (INIS)

Anderson, R.E.; Howarth, J.L.; Troup, G.M.

1978-01-01

The individual and combined effects of neonatal thymectomy and whole-body irradiation on the prevalence of benign and malignant tumors in germ-free female mice of the Charles Rivers line were studied to determine if a portion of the tumorigenic effects of irradiation can be attributed to injury of the thymic-dependent component of the immune response. Neonatal thymectomy increased (a) the incidence of benign and malignant tumors and (b) the prevalence of multiple primary neoplasms in an individual mouse. Whole-body exposure to 700 rad at 6 weeks of age further increased the incidence of tumors, but the relative magnitude of this increase was less pronounced than in sham-operated controls. Thus, the cumulative effects of thymectomy plus irradiation are less pronounced than the sum of the individual effects. One of several possible explanations for this observation is that a portion of the carcinogenic effects of whole-body irradiation is mediated by suppression of the thymic-dependent component of the immune response

Thymic hyperplasia in a patient with Grave's disease.

Science.gov (United States)

Hamzaoui, Amira A; Klii, Rim R; Salem, Randa R; Kochtali, Ines I; Golli, Mondher M; Mahjoub, Silvia S

2012-02-09

Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens

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Sergio Cepeda

2018-01-01

Full Text Available Although autoimmune disorders are a significant source of morbidity and mortality in older individuals, the mechanisms governing age-associated increases in susceptibility remain incompletely understood. Central T cell tolerance is mediated through presentation of self-antigens by cells constituting the thymic microenvironment, including epithelial cells, dendritic cells, and B cells. Medullary thymic epithelial cells (mTECs and B cells express distinct cohorts of self-antigens, including tissue-restricted self-antigens (TRAs, such that developing T cells are tolerized to antigens from peripheral tissues. We find that expression of the TRA transcriptional regulator Aire, as well as Aire-dependent genes, declines with age in thymic B cells in mice and humans and that cell-intrinsic and cell-extrinsic mechanisms contribute to the diminished capacity of peripheral B cells to express Aire within the thymus. Our findings indicate that aging may diminish the ability of thymic B cells to tolerize T cells, revealing a potential mechanistic link between aging and autoimmunity.

Bilateral cervical ectopic thymic nodules with accessory thyroid tissue and an ectopic parathyroid in the neck region

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Wea-Lung Lin

2011-03-01

Full Text Available Some remnants of thymic tissue may be deposited along the pathway of the descent of the neck during embryologic development of the thymus. Ectopic thymic tissue is usually deposited along the pathway from the mandibular angle to the manubrium of the sternum. Most reported cases of an ectopic thymus occurred in children, and cases are less common in adults. We report a 26-year-old woman, who was incidentally found to have 2 neck nodules on the posterior side of the bilateral upper pole of the thyroid gland while undergoing a subtotal thyroidectomy. The left-side neck nodule showed accessory thyroid follicles intermixed with ectopic thymic tissue, and the right-side neck nodule was ectopic parathyroid tissue together with ectopic thymic tissue.

Thymic irradiation and chronic myelogenous leukemia

International Nuclear Information System (INIS)

Shimaoka, K.; Sokal, J.E.

1977-01-01

Two cases of Ph positive chronic myelogenous leukemia with a history of thymic irradiation are presented. Both patients received radiation therapy from low voltage x-ray equipment at two to three months of age. Leukemia developed 18 and 22 years later. Presentation, response to antileukemic therapy, and clinical course did not differ from that of other patients with this disease treated in our department

Photoperiodic modulation of local melatonin synthesis and its role in regulation of thymic homeostasis in Funambulus pennanti.

Science.gov (United States)

Gupta, Sameer; Haldar, Chandana

2016-12-01

The effect of photo-neuroendocrine system on the thymic (immune) functions is mediated by gonadal steroid and the pineal hormone melatonin. The present study explored the effect of photoperiod on the thymic melatonergic system and its role in protection of thymic T-cells from the testosterone induced seasonal oxidative stress and apoptosis. Exposure to long day-length (LD) was noted to decrease local (thymic) melatonin content and induce oxidative stress and apoptosis in the thymus. Increased peripheral level of testosterone upregulated the androgen receptor expression and, consequently reduced proliferation response of the thymocytes. Short day conditions (SD) however, reversed the effect of LD on the thymic physiology. Low level of testosterone was concomitant with diminished nitro-oxidative stress and decreased expression of redox sensitive factors (NF-κB, p53 and Bax/Bcl-2 ratio) in the thymus. SD retarded activation of caspase-3 resulting in procaspase-3 accumulation. Further, in vitro treatment of thymocytes with AR antagonist flutamide impaired the sensitivity of thymocytes to androgen and reversed the deleterious effects of testosterone on the proliferative and apoptotic responses of thymocytes. Therefore, it can be suggested that thymus derived melatonin protects thymic T-cells from testosterone induced seasonal oxidative stress, apoptosis and also acts as a potent paracrine factor for maintenance of redox status to ensure thymocyte survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Thymic hyperplasia in a patient with Grave's disease

Directory of Open Access Journals (Sweden)

Hamzaoui Amira A

2012-02-01

Full Text Available Abstract Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia.

Effect of Boron on Thymic Cytokine Expression, Hormone Secretion, Antioxidant Functions, Cell Proliferation, and Apoptosis Potential via the Extracellular Signal-Regulated Kinases 1 and 2 Signaling Pathway.

Science.gov (United States)

Jin, Erhui; Ren, Man; Liu, Wenwen; Liang, Shuang; Hu, Qianqian; Gu, Youfang; Li, Shenghe

2017-12-27

Boron is an essential trace element in animals. Appropriate boron supplementation can promote thymus development; however, a high dose of boron can lead to adverse effects and cause toxicity. The influencing mechanism of boron on the animal body remains unclear. In this study, we examined the effect of boron on cytokine expression, thymosin and thymopoietin secretion, antioxidant function, cell proliferation and apoptosis, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the thymus of rats. We found that supplementation with 10 and 20 mg/L boron to the drinking water significantly elevated levels of interleukin 2 (IL-2), interferon γ (IFN-γ), interleukin 4 (IL-4), and thymosin α1 in the thymus of rats (p boron had no apparent effect on many of the above indicators. In contrast, supplementation with 480 and 640 mg/L boron had the opposite effect on the above indicators in rats and elevated levels of pro-inflammatory cytokines, such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α) (p boron to the drinking water had a U-shaped dose-effect relationship with thymic cytokine expression, hormone secretion, antioxidant function, cell proliferation, and apoptosis. Specifically, supplementation with 10 and 20 mg/L boron promoted thymocyte proliferation and enhanced thymic functions. However, supplementation with 480 and 640 mg/L boron inhibited thymic functions and increased the number of apoptotic thymocytes, suggesting that the effects of boron on thymic functions may be caused via the ERK1/2 signaling pathway.

MRI of breast tumors with emphasis on histopathologic correlation

International Nuclear Information System (INIS)

Kuwabara, Masako

1991-01-01

Breast MR imaging is now expected as the third most important diagnostic modality. The author investigated relationship between signal intensity of T2 weighted images (T2WI) and various pathological findings of 51 mass lesions in 51 female patients. T2WI were not effective in differentiation between malignant and benign lesions. High signal intensity areas defined visually well correlated with pathological tissues with large water content such as necrosis, edema, cyst, and dilatated ducts. There was also good correlation between low signal intensity areas and pathological tissue with less water content such as fibrosis, scar, and hyalinization. Signal intensity measured by tumor/fat ratio had no correlation with water content. It probably indicates that visually defined signal intensity is more reliable than the measured ratio. In conclusion, it is warrented to say that T2WI is a good tool for investigating secondary changes of breast tumors and helpful in diangosis of high intensity tumors described above. (author)

Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation

International Nuclear Information System (INIS)

Muto, M.; Kubo, E.; Kamisaku, H.; Sado, T.

1990-01-01

Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells

Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology

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Young Il Choi

2013-11-01

Full Text Available An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO mice where mislocalized CD69+ thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1-/- genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1flox/flox mice crossed to pLck-Cre, pKeratin14-Cre or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO lines involving thymocytes (D1ThyCKO, thymic epithelium (D1EpCKO and thymic endothelium (D1EnCKO, respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components.

A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma.

Science.gov (United States)

Sakane, Tadashi; Murase, Takayuki; Okuda, Katsuhiro; Takino, Hisashi; Masaki, Ayako; Oda, Risa; Watanabe, Takuya; Kawano, Osamu; Haneda, Hiroshi; Moriyama, Satoru; Saito, Yushi; Yamada, Takeshi; Nakanishi, Ryoichi; Inagaki, Hiroshi

2018-01-23

Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.

Perioperative Mortality and Long-Term Survival in 80 Dogs and 32 Cats Undergoing Excision of Thymic Epithelial Tumors.

Science.gov (United States)

Garneau, Mark S; Price, Lori Lyn; Withrow, Stephen J; Boston, Sarah E; Ewing, Patty J; McClaran, Janet Kovak; Liptak, Julius M; Berg, John

2015-07-01

To examine perioperative mortality, long-term survival, causes of death, and prognostic factors for dogs and cats undergoing surgical excision of thymic epithelial tumors (TETs). Multi-institutional case series. Eighty dogs and 32 cats. Follow-up information was obtained for dogs and cats that underwent surgical excision of a TET between 2001 and 2012. Perioperative mortality was 20% in dogs and 22% in cats. No independent risk factors for perioperative mortality were identified. The estimated median survival time for all dogs was 1.69 years (95% CI 0.56-4.32) and the 1- and 4-year survival rates were 55% (95% CI 44-67) and 44% (95% CI 32-56). The estimated median survival time for all cats was 3.71 years (95% CI 0.56-unestimatable) and the 1- and 4-year survival rates were 70% (95% CI 53-87) and 47% (95% CI 0-100). Of animals that survived to discharge, 42% of dogs and 20% of cats eventually died of TET-related causes. The presence of paraneoplastic syndromes (hazard ratio [HR] 5.78, 95% CI 1.64-20.45, P = .007) or incomplete histologic margins (HR 6.09, 95% CI 1.50-24.72, P = .01) were independently associated with decreased survival in dogs. No significant predictors of survival were identified in cats. Conclusions regarding the effect of chemotherapy or radiation therapy could not be made. While there is substantial risk of perioperative death in dogs and cats undergoing surgery for TETs, many animals that survive to discharge have prolonged survival. Survival is significantly decreased in dogs with paraneoplastic syndromes or incomplete histologic margins. © Copyright 2014 by The American College of Veterinary Surgeons.

Effect of granulocyte colony-stimulating factor on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation

International Nuclear Information System (INIS)

Zhao Hongxia; Guo Mei; Sun Xuedong; Ai Huisheng

2011-01-01

Objective: To investigate the effects of recombinant human granulocyte colony stimulating factor (G-CSF) on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation. Methods: Female BALB/c mice were irradiated with a 6.0 Gy of γ-ray total-body irradiation and then randomly divided into GCSF group and control group. For mice in the GCSF group, recombinant human G-CSF 100 μg · kg -1 · d -1 was injected subcutaneously once daily for 14 continuous days and mice in the control group were given the same volume of phosphate buffered solution (PBS). At 7, 14, 21 and 28 days later, mice were killed and thymus mononuclear cell suspension were analyzed by flow cytometry for the percentage of the four stages of thymic CD4 - CD8 - double negative cells (DN1-4) and the CD4 + CD8 + double positive ( CD4 + CD8 + DP), CD4 + CD8 - single positive (CD4 + SP), CD4 - CD8 + single positive cells (CD8 + SP).Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTRECs) of the thymic cells of 30 and 60 d after irradiation. Results: The percentage of thymic DN1 cells in GCSF group was significantly higher than that of the control group 7 d after irradiation (t=9.59, P<0.05). 21 d later, the proportion of thymic DN3 and DN4 cells were higher than those of the control group (t=16.37, 7.6, P<0.05). The percentage of thymic CD4 + CD8 + DP cells decreased 7 d after irradiation,increased at 14 d, decreased again at 21 days,and then got a permanent recover. The percentage of thymic CD4 + CD8 + DP cells in the GCSF group recovered to normal and was significantly higher than that of the control group 28 days after irradiation (t=12.22, P<0.05). The percentage of thymic CD8 + SP cells of the GCSF group was significantly higher than that of the control group 21 d after irradiation (t=3.77, P<0.05), while G-CSF had no obvious influence on the percentage of the thymic CD4 + SP cells. The sjTRECs copies in the

Correlation of MRI Biomarkers with Tumor Necrosis in Hras5 Tumor Xenograft in Athymic Rats

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Daniel P. Bradley

2007-05-01

Full Text Available Magnetic resonance imaging (MRI can measure the effects of therapies targeting the tumor vasculature and has demonstrated that vascular-damaging agents (VDA induce acute vascular shutdown in tumors in human and animal models. However, at subtherapeutic doses, blood flow may recover before the induction of significant levels of necrosis. We present the relationship between changes in MRI biomarkers and tumor necrosis. Multiple MRI measurements were taken at 4.7 T in athymic rats (n = 24 bearing 1.94 ± 0.2-cm3 subcutaneous Hras5 tumors (ATCC 41000 before and 24 hours after clinically relevant doses of the VDA, ZD6126 (0-10 mg/kg, i.v.. We measured effective transverse relaxation rate (R2*, initial area under the gadolinium concentration-time curve (IAUGC60/150, equivalent enhancing fractions (EHF60/150, time constant (Ktrans, proportion of hypoperfused voxels as estimated from fit failures in Ktrans analysis, and signal intensity (SI in T2-weighted MRI (T2W. ZD6126 treatment induced < 90% dose-dependent tumor necrosis at 10 mg/kg; correspondingly, SI changes were evident from T2W MRI. Although R2* did not correlate, other MRI biomarkers significantly correlated with necrosis at doses of ≥ 5 mg/kg ZD6126. These data on Hras5 tumors suggest that the quantification of hypoperfused voxels might provide a useful biomarker of tumor necrosis.

S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

Science.gov (United States)

Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

2014-05-01

Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

Thymic masses: A radiological review | Mittal | SA Journal of Radiology

African Journals Online (AJOL)

Abstract. Various thymic masses and their normal variations have different pathological and management consequences. Radiologists and clinicians should be aware of these entities so that appropriate and timely treatment can be given.

Cross-correlation enhanced stability in a tumor cell growth model with immune surveillance driven by cross-correlated noises

International Nuclear Information System (INIS)

Zeng Chunhua; Zhou Xiaofeng; Tao Shufen

2009-01-01

The transient properties of a tumor cell growth model with immune surveillance driven by cross-correlated multiplicative and additive noises are investigated. The explicit expression of extinction rate from the state of a stable tumor to the state of extinction is obtained. Based on the numerical computations, we find the following: (i) the intensity of multiplicative noise D and the intensity of additive noise α enhance the extinction rate for the case of λ ≤ 0 (i.e. λ denotes cross-correlation intensity between two noises), but for the case of λ > 0, a critical noise intensity D or α exists at which the extinction rate is the smallest; D and α at first weaken the extinction rate and then enhance it. (ii) The immune rate β and the cross-correlation intensity λ play opposite roles on the extinction rate, i.e. β enhances the extinction rate of the tumor cell, while λ weakens the extinction rate of the tumor cell. Namely, the immune rate can enhance the extinction of the tumor cell and the cross-correlation between two noises can enhance stability of the cancer state.

Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined immunodeficiency

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Francesca eRucci

2011-05-01

Full Text Available Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky SCID, carrying hypomorphic mutations in Rag1 and Lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs. While the ability of mTECs to express Aire is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens (TSAs is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in Rag1 and Lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation.

FOXN1: a master regulator gene of thymic epithelial development programme

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Rosa eRomano

2013-07-01

Full Text Available T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs drive T cell differentiation, education and selection processes, while the thymocyte-dependent signals allow TECs to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1 and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1 gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the postnatal thymus. An inborn null mutation in FOXN1 leads to Nude/SCID phenotype in mouse, rat and humans. In Foxn1-/- nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality.

Different mechanisms for the resistance of C3H and STS strain mice to the development of thymic lymphomas following fractionated whole-body irradiation

International Nuclear Information System (INIS)

Aizawa, Shiro; Kamisaku, Hitoko

1999-01-01

B10 strain mice are extremely susceptible for induction of thymic lymphomas by fractionated whole-body irradiation (FI), whereas C3H and STS mice are fairly resistant. In the present study, we constructed radiation bone marrow chimeras in the reciprocal donor-host combinations of susceptible and resistant mice with use of Thy1 markers that allow to determine genetic origins of donor- and host-type thymocytes, and then to analyze the influence of host/thymic environment on the strain-dependent susceptibility to thymic lymphomagenesis. B10.Thy1.1→C3H, B10.Thy1.1→STS as well as B10.Thy1.1→B10 bone marrow chimeras manifested a high incidence of thymic lymphomas after FI-treatment, whereas C3H. Thy1.1→B10 and STS→B10 as well as C3H→C3H and STS→STS chimeras manifested a low incidence of thymic lymphoma. Furthermore, FI-treatment of [B10.Thy1.1+C3H]→B10 mixed chimeras resulted in the generation of similar numbers of thymic lymphomas of B10 and C3H origins, whereas FI-treatment of [B10.Thy1.1+STS]→B10 mixed chimeras preferentially induced thymic lymphomas of B10 origin. These results indicated that host environments of C3H and STS resistant mice are not inhibitory for the development of thymic lymphomas, genetic factors responsible for the strain-dependent susceptibility and/or resistance to FI-induced lymphomagenesis exert their effects entirely on bone-marrow derived cells, and the resistance of STS mice to FI-induced thymic lymphomagenesis is an intrinsic property of thymocytes as the targets of thymic lymphoma induction, whereas bone marrow-derived thymic stroma cells seem to play a significant role in the resistance of C3H mice for the induction of thymic lymphomas. (author)

Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

International Nuclear Information System (INIS)

Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A.; Beham-Schmid, C.; Groell, R.; Smolle-Juettner, F.M.; Renner, H.; Quehenberger, F.

1999-01-01

All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [de

Stimulation of anti-tumor effect by low-dose irradiation. Pt. 2. The prolongation of life span in AKR mice

International Nuclear Information System (INIS)

Ishii, Keiichiro; Misonoh, Jun; Hosoi, Yoshio; Ono, Tetsuya; Sakamoto, Kiyohiko.

1994-01-01

To elucidate the antileukemic effect of low-dose X-irradiation, we studied the influence of periodical low-dose X-irradiation on survival and tumor incidence of thymus using AKR mice. The findings of the experiments were as follows; (1) The median survival time of control AKR mice was 283±3 days. It of irradiation group of 15 cGy/week and 30cGy was 309±14 days and 316±10 days respectively. The life span was significantly prolonged (p < 0.05 and p < 0.01 respectively by Wilcoxon test) by periodical low-dose X-irradiation in term of breeding. (2) The incidence of thymus tumor which is observed remarkably in control AKR mice was 48.8%. It of irradiation group of 15 cGy/week and 30 cGy/week was 40% and 20% respectively. Inversely, the non-tumor incidence of tymus in control AKR mice was 19.5%. It of irradiation group of 15 cGy/week and 30 cGy/week was 32.5% and 51.4% respectively. The thymic tumor incidence was significantly decreased (p < 0.01 by chi-square test) in irradiation group of 30 cGy/week. (3) The incidence of thymic lymphoma as a death cause in control AKR mice was 80.4%. It of irradiation group of 15 cGy/week and 30cGy/week was 67.5% and 48.6% respectively. The incidence of thymic lymphoma was significantly decreased (p < 0.05 by chi-square test) in irradiation group of 30 cGy/week. (author)

MUC2 Expression Is Correlated with Tumor Differentiation and Inhibits Tumor Invasion in Gastric Carcinomas: A Systematic Review and Meta-analysis

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Jung-Soo Pyo

2015-05-01

Full Text Available Background: While MUC2 is expressed in intestinal metaplasia and malignant lesions, the clinicopathological significance of MUC2 expression is not fully elucidated in gastric carcinoma (GC. Methods: The present study investigated the correlation between MUC2 expression and clinicopathological parameters in 167 human GCs. In addition, to confirm the clinicopathological significance of MUC2 expression, we performed a systematic review and meta-analysis in 1,832 GCs. Results: MUC2 expression was found in 58 of 167 GCs (34.7%. MUC2-expressing GC showed lower primary tumor (T, regional lymph node (N, and tumor node metastasis (TNM stages compared with GCs without MUC2 expression (p=.001, p=.001, and p=.011, respectively. However, MUC2 expression was not correlated with Lauren’s classification and tumor differentiation. In meta-analysis, MUC2 expression was significantly correlated with differentiation and lower tumor stage (odds ratio [OR], 1.303; 95% confidence interval [CI], 1.020 to 1.664; p = .034 and OR, 1.352; 95% CI, 1.055 to 1.734; p = .017, respectively but not with Lauren’s classification, pN stage, or pTNM stage. Conclusions: MUC2 expression was correlated with a lower tumor depth and lower lymph node metastasis in our study; the meta-analysis showed a correlation of MUC2 expression with tumor differentiation and lower tumor depth.

Can a Proper T-Cell Development Occur in an Altered Thymic Epithelium? Lessons From EphB-Deficient Thymi

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Juan José Muñoz

2018-04-01

Full Text Available For a long time, the effects of distinct Eph tyrosine kinase receptors and their ligands, ephrins on the structure, immunophenotype, and development of thymus and their main cell components, thymocytes (T and thymic epithelial cells (TECs, have been studied. In recent years, the thymic phenotype of mutant mice deficient in several Ephs and ephrins B has been determined. Remarkably, thymic stroma in these animals exhibits important defects that appear early in ontogeny but little alterations in the proportions of distinct lymphoid cell populations. In the present manuscript, we summarize and extend these results discussing possible mechanisms governing phenotypical and functional thymocyte maturation in an absence of the critical T–TEC interactions, concluding that some signaling mediated by key molecules, such as MHCII, CD80, β5t, Aire, etc. could be sufficient to enable a proper maturation of thymocytes, independently of morphological alterations affecting thymic epithelium.

Cellular and Tumor Radiosensitivity is Correlated to Epidermal Growth Factor Receptor Protein Expression Level in Tumors Without EGFR Amplification

International Nuclear Information System (INIS)

Kasten-Pisula, Ulla; Saker, Jarob; Eicheler, Wolfgang; Krause, Mechthild; Yaromina, Ala; Meyer-Staeckling, Soenke; Scherkl, Benjamin; Kriegs, Malte; Brandt, Burkhard; Grenman, Reidar; Petersen, Cordula; Baumann, Michael; Dikomey, Ekkehard

2011-01-01

Purpose: There is conflicting evidence for whether the expression of epidermal growth factor receptor in human tumors can be used as a marker of radioresponse. Therefore, this association was studied in a systematic manner using squamous cell carcinoma (SCC) cell lines grown as cell cultures and xenografts. Methods and Materials: The study was performed with 24 tumor cell lines of different tumor types, including 10 SCC lines, which were also investigated as xenografts on nude mice. Egfr gene dose and the length of CA-repeats in intron 1 were determined by polymerase chain reaction, protein expression in vitro by Western blot and in vivo by enzyme-linked immunosorbent assay, and radiosensitivity in vitro by colony formation. Data were correlated with previously published tumor control dose 50% data after fractionated irradiation of xenografts of the 10 SCC. Results: EGFR protein expression varies considerably, with most tumor cell lines showing moderate and only few showing pronounced upregulation. EGFR upregulation could only be attributed to massive gene amplification in the latter. In the case of little or no amplification, in vitro EGFR expression correlated with both cellular and tumor radioresponse. In vivo EGFR expression did not show this correlation. Conclusions: Local tumor control after the fractionated irradiation of tumors with little or no gene amplification seems to be dependent on in vitro EGFR via its effect on cellular radiosensitivity.

A stromal myoid cell line provokes thymic erythropoiesis between ...

African Journals Online (AJOL)

Background: The thymus provides an optimal cellular and humoral microenvironment for cell line committed differentiation of haematopoietic stem cells. The immigration process requires the secretion of at least one peptide called thymotaxine by cells of the reticulo-epithelial (RE) network of the thymic stromal cellular ...

The correlation between internal and external markers for abdominal tumors: Implications for respiratory gating

International Nuclear Information System (INIS)

Gierga, David P.; Brewer, Johanna; Sharp, Gregory C.; Betke, Margrit; Willett, Christopher G.; Chen, George T.Y.

2005-01-01

Purpose: The correlation of the respiratory motion of external patient markers and abdominal tumors was examined. Data of this type are important for image-guided therapy techniques, such as respiratory gating, that monitor the movement of external fiducials. Methods and Materials: Fluoroscopy sessions for 4 patients with internal, radiopaque tumor fiducial clips were analyzed by computer vision techniques. The motion of the internal clips and the external markers placed on the patient's abdominal skin surface were quantified and correlated. Results: In general, the motion of the tumor and external markers were well correlated. The maximum amount of peak-to-peak craniocaudal tumor motion was 2.5 cm. The ratio of tumor motion to external-marker motion ranged from 0.85 to 7.1. The variation in tumor position for a given external-marker position ranged from 2 to 9 mm. The period of the breathing cycle ranged from 2.7 to 4.5 seconds, and the frequency patterns for both the tumor and the external markers were similar. Conclusions: Although tumor motion generally correlated well with external fiducial marker motion, relatively large underlying tumor motion can occur compared with external-marker motion and variations in the tumor position for a given marker position. Treatment margins should be determined on the basis of a detailed understanding of tumor motion, as opposed to relying only on external-marker information

Effect of Audio Coaching on Correlation of Abdominal Displacement With Lung Tumor Motion

International Nuclear Information System (INIS)

Nakamura, Mitsuhiro; Narita, Yuichiro; Matsuo, Yukinori; Narabayashi, Masaru; Nakata, Manabu; Sawada, Akira; Mizowaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

2009-01-01

Purpose: To assess the effect of audio coaching on the time-dependent behavior of the correlation between abdominal motion and lung tumor motion and the corresponding lung tumor position mismatches. Methods and Materials: Six patients who had a lung tumor with a motion range >8 mm were enrolled in the present study. Breathing-synchronized fluoroscopy was performed initially without audio coaching, followed by fluoroscopy with recorded audio coaching for multiple days. Two different measurements, anteroposterior abdominal displacement using the real-time positioning management system and superoinferior (SI) lung tumor motion by X-ray fluoroscopy, were performed simultaneously. Their sequential images were recorded using one display system. The lung tumor position was automatically detected with a template matching technique. The relationship between the abdominal and lung tumor motion was analyzed with and without audio coaching. Results: The mean SI tumor displacement was 10.4 mm without audio coaching and increased to 23.0 mm with audio coaching (p < .01). The correlation coefficients ranged from 0.89 to 0.97 with free breathing. Applying audio coaching, the correlation coefficients improved significantly (range, 0.93-0.99; p < .01), and the SI lung tumor position mismatches became larger in 75% of all sessions. Conclusion: Audio coaching served to increase the degree of correlation and make it more reproducible. In addition, the phase shifts between tumor motion and abdominal displacement were improved; however, all patients breathed more deeply, and the SI lung tumor position mismatches became slightly larger with audio coaching than without audio coaching.

Spindle epithelial tumor with thymus-like differentiation of thyroid gland: Report of two cases with follow-up

Directory of Open Access Journals (Sweden)

Nisa Azizun

2010-10-01

Full Text Available Spindle epithelial tumor with thymus-like differentiation (SETTLE is a rare malignant thyroid tumor showing thymic or related branchial pouch differentiation. The tumors are composed predominantly of spindle cells along with focal epithelial component and ductular formations. SETTLE occurs in young patients, with indolent growth and a tendency to develop delayed blood-borne metastases. We herein report two cases of SETTLE with a follow-up period of 64 months and 30 months, respectively.

Association of murine lupus and thymic full-length endogenous retroviral expression maps to a bone marrow stem cell

International Nuclear Information System (INIS)

Krieg, A.M.; Gourley, M.F.; Steinberg, A.D.

1991-01-01

Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells

DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

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Masako Osada

2010-02-01

Full Text Available Thymic epithelial cell (TEC microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus.Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+ Foxn1(+ and Aire(+ TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments.Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic

A case of congenital Langerhans cell histiocytosis with skin and thymic lesions: Exploring the prognostic value of thymus involvement

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M.M. Escudero-Góngora

2016-10-01

Full Text Available Thymus evaluation is not included in the guidelines of the Histiocyte Society, so its prevalence, management and prognosis are not well established. We present a newborn with self-healing cutaneous LCH and thymic involvement that was evaluated with a thoracic ultrasound. With the current evidence we are unable to predict the prognosis of the thymus association in neonatal LCH. We suggest that performing thymic ultrasound study, which is a non-invasive technique, would allow us to know the incidence of thymic involvement and its role on prognosis.

A pediatric case of life-threatening airway obstruction caused by a cervicomediastinal thymic cyst

Energy Technology Data Exchange (ETDEWEB)

Komura, Makoto; Kanamori, Yutaka; Sugiyama, Masahiko; Iwanaka, Tadashi [University of Tokyo Hospital, Department of Pediatric Surgery, Tokyo (Japan); Fukushima, Noriyoshi [University of Tokyo Hospital, Department of Pathology, Tokyo (Japan)

2010-09-15

Most patients with thymic cysts complain of a slowly enlarging, asymptomatic cervical mass. Only 6-10% suffer dysphagia, dyspnoea, stridor, cervical pain or vocal paralysis. In some rare cases sudden onset of severe dyspnoea or asphyxia is the first symptom, especially in neonates and small infants. We report a unique case of a 20-month-old child, who required emergency tracheal intubation due to asphyxia. Cervicomediastinal thymic cyst might need to be included in causes of life-threatening airway obstruction in young children. (orig.)

Expression of tyrosine kinase gene in mouse thymic stromal cells

NARCIS (Netherlands)

Rinke de Wit, T. F.; Izon, D. J.; Revilla, C.; Oosterwegel, M.; Bakker, A. Q.; van Ewijk, W.; Kruisbeek, A. M.

1996-01-01

Amongst the most important signal transduction molecules involved in regulating growth and differentiation are the protein tyrosine kinases (PTK). Since T cell development is a consequence of interactions between thymic stromal cells (TSC) and thymocytes, identification of the PTK in both

Thymic size at birth in preterm infants with severe respiratory ...

African Journals Online (AJOL)

To determine whether the thymic size in preterm infants with severe respiratory distress syndrome (RDS) can be used to predict ... chorio-amnionitis is associated with a small thymus at birth.4,7. In those ..... Acta Paediatr 2000; 89: 975-978. 6.

Effects of neonatal thymic exposure to high doses of X-irradiation

International Nuclear Information System (INIS)

Bains, G.S.; Sundaram, K.

1979-01-01

The thymic region of neonatal Swiss mice was exposed to doses varying from 1000 R to 2000 R of X-irradiation. The animals did not show any signs of wasting syndrome up to 6 months after irradiation. At this time hyperplasia of the thymus with an associated lymphocytosis was evident in irradiated animals. Antibody production to sheep red blood cells (SRBC) was not affected. However, at 12 months post-irradiation the animals showed signs of wasting disease with a progressive increase in their numbers at 18 and 24 months of age. The percentage incidence of animals with wasting disease was dose dependent. At this stage in the majority of the animals with the disease the thymus showed varying degrees of atrophy along with splenomegaly. There were no significant differences in the number of lymphocytes but the number of granulocytes showed a substantial increase. This was more evident in animals exposed to 2000 R to the thymic region. Though one observed a lowered ability to form antibodies to bovine serum albumin (BSA) with advancing age, the thymic irradiation did not affect the immune response to BSA even in animals manifesting wasting disease. An interesting observation has been the development of a severe loss of muscle power and tone in the hind limbs in a large majority of animals. (author)

Alteration of T cell function in healthy persons with a history of thymic x irradiation

International Nuclear Information System (INIS)

Rieger, C.H.L.; Kraft, S.C.; Rothberg, R.M.

1975-01-01

The possible late effects of x irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytohemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptokinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis

Alteration of T cell function in healthy persons with a history of thymic x irradiation

Energy Technology Data Exchange (ETDEWEB)

Rieger, C.H.L.; Kraft, S.C.; Rothberg, R.M.

1975-10-01

The possible late effects of x irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytohemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptokinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

Science.gov (United States)

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

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)

Correlation between radiosensitivity of transplanted solid tumor and nutritive condition of host animal

Energy Technology Data Exchange (ETDEWEB)

Ando, K [Showa Univ., Tokyo (Japan). School of Medicine

1975-04-01

Studies on radiosensitivity of the transplanted tumor were carried out and the following results were obtained: 1. Radiosensitivity of the tumor ran parallel to the growth rate. 2. Malnutrition of the host after irradiation made the tumor radiosensitive, probably because the sublethally damaged tumor cell did not recover. 3. Mitotic index correlated well with radiosensitivity, and the low mitotic index caused by starvation made the tumor cell recover poorly. 4. The DNA synthetic rate measured by means of iodine labeled IUdR did not successfully correlate with the mitotic rate, presumably because of the role of thymidine pool size in this experiment. 5. The serum protein level possibly with the tumor growth, which modified the radiosensitivity. 6. Serum oxygen was difficult to interpret, however, it might be compensated by erythrocytosis in a starved condition.

A False Positive I-131 Metastatic Survey Caused by Radioactive Iodine Uptake by a Benign Thymic Cyst

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Avneet K. Singh

2017-01-01

Full Text Available Thyroid carcinoma is the most common endocrine malignancy in the United States with increasing incidence and diagnosis but stable mortality. Differentiated thyroid cancer rarely presents with distant metastases and is associated with a low risk of morbidity and mortality. Despite this, current protocols recommend remnant ablation with radioactive iodine and evaluation for local and distant metastasis in some patients with higher risk disease. There are several case reports of false positive results of metastatic surveys that are either normal physiologic variants or other pathological findings. Most false positive findings are associated with tissue that has physiologic increased uptake of I-131, such as breast tissue or lung tissue; pathological findings such as thymic cysts are also known to have increased uptake. Our case describes a rare finding of a thymic cyst found on a false positive I-131 metastatic survey. The patient was taken for surgical excision and the final pathology was a benign thymic cyst. Given that pulmonary metastases of differentiated thyroid cancer are rare, thymic cysts, though also rare, must be part of the differential diagnosis for false positive findings on an I-131 survey.

Distribution of Selenium and Oxidative Stress in Breast Tumor-Bearing Mice

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Pei-Chung Chen

2013-02-01

Full Text Available The present study investigated the effects of breast tumors on the blood and tissue distribution of essential trace mineral selenium (Se, and oxidative stress status of mice. Female 10-week-old BALB/cByJNarl mice were randomly assigned into control (CNL and breast tumor-bearing (TB groups. TB mice were injected subcutaneously into the right hind thigh with 5 × 106 EMT6 mouse mammary tumor cells. After 22 days, we measured Se concentrations, Se-dependent glutathione peroxidase (GPx activities, and malondialdehyde (MDA products (indicator of oxidative stress in plasma, various tissues, and plasma vascular endothelial growth factor (VEGF concentrations. There were no significant differences in body weights and daily intake between both groups. Compared with the CNL group, TB mice have decreases in plasma Se concentrations and GPx activities, as well as higher plasma VEGF and MDA concentrations. Plasma Se concentrations were also negatively correlated with plasma MDA and VEGF concentrations. Furthermore, tissue Se concentrations and GPx activities in TB animals were lower; whereas the MDA concentrations higher in various tissues including liver, kidney, brain, lung, spleen, and thymic tissues. In conclusion, disruption of Se homeostasis critically reflects oxidative stress in target tissues, thus may increase the risk for progression of breast cancer and metastasis.

Updates in MRI characterization of the thymus in myasthenic patients.

Science.gov (United States)

Popa, G A; Preda, E M; Scheau, C; Vilciu, C; Lupescu, I G

2012-06-12

To evaluate the imaging appearance of the thymus in the myasthenic patients by using chemical shift magnetic resonance imaging, and, to correlate the chemical shift ratio (CSR) with pathologic findings after surgical excision. In the past year, a total of 11 myasthenic patients (4 males, 7 females; age range of 26-65 years), have been investigated by MRI centered at the thymic lodge. Our protocol included a Dual-Echo technique, T1-weighted In-phase/Opposed-phase MR images in all patients. A chemical shift ratio (CSR) was calculated by comparing the signal intensity of the thymus gland with that of the chest wall muscle for quantitative analysis. For this purpose, we have used standard region-of-interest electronic cursors at a slice level of the maximum axial surface of the thymus. We have identified two patients groups: a thymic hyperplasia group and a thymic tumoral group. With the decrease in the signal intensity of the thymus gland at chemical shift, the MR imaging was evident only in the hyperplasia group. The mean CSR in the hyperplasia group was considerably lower than that in the tumor group, 0,4964 ± 0,1841, compared with 1,0398 ± 0,0244. The difference in CSR between the hyperplasia and tumor groups was statistically significant (P=0,0028). MR imaging using T1-weighted In-phase/Opposed-phase images could be a useful diagnostic tool in the preoperative assessment of the thymic lodge and may help differentiate thymic hyperplasia from tumors of the thymus gland.

Models of Aire-dependent gene regulation for thymic negative selection

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Dina eDanso-Abeam

2011-05-01

Full Text Available Mutations in the Autoimmune Regulator (AIRE gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1, characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue restricted antigens (TRAs in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses.

Effects of marrow grafting on preleukemia cells and thymic nurse cells in C57BL/Ka mice after a leukemogenic split-dose irradiation

International Nuclear Information System (INIS)

Defresne, M.P.; Greimers, R.; Lenaerts, P.; Boniver, J.

1986-01-01

A split-dose regimen of whole-body irradiation (4 X 175 rad at weekly intervals) induced thymic lymphomas in C57BL/Ka mice after a latent period of 3-9 months. Meanwhile, preleukemia cells arose in the thymus and bone marrow and persisted until the onset of lymphomas. Simultaneously, thymic lymphopoiesis was impaired; thymocyte numbers were subnormal and thymic nurse cells disappeared in a progressive but irreversible fashion. The depletion of these lymphoepithelial complexes, which are normally involved in the early steps of thymic lymphopoiesis, was related to altered prothymocyte activity in bone marrow and to damaged thymic microenvironment, perhaps as a consequence of the presence of preleukemia cells. The grafting of normal bone marrow cells after irradiation prevented the development of lymphomas. However, marrow reconstitution did not inhibit the induction of preleukemia cells. They disappeared from the thymus during the second part of the latent period. At the same time, thymic lymphopoiesis was restored; thymocytes and nurse cell numbers returned to normal as a consequence of the proliferation of grafted marrow-derived cells within the thymus. The results thus demonstrated an intimate relationship between preleukemia cells and an alteration of thymic lymphopoiesis, which particularly involved the nurse cell microenvironment. Some preleukemia cells in marrow-reconstituted, irradiated mice derived from the unirradiated marrow inoculate. Thus these cells acquired neoplastic potential through a factor present in the irradiated tissues. The nature of this indirect mechanism was briefly discussed

Implantation of cultured thymic fragments in patients with acquired immunodeficiency syndrome

NARCIS (Netherlands)

Danner, S. A.; Schuurman, H. J.; Lange, J. M.; Gmelig Meyling, F. H.; Schellekens, P. T.; Huber, J.; Kater, L.

1986-01-01

Cultured thymic fragments were implanted in one patient with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and in eight AIDS patients with opportunistic infections (OIs, four patients), Kaposi's sarcoma (KS, two patients), or both (two patients). Thereafter, objective clinical

IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

NARCIS (Netherlands)

Saluja, Rohit; Zoltowska, Anna; Ketelaar, Maria Elizabeth; Nilsson, Gunnar

2016-01-01

Thymic Stromal Lymphopoietin (TSLP) and Interleukin 33 (IL-33) are two cytokines released by cells that are in proximity to our environment, e.g., keratinocytes of the skin and epithelial cells of the airways. Pathogens, allergens, chemicals and other agents induce the release of TSLP and IL-33,

Imaging of brain tumors with histological correlations. 2. ed.

Energy Technology Data Exchange (ETDEWEB)

Drevelegas, Antonios (ed.)

2011-07-01

This volume provides a deeper understanding of the diagnosis of brain tumors by correlating radiographic imaging features with the underlying pathological abnormalities. All modern imaging modalities are used to complete a diagnostic overview of brain tumors with emphasis on recent advances in diagnostic neuroradiology. High-quality illustrations depicting common and uncommon imaging characteristics of a wide range of brain tumors are presented and analysed, drawing attention to the ways in which these characteristics reflect different aspects of pathology. Important theoretical considerations are also discussed. Since the first edition, chapters have been revised and updated and new material has been added, including detailed information on the clinical application of functional MRI and diffusion tensor imaging. Radiologists and other clinicians interested in the current diagnostic approach to brain tumors will find this book to be an invaluable and enlightening clinical tool. (orig.)

Single-level dynamic spiral CT of hepatocellular carcinoma: correlation between imaging features and tumor angiogenesis

International Nuclear Information System (INIS)

Chen Weixia; Min Pengqiu; Song Bin; Xiao Bangliang; Liu Yan; Wang Wendong; Chen Xian; Xu Jianying

2001-01-01

Objective: To investigate the correlation of the enhancement imaging features of hepatocellular carcinoma (HCC) and relevant parameters revealed by single-level dynamic spiral CT scanning with tumor microvessel counting (MVC). Methods: The study included 26 histopathologically proven HCC patients. Target-slice dynamic scanning and portal venous phase scanning were performed for all patients. The time-density curves were generated with measurement of relevant parameters including: peak value (PV) and contrast enhancement ratio (CER), and the gross enhancement morphology analyzed. Histopathological slides were carefully prepared for the standard F8RA and VEGF immunohistochemical staining and tumor microvessel counting and calculation of VEGF expression percentage of tumor cells. The enhancement imaging features of HCC lesions were correlatively studied with tumor MVC and VEGF expression. Results: Peak value of HCC lesions were 7.9 to 75.2 HU, CER were 3.8% to 36.0%. MVC were 6 to 91, and the VEGF expression percentage were 32.1% to 78.3%. The PV and CER were significantly correlated with tumor tissue MVC (r = 0.508 and 0.423, P < 0.01 and 0.05 respectively). There were no correlations between PV and CER and VEGF expression percentage. Both the patterns of time-density curve and the gross enhancement morphology of HCC lesions were also correlated with tumor MVC, and reflected the distribution characteristics of tumor microvessels within HCC lesions. A close association was found between the likelihood of intrahepatic metastasis of HCC lesions with densely enhanced pseudo capsules and the presence of rich tumor microvessels within these pseudo capsules. Conclusion: The parameters and the enhancement imaging features of HCC lesions on target-slice dynamic scanning are correlated with tumor MVC, and can reflect the distribution characteristics of tumor microvessels within HCC lesions. Dynamic spiral CT scanning is a valuable means to assess the angiogenic activity and

Thymic size at birth in preterm infants with severe respiratory ...

African Journals Online (AJOL)

The only maternal and postnatal factors influencing CT/T ratio were the presence of pre-eclamptic toxaemia (PET) and birth by caesarean section (CS), but these factors did not influence likelihood of survival. Factors found to be not associated with thymic size were antenatal steroid administration, maternal HIV status, ...

The diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis; Dignostikk av tymom og thymusatrofi hos pasienter med myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E. [Haukeland Sykehus, Bergen (Norway)

1997-11-01

The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs.

Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation

International Nuclear Information System (INIS)

Zuniga-Pfluecker, J.C.K.; Kruisbeek, A.M.

1990-01-01

Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells

The correlation between apparent diffusion coefficient and tumor cellularity in patients: a meta-analysis.

Science.gov (United States)

Chen, Lihua; Liu, Min; Bao, Jing; Xia, Yunbao; Zhang, Jiuquan; Zhang, Lin; Huang, Xuequan; Wang, Jian

2013-01-01

To perform a meta-analysis exploring the correlation between the apparent diffusion coefficient (ADC) and tumor cellularity in patients. We searched medical and scientific literature databases for studies discussing the correlation between the ADC and tumor cellularity in patients. Only studies that were published in English or Chinese prior to November 2012 were considered for inclusion. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to investigate potential heterogeneity. Of 189 studies, 28 were included in the meta-analysis, comprising 729 patients. The pooled r for all studies was -0.57 (95% CI: -0.62, -0.52), indicating notable heterogeneity (Pcorrelation between the ADC and cellularity for brain tumors. There was no notable evidence of publication bias. There is a strong negative correlation between the ADC and tumor cellularity in patients, particularly in the brain. However, larger, prospective studies are warranted to validate these findings in other cancer types.

CT findings of the mediastinal tumors -excluding mediastinal granuloma and primary carcinoma-

International Nuclear Information System (INIS)

Lee, Kyung Soo; Im, Chung Kie; Han, Man Chung

1985-01-01

Computerized Tomography can make accurate diagnosis in most of the mediastinal tumors and cysts by assessing their location, shape and internal architecture. Authors analysed and present CT findings of 89 surgically proven mediastinal tumors and cysts that were studied and treated in Seoul National University Hospital during recent 5 years. The results are as follows; 1. The most common tumor was teratoma (25 cases). Neurogenic tumor (20 cases), thymic tumor or cyst (16 cases), lymphoma (7 cases), bronchogenic cyst (6 cases), intrathoracic goiter (6 cases), pericardial cyst (3 cases) and cystic hygroma (2 cases) were next in order of frequency. 2. The most constant findings of teratoma was thick walled cystic area (100%), while pathognomonic fat and calcified density were seen only in 52% and 48% of cases, respectively. 22 cases were located in anterior mediastinum, 2 cases were in posterior mediastinum and a case is in middle mediastinum. 3. There were 20 cases of neurogenic tumor consisting of 6 neurilemmomas, 7 ganglioneuromas, 4 neurofibromas, 1 ganglioneuroblastoma, 1 neuroblastoma and 1 malignant schwannoma. Most of them were located in posterior mediastinum with exception of 2 neurilemmomas arising from left vagus nerve and left recurrent laryngeal nerve in middle mediastinum. Cystic change was seen in 2 cases of neurilemmoma and in a case of ganglioneuroma. Calcification was seen in 3 cases, of neuroblastoma, a neurilemmoma, and a ganglioneuroma. 4. There were 11 cases of thymoma showing homogeneous solid mass with speckeld calcification in 4 cases and irregular cystic change in 3 cases. 2 cases were invasive thymoma and myasthenia gravis was present in 4 cases. A cases of thymolipoma and a case of thymic cyst were included. 5. Lymphoma (2 Hodgkin's and 4 non-Hodgkin's) appeared as lobulated, matted mass in anterior mediastinum especially in prevascular area expanding bilaterally

CT findings of the mediastinal tumors -excluding mediastinal granuloma and primary carcinoma-

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Soo; Im, Chung Kie; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

1985-06-15

Computerized Tomography can make accurate diagnosis in most of the mediastinal tumors and cysts by assessing their location, shape and internal architecture. Authors analysed and present CT findings of 89 surgically proven mediastinal tumors and cysts that were studied and treated in Seoul National University Hospital during recent 5 years. The results are as follows; 1. The most common tumor was teratoma (25 cases). Neurogenic tumor (20 cases), thymic tumor or cyst (16 cases), lymphoma (7 cases), bronchogenic cyst (6 cases), intrathoracic goiter (6 cases), pericardial cyst (3 cases) and cystic hygroma (2 cases) were next in order of frequency. 2. The most constant findings of teratoma was thick walled cystic area (100%), while pathognomonic fat and calcified density were seen only in 52% and 48% of cases, respectively. 22 cases were located in anterior mediastinum, 2 cases were in posterior mediastinum and a case is in middle mediastinum. 3. There were 20 cases of neurogenic tumor consisting of 6 neurilemmomas, 7 ganglioneuromas, 4 neurofibromas, 1 ganglioneuroblastoma, 1 neuroblastoma and 1 malignant schwannoma. Most of them were located in posterior mediastinum with exception of 2 neurilemmomas arising from left vagus nerve and left recurrent laryngeal nerve in middle mediastinum. Cystic change was seen in 2 cases of neurilemmoma and in a case of ganglioneuroma. Calcification was seen in 3 cases, of neuroblastoma, a neurilemmoma, and a ganglioneuroma. 4. There were 11 cases of thymoma showing homogeneous solid mass with speckeld calcification in 4 cases and irregular cystic change in 3 cases. 2 cases were invasive thymoma and myasthenia gravis was present in 4 cases. A cases of thymolipoma and a case of thymic cyst were included. 5. Lymphoma (2 Hodgkin's and 4 non-Hodgkin's) appeared as lobulated, matted mass in anterior mediastinum especially in prevascular area expanding bilaterally.

Measurement of tumor volumes of hepatocellular carcinoma (HCC) by computed tomography (CT). Correlation with several tumor markers

Energy Technology Data Exchange (ETDEWEB)

Yoneshima, Manabu; Sawabu, Norio; Toya, Daishu

1984-09-01

Tumor volumes of HCC were measured by CT using planimeter and the clinical value of this measurement was evaluated by comparing several tumor markers. Tumor volumes measured by CT roughly agreed with those measured by angiography. In some cases, volumes from ultrasonography were smaller than those from CT and angiography. Tumor volumes measured by CT correlated significantly with the levels of ..cap alpha..-fetoprotein (AFP) but didn't relate to the presence of hepatoma specific ..gamma..-GTP isoenzyme (novel ..gamma..-GTP) nor to the values and positivities of LAI assay. In small HCCs (<=30 cm/sup 3/), the presence of novel ..gamma..-GTP and the levels of AFP were significantly lower than for larger tumors of HCC, but LAI assay wasn't lower. The non-tumorous volumes and the ratio of the non-tumorous volume to the whole liver volume didn't relate to the tests of liver function except for the presence of ascites.

Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.

Science.gov (United States)

Burns, Michael B; Montassier, Emmanuel; Abrahante, Juan; Priya, Sambhawa; Niccum, David E; Khoruts, Alexander; Starr, Timothy K; Knights, Dan; Blekhman, Ran

2018-06-20

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues. We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction. This correlation allows us to statistically predict interactions between loss-of-function tumor mutations in cancer-related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiome. In conclusion, our study shows that CRC microbiomes are correlated with tumor mutational profiles, pointing towards possible mechanisms of molecular interaction.

[Correlation analysis of G870A CCND1 gene polymorphism with digestive system tumors].

Science.gov (United States)

Yang, Shu-Min; Shi, Ya-Lin

2016-11-20

To study the correlation of G870A CCND1 gene polymorphism and digestive system tumors. From August 2010 to August 2014, 164 digestive system cancer patients (including 82 patients with gastric cancer and 82 with colorectal cancer) and 82 healthy subjects (control group) were examined with PCR-restriction fragment length polymorphism (PCR-RFLP). The distribution of CCND1 gene G870A frequency in the 3 groups and its association with tumor staging and grading were analyzed. The frequencies of the GG, GA and AA genotypes in G870A CCND1 gene loci in patients with gastric cancer and colorectal cancer differed significantly from those in the control group (Pdigestive system tumors (Pdigestive system cancer risk than the GG genotype (Pdigestive system tumors. The allele A is associated with an increased risk of digestive system tumors and correlated with the tumor differentiation and staging of the tumor.

Fate of thymic lymphocytes. [/sup 125/IudR and /sup 3/HTdR tracer studies in mice

Energy Technology Data Exchange (ETDEWEB)

Laissue, J A; Chanana, A D; Cronkite, E P; Joel, D D

1976-01-01

Data are summarized from a number of studies on the fate of thymic lymphocytes. Results are reported from studies in mice in which /sup 125/IudR and /sup 3/HTdR were used as tracers to study the production, maturation, migration, and life span of thymic lymphocytes. It is pointed out that thymus-derived cells constitute the majority of recirculating lymphocytes and that peripheral, differentiated thymus-derived lymphocytes exhibit a number of immunological functions. 114 references.

Tumoral calcinosis presenting as an extradural mass: MR findings and pathological correlation

Energy Technology Data Exchange (ETDEWEB)

Iglesias, A.; Arias, M.; Brasa, J. [Unidad de Resonancia Magnetica (MEDTEC), Hospital Xeral-Cies, 36204 Vigo (Spain); Gonzalez, A. [Servicio de Anatomia Patologica, Hospital Xeral-Cies, 36204 Vigo (Spain); Conde, C. [Servicio de Neurocirugia, Hospital Xeral-Cies, 36204 Vigo (Spain)

2002-09-01

Two cases of idiopathic tumoral calcinosis presenting as an extradural mass are reported. There are few reports in the literature of this pathological process presenting as extradural masses, so both cases represent very unusual locations for tumoral calcinosis. Magnetic resonance imaging features and pathological correlation of these two cases are presented. Tumoral calcinosis might be considered as a rare but possible cause of extradural mass. (orig.)

Tumoral calcinosis presenting as an extradural mass: MR findings and pathological correlation

International Nuclear Information System (INIS)

Iglesias, A.; Arias, M.; Brasa, J.; Gonzalez, A.; Conde, C.

2002-01-01

Two cases of idiopathic tumoral calcinosis presenting as an extradural mass are reported. There are few reports in the literature of this pathological process presenting as extradural masses, so both cases represent very unusual locations for tumoral calcinosis. Magnetic resonance imaging features and pathological correlation of these two cases are presented. Tumoral calcinosis might be considered as a rare but possible cause of extradural mass. (orig.)

Case Report: CT diagnosis of thymic remnant cyst/thymopharyngeal duct cyst

International Nuclear Information System (INIS)

Daga, Bipin V; Chaudhary, VA; Dhamangaokar, VB

2009-01-01

A 4-year-old boy presented with history of left anterolateral neck swelling since birth. He was clinically diagnosed to have a branchial cleft cyst. A CT scan revealed findings suggestive of a thymic remnant cyst. The lesion was excised and the diagnosis was confirmed by histopathology

Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity

International Nuclear Information System (INIS)

Murphy, James D.; Chisholm, Karen M.; Daly, Megan E.; Wiegner, Ellen A.; Truong, Daniel; Iagaru, Andrei; Maxim, Peter G.; Loo, Billy W.; Graves, Edward E.; Kaplan, Michael J.; Kong, Christina; Le, Quynh-Thu

2011-01-01

Purpose: To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer. Materials and methods: Twenty-three patients with squamous cell carcinoma of the oral tongue had PET–CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET–CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques. Results: Multiple MTV’s were associated with pathologic tumor volume; however the correlation was poor (R 2 range 0.29–0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p = 0.0005) and tumor grade (p = 0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R 2 = 0.63). Conclusions: Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET–CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

Factors associated with thymic size at birth among low and normal birth-weight infants

DEFF Research Database (Denmark)

Eriksen, Helle Brander; Biering-Sørensen, Sofie; Lund, Najaaraq

2014-01-01

treatment at the time of labor (0.84 [0.70-1.00]), number of pregnancy consultations (1.03 [1.00-1.05]), maternal age (0.91 [0.84-0.98]), Apgar score (1.06 [1.03-1.10]), and infant convulsions (0.44 [0.29-0.65]) were all independent determinants of thymic index but not all were determinants of thymus....../weight index. Pathologic amniotic fluid and cesarean delivery were associated with thymus/weight index among LBW infants (0.85 [0.75-0.95] and 0.80 [0.67-0.96]) but were only borderline significant for thymic index. CONCLUSION: Exposures mainly related to stress and infections were associated with a smaller...

The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture

Directory of Open Access Journals (Sweden)

Masako Osada

2006-01-01

Full Text Available Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs. Kremen1 (Krm1 is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk by competing for the lipoprotein receptor-related protein (LRP-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2 stage and continuing until the CD4+CD8+(DP stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5 Keratin 8+(K8 stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+ and medullary (UEA-1+ EpCAMhi epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

Liver tumors, correlation of computed tomography (CT) and pathology

Energy Technology Data Exchange (ETDEWEB)

Okazaki, Atsushi; Niibe, Hideo; Mitsuhashi, Norio

1984-09-01

Computed tomographic and pathologic correlation was studied in 12 autopsied cases with 11 cases of metastatic liver tumors and 1 case of hepatocellular carcinoma. Despite of proliferative patterns of the tumors, nodular low attenuations on CT showed scattered nodular lesions and geographic low attenuations on CT showed groups of multiple small nodular lesions, macroscopically. Abnormal areas of low attenuation were generally diminished by drip infusion contrast enhancement, which was more significant on tumors of infiltrative proliferation. Tumors of infiltrative proliferation revealed little degeneration of surrounding liver cells and abnormal areas of low attenuation were more distinct before contrast enhancement. Tumors of expansive proliferation revealed obvious degeneration of surrounding liver cells and a case having about 200 layers of degenerated liver cells revealed more distinct after contrast enhancement. The central lower density areas in abnormal areas of low attenuation on CT coincided with liquefactive necroses with scanty capillary. vessels and fibrotic changes, histopathologically. But coagulative necroses without decrease of surrouding blood flows were not visualized on CT. CT could not demonstrate the liquefactive necroses in more small nodules than 2 cm in diameter. (J.P.N.).

Correlation Between Minimum Apparent Diffusion Coefficient (ADCmin) and Tumor Cellularity: A Meta-analysis.

Science.gov (United States)

Surov, Alexey; Meyer, Hans Jonas; Wienke, Andreas

2017-07-01

Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique based on measure of water diffusion that can provide information about tissue microstructure, especially about cell count. Increase of cell density induces restriction of water diffusion and decreases apparent diffusion coefficient (ADC). ADC can be divided into three sub-parameters: ADC minimum or ADC min , mean ADC or ADC mean and ADC maximum or ADC max Some studies have suggested that ADC min shows stronger correlations with cell count in comparison to other ADC fractions and may be used as a parameter for estimation of tumor cellularity. The aim of the present meta-analysis was to summarize correlation coefficients between ADC min and cellularity in different tumors based on large patient data. For this analysis, MEDLINE database was screened for associations between ADC and cell count in different tumors up to September 2016. For this work, only data regarding ADC min were included. Overall, 12 publications with 317 patients were identified. Spearman's correlation coefficient was used to analyze associations between ADC min and cellularity. The reported Pearson correlation coefficients in some publications were converted into Spearman correlation coefficients. The pooled correlation coefficient for all included studies was ρ=-0.59 (95% confidence interval (CI)=-0.72 to -0.45), heterogeneity Tau 2 =0.04 (pcorrelated moderately with tumor cellularity. The calculated correlation coefficient is not stronger in comparison to the reported coefficient for ADC mean and, therefore, ADC min does not represent a better means to reflect cellularity. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Correlation Between Bone Scintigraphy and Tumor Markers in Patients with Breast Carcinoma

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Amela Begić

2006-02-01

Full Text Available A characteristic feature of many cancer types is their ability to metastasise to the skeleton. Bone is the most common site of metastatic invasion, after hematogenous spreading of breast cancer. Early detection of bone metastases is mandatory in the evaluation and management of these patients. Bone scintigraphy is commonly performed in detection and evaluation bone metastases. Tumor markers are present in healthy individuals as well as in patients with malignant diseases but in different concentration. Aim of study was to correlate serum levels of tumor marker Ca (15-3, CEA and presence of bone metastases detected by bone scintigraphy. Study included 25 patients with breast cancer, previously surgically treated. All patients underwent whole body scintigraphy. Ca (15-3 and CEA was measured by radioimmunoassay. Presence, number of bone metastases were correlated with Ca (15-3 and CEA levels. Median age of patients included in study was 50 varying from 30 to 67. Bone scintigraphy revealed bone metastases in 16 (64% patients. A weak correlation was found between number of metastases and level of Ca (15-3 (r=0.139, p=0.254. Significant differences in Ca (15-3 level was found in patient with metastases compared to patients without metastases (chi square 0, p=1.0. Good correlation was found between number of metastases and serum level of CEA. Correlation between level of two tumor markers Ca (15-3 and CEA was a weak (r = 0.096 , p=0.323. Bone scintigraphy is a sensitive diagnostic toll for detecting breast cancer metastases to bone. Serum levels of tumor markes in isolation can not give complete accuracy about bone metastases.

Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

International Nuclear Information System (INIS)

Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

2008-01-01

Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors.

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Vajapeyam, S; Stamoulis, C; Ricci, K; Kieran, M; Poussaint, T Young

2017-01-01

Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extracellular extravascular space (K trans ), rate constant from extracellular extravascular space back into blood plasma (K ep ), and extracellular extravascular volume fraction (V e ) were all significantly correlated with tumor grade; high-grade tumors showed higher K trans , higher K ep , and lower V e . Although all 3 parameters had high specificity (range, 82%-100%), K ep had the highest specificity for both grades. Optimal sensitivity was achieved for V e , with a combined sensitivity of 76% (compared with 71% for K trans and K ep ). Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low- and high-grade pediatric brain tumors. © 2017 by American Journal of Neuroradiology.

Resultado de la timectomía en los tumores epiteliales Result of thymectomy in epithelial tumors

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Miguel Ángel Martín González

2013-03-01

Full Text Available Introducción: el timoma describe las neoplasias que no presentan atipia manifiesta del componente epitelial, cuando se exhibe claramente atipia citológica se le conoce como carcinoma tímico, y la cirugía es el tratamiento de elección. Nuestro objetivo es evaluar la eficacia de la timectomía en los enfermos con tumores epiteliales del timo (timoma, carcinoma tímico. Métodos: se estudiaron 26 enfermos entre enero 2007 a enero 2012 que, con este diagnóstico, fueron operados en nuestro centro. Resultados: la miastenia gravis estuvo presente en 16 (61,5 % pacientes, de ellos en el posoperatorio se extubaron 11 (68,7 % después de 12 horas. La esternotomía total fue el abordaje principal 13 (50 %, cuando la lesión era superior a los 7 centímetros fue más probable la ampliación a un hemitórax. Cuando se necesitó resección de pulmón, pericardio o ambos, el tiempo quirúrgico fue superior a los 120 minutos. Se complicaron 7 (29,6 %, de ellos 5 (71,4 % de causa respiratoria. En 19 (73,9 % los tumores se clasificaron como estadio I de Masaoka y en 6 (23,1 % hubo carcinoma tímico.Tuvimos 1 fallecido (3,8 %. Todos los miasténicos tuvieron remisión completa o farmacológica, en 2 hubo recidiva local y en ninguno fallecimiento durante el seguimiento. Conclusiones: la timectomía transesternal es el tratamiento de elección, y se necesita ampliar a un hemitórax cuando la lesión es más de 7 cm con resección de pericardio, pulmón o ambos. En este caso, se obtendrán resultados favorables en los miasténicos y en el control del tumor durante el seguimiento.Introduction: Thymomea describes the neoplasias that do not present evident atypia of the epithelial component; the clear cytological atypia indicated thymic carcinoma and surgery is the treatment of choice. The objective of this paper was to evaluate the efficacy of thymectomy aimed at patients with epithelial tumors in the thymus (thymoma, thymic carcinoma. Methods: Twenty six

Study on the correlation between VEGF and peritumoral edema and tumor border in astrocytoma by CT

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Ye Yuxiang; Tan Siping; Liu Bo; Liu Guorui; Zhen Zhichao; Fan Miao

2004-01-01

Objective: To study the correlation between VEGF and peritumoral edema and tumor border in human astrocytoma, investigate the significance of its CT features in molecular-biology. Methods: The VEGF was examined by means of SP immunohistochemical technique in 52 cases of astrocytoma proved by pathology. The correlation of tumor VEGF with peritumoral edema, and tumor border was analyzed. Results: The peritumoral edema, tumor border and mass effect of astrocytoma was positively correlated with its VEGF. The VEGF increased with peritumoral edema and mass effect (P<0.01). VEGF were significantly higher in uncertain border group than those the clear border group (P<0.05), which VEGF were 69.2 ± 19.0. Conclusion: The over expression of VEGF obviously effect CT features in astrocytoma, such as peritumoral edema and tumor border

Regression of uveal malignant melanomas following cobalt-60 plaque. Correlates between acoustic spectrum analysis and tumor regression

International Nuclear Information System (INIS)

Coleman, D.J.; Lizzi, F.L.; Silverman, R.H.; Ellsworth, R.M.; Haik, B.G.; Abramson, D.H.; Smith, M.E.; Rondeau, M.J.

1985-01-01

Parameters derived from computer analysis of digital radio-frequency (rf) ultrasound scan data of untreated uveal malignant melanomas were examined for correlations with tumor regression following cobalt-60 plaque. Parameters included tumor height, normalized power spectrum and acoustic tissue type (ATT). Acoustic tissue type was based upon discriminant analysis of tumor power spectra, with spectra of tumors of known pathology serving as a model. Results showed ATT to be correlated with tumor regression during the first 18 months following treatment. Tumors with ATT associated with spindle cell malignant melanoma showed over twice the percentage reduction in height as those with ATT associated with mixed/epithelioid melanomas. Pre-treatment height was only weakly correlated with regression. Additionally, significant spectral changes were observed following treatment. Ultrasonic spectrum analysis thus provides a noninvasive tool for classification, prediction and monitoring of tumor response to cobalt-60 plaque

Tumor-derived Matrix Metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer

International Nuclear Information System (INIS)

Zhang, Bin; Niu, Yun; Niu, Ruifang; Sun, Baocun; Hao, Xishan; Cao, Xuchen; Liu, Yanxue; Cao, Wenfeng; Zhang, Fei; Zhang, Shiwu; Li, Hongtao; Ning, Liansheng; Fu, Li

2008-01-01

Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. However, its relevance to the progression of human breast cancer is yet to be established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2). Immunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray containing specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists in blind fashion. The correlation of the gene expression profiles with patients' clinicopathological features and clinical outcomes were analyzed for statistical significance. MMP-13 protein was detected in the cytoplasm of the malignant cells and the peritumoral stromal cells. MMP-13 expression by tumor cells (p < 0.001) and stromal fibroblasts (p <0.001) both correlated with carcinoma infiltration of lymph nodes. MMP-13 also correlated with the expression of Her-2/neu (p = 0.015) and TIMP-1 (p < 0.010), respectively in tumor cells. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes. Moreover, high levels of MMP-13 expression were associated with decreased overall survival. In parallel, the prognostic value of MMP-13 expressed by peritumoral fibroblasts seems less significant. Our data suggest that lymph node status, tumor size, Her-2/neu expression, TIMP-1 and MMP-13 expression in cancer cells are independent prognostic factors. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with the

HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

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Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J; Chapman, Harold D; Serreze, David V; DiLorenzo, Teresa P

2018-04-09

Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles. Copyright © 2018 by The American Association of Immunologists, Inc.

Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

International Nuclear Information System (INIS)

Mori, Kazumasa; Hiroi, Miki; Shimada, Jun; Ohmori, Yoshihiro

2011-01-01

Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163 + cells were significantly increased based on the pathological grade. CD163 + cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163 + cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4 + and CD8 + T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163 + TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC

Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

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Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

2011-09-28

Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

Associated relaxation time and the correlation function for a tumor cell growth system subjected to color noises

Science.gov (United States)

Wang, Can-Jun; Wei, Qun; Mei, Dong-Cheng

2008-03-01

The associated relaxation time T and the normalized correlation function C(s) for a tumor cell growth system subjected to color noises are investigated. Using the Novikov theorem and Fox approach, the steady probability distribution is obtained. Based on them, the expressions of T and C(s) are derived by means of projection operator method, in which the effects of the memory kernels of the correlation function are taken into account. Performing the numerical computations, it is found: (1) With the cross-correlation intensity |λ|, the additive noise intensity α and the multiplicative noise self-correlation time τ increasing, the tumor cell numbers can be restrained; And the cross-correlation time τ, the multiplicative noise intensity D can induce the tumor cell numbers increasing; However, the additive noise self-correlation time τ cannot affect the tumor cell numbers; The relaxation time T is a stochastic resonant phenomenon, and the distribution curves exhibit a single-maximum structure with D increasing. (2) The cross-correlation strength λ weakens the related activity between two states of the tumor cell numbers at different time, and enhances the stability of the tumor cell growth system in the steady state; On the contrast, τ and τ enhance the related activity between two states at different time; However, τ has no effect on the related activity between two states at different time.

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study.

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Bond, Jonathan; Marchand, Tony; Touzart, Aurore; Cieslak, Agata; Trinquand, Amélie; Sutton, Laurent; Radford-Weiss, Isabelle; Lhermitte, Ludovic; Spicuglia, Salvatore; Dombret, Hervé; Macintyre, Elizabeth; Ifrah, Norbert; Hamel, Jean-François; Asnafi, Vahid

2016-06-01

Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute a homogeneous clinical entity, and the biological consequences of HOXA overexpression have not been systematically examined. We characterized the biology and outcome of 55 HOXA-positive cases among 209 patients with adult T-cell acute lymphoblastic leukemia uniformly treated during the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 and -2005 studies. HOXA-positive patients had markedly higher rates of an early thymic precursor-like immunophenotype (40.8% versus 14.5%, P=0.0004), chemoresistance (59.3% versus 40.8%, P=0.026) and positivity for minimal residual disease (48.5% versus 23.5%, P=0.01) than the HOXA-negative group. These differences were due to particularly high frequencies of chemoresistant early thymic precursor-like acute lymphoblastic leukemia in HOXA-positive cases harboring fusion oncoproteins that transactivate HOXA Strikingly, the presence of an early thymic precursor-like immunophenotype was associated with marked outcome differences within the HOXA-positive group (5-year overall survival 31.2% in HOXA-positive early thymic precursor versus 66.7% in HOXA-positive non-early thymic precursor, P=0.03), but not in HOXA-negative cases (5-year overall survival 74.2% in HOXA-negative early thymic precursor versus 57.2% in HOXA-negative non-early thymic precursor, P=0.44). Multivariate analysis further revealed that HOXA positivity independently affected event-free survival (P=0.053) and relapse risk (P=0.039) of chemoresistant T-cell acute lymphoblastic leukemia. These results show that the underlying mechanism of HOXA deregulation dictates the clinico-biological phenotype, and that the negative prognosis of early thymic precursor acute lymphoblastic leukemia is exclusive to HOXA-positive patients, suggesting that early treatment intensification is currently

Thymic stromal lymphopoietin as a novel mediator amplifying immunopathology in rheumatic disease

NARCIS (Netherlands)

Hillen, Maarten R.; Radstake, Timothy R. D. J.; Hack, Cornelis E.; van Roon, Joel A. G.

2015-01-01

Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine that has been studied extensively in atopic diseases and more recently in various rheumatic disorders. It is involved in T cell development in the thymus and promotes homeostatic T cell expansion by classical dendritic cells. However,

Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

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Hamid R Molavian

Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT).

Science.gov (United States)

Turpin, Sophie; Carret, Anne-Sophie; Dubois, Josée; Buteau, Chantal; Patey, Natalie

2015-11-01

The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis.

Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT)

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Turpin, Sophie [CHU Sainte-Justine, Nuclear Medicine, Montreal (Canada); Carret, Anne-Sophie [CHU Sainte-Justine, Hemato-Oncology, Montreal (Canada); Dubois, Josee [CHU Sainte-Justine, Radiology, Montreal (Canada); Buteau, Chantal [CHU Sainte-Justine, Infectious Diseases, Montreal (Canada); Patey, Natalie [CHU Sainte-Justine, Pathology, Montreal (Canada)

2015-11-15

The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis. (orig.)

Early thymic T cell development in young transgenic mice overexpressing human Cu/Zn superoxide dismutase, a model of Down syndrome.

Science.gov (United States)

Laurent, Julien; Paly, Evelyne; Marche, Patrice N; London, Jacqueline

2006-06-01

Previous studies have shown that transgenic mice overexpressing Cu/Zn superoxide dismutase, a model of Down syndrome, exhibit premature thymic involution. We have performed a flow cytometry analysis of the developing thymus in these homozygous transgenic mice (hSOD1/hSOD1: Tg-SOD). Longitudinal follow-up analysis from day 3 to day 280 showed an early thymic development in Tg-SOD mice compared with controls. This early thymic development was associated with an increased migration of mature T cells to peripheral lymphoid organs. BrdU labeling showed no difference between Tg-SOD and control mice, confirming that the greater number of peripheral T cells in Tg-SOD mice was not due to extensive proliferation of these cells but rather to a greater pool of emigrant T cells in Tg-SOD.

HTLV-1-infected thymic epithelial cells convey the virus to CD4+ T lymphocytes.

Science.gov (United States)

Carvalho Barros, Luciana Rodrigues; Linhares-Lacerda, Leandra; Moreira-Ramos, Klaysa; Ribeiro-Alves, Marcelo; Machado Motta, Maria Cristina; Bou-Habib, Dumith Chequer; Savino, Wilson

2017-12-01

The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4 + T cells are the main target of HTLV-1, but other cell types are known to be infected, including immature lymphocytes. Developing T cells undergo differentiation in the thymus, through migration and interaction with the thymic microenvironment, in particular with thymic epithelial cells (TEC) the major component of this three dimensional meshwork of non-lymphoid cells. Herein, we show that TEC express the receptors for HTLV-1 and can be infected by this virus through cell-cell contact and by cell-free virus suspensions. The expression of anti-apoptosis, chemokine and adhesion molecules genes are altered in HTLV-1-infected TEC, although gene expression of antigen presentation molecules remained unchanged. Furthermore, HTLV-1-infected TEC transmitted the virus to a CD4 + T cell line and to CD4 + T cells from healthy donors, during in vitro cellular co-cultures. Altogether, our data point to the possibility that the human thymic epithelial cells play a role in the establishment and progression of HTLV-1 infection, functioning as a reservoir and transmitting the virus to maturing CD4 + T lymphocytes, which in turn will cause disease in the periphery. Copyright © 2017. Published by Elsevier GmbH.

Associated relaxation time and the correlation function for a tumor cell growth system subjected to color noises

International Nuclear Information System (INIS)

Wang Canjun; Wei Qun; Mei Dongcheng

2008-01-01

The associated relaxation time T c and the normalized correlation function C(s) for a tumor cell growth system subjected to color noises are investigated. Using the Novikov theorem and Fox approach, the steady probability distribution is obtained. Based on them, the expressions of T c and C(s) are derived by means of projection operator method, in which the effects of the memory kernels of the correlation function are taken into account. Performing the numerical computations, it is found: (1) With the cross-correlation intensity |λ|, the additive noise intensity α and the multiplicative noise self-correlation time τ 1 increasing, the tumor cell numbers can be restrained; And the cross-correlation time τ 3 , the multiplicative noise intensity D can induce the tumor cell numbers increasing; However, the additive noise self-correlation time τ 2 cannot affect the tumor cell numbers; The relaxation time T c is a stochastic resonant phenomenon, and the distribution curves exhibit a single-maximum structure with D increasing. (2) The cross-correlation strength λ weakens the related activity between two states of the tumor cell numbers at different time, and enhances the stability of the tumor cell growth system in the steady state; On the contrast, τ 1 and τ 3 enhance the related activity between two states at different time; However, τ 2 has no effect on the related activity between two states at different time

Relook TURBT in superficial bladder cancer: its importance and its correlation with the tumor ploidy.

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Dwivedi, Udai S; Kumar, Abhay; Das, Suren K; Trivedi, Sameer; Kumar, Mohan; Sunder, Shyam; Singh, Pratap B

2009-01-01

To evaluate various prognostic factor predictors of residual growth in Relook transurethral resection of bladder tumor (TURBT) in superficial bladder cancer. Also, to evaluate the role of Relook TURBT along with the ploidy for prediction of recurrence and stage progression in these patients. Fifty patients with superficial bladder cancer underwent TURBT after complete evaluation. Ploidy of the tumor specimen was evaluated by flow cytometry. After 4 to 6 weeks of initial TURBT, these patients underwent Relook TURBT. Final treatment was given after the results of the histological evaluation of these specimens. Patients who underwent bladder sparing treatment were followed-up. Of the patients, 28.5% had residual tumor in Relook TURBT. Growth was found to be at the same site in 66.7% and at a different site 33.3%; 75% had single while 25% had multiple residual growth. Residual malignant tissue had a statistically significant correlation with size of the tumor (>3 cm), appearance (solid tumor), number (>3), grade (high), and multiple previous resections. Overall, the up-migration of stage and grade leads to change in treatment in 41.6%; 5 underwent radical cystectomy and 1 opted for radiotherapy; in 2 patients, intravesical BCG was given. In follow-up of mean 11.5 months, 16.6% had recurrence. Presence of residual growth in Relook TURBT along with number, size, morphology, and multiple previous resections were found to have significant correlation with the recurrence in these patients. Ploidy and grade of the tumor were not found to have correlation. Multiple, more than 3 cm, solid high grade tumor with > 3 previous resections were predictors of presence of residual tumor in Relook TURBT. Presence of residual growth is a significant risk factor for recurrence. Ploidy was not found to be significantly correlated with recurrence.

Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

International Nuclear Information System (INIS)

Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

2010-01-01

Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% ± 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p 80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of ≥60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

PRESENCE OF THYMIC TISSUE IN THE ANTERIOR MEDIASTINAL FATTY TISSUE AND ITS SIGNIFICANCE IN THYMECTOMY FOR MYASTHENIA GRAVIS PATIENT: A CASE REPORT

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Athouba

2016-03-01

Full Text Available In 1970s, presence of thymic tissue in anterior mediastinal adipose tissue around the thymus was found. Here we report a case of ectopic thymic tissue in the mediastinum and the possible relevance of this distribution of thymic tissue outside thymus to the therapeutic yield of thymectomies in myasthenia gravis. A 30-year lady with myasthenia gravis (nonthymomatous presented with difficulty in swallowing and breathing for the last 1 years. She was under medical treatment but with little improvement. She underwent extended thymectomy, after which an en bloc resection of the anterior mediastinal fat tissues from pericardium and pleura, including the thymus, was performed. Grossly the soft tissue specimen taken from near left lateral area of heart was fibrofatty tissue. Microscopically isolated thymic tissues were seen interspersed among the fatty tissues composed of mature lymphocytes, epithelial cells and few Hassall's corpuscles were observed. Thymus specimen was within normal histological limits. To ensure complete removal, the adipose tissue at the anterior mediastinum as well as the gross thymus should be removed. Thymic tissue incidence in individual locations was as follows: Retrothyroid, 3(6%; peritracheal, 5 (10%; retrotracheal, 1 (2%; right phrenic nerve, 2 (4%; left phrenic nerve, 14 (28%; right recurrent laryngeal nerve, 2 (4%; left recurrent laryngeal nerve, 2 (4% and periaortic, 0. Trans-sternal thymectomy was found to be beneficial to all patients of mild-to-moderate myasthenia gravis with 70.2% patients showing improvement postoperatively.

Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin

DEFF Research Database (Denmark)

Gelpi, Marco; Hartling, Hans J; Thorsteinsson, Kristina

2016-01-01

was comparable in all groups, and no differences in immune homeostasis were found between primary HIV infection and early presenters, whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters. TSLP was elevated in primary HIV...... thymic output, but not with immune recovery. These findings indicate a possible role of TSLP in immune homeostasis in HIV infection but do not support TSLP to affect immune recovery in primary HIV infection.......BACKGROUND: Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine...

Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: Two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor β1 (TGF-β1) in age-related thymic involution.

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Tan, Jianxin; Wang, Yajun; Zhang, Nannan; Zhu, Xike

2016-08-01

Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been reported to be up-regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-β1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-β1 functions a dual role in age-related thymic involution. On one hand, up-regulation of TGF-β1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-β1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-β1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-β1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly. © 2016 International Federation for Cell Biology.

Is a positron emission tomography-computed tomography scan useful in the staging of thymic epithelial neoplasms?

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Viti, Andrea; Terzi, Alberto; Bianchi, Andrea; Bertolaccini, Luca

2014-07-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed concerned the employment of 18-fluorine fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) in the preoperative evaluation of thymic epithelial neoplasms (TENs). We reviewed its role as a predictor of Masaoka stage and histology (according to the WHO). In clinical practice, stage is considered the most important determinant in the therapeutic approach. A total of 265 papers were found as a result of the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. All the studies are retrospective analyses. Patient numbers varied from 13 to 58. Our research showed that PET-CT could clearly add information about the histology of the tumour. Thymic carcinoma constantly showed a higher standard uptake value (SUVmax) than thymomas. Furthermore, in one retrospective study of 36 patients, when using a derived PET indicator, the T/M ratio (ratio between SUVmax of the tumour and SUVmax of mediastinum, as conventionally measured at the level of the aortic arc), PET-CT could also differentiate between low- and high-risk thymomas (low risk vs high risk P = 0.01). In another study, a cut-off value of T/M ratio of 2.75 was identified between low- and high-risk TENs. The role of PET-CT in prediction of stage is harder to recognize. In one study, there was a statistically significant correlation between SUVmax, T/M ratio and Masaoka stage (P = 0.781 and 0.718, respectively). When analysing the data from the three larger series on this topic (58, 51 and 47 patients, the latter group selected in a multicentre study), only one study identified a correlation between SUVmax and Masaoka stage (Spearman correlation coefficient 0.30, P = 0.0436), while the other two failed

Correlation of SHOX2 Gene Amplification and DNA Methylation in Lung Cancer Tumors

International Nuclear Information System (INIS)

Schneider, Katja U; Liebenberg, Volker; Kneip, Christoph; Seegebarth, Anke; Erdogan, Fikret; Rappold, Gudrun; Schmidt, Bernd; Dietrich, Dimo; Fleischhacker, Michael; Leschber, Gunda; Merk, Johannes; Schäper, Frank; Stapert, Henk R; Vossenaar, Erik R; Weickmann, Sabine

2011-01-01

DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference. Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples

Development of donor-derived thymic lymphomas after allogeneic bone marrow transplantation in AKR/J mice

International Nuclear Information System (INIS)

Yasumizu, R.; Hiai, H.; Sugiura, K.

1988-01-01

The transplantation of bone marrow cells from BALB/c (but not C57BL/6 and C3H/HeN) mice was observed to lead to the development of thymic lymphomas (leukemias) in AKR/J mice. Two leukemic cell lines, CAK1.3 and CAK4.4, were established from the primary culture of two thymic lymphoma, and surface phenotypes of these cell lines found to be H-2d and Thy-1.2+, indicating that these lymphoma cells are derived from BALB/c donor bone marrow cells. Further analyses of surface markers revealed that CAK1.3 is L3T4+ Lyt2+ IL2R-, whereas CAK4.4 is L3T4- Lyt2- IL2R+. Both CAK1.3 and CAK4.4 were transplantable into BALB/c but not AKR/J mice, further indicating that these cells are of BALB/c bone marrow donor origin. The cells were found to produce XC+-ecotropic viruses, but xenotropic and mink cell focus-forming viruses were undetectable. Inasmuch as thymic lymphomas are derived from bone marrow cells of leukemia-resistant BALB/c strain of mice under the allogeneic environment of leukemia-prone AKR/J mice, this animal model may serve as a useful tool not only for the analysis of leukemic relapse after bone marrow transplantation but also for elucidation of the mechanism of leukemogenesis

How nonuniform contact profiles of T cell receptors modulate thymic selection outcomes

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Chen, Hanrong; Chakraborty, Arup K.; Kardar, Mehran

2018-03-01

T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a diversity of foreign peptides yet be tolerant of self-peptides is crucial for the adaptive immune system to properly function. This is achieved by selection of T cells in the thymus, where immature T cells expressing unique, stochastically generated TCRs interact with a large number of self-peptide-MHC; if a TCR does not bind strongly enough to any self-peptide-MHC, or too strongly with at least one self-peptide-MHC, the T cell dies. Past theoretical work cast thymic selection as an extreme value problem and characterized the statistical enrichment or depletion of amino acids in the postselection TCR repertoire, showing how T cells are selected to be able to specifically recognize peptides derived from diverse pathogens yet have limited self-reactivity. Here, we investigate how the diversity of the postselection TCR repertoire is modified when TCRs make nonuniform contacts with peptide-MHC. Specifically, we were motivated by recent experiments showing that amino acids at certain positions of a TCR sequence have large effects on thymic selection outcomes, and crystal structure data that reveal a nonuniform contact profile between a TCR and its peptide-MHC ligand. Using a representative TCR contact profile as an illustration, we show via simulations that the statistical enrichment or depletion of amino acids now varies by position according to the contact profile, and, importantly, it depends on the implementation of nonuniform contacts during thymic selection. We explain these nontrivial results analytically. Our study has implications for understanding the selection forces that shape the functionality of the postselection TCR repertoire.

Measurement of lung tumor motion using respiration-correlated CT

International Nuclear Information System (INIS)

Mageras, Gig S.; Pevsner, Alex; Yorke, Ellen D.; Rosenzweig, Kenneth E.; Ford, Eric C.; Hertanto, Agung; Larson, Steven M.; Lovelock, D. Michael; Erdi, Yusuf E.; Nehmeh, Sadek A.; Humm, John L.; Ling, C. Clifton

2004-01-01

Purpose: We investigate the characteristics of lung tumor motion measured with respiration-correlated computed tomography (RCCT) and examine the method's applicability to radiotherapy planning and treatment. Methods and materials: Six patients treated for non-small-cell lung carcinoma received a helical single-slice computed tomography (CT) scan with a slow couch movement (1 mm/s), while simultaneously respiration is recorded with an external position-sensitive monitor. Another 6 patients receive a 4-slice CT scan in a cine mode, in which sequential images are acquired for a complete respiratory cycle at each couch position while respiration is recorded. The images are retrospectively resorted into different respiration phases as measured with the external monitor (4-slice data) or patient surface displacement observed in the images (single-slice data). The gross tumor volume (GTV) in lung is delineated at one phase and serves as a visual guide for delineation at other phases. Interfractional GTV variation is estimated by scaling diaphragm position variations measured in gated radiographs at treatment with the ratio of GTV:diaphragm displacement observed in the RCCT data. Results: Seven out of 12 patients show GTV displacement with respiration of more than 1 cm, primarily in the superior-inferior (SI) direction; 2 patients show anterior-posterior displacement of more than 1 cm. In all cases, extremes in GTV position in the SI direction are consistent with externally measured extremes in respiration. Three patients show evidence of hysteresis in GTV motion, in which the tumor trajectory is displaced 0.2 to 0.5 cm anteriorly during expiration relative to inspiration. Significant (>1 cm) expansion of the GTV in the SI direction with respiration is observed in 1 patient. Estimated intrafractional GTV motion for gated treatment at end expiration is 0.6 cm or less in all cases; however; interfraction variation estimates (systematic plus random) are more than 1 cm in 3

Correlation Between PSMA and VEGF Expression as Markers for LNCaP Tumor Angiogenesis

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Paulus Tsui

2005-01-01

Full Text Available Our aim is the identification and correlation of changes in tumor-associated protein expression which results from therapy. LNCaP tumors, excised from nude mice treated either by orchiectomy or with the chemotherapeutic agent paclitaxel, were evaluated for the expression of proteins and receptors associated with growth, differentiation, and angiogenesis using immunohistologic procedures. Compared to untreated control tumors, both treatments reduced the expression of vascular endothelial growth factor (VEGF, prostate-specific membrane antigen (PSMA, prostate-specific antigen (PSA, androgen receptor (AR, and epidermal growth factor receptor (EGFR. The effect of paclitaxel treatment on AR expression was the most significant (P=.005. Of particular interest was identifying a significant correlation (P<.000801 between PSMA and VEGF expression regardless of treatment modality. These altered expressions suggest that PSMA may also be a marker for angiogenesis and could represent a target for deliverable agents recognizing either prostatic tumors or endothelial development. Cell surface PSMA would then present a unique target for treatment of patients early in their development of prostatic metastases.

SUVmax of 18F-FDG PET/CT correlates to expression of major chemotherapy-related tumor markers and serum tumor markers in gastric adenocarcinoma patients.

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Bai, Lu; Guo, Chi-Hua; Zhao, Yan; Gao, Jun-Gang; Li, Miao; Shen, Cong; Guo, You-Min; Duan, Xiao-Yi

2017-06-01

The expression of P53 was previously found by us significantly correlated with maximal standardized uptake value (SUVmax) in non-small cell lung cancer (NSCLC) patients. Hence, the aim of this study was to clarify the relationship between SUVmax and the status of the chemotherapy-related tumor marker expression or serum tumor markers in gastric adenocarcinoma patients. Sixty-four gastric adenocarcinoma patients who underwent 18F-FDG PET/CT prior to treatment were enrolled in this study. Immunohistochemistry was performed to detect changes of Her-2, P53 and Survivin in lesions, and electrochemiluminescence (ECL) method was used to quantify expression of serum CA72-4, CA19-9 and CEA of these patients. Then, the relationships between these parameters above were assessed by Spearman correlation analysis. Also, receiver-operating characteristic (ROC) curve was performed to determine the best cut-off value of SUVmax for suggesting chemotherapy resistant tumor markers. Besides, we identified a linear correlation to estimate the equations between SUVmax and the serum tumor markers. Our results showed that higher SUVmax was detected in patients with positive expression of Her-2 and P53, compared with negative groups. The Spearman correlation analysis showed that SUVmax was associated with Her-2 or P53 with the moderate relevant Pearson correlation coefficient. ROC curve analysis showed that the sensitivity and specificity of SUVmax for suggesting Her-2 or P53-positive, when the cut-off value of SUVmax was set at 3.25 or 5.45, respectively. Moreover, the relationship between SUVmax and serum tumor markers were analyzed by linear correlation analysis, and serum CA72-4 and CA19-9 could be used as independent parameters to establish an equation for SUVmax by the linear regression models. These results suggested that SUVmax of 18F-FDG PET/CT could be used to predict and evaluate Her-2 or P53 related chemotherapy resistance of gastric adenocarcinoma patients. However, before PET

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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Joel Saltz

2018-04-01

Full Text Available Summary: Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment. : Tumor-infiltrating lymphocytes (TILs were identified from standard pathology cancer images by a deep-learning-derived “computational stain” developed by Saltz et al. They processed 5,202 digital images from 13 cancer types. Resulting TIL maps were correlated with TCGA molecular data, relating TIL content to survival, tumor subtypes, and immune profiles. Keywords: digital pathology, immuno-oncology, machine learning, lymphocytes, tumor microenvironment, deep learning, tumor-infiltrating lymphocytes, artificial intelligence, bioinformatics, computer vision

Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies.

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Yasushi Sawanobori

Full Text Available Thymic epithelial cells (TECs are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies and compare it with a map from mouse counterparts and that of rat thymic dendritic cells.Rat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/-keratin 5 (K5+K8+CD205+ class II MHC (MHCII+ cortical TECs (cTECs, ED18+ED21-K5-K8+Ulex europaeus lectin 1 (UEA-1+CD205- medullary TECs (mTEC1s, and ED18+ED21+K5+K8dullUEA-1-CD205- medullary TECs (mTEC2s. Thymic nurse cells were defined in cytosmears as an ED18+ED19+/-K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE. Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area.Both rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

International Nuclear Information System (INIS)

Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

2006-01-01

Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

Lack of Correlation Between External Fiducial Positions and Internal Tumor Positions During Breath-Hold CT

International Nuclear Information System (INIS)

Hunjan, Sandeep; Starkschall, George; Prado, Karl; Dong Lei; Balter, Peter

2010-01-01

Purpose: For thoracic tumors, if four-dimensional computed tomography (4DCT) is unavailable, the internal margin can be estimated by use of breath-hold (BH) CT scans acquired at end inspiration (EI) and end expiration (EE). By use of external surrogates for tumor position, BH accuracy is estimated by minimizing the difference between respiratory extrema BH and mean equivalent-phase free breathing (FB) positions. We tested the assumption that an external surrogate for BH accuracy correlates with internal tumor positional accuracy during BH CT. Methods and Materials: In 16 lung cancer patients, 4DCT images, as well as BH CT images at EI and EE, were acquired. Absolute differences between BH and mean equivalent-phase (FB) positions were calculated for both external fiducials and gross tumor volume (GTV) centroids as metrics of external and internal BH accuracy, respectively, and the results were correlated. Results: At EI, the absolute difference between mean FB and BH fiducial displacement correlated poorly with the absolute difference between FB and BH GTV centroid positions on CT images (R 2 = 0.11). Similarly, at EE, the absolute difference between mean FB and BH fiducial displacements correlated poorly with the absolute difference between FB and BH GTV centroid positions on CT images (R 2 = 0.18). Conclusions: External surrogates for tumor position are not an accurate metric of BH accuracy for lung cancer patients. This implies that care should be taken when using such an approach because an incorrect internal margin could be generated.

Histopathologic correlation of parotid tumors

International Nuclear Information System (INIS)

Ramirez Valverde, Jose Miguel

2014-01-01

Malignization percentage of parotid pleomorphic adenoma is defined with fine needle aspiration biopsy (FNAB), prior negative in patients operated by parotid tumor in the Hospital San Juan de Dios between 2008-2012. Patients diagnosed with pleomorphic adenoma by FNAB are described in time, place and person. The histological type of parotid tumors diagnosed are defined. Management offered to patients diagnosed with parotid tumors is understood in the Hospital San Juan de Dios. Complications associated with surgical procedure in patients are specified. A quarter part the of parotid tumors from the series analyzed have been malignant, a similar percentage described in the literature [es

A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors.

Science.gov (United States)

Kempen, Paul J; Kircher, Moritz F; de la Zerda, Adam; Zavaleta, Cristina L; Jokerst, Jesse V; Mellinghoff, Ingo K; Gambhir, Sanjiv S; Sinclair, Robert

2015-01-01

The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

DEFF Research Database (Denmark)

Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette

2002-01-01

In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...

Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection

NARCIS (Netherlands)

Hazenberg, Mette D.; Borleffs, J.C.C.; Otto, S.A.; Cohen Stuart, J.W.T. (James Willem Theodoor); Verschuren, M.C.M. (Martie); Boucher, C.A.B.; Coutinho, R.A.; Lange, Joep M.A.; Rinke de Wit, T.F. (Tobias); Tsegaye, A. (Aster); Dongen, J.J.M. (Jaques) van; Hamann, D. (Dörte); Boer, R.J. de; Miedema, F.

2000-01-01

Recent thymic emigrants can be identified by T cell receptor excision circles (TRECs) formed during T-cell receptor rearrangement. Decreasing numbers of TRECs have been observed with aging and in human immunodeficiency virus (HIV)-1 infected individuals, suggesting for thymic impairment. Here,

Human thymic epithelial cells express functional HLA-DP molecules

DEFF Research Database (Denmark)

Jørgensen, A; Röpke, C; Nielsen, M

1996-01-01

T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

Correlation of FMISO simulations with pimonidazole-stained tumor xenografts: A question of O{sub 2} consumption?

Energy Technology Data Exchange (ETDEWEB)

Wack, L. J., E-mail: linda-jacqueline.wack@med.uni-tuebingen.de; Thorwarth, D. [Section for Biomedical Physics, Department of Radiation Oncology, University Hospital Tübingen, Tübingen 72076 (Germany); Mönnich, D. [Section for Biomedical Physics, Department of Radiation Oncology, University Hospital Tübingen, Tübingen 72076 (Germany); German Cancer Consortium (DKTK), Tübingen 72076 (Germany); German Cancer Research Center (DKFZ), Heidelberg 69121 (Germany); Yaromina, A. [OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01309, Germany and Department of Radiation Oncology (MAASTRO), GROW—School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht 6229 ET (Netherlands); Zips, D. [German Cancer Consortium (DKTK), Tübingen 72076 (Germany); German Cancer Research Center (DKFZ), Heidelberg 69121 (Germany); Department of Radiation Oncology, University Hospital Tübingen, Tübingen 72076 (Germany); and others

2016-07-15

Purpose: To compare a dedicated simulation model for hypoxia PET against tumor microsections stained for different parameters of the tumor microenvironment. The model can readily be adapted to a variety of conditions, such as different human head and neck squamous cell carcinoma (HNSCC) xenograft tumors. Methods: Nine different HNSCC tumor models were transplanted subcutaneously into nude mice. Tumors were excised and immunoflourescently labeled with pimonidazole, Hoechst 33342, and CD31, providing information on hypoxia, perfusion, and vessel distribution, respectively. Hoechst and CD31 images were used to generate maps of perfused blood vessels on which tissue oxygenation and the accumulation of the hypoxia tracer FMISO were mathematically simulated. The model includes a Michaelis–Menten relation to describe the oxygen consumption inside tissue. The maximum oxygen consumption rate M{sub 0} was chosen as the parameter for a tumor-specific optimization as it strongly influences tracer distribution. M{sub 0} was optimized on each tumor slice to reach optimum correlations between FMISO concentration 4 h postinjection and pimonidazole staining intensity. Results: After optimization, high pixel-based correlations up to R{sup 2} = 0.85 were found for individual tissue sections. Experimental pimonidazole images and FMISO simulations showed good visual agreement, confirming the validity of the approach. Median correlations per tumor model varied significantly (p < 0.05), with R{sup 2} ranging from 0.20 to 0.54. The optimum maximum oxygen consumption rate M{sub 0} differed significantly (p < 0.05) between tumor models, ranging from 2.4 to 5.2 mm Hg/s. Conclusions: It is feasible to simulate FMISO distributions that match the pimonidazole retention patterns observed in vivo. Good agreement was obtained for multiple tumor models by optimizing the oxygen consumption rate, M{sub 0}, whose optimum value differed significantly between tumor models.

Thin section helical CT findings of klastskin tumor and benign stricture: cholangiographic correlation

International Nuclear Information System (INIS)

Choi, Guk Myeong; Han, Joon Koo; Kim, Tae Kyoung; Choi, Byung Ihn; Kim, Sun Whe; Cho, Yun Ku; Han, Man Chung; Yeon, Kyung Mo

1997-01-01

The purpose of this study was 1) to describe the thin section helical CT findings of hilar cholangiocarcinoma and of benign strcture, and to discuss the differential points between the two disease entities and 2) using cholangiographic correlation, to evaluate the diagnostic accuracy of helical CT in determining the extent of hilar cholangiocarcinoma. Twenty-seven patients with hilar cholangiocarcinoma and eight with benign biliary dilatation were studied. All except four with hilar cholangiocarcinoma, who underwentCT using a conventional scanner, were studied with two-phase helical CT. In all patients, cholangiographs were obtained by digital fluoroscopy after the injection of contrast materials into PTBD catheters. The level of obstruction was classified according to Bismuth, and 35 CT scans were studied blindly and retrospectively by two radiologists. The findings were analyzed for the presence of tumor, and then divided into two groups(cholangiocarcinomas and benign strictures), and the positive predictive value was calculated. The CT images of klatskin tumor were analyzed with special emphasis on the level and shape of the hilar obstruction. The level of biliary obstruction and extent of the tumor were carefully correlated with the results of cholangiography. Thin-section spiral CT correctly identified all tumor mass as a focal wall thickening obliterating the lumen. On arterial/portal phase CT scanning, 81% of infilterative tumors showed high attenuation. In all patients, differentiation between benign stricture and klaskin tumor was possible;correct identification of the level of obstruction and extent of tumor, according to Bismuth's classification, was possible in 63% of cases. For correct diagnosis of hilar cholangiocarcinoma and differentiation of benign stricture, helical CT was highly accurate and effective. Because of limital Z-axis resolution, however, the exact intraductal extent of the tumor was less accorately diagnosed.=20

Correlation of intra-tumor 18F-FDG uptake heterogeneity indices with perfusion CT derived parameters in colorectal cancer.

Science.gov (United States)

Tixier, Florent; Groves, Ashley M; Goh, Vicky; Hatt, Mathieu; Ingrand, Pierre; Le Rest, Catherine Cheze; Visvikis, Dimitris

2014-01-01

Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis. Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-valueheterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization.

Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas

Energy Technology Data Exchange (ETDEWEB)

Yamaguchi, Yu [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Takabatake, Takashi; Kakinuma, Shizuko; Amasaki, Yoshiko; Nishimura, Mayumi; Imaoka, Tatsuhiko; Yamauchi, Kazumi; Shang, Yi [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Miyoshi-Imamura, Tomoko [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Genetic Counseling Program, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyou-ku, Tokyo 112-8610 (Japan); Nogawa, Hiroyuki [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Kobayashi, Yoshiro [Department of Biomolecular Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510 (Japan); Shimada, Yoshiya, E-mail: y_shimad@nirsgo.jp [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2010-04-01

Inactivation of the phosphatase and tensin homolog gene (Pten) occurs via multiple tissue-dependent mechanisms including epigenetic silencing, point mutations, insertions, and deletions. Although frequent loss of heterozygosity around the Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the proportion of lymphomas with inactivated Pten and the spectrum of causal aberrations have not been extensively characterized. Here, we assessed the mode of Pten inactivation by comprehensive analysis of the expression and alteration of Pten in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten; rather, complex structural abnormalities comprised of missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions were identified in 8 of 23 lymphomas (35%). Sequencing of deletion breakpoints suggested that aberrant V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven of the 8 lymphomas had biallelic alterations, and 4 of them did not express Pten protein. These Pten aberrations coincided with downstream Akt phosphorylation. In conclusion, we demonstrate that Pten inactivation is frequently biallelic and is caused by a variety of structural abnormalities (rather than by epigenetic silencing) and is involved in radiation-induced lymphomagenesis.

MRI evaluation of residual breast cancer after neoadjuvant chemotherapy: influence of patient, tumor and chemotherapy characteristics on the correlation with pathological response.

Science.gov (United States)

Diguisto, Caroline; Ouldamer, Lobna; Arbion, Flavie; Vildé, Anne; Body, Gilles

2015-01-01

The aim of this study was to evaluate the correlation between the residual tumor measured on magnetic resonance imaging and pathological results and to assess whether this correlation varies according to patient, tumor or chemotherapy characteristics. The study population included women treated for breast cancer with indication of neoadjuvant chemotherapy in our tertiary breast cancer Unit between January 2008 and December 2011. Factors related to patients, tumor and chemotherapy were studied. Pearson's correlation coefficient between the size of the tumor on MRI and pathological response was calculated for the entire population. It was also calculated according to patient, tumor and chemotherapy characteristics. During the study period, 107 consecutive women were included. The size of residual tumor on the MRI significantly correlated with the size on pathological result with a Pearson correlation coefficient of 0.52 (pcorrelation was stronger for women aged 50 years and older (r=0.64, pcorrelation was stronger for those with triple-negative tumors (r=0.69, p=0.002) but weaker for those with tumors with a ductal carcinoma in situ component (r =0.18, p=0.42). The size of breast cancer obtained by MRI is significantly correlated to the pathological size of the tumor. This correlation was stronger among women aged 50 years and more, among post-menopausal women, and among women who had triple-negative tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Thymoma (World Health Organization type B3) with neuroendocrine differentiation in multiple endocrine neoplasia type 1

OpenAIRE

Tomita, Masaki; Ichiki, Nobuhiko; Ayabe, Takanori; Tanaka, Hiroyuki; Kataoka, Hiroaki; Nakamura, Kunihide

2017-01-01

Abstract Thymic epithelial tumors occur in 1?5% of patients with multiple endocrine neoplasia type 1 (MEN 1). Majority of these thymic epithelial tumors are thymic carcinoids and patients with thymoma in MEN 1 is rare. Furthermore, thymoma with neuroendocrine differentiation was also rarely reported. Herein, we report a 68-year-old man having type B3 thymoma with neuroendocrine differentiation in MEN 1 and to the best of our knowledge this is the first such case ever reported.

Correlation analysis of expressions of PTEN and p53 with the value obtained by magnetic resonance spectroscopy and apparent diffusion coefficient in the tumor and the tumor-adjacent area in magnetic resonance imaging for glioblastoma.

Science.gov (United States)

Li, Yunyun; Ji, Feng; Jiang, Yuzhi; Zhao, Ting; Xu, Chongfu

2018-01-01

To explore the correlation of the expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) and p53 of glioblastoma multiforme (GBM) with the value obtained by magnetic resonance spectroscopy (MRS) and apparent diffusion coefficient (ADC) in the tumor and the tumor-adjacent area in magnetic resonance imaging (MRI). A total of 38 patients were operated for GBM. All the patients had received diffusion-weighted imaging (DWI) and MRS prior to surgery. ADC of water molecules and values of metabolite indexes of MRS, including n-acetyl aspartate (NAA), choline (Cho) and creatine (Cr), were recorded, and the ratios of Cho/NAA, Cho/Cr and NAA/Cr were calculated. Hematoxylin-eosin (H&E) staining was done to examine the morphology of tumor and of tumor-adjacent tissues; immunohistochemistry (IHC) was performed to examine the expressions of PTEN and p53 in the tumor and the tumor-adjacent area. Finally, the correlations of the expressions of PTEN and p53 with ADC, Cho/NAA, Cho/Cr and NAA/Cr of the tumor and the tumor-adjacent area were analyzed. H&E staining showed that GBM tissues had disordered morphology, different sizes of cells, large cell nuclei and significant cell heterogeneity. IHC indicated that the expression level of p53 protein in the tumor was significantly higher than in the tumor-adjacent tissues (pCorrelation analysis indicated that PTEN levels in the tumor and the tumor-adjacent area were positively correlated with ADC in the corresponding area, while p53 in the tumor and the tumor-adjacent area was negatively correlated with ADC in the corresponding area. Cho/NAA and Cho/Cr in the tumor were positively correlated with p53 in the tumor, but negatively correlated with PTEN in the tumor. However, NAA/Cr of the tumor was irrelevant to the levels of PTEN and p53. The test results of DWI and MRS of patients with GBM can accurately reflect the inactivation or mutation of PTEN and p53.

Correlation between diagnostic capability of MR-mammography and histology of tissue adjacent to tumor

Energy Technology Data Exchange (ETDEWEB)

Takahara, Taro [St. Marianna Univ., Kawasaki, Kanagawa (Japan)

1996-12-01

The purpose of this paper is to evaluate correlation between the capability in the diagnosis of tumor extent and histology of adjacent tissue. MR-mammography (MRM) was obtained in twenty-one patients with surgically resected breast cancer by 0.5 T superconducting magnet (PHILIPS GY-ROSCAN T5-II, release 3.1). Pre and postcontrast 3D-spoiled gradient echo sequence were employed for MRM with spectral presaturation with inversion recovery (SPIR) and on-resonance MTC. The contrast determination time, the passing time of the center of k-space, was 1 min 50 s in 14 cases with key-hole imaging, and 2 min 46 s in 7 cases without key-hole imaging. Early enhancing area was considered as a tumor and an accuracy of tumor extent was evaluated by two radiologists. Accurate interpretation was obtained in 9 of 9 cases with atrophic mammary gland with fatty replacement and 3 of 3 cases with severe fibrosis in mammary gland. Seven cases were unclear in tumor margin due to intense enhancement of the adjacent tissue. One of 3 cases with normal mammary gland showed unclear margin of the tumor, which corresponded to the area of rich population of lobules in a young patient. Two of 2 cases of fibrocystic change with nonproliferative lesions in one case and proliferative lesions without atypia in another, showed unclear margin of tumor. Two cases of 2 intraductal spreading and 2 of 2 cases of massive interstitial invasion also showed unclear margin. The accuracy of tumor extent was found to have no correlation with either histology or enhancing ratio of the tumor. In conclusion, it is warranted to say that histology of adjacent tissue is an important factor to determine diagnostic capability of tumor extent by MRM. Fat replacement and fibrosis of the surrounding tissue are main causes of clear visualization of tumor, while normal mammary gland in young patients, fibrocystic change, intraductal spreading and invasion lead to the unclearness of tumor margin. (author)

Correlation between diagnostic capability of MR-mammography and histology of tissue adjacent to tumor

International Nuclear Information System (INIS)

Takahara, Taro

1996-01-01

The purpose of this paper is to evaluate correlation between the capability in the diagnosis of tumor extent and histology of adjacent tissue. MR-mammography (MRM) was obtained in twenty-one patients with surgically resected breast cancer by 0.5 T superconducting magnet (PHILIPS GY-ROSCAN T5-II, release 3.1). Pre and postcontrast 3D-spoiled gradient echo sequence were employed for MRM with spectral presaturation with inversion recovery (SPIR) and on-resonance MTC. The contrast determination time, the passing time of the center of k-space, was 1 min 50 s in 14 cases with key-hole imaging, and 2 min 46 s in 7 cases without key-hole imaging. Early enhancing area was considered as a tumor and an accuracy of tumor extent was evaluated by two radiologists. Accurate interpretation was obtained in 9 of 9 cases with atrophic mammary gland with fatty replacement and 3 of 3 cases with severe fibrosis in mammary gland. Seven cases were unclear in tumor margin due to intense enhancement of the adjacent tissue. One of 3 cases with normal mammary gland showed unclear margin of the tumor, which corresponded to the area of rich population of lobules in a young patient. Two of 2 cases of fibrocystic change with nonproliferative lesions in one case and proliferative lesions without atypia in another, showed unclear margin of tumor. Two cases of 2 intraductal spreading and 2 of 2 cases of massive interstitial invasion also showed unclear margin. The accuracy of tumor extent was found to have no correlation with either histology or enhancing ratio of the tumor. In conclusion, it is warranted to say that histology of adjacent tissue is an important factor to determine diagnostic capability of tumor extent by MRM. Fat replacement and fibrosis of the surrounding tissue are main causes of clear visualization of tumor, while normal mammary gland in young patients, fibrocystic change, intraductal spreading and invasion lead to the unclearness of tumor margin. (author)

Expression of p63 and Cyclooxygenase-2 and Their Correlation in Skin Tumors

Institute of Scientific and Technical Information of China (English)

WU Yan; LIU Houjun; LI Jiawen

2007-01-01

To study the expression of p63 and cyclooxygenase-2 (cox-2) in skin tumors and evaluate the correlation between p63 and cox-2, the expressions of cox-2 and p63 were measured by streptavidin-peroxidase complex immunohistochemical technique in 17 cases of skin squamous cell carcinoma (SCC), 19 cases of Bowen's disease(Bowen), 11 cases of actinic keratosis(AK), 12 cases of seborreic keratosis(SK) and 13 specimens of normal skin. Our results showed that the expression of p63 in skin squamous cell carcinoma, Bowen's disease and actinic keratosis were significantly higher than that in seborreic keratosis, while the expression of p63 in seborreic keratosis was significantly higher than that in normal skin. The expression of cox-2 in skin squamous cell carcinoma,Bowen's disease and actinic keratosis were significantly higher than that in seborreic keratosis, while no statistical difference was noted in the expression of cox-2 between seborreic keratosis and normal skin. Cox-2 expression was positively correlated with the high p63 expression in malignant skin tumors. The increased expression of cox-2 and p63 may play an important role in the development of skin tumors and work synergetically in malignant skin tumors.

Dynamic contrast-enhanced MR imaging of the rectum: Correlations between single-section and whole-tumor histogram analyses.

Science.gov (United States)

Choi, M H; Oh, S N; Park, G E; Yeo, D-M; Jung, S E

2018-05-10

To evaluate the interobserver and intermethod correlations of histogram metrics of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters acquired by multiple readers using the single-section and whole-tumor volume methods. Four DCE parameters (K trans , K ep , V e , V p ) were evaluated in 45 patients (31 men and 14 women; mean age, 61±11 years [range, 29-83 years]) with locally advanced rectal cancer using pre-chemoradiotherapy (CRT) MRI. Ten histogram metrics were extracted using two methods of lesion selection performed by three radiologists: the whole-tumor volume method for the whole tumor on axial section-by-section images and the single-section method for the entire area of the tumor on one axial image. The interobserver and intermethod correlations were evaluated using the intraclass correlation coefficients (ICCs). The ICCs showed excellent interobserver and intermethod correlations in most of histogram metrics of the DCE parameters. The ICCs among the three readers were > 0.7 (Phistogram metrics, except for the minimum and maximum. The intermethod correlations for most of the histogram metrics were excellent for each radiologist, regardless of the differences in the radiologists' experience. The interobserver and intermethod correlations for most of the histogram metrics of the DCE parameters are excellent in rectal cancer. Therefore, the single-section method may be a potential alternative to the whole-tumor volume method using pre-CRT MRI, despite the fact that the high agreement between the two methods cannot be extrapolated to post-CRT MRI. Copyright © 2018 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

DEFF Research Database (Denmark)

Jin, Xin; Nowell, Craig S; Ulyanchenko, Svetlana

2014-01-01

does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6...... months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove...... a valuable method for long term maintenance of TEPC in vitro....

Correlation between magnetic resonance image and content of water and fat in experimental tumor

International Nuclear Information System (INIS)

Sato, Tachio; Yamada, Kenji; Yamada, Susumu; Yoshioka, Seiro; Ono, Shuichi; Hishinuma, Takashi; Abe, Yoshinao; Matsuzawa, Taiju; Ogata, Yuko.

1987-01-01

Water and fat are considered to be major protons contributing to magnetic resonance (MR) signals in living tissues. This study compared proton density and T1 and T2 relaxation times with content of water and fat in tumor bearing rabbits. MR scans were performed using a Carr-Purcell-Meiboom-Gill pulse sequence with short and long repetition times. There was a strong correlation between proton density and the content of water and fat. The correlation of the content of water and fat to T1 and T2 relaxation times was not so strong as that to proton density. Viable tumor tissues had significantly shorter T2 relaxation time than the surrounding edematous tissues (p < 0.005), although the content of water and fat did not differ in the two types of tissues. T1 relaxation time did not differ in viable tumorous and edematous tissues. (Namekawa, K.)

Hepatocarcinogenesis tumor grading correlated with in vivo image-guided 1H-NMR spectroscopy in a rat model

International Nuclear Information System (INIS)

Towner, Rheal A.; Foley, Lesley M.; Painter, Dorothy M.

2005-01-01

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, the occurrence of which is unevenly distributed. Most hepatocellular carcinoma cases present late and have a poor prognosis; therefore, early diagnosis is essential to prolong survival. Differential diagnosis with magnetic resonance imaging (MRI) is difficult. We studied the feasibility of using magnetic resonance spectroscopy (MRS) at 7.0 T for the diagnosis and grading of liver tumors. An animal model of hepatocarcinogenesis was used, which allowed tumor progression from precancerous lesions to hepatocellular carcinomas. This study was focused primarily on the grading of the tumors and its correlation with the ratio between the MRS peaks arising from MRS-detected lipid hydrogens (0.9, 1.3 and 5.3 ppm) and compared to the γ-methylene hydrogens of glutamate (Glu) and glutamine (Gln) which was used as an internal reference (2.4 ppm). The lipid methylene hydrogen (1.3 ppm) to (Glu + Gln) ratio was found to correlate with the formation of differentiated small foci and (precancerous) hepatic nodules, whereas the unsaturated olefinic lipid hydrogen (5.3 ppm) to (Glu + Gln) ratio was able to correlate with the formation of late stage tumors such as adenomas and hepatocellular carcinomas. The results of our study suggest that MRS-detected alterations in lipid metabolism can be correlated with the grading of liver tumor tissue at different stages during the carcinogenesis process

Molecular characterization of non-thymic lymphomas in mice exposed to continuous low-dose-rate g-ray irradiation

International Nuclear Information System (INIS)

Takabatake, T.; Fujikawa, K.; Nakamura, S.; Tanaka, S.; Tanaka, I.; Tanaka-Braga III, I.; Sunaga, Y.; Ichinoche, K.; Sato, F.; Tanaka, K.; Matsumoto, T.

2004-01-01

To investigate the effects of continuous low-dose-rate irradiation on life span and neoplasm incidence, SPE B6C3 F1 mice were irradiated with 137Cs-ray at dose-rates of 20, 1 and 0.05 mGy/day with accumulated doses equivalent to 8000, 40 and 20 mGy, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day were significantly shorter than that of the non-irradiated group. No significant difference in the cause of death and mortality rates was found between the groups. However, non-thymic lymphomas, the most common lethal neoplasm, showed a tendency to develop at an earlier age in mice irradiated with 20 mGy/day, regardless of sex. to obtain clues on the molecular mechanisms underlying the earlier development of non-thymic lymphomas in 20 mGy/day irradiated group, detailed molecular characterizations of non-thymic lymphomas with respect to B-cell or T-cell origin was done by detecting rearrangements in immunoglobulin heavy gene and in T-cell receptor b-and g chain genes by Southem hybridization method. to determine whether the early development of non-thymic lymphomas in 20 mGy/day irradiated group is associated wi the any recurrent chromosomal imbalance such as deletions and amplifications, the genome-wide scanning is also currently in progress by both LOH and array CGH methods. Present data obtained by LOH method show that deletions in parts of chromosomes 11 and 12 were more frequent than in chromosomes 2, 4 and 14 in both the non-irradiated control and 20 mGy/day irradiated groups. this work is supported by grants from Aomori Prefecture, Japan. (Author)

Magnetic resonance characterization of tumor microvessels in experimental breast tumors using a slow clearance blood pool contrast agent (carboxymethyldextran-A2-Gd-DOTA) with histopathological correlation

International Nuclear Information System (INIS)

Preda, Anda; Novikov, Viktor; Moeglich, Martina; Turetschek, Karl; Shames, David M.; Roberts, Timothy P.L.; Brasch, Robert C.; Floyd, Eugenia; Carter, Wayne O.; Corot, Claire

2005-01-01

Carboxymethyldextran (CMD)-A2-Gd-DOTA, a slow clearance blood pool contrast agent with a molecular weight of 52.1 kDa, designed to have intravascular residence for more than 1 h, was evaluated for its potential to characterize and differentiate the microvessels of malignant and benign breast tumors. Precontrast single-slice inversion-recovery snapshot FLASH and dynamic contrast-enhanced MRI using an axial T1-weighted three-dimensional spoiled gradient recalled sequence was performed in 30 Sprague-Dawley rats with chemically induced breast tumors. Endothelial transfer coefficient and fractional plasma volume of the breast tumors were estimated from MRI data acquired with CMD-A2-Gd-DOTA enhancement injected at a dose of 0.1 mmol Gd/kg body weight using a two-compartment bidirectional model of the tumor tissue. The correlation between MRI microvessel characteristics and histopathological tumor grade was determined using the Scarff-Bloom-Richardson method. Using CMD-A2-Gd-DOTA, no significant correlations were found between the MR-estimated endothelial transfer coefficient or plasma volumes with histological tumor grade. Analysis of CMD-A2-Gd-DOTA-enhanced MR kinetic data failed to demonstrate feasibility for the differentiation of benign from malignant tumors or for image-based tumor grading. (orig.)

The effect of early measles vaccination on thymic size. A randomized study from Guinea-Bissau

DEFF Research Database (Denmark)

Christensen, Lone Damkjær; Eriksen, Helle Brander; Biering-Sørensen, Sofie

2014-01-01

In low-income countries early measles vaccine (MV) is associated with reduced child mortality which cannot be explained by prevention of measles. A large thymus gland in infancy is also associated with reduced mortality. We hypothesized that early MV is associated with increased thymic size. Within...

Correlating Intravital Multi-Photon Microscopy to 3D Electron Microscopy of Invading Tumor Cells Using Anatomical Reference Points

Science.gov (United States)

Karreman, Matthia A.; Mercier, Luc; Schieber, Nicole L.; Shibue, Tsukasa; Schwab, Yannick; Goetz, Jacky G.

2014-01-01

Correlative microscopy combines the advantages of both light and electron microscopy to enable imaging of rare and transient events at high resolution. Performing correlative microscopy in complex and bulky samples such as an entire living organism is a time-consuming and error-prone task. Here, we investigate correlative methods that rely on the use of artificial and endogenous structural features of the sample as reference points for correlating intravital fluorescence microscopy and electron microscopy. To investigate tumor cell behavior in vivo with ultrastructural accuracy, a reliable approach is needed to retrieve single tumor cells imaged deep within the tissue. For this purpose, fluorescently labeled tumor cells were subcutaneously injected into a mouse ear and imaged using two-photon-excitation microscopy. Using near-infrared branding, the position of the imaged area within the sample was labeled at the skin level, allowing for its precise recollection. Following sample preparation for electron microscopy, concerted usage of the artificial branding and anatomical landmarks enables targeting and approaching the cells of interest while serial sectioning through the specimen. We describe here three procedures showing how three-dimensional (3D) mapping of structural features in the tissue can be exploited to accurately correlate between the two imaging modalities, without having to rely on the use of artificially introduced markers of the region of interest. The methods employed here facilitate the link between intravital and nanoscale imaging of invasive tumor cells, enabling correlating function to structure in the study of tumor invasion and metastasis. PMID:25479106

MRI findings and correlation with pathological features in breast phyllodes tumor

International Nuclear Information System (INIS)

Shen Xigang; Tan Hongna; Peng Weijun; Li Ruimin; Gu Yajia; Huang Dan; Mao Jian; Zhou Liangping

2011-01-01

Objective: To study the MR Imaging features of breast phyllodes tumor (PT), and to correlate it with pathological results. Method: Clinical and MRI findings were retrospectively reviewed in twenty-seven women with 28 PTs lesions confirmed by surgical pathology. Statistical analyses were one-way ANOVA for size analysis, Fisher exact test for analysis of MR appearances and Spearman correlation to study the relationship between MRI findings and BI-RADS categories. Results: (1) The histologic findings were benign, borderline and malignant PTs in 14.3% (4/28), 53.6% (15/28) and 32.1% (9/28) of lesions, respectively. (2) The mean maximum-diameter were (6.4±3.9) cm, (5.7±2.2) cm in borderline type and (4.8±1.8) cm in benign type respectively. The results showed differences in lesion's size among the three type (F= 287.541, P=0.000), especially between malignant and benign type (P=0.033). (3) Internal non-enhanced septation and silt-like changes on enhanced images, as well as time-signal curve on MRI correlated significantly with the histological grade (P<0.05). (4) If the category BI-RADS ≥ 4a was considered to be a suspicious sign for malignant lesion, the diagnostic accuracy of MRI would be 96.4% (27/28), and the BI-RADS category of the MRI could reflect the PT's histological grade with a low correlation coefficient (r=0.382, P=0.045). Conclusion: The findings of PT on MRI have some characteristics, with tumor size and several MRI features correlating with the histological grade of breast PT. (authors)

Identification of differentially expressed proteins in spontaneous thymic lymphomas from knockout mice with deletion of p53

DEFF Research Database (Denmark)

Honoré, Bent; Buus, Søren; Claësson, Mogens H

2008-01-01

ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two-dimensiona......ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two...... alpha type 3, transforming acidic coiled-coil containing protein 3, mitochondrial ornithine aminotransferase and epidermal fatty acid binding protein and down-regulation of adenylosuccinate synthetase, tubulin beta-3 chain, a 25 kDa actin fragment, proteasome subunit beta type 9, cofilin-1 and glia...

Perioperative Outcomes and Long-term Survival in Clinically Early-stage Thymic 
Malignancies: Video-assisted Thoracoscopic Thymectomy versus Open Approaches

Directory of Open Access Journals (Sweden)

Hao WANG

2016-07-01

Full Text Available Background and objective Video-assisted thoracoscopic surgery (VATS theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II thymic malignancies. However, longterm outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART. Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group, while 876 cases underwent open thymectomy (Open group. Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs 73.9%, P=0.028, resection rate (98.8% vs 88.7%, P<0.001 and less recurrence (2.9% vs 16.0%, P<0.001. Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15. However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011. Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusion This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival.

Low thymic output in the 22q11.2 deletion syndrome measured by CCR9+CD45RA+ T cell counts and T cell receptor rearrangement excision circles

DEFF Research Database (Denmark)

Lima, K; Abrahamsen, Gitte Meldgaard; Foelling, I

2010-01-01

Thymic hypoplasia is a frequent feature of the 22q11.2 deletion syndrome, but we know little about patients' age-related thymic output and long-term consequences for their immune system. We measured the expression of T cell receptor rearrangement excision circles (TREC) and used flow cytometry...

Cell-intrinsic role for NF-kappa B-inducing kinase in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice.

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Susan E Murray

Full Text Available NF-κB inducing kinase (NIK, MAP3K14 is a key signaling molecule in non-canonical NF-κB activation, and NIK deficient mice have been instrumental in deciphering the immunologic role of this pathway. Global ablation of NIK prevents lymph node development, impairs thymic stromal development, and drastically reduces B cells. Despite altered thymic selection, T cell numbers are near normal in NIK deficient mice. The exception is CD4(+ regulatory T cells (Tregs, which are reduced in the thymus and periphery. Defects in thymic stroma are known to contribute to impaired Treg generation, but whether NIK also plays a cell intrinsic role in Tregs is unknown. Here, we compared intact mice with single and mixed BM chimeric mice to assess the intrinsic role of NIK in Treg generation and maintenance. We found that while NIK expression in stromal cells suffices for normal thymic Treg development, NIK is required cell-intrinsically to maintain peripheral Tregs. In addition, we unexpectedly discovered a cell-intrinsic role for NIK in memory phenotype conventional T cells that is masked in intact mice, but revealed in BM chimeras. These results demonstrate a novel role for NIK in peripheral regulatory and memory phenotype T cell homeostasis.

S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

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Kumar, Ashok; Zamora-Pineda, Jesus; Degagné, Emilie

2017-01-01

Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC). Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes. PMID:29333002

S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling

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Ashok Kumar

2017-01-01

Full Text Available Sphingosine-1-phosphate (S1P is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL. SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC. Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes.

Survivin-specific T-cell reactivity correlates with tumor response and patient survival

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Becker, Jürgen C; Andersen, Mads H; Hofmeister-Müller, Valeska

2012-01-01

Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has...

The correlation between pre-operative serum tumor markers and lymph node metastasis in gastric cancer patients undergoing curative treatment.

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Li, Fangxuan; Li, Shixia; Wei, Lijuan; Liang, Xiaofeng; Zhang, Huan; Liu, Juntian

2013-11-01

There was few study concentrated on the correlation between the evaluated tumor markers and lymph node metastasis. In this study, we aimed to evaluate the correlation between the CA724, CA242, CA199, CEA and the lymph node metastasis of gastric cancer and assess the prognostic value of them in different N stage patients. We analyzed the correlation between serum level of CA724, CA242, CA199, CEA and lymph node metastasis in 1501 gastric cancer patients. Lymph node metastasis of gastric cancer was related with tumor location, Bormann type, tumor size, histological type, depth of invasion and TNM stage (p CEA were positively correlated with the metastatic lymph node counts and the N stage (p tumor markers were higher (p tumor markers, the positive rates of tumor markers combination were higher. The combination of CA724 + CA242 + CA199 + CEA had highest positive rate. The higher CEA level related to N1 stage patients while higher CA199 was related with poor prognosis for N1 stage patients. For N0 and N2 stage patients, evaluation of CA724 indicated poorer prognosis. For N1 and N2 stage gastric patients, the patients with increased CA242 inclined to have shorter survival time. The tumor makers CA724, CA242, CA199 and CEA were evaluated significantly in the gastric patients with later N stage. The combination of these four tumor markers maybe prefer diagnostic index of gastric cancer and its lymph node metastasis. These tumor markers can be a possible indicator of poorer prognosis in different N stage patients.

Hematological alterations and thymic function in newborns of HIV-infected mothers receiving antiretroviral drugs.

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Wongnoi, Rotjanee; Penvieng, Nawaporn; Singboottra, Panthong; Kingkeow, Doungnapa; Oberdorfer, Peninnah; Sirivatanapa, Pannee; Pornprasert, Sakorn

2013-06-08

To investigate the effects of antiretroviral (ARV) drugs on hematological parameters and thymic function in HIV-uninfected newborns of HIV-infected mothers. Cross sectional study. Chiang-Mai University Hospital, Chiang-Mai, Thailand. 49 HIV-uninfected and 26 HIV-infected pregnancies. Cord blood samples of newborns from HIV-uninfected and HIV-infected mothers were collected. Hematological parameters were measured using automatic blood cell count. T-cell receptor excision circles (TRECs) levels in cord blood mononuclear cells (CBMCs), CD4+ and CD8+ T-cells were quantified using real-time PCR.. Hemotological parameters and thymic function. Newborn of HIV-infected mother tended to have lower mean levels of hemoglobin than those of HIV-uninfected mother (137 ±22 vs 146 ±17 g/L, P = 0.05). Furthermore, mean of red blood cell (RBC) counts and hematocrit and median of TRECs in CD4+ T-cells in the newborns of the former were significantly lower than those of the latter [3.6 ±0.7 vs 4.8 ±0.6 x 1012 cells/L, P cells) in HIV-uninfected newborns of HIV-infected mothers.

High Incidence of Thymic Epithelial Tumors in E2F2 Transgenic Mice

NARCIS (Netherlands)

Scheijen, B.; Bronk, M.; Meer, T. van der; Jong, D. de; Bernards, R.A.

2004-01-01

In virtually all human tumors, genetic and epigenetic alterations have been found which affect the INK4/-CYCLIN D/RB pathway, which regulates cell cycle entry and exit in normal cells. E2F transcription factors are important downstream components of this pathway, which act by controlling the

Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

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Brian C. Wilson

2015-01-01

Full Text Available Excited-state singlet oxygen (1O2, generated during photodynamic therapy (PDT, is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC in an animal model comprising luciferase- and green fluorescent protein (GFP-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classified in individual tumors as "non", "moderate" and "strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the 1O2 counts demonstrated clear correlation, indicating that 1O2 luminescence provides a valid dosimetric technique for PDT in tumor tissue.

Changes of serum endocrine hormone levels in patients with cancerrelated fatigue and their correlation with anti-tumor immune response and tumor load

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Lu Yang

2017-08-01

Full Text Available Objective: To study the changes of serum endocrine hormone levels in patients with cancerrelated fatigue (CRF and their correlation with anti-tumor immune response and tumor load. Methods: A total of 137 patients who were diagnosed with primary lung cancer in West China Hospital, Sichuan University between June 2014 and November 2016 were selected and then divided into CRF group and control group according to their self-reported symptoms, serum was collected to determine the levels of endocrine hormones and tumor markers, and peripheral blood was collected to detect the levels of immune cells. Results: Serum ACTH and TSH levels of CRF group were significantly higher than those of control group while Cor, FT3 and FT4 levels were significantly lower than those of control group; peripheral blood CD11b+ CD15 - CD33+ CD14+ M-MDSC, CD11b+ CD15-CD33+ CD14- G-MDSC, CD4+ CD25+ CD127lowTreg and CD19+ CD5+ CD1d+ Breg levels as well as serum CEA, Cyfra21-1, SCC-Ag, HE4, GDF- 15 and PCNA levels of CRF group were significantly higher than those of control group, positively correlated with serum ACTH and TSH levels, and negatively correlated with Cor, FT3 and FT4 levels. Conclusion: The changes of thyroid hormone and adrenal cortical hormone levels in patients with cancer-related fatigue are closely related to the inhibited antitumor immune response and increased tumor load.

Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes.

OpenAIRE

Young, D A; Voris, B P; Nicholson, M L

1981-01-01

The molecular, biochemical, and cellular effects of adrenal glucocorticoid hormones on thymic lymphocytes are reviewed, with emphasis on their relationship to the growth suppressive and lethal actions that occur in lymphoid tissues when glucocorticoids are administered to the whole animal. The data support the hypothesis that the hormonal inhibition of growth and development is a consequence of its ability to suppress cellular energy production, causing the cells to behave as though they were...

Osseous oligometastases from thymic carcinoma: a case report suggesting the effectiveness of palliative-intent radiotherapy treatment.

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Kashima, Jumpei; Horio, Hirotoshi; Okuma, Yusuke; Hosomi, Yukio; Hishima, Tsunekazu

2016-01-01

Oligometastasis, a recently proposed concept, is defined as an intermediate state of cancer, between localized and systemic disease, that may be well controlled by local ablative treatment. Thymic carcinoma is a rare cancer with a poor prognosis. A definitive management approach has yet to be confirmed by a high level of evidence. We present the case of a 41-year-old female who underwent curative-intent surgery for a stage III squamous cell carcinoma of the thymus. Bone metastases were detected 1 year later by magnetic resonance imaging. These were treated with palliative-intent radiotherapy. Disease progression has not been observed in more than 15 years since the achievement of complete radiological remission. The treatment outcomes in this and other reported cases suggest that some patients with oligometastatic thymic carcinoma may achieve prolonged survival or even cure with low-dose radiotherapy delivered to the metastases.

Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

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Mosier, D.E.; Mond, J.J.; Goldings, E.A.

1977-12-01

The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other.

Ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an x-linked B cell defect

International Nuclear Information System (INIS)

Mosier, D.E.; Mond, J.J.; Goldings, E.A.

1977-01-01

The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other

CD4+ and Perivascular Foxp3+ T Cells in Glioma Correlate with Angiogenesis and Tumor Progression

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Luyan Mu

2017-11-01

Full Text Available BackgroundAngiogenesis and immune cell infiltration are key features of gliomas and their manipulation of the microenvironment, but their prognostic significance remains indeterminate. We evaluate the interconnection between tumor-infiltrating lymphocyte (TIL and tumor blood-vasculatures in the context of glioma progression.MethodsPaired tumor tissues of 44 patients from three tumor-recurrent groups: diffuse astrocytomas (DA recurred as DA, DA recurred as glioblastomas (GBM, and GBM recurred as GBM were evaluated by genetic analysis, immunohistochemistry for tumor blood vessel density, TIL subsets, and clinical outcomes. These cells were geographically divided into perivascular and intratumoral TILs. Associations were examined between these TILs, CD34+ tumor blood vessels, and clinical outcomes. To determine key changes in TIL subsets, microarray data of 15-paired tumors from patients who failed antiangiogenic therapy- bevacizumab, and 16-paired tumors from chemo-naïve recurrent GBM were also evaluated and compared.ResultsUpon recurrence in primary gliomas, similar kinetic changes were found between tumor blood vessels and each TIL subset in all groups, but only CD4+ including Foxp3+ TILs, positively correlated with the density of tumor blood vessels. CD4 was the predominant T cell population based on the expression of gene-transcripts in primary GBMs, and increased activated CD4+ T cells were revealed in Bevacizumab-resistant recurrent tumors (not in chemo-naïve recurrent tumors. Among these TILs, 2/3 of them were found in the perivascular niche; Foxp3+ T cells in these niches not only correlated with the tumor vessels but were also an independent predictor of shortened recurrence-free survival (RFS (HR = 4.199, 95% CI 1.522–11.584, p = 0.006.ConclusionThe minimal intratumoral T cell infiltration and low detection of CD8 transcripts expression in primary GBMs can potentially limit antitumor response. CD4+ and perivascular Foxp3

Permeability to macromolecular contrast media quantified by dynamic MRI correlates with tumor tissue assays of vascular endothelial growth factor (VEGF)

International Nuclear Information System (INIS)

Cyran, Clemens C.; Sennino, Barbara; Fu, Yanjun; Rogut, Victor; Shames, David M.; Chaopathomkul, Bundit; Wendland, Michael F.; McDonald, Donald M.; Brasch, Robert C.; Raatschen, Hans-Juergen

2012-01-01

Purpose: To correlate dynamic MRI assays of macromolecular endothelial permeability with microscopic area–density measurements of vascular endothelial growth factor (VEGF) in tumors. Methods and material: This study compared tumor xenografts from two different human cancer cell lines, MDA-MB-231 tumors (n = 5), and MDA-MB-435 (n = 8), reported to express respectively higher and lower levels of VEGF. Dynamic MRI was enhanced by a prototype macromolecular contrast medium (MMCM), albumin-(Gd-DTPA)35. Quantitative estimates of tumor microvascular permeability (K PS ; μl/min × 100 cm 3 ), obtained using a two-compartment kinetic model, were correlated with immunohistochemical measurements of VEGF in each tumor. Results: Mean K PS was 2.4 times greater in MDA-MB-231 tumors (K PS = 58 ± 30.9 μl/min × 100 cm 3 ) than in MDA-MB-435 tumors (K PS = 24 ± 8.4 μl/min × 100 cm 3 ) (p < 0.05). Correspondingly, the area–density of VEGF in MDA-MB-231 tumors was 2.6 times greater (27.3 ± 2.2%, p < 0.05) than in MDA-MB-435 cancers (10.5 ± 0.5%, p < 0.05). Considering all tumors without regard to cell type, a significant positive correlation (r = 0.67, p < 0.05) was observed between MRI-estimated endothelial permeability and VEGF immunoreactivity. Conclusion: Correlation of MRI assays of endothelial permeability to a MMCM and VEGF immunoreactivity of tumors support the hypothesis that VEGF is a major contributor to increased macromolecular permeability in cancers. When applied clinically, the MMCM-enhanced MRI approach could help to optimize the appropriate application of VEGF-inhibiting therapy on an individual patient basis.

Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood.

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Duggal, Niharika Arora; Pollock, Ross D; Lazarus, Norman R; Harridge, Stephen; Lord, Janet M

2018-04-01

It is widely accepted that aging is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, leading to immune compromise. However, physical activity, which influences immunity but declines dramatically with age, is not considered in this literature. We assessed immune profiles in 125 adults (55-79 years) who had maintained a high level of physical activity (cycling) for much of their adult lives, 75 age-matched older adults and 55 young adults not involved in regular exercise. The frequency of naïve T cells and recent thymic emigrants (RTE) were both higher in cyclists compared with inactive elders, and RTE frequency in cyclists was no different to young adults. Compared with their less active counterparts, the cyclists had significantly higher serum levels of the thymoprotective cytokine IL-7 and lower IL-6, which promotes thymic atrophy. Cyclists also showed additional evidence of reduced immunesenescence, namely lower Th17 polarization and higher B regulatory cell frequency than inactive elders. Physical activity did not protect against all aspects of immunesenescence: CD28 -ve CD57 +ve senescent CD8 T-cell frequency did not differ between cyclists and inactive elders. We conclude that many features of immunesenescence may be driven by reduced physical activity with age. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Computed tomography of the abnormal thymus

International Nuclear Information System (INIS)

Baron, R.L.; Lee, J.K.T.; Sagel, S.S.; Levitt, R.G.

1982-01-01

Computed tomography (CT) should be the imaging method of choice following plain chest radiographs when a suspected thymic abnormality requires further evaluation. Based upon a six-year experience, including the evaluation of 25 patients with thymic pathology, CT was found useful in suggesting or excluding a diagnosis of thymoma and in distinguishing thymic hyperplasis from thymoma in patients with myasthenia gravis. The thickness of the thymic lobes determined by CT was found to be a more accurate indicator of infiltrative disease (thymic hyperplasia and lymphoma) than the width. CT was helpful in differentiating benign thymic cysts from solid tumors, and in defining the extent of a thymic neoplasms. On occasion, CT may suggest the specific histologic nature of a thymic lesion

Computed tomography of the abnormal thymus

Energy Technology Data Exchange (ETDEWEB)

Baron, R.L.; Lee, J.K.T.; Sagel, S.S.; Levitt, R.G.

1982-01-01

Computed tomography (CT) should be the imaging method of choice following plain chest radiographs when a suspected thymic abnormality requires further evaluation. Based upon a six-year experience, including the evaluation of 25 patients with thymic pathology, CT was found useful in suggesting or excluding a diagnosis of thymoma and in distinguishing thymic hyperplasis from thymoma in patients with myasthenia gravis. The thickness of the thymic lobes determined by CT was found to be a more accurate indicator of infiltrative disease (thymic hyperplasia and lymphoma) than the width. CT was helpful in differentiating benign thymic cysts from solid tumors, and in defining the extent of a thymic neoplasms. On occasion, CT may suggest the specific histologic nature of a thymic lesion.

Correlation of Tumor and Peritumoral Edema Volumes with Survival in Patients with Cerebral Metastases.

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Kerschbaumer, Johannes; Bauer, Marlies; Popovscaia, Marina; Grams, Astrid E; Thomé, Claudius; Freyschlag, Christian F

2017-02-01

Surgical resection in combination with radiotherapy in selected cases remains the best option for patients with cerebral metastases. Postoperative relapse of brain metastases occurs frequently and can be reduced by postoperative whole-brain radiotherapy (WBRT). Continuous spread of tumor cells from the primary lesions is debated as a cause of recurrence. It is well known that in gliomas, infiltration takes place within the surrounding edema. Obviously, most brain metastases are usually associated with peritumoral edema, which may act as an indicator of infiltration and more aggressive tumor biology. Therefore, we aimed to investigate the correlation of tumor and edema volumes with overall survival in patients with cerebral metastases. A total of 143 patients diagnosed with brain metastasis (male:female=1.1:1) who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient files. The volumes of tumor and edema calculated by manual delineation. The ratio of edema to tumor volume was calculated, leading to dichotomization of the patients. The median tumor volume was 20.1 cc (range=0.8-90.8 cc) and the median volume of edema 49.5 cc (range=0-179.9 cc). The volume of metastases did not significantly correlate with overall survival. The ratio of edema to tumor volume was also not a prognostic factor in terms of overall survival. Only surgical resection, preoperative recursive partitioning analysis class, and postoperative addition of WBRT, as well as female sex, demonstrated beneficial effects. The extent of edema surrounding cerebral metastases does not appear to influence overall survival in patients suffering from brain metastases, although it seems to be responsible for most of the patients' symptoms. The hypothesis that the extent of edema was disadvantageous concerning survival was supported by our data. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios

Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

International Nuclear Information System (INIS)

Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee; Zeon, Seok Kil; Kim, Su Jin

2015-01-01

The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUV max ) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV max of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUV max compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer

Correlation of bone scintigraphy findings and tumor markers during follow-up prostate cancer

International Nuclear Information System (INIS)

Aizawa, Taku

1996-01-01

In the last 9 years, 217 patients with prostate cancer were treated at our department. Of these patients 153 cases treated by estrogen therapy were followed up by bone scintigraphy and tumor marker examinations (prostate specific antigen [PSA], prostate acid phosphatase [PAP], gamma-seminoprotein [γ-SM) . The correlation between changes on bone scintigrams and synchronous changes in tumor markers was evaluated retrospectively. In cases in which bone metastasis was not recognized on bone scintigrams before treatment, changes of tumor markers corresponded with subsequent changes on bone scintigrams in more than 90%. However, in cases with bone metastasis on bone scintigrams before treatment, changes of bone scintigrams and changes of tumor markers corresponded in only 55% of cases. Changes of bone scintigrams do not always correspond with changes of tumor markers. However, by taking into consideration physical examination parameters such as bone pain, in addition to changes of tumor markers, most changes on bone scintigrams can be anticipated. The reasons for lack of correspondence between changes of bone scintigrams and changes of tumor markers may be, changes of tumor markers are more rapid than the changes on bone scintigram, some poorly differentiated cancers do not have increased tumor marker levels and bone scintigrams do not demonstrate soft tissue involvement. In the follow-up of patients with prostate cancer, it is not necessary to perform bone scintigraphy regularly at 3-month intervals. Bone scintigraphy should only be performed when serum levels of tumor markers increase or bone pain appears. (author)

The correlation of vascularization index and flow index of thyroid cancer ultrasound with tumor malignancy

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Bing Liao

2017-06-01

Full Text Available Objective: To study the correlation of ultrasound vascularization index and flow index of thyroid cancer with tumor malignancy. Methods: A total of 140 patients with thyroid nodule who accepted surgical resection in our hospital between May 2013 and June 2016 were selected as the research subjects, the patients with malignant thyroid nodule were included in the malignant group of the research and patients with benign thyroid nodule were included in the benign group of research. Three-dimensional power Doppler ultrasonography was conducted before operation to determine vascularization index (VI, flow index (FI and vascularization flow index (VFI; tumor tissues were collected after operation to detect the expression of angiogenesis as well as cell proliferation, apoptosis and invasion-related molecules. Results: VI, FI and VFI levels of tumor tissue of malignant group were significantly higher than those of benign group; VEGF, MK, Ang-2, IGF-II, Bcl-2, Livin, Wip1, S100A4, TCF, β-catenin and SATB1 protein expression in tumor tissue of malignant group were significantly higher than those of benign group and positively correlated with VI, FI and VFI levels while CCNG2 and p27 protein expression were significantly lower than those of benign group and negatively correlated with VI, FI and VFI levels. Conclusion: Ultrasound vascularization index and flow index of thyroid cancer increase significantly and are closely related to the angiogenesis as well as cell proliferation, apoptosis and invasion.

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk

DEFF Research Database (Denmark)

Jeppesen, Dorthe Lisbeth; Hasselbalch, H; Ersbøll, A K

2003-01-01

AIM: To examine the size of the thymus in uninfected infants born to HIV-positive mothers and to study the effects of feeding by human donor milk on the size of the thymus in these infants. METHODS: The absolute and relative thymic size was assessed by sonography as thymic index (Ti), and the Ti....../weight-ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HlV-infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula......-fed infants. RESULTS: At birth the Ti was reduced in infants born to HIV-infected mothers in comparison with that in control infants but this difference disappeared when their birthweights were taken into consideration (Ti/w-ratio). At 4 mo of age the geometric mean Ti of infants fed donor milk was 23...

Tumor p-glycoprotein correlates with efficacy of PF-3758309 in in vitro and in vivo models of colorectal cancer.

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Erica Lynn Bradshaw-Pierce

2013-03-01

Full Text Available P-glycoprotein (P-gp, a member of the ATP-binding cassette transporter family, is overexpressed in a number of different cancers and some studies show that P-gp overexpression can be correlated to poor prognosis or therapeutic resistance. Here we sought to elucidate if PF-3758309 (PF-309, a novel p-21 activated kinase inhibitor, efficacy was influenced by tumor P-gp. Based on in vitro proliferation data, a panel of colorectal cancer cell lines were ranked as sensitive or resistant and ABCB1 (P-gp expression was evaluated by microarray for these cell lines. P-gp expression was determined by western blot and activity determined by rhodamine efflux assay. Knock down of P-gp and pharmacologic inhibition of P-gp to restore PF-309 activity was performed in vitro. PF-309 activity was evaluated in vivo in cell line xenograft models and in primary patient derived tumor xenografts (PDTX. Mice were treated with 25 mg/kg PF-309 orally, twice daily. On the last day of treatment, tumor and plasma were collected for PF-309 analysis. Here we show that ABCB1 gene expression correlates with resistance to PF-309 treatment in vitro and the expression and activity of P-gp was verified in a panel of resistant cells. Furthermore, inhibition of P-gp increased the sensitivity of resistant cells, resulting in a 4-100 fold decrease in the IC50s. Eleven cell line xenografts and 12 PDTX models were treated with PF-309. From the cell line xenografts, we found a significant correlation between ABCB1 gene expression profiles and tumor response. We evaluated tumor and plasma concentrations for 8 tumor models (3 cell line xenografts and 5 PDTX models and a significant correlation was found between tumor concentration and response. Additionally, we show that tumor concentration is approximately 4-fold lower in tumors that express P-gp, verified by western blot. Our in vitro and in vivo data strongly suggests that PF-309 efficacy is influenced by the expression of tumor P-gp.

Glypican-3 mRNA expression level in Wilms tumor: correlation with histological type, stage, and outcome.

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Wari, Md Nahidul; Vallonthaiel, Archana George; Ahmed, Aijaz; Saxena, Deepali; Iyer, Venkateswaran K; Mathur, Sandeep R; Agarwala, Sandeep; Bakhshi, Sameer; Srinivas, V; Chattopadhyaya, P; Sharma, Arundhati; Gupta, S Datta; Dinda, Amit

2017-06-01

To correlate expression of Glypican-3 in Wilms tumor with histopathology, stage, and outcome. Glypican-3 mRNA expression by real-time PCR on tumor and normal germline samples from 75 fresh nephrectomies for Wilms tumor with fold change after normalization against GAPDH was compared. Survival analysis for event-free and overall survival (EFS, OS) with 2-year follow-up for Glypican-3 overexpression (>1.5 times) and clinicopathological parameters was performed. Glypican-3 was overexpressed in 37/75 (49.3%). It was overexpressed in 77% (10/13) cases with blastema predominance or anaplastic histology, as compared to 44% of other histologies (27/62) (p = 0.03). OS was 73 and 93%, respectively (p = 0.016), for those with and without GPC-3 overexpression. EFS was not significantly different with Glypican-3 overexpression (p = 0.11). All 5 deaths among blastema predominant tumors and 4/5 deaths among triphasic tumors had overexpressed Glypican-3. Most deaths in Stage IV, Stage III, and Stage I + II (5/7, 3/3, 1/1) had GPC-3 overexpression. On multivariate analysis, only histology and stage were found to have independent prognostic value. Glypican-3 overexpression in Wilms tumor correlates with poor OS on univariate analysis. However, only histology and stage have independent prognostic value. Glypican-3 levels may help to stratify intermediate outcome histology (triphasic) and Stage III Wilms tumors.

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

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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.

Primary thymic extranodal marginal zone B cell lymphoma as an incidental finding in a Caucasian woman

DEFF Research Database (Denmark)

Krogh Petersen, Jeanette; Larsen, Thomas Stauffer; Møller, Michael Boe

2015-01-01

Primary thymic extranodal marginal zone B cell lymphoma (TML) is an extremely rare lymphoma strongly associated with autoimmune disease. We report an exceedingly rare case of TML found in a non-Asian population. TML was found incidentally in a 60-year-old Caucasian woman with a short history...

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

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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

Synergistic action of radiation and chemical carcinogen in induction of thymic lymphoma in mice

International Nuclear Information System (INIS)

Kajitani, Takashi; Kamiya, Kenji; Seyama, Toshio; Ito, Takaaki; Yokoro, Kenjiro

1980-01-01

Young adult C57BL/6 female mice were used to study the induction of leukemia by a combined treatment of x-rays and N-nitrosoethylurea (NEU). Administration of NEU after x-ray irradiation induced the leukemia in 100% with shortening latent period, which indicated that the combined treatment enhanced the leukemia induction. Thymic localized X-irradiation decreased the leukemia induction ratio from 100 to 55% and prolonged the latent period from 86 days to 128 days, compared with the whole body irradiation. For whole body irradiation, thymus weights, cell counts, rates of DNA-synthesizing cells, and rates, of mitotic index were decreased markedly after irradiation. For thymus weights and cell counts minimum values were observed after 3 days, and recovered by 10 days. DNA-synthesizing cells and the rates of mitotic index began to increase from the minimum value at the first day to the maximum value at the 5th day after irradiation. By thymic localized irradiation, no marked damage nor recovering process could be followed. It was suggested that the administration of NEU after irradiation, especially, to the young recovering cells with high potential for proliferation derived the high induction rate of leukemia. (Nakanishi, T.)

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk.

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Jeppesen, D; Hasselbalch, H; Ersbøll, A K; Heilmann, C; Valerius, N H

2003-06-01

To examine the size of the thymus in uninfected infants born to HIV-positive mothers and to study the effects of feeding by human donor milk on the size of the thymus in these infants. The absolute and relative thymic size was assessed by sonography as thymic index (Ti), and the Ti/weight-ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HlV-infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula-fed infants. At birth the Ti was reduced in infants born to HIV-infected mothers in comparison with that in control infants but this difference disappeared when their birthweights were taken into consideration (Ti/w-ratio). At 4 mo of age the geometric mean Ti of infants fed donor milk was 23.8 and the mean Ti/w-ratio was 4.2. Compared with those of exclusively breastfed infants, the Ti and Ti/w-ratio of infants fed donor milk were significantly reduced (p milk-fed infants compared with that in the formula-fed infants (p = 0.02). At birth the size of the thymus was smaller in uninfected infants of HIV-positive mothers compared with infants of HIV-negative mothers but when birthweight was taken into account this difference disappeared. Feeding by human donor milk seemed to result in an increased size of the thymus at 4 mo of age compared with thymic size in infants that were exclusively formula fed.

Correlation between ploidy status using flow cytometry and nucleolar organizer regions in benign and malignant epithelial odontogenic tumors.

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Mohamed Mahmoud, Sarah Ahmed; El-Rouby, Dalia Hussein; El-Ghani, Safa Fathy Abd; Badawy, Omnia Mohamed

2017-06-01

Differentiation between the aggressive benign odontogenic tumors and their malignant counterparts is controversial and difficult. While flow cytometry (FCM) allowed DNA analysis in neoplasia, argyrophilic organizer regions (AgNORs) number and/or size in a nucleus are correlated with the ribosomal gene activity and therefore with cellular proliferation. The aim of this research was to study the diagnostic accuracy of FCM and AgNORs staining in differentiating between benign and malignant epithelial odontogenic tumors and to correlate between these two interventions. Sixteen benign cases [8 cases of ameloblastoma (AB) and 8 cases of keratocystic odontogenic tumor (KCOT)] and 13 malignant epithelial odontogenic tumors [8 cases of ameloblastic carcinoma (ABC) and 5 cases of clear cell odontogenic carcinoma(CCOC)] were included in the current study. For FCM analysis, a single cell suspension from Formalin fixed paraffin-embedded (FFPE) tumors was prepared according to a modified method described by Hedley (1989) and AgNORs staining were performed in accordance to the Ploton protocol (1986). Analysis of AgNORs was performed using both quantitative and qualitative methods. The work revealed that all the examined tumors were diploid, except for 40% of CCOC cases. The S-phase fraction (SPF) value, AgNORs count and AgNORs area/cell showed statistically significant difference on comparing benign and malignant groups. A weak positive correlation was observed between SPF and AgNORs count. The SPF value was considered to be more sensitive and specific in differentiation between aggressive benign and malignant epithelial odontogenic tumors in comparison to AgNORs counting. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heparanase Expression in Malignant Salivary Gl, Tumors Inversely Correlates with Long-Term Survival

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Ofer Ben-Izhak

2006-10-01

Full Text Available BACKGROUND: Upregulation of the endo-b-Dglucuronidase, heparanase, was noted in an increasing number of human malignancies. Heparanase expression correlated with enhanced local, distant metastatic spread, increased vascular density, reduced postoperative survival. PATIENTS, METHODS: We analyzed heparanase expression in 60 patients (aged 59 ± 17 years with malignant salivary tumors (39 males, 21 females using immunohistochemistry. We applied antiheparanase antibody 733, which has previously been shown to preferentially recognize a 50-kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining can directly be correlated with enzymatic activity. RESULTS: Heparanase staining was positive (> 0 in 70% of tumors (42 of 60 patients, was negative (0 in the remaining 30% (18 patients. The cumulative survival of patients diagnosed as heparanase-negative (n = 18 at 300 months was 70% (95% confidence interval = 35-88. In contrast, the cumulative survival of patients diagnosed as heparanase-positive (n = 42 at 300 months was 0% (statistically significant difference, P = .035. CONCLUSIONS: Heparanase expression levels inversely correlate with the survival rates of salivary gl, cancer patients, clearly indicating that heparanase is a reliable prognostic factor for this malignancy, an attractive target for anticancer drug development.

Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms.

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Feyerabend, Thorsten B; Terszowski, Grzegorz; Tietz, Annette; Blum, Carmen; Luche, Hervé; Gossler, Achim; Gale, Nicholas W; Radtke, Freddy; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2009-01-16

Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1-deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (Dll4) in thymus epithelium revealed an essential role for Dll4 in T cell development. Thus, Notch1-Dll4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.

Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

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Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A. [Univ. Graz (Austria). Dept. of Radiotherapy; Beham-Schmid, C. [Univ. Graz (Austria). Dept. of Pathology; Groell, R. [Univ. Graz (Austria). Dept. of Radiology; Smolle-Juettner, F.M.; Renner, H. [Univ. Graz (Austria). Dept. of Thoracic and Hyperbaric Surgery; Quehenberger, F. [Univ. Graz (Austria). Dept. of Medical Informatics, Statistics and Documentation

1999-06-01

All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [Deutsch] Alle 33 Patienten wurden nach kompletter Resektion (n=16), Teilresektion (n=9) oder Biopsie (n=8) mit einer mittleren Dosis von 50 Gy (30 bis 60 Gy) bestrahlt. Die Stadieneinteilung nach Masaoka ergab jeweils zwoelf Patienten in Stadium II und III sowie neun Patienten im Stadium IV. Ergebnisse: Patienten mit einem invasivem Thymom Masaoka-Stadium II bis IV (mediane Nachsorgezeit 54,4 Monate) hatten ein Fuenf-Jahres-Gesamtueberleben, krankheitsspezifisches und

Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response.

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Hallac, Rami R; Zhou, Heling; Pidikiti, Rajesh; Song, Kwang; Stojadinovic, Strahinja; Zhao, Dawen; Solberg, Timothy; Peschke, Peter; Mason, Ralph P

2014-05-01

To examine the potential use of blood oxygenation level dependent (BOLD) and tissue oxygenation level dependent (TOLD) contrast MRI to assess tumor oxygenation and predict radiation response. BOLD and TOLD MRI were performed on Dunning R3327-AT1 rat prostate tumors during hyperoxic gas breathing challenge at 4.7 T. Animals were divided into two groups. In Group 1 (n = 9), subsequent (19) F MRI based on spin lattice relaxation of hexafluorobenzene reporter molecule provided quantitative oximetry for comparison. For Group 2 rats (n = 13) growth delay following a single dose of 30 Gy was compared with preirradiation BOLD and TOLD assessments. Oxygen (100%O2 ) and carbogen (95%O2 /5%CO2 ) challenge elicited similar BOLD, TOLD and pO2 responses. Strong correlations were observed between BOLD or R2* response and quantitative (19) F pO2 measurements. TOLD response showed a general trend with weaker correlation. Irradiation caused a significant tumor growth delay and tumors with larger changes in TOLD and R1 values upon oxygen breathing exhibited significantly increased tumor growth delay. These results provide further insight into the relationships between oxygen sensitive (BOLD/TOLD) MRI and tumor pO2 . Moreover, a larger increase in R1 response to hyperoxic gas challenge coincided with greater tumor growth delay following irradiation. Copyright © 2013 Wiley Periodicals, Inc.

Correlation between the Uptake of 18F-Fluorodeoxyglucose (18F-FDG and the Expression of Proliferation-Associated Antigen Ki-67 in Cancer Patients: A Meta-Analysis.

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Sheng-Ming Deng

Full Text Available To study the correlation between 18F-FDG uptake and cell proliferation in cancer patients by meta-analysis of published articles.We searched PubMed (MEDLINE included, EMBASE, and Cochrane Database of Systematic Review, and selected research articles on the relationship between 18F-FDG uptake and Ki-67 expression (published between August 1, 1994-August 1, 2014, according to the literature inclusion and exclusion criteria. The publishing language was limited to English. The quality of included articles was evaluated according to the Quality Assessment of Diagnosis Accuracy Studies-2 (QUADAS-2. The correlation coefficient (r was extracted from the included articles and processed by Fisher's r-to-z transformation. The combined correlation coefficient (r and the 95% confidence interval (CI were calculated with STATA 11.0 software under a random-effects model. Begg's test was used to analyze the existence of publication bias and draw funnel plot, and the sources of heterogeneity were explored by sensitivity and subgroup analyses.According to the inclusion and exclusion criteria, 79 articles were finally included, including 81 studies involving a total of 3242 patients. All the studies had a combined r of 0.44 (95% CI, 0.41-0.46, but with a significant heterogeneity (I2 = 80.9%, P<0.01. Subgroup analysis for different tumor types indicated that most subgroups showed a reduced heterogeneity. Malignant melanoma (n = 1 had the minimum correlation coefficient (-0.22 between 18F-FDG uptake and Ki-67 expression, while the thymic epithelial tumors (TETs; n = 2 showed the maximum correlation coefficient of 0.81. The analytical results confirmed that correlation between 18F-FDG uptake and Ki-67 expression was extremely significant in TETs, significant in gastrointestinal stromal tumors (GISTs, moderate in patients with lung, breast, bone and soft tissue, pancreatic, oral, thoracic, and uterine and ovarian cancers, average in brain, esophageal and colorectal

Correlation of proliferative and clonogenic tumor cells in multiple myeloma

International Nuclear Information System (INIS)

Karp, J.E.; Burke, P.J.; Saylor, P.L.; Humphrey, R.L.

1984-01-01

To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [ 3 H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [ 3 H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [ 3 H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity

Correlation between dose and tumor response in the radiotherapy of lung cancer of various histological types

International Nuclear Information System (INIS)

Koga, Kenji; Kusuhara, Toshiyuki; Nishikawa, Kiyoshi; Asada, Keiko; Watanabe, Katsushi

1984-01-01

Correlation between dose and tumor response by cell types was determined in 50 patients with lung cancer in order to predict the possibility of further tumor regression. The TDF (time-dose-fractionation) concept was used as dose factor. The radiation source was a cobalt-60 γ-ray or linear accelerator 10 MV X-ray. As a routine regime a fraction dose of 2 Gy five times per week was given to 39 of the 50 patients, but a dose of 2 Gy three times per week or of 1.5 Gy five times per week was given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma and better in adenocarcinoma than in squamous cell carcinoma, showing a tumor regression rate of 50% or more in 90%, 80% and 58% of the patients, respectively. The correlation between tumor regression rate and TDF values was good in squamous cell carcinoma (r = 0.73) and small cell carcinoma (r = - 0.72), but poor in adenocarcinoma (r = - 0.10). These results suggest that in squamous cell carcinoma improvement of tumor regression can be expected by increasing TDF values, and in adenocarcinoma and small cell carcinoma the optimal TDF values are about 100 and 60 to 80, respectively. (author)

High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma.

Science.gov (United States)

Miura, Yosuke; Kaira, Kyoichi; Sakurai, Reiko; Imai, Hisao; Tomizawa, Yoshio; Sunaga, Noriaki; Minato, Koichi; Hisada, Takeshi; Oyama, Tetsunari; Yamada, Masanobu

2017-10-01

Glucose-regulated protein (GRP) 78/immunoglobulin heavy chain binding protein (BiP) is a member of the endoplasmic reticulum chaperone family, and its role in various types of human malignancies has recently been investigated. However, the clinicopathological characteristics of GRP78/BiP in advanced thymic carcinoma (ATC) remain unknown. We aimed to examine the relationship between GRP78/BiP expression and the clinical outcomes of ATC patients. Thirty-four patients with ATC receiving combination chemotherapy at three institutions between April 1998 and April 2014 were enrolled in this study. We retrospectively collected patient characteristics such as therapeutic efficacy, pathological findings, and survival data from their medical records. We performed immunohistochemical analysis to evaluate the expression of GRP78/BiP in tumor specimens obtained from surgical resection or biopsy. This study included 21 men (68%) and 13 women (32%) with a median age of 62 years (range 36-75 years). GRP78/BiP overexpression was observed in 65% of the patients (22 of 34 patients). There was no correlation between GRP78/BiP expression and any patient characteristic. Patients with a high level of GRP78/BiP expression had significantly longer overall survival (OS) compared to those with a low level (46.2 vs. 16.8 months, p = 0.04). Multivariate analysis demonstrated that a high level of GRP78/BiP expression was an independent prognostic factor for prolonged OS. Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.

Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors.

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Larson, Allison R; Dresser, Karen A; Zhan, Qian; Lezcano, Cecilia; Woda, Bruce A; Yosufi, Benafsha; Thompson, John F; Scolyer, Richard A; Mihm, Martin C; Shi, Yujiang G; Murphy, George F; Lian, Christine Guo

2014-07-01

DNA methylation is the most well-studied epigenetic modification in cancer biology. 5-hydroxymethylcytosine is an epigenetic mark that can be converted from 5-methylcytosine by the ten-eleven translocation gene family. We recently reported the loss of 5-hydroxymethylcytosine in melanoma compared with benign nevi and suggested that loss of this epigenetic marker is correlated with tumor virulence based on its association with a worse prognosis. In this study, we further characterize the immunoreactivity patterns of 5-hydroxymethylcytosine in the full spectrum of melanocytic lesions to further validate the potential practical application of this epigenetic marker. One hundred and seventy-five cases were evaluated: 18 benign nevi, 20 dysplastic nevi (10 low-grade and 10 high-grade lesions), 10 atypical Spitz nevi, 20 borderline tumors, 5 melanomas arising within nevi, and 102 primary melanomas. Progressive loss of 5-hydroxymethylcytosine from benign dermal nevi to high-grade dysplastic nevi to borderline melanocytic neoplasms to melanoma was observed. In addition, an analysis of the relationship of nuclear diameter with 5-hydroxymethylcytosine staining intensity within lesional cells revealed a significant correlation between larger nuclear diameter and decreased levels of 5-hydroxymethylcytosine. Furthermore, borderline lesions uniquely exhibited a diverse spectrum of staining of each individual case. This study further substantiates the association of 5-hydroxymethylcytosine loss with dysplastic cytomorphologic features and tumor progression and supports the classification of borderline lesions as a biologically distinct category of melanocytic lesions.

Correlation between the respiratory waveform measured using a respiratory sensor and 3D tumor motion in gated radiotherapy

International Nuclear Information System (INIS)

Tsunashima, Yoshikazu; Sakae, Takeji; Shioyama, Yoshiyuki; Kagei, Kenji; Terunuma, Toshiyuki; Nohtomi, Akihiro; Akine, Yasuyuki

2004-01-01

Purpose: The purpose of this study is to investigate the correlation between the respiratory waveform measured using a respiratory sensor and three-dimensional (3D) tumor motion. Methods and materials: A laser displacement sensor (LDS: KEYENCE LB-300) that measures distance using infrared light was used as the respiratory sensor. This was placed such that the focus was in an area around the patient's navel. When the distance from the LDS to the body surface changes as the patient breathes, the displacement is detected as a respiratory waveform. To obtain the 3D tumor motion, a biplane digital radiography unit was used. For the tumor in the lung, liver, and esophagus of 26 patients, the waveform was compared with the 3D tumor motion. The relationship between the respiratory waveform and the 3D tumor motion was analyzed by means of the Fourier transform and a cross-correlation function. Results: The respiratory waveform cycle agreed with that of the cranial-caudal and dorsal-ventral tumor motion. A phase shift observed between the respiratory waveform and the 3D tumor motion was principally in the range 0.0 to 0.3 s, regardless of the organ being measured, which means that the respiratory waveform does not always express the 3D tumor motion with fidelity. For this reason, the standard deviation of the tumor position in the expiration phase, as indicated by the respiratory waveform, was derived, which should be helpful in suggesting the internal margin required in the case of respiratory gated radiotherapy. Conclusion: Although obtained from only a few breathing cycles for each patient, the correlation between the respiratory waveform and the 3D tumor motion was evident in this study. If this relationship is analyzed carefully and an internal margin is applied, the accuracy and convenience of respiratory gated radiotherapy could be improved by use of the respiratory sensor.Thus, it is expected that this procedure will come into wider use

Radiomodifying effect of hyperglycemia: correlation between a glucose dose and a tumor size

International Nuclear Information System (INIS)

Ul'yanenko, S.E.; Polityukova, N.A.

1991-01-01

Experiments were made on rats with trasplantable sarcoma-45 and sarcoma M-1. Dose correlation was established during a study of hyperglycemic radiomodifying action. Glucose injection at a dose of 6-17.5 g/kg was shown to enhance irradiation action. Glucose injection below or above these doses might cause worse radiotherapy results or even the death of animals. The best effect was obtained with small-size tumors. Large tumors(over 2 cm 3 ) were less sensitive to hyperglycemia combined with irradiation. Skin radioprotective action of hyperglycemia before irradiation increased with an increase in a dose

Correlation of primary tumor FDG uptake with histopathologic features of advanced gastric cancer

International Nuclear Information System (INIS)

Kim, Hae Won; Won, Kyoung Sook; Song, Bong Il; Kang, Yu Na

2015-01-01

Histopathologic features could affect the FDG uptake of primary gastric cancer and detection rate on FDG PET/CT. The aim of this study was to evaluate the FDG uptake of primary gastric cancer by correlating it with the histopathologic features of the tumors. Fifty patients with locally advanced gastric adenocarcinoma who were referred for preoperative FDG-PET/CT scans were enrolled in this study. The detection rate of PET/CT and maximum standardized uptake values (SUV max ) of the primary tumor were compared using the WHO, Lauren, Ming and Borrmann classifications and tumor size and location. In 45 of the 50 patients (90 %), the primary gastric tumors were detected by FDG PET/CT. On comparison using the WHO classification, the detection rate and SUV max of the tubular type were significantly higher than those of the poorly cohesive type. On comparison using the Lauren and Ming classifications, the SUV maxs of the intestinal type and expanding type were significantly higher than those of the diffuse and infiltrative type, respectively. On comparison using the Borrmann classification and tumor size and location, there was no significant difference in the detection rate and SUV max of primary gastric tumors. This study demonstrates that the poorly cohesive type according to the WHO classification, diffuse type according to the Lauren classification and infiltrative type according to the Ming classification have low FDG uptake in patients with locally advanced gastric carcinoma. Understanding the relationship between primary tumor FDG uptake and histopathologic features would be helpful in detecting the primary tumor by FDG PET/CT in patients with gastric cancer

Contrast-enhanced color Doppler US in breast cancer: Tumoral vascularity correlated with angiogenesis

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Kim, Eun A; Yoon, Kwon Ha; Yun, Ki Jung; Lee, Kwang Man; Park, Ki Han; Juhng, Seon Kwan; Won, Jong Jin [Wonkwang University School of Medicine, Seoul (Korea, Republic of)

2000-12-15

To evaluate the effects of contrast-enhanced color Doppler ultrasonography (CDUS) on the depiction of vascularity and flow pattern in breast cancer and to determine the relationship between tumoral vascularity and angiogenesis. Twenty-one patients with breast cancer were prospectively evaluated with CDUS before and after injection of the contrast agent (SH U 508A, 2.5g, 300 mg/ml ). The tumoral vascularity was expressed as percentage of color Doppler area, which was measured quantitatively by a computerized program (Ultrasonic Imaging Tool; Soongsil University, Seoul, Korea). The flow pattern (four-patterns; spotty, linear, branching, marginal) of the vascularity was analyzed. After surgery, tumor angiogenesis was assessed by microvessel density. The relationship between the vascularity on CDUS and microvessel density was statistically analyzed. At unenhanced CDUS, tumoral flow signals were detected in 12 lesions (48%); at contrast-enhanced CDUS, 18 lesions (86%). All These 18 lesions showed increased signals, compared with those at unenhanced CDUS. The percentage color Doppler area was 1.86 {+-} 0.48% at unenhanced CDUS and 5.23 {+-} 1.18% at contrast-enhanced CDUS. The flow patterns before contrast injection were spotty pattern in 11 tumors and linear pattern in one; after contrast injection, spotty in 8, linear in 4, branching in 5, and marginal in one. The tumoral vascularity at contrast-enhanced CDUS showed no significant correlation with microvessel density. Contrast-enhanced CDUS seems to be a valuable tool in the depiction of vascularity and characterization of flow pattern in breast cancer. However, tumoral vascularity on CDUS may not reflect tumoral angiogenesis.

Correlation of Dynamic PET and Gene Array Data in Patients with Gastrointestinal Stromal Tumors

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Ludwig G. Strauss

2012-01-01

Full Text Available Introduction. The results obtained with dynamic PET (dPET were compared to gene expression data obtained in patients with gastrointestinal stromal tumors (GIST. The primary aim was to assess the association of the dPET results and gene expression data. Material and Methods. dPET was performed following the injection of F-18-fluorodeoxyglucose (FDG in 22 patients with GIST. All patients were examined prior to surgery for staging purpose. Compartment and noncompartment models were used for the quantitative evaluation of the dPET examinations. Gene array data were based on tumor specimen obtained by surgery after the PET examinations. Results. The data analysis revealed significant correlations for the dPET parameters and the expression of zinc finger genes (znf43, znf85, znf91, znf189. Furthermore, the transport of FDG (k1 was associated with VEGF-A. The cell cycle gene cyclin-dependent kinase inhibitor 1C was correlated with the maximum tracer uptake (SUVmax in the tumors. Conclusions. The data demonstrate a dependency of the tracer kinetics on genes associated with prognosis in GIST. Furthermore, angiogenesis and cell proliferation have an impact on the tracer uptake.

Ectopic cervical thymoma in a patient with Myasthenia gravis

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Chang Hung

2011-07-01

Full Text Available Abstract Ectopic cervical thymoma is rare and is often misdiagnosed as a thyroid tumor or other malignancy. Ectopic thymic tissue can be found along the entire thymic descent path during embryogenesis. However, a thymoma arising from such ectopic thymic tissue is extremely rare. Herein we report a patient with ectopic cervical thymoma and myasthenia gravis (MG and discuss the management.

SU-G-JeP1-06: Correlation of Lung Tumor Motion with Tumor Location Using Electromagnetic Tracking

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Muccigrosso, D; Maughan, N; Parikh, P [Washington University School of Medicine, Saint Louis, MO (United States); Schultejans, H; Bera, R [Lindbergh High School, St. Louis, MO (United States)

2016-06-15

Purpose: It is well known that lung tumors move with respiration. However, most measurements of lung tumor motion have studied long treatment times with intermittent imaging; those populations may not necessarily represent conventional LINAC patients. We summarized the correlation between tumor motion and location in a multi-institutional trial with electromagnetic tracking, and identified the patient cohort that would most benefit from respiratory gating. Methods: Continuous electromagnetic transponder data (Varian Medical, Seattle, WA) of lung tumor motion was collected from 14 patients (214 total fractions) across 3 institutions during external beam radiation therapy in a prospective clinical trial (NCT01396551). External intervention from the clinician, such as couch shifts, instructed breath-holds, and acquisition pauses, were manually removed from the 10 Hz tracking data according to recorded notes. The average three-dimensional displacement from the breathing cycle’s end-expiratory to end-inhalation phases (peak-to-peak distance) of the transponders’ isocenter was calculated for each patient’s treatment. A weighted average of each isocenter was used to assess the effects of location on motion. A total of 14 patients were included in this analysis, grouped by their transponders’ location in the lung: upper, medial, and lower. Results: 8 patients had transponders in the upper lung, and 3 patients each in the medial lobe and lower lung. The weighted average ± standard deviation of all peak-to-peak distances for each group was: 1.04 ± 0.39 cm in the lower lung, 0.56 ± 0.14 cm in the medial lung, and 0.30 ± 0.06 cm in the upper lung. Conclusion: Tumors in the lower lung are most susceptible to excessive motion and daily variation, and would benefit most from continuous motion tracking and gating. Those in the medial lobe might be at moderate risk. The upper lobes have limited motion. These results can guide different motion management strategies

Folate receptor expression in bladder cancer and its correlation with tumor behaviors and clinical outcome

Directory of Open Access Journals (Sweden)

Dah-Shyong Yu

2017-12-01

Conclusion: In addition to tumor grade and stage, the expression of FR in bladder cancer is related to cellular differentiation. However, no correlation with patient survival was seen in this limited study.

Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors.

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Kaewput, Chalermrat; Suppiah, Subapriya; Vinjamuri, Sobhan

2018-01-01

The aim of our study was to correlate tumor uptake of 68 Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68 Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUV max ) and averaged SUV SUV mean of "main tumor lesions" were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUV max of tumor and Ki-67 index ( r = -0.241) and negatively poor agreement between SUV mean of tumor and Ki-67 index ( r = -0.094). SUV max of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUV mean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUV max and SUV mean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68 Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68 Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68 Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.

Fibroblastic and myofibroblastic tumors of the head and neck: Comprehensive imaging-based review with pathologic correlation

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Hourani, Roula, E-mail: rh64@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Taslakian, Bedros, E-mail: bt05@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Shabb, Nina S., E-mail: ns04@aub.edu.lb [Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut (Lebanon); Nassar, Lara, E-mail: ln07@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Hourani, Mukbil H., E-mail: mh17@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Moukarbel, Roger, E-mail: rm17@aub.edu.lb [Department of Otolaryngology – Head and Neck Surgery, American University of Beirut Medical Center, Beirut (Lebanon); Sabri, Alain, E-mail: as71@aub.edu.lb [Department of Otolaryngology – Head and Neck Surgery, American University of Beirut Medical Center, Beirut (Lebanon); Rizk, Toni, E-mail: tonirisk@hotmail.com [Department of Neurosurgery, Hôtel-Dieu de France, Saint-Joseph University, Beirut (Lebanon)

2015-02-15

Highlights: • Almost all fibroblastic tumors are evaluated with non-invasive imaging. • Radiologists should be familiar with the imaging appearance of fibroblastic tumors. • Most appropriate initial examination when fibromatosis coli suspected is ultrasound. • Most common location of ossifying fibromas is the tooth-bearing regions. - Abstract: Fibroblastic and myofibroblastic tumors of the head and neck are a heterogeneous group of disorders characterized by the proliferation of fibroblasts, myofibroblasts, or both. These tumors may be further subclassified on the basis of their behavior as benign, intermediate with malignant potential, or malignant. There are different types of fibroblastic and myofibroblastic tumors that can involve the head and neck including desmoid-type fibromatosis, solitary fibrous tumor, myofibroma/myofibromatosis, nodular fasciitis, nasopharyngeal angiofibroma, fibrosarcoma, dermatofibrosarcoma protuberans, fibromatosis coli, inflammatory myofibroblastic tumor, ossifying fibroma, fibrous histiocytoma, nodular fasciitis, fibromyxoma, hyaline fibromatosis and fibrous hamartoma. Although the imaging characteristics of fibroblastic and myofibroblastic tumors of the head and neck are nonspecific, imaging plays a pivotal role in the noninvasive diagnosis and characterization of these tumors, providing information about the constitution of tumors, their extension and invasion of adjacent structures. Correlation with the clinical history may help limit the differential diagnosis and radiologists should be familiar with the imaging appearance of these tumors to reach an accurate diagnosis.

Fibroblastic and myofibroblastic tumors of the head and neck: Comprehensive imaging-based review with pathologic correlation

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Hourani, Roula; Taslakian, Bedros; Shabb, Nina S.; Nassar, Lara; Hourani, Mukbil H.; Moukarbel, Roger; Sabri, Alain; Rizk, Toni

2015-01-01

Highlights: • Almost all fibroblastic tumors are evaluated with non-invasive imaging. • Radiologists should be familiar with the imaging appearance of fibroblastic tumors. • Most appropriate initial examination when fibromatosis coli suspected is ultrasound. • Most common location of ossifying fibromas is the tooth-bearing regions. - Abstract: Fibroblastic and myofibroblastic tumors of the head and neck are a heterogeneous group of disorders characterized by the proliferation of fibroblasts, myofibroblasts, or both. These tumors may be further subclassified on the basis of their behavior as benign, intermediate with malignant potential, or malignant. There are different types of fibroblastic and myofibroblastic tumors that can involve the head and neck including desmoid-type fibromatosis, solitary fibrous tumor, myofibroma/myofibromatosis, nodular fasciitis, nasopharyngeal angiofibroma, fibrosarcoma, dermatofibrosarcoma protuberans, fibromatosis coli, inflammatory myofibroblastic tumor, ossifying fibroma, fibrous histiocytoma, nodular fasciitis, fibromyxoma, hyaline fibromatosis and fibrous hamartoma. Although the imaging characteristics of fibroblastic and myofibroblastic tumors of the head and neck are nonspecific, imaging plays a pivotal role in the noninvasive diagnosis and characterization of these tumors, providing information about the constitution of tumors, their extension and invasion of adjacent structures. Correlation with the clinical history may help limit the differential diagnosis and radiologists should be familiar with the imaging appearance of these tumors to reach an accurate diagnosis

Expression of the BRCA1 gene in a breast tumor: Correlation with the effect of neoadjuvant chemotherapy

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Tsyganov, M. M.; Ibragimova, M. K.; Deryusheva, I. V.; Slonimskaya, E. M.; Litviakov, N. V.

2017-09-01

Most current research is limited by only germinal mutations of the BRCA1 gene (more often 5382insC) and the number of studies, which characterize various somatic alterations of the BRCA1 gene in a tumor, namely the expression of this gene and its correlation with the efficiency of chemotherapy, which is scarce. Taking into account the data on the connection between the genetic mutation of BRCA1 with the high efficiency of the platinum medication one may suggest that the expression of the BRCA1 gene is also associated with the high sensitivity of the tumor to the platinum medication. Aim: to evaluate the correlation between the expression of the BRCA1 gene in a breast tumor with the neoadjuvant chemotherapy (NACT) efficiency. The research included 86 patients with BC. We evaluated the expression of BRCA1 in the tumor material before and after NACT. We established that objective response to NACT is connected with a high level of BRCA1 in the general group of patients (p = 0.01) and in case of docetaxel monotherapy (p < 0.05).

Correlation between 11C-choline or 18F-FDG uptake and tumor proliferation: a rabbit bearing lung cancer model study

International Nuclear Information System (INIS)

Li Yajun; Bai Renju; Gao Shuo; Li Yansheng; Liu Lei; Jia Wei; Cai Li; Xing Xiling

2009-01-01

Objective: Tumor proliferative activity has been recognized as an indicator of malignant degree in lung cancer and related to prognosis. The purpose of this study was to evaluate the feasibility of assessing proliferative activity with 11 C-choline and 18 F-fluorodeoxyglucose (FDG) PET on a rabbit bearing lung VX2 tumor model. Methods: About 0.5 ml of viable VX2 tumor cell suspension was slowly injected into the right lungs of 54 New Zealand white rabbits through a transthoracical needle insertion. 11 C-choline and 18 F-FDG PET scan were performed 10-11 d after tumor implantation. One ear vein was cannulated for administration of the tracers, 11 C-choline PET scan (with Discovery LS PET/CT scanner, GE) was performed 5 rain after intravenously injection of 37 MBq 11 C-choline. Then 18.7 MBq 18 F-FDG was infused at 60 min after 11 C-choline administration and 18 F-FDG PET scan was performed at 60 min after 18 F-FDG administration. The maximal standardized uptake value of tumor was calculated. The animals were euthanized after examination. Histochemical stain with proliferating cell nuclear antigen (PCNA) was performed and PCNA index was obtained to assess tumor proliferation. The difference of 11 C-choline and 18 F-FDG was analyzed using paired student t-test. The correlation of 11 C-choline 18 F-FDG and tumor cell density and PCNA index was analyzed using Pearson linear regression. Results: Of the 54 rabbits, 36 had a solitary pulmonary tumor. The rate of successful generation of a solitary VX2 tumor was 66.7% (36/54). Only 33 rabbits underwent both 11 C-choline and 18 F-FDG PET, and enrolled in this study. The mean cellular density was (547.36 ± 64.78) cells/field and the mean PCNA index was (42.34 ± 15.26)%. 18 F-FDG was higher than 11 C-choline (5.70 ± 3.45 vs 4.02 ± 3.07, t=-3.188, P=0.003). 11 C-choline significantly and positively correlated with PCNA index (r=0.786, P 11 C-choline and tumor cellular density (r=-0.176, P=0.327). 18 F-FDG significantly and

Correlation between the progressive cytoplasmic expression of a novel small heat shock protein (Hsp16.2) and malignancy in brain tumors

International Nuclear Information System (INIS)

Pozsgai, Eva; Gomori, Eva; Szigeti, Andras; Boronkai, Arpad; Gallyas, Ferenc Jr; Sumegi, Balazs; Bellyei, Szabolcs

2007-01-01

Small heat shock proteins are molecular chaperones that protect proteins against stress-induced aggregation. They have also been found to have anti-apoptotic activity and to play a part in the development of tumors. Recently, we identified a new small heat shock protein, Hsp16.2 which displayed increased expression in neuroectodermal tumors. Our aim was to investigate the expression of Hsp16.2 in different types of brain tumors and to correlate its expression with the histological grade of the tumor. Immunohistochemistry with a polyclonal antibody to Hsp16.2 was carried out on formalin-fixed, paraffin-wax-embedded sections using the streptavidin-biotin method. 91 samples were examined and their histological grade was defined. According to the intensity of Hsp16.2 immunoreactivity, low (+), moderate (++), high (+++) or none (-) scores were given. Immunoblotting was carried out on 30 samples of brain tumors using SDS-polyacrylamide gel electrophoresis and Western-blotting. Low grade (grades 1–2) brain tumors displayed low cytoplasmic Hsp16.2 immunoreactivity, grade 3 tumors showed moderate cytoplasmic staining, while high grade (grade 4) tumors exhibited intensive cytoplasmic Hsp16.2 staining. Immunoblotting supported the above mentioned results. Normal brain tissue acted as a negative control for the experiment, since the cytoplasm did not stain for Hsp16.2. There was a positive correlation between the level of Hsp16.2 expression and the level of anaplasia in different malignant tissue samples. Hsp16.2 expression was directly correlated with the histological grade of brain tumors, therefore Hsp16.2 may have relevance as becoming a possible tumor marker

Tumor carcinóide do timo – Caso clínico

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Lina Carvalho

2010-01-01

Full Text Available Resumo: Os tumores neuroendócrinos primários representam cerca de 4% do total dos tumores do mediastino anterior, incluindo o timo, afectando mais homens que mulheres numa razão de 3:1 e apresentando uma maior incidência entre os 40 e os 60 anos. Antigamente classificados como timomas, desde 1972 são considerados um grupo distinto de neoplasias tímicas, podendo ser biologicamente activos, estando sobretudo associados à síndroma NEM-1 (19 a 25% dos doentes, sendo nestes casos mais agressivos.São descritos como tendo grande progressão local, recorrência e metástases em elevada percentagem de casos, o que determina um mau prognóstico. O estadiamento é o parâmetro mais importante para determinar a sobrevida. Tumores detectados em fase precoce e capsulados associam-se a um excelente prognóstico, enquanto em estádios avançados, localmente invasivos, têm prognóstico relativamente pobre.A remoção cirúrgica completa, para todos os tumores tímicos, é a base da terapêutica e o factor crítico para a sobrevivência a longo prazo, independentemente do tipo histológico. São uma causa de morte importante, nomeadamente os tumores associados a NEM-1 e síndroma de Cushing, e há autores que defendem a realização de timectomia profiláctica nestes doentes.Rev Port Pneumol 2010; XVI (1: 177-185 Abstract: Primary neuroendocrine tumours (carcinoid tumours account for about 4% of anterior mediastinal tumours concerning thymus localization. They appear to have a male predilection (3:1 ratio and occur mostly between 40 and 60 years of age. Classified primarily as thymomas, they have been considered a different group of thymic neoplasia since 1972. They can be biologically active, mostly associated with MEN-1 (19-25% of patients and more aggressive in these cases.As a locally invasive disease, with recurrence and metastasis in a high percentage of cases, it correlates

Correlation between spiral CT features of pericolic infiltration and tumor angiogenesis in colorectal carcinoma

International Nuclear Information System (INIS)

Zhang Ruiping; Li Jianding

2007-01-01

Objective: To investigate the correlation of spiral CT (SCT) features with pathology, microvessel density (MVD), expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2( MMP-2) in colorectal carcinoma. Methods: Forty patients with colorectal carcinoma confirmed by operation were examined by SCT. The resected tumor specimens were immunohistochemically stained for the expression of VEGF, MMP-2 and the calculation of MVD. Results: The accuracy of SCT in depicting the pericolic and wall infiltration was 92.5%. The metastasis rates of colorectal cancer with pericolic infiltration and wall infiltration were 75.0% and 33.3%, respectively, the differences were statistically significant between the two groups (P<0.05). The differences of CT enhancement value, MVD, expressions of VEGF and MMP-2 between the two groups were statistically significant (P<0.05). The enhancement degree of CT had a positive correlation with MVD (P<0.05). Conclusion: SCT is accurate for depicting pericolic and wall infiltration, pericolic infiltration in colorectal carcinoma indicates the tendency of metastasis. The enhancement degree of CT might be used to quantitatively evaluate the tumor angiogenesis, expressions of VEGF and MMP-2 and MVD are closely correlated with the infiltration of colorectal cancer. (authors)

Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis

International Nuclear Information System (INIS)

Muto, Masahiro; Ying Chen; Kubo, Eiko; Mita, Kazuei

1996-01-01

Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of γ T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2 + (TL-2 + ) thymocytes. Limited numbers of TL-2 + cells from individual irradiated B10.Thy-1.1 mice were injected into B10.Thy-1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F; 10C), t(1A; 13D) or t(6A; XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after γ T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after γ TCR rearrangements. (author)

A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses.

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Nasreldin, Magda H A; Ibrahim, Eman A; Saad El-Din, Somaia A

2016-01-01

Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year-old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations.

A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses

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Magda H. A. Nasreldin

2016-01-01

Full Text Available Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year-old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations.

Spindle epithelial tumor with thymus-like differentiation of the thyroid gland: A case report with ultrasonography and CT features, cytological findings and histopathological results

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Kang, Dong Joo; Lee, Yoo Jin; Kim, Dong Wook; Jung, Soo Jin [Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

2016-11-15

Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid gland is a very rare tumor. It is believed to originate from ectopic thymus tissue within the thyroid gland or from branchial pouch remnants that differentiate along the thymic line. A few reports of SETTLE have been presented, but to the best of our knowledge, there is no case report in which detailed preoperative imaging features of SETTLE have been described. In addition, there are no case reports of SETTLE in Korean patients. Thus, we report a case of SETTLE with detailed preoperative ultrasonography and computed tomography features, cytological findings and histopathological results.

Spindle epithelial tumor with thymus-like differentiation of the thyroid gland: A case report with ultrasonography and CT features, cytological findings and histopathological results

International Nuclear Information System (INIS)

Kang, Dong Joo; Lee, Yoo Jin; Kim, Dong Wook; Jung, Soo Jin

2016-01-01

Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid gland is a very rare tumor. It is believed to originate from ectopic thymus tissue within the thyroid gland or from branchial pouch remnants that differentiate along the thymic line. A few reports of SETTLE have been presented, but to the best of our knowledge, there is no case report in which detailed preoperative imaging features of SETTLE have been described. In addition, there are no case reports of SETTLE in Korean patients. Thus, we report a case of SETTLE with detailed preoperative ultrasonography and computed tomography features, cytological findings and histopathological results

Enhancement pattern analysis of hypervascular hepatocellular carcinoma on dynamic MR imaging with histopathological correlation: Validity of portal phase imaging for predicting tumor grade

International Nuclear Information System (INIS)

Okamoto, Daisuke; Yoshimitsu, Kengo; Nishie, Akihiro; Tajima, Tsuyoshi; Asayama, Yoshiki; Ishigami, Kousei; Hirakawa, Masakazu; Ushijima, Yasuhiro; Kakihara, Daisuke; Nakayama, Tomohiro; Nishihara, Yunosuke; Aishima, Shinichi; Taketomi, Akinobu; Kishimoto, Junji; Honda, Hiroshi

2012-01-01

Purpose: To elucidate the correlation between hypervascular hepatocellular carcinoma (HCC) enhancement patterns on dynamic MR imaging and histological findings. Materials and methods: Surgically proven 46 hypervascular HCCs of forty-one patients were enrolled. For each HCC, the signal intensity in the portal phase (SIPP) was evaluated. In this study, high, iso-, or low intensity in the portal phase was hypothesized as late, moderate, or early washout pattern, respectively. The SIPP of each HCC was correlated to histological grade and architectural subtypes that represent degrees of trabecular structure. For the trabecular HCCs, the thickness of tumor plate was also correlated for indirect estimation of tumor sinusoid. Results: There was a significant correlation between the SIPP vs. histological grade and also vs. architectural subtypes, namely the degree of trabecular structure. Washout of hypervascular HCC occurred earlier as the histological grade advanced and the histological architecture got closer to pure trabecular HCC. For the trabecular HCCs, the thickness of tumor plate correlated significantly with SIPP or histological grade. Hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern. Conclusions: Histological grade of hypervascular HCC may be predicted using SIPP. The thickness of tumor plate, resultantly the size of sinusoid between tumor plates, can account for the relationship between washout pattern and histological grade in the trabecular HCCs.

MR staging of malignant musculoskeletal tumors: An experimental study on MR and pathologic correlation of rabbit VX-2 carcinoma

International Nuclear Information System (INIS)

Kang, Heung Sik; Chung, Sung Hoon; KIm, Cheol Woo; Kim, Seong Moon; Im, Jung Gi; Han, Man Chung

1993-01-01

To evaluate the reliability of MR imaging in tissue characterization and depiction of tumor boundaries, we performed MR pathologic correlation using parosteally implanted VX-2 carcinoma in 17 rabbit thighs. T1-weighted, T2-weighted and Gd-DTPA enhanced T1-weighted axial images were obtained 10-30 days after tumor implantation. After the animals were killed, frozen and sectioned along the MR imaging planes, and histopathologic examination were done. For accurate MR pathologic correlation, rabbit were fixed on the cardboard plate to minimize position change during the procedure. Tumor boundaries depicted on MR images were larger than those depicted on the specimen. Small tumors were surrounded by capsule-like loose connective tissue. Loose connective tissue became compact with tumor growth. This connective tissue showed high signal intensity on both T2-weighted and Gd-DTPA enhanced T1-weighted images. Muscle atrophy with fatty tissue accumulation around the tumor also contributed to the high signal intensity on MR images. Peritumoral edema and inflammatory reaction were not remarkable. Six of 8 cases with bone marrow fibrosis were detected on MR images. We concluded that peritumoral loose connective tissue and muscle atrophy exaggerated the size of experimentally induced malignant musculoskeletal tumors on MR images

Correlation between the progressive cytoplasmic expression of a novel small heat shock protein (Hsp16.2 and malignancy in brain tumors

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Gallyas Ferenc

2007-12-01

Full Text Available Abstract Background Small heat shock proteins are molecular chaperones that protect proteins against stress-induced aggregation. They have also been found to have anti-apoptotic activity and to play a part in the development of tumors. Recently, we identified a new small heat shock protein, Hsp16.2 which displayed increased expression in neuroectodermal tumors. Our aim was to investigate the expression of Hsp16.2 in different types of brain tumors and to correlate its expression with the histological grade of the tumor. Methods Immunohistochemistry with a polyclonal antibody to Hsp16.2 was carried out on formalin-fixed, paraffin-wax-embedded sections using the streptavidin-biotin method. 91 samples were examined and their histological grade was defined. According to the intensity of Hsp16.2 immunoreactivity, low (+, moderate (++, high (+++ or none (- scores were given. Immunoblotting was carried out on 30 samples of brain tumors using SDS-polyacrylamide gel electrophoresis and Western-blotting. Results Low grade (grades 1–2 brain tumors displayed low cytoplasmic Hsp16.2 immunoreactivity, grade 3 tumors showed moderate cytoplasmic staining, while high grade (grade 4 tumors exhibited intensive cytoplasmic Hsp16.2 staining. Immunoblotting supported the above mentioned results. Normal brain tissue acted as a negative control for the experiment, since the cytoplasm did not stain for Hsp16.2. There was a positive correlation between the level of Hsp16.2 expression and the level of anaplasia in different malignant tissue samples. Conclusion Hsp16.2 expression was directly correlated with the histological grade of brain tumors, therefore Hsp16.2 may have relevance as becoming a possible tumor marker.

Dynamical properties of a tumor growth system in the presence of immunization and colored cross-correlated noises

International Nuclear Information System (INIS)

Jia Zhenglin; Mei Dongcheng

2010-01-01

We investigate the effects of the noise parameters and immunization strength β on the dynamical properties of a tumor growth system with both immunization and colored cross-correlated noises. The analytical expressions for the associated relaxation time T C and the normalized correlation function C(s) are derived by means of the projection operator method. The results indicate that: (i) T C as a function of the multiplicative noise intensity α shows resonance-like behavior, i.e. the curves of T C versus α exhibit a single-peak structure and its peak position changes with increasing correlation strength between noises λ, the autocorrelation time of multiplicative noise τ 1 , the autocorrelation time of additive noise τ 2 and the cross-correlation time τ 3 . This behavior can be understood in terms of the noise-enhanced stability effect and the influence of the memory effects on it. (ii) The increasing λ, τ 1 , τ 2 and the additive noise intensity D slow down the fluctuation decay of the tumor population, whereas the increasing τ 3 and β speed it up. (iii) C(s) increases as λ, τ 1 , τ 2 and β increase, while it decreases with τ 3 increasing. Our study shows that the effects of some noise parameters on tumor growth can be modified due to the presence of the immunization effect.

Dynamical properties of a tumor growth system in the presence of immunization and colored cross-correlated noises

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Jia, Zheng-Lin; Mei, Dong-Cheng

2010-05-01

We investigate the effects of the noise parameters and immunization strength β on the dynamical properties of a tumor growth system with both immunization and colored cross-correlated noises. The analytical expressions for the associated relaxation time TC and the normalized correlation function C(s) are derived by means of the projection operator method. The results indicate that: (i) TC as a function of the multiplicative noise intensity α shows resonance-like behavior, i.e. the curves of TC versus α exhibit a single-peak structure and its peak position changes with increasing correlation strength between noises λ, the autocorrelation time of multiplicative noise τ1, the autocorrelation time of additive noise τ2 and the cross-correlation time τ3. This behavior can be understood in terms of the noise-enhanced stability effect and the influence of the memory effects on it. (ii) The increasing λ, τ1, τ2 and the additive noise intensity D slow down the fluctuation decay of the tumor population, whereas the increasing τ3 and β speed it up. (iii) C(s) increases as λ, τ1, τ2 and β increase, while it decreases with τ3 increasing. Our study shows that the effects of some noise parameters on tumor growth can be modified due to the presence of the immunization effect.

Thymic lymphocytes. III. Cooperative phenomenon in the proliferation of thymocytes under Con A stimulation.

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Papiernik, M; Jacobson, J B

1986-01-01

In the present paper, the response of thymocytes to Con A is analyzed in terms of a cooperative phenomenon between medullary thymocytes, cortical thymocytes, thymic accessory cells, and interleukin 2. Medullary thymocytes respond spontaneously to Con A and produce IL-2. The addition of exogenously produced IL-2 enhances their proliferation. Small numbers of cortical (PNA+) thymocytes do not respond to Con A, even in the presence of IL-2-containing supernatant. By increasing the number of PNA+ cells per well, sensitivity to Con A and IL-2 appears. This response may be linked either to the increase in a minor PNA+-responding population and/or to the enhanced contamination by medullary thymocytes and macrophages in non-responding PNA+ thymocyte population. In this hypothesis, either the contaminating cells respond by themselves and/or cooperate with PNA+ cells to induce their proliferation. Coculture of non-responding low numbers of PNA+ thymocytes with Con A- and IL-2-containing supernatant in the presence of PNA- cells containing thymic medullary thymocytes and macrophages always produces a higher response than that of each individual population. These results show that a cooperative phenomenon occurs in the cocultures of PNA+ and PNA- thymic cells. We can show using PNA+ and PNA- thymocytes with different Thy 1 alleles, that indeed both PNA+ and populations participate PNA-thymocytes with different Thy 1 alleles, that indeed both PNA+ and PNA- populations participate in the generation of proliferating cells. We can demonstrate, by lysis experiments with monoclonal antibodies and complement that at the end of coculture, most of the proliferating cells are Lyt 1+, and part are Lyt 2+ or L3T4+. We discuss the fact that the phenotype of the cells after activation does not allow us to deduce the phenotype of their precursors. Lysis of Ia+ cells prior to coculture, reduces the level of the proliferative response but does not modify the percentage of cooperation produced

B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

International Nuclear Information System (INIS)

Reddy, M.M.; Goh, K.; Hempelmann, L.H.

1976-01-01

B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

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Neves-dos-Santos Sandra

2010-01-01

Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

The correlation between aldehyde dehydrogenase-1A1 level and tumor shrinkage after preoperative chemoradiation in locally advanced rectal cancer

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Rhandyka Rafli

2015-12-01

Full Text Available This study was performed to determine the correlation between aldehyde dehydrogenase-1A1 (ALDH1A1 level and tumor shrinkage after chemoradiation in locally advanced rectal cancer. This is a retrospective study of 14 locally advanced rectal cancer patients with long course neoadjuvant chemoradiation. ALDH1A1 level was measured using ELISA from paraffin embedded tissue. Tumor shrinkage was measured from computed tomography (CT scan or magnetic resonance imaging (MRI based on Response Evaluation Criteria in Solid Tumor v1.1 (RECIST v1.1. The mean of ALDH1A1 level was 9.014 ± 3.3 pg/mL and the mean of tumor shrinkage was 7.89 ± 35.7%. Partial response proportion was 28.6%, stable disease proportion was 50% and progressive disease proportion was 21.4%. There was a significant strong negative correlation (r = –0.890, plt; 0.001 between ALDH1A1 and tumor shrinkage. In conclusion, tumor shrinkage in locally advanced rectal cancer after preoperative chemoradiation was influenced by ALDH1A1 level. Higher level of ALDH1A1 suggests decreased tumor shrinkage after preoperative chemoradiation.

Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis.

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Xing, Chen; Ma, Ning; Xiao, He; Wang, Xiaoqian; Zheng, Mingke; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi

2015-03-01

This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis. © Society for Leukocyte Biology.

Assessment of tumor blood flow and its correlation with histopathologic features in skull base meningiomas and schwannomas by using pseudo-continuous arterial spin labeling images

International Nuclear Information System (INIS)

Yamamoto, Tatsuya; Takeuchi, Hiroaki; Kinoshita, Kazuyuki; Kosaka, Nobuyuki; Kimura, Hirohiko

2014-01-01

Objective: We aimed to investigate whether pseudo-continuous arterial spin labeling (pcASL)-MRI can adequately evaluate tumor perfusion even if the tumors are located in the skull base region and evaluate the correlation between tumor blood flow (TBF) and the histopathologic features of skull base meningiomas and schwannomas. Materials and methods: We enrolled 31 patients with skull base meningioma (n = 14) and schwannoma (n = 17) who underwent surgical resection. TBF was calculated from pcASL. Tissue sections were stained with CD34 to evaluate microvessel area (MVA). TBF and MVA ratio were compared between meningiomas and schwannomas using Mann–Whitney U-test. The correlations between MVA ratio and TBF were evaluated in each tumor by using single linear regression analysis and Spearman's rank correlation coefficients (r s ). Results: MVA ratio and TBF were significantly higher in meningioma than in schwannoma (both p < 0.01). Correlation analyses revealed significant positive correlations between MVA ratio and both mean and max TBF for meningiomas (r s = 0.89, 0.81, both p < 0.01). There was a weak positive correlation between MVA ratio and mean TBF for schwannomas (r s = 0.43, p = 0.04). However, no significant correlation was found between MVA ratio and max TBF for schwannoma. Conclusions: pcASL-MRI is useful for evaluating tumor perfusion even if the tumors are located in the skull base region. Moreover, pcASL-TBF was significantly higher in most meningiomas compared to schwannomas, which can help in the differential diagnosis of the 2 tumor types even without the use of contrast material

Life-shortening and carcinogenesis in mice irradiated neonatally with x rays

International Nuclear Information System (INIS)

Sasaki, S.; Kasuga, T.

1981-01-01

The characteristics of life-shortening and carcinogenesis were investigated in x-irradiated neonatal B6WFr mice. Animals were irradiated with 24 hr after birth and allowed to complete their normal life span. Mean life span was shortened linearly with doses at a rate of 9.1% per 100 R for females and 9.8% for males. The spectrum of neoplastic diseases was apparently modulated by x irradiation, showing neonatal B6WFr mice to be highly susceptible to the induction of thymic lymphoma, liver tumor, and pituitary tumor. The dose-response relationship for thymice lymphoma could be described by a linear-quadratic model, and linearity could be rejected. Thymic lymphoma developed after a short latent period, resulting in death between 100 and 450 days of age. Liver and pituitary tumors increased with increasing dose up to 400 R and decreased thereafter. The latent period for liver tumor development was apparently shortened with increasing doses. Pituitary tumor developed in excess only in females after a long latent period

Self-scaling tumor growth

DEFF Research Database (Denmark)

Schmiegel, Jürgen

We study the statistical properties of the star-shaped approximation of in vitro tumor profiles. The emphasis is on the two-point correlation structure of the radii of the tumor as a function of time and angle. In particular, we show that spatial two-point correlators follow a cosine law. Further......We study the statistical properties of the star-shaped approximation of in vitro tumor profiles. The emphasis is on the two-point correlation structure of the radii of the tumor as a function of time and angle. In particular, we show that spatial two-point correlators follow a cosine law....... Furthermore, we observe self-scaling behaviour of two-point correlators of different orders, i.e. correlators of a given order are a power law of the correlators of some other order. This power-law dependence is similar to what has been observed for the statistics of the energy-dissipation in a turbulent flow....... Based on this similarity, we provide a Lévy based model that captures the correlation structure of the radii of the star-shaped tumor profiles....

Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

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Jie Dong

Full Text Available After a tightly regulated developmental program in the thymus, "mature" single positive (SP thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+ pre-RTEs, a population of CD4(+ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+ pre-RTEs is independent of MHC class II and Aire molecules.

Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.

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Jen, Kuang-Yu; Song, Ihn Young; Banta, Karl Luke; Wu, Di; Mao, Jian-Hua; Balmain, Allan

2012-01-19

T-cell acute lymphoblastic lymphomas commonly demonstrate activating Notch1 mutations as well as mutations or deletions in Fbxw7. However, because Fbxw7 targets Notch1 for degradation, genetic alterations in these genes are expected to be mutually exclusive events in lymphomagenesis. Previously, by using a radiation-induced Tp53-deficient mouse model for T-cell acute lymphoblastic lymphoma, we reported that loss of heterozygosity at the Fbxw7 locus occurs frequently in a Tp53-dependent manner. In the current study, we show that these thymic lymphomas also commonly exhibit activating Notch1 mutations in the proline-glutamic acid-serine-threonine (PEST) domain. Moreover, concurrent activating Notch1 PEST domain mutations and single-copy deletions at the Fbxw7 locus occur with high frequency in the same individual tumors, indicating that these changes are not mutually exclusive events. We further demonstrate that although Notch1 PEST domain mutations are independent of Tp53 status, they are completely abolished in mice with germline Fbxw7 haploinsufficiency. Therefore, Notch1 PEST domain mutations only occur when Fbxw7 expression levels are intact. These data suggest a temporal sequence of mutational events involving these important cancer-related genes, with Notch1 PEST domain mutations occurring first, followed by Fbxw7 deletion, and eventually by complete loss of Tp53.

Tumor cell proliferation kinetics and tumor growth rate

Energy Technology Data Exchange (ETDEWEB)

Tubiana, M

1989-01-01

The present knowledge on the growth rate and the proliferation kinetics of human tumor is based on the measurement of the tumor doubling times (DT) in several hundred patients and on the determination of the proportion of proliferating cells with radioactive thymidine or by flow cytometry in large numbers of patients. The results show that the DT of human tumor varies widely, from less than one week to over one year with a median value of approximately 2 months. The DTs are significantly correlated with the histological type. They depend upon (1) the duration of the cell cycle whose mean duration is 2 days with small variations from tumor to tumor, (2) the proportion of proliferating cells and consequently the cell birth rate which varies widely among tumors and which is significantly correlated to the DT, (3) the cell loss factors which also vary widely and which are the greatest when proliferation is most intensive. These studies have several clinical implications: (a) they have further increased our understanding of the natural history of human tumor, (b) they have therapeutic implications since tumor responsiveness and curability by radiation and drugs are strongly influenced by the cell kinetic parameters of the tumor, (c) the proportion of proliferating cells is of great prognostic value in several types of human cancers. The investigation of the molecular defects, which are correlated with the perturbation of control of cell proliferation, should lead to significant fundamental and therapeutic advances. (orig.).

EMMPRIN Expression in Oral Squamous Cell Carcinomas: Correlation with Tumor Proliferation and Patient Survival

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Luís Silva Monteiro

2014-01-01

Full Text Available The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN expression in oral squamous cell carcinomas (OSCC, and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%. EMMPRIN overexpression was observed in 56 cases (75.7%. Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P=0.002. Overexpression of EMMPRIN was correlated with high Ki-67 expression (P=0.004. In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS (P=0.034. Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survival.

Science.gov (United States)

Monteiro, Luís Silva; Delgado, Maria Leonor; Ricardo, Sara; Garcez, Fernanda; do Amaral, Barbas; Pacheco, José Júlio; Lopes, Carlos; Bousbaa, Hassan

2014-01-01

The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P = 0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression (P = 0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS) (P = 0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

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

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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.

Cushing Syndrome: Diagnostic Workup and Imaging Features, With Clinical and Pathologic Correlation.

Science.gov (United States)

Wagner-Bartak, Nicolaus A; Baiomy, Ali; Habra, Mouhammed Amir; Mukhi, Shalini V; Morani, Ajaykumar C; Korivi, Brinda R; Waguespack, Steven G; Elsayes, Khaled M

2017-07-01

Cushing syndrome (CS) is a constellation of clinical signs and symptoms resulting from chronic exposure to excess cortisol, either exogenous or endogenous. Exogenous CS is most commonly caused by administration of glucocorticoids. Endogenous CS is subdivided into two types: adrenocorticotropic hormone (ACTH) dependent and ACTH independent. Cushing disease, which is caused by a pituitary adenoma, is the most common cause of ACTH-dependent CS for which pituitary MRI can be diagnostic, with bilateral inferior petrosal sinus sampling useful in equivocal cases. In ectopic ACTH production, which is usually caused by a tumor in the thorax (e.g., small cell lung carcinoma, bronchial and thymic carcinoids, or medullary thyroid carcinoma) or abdomen (e.g., gastroenteropancreatic neuroendocrine tumors or pheochromocytoma), CT, MRI, and nuclear medicine tests are used for localizing the source of ACTH. In ACTH-independent CS, which is caused by various adrenal abnormalities, adrenal protocol CT or MRI is usually diagnostic.

CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

International Nuclear Information System (INIS)

Olsson, Eleonor; Lövgren, Kristina; Fernö, Mårten; Grabau, Dorthe; Borg, Åke; Hegardt, Cecilia; Honeth, Gabriella; Bendahl, Pär-Ola; Saal, Lao H; Gruvberger-Saal, Sofia; Ringnér, Markus; Vallon-Christersson, Johan; Jönsson, Göran; Holm, Karolina

2011-01-01

The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC) compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44 + /CD24 - phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to

CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

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Vallon-Christersson Johan

2011-09-01

Full Text Available Abstract Background The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. Methods We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Results Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. Conclusions We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in

Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy.

Science.gov (United States)

Michl, M; Koch, J; Laubender, R P; Modest, D P; Giessen, C; Schulz, Ch; Heinemann, V

2014-10-01

In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in

In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes.

NARCIS (Netherlands)

Small, M; Kraal, G.

2003-01-01

Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were

Mechanistic target of rapamycin (MTOR) protein expression in the tumor and its microenvironment correlates with more aggressive pathology at cystectomy

NARCIS (Netherlands)

Winters, B.R. (Brian R.); Vakar-Lopez, F. (Funda); Brown, L. (Lisha); Montgomery, B. (Bruce); Seiler, R. (Roland); P.C. Black (Peter C.); J.L. Boormans (Joost); Dall′Era, M. (Marc); Davincioni, E. (Elai); Douglas, J. (James); Gibb, E.A. (Ewan A.); B.W. van Rhijn (Bas); M.S. van der Heijden (Michiel); Hsieh, A.C. (Andrew C.); Wright, J.L. (Jonathan L.); Lam, H.-M. (Hung-Ming)

2018-01-01

textabstractBackground: The mechanistic target of rapamycin (mTOR) has been implicated in driving tumor biology in multiple malignancies, including urothelial carcinoma (UC). We investigate how mTOR and phosphorylated mTOR (pmTOR) protein expression correlate with chemoresponsiveness in the tumor

Cyclooxygenase-2 Pathway Correlates with VEGF Expression in Head and Neck Cancer. Implications for Tumor Angiogenesis and Metastasis

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Oreste Gallo

2001-01-01

Full Text Available We evaluated the role of COX-2 pathway in 35 head and neck cancers (HNCs by analyzing COX-2 expression and prostaglandin E2 (PGE2 production in relation to tumor angiogenesis and lymph node metastasis. COX-2 activity was also correlated to vascular endothelial growth factor (VEGF mRNA and protein expression. COX-2 mRNA and protein expression was higher in tumor samples than in normal mucosa. PGE2 levels were higher in the tumor front zone in comparison with tumor core and normal mucosa (P<0001. Specimens from patients with lymph node metastasis exhibited higher COX-2 protein expression (P=.0074, PGEZ levels (P=.0011 and microvessel density (P<.0001 than specimens from patients without metastasis. A significant correlation between COX-2 and tumor vascularization (rs=0.450, P=.007 as well as between COX-2 and microvessel density with VEGF expression in tumor tissues was found (rs=0.450, P=.007; rs=0.620, P=.0001, respectively. The induction of COX-2 mRNA and PGE2 synthesis by EGF and Escherichia coli lipopolysaccharide (LPS in A-431 and SCC-9 cell lines, resulted in an increase in VEGF mRNA and protein production. Indomethacin and celecoxib reversed the EGF- and LPS-dependent COX-2, VEGF, and PGE2 increases. This study suggests a central role of COX-2 pathway in HNC angiogenesis by modulating VEGF production and indicates that COX-2 inhibitors may be useful in HNC treatment.

Study of RpI22 in MDS and AML

Science.gov (United States)

2016-12-01

developed significantly larger and markedly more vascularized thymic tumors than those observed in Rpl22þ/þ control mice. But, unlike Rpl22þ/þ or Rpl22þ...hypoxia (31). Alternatively, we did not observe obvious necrosis in the center of the large thymic tumors from Rpl22-deficent mice, suggesting Rpl22...Orthop Res 2004;22:1175–81. 32. Loeffler S, Fayard B, Weis J, Weissenberger J. Interleukin-6 induces tran- scriptional activation of vascular endothelial

Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts

DEFF Research Database (Denmark)

Nielsen, S. D.; Jeppesen, D. L.; Kolte, L.

2001-01-01

and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P ...). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T...... cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function....

Macrophage content of murine tumors: Associations with TD50 and tumor radiocurability

International Nuclear Information System (INIS)

Wike, J.; Hunter, N.; Volpe, J.; Milas, L.

1987-01-01

The experiments were designed to investigate whether the tumor-associated macrophage (TAM) content of murine solid tumors correlates with tumor response to ionizing radiation and with the clonogenic ability of tumor cells to establish s.c. tumors. Of 13 tumors studied, 6 were sarcomas and 7 were carcinomas; all tumors were of spontaneous origin in C/sub 3/Hf/Kam mice, with the exception of one sarcoma that was induced by 3-methylcholanthrene. Tumors were growing in the hind thighs of syngeneic mice, and their TAM content was determined when they were 8 mm in diameter. Their macrophage content varied greatly, ranging from 9 to 83%. Radiocurability of 8 mm tumors, determined by TCD50, ranged from 42 Gy (fibrosarcoma FSA) to > 80 Gy (hepatocarcinoma HCA-I). There was an obvious trend toward positive correlation (r = 0.43) between TAM content and reduced local tumor radiocurability. However, there was a significant negative correlation between TAM content and TD50 values, implying that cells from tumors with higher macrophage content were more clonogenic. TAM from the NFSA sarcoma, a tumor with a low TD50 value and poorly responsive to radiation, stimulated the in vitro growth of NFSA tumor cells. These observations suggest that high TAM content could be conducive to tumor cell proliferation and could be a factor in poor tumor radioresponse

T-cell receptor excision circles (TREC) in CD4+ and CD8+ T-cell subpopulations in atopic dermatitis and psoriasis show major differences in the emission of recent thymic emigrants

DEFF Research Database (Denmark)

Just, Helle L; Deleuran, Mette; Vestergaard, Christian

2008-01-01

. In contrast, both men and women with psoriasis had significantly reduced TREC levels, which were, on average, only 30% of that of healthy persons. In atopic dermatitis the levels of TREC declined with increasing levels of IgE, disease intensity and extent of eczema. Furthermore, patients with atopic......-cells, this indicates that atopic dermatitis patients can have compensatory emissions of thymic emigrants, whereas psoriatic patients do not, thus supporting different thymic function in these two diseases....

Cisto tímico como diagnóstico diferencial de doença aguda da aorta torácica Thymic cyst as a differencial diagnosis of acute thoracic aortic disease

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Marcos Gradim Tiveron

2008-12-01

Full Text Available Paciente encaminhada de outro serviço com história de dor torácica aguda de forte intensidade com diagnóstico de hematoma intramural na aorta ascendente para correção cirúrgica. Após investigação diagnóstica, identificou-se tumoração cística no mediastino anterior, que envolvia toda a aorta ascendente e que produzia restrição ao enchimento diastólico do ventrículo direito. A análise histológica do tumor ressecado revelou o diagnóstico de cisto tímico. Objetivo deste relato é descrever tumoração mediastinal de baixa prevalência, que pode produzir imagem radiológica com características de hematoma intramural e resultar em conduta terapêutica equivocada.Patient was referred to our Service with acute thoracic pain and diagnosis of intramural hematoma of the ascending aorta for surgical correction. The diagnostic investigation showed a cystic tumor involving the ascending aorta causing restriction of the right ventricular inflow. After resection, the histologic analysis disclosed the diagnosis of thymic cyst. The aim of this study is to describe a rare mediastinal tumor that may simulate a radiologic feature with characteristics of intramural hematoma and may result in a wrong therapeutic approach.

Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis.

Science.gov (United States)

Surov, Alexey; Meyer, Hans Jonas; Wienke, Andreas

2017-08-29

The purpose of this meta-analysis was to provide clinical evidence regarding relationship between ADC and cellularity in different tumors based on large patient data. Medline library was screened for associations between ADC and cell count in different tumors up to September 2016. Only publications in English were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) was used for the research. Overall, 39 publications with 1530 patients were included into the analysis. The following data were extracted from the literature: authors, year of publication, number of patients, tumor type, and correlation coefficients. The pooled correlation coefficient for all studies was ρ = -0.56 (95 % CI = [-0.62; -0.50]),. Correlation coefficients ranged from ρ =-0.25 (95 % CI = [-0.63; 0.12]) in lymphoma to ρ=-0.66 (95 % CI = [-0.85; -0.47]) in glioma. Other coefficients were as follows: ovarian cancer, ρ = -0.64 (95% CI = [-0.76; -0.52]); lung cancer, ρ = -0.63 (95 % CI = [-0.78; -0.48]); uterine cervical cancer, ρ = -0.57 (95 % CI = [-0.80; -0.34]); prostatic cancer, ρ = -0.56 (95 % CI = [-0.69; -0.42]); renal cell carcinoma, ρ = -0.53 (95 % CI = [-0.93; -0.13]); head and neck squamous cell carcinoma, ρ = -0.53 (95 % CI = [-0.74; -0.32]); breast cancer, ρ = -0.48 (95 % CI = [-0.74; -0.23]); and meningioma, ρ = -0.45 (95 % CI = [-0.73; -0.17]).

Peripheral nerve tumors in neurofibromatosis type 1. Correlation of MR imaging and histopathologic findings

International Nuclear Information System (INIS)

Karube, Sachiko

1995-01-01

Magnetic resonance imaging (MRI) of peripheral nerve tumors in neurofibromatosis type I was correlated with histopathologic findings. MRI of 2 of 5 pachydermatoceles revealed T1-weighted image (T1WI) low-intensity and STIR high-intensity areas in the adipose tissue (fine marbled appearance) corresponding to mixtures of tumor and small amounts of adipose tissue. The pachydermatoceles in the 3 remaining cases showed coarse-marbled T1WI low, and STIR high areas reflecting histopathological changes due to proliferation of neurofibroma tissue mainly within the connective tissue septa between the fat lobules. All of the six plexiform neurofibromas exhibited central iso- to low-intensity, and peripheral high-intensity (target appearance) on STIR. Histopathologically, the tumors were composed of a central hypercellular area and peripheral myxomatous area. Low-grade neurofibrosarcoma showed the same MRI patterns as plexiform neurofibromas. High-grade neurofibrosarcoma showed heterogeneous signal intensity on T1WI and Gd-DTPA T1WI coincided with the histopathologic findings, such as necrosis and hemorrhage. (author)

Thymic Nurse Cells Participate in Heterotypic Internalization and Repertoire Selection of Immature Thymocytes; Their Removal from the Thymus of Autoimmune Animals May be Important to Disease Etiology.

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Guyden, J C; Martinez, M; Chilukuri, R V E; Reid, V; Kelly, F; Samms, M-O D

2015-01-01

Thymic nurse cells (TNCs) are specialized epithelial cells that reside in the thymic cortex. The initial report of their discovery in 1980 showed TNCs to contain up to 200 thymocytes within specialized vacuoles in their cytoplasm. Much has been reported since that time to determine the function of this heterotypic internalization event that exists between TNCs and developing thymocytes. In this review, we discuss the literature reported that describes the internalization event and the role TNCs play during T cell development in the thymus as well as why these multicellular complexes may be important in inhibiting the development of autoimmune diseases.

Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

International Nuclear Information System (INIS)

Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K.; Kim, Grace E.; Lin, Lawrence; Giacomini, Kathy; Naranjo, Arlene; Van Ryn, Collin; Yanik, Gregory A.; Kreissman, Susan G.; Hogarty, Michael; DuBois, Steven G.

2016-01-01

Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children's Oncology Group

Energy Technology Data Exchange (ETDEWEB)

Temple, William; Mendelsohn, Lori; Nekritz, Erin; Gustafson, W.C.; Matthay, Katherine K. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); Kim, Grace E. [UCSF School of Medicine, Department of Pathology, San Francisco, CA (United States); Lin, Lawrence; Giacomini, Kathy [UCSF School of Pharmacy, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA (United States); Naranjo, Arlene; Van Ryn, Collin [University of Florida, Children' s Oncology Group Statistics and Data Center, Gainesville, FL (United States); Yanik, Gregory A. [University of Michigan, CS Mott Children' s Hospital, Ann Arbor, MI (United States); Kreissman, Susan G. [Duke University Medical Center, Durham, NC (United States); Hogarty, Michael [University of Pennsylvania, Children' s Hospital of Philadelphia and Perelman School of Medicine, Philadelphia, PA (United States); DuBois, Steven G. [UCSF School of Medicine, Department of Pediatrics, San Francisco, CA (United States); UCSF Benioff Children' s Hospital, San Francisco, CA (United States); UCSF School of Medicine, San Francisco, CA (United States)

2016-03-15

Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features. We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 - 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests. Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (n = 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in MYCN amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45; p = 0.04). VMAT1 expression did not correlate with MIBG avidity. VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. (orig.)

[Correlation between typing of peripheral neuroblastic tumors and prognosis: a clinicopathologic study of 135 cases].

Science.gov (United States)

YIN, Min-zhi; ZHANG, Zhong-de; MA, Jing; SHEN, Ping; CHEN, Jie-feng; ZHANG, Hui-zhen

2011-03-01

To study the clinicopathologic characteristics of peripheral neuroblastic tumors and to investigate the prognostic significance of International Neuroblastoma Pathology Classification (INPC). One hundred and thirty-five cases of peripheral neuroblastic tumors encountered in Shanghai Children's Medical Center were enrolled into the study. All the cases were classified according to INPC and International Neuroblastoma Staging System (INSS). The follow-up data were analyzed. The consensus diagnoses of the 135 cases were as follows: 80 cases (59.2%) of neuroblastoma, 24 cases (17.8%) of ganglioneuroblastoma, intermixed, 17 cases (12.6%) of ganglioneuroma and 14 cases (10.4%) of ganglioneuroblastoma, nodular. The cases were subdivided into 2 subgroups: favorable histology (number = 90, 66.7%) and unfavorable histology (number = 45, 33.3%). According to INSS, the number of cases in stages I, II, III and IV was 22 (16.3%), 24 (17.8%), 34 (25.2%) and 55 (40.7%), respectively. The survival of peripheral neuroblastic tumors correlated with histologic diagnosis, INPC and INSS (P < 0.05). Diagnostic categorization of peripheral neuroblastic tumors according to INPC is of prognostic value.

Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts

International Nuclear Information System (INIS)

Shin, H.S.; Hayden, M.; Langley, S.; Kaliss, N.; Smith, M.R.

1975-01-01

Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were active in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls. (U.S.)

Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

International Nuclear Information System (INIS)

Kim, Jong-Hyuk; Yu, Chi-Ho; Yhee, Ji-Young; Im, Keum-Soon; Kim, Na-Hyun; Sur, Jung-Hyang

2010-01-01

Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses. The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although

Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

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Kim Jong-Hyuk

2010-05-01

Full Text Available Abstract Background Human seminoma is classified as classical seminoma (SE and spermatocytic seminoma (SS. Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Methods Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns were classified as SE or SS by immunohistochemistry (IHC using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS program was used for various statistical analyses. Results The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8% and PLAP-/PAS- SSs were 15/23 (61.2%. All SE cases (8/8, 100% were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%, 9 diffuse (9/15, 60%, and 4 intratubular/diffuse (4/15, 26.7% types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. Conclusion In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels

The correlation between the rise of the tumor temperature during the hyperthermia treatment and the tumor blood flow measured by dynamic CT and 15O gas-positron emission tomography

International Nuclear Information System (INIS)

Hattori, Hideyuki

1993-01-01

This study was designed to determine the correlation between the rise of tumor temperature during hyperthermia treatment and the blood flow of the tumors measured by dynamic CT (DCT) and 15 O gas-positron emission tomography. In this report, we observed 20 patients with malignant tumors which underwent hyperthermia treatment. In each case, the temperature of the tumor was monitored with a photofiber sensor. DCT's and 15 O gas-positron emission tomographies were applied before the hyperthermia treatment. During the DCT, the tumor blood flow of each tumor was estimated by analyzing the time-dependent activity curve after a bolus injection. During the 15 O gas-positron emission tomography, the tumor blood flow was estimated by the C 15 O 2 -steady-state method. The value of the tumor blood flow estimated by DCT were proportional to those calculated by the 15 O gas-positron emission tomography. These values were inversely proportional to the rise of the temperature of the tumors during hyperthermia treatment. Our results imply that DCT as well as the 15 O gas-positron emission tomography can be used for the prediction of the tumor temperature rise during the hyperthermia treatment. (author)

May positron emission tomography reveal ectopic or active thymus in preoperative evaluation of non-thymomatous myasthenia gravis?

Science.gov (United States)

Mineo, Tommaso Claudio; Ambrogi, Vincenzo; Schillaci, Orazio

2014-09-05

In myasthenia gravis (MG) both native and ectopic thymic tissue containing germinal centers should show greater metabolism compared to adjacent tissues. We evaluated whether preoperative standardized uptake value (SUV) of 18fluoro-deoxy-glucose on Positron Emission Tomography (PET) might be increased and correlated with the presence of native or ectopic germinal centers. From 2005 to 2012 we performed extended thymectomy in 68 patients with non-thymomatous MG. All patients underwent PET-scan preoperatively and one-year postoperatively. SUVs were assessed in thymic and perithymic regions. Then it was matched with same-age, non-MG and non-neoplastic control group and finally correlated with presence of germinal centers in native thymus or in the ectopic tissue found in the surgical specimens. Mean SUV was significantly increased in MG patients compared to control group. Thymic SUV was significantly higher in presence of thymic germinal centers [3.5 (2.4-5.0) Vs 2.1 (1.4-2.5), p = 0.021] while perithymic SUV was significantly higher in presence of ectopic germinal centers [3.1 (2.7-3.5) Vs 1.3 (0.9-1.7), p = 0.001]. SUV was significantly correlated with MG score (rho = 0.289, p = 0.017) and marginally with antibodies anti-acetylcholine receptors (rho = 0.129, p = 0.05). At Kaplan Meier analysis, ectopic thymic tissue (p = 0.045) and ectopic germinal centers (p = 0.036) were significant predictors of complete stable remission, but preoperative dichotomized thymic (3.5 or more Vs less) (p = 0.083) and perithymic (2.1 or more Vs less) (p = 0.052) SUVs did not. Thymic and perithymic SUVs were significantly higher in patients with MG than non-MG and non-neoplastic patients. Thymic SUV was significantly correlated with the presence of germinal centers. Perithymic SUV resulted significantly correlated with the discovery of ectopic active thymic tissue. Neither thymic nor perithymic high SUVs predicted remission.

Central nervous system tumors: Radiologic pathologic correlation and diagnostic approach

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Ishita Pant

2015-01-01

Full Text Available Objective: This study was conducted to formulate location-wise radiologic diagnostic algorithms and assess their concordance with the final histopathological diagnosis so as to evaluate their utility in a rural setting where only basic facilities are available. Materials and Methods: A retrospective analysis to assess the concordance of radiology (primarily MRI with final histopathology report was done. Based on the most common incidence of tumor location and basic radiology findings, diagnostic algorithms were prepared. Results: For supratentorial intraaxial parenchymal location concordance was seen in all high-grade astrocytomas, low- and high-grade oligodendrogliomas, metastatic tumors, primitive neuroectodermal tumors, high-grade ependymomas, neuronal and mixed neuro-glial tumors and tumors of hematopoietic system. Lowest concordance was seen in low-grade astrocytomas. In the supratentorial intraaxial ventricular location, agreement was observed in choroid plexus tumors, ependymomas, low-grade astrocytomas and meningiomas; in the supratentorial extraaxial location, except for the lack of concordance in the only case of metastatic tumor, concordance was observed in meningeal tumors, tumors of the sellar region, tumors of cranial and paraspinal nerves; the infratentorial intraaxial parenchymal location showed agreement in low- as well as high-grade astrocytomas, metastatic tumors, high-grade ependymoma, embryonal tumors and hematopoietic tumors; in the infratentorial intraaxial ventricular location, except for the lack of concordance in one case of low-grade astrocytoma and two cases of medulloblastomas, agreement was observed in low- and high-grade ependymoma; infratentorial extraaxial tumors showed complete agreement in all tumors of cranial and paraspinal nerves, meningiomas, and hematopoietic tumors. Conclusion: A location-based approach to central nervous system (CNS tumors is helpful in establishing an appropriate differential diagnosis.

Thymic and lymph node mesenchymal subsets can be derived from PDGFRα/β+Gp38+CD34+ICAM1- vascular adventitial precursors

DEFF Research Database (Denmark)

Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger

While discrete Gp38- and Gp38+ mesenchymal populations have previously been described in the lymph nodes (LNs) and in the thymus the putative relationship between LN and thymic mesenchymal cells remains unclear. Here, using transcriptome profiling as well as phenotypic and localization studies we...

Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor alpha combination treatment of EL4-lymphoma-bearing C57BL/6 mice.

Science.gov (United States)

Krawczyk, C M; Verstovsek, S; Ujházy, P; Maccubbin, D; Ehrke, M J

1995-06-01

A combination treatment protocol initiated 12 days after tumor injection, when the tumor was large, by administering cyclophosphamide (CY, 150 or 250 mg/kg) intraperitoneally followed by intravenous tumor necrosis factor alpha (TNF alpha, 1000 units injection) on days 13, 16, 18, 21, and 23, resulted in about 60% long-term survival (i.e., survival for at least 60 days) in the syngeneic C57BL/6 mouse/EL4 lymphoma model system. The establishment of a specific antitumor immune memory and its possible therapeutic relevance was verified by reinjecting 60-day survivors with EL4 cells; all 60-day survivors that had received the combination treatments rejected the implants and survived for a further 60 days. Thymic cellularity was reduced during treatment and its recovery appeared to correlate with long-term survival and immunity. Thymocytes from mice treated with the combination were found to express significant levels of specific anti-EL4 cytolytic activity following a 4-day stimulation culture with X-irradiated EL4 cells and low concentrations of interleukin-2. This response could not be generated with thymocytes from naive animals. In each case the effect seen with the combination of a moderate CY dose (150 mg/kg) with TNF alpha was better than that seen with either dose of CY alone and equal to or better than that seen with the higher dose of CY combined with TNF alpha. These results indicate that treatment with a single moderate dose of CY in combination with TNF alpha is effective against a large, established tumor in this murine model. Furthermore, all the long-term survivors induced by this treatment developed protective immunity against reimplanted tumor and demonstrated a long-term specific immune memory in the thymus.

Clinical investigation on usefulness of MRI in the diagnosis of mediastinal masses

Energy Technology Data Exchange (ETDEWEB)

Oyama, Takao (Kagoshima Univ. (Japan). Faculty of Medicine)

1994-02-01

This study evaluated the utility of magnetic resonance imaging (MRI) in diagnosing mediastinal masses. The subjects were 96 patients with pathologically (n=82) and clinically (n=14) proven mediastinal masses, consisting of thymomas (30), teratomas (4), other thymic tumors (5), intrathoracic goiters (4), neurogenic tumors (7), congenital cysts (12), mesenchymal tumors (10), vascular masses (5), phrenic hernia (3), malignant lymphomas (6), and sarcoidosis (10). MRI findings, including marginal and capsular appearances, internal structures and signal intensities, were analyzed. Internal structure characteristic to thymomas were seen in 24 teratoma patients (80%). In 4 teratomas, MRI was capable of distinguishing benign (2) from malignant (2) ones. In the other 5 thymic tumors, MRI delineated chemical characteristics of fluids for thymic cysts (2) and internal structures for thymic cancer (2) and lipoma (one). It also delineated the continuity of intrathoracic goiter from the cervical to intrathoracic regions. For neurogenic tumors, MRI was capable of distinguishing neurofibromas from schwannomas and also benign from malignant schwannomas. A well-defined smooth margin and very high signal intensity, which were characteristic to congenital cysts, were seen on T2-weighted images. Signal intensities on T1-weighted images reflected fluid features in cysts. For mesenchymal tumors, consisting of hemangioma, hemangiosarcoma, malignant melanoma, aneurysmal bone cyst and osteosarcoma, lymphangioma and chondrosarcoma, all but osteosarcoma showed their respective characteristic MRI findings. Vascular masses were delineated as flow void structures. MRI delineated herniated contents. Malignant lymphoma was shown as irregular and inhomogeneous swollen lymph nodes, but sarcoidosis was shown as regular and homogeneous ones on MRI. In conclusion, MRI is a useful, informative modality for diagnosing mediastinal masses. (N.K.) 84 refs.

Clinical investigation on usefulness of MRI in the diagnosis of mediastinal masses

International Nuclear Information System (INIS)

Oyama, Takao

1994-01-01

This study evaluated the utility of magnetic resonance imaging (MRI) in diagnosing mediastinal masses. The subjects were 96 patients with pathologically (n=82) and clinically (n=14) proven mediastinal masses, consisting of thymomas (30), teratomas (4), other thymic tumors (5), intrathoracic goiters (4), neurogenic tumors (7), congenital cysts (12), mesenchymal tumors (10), vascular masses (5), phrenic hernia (3), malignant lymphomas (6), and sarcoidosis (10). MRI findings, including marginal and capsular appearances, internal structures and signal intensities, were analyzed. Internal structure characteristic to thymomas were seen in 24 teratoma patients (80%). In 4 teratomas, MRI was capable of distinguishing benign (2) from malignant (2) ones. In the other 5 thymic tumors, MRI delineated chemical characteristics of fluids for thymic cysts (2) and internal structures for thymic cancer (2) and lipoma (one). It also delineated the continuity of intrathoracic goiter from the cervical to intrathoracic regions. For neurogenic tumors, MRI was capable of distinguishing neurofibromas from schwannomas and also benign from malignant schwannomas. A well-defined smooth margin and very high signal intensity, which were characteristic to congenital cysts, were seen on T2-weighted images. Signal intensities on T1-weighted images reflected fluid features in cysts. For mesenchymal tumors, consisting of hemangioma, hemangiosarcoma, malignant melanoma, aneurysmal bone cyst and osteosarcoma, lymphangioma and chondrosarcoma, all but osteosarcoma showed their respective characteristic MRI findings. Vascular masses were delineated as flow void structures. MRI delineated herniated contents. Malignant lymphoma was shown as irregular and inhomogeneous swollen lymph nodes, but sarcoidosis was shown as regular and homogeneous ones on MRI. In conclusion, MRI is a useful, informative modality for diagnosing mediastinal masses. (N.K.) 84 refs

Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development

OpenAIRE

Parent, Audrey V.; Russ, Holger A.; Khan, Imran S.; LaFlam, Taylor N.; Metzger, Todd C.; Anderson, Mark S.; Hebrok, Matthias

2013-01-01

Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into th...

Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

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Marvin Paulo Lins

Full Text Available BACKGROUND: Several evidences indicate that hormones and neuropeptides function as immunomodulators. Among these, growth hormone (GH is known to act on the thymic microenvironment, supporting its role in thymocyte differentiation. The aim of this study was to evaluate the effect of GH on human thymocytes and thymic epithelial cells (TEC in the presence of laminin. RESULTS: GH increased thymocyte adhesion on BSA-coated and further on laminin-coated surfaces. The number of migrating cells in laminin-coated membrane was higher in GH-treated thymocyte group. In both results, VLA-6 expression on thymocytes was constant. Also, treatment with GH enhanced laminin production by TEC after 24 h in culture. However, VLA-6 integrin expression on TEC remained unchanged. Finally, TEC/thymocyte co-culture model demonstrated that GH elevated absolute number of double-negative (CD4-CD8- and single-positive CD4+ and CD8+ thymocytes. A decrease in cell number was noted in double-positive (CD4+CD8+ thymocytes. CONCLUSIONS: The results of this study demonstrate that GH is capable of enhancing the migratory capacity of human thymocytes in the presence of laminin and promotes modulation of thymocyte subsets after co-culture with TEC.

Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy.

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Geng, Jie-Jie; Tang, Juan; Yang, Xiang-Min; Chen, Ruo; Zhang, Yang; Zhang, Kui; Miao, Jin-Lin; Chen, Zhi-Nan; Zhu, Ping

2017-06-01

CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy. Copyright © 2017. Published by Elsevier B.V.

Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy

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Jie-Jie Geng

2017-06-01

Full Text Available CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative and fully committed DP (double positive cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy.

Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

Directory of Open Access Journals (Sweden)

Samantha J Westrop

Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

Effects of Perfectly Correlated and Anti-Correlated Noise in a Logistic Growth Model

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Zhang Li; Cao Li

2011-01-01

The logistic growth model with correlated additive and multiplicative Gaussian white noise is used to analyze tumor cell population. The effects of perfectly correlated and anti-correlated noise on the stationary properties of tumor cell population are studied. As in both cases the diffusion coefficient has zero point in real number field, some special features of the system are arisen. It is found that in both cases, the increase of the multiplicative noise intensity cause tumor cell extinction. In the perfectly anti-correlated case, the stationary probability distribution as a function of tumor cell population exhibit two extrema. (general)

Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

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Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

2011-03-01

The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

Experimental study of the correlation between 99Tcm-EC-MNZ SPECT imaging and the expression of hypoxia inducible factor-1α in tumor tissuse

International Nuclear Information System (INIS)

Chen Jie; Lu Xueguan; Tang Jun; Fan Wo

2005-01-01

Objective: To evaluate the correlation between 99 Tc m -ethylene dicysteinc-metronidazaole ( 99 Tc M -EC-MNZ) SPECT imaging and the expression of hypoxia inducible factor-1α (HIF-1α) in tumor tissue. Methods: Twelve S180 sarcoma-bearing Kunming mice tumor models were established. Hypoxic imaging was obtained by SPECT with 99 Tc m -EC-MNZ and the corresponding tumor/muscle ratios (T/M) were measured. Then the animals were sacrificed and the tumor specimen was resected, the expression of HIF-1α and vascular endothelial growth factor (VEGF) was measured by immunohistochemistry. Results: Three hours after injection of 99 Tc m -EC-MNZ, the T/M ranged from 1.93 to 4.46 (median 3.13). The expression of HIF-1α ranged from 31.2% to 60.8% (median 50.4%) and was linearly correlated with the T/M (t=2.732, r=0.654, P=0.021). The expression of VEGF ranged from 33.8% to 57.5% (median 53.1%) and also linearly correlated with the expression of HIF-1α (t=3.011, r=0.690, P=0.0131). Conclusions: There is linear correlation between 99 Tc m -EC-MNZ hypoxic SPECT imaging and the expression of HIF-1α. Combining them can reliably reflect the hypoxic status of the tumor. (authors)

Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

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Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

2016-01-15

Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not

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)

Histological-subtypes and anatomical location correlated in meningeal brain tumors (meningiomas

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Abdul Rashid Bhat

2014-01-01

Full Text Available Context: Not enough literature is available to suggest a link between the histological subtypes of intracranial meningeal brain tumors, called ′meningiomas′ and their location of origin. Aim: The evidence of correlation between the anatomical location of the intracranial meningiomas and the histopathological grades will facilitate specific diagnosis and accurate treatment. Materials and Methods: The retrospective study was conducted in a single high-patient-inflow Neurosurgical Center, under a standard and uniform medical protocol, over a period of 30 years from December 1982 to December 2012. The records of all the operated 729 meningiomas were analyzed from the patient files in the Medical Records Department. The biodata, x-rays, angiography, computed tomography (CT scans, imaging, histopathological reports, and mortality were evaluated and results drawn. Results: The uncommon histopathological types of meningiomas (16.88% had common locations of origin in the sphenoid ridge, posterior parafalcine, jugular foramen, peritorcular and intraventricular regions, cerebellopontine angle, and tentorial and petroclival areas. The histopathological World Health Organization (WHO Grade I (Benign Type meningiomas were noted in 89.30%, WHO Grade II (Atypical Type in 5.90%, and WHO Grade III (Malignant Type in 4.80% of all meningiomas. Meningiomas of 64.60% were found in females, 47.32% were in the age group of 41-50 years, and 3.43% meningiomas were found in children. An overall mortality of 6.04% was noted. WHO Grade III (malignant meningiomas carried a high mortality (25.71% and the most common sites of meningiomas with high mortality were: The cerebellopontine angles, intraventricular region, sphenoid ridge, tuberculum sellae, and the posterior parafalcine areas. Conclusion: The correlation between the histological subtypes and the anatomical location of intracranial meningeal brain tumors, called meningiomas, is evident, but further research is

Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

International Nuclear Information System (INIS)

Bourke, Vincent A.; Zhao Dawen; Gilio, Joseph; Chang, C.-H.; Jiang Lan; Hahn, Eric W.; Mason, Ralph P.

2007-01-01

Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by 19 F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm 3 ) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO 2 ) than their smaller counterparts ( 3 ). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO 2 , and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO 2 > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy

Pulmonary Metastasis from Rectal Cancer on Chest CT Is Correlated with 3T MRI Primary Tumor Location

International Nuclear Information System (INIS)

Han, Na Yeon; Kim, Min Ju; Park, Beon Jin; Sung, Deuk Jae; Chung, Kyoo Byung; Oh, Yu Whan

2011-01-01

To evaluate the association between the incidence of pulmonary metastasis on chest CT and the location of the primary tumor on rectal MRI. One hundred and nine consecutive patients with rectal adenocarcinoma underwent chest CT and 3T rectal MRI. Two radiologists classified the tumor on MRI as an upper (> 10 cm from the anal verge), mid (5-10 cm), or lower rectal tumor (< 5 cm) by consensus. All chest CT scans were retrospectively reviewed for the presence of metastasis. We used Fisher's exact test to evaluate the correlation between the incidence of pulmonary metastasis with the location of the rectal cancer and the Mantel-Haenszel test to control for local tumor stage. We only included the 60 patients with upper (n = 26) or lower (n = 34) rectal cancer, because of the complicated venous drainage system of the mid rectum. Among these, 9 (15%) showed evidence of pulmonary metastasis on chest CT and almost all (89%, 8/9) patients had lower rectal cancer. The incidence of pulmonary metastasis between the two groups was statistically different (p < 0.05) when local tumor stage was controlled. The incidence of pulmonary metastasis was significantly higher for lower than upper rectal cancers when the T-stage of the tumor was accounted for.

Correlation between histological and ultrasonographic findings of soft tissue tumors: To verify the possibility of cell-like resolution in ultrasonography.

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Wu, Ching-Lan; Lai, Yi-Chen; Wang, Hsin-Kai; Chen, Paul Chih-Hsueh; Chiou, Hong-Jen

2017-11-01

The purpose of this study is to test the possibility of obtained cell-like resolution in soft tissue tumors on the basis of ultrasound echotexture. This is a prospective study consisting of 57 patients (29 females and 28 males, age range: 9-83 years, average age: 44.5 years) with palpable soft tissue mass, referred from the Departments of Orthopedics and Oncology for ultrasound (US)-guided biopsy. The study was approved by the institutional review board (IRB) of our hospital. Ultrasonographic images were recorded by still imaging in the biopsy tract in each biopsy session. Equipment included curvilinear and linear array probes. After biopsy, a radiologist and a pathologist correlated the US image and the observations regarding the histology of the tissue specimen in low-power (40 × magnification) and high-power (100-400 × magnification) fields. The histologic results included 22 benign and 35 malignant lesions. The echotexture of the soft tissue tumors correlated well with the cellular distribution and arrangement: the greater the number of cells and the more regular their arrangement as seen histologically, the greater is the hypoechogenicity on the ultrasound. The echogenicity of the soft tissue tumor also correlated well with the presence of fat cells, hemorrhage, cartilage, and osteoid tissue, all of which cause an increase in echogenicity. This study showed that the echotexture of soft tissue tumors can predict some details of cellular histology. Copyright © 2017. Published by Elsevier Taiwan LLC.

Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

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Bourke, Vincent A [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Dawen, Zhao [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Gilio, Joseph [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Chang, C -H [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Lan, Jiang [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Hahn, Eric W [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Mason, Ralph P [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States)

2007-03-15

Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by {sup 19}F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm{sup 3}) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO{sub 2}) than their smaller counterparts (<1.5 cm{sup 3}). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO{sub 2}, and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO{sub 2} > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy.

Increased aPKC Expression Correlates with Prostatic Adenocarcinoma Gleason Score and Tumor Stage in the Japanese Population

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Anthony S. Perry

2014-01-01

Full Text Available Background. Levels of the protein kinase aPKC have been previously correlated with prostate cancer prognosis in a British cohort. However, prostate cancer incidence and progression rates, as well as genetic changes in this disease, show strong ethnic variance, particularly in Asian populations. Objective. The aim of this study was to validate association of aPKC expression with prostatic adenocarcinoma stages in a Japanese cohort. Methods. Tissue microarrays consisting of 142 malignant prostate cancer cases and 21 benign prostate tissues were subject to immunohistological staining for aPKC. aPKC staining intensity was scored by three independent pathologists and categorized as absent (0, dim (1+, intermediate (2+, and bright (3+. aPKC staining intensities were correlated with Gleason score and tumor stage. Results. Increased aPKC staining was observed in malignant prostate cancer, in comparison to benign tissue. Additionally, aPKC staining levels correlated with Gleason score and tumor stage. Our results extend the association of aPKC with prostate cancer to a Japanese population and establish the suitability of aPKC as a universal prostate cancer biomarker that performs consistently across ethnicities.

Nur77 nuclear import and its NBRE-binding activity in thymic lymphoma cells are regulated by different mechanisms sensitive to FK506 or HA1004

International Nuclear Information System (INIS)

Kochel, Izabela; Rapak, Andrzej; Ziolo, Ewa; Strzadala, Leon

2005-01-01

Thymic lymphoma cells restore their sensitivity to ionomycin-induced apoptosis when treated with FK506 or HA1004. In apoptosis-resistant cells, ionomycin-induced Nur77 strongly binds DNA during the first 2 h of response, in contrast to lymphoma cells treated with ionomycin together with FK506 or HA1004, which undergo massive apoptosis. We show that Nur77 could discriminate between calcium signals sensitive to FK506 and those sensitive to HA1004, as the inhibitors differentially regulate the kinetics of Nur77 nuclear import, and FK506, unlike HA1004, inhibits Nur77 DNA-binding activity. In the presence of HA1004, NBRE binding by Nur77 protein increases with time (6 h vs 2 h), whereas the final outcome of both inhibitors is apoptosis of thymic lymphoma cells

Dural invasion of meningiomas adjacent to the tumor margin on Gd-DTPA-enhanced MR images: histopathologic correlation

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Hutzelmann, A.; Palmie, S.; Freund, M.; Heller, M.; Buhl, R.

1998-01-01

In intracranial meningiomas a flat, contrast-enhancing, dural structure adjacent to the tumor can occasionally be observed on gadolinium-DTPA-enhanced MR images. We wished to evaluate whether there is a correlation between MR images and meningeal invasion of intracranial meningiomas. The study included 54 patients with intracranial meningioma and the meningeal sign. MR studies included T2-weighted and gadolinium-DTPA-enhanced T1-weighted images in axial, coronal, and sagittal planes. Histopathologic examinations were done on the meningiomas adjacent to the dura mater. The meningeal sign on MRI was observed from 2 up to 35 mm from the main tumor mass in 31 (57 %) of the 54 patients. In 20 of these 31 the histopathologic examination showed tumor invasion, while 11 patients had no tumor invasion but tissue proliferation, hypervascularity, and vascular dilatation. Seven of the 23 meningiomas without the meningeal sign had histologically proven infiltration of the adjacent dura. MR imaging is not able to determine definitive whether or not there is dural infiltration of the meningiomas. In conclusion, resection of the tumor with a wide margin is necessary to achieve complete excision of meningioma and to avoid recurrence. (orig.)

Hepatocellular carcinoma with bile duct tumor thrombi: Correlation of magnetic resonance imaging features to histopathologic manifestations

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Liu Qingyu, E-mail: liu.qingyu@163.co [Department of Radiology, Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China); Chen Jianyu, E-mail: chenjianyu5562@sina.co [Department of Radiology, The Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China); Li Haigang, E-mail: lhg00433@yahoo.com.c [Department of Pathology, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province (China); Liang Biling, E-mail: liangbl@163.ne [Department of Radiology, Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China); Zhang Lei, E-mail: zhanglei646@126.co [Department of Hepatobiliary Surgery, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province (China); Hu Tao, E-mail: htwuaini@hotmail.co [Department of Radiology, Second Affiliated Hospital of Sun Yat-sen University, 107 Yan Jiang Xi Road, Guangzhou, 510120, Guangdong Province (China)

2010-10-15

Purpose: This study was to analyze the magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with bile duct tumor thrombi, and explore their correlations to histopathology to improve the accuracy of diagnosis. Materials and methods: 21 patients with pathologically confirmed HCC with bile duct tumor thrombi was performed with a superconducting 1.5-T MR imager within two weeks before operation. Magnetic resonance cholangiopancreatography (MRCP) was performed on 18 patients. Images were retrospectively assessed for the size, location and MRI manifestations of HCC lesions and associated bile duct tumor thrombi. The differentiation of HCC lesions and the pathologic changes of bile duct tumor thrombi were retrospectively analyzed under microscope. Results: The average diameter of HCC lesions was 5.8 {+-} 2.8 cm, and {<=}5.0 cm in nine cases. Capsule formation was observed on MRI or pathology in 4 cases of HCC (19%). Of the 21 cases with bile duct tumor thrombi, 20 were clearly presented on MRI as cord-like or columnar masses in the bile duct with proximal cholangiectasis. The tumor thrombi showed slightly hypointense on T1WI and slightly hyperintense on T2WI. On enhanced scan, three cases of tumor thrombi, which were mainly consisted of necrotic tissue, did not show enhancement; 17 cases, which were mainly consisted of cancer cells, showed mild or moderate enhancement. On magnetic resonance cholangiopancreatogram (MRCP), 14 cases of tumor thrombi presented as filling defect in the bile duct, abrupt obstruction of the bile duct, and cholangiectasis above the obstruction; four presented as dilated intra-hepatic bile ducts with missing common bile duct. Of the 21 patients, 16 had biliary hemorrhage; three also had tumor thrombi in the portal vein. Seventeen of the 21 HCC with biliary thrombi were poorly differentiated, unencapsulated and with an invasive growth. Nineteen of 21 bile duct tumor thrombi did not invade the bile duct wall and could be

Hepatocellular carcinoma with bile duct tumor thrombi: Correlation of magnetic resonance imaging features to histopathologic manifestations

International Nuclear Information System (INIS)

Liu Qingyu; Chen Jianyu; Li Haigang; Liang Biling; Zhang Lei; Hu Tao

2010-01-01

Purpose: This study was to analyze the magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with bile duct tumor thrombi, and explore their correlations to histopathology to improve the accuracy of diagnosis. Materials and methods: 21 patients with pathologically confirmed HCC with bile duct tumor thrombi was performed with a superconducting 1.5-T MR imager within two weeks before operation. Magnetic resonance cholangiopancreatography (MRCP) was performed on 18 patients. Images were retrospectively assessed for the size, location and MRI manifestations of HCC lesions and associated bile duct tumor thrombi. The differentiation of HCC lesions and the pathologic changes of bile duct tumor thrombi were retrospectively analyzed under microscope. Results: The average diameter of HCC lesions was 5.8 ± 2.8 cm, and ≤5.0 cm in nine cases. Capsule formation was observed on MRI or pathology in 4 cases of HCC (19%). Of the 21 cases with bile duct tumor thrombi, 20 were clearly presented on MRI as cord-like or columnar masses in the bile duct with proximal cholangiectasis. The tumor thrombi showed slightly hypointense on T1WI and slightly hyperintense on T2WI. On enhanced scan, three cases of tumor thrombi, which were mainly consisted of necrotic tissue, did not show enhancement; 17 cases, which were mainly consisted of cancer cells, showed mild or moderate enhancement. On magnetic resonance cholangiopancreatogram (MRCP), 14 cases of tumor thrombi presented as filling defect in the bile duct, abrupt obstruction of the bile duct, and cholangiectasis above the obstruction; four presented as dilated intra-hepatic bile ducts with missing common bile duct. Of the 21 patients, 16 had biliary hemorrhage; three also had tumor thrombi in the portal vein. Seventeen of the 21 HCC with biliary thrombi were poorly differentiated, unencapsulated and with an invasive growth. Nineteen of 21 bile duct tumor thrombi did not invade the bile duct wall and could be easily

Dependence of FDG uptake on tumor microenvironment

International Nuclear Information System (INIS)

Pugachev, Andrei; Ruan, Shutian; Carlin, Sean; Larson, Steven M.; Campa, Jose; Ling, C. Clifton; Humm, John L.

2005-01-01

Purpose: To investigate the factors affecting the 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake in tumors at a microscopic level, by correlating it with tumor hypoxia, cellular proliferation, and blood perfusion. Methods and Materials: Nude mice bearing Dunning prostate tumors (R3327-AT) were injected with 18 F-FDG and pimonidazole, bromodeoxyuridine, and, 1 min before sacrifice, with Hoechst 33342. Selected tumor sections were imaged by phosphor plate autoradiography, while adjacent sections were used to obtain the images of the spatial distribution of Hoechst 33342, pimonidazole, and bromodeoxyuridine. The images were co-registered and analyzed on a pixel-by-pixel basis. Results: Statistical analysis of the data obtained from these tumors demonstrated that 18 F-FDG uptake was positively correlated with pimonidazole staining intensity in each data set studied. Correlation of FDG uptake with bromodeoxyuridine staining intensity was always negative. In addition, FDG uptake was always negatively correlated with the staining intensity of Hoechst 33342. Conclusions: For the Dunning prostate tumors studied, FDG uptake was always positively correlated with hypoxia and negatively correlated with both cellular proliferation and blood flow. Therefore, for the tumor model studied, higher FDG uptake is indicative of tumor hypoxia, but neither blood flow nor cellular proliferation

Influence of age on the proliferation and peripheralization of thymic T cells

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Hirokawa, K.; Utsuyama, M.; Katsura, Y.; Sado, T.

1988-01-01

Bone marrow cells obtained from B10.Thy-1.1 mice (H-2b, Thy-1.1) were injected directly into the thymus of C57BL/6 mice (H-2b,Thy 1.2) of various ages. Thymocyte precursors in the injected donor-bone marrow cells could proliferate in the thymic microenvironment in the following manner: first, preferentially proliferating into the subcapsular cortex; and second, spreading to the whole layer of the cortex, a portion of them gradually moving into the medulla. The proliferation of donor-type thymocytes was most pronounced when intrathymic injection of bone marrow cells (ITB) was performed in newborn mice and especially prominent in week-old mice; it took approximately ten weeks for donor-type thymocytes to finish the whole course of proliferation, differentiation, and emigration to the periphery. When ITB was performed in mice 4 weeks of age and older, the proliferation of donor-type thymocytes was retarded at onset, less pronounced in magnitude, and disappeared earlier. Emigration of donor-type T cells from the thymus to the peripheral lymphoid tissues occurred most rapidly when ITB was performed in newborn mice, and these T cells continued to reside thereafter in the peripheral lymphoid tissues. However, when ITB was performed in mice 4 weeks of age and older, the number of emigrated T cells in the spleen decreased (about a tenth of that in newborn mice) and, moreover, these T cells resided only transiently in the spleen. It was suggested that T cells emigrating from the thymus of mice from newborn to 2 weeks of age are long-lived, whereas those from the thymus in mice 4 weeks of age and older are short-lived. However, when 4-week-old young adult mice were treated by irradiation or hydrocortisone, the thymic capacity was enhanced in terms of proliferation and peripheralization of thymocytes, and emigrated T cells became long-lived

CD163+ Tumor-Associated Macrophages Correlated with Poor Prognosis and Cancer Stem Cells in Oral Squamous Cell Carcinoma

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Ke-Fei He

2014-01-01

Full Text Available Tumor-associated macrophages (TAMs play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P<0.05. Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P<0.05. TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.

Selective lymphoid irradiation. V. Synergism with pretransplant thymectomy or thymic irradiation in cardiac transplantation in rats

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Iga, C.; Fawwaz, R.; Nowygrod, R.; Reemtsma, K.; Hardy, M.A.

1985-01-01

Selective lymphoid irradiation (SLI) using palladium-109-hematoporphyrin (Pd-H), given four days prior to transplantation, combined with two doses of antilymphocyte globulin (ALG) (10 mg, days -2 and -1), was evaluated as a method of induction of permanent heterotopic cardiac allograft survival in the highly histoincompatible rat strain combination of ACI (RT1(1))-to-Lewis (RT1a). Both Pd-H and ALG localize poorly in the thymus, so this study evaluated whether thymic irradiation (TI) or thymectomy (TX) of the adult recipient results in indefinite allograft survival. Immunosuppression with Pd-H or ALG alone gave a mean survival time (MST) of 6.7 +/- 0.6 days, but the combination of the two agents led to an MST of 17.6 +/- 3.4 days. When TI was combined with Pd-H and ALG, cardiac allograft survival was prolonged to 50.2 +/- 13.9 days, but TI alone showed an MST of 10.3 +/- 1.8 days. Permanent cardiac allograft survival (greater than 250 days) was achieved in all thymectomized recipients treated with the combination of Pd-H and a brief course of ALG. These animals also accepted second-set skin grafts and rejected third-party skin grafts following more than 150 days of ACI cardiac allograft survival. Thymic irradiation, although effective in acting synergistically with SLI and ALG, led to prolonged, but limited allograft survival, although thymectomy with SLI and ALG is synergistic in prolonging allograft survival permanently without chronic immunosuppression

Correlative study of dynamic MRI and tumor angiogenesis in gastric carcinoma

International Nuclear Information System (INIS)

Tang Qunfeng; Shen Junkang; Feng Yizhong; Qian Minghui; Chai Yuhai

2004-01-01

Objective: To investigate the correlation between the dynamic MRI enhancement characteristics and tumor angiogenesis in gastric carcinoma. Methods: Histopathological slides of 30 patients underwent CD34 and vascular endothelial growth factor (VEGF) immunohistochemical staining. Microvessel density (MVD) and VEGF protein expression were analyzed with their relationship to pathological features. The dynamic MRI characteristics, including the maximum contrast enhancement ratio (CERmax), were correlatively studied with MVD and VEGF expression. Results: In 30 cases, MVD was 13.00 to 68.25 per vision field with an average of 42.95 ±14.79. The low expression rate of VEGF was 30% (9/30), while the high expression rate of VEGF was 70% (21/30). MVD and VEGF expression correlated with lymph node metastasis (P>0.05), but their relationships to the degree of differentiation and depth of invasion were not significant (P>0.05). MVD was related to TNM-staging of gastric carcinoma (P>0.05). The expression of VEGF between the stage I and IV had significant differences (P>0.05). MVD was higher in VEGF-high expression than in VEGF-low expression [(47.30 ± 14.16) per vision versus (32.81 ± 11.25) per vision]. CERmax was significantly correlated with MVD (r=0.556, P=0.0014). The distribution features and shape of microvessels within gastric carcinoma were related to the enhancement characteristics such as irregular enhancement and delaminated enhancement. The correlation between CERmax and expression of VEGF was not significant (t=-0.847, P=0.404). Conclusion: The manifestations on dynamic MR images can reflect the distribution features and shape of microvessels within gastric carcinoma. Dynamic MR imaging may prove to be a valuable means in estimating the MVD of gastric carcinoma noninvasively, and further predicting the biological behavior of gastric carcinoma and judging the prognosis. (authors)

Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.

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Li He

Full Text Available BACKGROUND: The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT. METHODS: The karyopherin 2 (KPNA2 expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125, and the translation level (R = 0.6636, P<0.0001, was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS of OMGCT (P = 0.02. The 5-year overall survival (OS and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48 were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42(P = 0.0151, P = 0.0109, respectively. The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62 was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28(P = 0.0519, P = 0.0647, respectively. CONCLUSIONS: KPNA2 is

Deciphering the Correlation between Breast Tumor Samples and Cell Lines by Integrating Copy Number Changes and Gene Expression Profiles

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Yi Sun

2015-01-01

Full Text Available Breast cancer is one of the most common cancers with high incident rate and high mortality rate worldwide. Although different breast cancer cell lines were widely used in laboratory investigations, accumulated evidences have indicated that genomic differences exist between cancer cell lines and tissue samples in the past decades. The abundant molecular profiles of cancer cell lines and tumor samples deposited in the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas now allow a systematical comparison of the breast cancer cell lines with breast tumors. We depicted the genomic characteristics of breast primary tumors based on the copy number variation and gene expression profiles and the breast cancer cell lines were compared to different subgroups of breast tumors. We identified that some of the breast cancer cell lines show high correlation with the tumor group that agrees with previous knowledge, while a big part of them do not, including the most used MCF7, MDA-MB-231, and T-47D. We presented a computational framework to identify cell lines that mostly resemble a certain tumor group for the breast tumor study. Our investigation presents a useful guide to bridge the gap between cell lines and tumors and helps to select the most suitable cell line models for personalized cancer studies.

Erythropoietin receptor is not a surrogate marker for tumor hypoxia and does not correlate with survival in head and neck squamous cell carcinomas.

NARCIS (Netherlands)

Hoogsteen, I.J.; Peeters, W.J.M.; Marres, H.A.M.; Rijken, P.F.J.W.; Hoogen, F.J.A. van den; Kogel, A.J. van der; Kaanders, J.H.A.M.

2005-01-01

BACKGROUND AND PURPOSE: To evaluate erythropoietin receptor (EPOR) expression in human head and neck squamous cell carcinomas and correlate this to the presence of tumor hypoxia and treatment outcome. PATIENTS AND METHODS: Eighty-five patients with locally advanced tumors of the head and neck were

Computed tomography of the thymus after pneumomediastinography in patients with myasthenia gravis

International Nuclear Information System (INIS)

Hirose, Genjiro; Yamamoto, Teiji; Kosoegawa, Hiroshi; Saeki, Mitsuo; Hayashi, Toshiharu

1982-01-01

Nine patients with myasthenia gravis (MG) had plain chest X-ray, tomography, computed tomography (CT) of the thorax, pneumomediastinography (PMG) and post-PMG CT scans. Routine chest radiography detected mediastinal masses in two patients and conventional laminogram provided no additional informations. CT yielded anterior mediastinal increased densities in seven patients (78%), whereas post-PMG CT delineated masses (thymoma or thymic hyperplasia) or thymic gland in all cases (100%), but these procedures could not distinguish thymic tumor from nontumorous conditions. PMG and post-PMG CT scans are superior to other radiographic techniques in detecting mediastinal abnormalities with more clear delineation of thymoma or thymic gland. When an abnormal density is present in the mediastinum of a patient with MG, PMG and post-PMG CT scans should be done to outline the mediastinal anatomy, to determine the size, extent, invasiveness of thymoma or thymic gland prior to thymectomy. (author)

Computed tomography of the thymus after pneumomediastinography in patients with myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Hirose, Genjiro; Yamamoto, Teiji; Kosoegawa, Hiroshi; Saeki, Mitsuo; Hayashi, Toshiharu (Kanazawa Medical Univ., Ishikawa (Japan))

1982-09-01

Nine patients with myasthenia gravis (MG) had plain chest X-ray, tomography, computed tomography (CT) of the thorax, pneumomediastinography (PMG) and post-PMG CT scans. Routine chest radiography detected mediastinal masses in two patients and conventional laminogram provided no additional information. CT yielded anterior mediastinal increased densities in seven patients (78%), whereas post-PMG CT delineated masses (thymoma or thymic hyperplasia) or thymic gland in all cases (100%), but these procedures could not distinguish thymic tumor from nontumorous conditions. PMG and post-PMG CT scans are superior to other radiographic techniques in detecting mediastinal abnormalities with more clear delineation of thymoma or thymic gland. When an abnormal density is present in the mediastinum of a patient with MG, PMG and post-PMG CT scans should be done to outline the mediastinal anatomy, to determine the size, extent, invasiveness of thymoma or thymic gland prior to thymectomy.

Tenascin in meningioma: expression is correlated with anaplasia, vascular endothelial growth factor expression, and peritumoral edema but not with tumor border shape.

Science.gov (United States)

Kiliç, Türker; Bayri, Yaşar; Ozduman, Koray; Acar, Melih; Diren, Semin; Kurtkaya, Ozlem; Ekinci, Gazanfer; Buğra, Kuyaş; Sav, Aydin; Ozek, M Memet; Pamir, M Necmettin

2002-07-01

Tenascin is an extracellular matrix glycoprotein that is expressed during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of this study was to investigate how tenascin expression relates to histological grade, angiogenesis, and radiological findings in meningiomas. Twenty typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively. Tenascin expression and vascular endothelial growth factor (VEGF) expression in the tumor tissue were investigated by immunohistochemistry. Tenascin messenger ribonucleic acid expression was also studied by comparative reverse transcriptase-polymerase chain reaction. Magnetic resonance images from each case were assessed for peritumoral edema and tumor border shape. The atypical and malignant meningiomas showed higher levels of tenascin expression than the typical meningiomas. The more sensitive messenger ribonucleic acid-based methods confirmed this finding. Tenascin expression was correlated with peritumoral edema and VEGF expression but not with tumor border shape. In the 13 tumors with marked tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in five and Grade 2 in eight specimens, and the findings for tumor border shape were Grade 0 in seven, Grade 1 in four, and Grade 2 in two specimens. In meningiomas, tenascin expression is correlated with anaplasia, tumor-associated edema, and VEGF expression but not with tumor border shape. This protein may play a role in the neoplastic and/or angiogenic processes in atypical and malignant meningiomas and may thus be a potential target for meningioma therapy.

SU-E-T-81: A Study On Correlation Between Gamma Analysis for Midline and Lateralized Tumors Using VMAT

International Nuclear Information System (INIS)

Kumar, Syam; Anjana

2015-01-01

Purpose: To evaluate the fluence for the midline and lateralized tumors for VMAT technique using 2D seven29 detector array combined with the Octavius phantom. Methods: 60 cases that are already being treated with volumetric modulated arc therapy (VMAT) have selected for this study. This includes tumors situated at the medial and lateral. Medial refers to the tumor situated at the midline of the body and lateral means toward the side or away from the midline of the body. Verification plans were created for each treatment plan in Varian Eclipse treatment planning system (version10, Varian medical systems, Palo Alto,CA) with the 2D Seven29 detector array and the Octavius phantom(PTW, Freiburg, Germany). Measurements were performed on a Varian Clinac 2100 iX, linear accelerator equipped with a millennium 120 leaf collimator. Analysis was done by comparing the fluence measured for the tumors situated on the midline and tumors situated laterally. Results: Fluence measured for all the delivered plans were analyzed using Verisoft software (PTW, Freiburg, Germany). The gamma pass percentage for midline tumors were found to be higher compared with the lateralized ones. The standard deviation between gamma values for midline and lateralized tumors is 2.18 and 3.5 respectively. Also the standard deviation between the point doses for midline and lateralized tumors is 0.38 and 0.29 respectively. The average gamma passing rate for midline tumors is 96.55% and for lateralized tumors are 94.94% for 3%DD and 3mm DTA criteria. From the T test, it was found that there is no significant difference between the gamma pass percentage between midline and lateralized tumors with p value of 0.28. Conclusion: There is no particular correlation found in the gamma pass criteria for midline and lateralized tumors