[Morphological studies in different avian species on artefacts induced by euthanasia with T 61 " or Pentobarbital (Narcoren)].

PubMed

Kummerfeld, Norbert; Legler, Marko; Wohlsein, Peter; Kummerfeld, Maren

2012-01-01

In mammals (e. g. macaques, dogs, cats, rats, sheep) as well as in men (suicides) euthanasia performed by intravenous injection of T 61 leads to serious lesions in lung, kidney or/and liver (endothelial damage, hyperemia, oedema, necrosis). This is caused by the solvent dimethylformamide (DMF). In this study, in contrast, in different species of birds (e. g. blackbird, carrion crow, kestrel, common buzzard, homer pigeon, common wood pigeon, mallard duck) and various modes of applications and dosages T 61, 1.0-3.0 ml/kg body mass, did not induce comparable artefacts in tissues of internal organs in the narcotized animals. Microscopically, only hyperemia and oedema of lung, kidney and/or liver were found. However, milder but similar lesions were detected also in groups of birds euthanized by pentobarbital (200 mg/kg body mass) as well as in control groups (overdosed ketamine intramusculary, 100 mg/kg body mass, and rapid exsanguination). In conclusion, euthanasia of narcotized birds performed by intravenous or intracardial injections ofT 61 seemed to be suitable. The observed lesions could therefore not be interpreted as T61 induced artefacts.

Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

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

Zitta, Karina; Meybohm, Patrick; Bein, Berthold

In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 {mu}M SA on CaCo-2 cells grownmore » under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: Black-Right-Pointing-Pointer Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions Black-Right-Pointing-Pointer Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia Black-Right-Pointing-Pointer Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia Black-Right-Pointing-Pointer Salicylic

7 CFR 929.61 - Outlets for excess cranberries.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 8 2012-01-01 2012-01-01 false Outlets for excess cranberries. 929.61 Section 929.61... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF... excess cranberries. (a) Noncommercial outlets. Excess cranberries may be disposed of in noncommercial...

7 CFR 929.61 - Outlets for excess cranberries.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 8 2013-01-01 2013-01-01 false Outlets for excess cranberries. 929.61 Section 929.61... AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF... excess cranberries. (a) Noncommercial outlets. Excess cranberries may be disposed of in noncommercial...

7 CFR 929.61 - Outlets for excess cranberries.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 8 2014-01-01 2014-01-01 false Outlets for excess cranberries. 929.61 Section 929.61... AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF... excess cranberries. (a) Noncommercial outlets. Excess cranberries may be disposed of in noncommercial...

7 CFR 929.61 - Outlets for excess cranberries.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Outlets for excess cranberries. 929.61 Section 929.61... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES OF... excess cranberries. (a) Noncommercial outlets. Excess cranberries may be disposed of in noncommercial...

Metastatic adrenal cortical carcinoma to T12 vertebrae.

PubMed

Lee, Daniel; Yanamadala, Vijay; Shankar, Ganesh M; Shin, John H

2016-05-01

We report spinal metastasis of adrenal cortical carcinoma (ACC) to the T12 vertebrae with epidural extension. ACC is a rare malignancy with poor prognosis and high rates of metastasis. However, spinal lesions of ACC are rare, and few have been reported in the literature. We discuss our management of this lesion and review the current understanding and treatment of ACC and spinal metastasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human papilloma virus status of penile squamous cell carcinoma is associated with differences in tumour-infiltrating T lymphocytes.

PubMed

Lohneis, Philipp; Boral, Sengül; Kaufmann, Andreas M; Lehmann, Annika; Schewe, Christiane; Dietel, Manfred; Anagnostopoulos, Ioannis; Jöhrens, Korinna

2015-03-01

Meta-analyses show that approximately half of all squamous cell carcinomas (SCCs) of the penis are associated with a human papillomavirus (HPV) infection. As data about the tumour microenvironment of HPV-positive and HPV-negative penile carcinomas is scarce and conflicting, we examined tumour-infiltrating lymphocyte populations in such cases. The HPV status of 28 penile SCCs was determined by polymerase chain reaction, while the number and distribution of different lymphocyte populations were analysed by immunohistochemistry on whole sections of paraffin-embedded tumour specimens. The average number of tumour-infiltrating T cells in HPV-associated SCC was higher than in HPV-negative SCC, and their phenotype showed strong polarization towards a T helper 1 and cytotoxic immune response. In addition, we identified more tumour-infiltrating regulatory T cells in HPV-positive carcinomas, which might represent a mechanism of immune evasion. The present study provides further evidence that the tumour microenvironment of HPV-positive carcinomas differs from that of HPV-negative carcinomas.

7 CFR 981.61 - Redetermination of kernel weight.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Redetermination of kernel weight. 981.61 Section 981... GROWN IN CALIFORNIA Order Regulating Handling Volume Regulation § 981.61 Redetermination of kernel weight. The Board, on the basis of reports by handlers, shall redetermine the kernel weight of almonds...

HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor immunity.

PubMed

Meng, Fanzhi; Zhen, Shoumei; Song, Bin

2017-08-01

In East Asia and sub-Saharan Africa, chronic infection is the main cause of the development of hepatocellular carcinoma, an aggressive cancer with low survival rate. Cytotoxic T cell-based immunotherapy is a promising treatment strategy. Here, we investigated the possibility of using HBV-specific CD4 + cytotoxic T cells to eliminate tumor cells. The naturally occurring HBV-specific cytotoxic CD4 + and CD8 + T cells were identified by HBV peptide pool stimulation. We found that in HBV-induced hepatocellular carcinoma patients, the HBV-specific cytotoxic CD4 + T cells and cytotoxic CD8 + T cells were present at similar numbers. But compared to the CD8 + cytotoxic T cells, the CD4 + cytotoxic T cells secreted less cytolytic factors granzyme A (GzmA) and granzyme B (GzmB), and were less effective at eliminating tumor cells. In addition, despite being able to secrete cytolytic factors, CD4 + T cells suppressed the cytotoxicity mediated by CD8 + T cells, even when CD4 + CD25 + regulator T cells were absent. Interestingly, we found that interleukin 10 (IL-10)-secreting Tr1 cells were enriched in the cytotoxic CD4 + T cells. Neutralization of IL-10 abrogated the suppression of CD8 + T cells by CD4 + CD25 - T cells. Neither the frequency nor the absolute number of HBV-specific CD4 + cytotoxic T cells were correlated with the clinical outcome of advanced stage hepatocellular carcinoma patients. Together, this study demonstrated that in HBV-related hepatocellular carcinoma, CD4 + T cell-mediated cytotoxicity was present naturally in the host and had the potential to exert antitumor immunity, but its capacity was limited and was associated with immunoregulatory properties. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure.

PubMed

Ishak, Siti Nor Hasmah; Aris, Sayangku Nor Ariati Mohamad; Halim, Khairul Bariyyah Abd; Ali, Mohd Shukuri Mohamad; Leow, Thean Chor; Kamarudin, Nor Hafizah Ahmad; Masomian, Malihe; Rahman, Raja Noor Zaliha Raja Abd

2017-09-25

Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition.

[Evaluation of central lymph node dissection for papillary thyroid carcinoma in cN0 T1/T2].

PubMed

Zhao, S Y; Ma, Y H; Yin, Z; Zhan, X X; Cheng, R C; Qian, J

2018-02-07

Objective: To evaluate the application of the central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC) in cN0 T1/T2. Methods: Retrospective analysis of 532 cases with PTC in cN0 T1/T2 who underwent CLND between October 2014 and September 2016 in the Department of Thyroid Surgery, the First Affiliated Hospital of the Kunming Medical University. The incidence of central lymph node (CLN) metastasis and risk factors were analyzed. Results: CLN metastasis rates: 41.2% (42/102) in males vs 34.9% (150/430) in females, P =0.252; 33.9% (116/342) in single focal carcinoma vs 40.4% (74/183) in multifocal carcinoma, P =0.157; 44.0% (125/284) in patients with 45 years old or less vs 27.0% (67/248) in patients more than 45 years old, P =0.000; 30.3% (113/373) in microcarcinoma vs 50.9% (81/159) in non-microcarcinoma, P =0.000.In unilateral lesions, ipsilateral CLN metastasis was correlated with the tumor diameter ( P =0.012), but not with the number of lesions ( P =0.653). also contralateral CLN metastasis was correlated with the tumor diameter ( P =0.000), but not with the number of lesions ( P =0.815). For the left or right unilateral single focal lesion, the tumor diameter was not correlated with the metastasis of the posterior to right recurrent laryngeal nerve central lymph nodes (LN-prRLN-CLN) ( P =0.652, P =0.088). But in bilateral multifocal carcinoma the tumor diameter was correlated with metastasis of LN-prRLN-CLN ( P =0.039). Conclusions: Prophylactic CLND is reasonable for PTC in cN0 T1/T2. A bilateral CLND should be conducted for patients with bilateral multi-focus cancer and unilateral or bilateral non-microcarcinoma, especially in patients more than 45 years old. For unilateral single focal microcarcinoma on the right, the content of CLND should be from laryngeal nerve on right center to posterior branche; for unilateral single focal microcarcinoma on the left side, the left CLND should be conducted. An ipsilateral CLND can be considered in

Transanal Endoscopic Microsurgery with or without Completion Total Mesorectal Excision for T2 and T3 Rectal Carcinoma.

PubMed

Leijtens, Jeroen W A; Koedam, Thomas W A; Borstlap, Wernard A A; Maas, Monique; Doornebosch, Pascal G; Karsten, Tom M; Derksen, Eric J; Stassen, Laurents P S; Rosman, Camiel; de Graaf, Eelco J R; Bremers, André J A; Heemskerk, Jeroen; Beets, Geerard L; Tuynman, Jurriaan B; Rademakers, Kevin L J

2018-05-23

Transanal endoscopic microsurgery (TEM) is used for the resection of large rectal adenomas and well or moderately differentiated T1 carcinomas. Due to difficulty in preoperative staging, final pathology may reveal a carcinoma not suitable for TEM. Although completion total mesorectal excision is considered standard of care in T2 or more invasive carcinomas, this completion surgery is not always performed. The purpose of this article is to evaluate the outcome of patients after TEM-only, when completion surgery would be indicated. In this retrospective multicenter, observational cohort study, outcome after TEM-only (n = 41) and completion surgery (n = 40) following TEM for a pT2-3 rectal adenocarcinoma was compared. Median follow-up was 29 months for the TEM-only group and 31 months for the completion surgery group. Local recurrence rate was 35 and 11% for the TEM-only and completion surgery groups respectively. Distant metastasis occurred in 16% of the patients in both groups. The 3-year overall survival was 63% in the TEM-only group and 91% in the completion surgery group respectively. Three-year disease-specific survival was 91 versus 93% respectively. Although local recurrence after TEM-only for pT2-3 rectal cancer is worse compared to the recurrence that occurs after completion surgery, disease-specific survival is comparable between both groups. The lower unadjusted overall survival in the TEM-only group indicates that TEM-only may be a valid alternative in older and frail patients, especially when high morbidity of completion surgery is taken into consideration. Nevertheless, completion surgery should always be advised when curation is intended. © 2018 The Author(s) Published by S. Karger AG, Basel.

Potent inhibition of OKT3-induced T cell proliferation and suppression of CD147 cell surface expression in HeLa cells by scFv-M6-1B9.

PubMed

Intasai, Nutjeera; Tragoolpua, Khajornsak; Pingmuang, Prakitnavin; Khunkaewla, Panida; Moonsom, Seangdeun; Kasinrerk, Watchara; Lieber, André; Tayapiwatana, Chatchai

2008-01-01

CD147, a multifunctional type I transmembrane glycoprotein, has been implicated in various physiological and pathological processes. It is involved in signal transduction pathways and also plays a crucial role in the invasive and metastatic activity of malignant tumor cells. Diminished expression of this molecule has been shown to be beneficial in suppression of tumor progression. In a previous study, we generated and characterized a recombinant antibody fragment, scFv, which reacted specifically to CD147. In the present study, we further investigated the biological properties, function and the effect of generated scFv on CD147 expression. The in vitro study showed that soluble scFv-M6-1B9 produced from E. coli HB2151 bound to CD147 surface molecule and inhibited OKT3-induced T cell proliferation. Furthermore, soluble lysate of scFv-M6-1B9 from 293A cells, transduced with a scFv-M6-1B9 expressing adenovirus vector, recognized both recombinant and native CD147. These results indicate that scFv-M6-1B9 binds with high efficiency and specificity. Importantly, scFv-M6-1B9 intrabody reduced the expression of CD147 on the cell surface of HeLa cells suggesting that scFv-M6-1B9 is biologically active. In conclusion, our present study demonstrated that scFv-M6-1B9 has a great potential to target both the intracellular and the extracellular CD147. The generated scFv-M6-1B9 may be an effective agent to clarify the cellular function of CD147 and may aid in efforts to develop a novel treatment in various human carcinomas.

T1 mapping combined with Gd-EOB-DTPA-enhanced magnetic resonance imaging in predicting the pathologic grading of hepatocellular carcinoma.

PubMed

Chen, C Y; Chen, J; Xia, C C; Huang, Z X; Song, B

2017-01-01

The aim of this study was to investigate the value of Gd-EOB-DTPA-enhanced MRI on hepatobiliary phase (HBP) imaging and T1 mapping sequence in the differentiation of hepatocellular carcinoma (HCC). A total of 45 patients with HCC who were to undergo a resection were enrolled in this study. Gd-EOB-DTPA-enhanced magnetic resonance examination was performed prior to resection. T1 mapping was performed before and 20 min after injection of Gd-EOB-DTPA. T1 values of the lesions were measured on pre-contrast (T1p) and during HBP (T1-HBP) on T1 maps. The signal intensity, the diameter and the margin of HCC lesions on HBP images were analyzed. The reduction in T1 value (T1d) and the reduction rate (ΔT1%) of T1 mapping between pre-contrast and HBP were calculated. The Edmondson-Steiner classification of each lesion was made after surgery. The SPSS software package was used for statistical analysis and the analysis of receiver operator characteristic (ROC) curve and area under the curve (AUC) were carried out by using MedCalc software package. Mean values of T1p and T1-HBP were 1935.4±730.8 ms and 1257.1±529.1 ms, respectively. T1p accuracy (AUC = 0.685, p = 0.037) in predicting pathological grading was similar to that of T1-HBP (AUC = 0.751, p = 0.005). A T1p of 1648.2 ms or greater had a sensitivity and specificity of 85.19% and 61.11%, respectively. A T1-HBP of 1006 ms or greater had a sensitivity and specificity of 81.84% and 61.11%, respectively. The number of HCCs with a non-smooth tumor margin was 20 (44.4%), and a non-smooth tumor margin correlated moderately with the Edmondson-Steiner grade (Spearman r = 0.491, p = 0.041). There was no significant correlation between T1d, ΔT1%, HCC signal intensity on HBP image and lesion diameter with pathologic grading. T1 mapping in pre-contrast and HBP of Gd-EOB-DTPA-enhanced MRI, a non-smooth tumor margin in the HBP of Gd-EOB-DTPA-enhanced MRI, are useful in predicting the pathologic grading of HCC.

Comorbidity between HTLV-1-associated adult T-cell lymphoma/leukemia and verrucous carcinoma: a case report

PubMed Central

Moreno, Luis

2017-01-01

Abstract Background: Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. Case report: We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. Treatment and outcome: The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. Clinical relevance: Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV). PMID:28559645

Cytotoxic T Cell Adoptive Immunotherapy as a Treatment for Nasopharyngeal Carcinoma

PubMed Central

Crooks, Pauline; Morrison, Leanne; Stevens, Natasha; Davis, Joanne E.; Corban, Monika; Hall, David; Panizza, Benedict; Coman, William B.; Coman, Scott; Moss, Denis J.

2014-01-01

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress. PMID:24351754

Cytotoxic T cell adoptive immunotherapy as a treatment for nasopharyngeal carcinoma.

PubMed

Lutzky, Viviana P; Crooks, Pauline; Morrison, Leanne; Stevens, Natasha; Davis, Joanne E; Corban, Monika; Hall, David; Panizza, Benedict; Coman, William B; Coman, Scott; Moss, Denis J

2014-02-01

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress.

Availability of sentinel lymph node biopsy for cutaneous squamous cell carcinoma.

PubMed

Maruyama, Hiroshi; Tanaka, Ryota; Fujisawa, Yasuhiro; Nakamura, Yasuhiro; Ito, Shusaku; Fujimoto, Manabu

2017-04-01

Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty-nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow-up period were included. Forty-nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false-negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post-treatment metastases. The metastasis-free and disease-specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2-T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis-free and disease-specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging. © 2016 Japanese Dermatological Association.

A worldwide comparison of the management of T1 and T2 anterior floor of the mouth and tongue squamous cell carcinoma - Extent of surgical resection and reconstructive measures.

PubMed

Kansy, Katinka; Mueller, Andreas Albert; Mücke, Thomas; Koersgen, Friederike; Wolff, Klaus Dietrich; Zeilhofer, Hans-Florian; Hölzle, Frank; Pradel, Winnie; Schneider, Matthias; Kolk, Andreas; Smeets, Ralf; Acero, Julio; Haers, Piet; Ghali, G E; Hoffmann, Jürgen

2017-12-01

Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the results on general aspects of current reconstructive practice in German-speaking countries, Europe and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the anterior floor of the mouth and tongue. The DOESAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated. A total of 188 OMFS units from 36 different countries documented their treatment strategies for T1/T2 anterior floor of the mouth squamous cell carcinoma and tongue carcinoma. For floor of mouth carcinoma close to the mandible, a wide variety of concepts are presented: subperiosteal removal of the tumor versus continuity resection of the mandible and reconstruction ranging from locoregional closure to microvascular bony reconstruction. For T2 tongue carcinoma, concepts are more uniform. These results demonstrate the lack of evidence and the controversy of different guidelines for the extent of safety margins and underline the crucial need of global prospective randomized trials on this topic to finally obtain evidence for a common guideline based on a strong community of OMFS units. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. All rights reserved.

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

PubMed

Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

2016-01-01

Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

Heterogeneity in Intratumor Correlations of 18F-FDG, 18F-FLT, and 61Cu-ATSM PET in Canine Sinonasal Tumors

PubMed Central

Bradshaw, Tyler J.; Bowen, Stephen R.; Jallow, Ngoneh; Forrest, Lisa J.; Jeraj, Robert

2014-01-01

Intratumor heterogeneity in biologic properties and in relationships between various phenotypes may present a challenge for biologically targeted therapies. Understanding the relationships between different phenotypes in individual tumor types could help inform treatment selection. The goal of this study was to characterize spatial correlations of glucose metabolism, proliferation, and hypoxia in 2 histologic types of tumors. Methods Twenty canine veterinary patients with spontaneously occurring sinonasal tumors (13 carcinomas and 7 sarcomas) were imaged with 18F-FDG, 18F-labeled 39-deoxy-39-fluorothymidine (18F-FLT), and 61Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone) (61Cu-ATSM) PET/CT on 3 consecutive days. Precise positioning and immobilization techniques coupled with anesthesia enabled motionless scans with repeatable positioning. Standardized uptake values (SUVs) of gross sarcoma and carcinoma volumes were compared by use of Mann– Whitney U tests. Patient images were rigidly registered together, and intratumor tracer uptake distributions were compared. Voxel-based Spearman correlation coefficients were used to quantify intertracer correlations, and the correlation coefficients of sarcomas and carcinomas were compared. The relative overlap of the highest uptake volumes of the 3 tracers was quantified, and the values were compared for sarcomas and carcinomas. Results Large degrees of heterogeneity in SUV measures and phenotype correlations were observed. Carcinoma and sarcoma tumors differed significantly in SUV measures, with carcinoma tumors having significantly higher 18F-FDG maximum SUVs than sarcoma tumors (11.1 vs. 5.0; P = 0.01) as well as higher 61Cu-ATSM mean SUVs (2.6 vs. 1.2; P = 0.02). Carcinomas had significantly higher population-averaged Spearman correlation coefficients than sarcomas in comparisons of 18F-FDG and 18F-FLT (0.80 vs. 0.61; P = 0.02), 18F-FLT and 61Cu-ATSM (0.83 vs. 0.38; P < 0.0001), and 18F-FDG and 61Cu-ATSM (0.82 vs. 0

[Expression of connective tissue growth factor (CTGF), osteopontin (OPN) and clinical significances in the laryngeal squamous cell carcinoma tissues].

PubMed

Li, Youzhong; Lu, Yongde; Ceng, Yici; Yang, Xinming

2007-02-01

To study the expressions of CTGF and OPN and detect their clinical value and correlation in the laryngeal squamous cell carcinoma tissues and paracancerous tissues. SP immunohistochemical method was used for the assays of CTGF and OPN on the routinely paraffin-embedded sections of surgical operated specimens of 41 cases with laryngeal squamous cell carcinoma and 20 ones with paracancerous tissues. The positive rate of CTGF and the score were significantly lower in cancer tissues than those in paracancerous tissues (61.0% vs 90.0%, P < 0.05; 2.41 +/- 1.60 vs 4.24 +/- 1.42, P < 0.01), but those of OPN were opposite (61.0% vs 15.0%, P < 0.01; 3. 10 +/- 1.63 vs 1.12 +/- 0.84, P < 0.01). The positive rates and scores of CTGF were significantly higher in the cases without-metastasis of lymph node and clinical stage T1 than those in the ones with-metastasis of lymph node and clinical stage T3 (P < 0.01) . The positive rates and scores of OPN were significantly lower in the cases without-metastasis of lymph node, clinical stage T1 and histological grade I those that in the ones with-metastasis of lymph node, Clinical stage T3 and histological grade III (P < 0.01). The closely negative correlation was found between the score of CTGF and that of OPN. The expression of CTGF and/or OPN might be important biological markers in reflecting the progression, biological behaviors, metastatic potential and prognosis of the laryngeal squamous cell carcinoma.

Hadro-Production Measurements to Characterize the T2K Neutrino Flux with the NA61 Experiment at the CERN SPS

NASA Astrophysics Data System (ADS)

Bravar, Alessandro

2010-03-01

As the intensity of neutrino beams produced at accelerators increases, the systematic errors due to the poor characterization of the neutrino flux become a limiting factor for high precision neutrino oscillation experiments like T2K. This limitation comes mainly from the poor knowledge of production cross sections for pions and kaons at the same energy and over the same phase-space yielding these neutrino beams. Therefore new hadro-production measurements are mandatory. The NA61/SHINE is a large acceptance hadron spectrometer at the CERN-SPS designed for the study of the hadronic final states produced in interactions of various beam particles (protons, π's, and heavy ions) with a variety of fixed targets at the SPS energies. Ongoing measurements with the NA61 detector for characterizing the neutrino beam of the T2K experiment at J-PARC are introduced. These measurements are performed using a 30 GeV proton beam impinging on carbon targets of different lengths, including a replica of the T2K target. The performance of the NA61 detector and preliminary NA61 measurements from the 2007 run are presented.

Utility approach to decision-making in extended T1 and limited T2 glottic carcinoma.

PubMed

van Loon, Yda; Stiggelbout, Anne M; Hakkesteegt, Marieke M; Langeveld, Ton P M; de Jong, Rob J Baatenburg; Sjögren, Elisabeth V

2017-04-01

It is still undecided if endoscopic laser surgery or radiotherapy is the preferable treatment in extended T1 and limited T2 glottic tumors. Health utilities assessed from patients can aid in decision-making. Patients treated for extended T1 or limited T2 glottic carcinoma by laser surgery (n = 12) or radiotherapy (n = 14) assigned health utilities using a visual analog scale (VAS), time tradeoff (TTO) technique and scored their voice handicap using the Voice Handicap Index (VHI). VAS and TTO scores were slightly lower for the laser group compared to the radiotherapy group, however, not significantly so. The VHI showed a correlation with the VAS score, which was very low in both groups and can be considered (near) normal. Patients show no clear preference for the outcomes of laser surgery or radiotherapy from a quality of life (QOL) or voice handicap point of view. These data can now be incorporated into decision-making models. © 2017 Wiley Periodicals, Inc. Head Neck, 2017 © 2016 Wiley Periodicals, Inc. Head Neck 39: 779-785, 2017. © 2017 Wiley Periodicals, Inc.

Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

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

Fogg, Mark; Murphy, John R.; Lorch, Jochen

Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, asmore » well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients.« less

Colorectal carcinoma: Ex vivo evaluation using 3-T high-spatial-resolution quantitative T2 mapping and its correlation with histopathologic findings.

PubMed

Yamada, Ichiro; Yoshino, Norio; Hikishima, Keigo; Miyasaka, Naoyuki; Yamauchi, Shinichi; Uetake, Hiroyuki; Yasuno, Masamichi; Saida, Yukihisa; Tateishi, Ukihide; Kobayashi, Daisuke; Eishi, Yoshinobu

2017-05-01

In this study, we aimed to evaluate the feasibility of determining the mural invasion depths of colorectal carcinomas using high-spatial-resolution (HSR) quantitative T2 mapping on a 3-T magnetic resonance (MR) scanner. Twenty colorectal specimens containing adenocarcinomas were imaged on a 3-T MR system equipped with a 4-channel phased-array surface coil. HSR quantitative T2 maps were acquired using a spin-echo sequence with a repetition time/echo time of 7650/22.6-361.6ms (16 echoes), 87×43.5-mm field of view, 2-mm section thickness, 448×224 matrix, and average of 1. HSR fast-spin-echo T2-weighted images were also acquired. Differences between the T2 values (ms) of the tumor tissue, colorectal wall layers, and fibrosis were measured, and the MR images and histopathologic findings were compared. In all specimens (20/20, 100%), the HSR quantitative T2 maps clearly depicted an 8-layer normal colorectal wall in which the T2 values of each layer differed from those of the adjacent layer(s) (P<0.001). Using this technique, fibrosis (73.6±9.4ms) and tumor tissue (104.2±6.4ms) could also be clearly differentiated (P<0.001). In 19 samples (95%), the HSR quantitative T2 maps and histopathologic data yielded the same findings regarding the tumor invasion depth. Our results indicate that 3-T HSR quantitative T2 mapping is useful for distinguishing colorectal wall layers and differentiating tumor and fibrotic tissues. Accordingly, this technique could be used to determine mural invasion by colorectal carcinomas with a high level of accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

Cervical node metastasis in T1 squamous cell carcinoma of oral tongue- pattern and the predictive factors.

PubMed

S, Vishak; Rohan, Vinayak

2014-06-01

The squamous cell carcinoma (SCC) of the oral tongue is a common cancer in India. Elective lymphadenectomy is generally performed in all patients with T2-T4 tumors. In this study we have tried to analyze the pattern and risk factors associated with lymph node metastasis in T1 tongue cancers. A retrospective review of the records of 57 patients undergoing surgery for treatment of T1 sqamous cell carcinoma of oral tongue was carried out. The clinicopatological features of the tumor, pattern of nodal metastasis and the risk factors associated with lymph node metastasis were studied. Totally 57 patients with T1 tumor underwent excision of the primary and modified neck dissection (MND). Lymph node metastasis was found in 36.8 % of the patients. Level I to Level II was the commonest site of metastasis. Skip metastasis at level III and IV was found in 8.5 % of the patients and isolated skip metastasis at level IV in 1.5 % of the patients. The risk factors associated with the lymph node metastasis on univariete analysis were; higher grade, tumor size >1 cm and tumor thickness >3 mm. On multivariate analysis only the tumor thickness was found to be a risk factor for the lymph node metastasis (hazard ratio of 21.59). T1 sqamous cell carcinoma of tongue is associated with a high incidence of lymph node metastasis. Elective neck dissection should be considered in all patients with tumors more than 3 mm in thickness.

Immunosuppressive Environment in Basal Cell Carcinoma: The Role of Regulatory T Cells.

PubMed

Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R; Gniadecki, Robert

2016-11-02

Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed by immunohistochemistry followed by automated image analysis in facial BCC, peritumoural skin and normal, buttock skin. Quantitative real-time PCR (qRT-PCR) was performed for FOXP3 and cytokines involved in T-reg attraction and T-cell activation. T-regs comprised 45% of CD4-cells surrounding BCC. FOXP3 was highly expressed in BCC, but absent in buttock skin. Unexpectedly, expression of FOXP3 was increased in peritumoural skin, with the FOXP3/CD3 fractions exceeding those of BCC (p?=?0.0065). Transforming growth factor (TGF)-? and T-reg chemokine expression was increased in BCC and peritumoural skin, but not in buttock skin, with expression levels correlating with FOXP3. T-regs are abundantly present both in BCC and in peritumoural skin, mediating an immunosuppressed microenvironment permissive for skin cancer.

B61 Mod 12 Life Extension Program Tailkit Assembly (B61 Mod 12 LEP TKA)

DTIC Science & Technology

2013-12-01

Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-468 B61 Mod 12 Life Extension Program Tailkit Assembly ( B61 Mod 12 LEP TKA...REPORT TYPE 3. DATES COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE B61 Mod 12 Life Extension Program Tailkit Assembly ( B61 Mod 12 LEP...REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 B61 Mod 12

Salvage radiotherapy in patients with recurrent esophageal carcinoma.

PubMed

Fakhrian, K; Gamisch, N; Schuster, T; Thamm, R; Molls, M; Geinitz, H

2012-02-01

The feasibility and effectiveness of radiotherapy in the management of recurrent esophageal carcinoma (REC) is reported. A consecutive cohort of 54 patients with rcT1-4, rcN0-1, or cM0 recurrent esophageal carcinoma (69% squamous cell carcinoma, 31% adenocarcinoma) was treated between 1988 and 2010. The initial treatment for these patients was definitive radiochemotherapy, surgery alone, or neoadjuvant radiochemotherapy + surgical resection in 8 (15%), 33 (61%), and 13 (24%) patients, respectively. The median time to recurrence from initial treatment was 19 months (range 4-79 months). The site of the recurrence was anastomotic or local, nodal, or both in 63%, 30%, and 7% of patients, respectively. Salvage radio(chemo)therapy was carried out with a median dose of 45 Gy (range 30-68 Gy). Median follow-up time for surviving patients from the start of R(C)T was 38 months (range 10-105 months). Relief of symptoms was achieved in 19 of 28 symptomatic patients (68%). The median survival time was 12 months (95% confidence interval (CI) 7-17 months) and the median recurrence-free interval was 8 months (95% CI 4-12 months). The survival rates at 1, 2, and 3 years were 55 ± 7%, 29 ± 6%, and 19 ± 5%, respectively. The recurrence-free survival rates at 1, 2, and 3 years were 44 ± 7%, 22 ± 6%, and 15 ± 5%, respectively. A radiation dose ≥ 45 Gy and conformal RT were associated with a better prognosis. RT is feasible and effective in the management of recurrent esophageal carcinoma, especially for relief of symptoms. Toxicity is in an acceptable range. The outcome of REC is poor; however, long-term survival of patients with recurrent esophageal carcinoma after radiochemotherapy might be possible, even with a previous history of radiotherapy in the initial treatment. If re-irradiation of esophageal carcinoma is contemplated, three-dimensional conformal techniques and a minimum total dose of 45 Gy are recommended.

Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma

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

Bourgier, Celine; Coche-Dequeant, Bernard; Fournier, Charles

2005-10-01

Purpose: To evaluate the therapeutic results obtained with {sup 192}Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. Patients and Methods: Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. {sup 192}Ir brachytherapy was performed according to the 'Paris system' with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). Results: Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meiermore » method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). Conclusion: Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.« less

MiT family translocation renal cell carcinoma.

PubMed

Argani, Pedram

2015-03-01

The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Is there a role for neck dissection in T1 oral tongue squamous cell carcinoma? The UCLA experience.

PubMed

Peng, Kevin A; Chu, Alan C; Lai, Chi; Grogan, Tristan; Elashoff, David; Abemayor, Elliot; St John, Maie A

2014-01-01

We sought to examine prognostic and therapeutic implications, including cost-effectiveness, of elective neck dissection in the management of patients with clinically-determined T1N0 oral tongue carcinoma. A retrospective review of patients with cT1N0 oral tongue squamous cell carcinoma who underwent surgical extirpation of primary tumor, with or without elective neck dissection, at UCLA Medical Center from 1990 to 2009 was performed. Cox proportional hazards regression was used to assess effects of variables on time to first loco-regional recurrence. A healthcare costs analysis of elective neck dissection was performed by querying the SEER-Medicare linked database. Of the 123 patients identified with cT1N0 squamous cell carcinoma of the oral tongue, 88 underwent elective neck dissection at the time of tumor resection while 35 did not. For all patients, disease-free survival at 3, 5, and 10 years was 93%, 82%, and 79%. Of the 88 patients undergoing elective neck dissection, 20 (23%) demonstrated occult metastatic disease. Male gender, tumor size, perineural invasion, and occult metastatic disease were individually associated with higher rates of loco-regional recurrence. There was no significant difference in loco-regional recurrence between those who underwent elective neck dissection and those who did not (HR=0.76, p=0.52). On cost analysis, neck dissection was not associated with any significant difference in Medicare payments. The high rate of occult metastasis (23%) following elective neck dissection, which did not confer additional healthcare costs, leads to the recommendation of elective neck dissection in patients with cT1N0 oral tongue squamous cell carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Proliferation of CD4CD25Foxp3 regulatory T lymphocytes in ex vivo expanded ascitic fluid from primary and recurrent ovarian carcinoma.

PubMed

Lee, Shin Wha; Kim, Yong-Man; Lee, Ha-Young; Kim, Dae-Yeon; Kim, Jong-Hyeok; Nam, Joo-Hyun; Kim, Young-Tak

2010-03-01

Regulatory T lymphocytes evoke the immune tolerance by suppressing and inactivating cytotoxic T lymphocytes. The objective of this study was to compare the proportion of regulatory T lymphocytes, precisely defined as CD4(+)CD25(high+)Foxp3(+) T lymphocytes, in primary and recurrent ovarian carcinoma before and after ex vivo expansion of ascites with interleukin-2 (IL-2). Ascitic fluid samples were obtained from 26 patients with ovarian carcinoma. Lymphocytes were isolated from ascites and cell markers were analyzed by flow cytometry using anti-CD3/CD4/CD8/CD16/CD56/CD25 and anti-Foxp3 antibodies. Lymphocytes were incubated for 2 to 3 weeks and expanded ex vivo by IL-2 stimulation and their phenotypes were analyzed by flow cytometry. Following ex vivo expansion, ascitic fluid lymphocytes increased by a greater extent in the recurrent group than in the primary group. The proportion of ex vivo-expanded lymphocytes changed as follows; CD4(+) T lymphocytes increased, CD8(+) T lymphocytes decreased, and the proportion of CD3(-)CD16(+)56(+) NK cells was unchanged. The proportion of CD4(+)CD25(high+)Foxp3(+) regulatory T lymphocytes in CD4(+) T lymphocytes increased after ex vivo expansion in both groups, but to a greater degree in the recurrent group. This study showed that regulatory T lymphocytes, neither cytotoxic T lymphocytes nor NK cells, were extensively increased after ex vivo expansion, especially in recurrent ovarian carcinoma. These results may provide information that helps to guide the future development of adoptive immunotherapy against ovarian carcinoma.

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

PubMed

Moureau-Zabotto, L; Viret, F; Giovaninni, M; Lelong, B; Bories, E; Delpero, J R; Pesenti, C; Caillol, F; de Chaisemartin, C; Minsat, M; Monges, G; Sarran, A; Resbeut, M

2011-07-01

This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy. Copyright © 2011 Wiley-Liss, Inc.

PTPROt maintains T cell immunity in the microenvironment of hepatocellular carcinoma.

PubMed

Hou, Jiajie; Deng, Lei; Zhuo, Han; Lin, Zhe; Chen, Yun; Jiang, Runqiu; Chen, Dianyu; Zhang, Xudong; Huang, Xingxu; Sun, Beicheng

2015-08-01

Intratumoral T cells play a central role in anti-tumor immunity, and the balance between T effector cells (Teff) and regulatory T cells (Treg) affects the prognosis of cancer patients. However, educated by tumor microenvironment, T cells frequently fail in their responsibility. In this study, we aimed to investigate the role of truncated isoform of protein tyrosine phosphatase receptor-type O (PTPROt) in T cell-mediated anti-tumor immunity. We recruited 70 hepatocellular carcinoma (HCC) patients and 30 healthy volunteers for clinical investigation, and analyzed cellular tumor immunity by using ptpro(-/-) C57BL/6 mice and NOD/SCID mice. PTPROt expression was significantly downregulated in human HCC-infiltrating T cells due to the hypoxia microenvironment; PTPROt expression highly correlated with the intratumoral Teff/Treg ratio and clinicopathologic characteristics. Moreover, PTPROt deficiency attenuated T cell-mediated anti-tumor immunity and remarkably promoted mouse HCC growth. Mechanistically, deletion of PTPROt decreased Teff quantity and quality through phosphorylation of lymphocyte-specific tyrosine kinase, but increased Treg differentiation through phosphorylation of signal transducer and activator of transcription 5. In support of the Teff/Treg homeostasis, PTPROt serves as an important tumor suppressor in HCC microenvironment. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Liquid chromatography-tandem mass spectrometry detection of the quaternary ammonium compound mebezonium as an active ingredient in t61.

PubMed

Kirschbaum, Katrin M; Grellner, Wolfgang; Rochholz, Gertrud; Musshoff, Frank; Madea, Burkhard

2011-03-01

Quaternary ammonium compounds pose an analytical challenge. Mebezonium, a muscle-relaxing agent contained in veterinary euthanasia solution T61, was analyzed in body fluids, organs, and injection sites of a veterinarian by liquid chromatography-tandem mass spectrometry (LC-MS-MS) method. Additionally, embutramide and tetracaine, which are two other active ingredients contained in T61, methadone, xylazine, and analgesics were detected by LC-MS-MS and high-performance liquid chromatography-ultraviolet detection methods. For detection of mebezonium a solid-phase extraction (SPE) combined with ionpairing reagent heptafluorobutyric acid was developed. Separation was achieved on Phenomenex Synergi Hydro RP C(18) column combined with ammonium formate buffer and acetonitrile (pH 3.5). To enrich other drugs, liquid-liquid extraction procedures were used. Most of these drugs were separated on a Restek Allure PFP Propyl column using the mentioned mobile phase. Mebezonium and embutramide were detected in femoral vein serum in concentrations of 10.9 and 2.0 mg/L, respectively. The concentration of xylazine and methadone in serum was 2.0 and 0.4 mg/L, respectively. The LC-MS-MS method with SPE combined with an ion-pairing reagent allowed the quantitation of mebezonium. Methadone was detected in toxic concentrations and was, in combination with xylazine and T61, considered to be the cause of death.

Carcinomas of the urinary bladder simulating malignant lymphoma. A report of five cases.

PubMed

Zukerberg, L R; Harris, N L; Young, R H

1991-06-01

We report five carcinomas of the urinary bladder, four of them transitional cell carcinomas and one undifferentiated carcinoma, with unusual features that have received little or no comment in the literature and may be the cause of diagnostic difficulty because of their possible confusion with malignant lymphoma. Four patients were male and one female. They ranged from 61 to 76 years of age. Three tumors from these patients had a prominent (2 cases) or massive (1 case) lymphoid infiltrate that partially obscured the invasive carcinoma in two cases and largely obscured it in the third case, which closely resembled a lymphoepithelioma. The diagnosis of malignant lymphoma was only excluded with confidence in the last case after thorough immunohistochemical study. The lymphoid infiltrate was composed of numerous T-cells (UCHL-1 and Leu 22 positive) and polytypic plasma cells with admixed eosinophils; occasional germinal centers were present in one case. The tumors were deeply invasive in two patients, one of whom is alive with no evidence of disease 4 years after treatment with chemotherapy and radiation therapy; the other two cases are too recent for meaningful follow-up. Two other transitional cell carcinomas had diffuse patterns that simulated lymphoma or plasmacytoma. Recognition of these patterns of vesical carcinoma is important in order to avoid the misdiagnosis of the very rare malignant lymphoma of the urinary bladder.

Genome Sequence of Acidovorax avenae Strain T10_61 Associated with Sugarcane Red Stripe in Argentina

PubMed Central

Fontana, Cecilia A.; Bassi, Daniela; Puglisi, Edoardo; Salazar, Sergio M.; Vignolo, Graciela M.; Coccocelli, Pier S.

2016-01-01

Red stripe of sugarcane in Argentina is a bacterial disease caused by Acidovorax avenae. The genome sequence from the first isolate of this bacterium in Argentina is presented here. The draft genome of the A. avenae T10_61 strain contains 5,646,552 bp and has a G+C content of 68.6 mol%. PMID:26847889

Lobular Carcinoma In Situ (LCIS)

MedlinePlus

Lobular carcinoma in situ (LCIS) Overview Lobular carcinoma in situ (LCIS) is an uncommon condition in which abnormal cells form in the ... of developing invasive breast cancer. Symptoms Lobular carcinoma in situ (LCIS) doesn't cause signs or symptoms. Rather, ...

[Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and its related mechanism].

PubMed

Zhang, Shao-nan; Yong, Qun; Wu, Xin-li; Liu, Xiao-ping

2014-11-01

To investigate the synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and the down-regulating effect of curcumin on the Keapl-Nrf2 pathway, a well recognized anti-drug pathway in almost drugged tumor cells. T24 cells were cultured and treated with increasing concentrations of curcumin(5 ,10 and 20 µmol/mL) combined with cisplatin(30 µg/mL) for 24 hours. The inhibitory effects on T24 cells were tested with MTI colorimetric assay. Nuclear Nrf2 and Keapl , cytoplasmic Keapl and two typical phase II enzymes (GSTP1 and NQOl) were checked with Western blotting. The proliferation of T24 cells was significantly inhibited by different concentrations of curcumin combined with cisplatin. After the treatment with different concentrations of curcumin, Nuclear Nrf2 was decreased but Keapl was increased, and GSTP1 and NQO1 were decreased. Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells is observed in this research. The Keapl-Nrf2 pathway in T24 cells is down-regulated by curcumin. The expression of typical phase I enzymes (GSTP1 and NQO1) mediated by Nrf2 are decreased by curcumin. The sensitivity of tumor cells to chemotherapeutic drugs is then enhanced. These may be the mechanism of synergism effect of curcumin combined with cisplatin.

The ethyl acetate extract of Phellinus linteus grown on germinated brown rice induces G0/G1 cell cycle arrest and apoptosis in human colon carcinoma HT29 cells.

PubMed

Park, Hye-Jin; Choi, Se Young; Hong, Se Mi; Hwang, Sung Gu; Park, Dong Ki

2010-07-01

It is well known that Phellinus linteus has a variety of biological functions, such as antitumor and immunomodulating activities. In our previous studies, we developed a P. linteus grown on germinated brown rice (PBR) and found that organic solvent extracts of PBR possessed immunomodulating activity to regulate a balance of cytokine network in mice. The components of PBR are ergosterol peroxide, gamma-aminobutyric acid (GABA) and Beta-glucan. In this study, we demonstrate that an organic solvent extract of P. linteus grown on PBR induced apoptotic cell death through the induction of G(0)/G(1) arrest of cell cycle and the apoptosis via DNA fragmentation in human colon carcinoma HT-29 cells. Cell death induced by the extract of P. linteus grown on PBR was shown to be associated with the upregulation of p21(CIP1/WAF1), the downregulation of cyclin D1, anti-apoptotic protein, Bcl-2, the release of cytochrome c, and the activation of caspase-9, caspase-3 and caspase-8. This study suggests that the ethyl acetate extract of P. linteus grown on PBR induces apoptosis accompanied by cell cycle arrest at G(0)/G(1) phase and regulates apoptosis-regulatory proteins, which may be applicable to anticancer therapy.

Morphological heterogeneity of oral salivary gland carcinomas: A clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

PubMed Central

Schwarz, Stephan; Müller, Maximilian; Ettl, Tobias; Stockmann, Philipp; Zenk, Johannes; Agaimy, Abbas

2011-01-01

We analyzed 41 oral salivary gland carcinomas from consecutive 290 salivary gland carcinoma database (14%) with emphasis on the histological spectrum and clinical outcome of adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA). The cohort included 14 ACCs, 14 mucoepidermoid carcinomas (MECs), 8 PLGAs, 3 adenocarcinomas, not otherwise specified and 2 acinic cell carcinomas. Mean age was 48, 58 and 61 yrs for ACC, MEC and PLGA, respectively. Eight patients (19.5%) died of tumor at a mean interval of 66.5 months. ACC and PLGA showed similar mean age, gender distribution, predominant palatal localization, nodal metastasis, perineural invasion and MIB-1 index. However, ACC tended to show higher tumor stage and residual tumor (R1/R2) more frequently than PLGA, but this was statistically not significant. ACC and PLGA showed overlapping architectural patterns. However, ACCs displayed well organized basal-luminal differentiation, highlighted by CK5/CK7 immunostaining. In contrast, PLGA showed a disorganized histological and immunohistological pattern. C-Kit expression (CD117) was common in ACC, generally mirroring that of CK7 and virtually lacking in PLGA. Kaplan-Meier analysis demonstrated a similar clinical course for ACC and PLGA with 5 years survivals of 87% and 80%, respectively. Fluorescence in situ hybridization (FISH) performed on all 290 salivary carcinomas confirmed the specificity of the translocation t (11; 19) for MEC and its absence in all other carcinomas including ACC and PLGA. Our results emphasize the diversity of oral salivary gland carcinomas and the overlapping clinicopathological features of ACC and PLGA. PMID:21577319

B61 Mod 12 Life Extension Program Tailkit Assembly (B61 Mod 12 LEP TKA)

DTIC Science & Technology

2015-12-01

Selected Acquisition Report ( SAR ) RCS: DD-A&T(Q&A)823-468 B61 Mod 12 Life Extension Program Tailkit Assembly (B61 Mod 12 LEP TKA) As of FY 2017... SAR March 23, 2016 10:38:20 UNCLASSIFIED 2 Table of Contents Common Acronyms and Abbreviations for MDAP Programs 3 Program Information...Unit Cost B61 Mod 12 LEP TKA December 2015 SAR March 23, 2016 10:38:20 UNCLASSIFIED 3 PB - President’s Budget PE - Program Element PEO - Program

Discordance between Ureteroscopic Biopsy and Final Pathology for Upper Tract Urothelial Carcinoma.

PubMed

Margolin, Ezra J; Matulay, Justin T; Li, Gen; Meng, Xiaosong; Chao, Brian; Vijay, Varun; Silver, Hayley; Clinton, Timothy N; Krabbe, Laura-Maria; Woldu, Solomon L; Singla, Nirmish; Bagrodia, Aditya; Margulis, Vitaly; Huang, William C; Bjurlin, Marc A; Shah, Ojas; Anderson, Christopher B

2018-06-01

We evaluated the discordance between ureteroscopic biopsy and surgical pathology findings for grading and staging upper tract urothelial carcinoma. We also sought to establish preoperative predictors of aggressive tumors. We retrospectively reviewed the records of 314 patients who underwent ureteroscopic biopsy followed by surgical management of upper tract urothelial carcinoma from 2000 to 2016 at a total of 3 institutions. Our primary outcomes were muscle invasive (pT2 or greater) disease at surgical pathology and upgrading of clinical low grade tumors to pathological high grade. At biopsy 61% of the patients had clinical high grade tumors and 21% had subepithelial connective tissue invasion (cT1+). On final pathology 79% of the patients had pathological high grade tumors and 45% had stage pT2 or greater. On multivariate analysis advanced patient age, clinical high grade and cT1+ were independently associated with pT2 or greater. The combined presence of clinical high grade and cT1+ had 86% positive predictive value for muscle invasion while the combined absence of clinical high grade and cT1+ had 80% negative predictive value. The likelihood of missing invasion on biopsy in patients with muscle invasive disease was increased when biopsy fragments were limited to 1 mm or less. Of clinical low grade cases on biopsy 51% were upgraded at surgery. The presence of positive urine cytology was associated with an increased risk of upgrading but this was not statistically significant. Clinical high grade, cT1+ on biopsy and advanced patient age are independent risk factors for muscle invasive upper tract urothelial carcinoma. There is a significant risk of upgrading in patients with clinical low grade tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

Transoral laser microsurgery for locally advanced (T3-T4a) supraglottic squamous cell carcinoma: Sixteen years of experience.

PubMed

Vilaseca, Isabel; Blanch, José Luis; Berenguer, Joan; Grau, Juan José; Verger, Eugenia; Muxí, África; Bernal-Sprekelsen, Manuel

2016-07-01

Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016. © 2016 Wiley Periodicals, Inc.

High Rate of Induction of Human Autologous Cytotoxic T Lymphocytes against Renal Carcinoma Cells Cultured with an Interleukin Cocktail

PubMed Central

Liu, Shu Qin; Kawai, Koji; Shiraiwa, Hiroshi; Hayashi, Hitoshi; Akaza, Hideyuki; Hashizaki, Kazuko; Shiba, Reiko; Saijo, Kaoru

1998-01-01

A high rate of induction (9 of 10 cases) of human autologous cytotoxic T lymphocytes (CTL) was achieved in vitro from peripheral blood mononuclear cells of renal carcinoma patients by applying an interleukin (IL)‐cocktail consisting of IL‐1, ‐2, ‐4, and ‐6. The CTL specifically lysed their own target carcinoma cells within 24 h but did not kill neighboring autologous normal kidney cells or allogeneic renal cancer cell lines. In the case of TUHR4TKB, for which autologous CTL were not induced, no expression of MHC class‐I molecules was observed on the surface of these carcinoma cells, although they were sensitive to autologous natural killer cells. The results imply that adoptive immunotherapy for metastasized renal carcinoma will be feasible with autologous CTL in combination with natural killer cells. PMID:9914789

Gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein messenger RNAs as colonic carcinoma.

PubMed

Barnard, G F; Staniunas, R J; Mori, M; Puder, M; Jessup, M J; Steele, G D; Chen, L B

1993-09-01

The levels of a number of ribosomal protein mRNAs are reported to be increased in human colon cancer. We have assessed whether selected ribosomal protein mRNAs are overexpressed in other gastrointestinal malignancies, namely gastric and hepatocellular carcinomas. Subtracted complementary DNA libraries were generated from paired samples of human (a) colorectal carcinoma minus adjacent normal colonic mucosa and (b) hepatocellular carcinoma minus adjacent normal liver. Screening of approximately 3% of these library clones determined that ribosomal protein mRNAs encoding L18 and L37 (not previously reported) and P0 and S6 were overexpressed in one or the other library. Their complementary DNA inserts were then used as probes to evaluate their expression in a larger number of paired tumor/normal surgical samples of human colonic, gastric, and hepatocellular carcinomas, by Northern hybridization. The mRNA signal was greater in the colonic carcinoma than in paired adjacent normal colonic mucosa in 38 of 42 cases for P0 [tumor/normal (T/N) ratio = 3.0 +/- 0.3, mean +/- SE, P < 0.001] (G. F. Barnard, R. J. Staniunas, S. Bao, K. Mafune, J. L. Gollan, G. D. Steele, Jr., and L. B. Chen, Cancer Res., 52: 3067-3072, 1992), in 25 of 28 cases for L18 (T/N ratio = 3.7 +/- 0.5, P < 0.001), in 27 of 28 cases for L37 (T/N ratio = 5.3 +/- 0.4, P < 0.001), and in 24 of 28 cases for S6 (T/N ratio = 3.1 +/- 0.5, P < 0.01). The level of mRNA overexpression of L18 and S6 did not correlate with the Dukes' stage of disease. In hepatocellular carcinoma samples, using the same four ribosomal protein complementary DNA probes, only P0 mRNA was significantly increased (T/N ratio = 2.8 +/- 0.4, n = 6, P = 0.047). In gastric carcinoma samples, none of these mRNAs was increased (mean T/N ratios = 0.9-1.2, n = 6). Therefore, gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein mRNAs as do colonic carcinoma.

Comparative differences between T1a/b and T1e/m as substages in T1 urothelial carcinoma of the bladder.

PubMed

Turan, Turgay; Efiloğlu, Özgür; Günaydin, Bilal; Özkanli, Şeyma; Nikerel, Emrah; Atiş, Gökhan; Çaşkurlu, Turhan; Yildirim, Asif

2018-01-01

To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer and to display comparative differences between the T1a/b and T1e/m substaging systems. This study included 106 patients with primary stage T1 urothelial bladder tumours who underwent surgery between January 2009 and December 2014. Pathologic specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging system were investigated to detect the relation between disease progression and recurrence. The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively (p=0.446). There was no significant difference between the substaging groups for disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs. T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial method, recurrence-free survival was significantly different in patients with pT1a tumours compared with those with pT1b tumours (p=0.033). Substaging T1 provides a prediction of disease recurrence. Regarding recurrence, T1a/b substaging can provide better knowledge of disease behaviour because it is predicted as more superior than T1 m/e, and it can help in determining the requirement for early cystectomy. Copyright® by the International Brazilian Journal of Urology.

Deficiency of IL-18 Aggravates Esophageal Carcinoma Through Inhibiting IFN-γ Production by CD8+T Cells and NK Cells.

PubMed

Li, Jiantao; Qiu, Gang; Fang, Baoshuan; Dai, Xiaohui; Cai, Jianhui

2018-03-01

To investigate the potential role of interleukin-18 (IL-18) in immunomodulation during tumorigenesis of esophageal carcinoma and elucidate the underlying molecular mechanism, we employed IL-18 knockout mice for this purpose. Carcinogen 4-nitroquinoline 1-oxide (4NQO) was administrated in drinking water to induce occurrence of esophageal squamous cell carcinoma (ESCC). T cell activation as indicated by the surface CD molecules was analyzed with flow cytometry. The serous content of interferon-γ (IFN-γ) along with other cytokines was determined by inflammatory human cytokine cytometric bead array. The cytotoxicity assay was performed by co-culture of tumor cells with immune cells and relative cell viability was determined by lactate dehydrogenase (LDH) assay. Apoptotic cells were stained with Annexin-V/propidium iodide (PI) and analyzed by flow cytometry. Cell proliferation was measured with Cell Counting Kit-8 (CCK-8) assay. Our data demonstrated that deficiency of IL-18 promoted the progression and development of 4NQO-induced ESCC. Loss of IL-18 suppressed the activation of T cells in the esophagus. Deficiency of IL-18 inhibited the IFN-γ production by CD8 + T cells and natural killer (NK) cells. Absence of IL-18 inhibited the cytotoxicity of CD8 + T cells and NK cell in vitro. Moreover, deficiency of IL-18 promoted the apoptosis of CD8 + T cells and inhibited the proliferation of CD8 + T cells in vitro. Our data elucidated the immunomodulatory role of IL-18 during tumorigenesis of ESCC, whose deficiency compromised antitumor immunity and contributed to immune escape of esophageal carcinoma. Our results also indicated the therapeutic potential of exogenous IL-18 against ESCC, which warrants further investigations.

MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.

PubMed

Magers, Martin J; Udager, Aaron M; Mehra, Rohit

2015-10-01

Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease. Thus, distinguishing t-RCC from its morphologic, immunophenotypic, and molecular mimics may have important clinical implications. The differential diagnosis for t-RCC includes a variety of common renal neoplasms, particularly those demonstrating clear cell and papillary features; in addition, because of immunophenotypic overlap and/or shared molecular abnormalities (ie, TFE3 gene rearrangement), a distinctive set of nonepithelial renal tumors may also warrant consideration. Directed ancillary testing is an essential aspect to the workup of t-RCC cases and may include a panel of immunohistochemical stains, such as PAX8, pancytokeratins, epithelial membrane antigen, carbonic anhydrase IX, HMB-45, and Melan-A. Dual-color, break-apart fluorescent in situ hybridization for TFE3 or TFEB gene rearrangement may be helpful in diagnostically challenging cases or when molecular confirmation is needed.

CXCR6 and CCR5 localize T lymphocyte subsets in nasopharyngeal carcinoma.

PubMed

Parsonage, Greg; Machado, Lee Richard; Hui, Jan Wai-Ying; McLarnon, Andrew; Schmaler, Tilo; Balasothy, Meenarani; To, Ka-Fai; Vlantis, Alexander C; van Hasselt, Charles A; Lo, Kwok-Wai; Wong, Wai-Lap; Hui, Edwin Pun; Chan, Anthony Tak Cheung; Lee, Steven P

2012-03-01

The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T cell recruitment to this tumor are poorly understood. Comparing memory T cell subsets that have naturally infiltrated NPC tissue with their counterparts from matched blood revealed enrichment of CD8(+), CD4(+), and regulatory T cells expressing the chemokine receptor CXCR6 in tumor tissue. CD8(+) and (nonregulatory) CD4(+) T cells also were more frequently CCR5(+) in tumor than in blood. Ex vivo studies demonstrated that both receptors were functional. CXCL16 and CCL4, unique chemokine ligands for CXCR6 and CCR5, respectively, were expressed by the malignant cells in tumor tissue from the majority of NPC cases, as was another CCR5 ligand, CCL5. The strongest expression of CXCL16 was found on tumor-infiltrating cells. CCL4 was detected on the tumor vasculature in a majority of cases. These findings suggest that CXCR6 and CCR5 play important roles in T cell recruitment and/or retention in NPC and have implications for the pathogenesis and treatment of this tumor. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Radiotherapy in cT3 prostatic carcinoma: retrospective comparison between neoadjuvant and adjuvant hormonotherapy.

PubMed

Cellini, Numa; Luzi, Stefano; Morganti, Alessio Giuseppe; Valentini, Vincenzo; Mantini, Giovanna; Racioppi, Marco; Smaniotto, Daniela; Leone, Mariavittoria; Mattiucci, Gian Carlo; Digesù, Cinzia; Giustacchini, Mario; Destito, Antonio; Alcini, Eugenio

2004-01-01

The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy. One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present. Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0

Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: Implications for adjuvant therapy

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

Chen, Allen M.; Granchi, Phillip J.; Garcia, Joaquin

2007-03-15

Purpose: To determine factors predictive of local-regional recurrence (LRR) after surgery alone for carcinomas of the major salivary glands in an attempt to evaluate the potential role of postoperative radiation therapy. Methods and Materials: Between 1960 and 2004, 207 patients with carcinomas of the major salivary glands were treated with definitive surgery without postoperative radiation therapy. Histology was: 67 mucoepidermoid (32%), 50 adenoid cystic (24%), 34 acinic cell (16%), 23 malignant mixed (11%), 16 adenocarcinoma (8%), 6 oncocytic (3%), 6 myoepithelial (3%), and 5 other (2%). Distribution of pathologic T-stage was: 54 T1 (26%), 83 T2 (40%), 46 T3 (22%),more » and 24 T4 (12%). Sixty patients (29%) had microscopically positive margins. Median follow-up was 6.1 years (range, 0.5-18.7 years). Results: The 5-year and 10-year estimates of local-regional control were 86% and 74%, respectively. A Cox proportional hazard model identified pathologic lymph node metastasis (hazard ratio [HR], 4.8; p = 0.001), high histologic grade (HR, 4.2; p = 0.003), positive margins (HR, 2.6; p = 0.03), and T3-4 disease (HR, 2.0; p = 0.04) as independent predictors of LRR. The presence of any one of these factors was associated with 10-year local-regional control rates of 37% to 63%. Conclusion: Lymph node metastasis, high tumor grade, positive margins, and T3-4 stage predict for significant rates of LRR after surgery for carcinomas of the major salivary glands. Postoperative radiation therapy should be considered for patients with these disease characteristics.« less

Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

PubMed Central

Fogg, Mark; Murphy, John R.; Lorch, Jochen; Posner, Marshall; Wang, Fred

2013-01-01

Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. PMID:23601786

GLI1 inhibitor GANT61 exhibits antitumor efficacy in T-cell lymphoma cells through down-regulation of p-STAT3 and SOCS3

PubMed Central

Geng, Lingyun; Lu, Kang; Li, Peipei; Li, Xinyu; Zhou, Xiangxiang; Li, Ying; Wang, Xin

2017-01-01

T-cell lymphomas are lymphoid malignancies with aggressive clinical course and poor prognosis. Increasing evidences suggest that deregulation of signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) is associated with the pathogenesis of T-cell lymphomas. The hedgehog (Hh)/glioma-associated oncogene-1 (GLI1) pathway, aberrantly activated in a number of tumors, has also been extensively studied. We found that protein expressions of GL11, p-STAT3, STAT3, and SOCS3 were up-regulated in T-cell lymphoma tissues and cell lines. Moreover, the protein expressions of p-STAT3 and SOCS3 were positively correlated with GLI1 in T-cell lymphomas. GLI1 inhibitor GANT61 and lentivirus-mediated siGLI1 exhibited inhibitory effects in the three T-cell lines (Jurkat, Karpass299 and Myla3676 cells). The protein expressions of p-STAT3 and SOCS3 were decreased accompanied with the inhibition of GLI1. These findings indicated that GANT61 is a promising agent against T-cell lymphoma and the antitumor activity might be partly mediated by down-regulating p-STAT3 and SOCS3. PMID:27275540

Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.

PubMed

Xu, Ya-Ming; Wijeratne, E M Kithsiri; Babyak, Ashley L; Marks, Hanna R; Brooks, Alan D; Tewary, Poonam; Xuan, Li-Jiang; Wang, Wen-Qiong; Sayers, Thomas J; Gunatilaka, A A Leslie

2017-07-28

Investigation of aeroponically grown Physalis peruviana resulted in the isolation of 11 new withanolides, including perulactones I-L (1-4), 17-deoxy-23β-hydroxywithanolide E (5), 23β-hydroxywithanolide E (6), 4-deoxyphyperunolide A (7), 7β-hydroxywithanolide F (8), 7β-hydroxy-17-epi-withanolide K (9), 24,25-dihydro-23β,28-dihydroxywithanolide G (10), and 24,25-dihydrowithanolide E (11), together with 14 known withanolides (12-25). The structures of 1-11 were elucidated by the analysis of their spectroscopic data, and 12-25 were identified by comparison of their spectroscopic data with those reported. All withanolides were evaluated for their cytotoxic activity against a panel of tumor cell lines including LNCaP (androgen-sensitive human prostate adenocarcinoma), 22Rv1 (androgen-resistant human prostate adenocarcinoma), ACHN (human renal adenocarcinoma), M14 (human melanoma), SK-MEL-28 (human melanoma), and normal human foreskin fibroblast cells. Of these, the 17β-hydroxywithanolides (17-BHWs) 6, 8, 9, 11-13, 15, and 19-22 showed selective cytotoxic activity against the two prostate cancer cell lines LNCaP and 22Rv1, whereas 13 and 20 exhibited selective toxicity for the ACHN renal carcinoma cell line. These cytotoxicity data provide additional structure-activity relationship information for the 17-BHWs.

Carcinoma of the larynx: role of laser surgery

NASA Astrophysics Data System (ADS)

Inouye, Tetsuzo; Tanabe, Tetsuya; Nakanoboh, Manabu; Ohmae, Yukio; Ogura, Masami

1995-05-01

68 cases of glottic carcinomas (T1 53 and T2 15 cases) treated with CO2 laser or KTP/532 laser April 1982 through March 1992 were reviewed. The patients were followed up from 13 to 130 months (mean 60 months). The 3-year determinate survival rate was 100% and 5-year determinate survival rate was 100% for T1 and 80% for T2. The voice conservation rate was 97% for T1a, 83% for T1b, and 80% for T2 and vocal function was satisfactorily preserved for daily life. The results led to the following conclusions: (1) Glottic T1 carcinomas can be treated by laser surgery alone. (2) Lesions involving the anterior commissure can be treated by laser excision and vaporization. (3) Laser surgery followed by external radiation therapy for glottic T2 carcinomas improves the voice conservation rate.

Merkel cell polyomavirus small T antigen initiates Merkel cell carcinoma-like tumor development in mice

PubMed Central

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

2017-01-01

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a non-proliferative population of neuroendocrine cells which arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor’s cell of origin, are unknown. Using a panel of pre-term transgenic mice, we show that epidermis-targeted co-expression of sT and the cell fate determinant atonal bHLH transcription factor 1 (Atoh1) leads to development of widespread cellular aggregates with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Co-expression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with Atoh1. MCPyV sT, when co-expressed with Atoh1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. PMID:28512245

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

PubMed

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

2017-06-15

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

[Study of dynamic contrast-enhanced characteristics of stage-I endometrial carcinomas versus polyps with 3.0 T MRI].

PubMed

Wang, Xue; Lu, Yi; Zhang, Xiaoxia; Ji, Taotao; Liu, Kun; Ye, Xinjian; Bai, Guanghui; Yan, Zhihan

2015-01-20

To comparatively analyze the dynamic contrast-enhanced (DCE) characteristics and its clinical value between stage-I endometrial carcinomas versus polyps with 3.0T magnetic resonance imaging (MRI). A retrospective analysis was performed for DCE-MRI manifestation in 27 patients with histopathologically proved endometrial masses. There were stage-I endometrial carcinomas (n = 14) and polyps (n = 13). The signal intensity of solid component was measured and time-intensity curves (TIC) was obtained. TIC of lesions were divided into 4 subtypes. The time-to-peak (TTP) and signal intensity (SI) were determined from TICs. The arterial phase relative signal increase ratio (ARSIR), maximal relative signal increase ratio (MRSIR), signal enhancement ratio (SER) and signal intensity difference values (D) of each phase were calculated based on TIC curves respectively. The TIC of 14 stage-I endometrial carcinomas included type I (n = 4), type II (n = 6) and type IV (n = 4). The TIC of 13 polyps included type III (n = 3) and type IV (n = 10). The D values in each phase of 14 stage-I endometrial carcinomas were lower than normal muscle layers. There were statistic differences (P < 0.05) of each phase including 32, 48, 64, 109, 154, 199 s. For stage-I endometrial carcinomas, MRSIR and TTP were lower (P < 0.01) than normal muscle layers while SER was higher (P < 0.01) than normal muscle layers . The each phase of D of stage-I endometrial carcinomas were lower than polyps, and there were statistic differences (P < 0.05) of each phase including 32, 48, 64, 109, 154, 199 s. The MRSIR and TTP of stage-I endometrial carcinomas were lower (P < 0.01) than those of polyps while SER was higher (P < 0.01) than polyps. DCE-MRI can reflect enhanced features of stage-I endometrial carcinomas and polyps during different phases quantitatively. Parameters of DCE-MR and TIC are helpful in the diagnosis and differential diagnosis of stage-I endometrial carcinomas versus polyps.

19 CFR 123.61 - Baggage arriving in baggage car.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars. [T.D. 70-121, 35 FR 8215, May 26, 1970, as amended by T.D. 82-145, 47 FR 35478, Aug. 16, 1982] ...

19 CFR 123.61 - Baggage arriving in baggage car.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars. [T.D. 70-121, 35 FR 8215, May 26, 1970, as amended by T.D. 82-145, 47 FR 35478, Aug. 16, 1982] ...

19 CFR 123.61 - Baggage arriving in baggage car.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars. [T.D. 70-121, 35 FR 8215, May 26, 1970, as amended by T.D. 82-145, 47 FR 35478, Aug. 16, 1982] ...

19 CFR 123.61 - Baggage arriving in baggage car.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars. [T.D. 70-121, 35 FR 8215, May 26, 1970, as amended by T.D. 82-145, 47 FR 35478, Aug. 16, 1982] ...

WISP1 genetic variants as predictors of tumor development with urothelial cell carcinoma.

PubMed

Lee, Hsiang-Lin; Chiou, Hui-Ling; Wang, Shian-Shiang; Hung, Sheng-Chun; Chou, Ming-Chih; Yang, Shun-Fa; Hsieh, Ming-Ju; Chou, Ying-Erh

2018-04-01

Urothelial cell carcinoma (UCC) of the urinary bladder is a major malignancy of the genitourinary tract. Etiological factors, such as the environment, ethnicity, genetics, and diet, contribute to UCC carcinogenesis. WNT1-inducible signaling pathway protein 1 (WISP1), also known as CCN4, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and might be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms to evaluate UCC susceptibility and clinicopathological characteristics. Real-time polymerase chain reaction was used to analyze 4 single-nucleotide polymorphisms of WISP1 in 369 patients with UCC and 738 controls without cancer. The results showed that in 128 women with UCC who carried WISP1 rs2929973 (AG + GG) variants had a higher risk of developing an advanced muscle-invasive tumor stage (pT2-pT4, P = 0.007) and a large tumor (T1-T4, P = 0.030). Further analyses revealed that a correlation between the expressions of WISP1 and invasive tumor and large tumor size in urothelial carcinoma was observed in the TCGA (The Cancer Genome Atlas) dataset. Our results indicated that patients with UCC carrying rs2977530 genetic variants (AG + GG) have a higher risk of developing a more invasive tumor stage and a large tumor. WISP1 polymorphisms may serve as a marker or a therapeutic target in UCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinicopathological characteristics of head and neck Merkel cell carcinomas.

PubMed

Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

2017-01-01

There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p < .0001) despite comparable TNM classifications and treatment regimens. There were neither differences of RFI/OS between parotid gland Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.

PubMed

Curiel, Tyler J; Coukos, George; Zou, Linhua; Alvarez, Xavier; Cheng, Pui; Mottram, Peter; Evdemon-Hogan, Melina; Conejo-Garcia, Jose R; Zhang, Lin; Burow, Matthew; Zhu, Yun; Wei, Shuang; Kryczek, Ilona; Daniel, Ben; Gordon, Alan; Myers, Leann; Lackner, Andrew; Disis, Mary L; Knutson, Keith L; Chen, Lieping; Zou, Weiping

2004-09-01

Regulatory T (T(reg)) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by T(reg) cells; however, definitive evidence that T(reg) cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4(+)CD25(+)FOXP3(+) T(reg) cells in 104 individuals affected with ovarian carcinoma, that human tumor T(reg) cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. We also show that tumor T(reg) cells are associated with a high death hazard and reduced survival. Human T(reg) cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T(reg) cells to the tumor. This specific recruitment of T(reg) cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T(reg) cell migration or function may help to defeat human cancer.

Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

PubMed

Stravodimou, Aristea; Tzelepi, Vassiliki; Papadaki, Helen; Mouzaki, Athanasia; Georgiou, Sophia; Melachrinou, Maria; Kourea, Eleni P

2018-05-01

Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions. Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup-Mäkinen (K-M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

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

Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana; Sandoval, Alejandro

Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating themore » cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.« less

A human thyroid cancer cell line, DH-14-3, newly established from poorly differentiated thyroid carcinoma.

PubMed

Teshima, Jin; Doi, Hideyuki; Fujimori, Keisei; Watanabe, Michio; Nakajima, Noriaki; Nakano, Tomoyuki; Takahashi, Yoshio; Ohuchi, Noriaki; Satomi, Susumu

2013-06-01

Poorly differentiated thyroid carcinoma (PDTC) is a newly recognized histological type of malignant thyroid tumor, accounting for about 2 - 13% of all thyroid carcinomas. PDTC is considered as a morphologically and biologically intermediate stage between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma. PDTC preferentially manifests bone metastases. We here established a cell line from a resected tumor specimen from a 70-year-old male patient with PDTC who presented with multiple bone metastases. This new thyroid tumor cell line was designated as DH-14-3 and was subsequently grown in culture for several years. DH-14-3 cells express thyroglobulin in the cytoplasm and thyroid transcription factor-1 in the nuclei, both proteins of which are specific markers for the thyroid gland. Importantly, triiodothyronine (T3) was detected in the cultured medium of DH-14-3 cells, in which, however, thyroxine (T4) was undetectable. Moreover, DH-14-3 cells secreted interleukin-8, transforming growth factor-β1, vascular endothelial growth factor, matrix metalloproteinase-1 and parathyroid hormone-related protein, all of which may be responsible for the aggressiveness or bone metastasis of PDTC. Thus, the production of these proteins may reflect the metastatic potential of this cell line. DH-14-3 cells also express CXC chemokine receptor-4 and epidermal growth factor receptor, and carry a missense mutation in the p53 tumor suppressor gene. In fact, transplantation of DH-14-3 cells into the back of nude mice resulted in the formation of tumors, thereby confirming the capability of tumorigenesis. DH-14-3 cells may be useful for investigating the biological features of PDTC and will contribute to the therapeutic study of thyroid cancer.

Postoperative radiation therapy of pT2-3N0M0 esophageal carcinoma-a review.

PubMed

Luo, Yijun; Wang, Xiaoli; Yu, Jinming; Zhang, Bin; Li, Minghuan

2016-11-01

Esophageal cancer is one of the most malignant gastrointestinal cancers worldwide. Despite advances in surgical technique, 5-year survival in pathologic stage T2-3N0M0 esophageal squamous cell carcinoma patients who are treated with surgery alone is still poor. The addition of adjuvant radiotherapy may confer a benefit for these patients. However, not all patients could get a benefit from radiotherapy and patients with esophageal squamous cell carcinoma receiving radiotherapy seem to have a disparity in treatment response. Thus, identifying effective prognostic indicator to complement current clinical staging approaches is extremely important. Those prognostic factors could give rise to a novel prognostic stratification system, which serve as criteria for selecting patients for adjuvant therapy. Consequently, it may help to define the subgroups who are more likely to benefit from postoperative radiation therapy.

Mucoepidermoid carcinoma of the parotid gland treated by surgery and postoperative radiation therapy: clinicopathologic correlates of outcome.

PubMed

Chen, Allen M; Lau, Valerie H; Farwell, D Gregory; Luu, Quang; Donald, Paul J

2013-12-01

To determine clinical and pathological correlates of outcome among patients treated by surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Retrospective review. The medical records of 61 patients treated by surgery and postoperative radiation therapy for localized mucoepidermoid carcinoma of the parotid gland were retrospectively reviewed in an attempt to identify clinicopathologic correlates of overall survival. Secondary endpoints included local-regional control, distant metastasis-free survival, and complications. The 3- and 5-year estimates of overall survival were 85% and 79%, respectively. Multivariate analysis identified high tumor grade (hazard ratio [HR] = 7.92) and T4 disease (HR = 3.35) as independent predictors of decreased survival, with the former also predicting for distant metastasis and the latter predicting for local-regional recurrence. The 5-year estimate of overall survival was 83% for patients with non-high-grade tumors, compared to 52% for those with high-grade histology (P = 0.001). Late complications included trismus (2 patients), osteoradionecrosis (1 patient), and hearing loss (1 patient). Patients with high-grade tumors and T4 disease are at increased risk for treatment failure after surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Investigative strategies to improve outcome should be considered for these particular patients in the future. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

A photosensitizer delivered by bispecific antibody redirected T lymphocytes enhances cytotoxicity against EpCAM-expressing carcinoma cells upon light irradiation.

PubMed

Blaudszun, André-René; Moldenhauer, Gerhard; Schneider, Marc; Philippi, Anja

2015-01-10

Recently conducted clinical trials have provided impressive evidence that chemotherapy resistant metastatic melanoma and several hematological malignancies can be cured using adoptive T cell therapy or T cell-recruiting bispecific antibodies. However, a significant fraction of patients did not benefit from these treatments. Here we have evaluated the feasibility of a novel combination therapy which aims to further enhance the killing potential of bispecific antibody-redirected T lymphocytes by using these cells as targeted delivery system for photosensitizing agents. For a first in vitro proof-of-concept study, ex vivo activated human donor T cells were loaded with a poly(styrene sulfonate) (PSS)-complex of the model photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP). In the absence of light and when loading with the water-soluble PSS/mTHPP-complex occurred at a tolerable concentration, viability and cytotoxic function of loaded T lymphocytes were not impaired. When "drug-enhanced" T cells were co-cultivated with EpCAM-expressing human carcinoma cells, mTHPP was transferred to target cells. Notably, in the presence of a bispecific antibody, which cross-links effector and target cells thereby inducing the cytolytic activity of cytotoxic T lymphocytes, significantly more photosensitizer was transferred. Consequently, upon irradiation of co-cultures, redirected drug-loaded T cells were more effective in killing A549 lung and SKOV-3 ovarian carcinoma cells than retargeted unloaded T lymphocytes. Particularly, the additive approach using redirected unloaded T cells in combination with appropriate amounts of separately applied PSS/mTHPP was less efficient as well. Thus, by loading T lymphocytes with a stimulus-sensitive anti-cancer drug, we were able to enhance the cytotoxic capacity of carrier cells. Photosensitizer boosted T cells could open new perspectives for adoptive T cell therapy as well as targeted photodynamic therapy. Copyright © 2014

Hepatocellular carcinomas of the albumin SV40 T-antigen transgenic rat display fetal-like re-expression of lgf2 and deregulation of H19.

PubMed

Czarny, Matthew J; Babcock, Karlee; Baus, Rebecca M; Manoharan, Herbert; Pitot, Henry C

2007-09-01

Previous studies in our laboratory have shown that one of the earliest events during hepatocarcinogenesis in the albumin SV40 T antigen (Alb SV40 T Ag) transgenic rat is the duplication of chromosome 1q3.7-4.3, a region which contains the imprinted and coordinately regulated genes Igf2 and H19. We have also shown that this duplication is associated with the biallelic expression of the normally monoallelically-expressed H19. These results, however, are seemingly at odds with studies in the mouse that have shown a conservation of fetal regulatory patterns of these two genes in hepatic neoplasms. We therefore aimed in this study to determine the allelic origin of Igf2 expression in hepatocellular carcinomas of the Alb SV40 T Ag transgenic rat. Sprague-Dawley Alb SV40 T Ag transgenic rats and Brown Norway rats were reciprocally mated and the expression of Igf2 in hepatocellular carcinomas of the resulting F(1) transgene-positive female rats was analyzed by Northern blotting and RT-PCR. We determined that Igf2 was expressed exclusively from the paternal allele, which prompted the study (by the same methods) of the allelic origin of H19 in the same hepatocellular carcinomas in order to determine if the two genes remained coordinately regulated. Our results demonstrate fetal-like re-expression of Igf2 and deregulation of H19 in singular hepatocellular carcinomas of the rat. These results imply that another regulatory mechanism other than the generally accepted ICR/CTCF mechanism may play a role in the control of Igf2 and H19 expression. (c) 2007 Wiley-Liss, Inc.

The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin.

PubMed

Cazzaniga, Alessandra; Moscheni, Claudia; Trapani, Valentina; Wolf, Federica I; Farruggia, Giovanna; Sargenti, Azzurra; Iotti, Stefano; Maier, Jeanette A M; Castiglioni, Sara

2017-01-17

The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells. The resistant phenotype is accompanied by the upregulation of the magnesium transporter MagT1 and the downregulation of the ion channel kinase TRPM7. We demonstrate that the different amounts of TRPM7 and MagT1 account for the different proliferation rate of sensitive and resistant colon carcinoma cells. It remains to be verified whether they are also involved in the control of other "staminal" traits.

Optimization of the highly strained InGaAs/GaAs quantum well lasers grown by MOVPE

NASA Astrophysics Data System (ADS)

Su, Y. K.; Chen, W. C.; Wan, C. T.; Yu, H. C.; Chuang, R. W.; Tsai, M. C.; Cheng, K. Y.; Hu, C.; Tsau, Seth

2008-07-01

In this article, we study the highly compressive-strained InGaAs/GaAs quantum wells and the broad-area lasers grown by MOVPE. Several epitaxial parameters were optimized, including the growth temperature, pressure and group V to group III (V/III) ratio. Grown with the optimized epitaxial parameters, the highly strained In 0.39Ga 0.61As/GaAs lasers could be continuously operated at 1.22 μm and their threshold current density Jth was 140 A/cm 2. To the best of our knowledge, the demonstrated InGaAs QW laser has the lowest threshold current per quantum well (Jth/QW) of 46.7 A/cm 2. The fitted characteristic temperature ( T0) was 146.2 K, indicating the good electron confinement ability. Furthermore, by lowering the growth temperature down to 475 °C and the TBAs/III ratio to 5, the emission wavelength of the In 0.42Ga 0.58As/GaAs quantum wells was as long as 1245 nm and FWHM was 43 meV.

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

PubMed

Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

2018-03-25

To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (<4 cm) without visible fat (14 fat-poor angiomyolipomas, 92 clear cell renal cell carcinomas, six chromophobe renal cell carcinomas and nine papillary renal cell carcinomas) were retrospectively evaluated. An intensity ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

Squamous cell carcinoma arising in Hailey-Hailey disease of the vulva.

PubMed

Cockayne, S E; Rassl, D M; Thomas, S E

2000-03-01

A 61-year-old woman, who was known to have Hailey-Hailey disease, presented with increasing vulval soreness. Biopsy showed vulval intraepithelial neoplasia (VIN) 3 and subsequent histology from a vulvectomy specimen showed extensive VIN with early invasive squamous cell carcinoma. This may be another example of chronic inflammation of the vulval area leading to the development of squamous cell carcinoma. However, in this case, chronic human papillomavirus may also have played a part, leading to VIN and reactivation of the Hailey-Hailey disease. We can find no previous reports of squamous cell carcinoma developing in the setting of Hailey-Hailey disease.

In vitro effects of tetraiodothyroacetic acid combined with X-irradiation on basal cell carcinoma cells.

PubMed

Leith, John T; Davis, Paul J; Mousa, Shaker A; Hercbergs, Aleck A

2017-02-16

We investigated radiosensitization in an untreated basal cell carcinoma (TE.354.T) cell line and post-pretreatment with tetraiodothyroacetic acid (tetrac) X 1 h at 37°C, 0.2 and 2.0 µM tetrac. Radioresistant TE.354.T cells were grown in modified medium containing fibroblast growth factor-2, stem cell factor-1 and a reduced calcium level. We also added reproductively inactivated (30 Gy) "feeder cells" to the medium. The in vitro doubling time was 34.1 h, and the colony forming efficiency was 5.09 percent. These results were therefore suitable for clonogenic radiation survival assessment. The 250 kVp X-ray survival curve of control TE.354.T cells showed linear-quadratic survival parameters of α X-ray = 0.201 Gy -1 and β X-ray = 0.125 Gy -2 . Tetrac concentrations of either 0.2 or 2.0 µM produced α X-ray and β X-ray parameters of 2.010 and 0.282 Gy -1 and 2.050 and 0.837 Gy -2 , respectively. The surviving fraction at 2 Gy (SF 2 ) for control cells was 0.581, while values for 0.2 and 2.0 µM tetrac were 0.281 and 0.024. The SF 2 data show that tetrac concentrations of 0.2 and 2.0 µM sensitize otherwise radioresistant TE.354.T cells by factors of 2.1 and 24.0, respectively. Thus, radioresistant basal cell carcinoma cells may be radiosensitized pharmacologically by exposure to tetrac.

Are randomly grown graphs really random?

PubMed

Callaway, D S; Hopcroft, J E; Kleinberg, J M; Newman, M E; Strogatz, S H

2001-10-01

We analyze a minimal model of a growing network. At each time step, a new vertex is added; then, with probability delta, two vertices are chosen uniformly at random and joined by an undirected edge. This process is repeated for t time steps. In the limit of large t, the resulting graph displays surprisingly rich characteristics. In particular, a giant component emerges in an infinite-order phase transition at delta=1/8. At the transition, the average component size jumps discontinuously but remains finite. In contrast, a static random graph with the same degree distribution exhibits a second-order phase transition at delta=1/4, and the average component size diverges there. These dramatic differences between grown and static random graphs stem from a positive correlation between the degrees of connected vertices in the grown graph-older vertices tend to have higher degree, and to link with other high-degree vertices, merely by virtue of their age. We conclude that grown graphs, however randomly they are constructed, are fundamentally different from their static random graph counterparts.

Upregulated Glucose Metabolism Correlates Inversely with CD8+ T-cell Infiltration and Survival in Squamous Cell Carcinoma.

PubMed

Ottensmeier, Christian H; Perry, Kate L; Harden, Elena L; Stasakova, Jana; Jenei, Veronika; Fleming, Jason; Wood, Oliver; Woo, Jeongmin; Woelk, Christopher H; Thomas, Gareth J; Thirdborough, Stephen M

2016-07-15

Antibodies that block T-cell-regulatory checkpoints have recently emerged as a transformative approach to cancer treatment. However, the clinical efficacy of checkpoint blockade depends upon inherent tumor immunogenicity, with variation in infiltrating T cells contributing to differences in objective response rates. Here, we sought to understand the molecular correlates of tumor-infiltrating T lymphocytes (TIL) in squamous cell carcinoma (SCC), using a systems biologic approach to integrate publicly available omics datasets with histopathologic features. We provide evidence that links TIL abundance and therapeutic outcome to the regulation of tumor glycolysis by EGFR and HIF, both of which are attractive molecular targets for use in combination with immunotherapeutics. Cancer Res; 76(14); 4136-48. ©2016 AACR. ©2016 American Association for Cancer Research.

14 CFR 298.61 - Reporting of traffic statistics.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Reporting of traffic statistics. 298.61... Requirements § 298.61 Reporting of traffic statistics. (a) Each commuter air carrier and small certificated air... statistics shall be compiled in terms of each flight stage as actually performed. The detail T-100 data shall...

14 CFR 298.61 - Reporting of traffic statistics.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Reporting of traffic statistics. 298.61... Requirements § 298.61 Reporting of traffic statistics. (a) Each commuter air carrier and small certificated air... statistics shall be compiled in terms of each flight stage as actually performed. The detail T-100 data shall...

Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI.

PubMed

Wang, Xue; Zhao, Yu; Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen; Wang, Jinhong; Yan, Zhihan

2017-07-11

Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10-3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers.

Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI

PubMed Central

Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen

2017-01-01

Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10−3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers. PMID:28634318

The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin

PubMed Central

Cazzaniga, Alessandra; Moscheni, Claudia; Trapani, Valentina; Wolf, Federica I.; Farruggia, Giovanna; Sargenti, Azzurra; Iotti, Stefano; Maier, Jeanette A. M.; Castiglioni, Sara

2017-01-01

The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells. The resistant phenotype is accompanied by the upregulation of the magnesium transporter MagT1 and the downregulation of the ion channel kinase TRPM7. We demonstrate that the different amounts of TRPM7 and MagT1 account for the different proliferation rate of sensitive and resistant colon carcinoma cells. It remains to be verified whether they are also involved in the control of other “staminal” traits. PMID:28094304

The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study.

PubMed

Kawashima, Atsunari; Nakai, Yasutomo; Nakayama, Masashi; Ujike, Takeshi; Tanigawa, Go; Ono, Yutaka; Kamoto, Akihito; Takada, Tsuyosi; Yamaguchi, Yuichiro; Takayama, Hitoshi; Nishimura, Kazuo; Nonomura, Norio; Tsujimura, Akira

2012-10-01

To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required.

10 CFR 61.61 - Applicant qualifications and assurances.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Applicant qualifications and assurances. 61.61 Section 61.61 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.61 Applicant qualifications and assurances. Each applicant shall...

10 CFR 61.61 - Applicant qualifications and assurances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Applicant qualifications and assurances. 61.61 Section 61.61 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.61 Applicant qualifications and assurances. Each applicant shall...

10 CFR 61.61 - Applicant qualifications and assurances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Applicant qualifications and assurances. 61.61 Section 61.61 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.61 Applicant qualifications and assurances. Each applicant shall...

10 CFR 61.61 - Applicant qualifications and assurances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Applicant qualifications and assurances. 61.61 Section 61.61 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.61 Applicant qualifications and assurances. Each applicant shall...

10 CFR 61.61 - Applicant qualifications and assurances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Applicant qualifications and assurances. 61.61 Section 61.61 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.61 Applicant qualifications and assurances. Each applicant shall...

Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2 Squamous Cell Carcinoma.

PubMed

Persky, Michael J; Albergotti, William G; Rath, Tanya J; Kubik, Mark W; Abberbock, Shira; Geltzeiler, Mathew; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L

2018-04-01

Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.

[Exenteration of the Orbit for Basal Cell Carcinoma].

PubMed

Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

2015-08-01

Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

Use of fatty acid methyl ester profiles for discrimination of Bacillus cereus T-strain spores grown on different media.

PubMed

Ehrhardt, Christopher J; Chu, Vivian; Brown, TeeCie; Simmons, Terrie L; Swan, Brandon K; Bannan, Jason; Robertson, James M

2010-03-01

The goal of this study was to determine if cellular fatty acid methyl ester (FAME) profiling could be used to distinguish among spore samples from a single species (Bacillus cereus T strain) that were prepared on 10 different medium formulations. To analyze profile differences and identify FAME biomarkers diagnostic for the chemical constituents in each sporulation medium, a variety of statistical techniques were used, including nonmetric multidimensional scaling (nMDS), analysis of similarities (ANOSIM), and discriminant function analysis (DFA). The results showed that one FAME biomarker, oleic acid (18:1 omega9c), was exclusively associated with spores grown on Columbia agar supplemented with sheep blood and was indicative of blood supplements that were present in the sporulation medium. For spores grown in other formulations, multivariate comparisons across several FAME biomarkers were required to discern profile differences. Clustering patterns in nMDS plots and R values from ANOSIM revealed that dissimilarities among FAME profiles were most pronounced when spores grown with disparate sources of complex additives or protein supplements were compared (R > 0.8), although other factors also contributed to FAME differences. DFA indicated that differentiation could be maximized with a targeted subset of FAME variables, and the relative contributions of branched FAME biomarkers to group dissimilarities changed when different media were compared. When taken together, these analyses indicate that B. cereus spore samples grown in different media can be resolved with FAME profiling and that this may be a useful technique for providing intelligence about the production methods of Bacillus organisms in a forensic investigation.

Use of Fatty Acid Methyl Ester Profiles for Discrimination of Bacillus cereus T-Strain Spores Grown on Different Media▿

PubMed Central

Ehrhardt, Christopher J.; Chu, Vivian; Brown, TeeCie; Simmons, Terrie L.; Swan, Brandon K.; Bannan, Jason; Robertson, James M.

2010-01-01

The goal of this study was to determine if cellular fatty acid methyl ester (FAME) profiling could be used to distinguish among spore samples from a single species (Bacillus cereus T strain) that were prepared on 10 different medium formulations. To analyze profile differences and identify FAME biomarkers diagnostic for the chemical constituents in each sporulation medium, a variety of statistical techniques were used, including nonmetric multidimensional scaling (nMDS), analysis of similarities (ANOSIM), and discriminant function analysis (DFA). The results showed that one FAME biomarker, oleic acid (18:1 ω9c), was exclusively associated with spores grown on Columbia agar supplemented with sheep blood and was indicative of blood supplements that were present in the sporulation medium. For spores grown in other formulations, multivariate comparisons across several FAME biomarkers were required to discern profile differences. Clustering patterns in nMDS plots and R values from ANOSIM revealed that dissimilarities among FAME profiles were most pronounced when spores grown with disparate sources of complex additives or protein supplements were compared (R > 0.8), although other factors also contributed to FAME differences. DFA indicated that differentiation could be maximized with a targeted subset of FAME variables, and the relative contributions of branched FAME biomarkers to group dissimilarities changed when different media were compared. When taken together, these analyses indicate that B. cereus spore samples grown in different media can be resolved with FAME profiling and that this may be a useful technique for providing intelligence about the production methods of Bacillus organisms in a forensic investigation. PMID:20097814

Differentiating Laryngeal Carcinomas from Precursor Lesions by Diffusion-Weighted Magnetic Resonance Imaging at 3.0 T: A Preliminary Study

PubMed Central

Shang, De-Sheng; Ruan, Ling-Xiang; Zhou, Shui-Hong; Bao, Yang-Yang; Cheng, Ke-Jia; Wang, Qin-Ying

2013-01-01

Background Diffusion-weighted magnetic resonance imaging (DWI) has been introduced in head and neck cancers. Due to limitations in the performance of laryngeal DWI, including the complex anatomical structure of the larynx leading to susceptibility effects, the value of DWI in differentiating benign from malignant laryngeal lesions has largely been ignored. We assessed whether a threshold for the apparent diffusion coefficient (ADC) was useful in differentiating preoperative laryngeal carcinomas from precursor lesions by turbo spin-echo (TSE) DWI and 3.0-T magnetic resonance. Methods We evaluated DWI and the ADC value in 33 pathologically proven laryngeal carcinomas and 17 precancerous lesions. Results The sensitivity, specificity, and accuracy were 81.8%, 64.7%, 76.0% by laryngostroboscopy, respectively. The sensitivity, specificity, and accuracy of conventional magnetic resonance imaging were 90.9%, 76.5%, 86.0%, respectively. Qualitative DWI analysis produced sensitivity, specificity, and accuracy values of 100.0, 88.2, and 96.0%, respectively. The ADC values were lower for patients with laryngeal carcinoma (mean 1.195±0.32×10−3 mm2/s) versus those with laryngeal precancerous lesions (mean 1.780±0.32×10−3 mm2/s; P<0.001). ROC analysis showed that the area under the curve was 0.956 and the optimum threshold for the ADC was 1.455×10−3 mm2/s, resulting in a sensitivity of 94.1%, a specificity of 90.9%, and an accuracy of 92.9%. Conclusions Despite some limitations, including the small number of laryngeal carcinomas included, DWI may detect changes in tumor size and shape before they are visible by laryngostroboscopy. The ADC values were lower for patients with laryngeal carcinoma than for those with laryngeal precancerous lesions. The proposed cutoff for the ADC may help distinguish laryngeal carcinomas from laryngeal precancerous lesions. PMID:23874693

[Study on relationship between blood supply from pulmonary artery and pathological characteristics of patients with primary bronchogenic carcinoma].

PubMed

Zhang, Yongkui; Le, Hanbo; Chen, Zhijun; Wang, Chaoye; Zhang, Binjie

2006-01-01

At present, it has been known that the bronchogenic artery participates in the blood supply of primary bronchogenic carcinoma, but there is controversy about the blood supply from pulmonary artery in primary bronchogenic carcinoma. The aim of this study is to assess the relationship between the blood supply from pulmonary artery and pathological characteristis of patients with primary bronchogenic carcinoma. The pulmonary arteries in 43 surgical samples of bronchogenic carcinoma were marked, then the iopromide was used to selective pulmonary arteriography in digital subtraction angiography (DSA). The relationship between tumor with blood supply from pulmonary artery and the pathologic characteristics was observed. There were 34 samples with blood supply from pulmonary artery ( 79.07%) , and 9 samples without blood supply from pulmonary artery (20.93%). The development rate of peripheral lung cancer (100.00%) was significantly higher than that of central lung cancer (64.00%) (P < 0.01) . The development rate of squamous cell carcinoma (91.30%) was remarkably higher than that of adenocarcinoma (61.11%) (P < 0.05). The development rate of poorly differentiated lung cancer (95.00%) was remarkably higher than that of well and moderately differentiated lung cancer (65.22%) (P < 0.05). There was a positive relationship between the tumor size and the development rate (P < 0.05). In primary bronchogenic carcinoma, the pulmonary artery blood supply exists in most of tumors. There is relationship between the blood supply from pulmonary artery and general type, histopathology, cell differentiation and tumor size of lung cancer. The blood supply from pulmonary artery doesn't relate to tumor stage.

Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels

PubMed Central

Alzamora, Rodrigo; O’Mahony, Fiona; Ko, Wing-Hung; Yip, Tiffany Wai-Nga; Carter, Derek; Irnaten, Mustapha; Harvey, Brian Joseph

2011-01-01

Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl− secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl− secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC50 80 ± 8 μM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K+ current by 88%, suggesting inhibition of KCNQ1 K+ channels. Berberine did not affect either apical Cl− conductance or basolateral Na+–K+-ATPase activity. Berberine stimulated p38 MAPK, PKCα and PKA, but had no effect on p42/p44 MAPK and PKCδ. However, berberine pre-treatment prevented stimulation of p42/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl− secretion was partially blocked by HBDDE (∼65%), an inhibitor of PKCα and to a smaller extent by inhibition of p38 MAPK with SB202190 (∼15%). Berberine treatment induced an increase in association between PKCα and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl− secretion through inhibition of basolateral KCNQ1 channels responsible for K+ recycling via a PKCα-dependent pathway. PMID:21747769

Oxidoreductive Cellulose Depolymerization by the Enzymes Cellobiose Dehydrogenase and Glycoside Hydrolase 61▿†

PubMed Central

Langston, James A.; Shaghasi, Tarana; Abbate, Eric; Xu, Feng; Vlasenko, Elena; Sweeney, Matt D.

2011-01-01

Several members of the glycoside hydrolase 61 (GH61) family of proteins have recently been shown to dramatically increase the breakdown of lignocellulosic biomass by microbial hydrolytic cellulases. However, purified GH61 proteins have neither demonstrable direct hydrolase activity on various polysaccharide or lignacious components of biomass nor an apparent hydrolase active site. Cellobiose dehydrogenase (CDH) is a secreted flavocytochrome produced by many cellulose-degrading fungi with no well-understood biological function. Here we demonstrate that the binary combination of Thermoascus aurantiacus GH61A (TaGH61A) and Humicola insolens CDH (HiCDH) cleaves cellulose into soluble, oxidized oligosaccharides. TaGH61A-HiCDH activity on cellulose is shown to be nonredundant with the activities of canonical endocellulase and exocellulase enzymes in microcrystalline cellulose cleavage, and while the combination of TaGH61A and HiCDH cleaves highly crystalline bacterial cellulose, it does not cleave soluble cellodextrins. GH61 and CDH proteins are coexpressed and secreted by the thermophilic ascomycete Thielavia terrestris in response to environmental cellulose, and the combined activities of T. terrestris GH61 and T. terrestris CDH are shown to synergize with T. terrestris cellulose hydrolases in the breakdown of cellulose. The action of GH61 and CDH on cellulose may constitute an important, but overlooked, biological oxidoreductive system that functions in microbial lignocellulose degradation and has applications in industrial biomass utilization. PMID:21821740

PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection

PubMed Central

Kraft, Anke R. M.; Wlodarczyk, Myriam F.; Kenney, Laurie L.

2013-01-01

Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV) infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8+ T cells cross-reactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4+ Foxp3+ T-regulatory (Treg) cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses also contributes to enhancing lung pathology upon LCMV infection of IAV-immune mice. Treg cell and interleukin-10 (IL-10) levels remained elevated in the lungs and mediastinal lymph nodes (mLNs) throughout the acute LCMV response of IAV-immune mice. PC61 treatment, used to decrease Treg cell levels, did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection in IAV-immune but not in naive mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8+ T-cell responses only in IAV-immune mice. PC61 treatment did not affect cross-reactive memory CD8+ T-cell proliferation. These results suggest that in the absence of IAV-expanded Treg cells and in the presence of cross-reactive memory, the LCMV-specific response was overstimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Treg cells generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories, PC61 treatment may lead to unexpected results. PMID:24049180

Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord (RTOG 9512)

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

Trotti, Andy, E-mail: andy.trotti@moffitt.org; Zhang, Qiang; Bentzen, Søren M.

2014-08-01

Purpose: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. Methods and Materials: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. Results: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239more » patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. Conclusions: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.« less

27 CFR 22.61 - Change in name of permittee.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Change in name of permittee. 22.61 Section 22.61 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... the Office of Management and Budget under control number 1512-0335) [T.D. ATF-199, 50 FR 9183, Mar. 6...

27 CFR 22.61 - Change in name of permittee.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Change in name of permittee. 22.61 Section 22.61 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... the Office of Management and Budget under control number 1512-0335) [T.D. ATF-199, 50 FR 9183, Mar. 6...

Translocation Renal Cell Carcinoma t(6;11)(p21;q12) and Sickle Cell Anemia: First Report and Review of the Literature.

PubMed

Chaste, Damien; Vian, Emmanuel; Verhoest, Gregory; Blanchet, Pascal

2014-02-01

Translocation renal cell carcinoma (RCC) is a family of rare tumors recently identified in the pediatric and young adult population. We report the first case of a young woman from French West Indies with sickle cell anemia who developed a translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition are known to develop renal medullary carcinoma (RMC). To our knowledge, this is the first case described in the literature of a translocation RCC associated with sickle cell disease. Here we discuss the relation between translocation RCC, RMC, and sickle cell disease.

Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients.

PubMed

Maneenil, Kunlatida; Xue, Zhiqiang; Liu, Ming; Boland, Jennifer; Wu, Fengying; Stoddard, Shawn M; Molina, Julian; Yang, Ping

2018-05-01

Pulmonary sarcomatoid carcinoma (PSC) is an unusual form of non-small-cell lung cancer (NSCLC). Because of its rarity and heterogeneity, the treatment and prognosis of PSC have not been clearly described. We retrospectively evaluated all patients with a diagnosis of PSC from 1997 to 2015 at the Mayo Clinic (Rochester, MN). The clinical characteristics, treatment details, and outcomes were collected. The survival rates of the PSC patients were compared with those for other subtypes of NSCLC. We used propensity score matching to minimize the bias resulting from to imbalanced comparison groups. The study included 127 PSC patients. The median age at diagnosis was 68 years (range, 32-89 years), most of whom were men (61%) and smokers (82%). The clinical stage was I, II, III, and IV in 15.9%, 20.6%, 22.2%, and 41.3%, respectively. The median survival time was 9.9 months (95% confidence interval [CI], 7.6-12.6 months). The 1-, 2-, and 5-year survival rates were 42%, 23%, and 15%, respectively. Most patients received multimodality treatment. Of the 3 patients who received neoadjuvant chemotherapy, a partial response was demonstrated in 2. Twenty-five patients who underwent palliative chemotherapy were evaluated for tumor response: 52% experienced progression, 40% stable disease, 8.0% a partial response, and 0% a complete response. Multivariate analysis showed T stage, M stage, and treatment with surgery plus neoadjuvant chemotherapy or surgery plus adjuvant therapy were independent prognostic factors (P < .05). In matched analysis, multivariate models revealed worse overall survival for PSC compared with adenocarcinoma (hazard ratio, 2.38; 95% CI, 1.61-2.53) and squamous cell carcinoma (hazard ratio, 2.20; 95% CI, 1.44-2.34). We found the outcome of PSC to be significantly worse than that of adenocarcinoma and squamous cell carcinoma. Neoadjuvant or adjuvant chemotherapy, in addition to surgical resection, should be considered. Copyright © 2017 Elsevier Inc. All rights

Synchronous Parotid (Mammary Analog) Secretory Carcinoma and Acinic Cell Carcinoma: Report of a Case.

PubMed

Mossinelli, C; Pigni, C; Sovardi, F; Occhini, A; Preda, L; Benazzo, M; Morbini, P; Pagella, F

2018-06-06

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade salivary gland malignancy with histologic, immunohistochemical and molecular similarities to secretory carcinoma of the breast, including a specific t(12;15)(p13;q25) resulting in an ETV6-NTRK3 gene fusion. Ultrasound and magnetic resonance imaging frequently document a macrocystic structure. The main differential diagnosis of secretory carcinoma is with low grade acinic cell carcinoma (AciCC). The two can be differentiated with immunohistochemical stains for S100, mammaglobin, carbonic anhydrase VI and DOG-1; the identification of the specific translocation can help to characterize non-typical cases. We report a unique case of synchronous MASC and AciCC presenting in a parotid gland and discuss the implications of the correct identification of the two tumors.

A different representation of natural T cells and natural killer cells between tumor-infiltrating and periphery lymphocytes in human hepatocellular carcinoma.

PubMed

Li, Xiao-Feng; Dai, Dong; Song, Xiu-Yu; Liu, Jian-Jing; Zhu, Lei; Zhu, Xiang; Ma, Wenchao; Xu, Wengui

2017-05-01

Natural T cells [cluster of differentiation (CD) 3 + CD56 + ] and natural killer (NK) cells (CD3 - CD56 + ) are particularly abundant in the human liver and serve an important role in immune responses in the liver. The aim of the present study was to extensively determine the phenotypic and functional characteristics of natural T and NK cells in human hepatocellular carcinoma (HCC). Tumorous and non-tumorous tissue infiltrating lymphocytes (TILs and NILs, respectively) and peripheral blood mononuclear cells (PBMCs) from patients with hepatocellular carcinoma (HCC) were obtained to determine the frequency and phenotype of natural T/NK cells by a multicolor fluorescence activated cell sorting analysis. The abundance of natural T cells and NK cells was decreased in TILs vs. NILs (natural T cells, 6.315±1.002 vs. 17.16±1.804; NK cells, 6.324±1.559 vs. 14.52±2.336, respectively). However such results were not observed in PBMCs from HCC patients vs. that of healthy donors. Notably, a substantial fraction of the natural T cells (21.96±5.283) in TILs acquired forkhead box P3 (FOXP3) expression, and the FOXP3 + natural T cells lost the expression of interferon-γ and perforin. Conversely, being similar to the conventional FOXP3 + regulatory T cells, the FOXP3 + natural T cells assumed a specific phenotype that was characteristic of CD25 + , CD45RO + and cytotoxic T-lymphocyte-associated protein 4 + . Consistent with the phenotypic conversion, the present functional results indicate that FOXP3 expression in natural T cells contributes to the acquisition of a potent immunosuppressive capability. In conclusion, the present study describes a different representation of natural T cells and NK cells in local tumor tissues and in the periphery blood of patients with HCC, and identified a new type of FOXP3-expressing natural T cell spontaneously arising in the TILs of HCC.

Review of renal carcinoma with t(6;11)(p21;q12) with focus on clinical and pathobiological aspects.

PubMed

Kuroda, Naoto; Tanaka, Azusa; Sasaki, Naomi; Ishihara, Akira; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Inoue, Keiji; Petersson, Fredrik; Martignoni, Guido; Michal, Michal; Hes, Ondrej

2013-06-01

Recently, a new category of MiTF/TFE family translocation carcinomas of the kidney has been proposed. This category includes Xp11.2 renal cell carcinoma (RCC) and the t(6;11) RCC. These tumors share clinical, morphological, immunohistochemical and molecular genetic features. In this article, we review t(6;11) RCC. This tumor predominantly affects children and young adults. Macroscopically, the tumor generally forms a well circumscribed mass. Satellite nodules may be observed. Histologically, the tumor comprises large cells and small cells surrounded by basement membrane material. Immunohistochemically, tumor cells show nuclear immunolabeling for TFEB and usually express Cathepsin-K in the cytoplasm. Karyotyping detects the rearrangement between chromosome 6p21 and chromosome 11q12. Alpha-TFEB fusion can be detected by reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Most cases affecting children and young adults seem to be indolent, but some adult cases have presented with metastasis or caused death. As previously reported cases remain limited to date, further examination in a large scale study will be needed in order to elucidate clinical behavior and molecular characteristics.

Analysis of the t(3;8) of Hereditary Renal Cell Carcinoma: A Palindrome-Mediated Translocation

PubMed Central

Kato, Takema; Franconi, Colleen P.; Sheridan, Molly B.; Hacker, April M.; Inagakai, Hidehito; Glover, Thomas W.; Arlt, Martin F.; Drabkin, Harry A.; Gemmill, Robert M.; Kurahashi, Hiroki; Emanuel, Beverly S.

2014-01-01

It has emerged that palindrome-mediated genomic instability generates DNA-based rearrangements. The presence of palindromic AT-rich repeats (PATRRs) at the translocation breakpoints suggested a palindrome-mediated mechanism in the generation of several recurrent constitutional rearrangements: the t(11;22), t(17;22) and t(8;22). To date, all reported PATRR mediated translocations include the PATRR on chromosome 22 (PATRR22) as a translocation partner. Here, the constitutional rearrangement, t(3;8)(p14.2;q24.1), segregating with renal cell carcinoma in two families, is examined. The chromosome 8 breakpoint lies in PATRR8 in the first intron of the RNF139 (TRC8) gene while the chromosome 3 breakpoint is located in an AT-rich palindromic sequence in intron 3 of the FHIT gene (PATRR3). Thus, the t(3;8) is the first PATRR-mediated, recurrent, constitutional translocation that does not involve PATRR22. Furthermore, similar to the t(11;22) and t(8;22), we detect de novo translocations involving PATRR3 in normal sperm. The breakpoint on chromosome 3 is in proximity to FRA3B, the most common fragile site in the human genome and a site of frequent deletions in tumor cells. However, the lack of involvement of PATRR3 sequence in numerous FRA3B-related deletions suggests that there are several different DNA sequence based etiologies responsible for chromosome 3p14.2 genomic rearrangements. PMID:24813807

Structural changes induced by L50P and I61T single mutations of ubiquitin affect cell cycle progression while impairing its regulatory and degradative functions in Saccharomyces cerevisiae.

PubMed

Doshi, Ankita; Sharma, Mrinal; Prabha, C Ratna

2017-06-01

Posttranslational conjugation of ubiquitin to proteins either regulates their function directly or concentration through ubiquitination dependent degradation. High degree of conservation of ubiquitin's sequence implies structural and functional importance of the conserved residues. Ubiquitin gene of Saccharomyces cerevisiae was evolved in vitro by us to study the significance of conserved residues. Present study investigates the structural changes in the protein resulting from the single mutations UbS20F, UbA46S, UbL50P, UbI61T and their functional consequences in the SUB60 strain of S. cerevisiae. Expression of UbL50P and UbI61T decreased Cdc28 protein kinase, enhanced Fus3 levels, caused dosage dependent lethality and at sublethal level produced drastic effects on stress tolerance, protein sorting, protein degradation by ubiquitin fusion degradation pathway and by lysosomes. UbS20F and UbA46S produced insignificant effects over the cells. All four mutations of ubiquitin were incorporated into polyubiquitin. However, polyubiquitination with K63 linkage decreased significantly in cells expressing UbL50P and UbI61T. Structural studies on UbL50P and UbI61T revealed distorted structure with greatly reduced α-helical and elevated β-sheet contents, while UbS20F and UbA46S show mild structural alterations. Our results on functional efficacy of ubiquitin in relation to structural integrity may be useful for designing inhibitors to investigate and modulate eukaryotic cellular dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine

PubMed Central

Heron, Valérie; Fortinsky, Kyle Joshua; Spiegle, Gillian; Hilzenrat, Nir; Szilagyi, Andrew

2016-01-01

Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID:27403102

Small (≤ 2 cm) hepatocellular carcinoma in patients with chronic liver disease: comparison of gadoxetic acid-enhanced 3.0 T MRI and multiphasic 64-multirow detector CT.

PubMed

Hwang, J; Kim, S H; Lee, M W; Lee, J Y

2012-07-01

To compare the diagnostic performance of gadoxetic acid-enhanced MRI using 3.0 T with that of multiphasic 64-multirow detector CT (MDCT) for the detection of small (≤2 cm) hepatocellular carcinoma (HCC) in patients with chronic liver disease. A total of 54 patients (44 men, 10 women; age range, 33-81 years) with 59 HCCs (≤2 cm in diameter) who underwent both multiphasic (arterial, portal venous, equilibrium) 64-MDCT and gadoxetic acid-enhanced 3.0 T MRI were enrolled in this study. Two observers independently and randomly reviewed the MR and CT images on a lesion-by-lesion basis. The diagnostic performance of these techniques for the detection of HCC was assessed by alternative free-response receiver operating characteristic (ROC) analysis, in addition to evaluating the sensitivity and positive predictive value. For each observer, the areas under the ROC curve were 0.874 and 0.863 for MRI, respectively, as opposed to 0.660 and 0.687 for CT, respectively. The differences between the two techniques were statistically significant for each observer (p<0.001). The sensitivities (89.8% and 86.4%) of MRI for both observers were significantly higher than those (57.6% and 61.0% for each observer, respectively) of MDCT. No significant difference was seen between the positive predictive values for the two techniques (p>0.05). Gadoxetic acid-enhanced 3.0 T MRI shows a better diagnostic performance than that of 64-MDCT for the detection of small (≤2 cm) HCCs in patients with chronic liver disease.

Concentration of potentially toxic elements in field crops grown near and far from cities of the Pampas (Argentina).

PubMed

Lavado, Raúl S

2006-07-01

Soils of the Pampas show no signs of contamination with potentially toxic elements (PTEs), except in the areas that surround cities. The concentration of PTE in crops grown in this region is in most cases unknown. Our objective was to determine the PTE concentration in main field crops and pastures grown in 'a priori' non-contaminated areas and in potentially contaminated areas around cities. Forty-eight plots from farms located far from cities or roads and 36 plots from farms located very close to cities or to high traffic roads were sampled. The area ranged from 33 degrees 40' S to 36 degrees 0' S and from 57 degrees 35' W to 61 degrees 22' W. Maize, soybean, wheat, grazed grassland and pastures, and their top soils were sampled. All samples were acid digested. Cadmium, zinc, chromium, copper, nickel and lead were determined using ICPES. Standard t-tests were performed. All soils were within the known normal values of soil PTE concentrations, with the exception of a few cases around cities. PTE accumulation on grains and aerial biomass is considered almost negligible in crops grown in both studied areas, with the exception of a few elements in soybean. PTE concentrations in crops and pastures are in keeping with the low content of trace metals found in soils of the Pampas.

SU-E-T-352: Why Is the Survival Rate Low in Oropharyngeal Squamous Cell Carcinoma?

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

Huang, Z; Feng, Y; Rasmussen, K

2014-06-01

Purpose: Tumors are composed of a large number of clonogens that have the capability of indefinite reproduction. Even when there is complete clinical or radiographic regression of the gross tumor mass after treatment, tumor recurrence can occur if the clonogens are not completely eradicated by radiotherapy. This study was to investigate the colonogen number and its association with the tumor control probability (TCP) in oropharyngeal squamous cell carcinoma (OSCCA). Methods: A literature search was conducted to collect clinical information of patients with OSCCA, including the prescription dose, tumor volume and survival rate. The linear-quadratic (LQ) model was incorporated into TCPmore » model for clinical data analysis. The total dose ranged from 60 to 70 Gy and tumor volume ranged from 10 to 50 cc. The TCP was calculated for each group according to tumor size and dose. The least χ{sup 2} method was used to fit the TCP calculation to clinical data while other LQ model parameters (α, β) were adopted from the literature, due to the limited patient data. Results: A total of 190 patients with T2–T4 OSCCA were included. The association with HPV was not available for all the patients. The 3-year survival rate was about 82% for T2 squamous cell carcinoma and 40% for advanced tumors. Fitting the TCP model to the survival data, the average clonogen number was 1.56×10{sup 12}. For the prescription dose of 70 Gy, the calculated TCP ranged from 40% to 90% when the tumor volume varied from 10 to 50 cc. Conclusion: Our data suggests variation between the clonogen number and TCP in OSCCA. Tumors with larger colonogen number tend to have lower TCP and therefore dose escalation above 70 Gy may be indicated in order to improve the TCP and survival rate. Our result will require future confirmation with a large number of patients.« less

Phenotypic Intratumoral Heterogeneity of Endometrial Carcinomas.

PubMed

Silva, Cátia; Pires-Luís, Ana S; Rocha, Eduardo; Bartosch, Carla; Lopes, José M

2018-03-01

Intratumoral heterogeneity has been shown to play an important role in diagnostic accuracy, development of treatment resistance, and prognosis of cancer patients. Recent studies have proposed quantitative measurement of phenotypic intratumoral heterogeneity, but no study is yet available in endometrial carcinomas. In our study we evaluated the phenotypic intratumoral heterogeneity of a consecutive series of 10 endometrial carcinomas using measures of dispersion and diversity. Morphometric architectural (%tumor cells, %solid tumor, %differentiated tumor, and %lumens) and nuclear [volume-weighted mean nuclear volume ((Equation is included in full-text article.))] parameters, as well as estrogen receptor, progesterone receptor, p53, vimentin, and beta-catenin immunoexpression (H-score) were digitally analyzed in 20 microscopic fields per carcinoma. Quantitative measures of intratumoral heterogeneity included coefficient of variation (CV) and relative quadratic entropy (rQE). In each endometrial carcinoma there was slight variation of architecture from field to field, resulting in globally low levels of heterogeneity measures (mean CV %tumor cells: 0.10, %solid tumor: 0.73, %differentiated tumor: 0.19, %lumens: 0.61 and mean rQE %tumor cells: 18.5, %solid tumor: 20.3, %differentiated tumor: 25.6, %lumens: 21.8). Nuclear intratumoral heterogeneity was also globally low (mean (Equation is included in full-text article.)CV: 0.23 and rQE: 27.3), but significantly higher than the heterogeneity of architectural parameters within most carcinomas. In general, there was low to moderate variability of immunoexpression markers within each carcinoma, but estrogen receptor (mean CV: 0.56 and rQE: 46.2) and progesterone receptor (mean CV: 0.60 and rQE: 39.3) displayed the highest values of heterogeneity measures. Intratumoral heterogeneity of immunoexpression was significantly higher than that observed for morphometric parameters. In conclusion, our study indicates that endometrial

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features

PubMed Central

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2014-01-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts—we designate this variant as ‘chromophobe hepatocellular carcinoma with abrupt anaplasia’. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P = 0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

PubMed

Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

2013-12-01

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of

Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor.

PubMed

Tu, Zheng; Gui, Liming; Wang, Jianliu; Li, Xiaoping; Sun, Pengming; Wei, Lihui

2006-05-01

To investigate the tumorigenesis of mutant [12Asp]-K-ras in endometrial carcinoma and its relationship with ER. We constructed pcDI-[12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell transformation was determined by colony formation and tumor nodule development. [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV-RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to determine the expression and transcriptional activity of ERalpha and ERbeta, respectively. [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after 48 h post-transfection (P < 0.05). More colonies were grown 10 days after incubating pcDI-[12Asp]-K-ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12 days. An increase of ERalpha and ERbeta was observed in pcDI-[12Asp]-K-ras4B-NIH3T3 cells. RafS621A downregulated ERalpha and ERbeta expression. Estrogen induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER transcriptional activity. K-ras mutation induces tumorigenesis in endometrium, and this malignant transformation involves Raf signaling pathway and ER.

Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma.

PubMed

Zeng, Dingyuan; Lin, Jiajing; He, Hongying; Tan, Guangping; Lan, Ying; Jiang, Fuyan; Sheng, Shuting

2018-02-01

The present study aimed to investigate the therapeutic effect and safety of targeted use of Fas-expressing adenoviruses combined with γδ T cell-mediated killing to treat human ovarian cancer xenografts in BALB/c mice. Shuttle plasmids containing control elements of human telomerase reverse transcriptase promoter and two-step transcriptional amplification system were constructed and packaged into adenovirus-5 vectors to generate expression of an exogenous Fas gene. A mouse xenograft model of human ovarian carcinoma was constructed. A total of 35 BALB/c mice were randomly divided into five groups, which were injected with PBS, γδ T cells, Fas-expressing adenoviruses, taxol, or Fas-expressing adenovirus and γδ T cells. The weight and volume of tumors in mice in each group was monitored. Tissue sections of the various tissues of mice in the Fas-expressing adenovirus and γδ T cells group was compared with those in the PBS group to evaluate the safety of Fas-expressing adenovirus and γδ T cells in the treatment of human ovarian cancer xenograft tumors. The results of the present study indicated that mice in all treatment groups were alive at the end of the treatment course. Tumor weight and volume was the highest in the PBS group, followed successively by the adenovirus group, the γδ T cell group, the adenovirus and γδ T cell group, and the taxol group. The weight and volume inhibition rate in adenovirus and γδ T cell group were significantly higher compared with in the PBS group (P<0.05). Pathological observation of tissue samples revealed that none of vital organs in the adenovirus and γδ T cell group developed any evident morphological changes during treatment, when compared with healthy controls. In conclusion, the combined therapy with Fas-expressing adenoviruses and γδ T cells is efficient and safe for the treatment of mouse human ovarian carcinoma xenografts.

Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients.

PubMed

Park, Ji Young; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Kim, Dae-Yeon; Sohn, Insuk; Lee, Shin-Wha; Sung, Chang Ohk; Kim, Kyu-Rae

2013-03-01

Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62-2.27) was demonstrated in USC than in G3EC (P < 0.001). In conclusion, our study reveals that USC is associated with a poorer prognosis compared with G3EC, only in patients with early stage carcinoma, suggesting that different treatment strategies should be considered according to the histologic type in order to improve treatment outcome.

Tracheal epithelial-myoepithelial carcinoma associated with sarcoid-like reaction: A case report

PubMed Central

Dong, Huawei; Tatsuno, Brent K.; Betancourt, Jaime; Oh, Scott S.

2014-01-01

Epithelial-myoepithelial carcinomas are rare tumors that primarily originate in the salivary glands but have also been found in the tracheobronchial tree. We report the first case of epithelial-myoepithelial carcinoma associated with sarcoidosis. A 61 year old Hispanic man presented with altered mental status and hypercalcemia. Imaging revealed diffuse intra-thoracic and intra-abdominal lymphadenopathy. A diagnostic bronchoscopy was performed where an incidental tracheal nodule was discovered and biopsied. Pathology was consistent with epithelial-myoepithelial carcinoma. Lymph node biopsy demonstrated non-caseating granulomas consistent with sarcoidosis. Patient underwent tracheal resection of the primary tumor with primary tracheal reconstruction. Hypercalcemia subsequently normalized with clinical improvement. Repeat CT imaging demonstrated complete resolution of lymphadenopathy. Our findings are suggestive of a possible paraneoplastic sarcoid-like reaction to the epithelial-myoepithelial carcinoma with associated lymphadenopathy and symptomatic hypercalcemia. PMID:26029574

Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.

PubMed

Asma, Gati; Amal, Gorrab; Raja, Marrakchi; Amine, Derouiche; Mohammed, Chebil; Amel, Ben Ammar Elgaaied

2015-05-01

The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

The Proteome of Shigella flexneri 2a 2457T Grown at 30 and 37 °C*

PubMed Central

Zhu, Li; Zhao, Ge; Stein, Robert; Zheng, Xuexue; Hu, Wei; Shang, Na; Bu, Xin; Liu, Xiankai; Wang, Jie; Feng, Erling; Wang, Bin; Zhang, Xuemin; Ye, Qinong; Huang, Peitang; Zeng, Ming; Wang, Hengliang

2010-01-01

To upgrade the proteome reference map of Shigella flexneri 2a 2457T, the protein expression profiles of log phase and stationary phase cells grown at 30 and 37 °C were thoroughly analyzed using multiple overlapping narrow pH range (between pH 4.0 and 11.0) two-dimensional gel electrophoresis. A total of 723 spots representing 574 protein entries were identified by MALDI-TOF/TOF MS, including the majority of known key virulence factors. 64 hypothetical proteins and six misannotated proteins were also experimentally identified. A comparison between the four proteome maps showed that most of the virulence-related proteins were up-regulated at 37 °C, and the differences were more notable in stationary phase cells, suggesting that the expressions of these virulence factors were not only controlled by temperature but also controlled by the nutrients available in the environment. The expression patterns of some virulence-related genes under the four different conditions suggested that they might also be regulated at the post-transcriptional level. A further significant finding was that the expression of the protein ArgT was dramatically up-regulated at 30 °C. The results of semiquantitative RT-PCR analysis showed that expression of argT was not regulated at the transcriptional level. Therefore, we carried out a series of experiments to uncover the mechanism regulating ArgT levels and found that the differential expression of ArgT was due to its degradation by a periplasmic protease, HtrA, whose activity, but not its synthesis, was affected by temperature. The cleavage site in ArgT was between position 160 (Val) and position 161 (Ala). These results may provide useful insights for understanding the physiology and pathogenesis of S. flexneri. PMID:20164057

The proteome of Shigella flexneri 2a 2457T grown at 30 and 37 degrees C.

PubMed

Zhu, Li; Zhao, Ge; Stein, Robert; Zheng, Xuexue; Hu, Wei; Shang, Na; Bu, Xin; Liu, Xiankai; Wang, Jie; Feng, Erling; Wang, Bin; Zhang, Xuemin; Ye, Qinong; Huang, Peitang; Zeng, Ming; Wang, Hengliang

2010-06-01

To upgrade the proteome reference map of Shigella flexneri 2a 2457T, the protein expression profiles of log phase and stationary phase cells grown at 30 and 37 degrees C were thoroughly analyzed using multiple overlapping narrow pH range (between pH 4.0 and 11.0) two-dimensional gel electrophoresis. A total of 723 spots representing 574 protein entries were identified by MALDI-TOF/TOF MS, including the majority of known key virulence factors. 64 hypothetical proteins and six misannotated proteins were also experimentally identified. A comparison between the four proteome maps showed that most of the virulence-related proteins were up-regulated at 37 degrees C, and the differences were more notable in stationary phase cells, suggesting that the expressions of these virulence factors were not only controlled by temperature but also controlled by the nutrients available in the environment. The expression patterns of some virulence-related genes under the four different conditions suggested that they might also be regulated at the post-transcriptional level. A further significant finding was that the expression of the protein ArgT was dramatically up-regulated at 30 degrees C. The results of semiquantitative RT-PCR analysis showed that expression of argT was not regulated at the transcriptional level. Therefore, we carried out a series of experiments to uncover the mechanism regulating ArgT levels and found that the differential expression of ArgT was due to its degradation by a periplasmic protease, HtrA, whose activity, but not its synthesis, was affected by temperature. The cleavage site in ArgT was between position 160 (Val) and position 161 (Ala). These results may provide useful insights for understanding the physiology and pathogenesis of S. flexneri.

Carcinoma gallbladder.

PubMed

Biswas, P K

2010-07-01

Carcinoma gallbladder (CaGb) is a rare disease. The aetiology of CaGb is yet not known. However the risk of CaGb is increased in anomalous pancreaticobiliary duct junction (APBDJ), gall stones, xanthogranulomatus cholecystitis, calcified or porcelain gallbladder, cholelithiasis with typhoid carriers, gallbladder adenoma, red meat consumption and tobacco uses. There are protective effects of vegetables on CaGb. Most of the cases present with advanced disease. In early carcinoma of a gallbladder sign and symptoms mimic benign disease. The diagnosis is established by ultrasonography, computerized tomography and guided fine needle aspiration cytology (FNAC). Biochemical tests are of very little value in making a diagnosis. The treatment depends on the clinical stage at presentation. Surgery offers the best chance of cure. In stage T1a, laparoscopic or open cholecystectomy alone is curative, and in T1b, cholecystectomy with hepatoduodenal lymph node dissection without combined resection of an adjacent organ is required. Segment S4a+5 hepatectomy combined with extrahepatic bile duct resection (BDR) and D2 lymph node dissection is a highly recommended operation for the treatment of T2 and T3 CaGb. The dye injection method is useful in determining the appropriate extent of hepatic resection for advanced CaGb. Resurgery is required only in those cases where tumour has invaded the serosa and/ or adjacent structures when diagnosed postoperatively. Biliary bypass is required for palliation. Prognosis depends on early diagnosis and appropriate surgical excision.

Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma.

PubMed

Song, Y-P; Ma, J-B; Hu, L-K; Zhou, W; Chen, E-C; Zhang, W

2011-02-01

Compared to conventional fractionated-dose radiotherapy, high hypofractionated-dose radiotherapy could yield tumoricidal effects. However, few clinical trials of hypofractionated radiotherapy in loco-regionally advanced incurable esophageal cancer at present have yet been performed. The purpose of the current study was to evaluate the efficacy and toxicity of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. From September 2003 to December 2005, 45 patients with locally advanced esophageal carcinoma were grouped and received three-dimensional conformal hypofractioned radiotherapy (3D-CRT) whose fractionated dose was gradually increase per group. Radiotherapy was administered to a total dose of from 50 to 54 Gy (fractionated dose of from 3.0 to 6.0 Gy, 3 times weekly), over a 3-4 week period. And patients received 4 cycles chemotherapy. The median follow-up period for survivors was 38 months. Treatment tolerance rate was 78.8% with daily dose of from 3 to 5 Gy. There are 21.2% patients occurring Grade ≥ 3 acute toxicities. But patients couldn't tolerate daily dose of 6 Gy (55.6%). The 1-year, 2-year and 3-year local control rates were 62%, 49% and 39% respectively. And the 1-year, 2-year and 3-year overall survival rates were 34%, 21% and 9% respectively. The median overall survival time was 17 months. At the time of following up, 13 patients (31.0%) had occurred esophageal late complications, with mainly esophageal perforation, hemorrhage or stenosis, including initial stenosis aggravation. Therefore hypofractionated irradiation was thought to be feasible for clinical T3-4N0-1M0 stage esophageal carcinoma. And daily dose of ≤5 Gy was comparatively suitable in hypofractionated irradiation for esophageal carcinoma, and the patients tolerated well. But further research was in need also.

Inferior vena cava tumor thrombus after partial nephrectomy for renal cell carcinoma.

PubMed

Akatsuka, Jun; Suzuki, Yasutomo; Hamasaki, Tsutomu; Shindo, Takao; Yanagi, Masato; Kimura, Go; Yamamoto, Yoichiro; Kondo, Yukihiro

2014-03-29

Partial nephrectomy is now the gold standard treatment for small renal tumors. Local recurrence is a major problem after partial nephrectomy, and local recurrence in the remnant kidney after partial nephrectomy is common. A 77-year-old man underwent right partial nephrectomy for a T1 right renal cell carcinoma. Microscopic examination revealed a clear cell renal carcinoma, grade 2, stage pT3a. Although the surgical margin was negative, the carcinoma invaded the perirenal fat, and vascular involvement was strongly positive. Thirty months after partial nephrectomy, an enhanced computed tomographic scan showed local recurrence of the renal cell carcinoma extending into the inferior vena cava without renal mass. Hence, we performed right radical nephrectomy and intracaval thrombectomy. Microscopic examination revealed a clear cell carcinoma grade 2, stage pT3a + b. The patient is still alive with no evidence of recurrence 10 months post-procedure. To our knowledge, local recurrence of renal cell carcinoma extending into the inferior vena cava after partial nephrectomy has not been reported in the literature. Our case report emphasizes the importance of strict surveillance of patients after partial nephrectomy, especially for those with renal cell carcinoma positive for microvessel involvement.

TNF-alpha induction of GM2 expression on renal cell carcinomas promotes T cell dysfunction.

PubMed

Raval, Gira; Biswas, Soumika; Rayman, Patricia; Biswas, Kaushik; Sa, Gaurisankar; Ghosh, Sankar; Thornton, Mark; Hilston, Cynthia; Das, Tanya; Bukowski, Ronald; Finke, James; Tannenbaum, Charles S

2007-05-15

Previous studies from our laboratory demonstrated the role of tumor-derived gangliosides as important mediators of T cell apoptosis, and hence, as one mechanism by which tumors evade immune destruction. In this study, we report that TNF-alpha secreted by infiltrating inflammatory cells and/or genetically modified tumors augments tumor-associated GM2 levels, which leads to T cell death and immune dysfunction. The conversion of weakly apoptogenic renal cell carcinoma (RCC) clones to lines that can induce T cell death requires 3-5 days of TNF-alpha pretreatment, a time frame paralleling that needed for TNF-alpha to stimulate GM2 accumulation by SK-RC-45, SK-RC-54, and SK-RC-13. RCC tumor cell lines permanently transfected with the TNF-alpha transgene are similarly toxic for T lymphocytes, which correlates with their constitutively elevated levels of GM2. TNF-alpha increases GM2 ganglioside expression by enhancing the mRNA levels encoding its synthetic enzyme, GM2 synthase, as demonstrated by both RT-PCR and Southern analysis. The contribution of GM2 gangliosides to tumor-induced T cell death was supported by the finding that anti-GM2 Abs significantly blocked T cell apoptosis mediated by TNF-alpha-treated tumor cells, and by the observation that small interfering RNA directed against TNF-alpha abrogated GM2 synthase expression by TNF-transfected SK-RC-45, diminished its GM2 accumulation, and inhibited its apoptogenicity for T lymphocytes. Our results indicate that TNF-alpha signaling promotes RCC-induced killing of T cells by stimulating the acquisition of a distinct ganglioside assembly in RCC tumor cells.

Treatment and Prognosis of Squamous Cell Carcinoma of the External Auditory Canal and Middle Ear: A Multi-Institutional Retrospective Review of 87 Patients

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

Ogawa, Kazuhiko; Nakamura, Katsumasa; Hatano, Kazuo

Purpose: To examine the relative roles of surgery, radiotherapy, and chemotherapy in the management of patients with squamous cell carcinomas of the external auditory canal and middle ear. Methods and Materials: The records of 87 patients with histologically confirmed squamous cell carcinoma who were treated between 1984 and 2005 were reviewed. Fifty-three patients (61%) were treated with surgery and radiotherapy (S + RT group) and the remaining 34 patients with radiotherapy alone (RT group). Chemotherapy was administered in 34 patients (39%). Results: The 5-year actuarial overall and disease-free survival (DFS) rates for all patients were 55% and 54%, respectively. Onmore » univariate analysis, T stage (Stell's classification), treatment modality, and Karnofsky performance status had significant impact on DFS. On multivariate analysis, T stage and treatment modality were significant prognostic factors. Chemotherapy did not influence DFS. The 5-year DFS rate in T1, T2, and T3 patients was 83%, 45%, and 0 in the RT group (p < 0.0001) and 75%, 75%, and 46% in the S + RT group (p = 0.13), respectively. The 5-year DFS rate in patients with negative surgical margins, those with positive margins, and those with macroscopic residual disease was 83%, 55%, and 38%, respectively (p = 0.007). Conclusions: Radical radiotherapy is the treatment of choice for early-stage (T1) diseases, whereas surgery (negative surgical margins if possible) with radiotherapy is recommended as the standard care for advanced (T2-3) disease. Further clarification on the role of chemotherapy is necessary.« less

Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

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

Oberholzer, Katja, E-mail: oberholz@radiologie.klinik.uni-mainz.de; Menig, Matthias; Kreft, Andreas

2012-02-01

Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgicalmore » specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p {<=} 0.001). Positive resection margins (ypCRM {<=} 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p {<=} 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.« less

Treatment and prognosis of primary thymic carcinoma.

PubMed

Yano, T; Hara, N; Ichinose, Y; Asoh, H; Yokoyama, H; Ohta, M

1993-04-01

From 1972 to 1990, we treated eight cases of thymic carcinoma (6 squamous cell and 2 small cell carcinomas). According to the classification by Masaoka et al., they consisted of one stage I, four stage III, one stage IVa, and two stage IVb. A complete resection of the primary tumour could be done in only three patients; the others had diagnostic biopsy and then radiation treatment. Four of five patients had a prolonged regression of the primary tumors after irradiation at 40-61.2 Gy. Six patients suffered from extrathoracic metastases. All patients received systemic chemotherapy with different regimens to counter either metastatic or locally recurrent lesions. Only two patients (with a regimen including cyclophosphamide, doxorubicin, and vincristine) obtained a partial response. The median survival of the eight patients was 70 months after surgical operation. The identification of an effective drug combination may thus improve the long-term prognosis of thymic carcinoma since radiotherapy is able to control primary lesions, even in the case of unresectable advanced disease.

Utility of histogram analysis of apparent diffusion coefficient maps obtained using 3.0T MRI for distinguishing uterine carcinosarcoma from endometrial carcinoma.

PubMed

Takahashi, Masahiro; Kozawa, Eito; Tanisaka, Megumi; Hasegawa, Kousei; Yasuda, Masanori; Sakai, Fumikazu

2016-06-01

We explored the role of histogram analysis of apparent diffusion coefficient (ADC) maps for discriminating uterine carcinosarcoma and endometrial carcinoma. We retrospectively evaluated findings in 13 patients with uterine carcinosarcoma and 50 patients with endometrial carcinoma who underwent diffusion-weighted imaging (b = 0, 500, 1000 s/mm(2) ) at 3T with acquisition of corresponding ADC maps. We derived histogram data from regions of interest drawn on all slices of the ADC maps in which tumor was visualized, excluding areas of necrosis and hemorrhage in the tumor. We used the Mann-Whitney test to evaluate the capacity of histogram parameters (mean ADC value, 5th to 95th percentiles, skewness, kurtosis) to discriminate uterine carcinosarcoma and endometrial carcinoma and analyzed the receiver operating characteristic (ROC) curve to determine the optimum threshold value for each parameter and its corresponding sensitivity and specificity. Carcinosarcomas demonstrated significantly higher mean vales of ADC, 95th, 90th, 75th, 50th, 25th percentiles and kurtosis than endometrial carcinomas (P < 0.05). ROC curve analysis of the 75th percentile yielded the best area under the ROC curve (AUC; 0.904), sensitivity of 100%, and specificity of 78.0%, with a cutoff value of 1.034 × 10(-3) mm(2) /s. Histogram analysis of ADC maps might be helpful for discriminating uterine carcinosarcomas and endometrial carcinomas. J. Magn. Reson. Imaging 2016;43:1301-1307. © 2015 Wiley Periodicals, Inc.

Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma.

PubMed Central

Gamallo, C.; Palacios, J.; Suarez, A.; Pizarro, A.; Navarro, P.; Quintanilla, M.; Cano, A.

1993-01-01

Recently, a correlation has been suggested between a loss of E-cadherin (E-CD) and increased invasiveness of neoplastic cells. In this study, E-CD expression in breast cancer was investigated using an affinity-purified antibody (ECCD-2) in an immunoenzymatic (avidin-biotin-alkaline phosphatase) test. Intensity and extension of E-CD immunoreactivity were evaluated in 61 breast carcinomas and correlated with their histological type and grade, nodal involvement, and hormonal receptor status. Histological types were infiltrating ductal carcinoma of no special type (n = 54) and infiltrating lobular carcinoma (n = 7). All infiltrating ductal carcinomas of no special type except two grade 3 carcinomas showed positive immunoreactivity that was variable among different cases. Grade 1 breast carcinomas (n = 10) showed greater immunoreactivity than grade 2 (n = 25) and grade 3 (n = 19) carcinomas. E-CD immunoreactivity correlated positively with the degree of tubular formation and inversely with the mitoses number. None of the infiltrating lobular carcinomas expressed E-CD in their infiltrating cells, whereas they showed only weak immunostains in areas of atypical lobular hyperplasia and lobular carcinoma in situ. These results indicate that E-CD expression correlates with histological type and grade in breast carcinomas. Images Figure 1 Figure 2 Figure 3 PMID:7682767

Warburg phenotype in renal cell carcinoma: high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8(+) T-cell infiltration in the tumor.

PubMed

Singer, Katrin; Kastenberger, Michael; Gottfried, Eva; Hammerschmied, Christine G; Büttner, Maike; Aigner, Michael; Seliger, Barbara; Walter, Bernhard; Schlösser, Hans; Hartmann, Arndt; Andreesen, Reinhard; Mackensen, Andreas; Kreutz, Marina

2011-05-01

Many tumor cells are characterized by a dysregulated glucose metabolism associated with increased glycolysis in the presence of oxygen ("Warburg Effect"). Here, we analyzed for the first time a possible link between glucose metabolism and immune cell infiltration in renal cell carcinoma (RCC). RCC specimens revealed a highly significant increase in the expression of lactate dehydrogenase A (LDHA) and glucose-transporter 1 (GLUT-1) compared to the corresponding normal kidney tissue on mRNA level. Accordingly, tumor cell lines of different origin such as RCC, melanoma and hepatocellular carcinoma strongly expressed LDHA and GLUT-1 compared to their nonmalignant counterparts. In line with this finding, tumor cells secreted high amounts of lactate. High expression of GLUT-1 and LDH5, a tetramer of 4 LDHA subunits, was confirmed by tissue microarray analysis of 249 RCC specimens. Overall, 55/79 (69.6%) and 46/71 (64.7%) cases of clear cell carcinoma showed a constitutive, but heterogeneous expression of GLUT-1 and LDH5, respectively. The number of CD3(+), CD8(+) and FOXP3(+) T cells was significantly elevated in RCC lesions compared to normal kidney epithelium, but effector molecules such as granzyme B and perforin were decreased in tumor infiltrating T cells. Of interest, further analysis revealed an inverse correlation between GLUT-1 expression and the number of CD8(+) T cells in RCC lesions. Together, our data suggest that an accelerated glucose metabolism in RCC tissue is associated with a low infiltration of CD8(+) effector T cells. Targeting the glucose metabolism may represent an interesting tool to improve the efficacy of specific immunotherapeutic approaches in RCC. Copyright © 2010 UICC.

Expression and role of anion exchanger 1 in esophageal squamous cell carcinoma.

PubMed

Shiozaki, Atsushi; Kudou, Michihiro; Ichikawa, Daisuke; Shimizu, Hiroki; Arita, Tomohiro; Kosuga, Toshiyuki; Konishi, Hirotaka; Komatsu, Shuhei; Fujiwara, Hitoshi; Okamoto, Kazuma; Kishimoto, Mitsuo; Marunaka, Yoshinori; Otsuji, Eigo

2017-03-14

Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category. Among patients with pT2-3 ESCC, the 5-year survival rate of patients with diffuse AE1 expression (40.2%) was significantly lower than that of patients with focal expression (74.0%). AE1 was strongly expressed in KYSE150 and TE8 human ESCC cells. The depletion of AE1 using siRNA inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that MAPK and Hedgehog signaling pathway-related genes, such as DHH, and GLI1, were down-regulated in AE1-depleted KYSE150 cells. In conclusions, the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced ESCC, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for ESCC.

Defining the Risk of Involvement for Each Neck Nodal Level in Patients With Early T-Stage Node-Positive Oropharyngeal Carcinoma

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

Sanguineti, Giuseppe; Califano, Joseph; Stafford, Edward

Purpose: To assess the risk of ipsilateral subclinical neck nodal involvement for early T-stage/node-positive oropharyngeal squamous cell carcinoma. Methods and Materials: Patients undergoing multilevel upfront neck dissection (ND) at Johns Hopkins Hospital within the last 10 years for early clinical T-stage (cT1-2) node-positive (cN+) oropharyngeal squamous cell carcinoma were identified. Pathologic involvement of Levels IB-V was determined. For each nodal level, the negative predictive value of imaging results was computed by using sensitivity/specificity data for computed tomography (CT). This was used to calculate 1 - negative predictive value, or the risk that a negative level on CT harbors subclinical disease.more » Results: One hundred three patients met the criteria. Radical ND was performed in 14.6%; modified radical ND, in 70.9%; and selective ND, in 14.6%. Pathologic positivity rates were 9.5%, 91.3%, 40.8%, 18.0%, and 3.3% for Levels IB-V, respectively. Risks of subclinical disease despite negative CT imaging results were calculated as 3.1%, 76.3%, 17.5%, 6.3%, and 1.0% for Levels IB-V, respectively. Conclusions: Levels IB and V are at very low (<5%) risk of involvement, even with ipsilateral to pathologically proven neck disease; this can guide radiation planning. Levels II and III should be included in high-risk volumes regardless of imaging results, and Level IV should be included within the lowest risk volume.« less

CD8 down-regulation on cytotoxic T lymphocytes of patients with endometrioid endometrial carcinomas.

PubMed

Pascual-García, Mónica; Bértolo, Cristina; Nieto, Juan C; Serrat, Neus; Espinosa, Íñigo; D'Angelo, Emanuela; Muñoz, Raquel; Rovira, Ramón; Vidal, Silvia; Prat, Jaime

2016-10-01

Carcinogenesis is a multistep process in which cancer cells and tumor stroma cells play important roles. T lymphocytes are immune constituents of tumor stroma and play a crucial function in anti-tumor response. By immunohistochemistry and flow cytometry, we studied T cytotoxic (CTLs) and T helper lymphocyte distribution and percentage in the tumor microenvironment and peripheral blood from 35 patients with endometrioid endometrial carcinomas (EEC). We also studied 23 healthy donors' blood samples as a control group. Tumor and non-tumoral endometrium samples were obtained. Immunohistochemistry revealed a high number of CTLs and T helper lymphocytes in the tumor stroma of myoinvasive EECs. T lymphocytes were mostly located in the invasive front. By flow cytometry, the percentages of CTLs and T helper lymphocytes were significantly higher in the tumor compared with the non-neoplastic endometrium (P = .0492 and P = .002). The mean fluorescence intensity of CD8 staining was lower in the tumor compared to the non-neoplastic endometrium (P = .001). There was also reduction of the mean fluorescence intensity of CD8 staining on peripheral blood from patients with grade 3 EECs compare to the peripheral blood from healthy donors (P = .0093). No alterations in the expression of granzymes A and B were found in the CTLs from the EEC cases. Finally, in a proteome profiler cytokine array we found that the growth differentiation factor 15 (GDF15) increased in blood in parallel to the tumor grade. EECs are capable of down-regulating CD8 expression of CTLs. Most likely, this effect is mediated by a soluble molecule present in plasma and is not a result of anergy or exhaustion state. Copyright © 2016 Elsevier Inc. All rights reserved.

Mucinous breast carcinoma with tall columnar cells.

PubMed

Tsoukalas, N; Kiakou, M; Tolia, M; Kostakis, I D; Galanopoulos, M; Nakos, G; Tryfonopoulos, D; Kyrgias, G; Koumakis, G

2018-05-01

Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The World Health Organization classification divides this type of tumour into three different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and signet ring cell carcinoma. A 74-year-old woman presented a tumour with inflammatory features in the upper outer quadrant of her left breast, 7 cm in diameter. The core biopsy showed infiltrating ductal carcinoma of no specific type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She received neoadjuvant chemotherapy, underwent left mastectomy with radical axillary resection and subsequently received radiotherapy and chemotherapy. The histological examination of the surgical specimen revealed two solid tumors in the tail of Spence, which corresponded to adenocarcinoma with high columnar cells. The patient died 16 months after the diagnosis, suffering from pulmonary metastases and anterior chest wall infiltration. A review of the literature revealed only 21 reports of mucinous carcinoma of the breast with tall columnar cells, including our case. This is only the third time that the specific histological type of columnar cell mucinous carcinoma has been reported in the literature.

[Clinical value of para-recurrent laryngeal nerve lymphadenectomy for middle thoracic esophageal squamous cell carcinoma].

PubMed

Wang, Zhen; Liu, Shuoyan

2015-09-01

To analyze the pattern of lymphatic metastasis in middle thoracic esophageal squamous cell carcinoma (ESCC) with different T staging and to investigate the clinical value of para-recurrent laryngeal nerve lymphadenectomy. Clinicopathological data of 717 patients with middle thoracic ESCC undergoing Mckeown esophagectomy plus three-field lymph node dissection in Fujian Provincial Hospital from January 1999 to December 2007 were analyzed retrospectively. Lymph node metastatic rates of different T stages were calculated. Clinical value of each station lymphadenectomy, especially the para-recurrent laryngeal nerve lymphadenectomy, was evaluated by the efficacy index (EI, cross product of one station metastatic rate and 5-year survival of patient with positive lymph nodes of above station). Rates of lymph node metastasis were 29.0% (18/62), 61.1% (91/149) and 64.8% (328/506) in stage T1, T2 and T3 patients respectively. Despite T staging, metastatic rates of right para-recurrent laryngeal nerve lymph node (rRLN LN) were 21.0% (13/62), 28.9% (43/149) and 29.4% (149/506) in stage T1, T2 and T3 patients respectively, which was the most common among all lymph node stations. Metastatic rates of left para-recurrent laryngeal nerve lymph node (lRLN LN) were the second, with 8.1% (5/62), 17.4% (26/149) and 24.7% (125/506) in stage T1, T2, T3 patients respectively. Follow-up period lasted more than 5 years. The 5-year survival rates of positive rRLN LN were 53.8%, 39.5% and 32.2% in stage T1, T2 and T3 patients respectively, whose EI values were 11.3, 11.4 and 9.5 respectively. The 5-year survival rates of positive lRLN LN were 40.0%, 34.6% and 40.0% in stage T1, T2 and T3 patients respectively, whose EI values were 3.2, 6.0 and 9.9 respectively. Bilateral para-recurrent laryngeal nerve lymph nodes are the common sites of metastasis in middle thoracic esophageal squamous cell carcinoma. Right para-recurrent laryngeal nerve lymphadenectomy is of high clinical value despite the T

[Esophageal sarcomatoid carcinoma: report of a case with morphological, immunohistochemical and molecular study].

PubMed

Regragui, Asmaa; Lakhdar, Hind; Abderrahman Alaoui Belabbas, Moulay; Amrani, Meryem; Gamra, Lamia; Alaoui Belabbas, Mohamed

2004-05-01

Sarcomatoïd carcinoma is a rare tumor of the esophagus, characterized macroscopically by a polypoid aspect and histologically by the association of spindle cell carcinoma with sarcomatous pleomorphic component. We report here a case of esophagus sarcomatoïd carcinoma. Diagnosis was based on immunohistochemical analysis of tIssue samples. Human papillomavirus (HVP) detection by PCR amplification of DNA extracted from tumoral tIssue was negative, ruling out the role of HPV infection in this tumor.

p53 predictive value for pT1-2 N0 disease at radical cystectomy.

PubMed

Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

2009-09-01

Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.

PubMed

Liu, Yang; Wang, Yue-ru; Wang, Long; Song, Rui-mei; Zhou, Bo; Song, Zhen-shun

2014-01-01

Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating

Temperature dependence of single-crystal elastic constants of flux-grown alpha-GaPO(4).

PubMed

Armand, P; Beaurain, M; Rufflé, B; Menaert, B; Papet, P

2009-06-01

The lattice parameter change with respect to temperature (T) has been measured using high-temperature powder X-ray diffraction techniques for high-temperature flux-grown GaPO(4) single crystals with the alpha-quartz structure. The lattice and the volume linear thermal expansion coefficients in the temperature range 303-1173 K were computed from the X-ray data. The percentage linear thermal expansions along the a and c axes at 1173 K are 1.5 and 0.51, respectively. The temperature dependence of the mass density rho of flux-grown GaPO(4) single crystals was evaluated using the volume thermal expansion coefficient alpha(V)(T) = 3.291 x 10(-5) - 2.786 x 10(-8) [T] + 4.598 x 10(-11)[T](2). Single-crystal high-resolution Brillouin spectroscopy measurements have been carried out at ambient pressure from 303 to 1123 K to determine the elastic constants C(IJ) of high-temperature flux-grown GaPO(4) material. The single-crystal elastic moduli were calculated using the sound velocities via the measured Brillouin frequency shifts Deltanu(B). These are, to our knowledge, the highest temperatures at which single-crystal elastic constants of alpha-GaPO(4) have been measured. Most of the room-temperature elastic constant values measured on flux-grown GaPO(4) material are higher than the ones found for hydrothermally grown GaPO(4) single crystals. The fourth-order temperature coefficients of both the Brillouin frequency shifts T(nuB)((n)) and the single-crystal elastic moduli T(C(IJ))((n)) were obtained. The first-order temperature coefficients of the C(IJ) are in excellent agreement with previous reports on low-temperature hydrothermally grown alpha-GaPO(4) single crystals, while small discrepancies in the higher-order temperature coefficients are observed. This is explained in terms of the OH content in the GaPO(4) network, which is an important parameter in the crystal thermal behavior.

Hilar location is an independent prognostic factor for recurrence in T1 renal cell carcinoma after nephrectomy.

PubMed

Shim, Myungsun; Song, Cheryn; Park, Sejun; Kim, Aram; Choi, Seung-Kwon; Kim, Choung-Soo; Ahn, Hanjong

2015-01-01

We investigated the prognostic significance of tumor location at the renal hilum near the sinus structure on the recurrence in T1 renal cell carcinoma (RCC). A total of 1,818 T1 RCC patients who underwent radical (RN) or partial nephrectomy (PN) from 1997 to 2011 were retrospectively reviewed. A hilar tumor was defined as a tumor abutting the main renal artery and/or vein or its segmental branches, without invasion. We compared the recurrence-free survival (RFS) rates between hilar and nonhilar T1 RCC and analyzed predictors of RFS after nephrectomy. Patients with hilar tumors showed a poorer 5-year RFS compared with nonhilar tumors both in T1a (89.7 vs. 98.5 %, p < 0.001) and T1b (81.6 vs. 95.1 %, p < 0.001) RCCs. Among patients who underwent RN and PN, hilar tumors were associated with lower 5-year RFS (87.6 vs. 97.2 % for RN, 78.1 vs. 98.2 % for PN, both p < 0.001). In T1a hilar tumor, PN was associated with poorer 5-year RFS than RN (79.5 vs. 93.0 %, p < 0.001). In multivariate analysis, a hilar location remained as an independent predictor of recurrence in both T1a and T1b tumors (both p = 0.001). Hilar tumors show a higher recurrence rate than nonhilar counterparts in T1 RCC. In T1a hilar tumors, PN demonstrated poorer RFS than RN. Potential intrinsic renal anatomical or lymphovascular structural differences as well as differences in cancer characteristics need further investigations.

Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

PubMed

Linedale, Richard; Schmidt, Campbell; King, Brigid T; Ganko, Annabelle G; Simpson, Fiona; Panizza, Benedict J; Leggatt, Graham R

2017-01-01

Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

PubMed

Delogu, Daniele; Pisano, Ilia Patrizia; Pala, Carlo; Pulighe, Fabio; Denti, Salvatore; Cossu, Antonio; Trignano, Mario

2014-01-01

The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

Gallbladder carcinoma: Prognostic factors and therapeutic options

PubMed Central

Goetze, Thorsten Oliver

2015-01-01

The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma’’ (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2

Geochemically distinct carbon isotope distributions in Allochromatium vinosum DSM 180T grown photoautotrophically and photoheterotrophically.

PubMed

Tang, T; Mohr, W; Sattin, S R; Rogers, D R; Girguis, P R; Pearson, A

2017-03-01

Anoxygenic, photosynthetic bacteria are common at redox boundaries. They are of interest in microbial ecology and geosciences through their role in linking the carbon, sulfur, and iron cycles, yet much remains unknown about how their flexible carbon metabolism-permitting either autotrophic or heterotrophic growth-is recorded in the bulk sedimentary and lipid biomarker records. Here, we investigated patterns of carbon isotope fractionation in a model photosynthetic sulfur-oxidizing bacterium, Allochromatium vinosum DSM180 T . In one treatment, A. vinosum was grown with CO 2 as the sole carbon source, while in a second treatment, it was grown on acetate. Different intracellular isotope patterns were observed for fatty acids, phytol, individual amino acids, intact proteins, and total RNA between the two experiments. Photoautotrophic CO 2 fixation yielded typical isotopic ordering for the lipid biomarkers: δ 13 C values of phytol > n-alkyl lipids. In contrast, growth on acetate greatly suppressed intracellular isotopic heterogeneity across all molecular classes, except for a marked 13 C-depletion in phytol. This caused isotopic "inversion" in the lipids (δ 13 C values of phytol < n-alkyl lipids). The finding suggests that inverse δ 13 C patterns of n-alkanes and pristane/phytane in the geologic record may be at least in part a signal for photoheterotrophy. In both experimental scenarios, the relative isotope distributions could be predicted from an isotope flux-balance model, demonstrating that microbial carbon metabolisms can be interrogated by combining compound-specific stable isotope analysis with metabolic modeling. Isotopic differences among molecular classes may be a means of fingerprinting microbial carbon metabolism, both in the modern environment and the geologic record. © 2017 John Wiley & Sons Ltd.

Violation of geometrical scaling in pp collisions at NA61/SHINE

NASA Astrophysics Data System (ADS)

Praszalowicz, Michal

2013-04-01

We analyze geometrical scaling (GS) of negative pion multiplicity pT distributions at NA61/SHINE energies. We show that even though NA61/SHINE energies are low, one may expect to find GS in the particle spectra. We argue that qualitative behavior of ratios of multiplicities at different energies is in agreement with a simple picture of GS which is violated for pT smaller than some nonperturbative scale Λ and when larger Bjorken x of one of the scattering patrons crosses xmax⁡ above which a gluonic cloud becomes dilute and quark degrees of freedom become important.

[Prediction of occult carcinoma in contralateral nodules based on the ultrasonic features of unilateral papillary thyroid carcinoma].

PubMed

Yang, L M; Li, Q; Zhao, B W; Lyu, J G; Xu, H S; Xu, L L; Li, S Y; Gao, L; Zhu, J

2017-04-07

Objective: To investigate the occurrence of occult carcinoma in contralateral lobes based on the ultrasonic features of unilateral papillary thyroid carcinoma. Methods: The study included 202 consecutives cases of unilateral papillary thyroid carcinoma with benign nodules in the contralateral lobe identified by preoperative ultrasound or fine-needle aspiration from June 2014 to December 2015. All patients received total thyroidectomies, and with postoperative pathological examination they were divided into two groups, one including 60 cases with positive occult cancer and another one consisting of 142 cases with negative occult cancer. Univariate and multivariate analyses were performed to analyze the sonographic features of unilateral papillary thyroid carcinoma relevant to the occurrence of occult carcinoma in the contralateral nodules. Results: Univariate analysis indicated occult carcinoma in the contralateral lobes was associated with Hashimoto's thyroiditis(χ(2)=3.955, P =0.047), unclear border (χ(2)=4.375, P =0.036)and multifocality in the ipsilateral(χ(2)=7.375, P =0.007), but not with tumors maximum size, location, A/T, shape, internal structure, internal echo, acoustic halo, calcification, capsular invasion and blood flow signal in the lobe with carcinoma on another side. Multivariate analysis showed unclear border ( OR =2.727, P =0.010) and multifocality in the ipsilateral( OR =2.807, P =0.005)of carcinoma were independent predictive factor for contralateral occult PTC. Conclusions: Unclear border and multifocality of PTC in the ipsilateral were closely relevant to the occurrence of occult carcinoma in the contralateral nodules.

Colon tumor cells grown in NASA Bioreactor

NASA Technical Reports Server (NTRS)

2001-01-01

These photos compare the results of colon carcinoma cells grown in a NASA Bioreactor flown on the STS-70 Space Shuttle in 1995 flight and ground control experiments. The cells grown in microgravity (left) have aggregated to form masses that are larger and more similar to tissue found in the body than the cells cultured on the ground (right). The principal investigator is Milburn Jessup of the University of Texas M. D. Anderson Cancer Center. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Cell constructs grown in a rotating bioreactor on Earth (left) eventually become too large to stay suspended in the nutrient media. In the microgravity of orbit, the cells stay suspended. Rotation then is needed for gentle stirring to replenish the media around the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). Credit: NASA and University of Texas M. D. Anderson Cancer Center.

Choroidal metastasis of a minor salivary gland adenoid cystic carcinoma: A case report.

PubMed

Portilla Blanco, R R; Roberts Martínez-Aguirre, I; Pontón Méndez, P; Zarzosa Martín, M E; Pérez-Salvador García, E

2018-03-21

A 61-year-old man with a lower lip minor salivary gland adenoid cystic carcinoma, suffered from a unilateral progressive visual acuity loss due to choroidal metastasis. Adenoid cystic carcinoma is a rare primary tumour with significant metastatic potential. Our patient presented with a unilateral choroidal metastasis. According to the current literature, 8 cases of choroidal metastasis of salivary gland adenoid cystic carcinoma have been reported. This is the second case reported of choroidal metastasis with origin in a minor salivary gland, and the first one with origin in the minor salivary glands of the lower lip. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

HPV-related Multiphenotypic Sinonasal Carcinoma: An Expanded Series of 49 Cases of the Tumor Formerly Known as HPV-related Carcinoma With Adenoid Cystic Carcinoma-like Features.

PubMed

Bishop, Justin A; Andreasen, Simon; Hang, Jen-Fan; Bullock, Martin J; Chen, Tiffany Y; Franchi, Alessandro; Garcia, Joaquin J; Gnepp, Douglas R; Gomez-Fernandez, Carmen R; Ihrler, Stephan; Kuo, Ying-Ju; Lewis, James S; Magliocca, Kelly R; Pambuccian, Stefan; Sandison, Ann; Uro-Coste, Emmanuelle; Stelow, Edward; Kiss, Katalin; Westra, William H

2017-12-01

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC), originally known as HPV-related carcinoma with adenoid cystic carcinoma-like features, is a peculiar neoplasm that is restricted to the sinonasal tract, exhibits features of both a surface-derived and salivary gland carcinoma (particularly adenoid cystic carcinoma), and is associated with high-risk HPV. Given the limited number of published cases, the full clinicopathologic spectrum of this neoplasm is unclear. Here, we present an updated experience of 49 cases. All cases of HMSC were obtained from the authors' files. Immunohistochemistry for p16, c-kit, and myoepithelial cell markers (S100, actin, calponin, p63, and/or p40) was performed along with RNA in situ hybridization for HPV (type 33-specific as well as a high-risk cocktail). Fluorescence in situ hybridization studies for fusions of MYB, NFIB, and MYBL1 was performed on a subset of cases. Clinical follow-up was obtained from medical records. A total of 49 cases of HMSC were collected. Twenty-eight (57%) were from women and 18 (43%) from men, ranging in age from 28 to 90 years (mean, 54 y). Of 40 cases with detailed staging information, 43% of HMSCs presented with a high T-stage (T3 or T4). Histologically, most grew predominantly as solid nests of basaloid cells exhibiting high mitotic rates and frequent necrosis, with histologic and immunohistochemical evidence of myoepithelial differentiation. Most cases also demonstrated foci of cribriform and/or tubular growth, along with an inconspicuous population of ducts. Thirty-four (69%) cases demonstrated an unusual pattern of surface involvement where markedly atypical squamous cells colonized tracts of the sinonasal mucosa. Less consistent histologic features included squamous differentiation within the invasive tumor (n=6), sarcomatoid transformation (n=5) including overt chondroid differentiation (n=3), and prominent epithelial-myoepithelial carcinoma-like growth (n=3). All cases

Cervical lymph node metastasis in adenoid cystic carcinoma of the major salivary glands.

PubMed

2017-02-01

To verify the prevalence of cervical lymph node metastasis in adenoid cystic carcinoma of major salivary glands, and to establish recommendations for elective neck treatment. A search was conducted of the US National Library of Medicine database. Appropriate articles were selected from the abstracts, and the original publications were obtained to extract data. Among 483 cases of major salivary gland adenoid cystic carcinoma, a total of 90 (18.6 per cent) had cervical metastasis. The prevalence of positive nodes from adenoid cystic carcinoma was 14.5 per cent for parotid gland, 22.5 per cent for submandibular gland and 24.7 per cent for sublingual gland. Cervical lymph node metastasis occurred more frequently in patients with primary tumour stage T3-4 adenoid cystic carcinoma, and was usually located in levels II and III in the neck. Adenoid cystic carcinoma of the major salivary glands is associated with a significant prevalence of cervical node metastasis, and elective neck treatment is indicated for T3 and T4 primary tumours, as well as tumours with other histological risk factors.

HARP and NA61 (SHINE) hadron production experiments

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

Popov, Boris A.

2009-11-25

The hadroproduction experiments HARP and NA61 (SHINE) as well as their implications for neutrino physics are discussed. Recent HARP measurements have already been used for precise predictions of neutrino beams in K2K and MiniBooNE/SciBooNE experiments and are also being used to improve the atmospheric neutrino flux predictions and to help in the optimization of neutrino factory and super-beam designs. First preliminary data from NA61 are of significant importance for a precise prediction of a new neutrino beam at J-PARC to be used for the first stage of the T2K experiment. Both HARP and NA61 provide a large amount of inputmore » for validation and tuning of hadroproduction models in Monte-Carlo generators.« less

19 CFR 123.61 - Baggage arriving in baggage car.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Baggage arriving in baggage car. 123.61 Section... car. An inward foreign manifest on Customs Form 7533 shall be used for all baggage arriving in baggage cars. [T.D. 70-121, 35 FR 8215, May 26, 1970, as amended by T.D. 82-145, 47 FR 35478, Aug. 16, 1982] ...

Structural and optical inhomogeneities of Fe doped GaN grown by hydride vapor phase epitaxy

NASA Astrophysics Data System (ADS)

Malguth, E.; Hoffmann, A.; Phillips, M. R.

2008-12-01

We present the results of cathodoluminescence experiments on a set of Fe doped GaN samples with Fe concentrations of 5×1017, 1×1018, 1×1019, and 2×1020 cm-3. These specimens were grown by hydride vapor phase epitaxy with different concentrations of Fe. The introduction of Fe is found to promote the formation of structurally inhomogeneous regions of increased donor concentration. We detect a tendency of these regions to form hexagonal pits at the surface. The locally increased carrier concentration leads to enhanced emission from the band edge and the internal T41(G)-A61(S) transition of Fe3+. In these areas, the luminescence forms a finely structured highly symmetric pattern, which is attributed to defect migration along strain-field lines. Fe doping is found to quench the yellow defect luminescence band and to enhance the blue luminescence band due to the lowering of the Fermi level and the formation of point defects, respectively.

Prognostic relevance of Centromere protein H expression in esophageal carcinoma.

PubMed

Guo, Xian-Zhi; Zhang, Ge; Wang, Jun-Ye; Liu, Wan-Li; Wang, Fang; Dong, Ju-Qin; Xu, Li-Hua; Cao, Jing-Yan; Song, Li-Bing; Zeng, Mu-Sheng

2008-08-13

Many kinetochore proteins have been shown to be associated with human cancers. The aim of the present study was to clarify the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in esophageal carcinoma and its correlation with clinicopathological features. We examined the expression of CENP-H in immortalized esophageal epithelial cells as well as in esophageal carcinoma cells, and in 12 cases of esophageal carcinoma tissues and the paired normal esophageal tissues by RT-PCR and Western blot analysis. In addition, we analyzed CENP-H protein expression in 177 clinicopathologically characterized esophageal carcinoma cases by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. The level of CENP-H mRNA and protein were higher in the immortalized cells, cancer cell lines and most cancer tissues than in normal control tissues. Immunohistochemistry showed that CENP-H was expressed in 127 of 171 ESCC cases (74.3%) and in 3 of 6 esophageal adenocarcinoma cases (50%). Statistical analysis of ESCC cases showed that there was a significant difference of CENP-H expression in patients categorized according to gender (P = 0.013), stage (P = 0.023) and T classification (P = 0.019). Patients with lower CENP-H expression had longer overall survival time than those with higher CENP-H expression. Multivariate analysis suggested that CENP-H expression was an independent prognostic marker for esophageal carcinoma patients. A prognostic value of CENP-H was also found in the subgroup of T3 approximately T4 and N0 tumor classification. Our results suggest that CENP-H protein is a valuable marker of esophageal carcinoma progression. CENP-H might be used as a valuable prognostic marker for esophageal carcinoma patients.

Technical and clinical performance of a new assay to detect squamous cell carcinoma antigen levels for the differential diagnosis of cervical, lung, and head and neck cancer.

PubMed

Holdenrieder, Stefan; Molina, Rafael; Qiu, Ling; Zhi, Xiuyi; Rutz, Sandra; Engel, Christine; Kasper-Sauer, Pia; Dayyani, Farshid; Korse, Catharina M

2018-04-01

In squamous cell carcinoma, squamous cell carcinoma antigen levels are often elevated. This multi-center study evaluated the technical performance of a new Elecsys ® squamous cell carcinoma assay, which measures serum squamous cell carcinoma antigen 1 and 2 levels in an equimolar manner, and investigated the potential of squamous cell carcinoma antigen for differential diagnosis of cervical, lung, and head and neck squamous cell carcinoma.Assay precision and method comparison experiments were performed across three European sites. Reference ranges for reportedly healthy individuals were determined using samples from banked European and Chinese populations. Differential diagnosis experiments determined whether cervical, lung, or head and neck cancer could be differentiated from apparently healthy, benign, or other malignant cohorts using squamous cell carcinoma antigen levels alone. Squamous cell carcinoma antigen cut-off levels were calculated based on squamous cell carcinoma antigen levels at 95% specificity. Repeatability coefficients of variation across nine analyte concentrations were ≤5.3%, and intermediate precision coefficients of variation were ≤10.3%. Method comparisons showed good correlations with Architect and Kryptor systems (slopes of 1.1 and 1.5, respectively). Reference ranges for 95th percentiles for apparently healthy individuals were 2.3 ng/mL (95% confidence interval: 1.9-3.8; European cohort, n = 153) and 2.7 ng/mL (95% confidence interval: 2.2-3.3; Chinese cohort, n = 146). Strongest differential diagnosis results were observed for cervical squamous cell carcinoma: receiver operating characteristic analysis showed that squamous cell carcinoma antigen levels (2.9 ng/mL cut-off) differentiate cervical squamous cell carcinoma (n = 127) from apparently healthy females (n = 286; area under the curve: 86.2%; 95% confidence interval: 81.8-90.6; sensitivity: 61.4%; specificity: 95.6%), benign diseases (n = 187; area

Basaloid large cell lung carcinoma presenting as cutaneous metastasis at the colostomy site after abdominoperineal resection for rectal carcinoma.

PubMed

Sabater-Marco, Vicente; García-García, José Angel; Roig-Vila, José Vicente

2013-08-01

The occurrence of a tumor at the colostomy site after abdominoperineal resection for rectal carcinoma is rare and it may be related to a previously resected carcinoma or another primary tumor. We report a 61-year-old man who developed an ulcerated skin nodule at her colostomy site 6 years after resection of a rectal adenocarcinoma. Histopathologically, the skin nodule was composed of atypical large and pleomorphic cells with high mitotic rate and they were arranged in nests and within lymphatic channels in the dermis. The neoplastic cells were immunoreactive for cytokeratin (CK) AE1/3, CK7, CK34ßE12, epithelial membrane antigen and vimentin while detection of human papillomavirus and Epstein-Barr virus DNA was negative. A diagnosis of basaloid large cell carcinoma of pulmonary origin was suggested and it was confirmed by computed tomography-guided fine needle aspiration of a right subpleural mass. A metastatic tumor at the colostomy site is an exceptional finding and may be the first manifestation of lung cancer, especially if it consist of pleomorphic large cells with high mitotic rate and basaloid immunophenotype. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does elective neck dissection in T1/T2 carcinoma of the oral tongue and floor of the mouth influence recurrence and survival rates?

PubMed

Kelner, Natalie; Vartanian, José Guilherme; Pinto, Clóvis Antônio Lopes; Coutinho-Camillo, Cláudia Malheiros; Kowalski, Luiz Paulo

2014-09-01

The aim of this study was to evaluate the results of elective neck dissection compared with observation (control group) in selected cases of early carcinoma of the oral tongue and floor of the mouth. It was a retrospective analysis of 222 patients who had the tumour resected (161 also had elective neck dissection). Occult lymph node metastases were detected in 33/161 (21%), and neck recurrences were diagnosed in 10 of the 61 patients in the control group (16%). Occult lymph node metastases reduced the 5-year disease-specific survival from 90% to 65% (p=0.001) and it was 96% among the controls. The 5-year disease-specific survival was 85% in the group treated by neck dissection and 96% in the observation group (p=0.09). Rigorous follow-up of selected low risk patients is associated with high rates of salvage, and overall survival was similar to the observed survival in patients treated by elective neck dissection. Observation is a reasonable option in the treatment of selected patients. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Enhanced 4T1 breast carcinoma anticancer activity by co-delivery of doxorubicin and curcumin with core-shell drug-carrier based on heparin modified poly(L-lactide) grafted polyethylenimine cationic nanoparticles.

PubMed

Guo, Oingfa; Li, Xiaolu; Yang, Yi; Wei, Jing; Zhao, Qian; Luo, Feng; Qian, Zhiyong

2014-02-01

Use of single chemotherapy agents has shown some limitations in anti-tumor treatment, such as development of drug resistance, severe adverse reactions and limited regime for therapeutic use. Combination of two or more therapeutic drugs is a feasible strategy to overcome these limitations. This paper reports study of co-delivery by core-shell nanoparticles (NPs) with hydrophobic PLLA core loaded with curcumin (Cur) and hydrophilic heparin shell adsorbing Doxorubicin (DOX). Characterizations of Cur-PEA NPs, Cur-PEA/heparin NPs and DOX adsorbing into Cur-PEA/heparin NPs (DOX-Cur NPs) were also investigated by transmission electron microscope (TEM) and Malvern Zetasizer. Studies on cellular uptake of DOX-Cur NPs demonstrated that both drugs were effectively taken up by 4T1 tumor cells. Furthermore, DOX-Cur NPs suppressed 4T1 tumor cells growth more efficiently than either DOX or Cur alone at the same concentrations, as measured by flow cytometry (FCM). We found out that intravenous injection of DOX-Cur NPs efficiently inhibited growth of subcutaneous 4T1 breast carcinoma in vivo (p < 0.01) and prolonged survival of the treated 4T1 breast carcinoma mice. Moreover, the pathological damage to the cardiac tissue in mice treated with DOX-Cur NPs was significantly less severe than that of mice treated with free DOX. This study suggested that DOX-Cur NPs may have promising applications in breast carcinoma therapy.

Infiltrating T cells promote renal cell carcinoma (RCC) progression via altering the estrogen receptor β-DAB2IP signals.

PubMed

Yeh, Chiuan-Ren; Ou, Zheng-Yu; Xiao, Guang-Qian; Guancial, Elizabeth; Yeh, Shuyuan

2015-12-29

Previous studies indicated the T cells, one of the most common types of immune cells existing in the microenvironment of renal cell carcinoma (RCC), may influence the progression of RCC. The potential linkage of T cells and the estrogen receptor beta (ERβ), a key player to impact RCC progression, however, remains unclear. Our results demonstrate that RCC cells can recruit more T cells than non-malignant kidney cells. Using an in vitro matrigel invasion system, we found infiltrating T cells could promote RCC cells invasion via increasing ERβ expression and transcriptional activity. Mechanism dissection suggested that co-culturing T cells with RCC cells released more T cell attraction factors, including IFN-γ, CCL3 and CCL5, suggesting a positive regulatory feed-back mechanism. Meanwhile, infiltrating T cells may also promote RCC cell invasion via increased ERβ and decreased DAB2IP expressions, and knocking down DAB2IP can then reverse the T cells-promoted RCC cell invasion. Together, our results suggest that infiltrating T cells may promote RCC cell invasion via increasing the RCC cell ERβ expression to inhibit the tumor suppressor DAB2IP signals. Further mechanism dissection showed that co-culturing T cells with RCC cells could produce more IGF-1 and FGF-7, which may enhance the ERβ transcriptional activity. The newly identified relationship between infiltrating T cells/ERβ/DAB2IP signals may provide a novel therapeutic target in the development of agents against RCC.

Matrix metalloproteinase-7 expression in gastric carcinoma.

PubMed Central

Honda, M; Mori, M; Ueo, H; Sugimachi, K; Akiyoshi, T

1996-01-01

BACKGROUND/AIMS: Matrix metalloproteinase-7 (MMP-7) belongs to the same family as matrix degrading metalloproteinase (MMPs) that may play an important part in cancer cell invasion and metastasis. This study reports on the MMP-7 mRNA expression level both in human gastric carcinomas and the normal gastric mucosa. METHODS: From fresh specimens of 47 surgical pairs of primary gastric carcinomas and corresponding normal tissue specimens, cDNA was obtained by reverse transcription (RT) and thereafter MMP-7 mRNAs were detected by means of a polymerase chain reaction. The tumour/normal (T/N) ratio of MMP-7 expression was calculated after correcting for glyceraldehyde-3-phosphate dehydrogenase as an internal control. RESULTS: The expression corrected levels of MMP-7 mRNA of the tumour was greater than that of the normal mucosa in 41 of 47 cases (87%). The 13 cases whose T/N ratio was more than 2.1 showed a deeper invasion of the gastric wall, and more frequent lymphatic or vascular permeations than the 34 cases whose T/N ratio was less than 2.0. An immunohistochemical study showed that MMP-7 was predominantly expressed in the cancer cells, weakly expressed in normal epithelial cells, and not expressed in the surrounding stromal cells. CONCLUSIONS: These findings suggest that the overexpression of MMP-7 may thus play an important part in tumour invasion in gastric carcinomas while, in addition, MMP-7 may also prove to be a useful marker for determining the biological aggressiveness of gastric carcinoma. Images Figure 1 Figure 2 Figure 3 PMID:8949652

External validation of the proposed T and N categories of squamous cell carcinoma of the penis.

PubMed

Al-Najar, Amr; Alkatout, Ibrahim; Al-Sanabani, Sakhr; Korda, Joanna Beate; Hegele, Axel; Bolenz, Christian; Jünemann, Klaus-Peter; Naumann, Carsten Maik

2011-04-01

The aim of this study was to validate recently proposed modifications to the current TNM classification of penile squamous cell carcinoma (PSCC) by using data from four German urological centers. We identified 89 patients treated for histologically confirmed PSCC between 1996 and 2008 and reclassified them according to the proposed TNM staging revisions. The proposed changes restricted T2 to tumoral invasion of the corpus spongiosum, whereas invasion of the corpus cavernosum was considered as T3. No changes were made to T1 and T4. Furthermore, N1 was limited to unilateral and N2 to bilateral inguinal lymph node involvement regardless of their number. Pelvic lymph node involvement and fixed lymph node were considered as N3 tumors. The range of follow up after initial treatment was 1-142 months (mean 38). Node-negative cases following the current classification were 65.2% (30/46), 48.5% (16/33) and 87.5% (7/8) for T1, T2 and T3, respectively. According to the proposed classification, N0 cases were markedly reduced in the T3 group (55.5%, 10/18) and relatively changed in the T2 group (56.5%, 13/23). T4 patients had no negative disease status. The 3-year disease-specific survival (DSS) rates for the proposed categories were 85.4%, 71.6% and 62.4% for T1, T2 and T3, respectively. For the current categories, the 3-year DSS rates were 85.4%, 66.9% and 100% for T1, T2 and T3, respectively. The 3-year DSS of the current N categories was 78.7%, 51% and 13.3% for N1, N2 and N3, respectively. According to the newly proposed categories, the 3-year DSS was 70%, 50% and 13.3% for N1, N2 and N3, respectively. Tumor and nodal staging of the newly proposed TNM classification show a more distinctive survival compared to the current one. However, a multi-institutional validation is still required to further corroborate the proposed modifications. © 2011 The Japanese Urological Association.

Higher frequencies of GARP(+)CTLA-4(+)Foxp3(+) T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality.

PubMed

Kalathil, Suresh; Lugade, Amit A; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

2013-04-15

The extent to which T-cell-mediated immune surveillance is impaired in human cancer remains a question of major importance, given its potential impact on the development of generalized treatments of advanced disease where the highest degree of heterogeneity exists. Here, we report the first global analysis of immune dysfunction in patients with advanced hepatocellular carcinoma (HCC). Using multi-parameter fluorescence-activated cell sorting analysis, we quantified the cumulative frequency of regulatory T cells (Treg), exhausted CD4(+) helper T cells, and myeloid-derived suppressor cells (MDSC) to gain concurrent views on the overall level of immune dysfunction in these inoperable patients. We documented augmented numbers of Tregs, MDSC, PD-1(+)-exhausted T cells, and increased levels of immunosuppressive cytokines in patients with HCC, compared with normal controls, revealing a network of potential mechanisms of immune dysregulation in patients with HCC. In dampening T-cell-mediated antitumor immunity, we hypothesized that these processes may facilitate HCC progression and thwart the efficacy of immunotherapeutic interventions. In testing this hypothesis, we showed that combined regimens to deplete Tregs, MDSC, and PD-1(+) T cells in patients with advanced HCC restored production of granzyme B by CD8(+) T cells, reaching levels observed in normal controls and also modestly increased the number of IFN-γ producing CD4(+) T cells. These clinical findings encourage efforts to restore T-cell function in patients with advanced stage disease by highlighting combined approaches to deplete endogenous suppressor cell populations that can also expand effector T-cell populations. ©2013 AACR.

Production of biodiesel from microalgae Chlamydomonas polypyrenoideum grown on dairy industry wastewater.

PubMed

Kothari, Richa; Prasad, Ravindra; Kumar, Virendra; Singh, D P

2013-09-01

This study involves a process of phyco-remediation of dairy industry wastewater by algal strain Chlamydomonas polypyrenoideum. The results of selected algal strain indicated that dairy industry wastewater was good nutrient supplement for algal growth in comparable with BG-11 growth medium. Alga grown on dairy industry wastewater reduced the pollution load of nitrate (90%), nitrite (74%), phosphate (70%), chloride (61%), fluoride (58%), and ammonia (90%) on 10th day of its growth as compared to that of uninoculated wastewater. The lipid content of algal biomass grown on dairy wastewater on 10th day (1.6g) and 15th day (1.2 g) of batch experiment was found to be higher than the lipid content of algal biomass grown in BG-11 growth medium on 10th day (1.27 g) and 15th day (1.0 g) of batch experiment. The results on FTIR analysis of the extracted bio-oil through transesterification reaction was comparable with bio-oil obtained from other sources. Copyright © 2013 Elsevier Ltd. All rights reserved.

An immunohistochemical study of the inflammatory infiltrate associated with nasal carcinoma in dogs and cats.

PubMed

Vanherberghen, M; Day, M J; Delvaux, F; Gabriel, A; Clercx, C; Peeters, D

2009-07-01

The aims of this study were to characterize the inflammatory infiltrate associated with nasal carcinoma in dogs and cats and to determine whether this differed between the two species or with different types of carcinoma. Sections from fixed tissue biopsy samples of intranasal carcinoma from 31 dogs and six cats were labelled immunohistochemically to detect expression of the T-lymphocyte marker CD3, class II molecules of the major histocompatibility complex (MHC II), the myelomonocytic antigen MAC387 and immunoglobulin (Ig) G, IgA and IgM within the cytoplasm of plasma cells. All canine carcinomas were heavily infiltrated by MAC387(+) neutrophils, with smaller numbers of MAC387(+) macrophages. T cells were particularly prominent in the infiltrate associated with transitional carcinoma, and in such tumours were frequently mixed with MHC II(+) cells having macrophage or dendritic cell morphology. IgG(+) and IgA(+) plasma cells were detected at the peripheral margins of all types of canine carcinoma. In contrast, feline intranasal carcinoma was invariably associated with a marked infiltration of CD3(+) T cells. The feline tumour infiltrates contained sparse neutrophils and macrophages and few IgG(+) and IgA(+) plasma cells. These findings suggest that qualitatively different immune responses are induced in response to specific types of canine intranasal carcinoma, and that the canine and feline immune response to these neoplasms is also distinct.

Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung.

PubMed

Pavanello, Sofia; B'chir, Fatma; Pulliero, Alessandra; Saguem, Saâd; Ben Fraj, Radhia; El Aziz Hayouni, Abed; Clonfero, Erminio; Mastrangelo, Giuseppe

2007-09-01

This study aimed to identify new genetic characteristics contributing to individual susceptibility to smoke-induced lung cancer. Despite functional evidence of a possible role of cytochrome P450 1A2 (CYP1A2) in lung cancer susceptibility, no studies have evaluated the influence of CYP1A2 genotypes on lung cancer risk. We investigated the interaction between CYP1A2-T2467delT (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male smokers) separately for the histological types squamous cell carcinoma (SCC) (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a case-only study design. A significant interaction between CYP1A2-T/delT or delT/delT genotypes and tobacco consumption (pack-years) adjusted for age was evident (OR (95% CI) 7.78 (1.52-42.8)) in the SCC cases who smoked relatively less (< or =33 pack-years, I quartile value), but not in adenocarcinoma and controls. Our results suggest that CYP1A2-T2467delT polymorphism has an important role in lung carcinogenesis, especially SCC, among smokers.

Enabling screening in 3D microenvironments: probing matrix and stromal effects on the morphology and proliferation of T47D breast carcinoma cells.

PubMed

Montanez-Sauri, Sara I; Sung, Kyung Eun; Berthier, Erwin; Beebe, David J

2013-03-01

During breast carcinoma progression, the three-dimensional (3D) microenvironment is continuously remodeled, and changes in the composition of the extracellular matrix (ECM) occur. High throughput screening platforms have been used to decipher the complexity of the microenvironment and to identify ECM components responsible for cancer progression. However, traditional screening platforms are typically limited to two-dimensional (2D) cultures, and often exclude the influence of ECM and stromal components. In this work, a system that integrates 3-dimensional cell culture techniques with an automated microfluidic platform was used to create a new ECM screening platform that cultures cells in more physiologically relevant 3D in vitro microenvironments containing stromal cells and different ECM molecules. This new ECM screening platform was used to culture T47D breast carcinoma cells in mono- and co-culture with human mammary fibroblasts (HMF) with seven combinations of three different ECM proteins (collagen, fibronectin, laminin). Differences in the morphology of T47D clusters, and the proliferation of T47D cells were found in ECM compositions rich in fibronectin or laminin. In addition, an MMP enzyme activity inhibition screening showed the capabilities of the platform for small molecule screening. The platform presented in this work enables screening for the effects of matrix and stromal compositions and show promises for providing new insights in the identification of key ECM components involved in breast cancer.

t(6;11) Renal Cell Carcinoma (RCC) Expanded Immunohistochemical Profile Emphasizing Novel RCC Markers and Report of 10 New Genetically Confirmed Cases

PubMed Central

Smith, Nathaniel E.; Illei, Peter B.; Allaf, Mohamed; Gonzalez, Nilda; Morris, Kerry; Hicks, Jessica; DeMarzo, Angelo; Reuter, Victor E.; Amin, Mahul B.; Epstein, Jonathan I.; Netto, George J.; Argani, Pedram

2015-01-01

Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Uro-logical Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cath-epsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that

t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases.

PubMed

Smith, Nathaniel E; Illei, Peter B; Allaf, Mohamed; Gonzalez, Nilda; Morris, Kerry; Hicks, Jessica; Demarzo, Angelo; Reuter, Victor E; Amin, Mahul B; Epstein, Jonathan I; Netto, George J; Argani, Pedram

2014-05-01

Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cathepsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that

Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas.

PubMed

Fadare, Oluwole; Parkash, Vinita; Gwin, Katja; Hanley, Krisztina Z; Jarboe, Elke A; Liang, Sharon X; Quick, Charles M; Zheng, Wenxin; Rawish, Kojo R; Hecht, Jonathan L; Desouki, Mohamed M

2013-12-01

The expression of α-methylacyl-coenzyme-A racemase (AMACR) has previously been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad phenotypic overlap with their identically named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were assessed for AMACR immunoreactivity, with results scored semiquantitatively (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells, respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n = 22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% confidence interval [CI], 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively, with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases as well as its expression in 15% to 22% of the non-CCC histotypes. © 2013.

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays.

PubMed

Sotoudeh, Kambiz; Hashemi, Forough; Madjd, Zahra; Sadeghipour, Alireza; Molanaei, Saadat; Kalantary, Elham

2012-05-28

c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008-2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429.

MRI-Based Texture Analysis to Differentiate Sinonasal Squamous Cell Carcinoma from Inverted Papilloma.

PubMed

Ramkumar, S; Ranjbar, S; Ning, S; Lal, D; Zwart, C M; Wood, C P; Weindling, S M; Wu, T; Mitchell, J R; Li, J; Hoxworth, J M

2017-05-01

Because sinonasal inverted papilloma can harbor squamous cell carcinoma, differentiating these tumors is relevant. The objectives of this study were to determine whether MR imaging-based texture analysis can accurately classify cases of noncoexistent squamous cell carcinoma and inverted papilloma and to compare this classification performance with neuroradiologists' review. Adult patients who had inverted papilloma or squamous cell carcinoma resected were eligible (coexistent inverted papilloma and squamous cell carcinoma were excluded). Inclusion required tumor size of >1.5 cm and preoperative MR imaging with axial T1, axial T2, and axial T1 postcontrast sequences. Five well-established texture analysis algorithms were applied to an ROI from the largest tumor cross-section. For a training dataset, machine-learning algorithms were used to identify the most accurate model, and performance was also evaluated in a validation dataset. On the basis of 3 separate blinded reviews of the ROI, isolated tumor, and entire images, 2 neuroradiologists predicted tumor type in consensus. The inverted papilloma ( n = 24) and squamous cell carcinoma ( n = 22) cohorts were matched for age and sex, while squamous cell carcinoma tumor volume was larger ( P = .001). The best classification model achieved similar accuracies for training (17 squamous cell carcinomas, 16 inverted papillomas) and validation (7 squamous cell carcinomas, 6 inverted papillomas) datasets of 90.9% and 84.6%, respectively ( P = .537). For the combined training and validation cohorts, the machine-learning accuracy (89.1%) was better than that of the neuroradiologists' ROI review (56.5%, P = .0004) but not significantly different from the neuroradiologists' review of the tumors (73.9%, P = .060) or entire images (87.0%, P = .748). MR imaging-based texture analysis has the potential to differentiate squamous cell carcinoma from inverted papilloma and may, in the future, provide incremental information to the

Colonic metastasis from breast carcinoma: a case report.

PubMed

Tsujimura, Kazuma; Teruya, Tsuyoshi; Kiyuna, Masaya; Higa, Kuniki; Higa, Junko; Iha, Kouji; Chinen, Kiyoshi; Asato, Masaya; Takushi, Yasukatsu; Ota, Morihito; Dakeshita, Eijirou; Nakachi, Atsushi; Gakiya, Akira; Shiroma, Hiroshi

2017-07-05

Colonic metastasis from breast carcinoma is very rare. Here, we report a case of colonic metastasis from breast carcinoma. The patient was a 51-year-old woman. She had upper abdominal pain, vomiting, and diarrhea, repeatedly. We performed abdominal contrast-enhanced computed tomography (CT) to investigate these symptoms. The CT scan revealed a tumor in the ascending colon with contrast enhancement and showed an expanded small intestine. For further investigation of this tumor, we performed whole positron emission tomography-computed tomography (PET-CT). The PET-CT scan revealed fluorodeoxyglucose uptake in the ascending colon, mesentery, left breast, and left axillary region. Analysis of biopsy samples obtained during colonoscopy revealed signet ring cell-like carcinoma. Moreover, biopsy of the breast tumor revealed invasive lobular carcinoma. Therefore, the preoperative diagnosis was colonic metastasis from breast carcinoma. Open ileocecal resection was performed. The final diagnosis was multiple metastatic breast carcinomas, and the TNM classification was T2N1M1 Stage IV. We presented a rare case of colonic metastasis from breast carcinoma. PET-CT may be useful in the diagnosis of metastatic breast cancer. When analysis of biopsy samples obtained during colonoscopy reveals signet ring cell-like carcinoma, the possibility of breast cancer as the primary tumor should be considered.

Bioethanol Potential of Energy Sorghum Grown on Marginal and Arable Lands

PubMed Central

Tang, Chaochen; Li, Songbo; Li, Meng; Xie, Guang H.

2018-01-01

Field experiments were conducted in marginal lands, i.e., sub-humid climate and saline-land (SHS) and semi-arid climate and wasteland (SAW), to evaluate ethanol potential based on the biomass yield and chemical composition of biomass type (var. GN-2, GN-4, and GN-10) and sweet type (var. GT-3 and GT-7) hybrids of energy sorghum [Sorghum bicolor (L.) Moench] in comparison with sub-humid climate and cropland (SHC) in northern China. Results showed that environment significantly (p < 0.05) influenced plant growth, biomass yield and components, and subsequently the ethanol potential of energy sorghum. Biomass and theoretical ethanol yield of the crop grown at SHS (12.2 t ha−1 and 3,425 L ha−1, respectively) and SAW (8.6 t ha−1 and 2,091 L ha−1, respectively) were both statistically (p < 0.001) lower than values at the SHC site (32.6 t ha−1 and 11,853 L ha−1, respectively). Higher desirable contents of soluble sugar, cellulose, and hemicellulose were observed at SHS and SHC sites, while sorghum grown at SAW possessed higher lignin and ash contents. Biomass type sorghum was superior to sweet type as non-food ethanol feedstock. In particular, biomass type hybrid GN-10 achieved the highest biomass (17.4 t ha−1) and theoretical ethanol yields (5,423 L ha−1) after averaging data for all environmental sites. The most productive hybrid, biomass type GN-4, exhibited biomass and theoretical ethanol yields >42.1 t ha−1 and 14,913 L ha−1, respectively, at the cropland SHC site. In conclusion, energy sorghum grown on marginal lands showed a very lower ethanol potential, indicating a considerable lower possibility for being used as commercial feedstock supply when compared with that grown on regular croplands. Moreover, screening suitable varieties may improve energy sorghum growth and chemical properties for ethanol production on marginal lands. PMID:29686688

Performance of sorghum cultivars for biomass quality and biomethane yield grown in semi-arid area of Pakistan.

PubMed

Hassan, Muhammad Umair; Chattha, Muhammad Umer; Mahmood, Athar; Sahi, Shahbaz Talib

2018-05-01

Biomass is a promising renewable energy source and its significance is escalating in the context of climate change and depletion of fossil foils. This study was conducted for two consecutive years 2016 and 2017, using five sorghum cultivars, i.e., JS-263, Jawar-2011, Hagari, JS-2002, and YS-2016, in order to determine the best cultivars in terms of dry matter yield, chemical composition, and biomethane yield grown under semi-arid conditions in Pakistan. The results revealed that sorghum cultivars responded differently in terms of growth, biomass yield, chemical composition, and methane yield. Cultivars Jawar-2011 produced maximum leaf area index, leaf area duration, crop growth rate, plant height, and leaves per plant, however, they were comparable with Sorghum-2016, whereas cultivar JS-2002 performed poorly among the tested cultivars. Similarly, cultivar Jawar-2011 produced maximum dry matter yield (16.37 t ha -1 ) similar to that of YS-2016, further cultivar JS-2002 performed poorly and gave lower dry matter yield (12.87 t ha -1 ). The maximum protein concentration (10.95), neutral detergent fibers (61.20), and lignin contents (5.55) found in Jawar-2011 were comparable with those in YS-2016, while the lowest neutral detergent fiber and lignin contents were found in JS-2002. Although JS-2002 produced the highest specific methane yield per kilogram of volatile solids, it was overcompensated by Jawar-2011 owing to higher dry matter yield per hectare. These results suggested that cultivar Jawar-2011 can be grown successfully in semi-arid conditions of Pakistan in order to get good biomass yield along with higher methane yield.

Treatment Outcomes for T4 Oropharyngeal Squamous Cell Carcinoma.

PubMed

Zenga, Joseph; Wilson, Michael; Adkins, Douglas R; Gay, Hiram A; Haughey, Bruce H; Kallogjeri, Dorina; Michel, Loren S; Paniello, Randal C; Rich, Jason T; Thorstad, Wade L; Nussenbaum, Brian

2015-12-01

Little is known about treatment outcomes for T4 oropharyngeal squamous cell carcinoma (OPSCC), particularly in the era of human papillomavirus (HPV)-related disease. To evaluate oncologic outcomes for T4 OPSCC treated with primary surgical and nonsurgical therapies. Retrospective cohort study of 131 patients from a single academic hospital, who were treated for T4a or T4b OPSCC (with any N stage and without distant metastatic disease at presentation) between 1998 and 2012 and had a minimum 2-year follow-up (the median follow-up time was 34.6 months). This study was conducted between January 1, 1998, and November 1, 2012. Sixty-nine patients underwent nonsurgical therapy, 47 (68%) of whom had p16-positive tumors. Nonsurgical treatment paradigms included induction chemotherapy followed by chemoradiotherapy (n = 36 [54%]), concurrent chemoradiotherapy (n = 29 [43%]), and induction chemotherapy followed by radiation therapy alone (n = 2 [3%]). Sixty-two patients underwent surgical treatment, 50 (81%) of whom had p16-positive tumors. Fifty-seven surgical patients (92%) received adjuvant therapy. Overall survival (OS) was the primary outcome measure. Secondary outcome measures included disease-specific survival (DSS), disease-free survival (DFS), 2-year gastrostomy and tracheostomy tube rates, and major complication rates. Significant baseline differences between the surgical vs nonsurgical groups included age (mean 59.8 vs 55.4 years [P = .005]), sex (male, 95% vs 84% [P = .04]), body mass index (<18.5 [calculated as weight in kilograms divided by height in meters squared], 3% vs 16% [P = .02]), and smoking history of 10 or more pack-years (48% vs 77% [P = .003]). For p16-positive patients, Kaplan-Meier estimates of OS, DSS, and DFS were significantly higher for surgically treated patients than for the nonsurgical group (χ(2)(1) = 7.335 for log-rank P = .007, χ(2)(1) = 8.607 for log-rank P = .003, and χ(2)(1) = 7.763 for log-rank P = .005, respectively

Expanded Criteria for Hepatocellular Carcinoma in Liver Transplant.

PubMed

Haberal, Mehmet; Akdur, Aydıncan; Moray, Gökhan; Arslan, Gülnaz; Özçay, Figen; Selçuk, Haldun; Özdemir, Handan

2017-03-01

Hepatocellular carcinoma is the sixth most common cancer worldwide and is the third highest cause of malignancy-related death. Because of its typically late diagnosis, median survival is approximately 6 to 20 months, with 5-year survival of < 12%. Hepatocellular carcinoma typically arises in the background of cirrhosis, with liver transplant regarded as the optimal therapy for selected patients. Initially, orthotopic liver transplant was limited to patients with extensive unresectable tumors, resulting in uniformly dismal outcomes due to high tumor recurrence rates. Here, we evaluated our long-term results with expanded-criteria liver transplant. From December 1988 to January 2017, we performed 552 liver transplants at Baskent University. In candidates with hepatocellular carcinoma, our expanded criteria for liver transplant is applied regardless of tumor size and number, includes those without major vascular invasion and without distant metastasis, and those with negative cytology (if the patient has ascites). Since 1994, of 61 liver transplants for hepatocellular carcinoma, 36 patients received transplants according to our expanded criteria. Of 36 expanded-criteria patients, 11 were children and 25 were adults. Sixteen patients (4 pediatric, 12 adult) were within our expanded criteria both radiologically and pathologically before transplant. The other 20 patients (7 pediatric, 13 adult) were within Milan criteria radiologically before transplant; however, after liver transplant, when pathologic specimens were evaluated, patients were found to be within our center's expanded criteria. During follow-up, 9/36 patients (25%) had hepatocellular carcinoma recurrence. In pediatric patients, 5-year and 10-year survival rates were 90%; in adults, 5-year survival was 58.7% and 10-year survival was 49.7%. Overall 5-year and 10-year survival rates were 71.7% and 62.7%. Liver transplant is safe and effective in patients with hepatocellular carcinoma in combination with

Embryonal carcinoma antigen and the T/t locus of the mouse.

PubMed Central

Kemler, R; Babinet, C; Condamine, H; Gachelin, G; Guenet, J L; Jacob, F

1976-01-01

The presence of the F9 antigen and of four other antigens related to the T/t locus of the mouse was investigated by immunofluorescence on preimplantation embryos. In morulae heterozygous for any of these t haplotypes, both the appropriate t antigen and the F9 antigen are expressed. The F9 antigen segregates among the progeny of crosses producing embryos homozygous for some (tw32 and tw5) but not for other haplotypes. It is concluded that (i) whatever the time of action of a t haplotype, its corresponding antigen is expressed during cleavage and (ii) the F9 antigen is specified by a gene(s) in the region of the T/t locus. Images PMID:1069295

[Parametrial infiltration of cervix carcinoma: diagnostic value of contrast-enhanced fat-suppressed T1-weighted SE sequences at 1.5 tesla].

PubMed

Scheidler, J; Heuck, A; Wencke, K; Kimmig, R; Müller-Lisse, U; Reiser, M

1997-04-01

To determine whether contrast-enhanced and fat-suppressed sequences contribute to the MR imaging diagnosis of parametrial invasion. 21 patients with carcinoma of the cervix were prospectively examined with a phased-array coil and a 1.5T MR-scanner using the following sequences: transverse T2-weighted turbo spin echo (T2-TSE), T1-weighted spin echo (T1-SE) and fat suppressed T1-weighted SE sequences before and after Gd-DTPA. The sequences were evaluated separately for the presence of parametrial invasion. Image quality and diagnostic confidence were classified on a scale of 0-10 (nondiagnostic-excellent). Findings were compared to the results of the pathohistological examination. Sensitivity, specificity and diagnostic accuracy were highest for T2-TSE sequences (100%, 79% and 86%, respectively). Contrast-enhanced T1-SE sequences with fat-suppression (71%, 79%, and 76%) showed no improvement compared to T2-TSE. Unenhanced fat-suppressed T1-SE (100%, 30%, and 56%) and unenhanced T1-SE (100%, 7%, and 38%) as well as contrast-enhanced T1-SE (86%, 20%, and 47%) were significantly worse than T2-TSE. With similar image quality (p < 0.05) diagnostic confidence was higher on T2-TSE than on any of the other sequences (p < 0.001). Considering the cost-effectiveness of the examination, for the MR diagnosis of parametrial invasion the use of fat-suppressed contrast-enhanced sequences can be abandoned in favour of T2-weighted TSE sequences.

Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer

DTIC Science & Technology

2005-07-01

Morris, L. S., Coleman, N., and Alexander, G. J. Compromised lymphocytes infiltrate hepatocellular carcinoma : the role of T-regulatory cells...regulatory T cells in peripheral blood of patients with hepatocellular carcinoma . Cancer Res., 65: 2457-2464, 2005. 18. Schaefer, C., Kim, G. G., Albers, A

Papillary serous carcinoma of the uterus: increased risk of subsequent or concurrent development of breast carcinoma.

PubMed

Geisler, J P; Sorosky, J I; Duong, H L; Buekers, T E; Geisler, M J; Sood, A K; Anderson, B; Buller, R E

2001-12-01

Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus. (c)2001 Elsevier Science.

[Hyperthyroidism by autonomous metastasis of thyroid carcinoma (author's transl)].

PubMed

Mornex, R; Pousset, G; Briere, J; Daumont, M; Paffoy, J C

1976-01-01

Nine years after surgical ablation of a trabeculo-vesicular carcinoma of the tyroid, a patient developped bone and liver metastasis. She had clinical signs of thyrotoxicosis, clear increase of blood T3 and sligh increase of T4. The TSH secretion was blocked. Exogenous TSH increased iodine uptake in the thyroid and not in the metastasis. After 2 doses of 120 mCi of 131I, she became hypothyroid, the liver was normal and the scan revealed the disappearance of uptake in thyroid and in metastasis. Such a clinical course was previously found in only 10 cases despite the frequent funcitonal differenciation of the metastasis of thyroid carcinomas.

Plasma Level of Interleukin-35 as an Independent Prognostic Indicator in Hepatocellular Carcinoma.

PubMed

Qiu, Xiangting; Wang, Xinhua; Song, Yucui; Chen, Lingling

2016-12-01

Hepatocellular carcinoma is a major type of liver cancer with poor prognosis. The aim of the study was to determine the prognostic significance of plasma interleukin-35 level in hepatocellular carcinoma. A total of 153 hepatocellular carcinoma patients and 153 healthy controls were enrolled. Blood samples were obtained at admission. Plasma interleukin-35 level was analyzed by enzyme-linked immunosorbent assay. Distribution of T cell subset and expression of Fas/FasL protein were detected by flow cytometry. The patients were followed up for 2 years. Poor prognosis was defined as death of hepatocellular carcinoma. The plasma levels of interleukin-35 were significantly higher in the patients than the controls (25.1 ± 13.1, 9.3 ± 6.3 pg/mL, P < 0.001). After adjusted for multiple confounding factors, the multivariate logistic regression analyses reported that high level of interleukin-35 (≥25.0 pg/mL) was associated with the poor prognosis in the patients (OR 6.63, 95 % CI 3.27-13.47). Compared with the patients with low level of interleukin-35 (<25.0 pg/mL), the patients with high level of interleukin-35 showed higher frequencies of CD4+CD25+FoxP3+ and CD3+Foxp3+ regulatory T cells (P < 0.001 and P < 0.001) and also showed higher apoptosis levels of CD8+ T cells (P < 0.001). Circulating interleukin-35 concentration might be an independent prognostic indicator in hepatocellular carcinoma. Such prognostic significance could be partly involved in the activation of regulatory T cell and the apoptosis of CD8+ T cell.

The role of postoperative radiation therapy in carcinoma ex pleomorphic adenoma of the parotid gland

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

Chen, Allen M.; Garcia, Joaquin; Bucci, M. Kara

2007-01-01

Purpose: To evaluate the impact of postoperative radiation therapy on the clinical course of patients with carcinoma ex pleomorphic adenoma of the parotid gland. Methods and Materials: Between 1960 and 2004, 63 patients were treated with definitive surgery for carcinoma ex pleomorphic adenoma of the parotid gland. Forty patients (63%) received postoperative radiation therapy to a median dose of 60 Gy (range, 45-71 Gy). Adenocarcinoma (29 patients), salivary duct carcinoma (16 patients), and adenoid cystic carcinoma (9 patients) were the most common malignant subtypes. Pathologic T -stage was: 16% T1, 33% T2, 32% T3, and 19% T4. Twenty-one patients (33%)more » had microscopically positive margins and 39 (62%) had perineural invasion. Median follow-up was 50 months (range, 2-96 months). Results: The use of postoperative therapy significantly improved 5-year local control from 49% to 75% (p = 0.005) and was associated with an improvement in survival among patients without evidence of cervical lymph node metastasis (p = 0.01). A Cox proportional hazard model identified pathologic involvement of cervical lymph nodes as an independent predictor of overall survival. Overall survival was 16% for patients with pathologic N-positive disease compared with 67% for those whose lymph node status was negative or unknown (p = 0.001). Conclusion: Surgery followed by postoperative radiation should be considered the standard of care for patients with carcinoma ex pleomorphic adenoma.« less

Surgical perspective of T1799A BRAF mutation diagnostic value in papillary thyroid carcinoma.

PubMed

Brahma, Bayu; Yulian, Erwin Danil; Ramli, Muchlis; Setianingsih, Iswari; Gautama, Walta; Brahma, Putri; Sastroasmoro, Sudigdo; Harimurti, Kuntjoro

2013-01-01

Throughout Indonesia, thyroid cancer is one of the ten commonest malignancies, with papillary thyroid carcinoma (PTC) in our hospital accounting for about 60% of all thyroid nodules. Although fine needle aspiration biopsy (FNAB) is the most reliable diagnostic tool, some nodules are diagnosed as indeterminate and second surgery is common for PTC. The aim of this study was to establish the diagnostic value and feasibility of testing the BRAF T1799A mutation on FNA specimens for improving PTC diagnosis. This prospective study enrolled 95 patients with thyroid nodules and future surgery planned. Results of mutational status were compared with surgical pathology diagnosis. Of the 70 cases included in the final analysis, 62.8% were PTC and the prevalence of BRAF mutation was 38.6%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for BRAF mutation analysis were 36%, 100%, 100% and 48%, respectively. With other data findings, nodules with "onset less than 5 year" and "hard consistency" were proven as diagnostic determinants for BRAF mutation with a probability of 62.5%. This mutation was also a significant risk factor for extra-capsular extension. Molecular analysis of the BRAF T1799A mutation in FNAB specimens has high specificity and positive predictive value for PTC. It could be used in the selective patients with clinical characteristics to facilitate PTC diagnosis and for guidance regarding extent of thyroidectomy.

Looking for the Phase Transition—Recent NA61/SHINE Results

NASA Astrophysics Data System (ADS)

Turko, Ludwik

2018-03-01

The fixed-target NA61/SHINE experiment (SPS CERN) looks for the critical point of strongly interacting matter and the properties of the onset of deconfinement. It is a two dimensional scan of measurements of particle spectra and fluctuations in proton-proton, proton-nucleus and nucleus-nucleus interactions as a function of collision energy and system size, corresponding to a two dimensional phase diagram (temperature T - baryonic chemical potential $\\mu_B$). New NA61/SHINE results are presented here, such as transverse momentum and multiplicity fluctuations in Ar+Sc collisions compared to NA61/SHINE p+p and Be+Be data, as well as to earlier NA49 A+A results. Recently, a preliminary signature for the new size dependent effect - rapid changes in system size dependence was observed in NA61-SHINE data, labeled as percolation threshold or onset of fireball. This would be closely related to the vicinity of the hadronic phase transition region.

38 CFR 61.61 - Agreement and funding actions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Agreement and funding... (CONTINUED) VA HOMELESS PROVIDERS GRANT AND PER DIEM PROGRAM § 61.61 Agreement and funding actions. (a) When... meets all of the requirements under this part for the type of assistance requested and VA has funding...

Risk of Nodal Metastasis in Major Salivary Gland Adenoid Cystic Carcinoma.

PubMed

Megwalu, Uchechukwu C; Sirjani, Davud

2017-04-01

Objective To determine the risk of nodal metastasis, examine risk factors for nodal metastasis, and evaluate the impact of nodal metastasis on survival in patients with major salivary gland adenoid cystic carcinoma. Study Design Retrospective cohort study from a large population- based cancer database. Methods Data were extracted from the SEER 18 database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute. The study cohort included 720 patients diagnosed with major salivary gland adenoid cystic carcinoma between 1988 and 2013. Results The overall rate of lymph node metastasis was 17%. T3 disease (odds ratio, 4.74) and T4 disease (odds ratio, 9.24) were associated with increased risk of nodal metastasis. Age, sex, and site were not associated with nodal metastasis. Nodal metastasis was associated with worse overall survival (hazard ratio, 2.56) and disease-specific survival (hazard ratio, 3.27), after adjusting for T stage, presence of distant metastasis, site, surgical resection, radiotherapy, neck dissection, age, sex, race, marital status, and year of diagnosis. Conclusion Major salivary gland adenoid cystic carcinoma carries significant risk of nodal metastasis. Advanced T stage is associated with increased risk of nodal metastasis. Nodal metastasis is associated with worse survival.

Clovamide and Flavonoids from Leaves of Trifolium pratense and T. pratense subsp. nivale Grown in Italy.

PubMed

Tava, Aldo; Pecio, Łukasz; Stochmal, Anna; Pecetti, Luciano

2015-06-01

The phenolic content and composition in leaves of Trifolium pratense (red clover) and T. pratense subsp. nivale (snow clover) grown in Italy were evaluated by means of ultraperformance liquid chromatography (UPLC) coupled with photodiode array and mass spectrometry detectors. Compound identification was based on UV and MS data comparing results with those of reference compounds. Quantitative evaluation of all detected compounds was based on calibration curves obtained with available standards. Several phenolics were identified in both extracts, including clovamide, flavonols and isoflavones as their glycosilated and malonated derivatives. The total phenolic content was higher in red clover (53.7 ± 2.2 mg/g dry weight) than in snow clover (44.4 ± 4.9 mg/g dry weight). Red clover contained higher amounts of clovamide and isoflavones (15.6 ± 0.6 and 24.6 ± 1.6 mg/g dry weight, respectively) than snow clover (8.2 ± 0.1 mg/g and 16.9 ± 0.4 mg/g dry weight, respectively), while flavonols were quantified almost in the same amount in both extracts (13.2 ± 0.6 mg/g and 15.8 ± 0.6 mg/g dry weight in red clover and snow clover, respectively). Red clover was characterized by the presence of quercetin, formononetin and biochanin A derivatives as the most abundant flavonoids, whereas snow clover was characterized by higher amounts of quercetin and prunetin derivatives. This investigation, conducted for the first time on phenolics from T. pratense subsp. nivale, revealed the presence in this plant of several flavonoid derivatives the same as in T. pratense. The higher amount of prunetin in snow clover suggest a possible role of this isoflavone as a chemotaxonomic marker for this subspecies. Moreover, snow clover may represent an interesting new source of natural isoflavones with a different concentration pattern than in red clover.

CT volumetry for gastric carcinoma: association with TNM stage.

PubMed

Hallinan, James T P D; Venkatesh, Sudhakar K; Peter, Luke; Makmur, Andrew; Yong, Wei Peng; So, Jimmy B Y

2014-12-01

We evaluated the feasibility of performing CT volumetry of gastric carcinoma (GC) and its correlation with TNM stage. This institutional review board-approved retrospective study was performed on 153 patients who underwent a staging CT study for histologically confirmed GC. CT volumetry was performed by drawing regions of interest including abnormal thickening of the stomach wall. Reproducibility of tumour volume (Tvol) between two readers was assessed. Correlation between Tvol and TNM/peritoneal staging derived from histology/surgical findings was evaluated using ROC analysis and compared with CT evaluation of TNM/peritoneal staging. Tvol was successfully performed in all patients. Reproducibility among readers was excellent (r = 0.97; P = 0.0001). The median Tvol of GC showed an incremental trend with T-stage (T1 = 27 ml; T2 = 32 ml; T3 = 53 ml and T4 = 121 ml, P < 0.01). Tvol predicted with good accuracy T-stage (≥T2:0.95; ≥T3:0.89 and T4:0.83, P = 0.0001), M-stage (0.87, P = 0.0001), peritoneal metastases (0.87, P = 0.0001) and final stage (≥stage 2:0.89; ≥stage 3:0.86 and stage 4:0.87, P = 0.0001), with moderate accuracy for N-stage (≥N1:0.75; ≥N2:0.74 and N3:0.75, P = 0.0001). Tvol was significantly (P < 0.05) more accurate than standard CT staging for prediction of T-stage, N3-stage, M-stage and peritoneal metastases. CT volumetry may provide useful adjunct information for preoperative staging of GC. CT volumetry of gastric carcinoma is feasible and reproducible. Tumour volume <19.4 ml predicts T1-stage gastric cancer with 91% sensitivity and 100% specificity (P = 0.0001). Tumour volume >95.7 ml predicts metastatic gastric cancer with 87% sensitivity and 78.5% specificity (P = 0.0001). CT volumetry may be a useful adjunct for staging gastric carcinoma.

Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma

PubMed Central

Thelen, Martin; Reuter, Sabrina; Zentis, Peter; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; Wennhold, Kerstin; Garcia-Marquez, Maria; Tharun, Lars; Quaas, Alexander; Schauss, Astrid; Isensee, Jörg; Hucho, Tim; Huebbers, Christian

2017-01-01

The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naïve HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA−/CCR7−). Naïve T cells (CD45RA+/CCR7+) were decreased in the microenvironment compared to PBMC of patients, while regulatory T cells (CD4+/CD25+/CD127low and CD4+/CD39+) were elevated. Furthermore, we performed digital image analyses of entire cross sections of HNSCC to define the ‘Immunoscore’ (CD3+ and CD8+ cell infiltration in tumor core and invasive margin) and quantified MHC class I expression on tumor cells by immunohistochemistry. Immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) were increased in TILs compared to peripheral T cells in flow-cytometric analysis. Human papillomavirus (HPV) positive tumors showed higher numbers of TILs, but a similar composition of T-cell subsets and checkpoint molecule expression compared to HPV negative tumors. Taken together, the tumor microenvironment of HNSCC is characterized by a strong infiltration of regulatory T cells and high checkpoint molecule expression on T-cell subsets. In view of increasingly used immunotherapies, a detailed knowledge of TILs and checkpoint molecule expression on TILs is of high translational relevance. PMID:28574843

Phospho-T356RB1 predicts survival in HPV-negative squamous cell carcinoma of the head and neck

PubMed Central

Handorf, Elizabeth; Nikonova, Anna; Dubyk, Cara; Peri, Suraj; Lango, Miriam; Ridge, John A.; Serebriiskii, Ilya G.; Burtness, Barbara; Golemis, Erica A.; Mehra, Ranee

2015-01-01

Locally advanced squamous cell carcinoma of the head and neck (SCCHN) that is not associated with human papillomavirus (HPV) has a poor prognosis in contrast to HPV-positive disease. To better understand the importance of RB1 activity in HPV-negative SCCHN, we investigated the prognostic value of inhibitory CDK4/6 phosphorylation of RB1 on threonine 356 (T356) in archival HPV-negative tumor specimens from patients who underwent surgical resection and adjuvant radiation. We benchmarked pT356RB1 to total RB1, Ki67, pT202/Y204ERK1/2, and TP53, as quantified by automatic quantitative analysis (AQUA), and correlated protein expression with tumor stage and grade. High expression of pT356RB1 but not total RB1 predicted reduced overall survival (OS; P = 0.0295), indicating the potential relevance of post-translational phosphorylation. Paired analysis of The Cancer Genome Atlas (TCGA) data for regulators of this RB1 phosphorylation identified loss or truncating mutation of negative regulator CDKN2A (p16) and elevated expression of the CDK4/6 activator CCND1 (cyclin D) as also predicting poor survival. Given that CDK4/6 inhibitors have been most effective in the context of functional RB1 and low expression or deletion of p16 in other tumor types, these data suggest such agents may merit evaluation in HPV-negative SCCHN, specifically in cases associated with high pT356RB1. PMID:26265441

Cervical lymph node metastases in squamous cell carcinoma of tongue and floor of mouth.

PubMed

Ehsan-ul-Haq, Muhammad; Warraich, Riaz Ahmed; Abid, Hina; Sajid, Malik Ali Hassan

2011-01-01

Oral squamous cell carcinoma has high chances of cervical lymph node metastasis. This case series describes the distribution of cervical lymph nodes in 50 cases of squamous cell carcinoma of tongue and floor of mouth. The mean age was 47.28±10.5 years. Thirty positive metastatic lymph nodes were found; 90% occurring at level I-II mostly in T4 size but also in T1 and T2 cases. The distribution of involved lymph nodes in oral cancer affects the neck dissection extent and is, therefore, an important pre-operative feature.

T-category remains an important prognostic factor for oropharyngeal carcinoma in the era of human papillomavirus.

PubMed

Mackenzie, P; Pryor, D; Burmeister, E; Foote, M; Panizza, B; Burmeister, B; Porceddu, S

2014-10-01

To determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. OSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. In total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05-0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14-0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22-1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08-2.99), death (hazard ratio 1.37, 95% confidence interval 1.06-1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00-1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. Tumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Vulvar intraepithelial neoplasia with superficially invasive carcinoma of the vulva.

PubMed

Herod, J J; Shafi, M I; Rollason, T P; Jordan, J A; Luesley, D M

1996-05-01

To investigate the long-term outcome of patients presenting with vulvar intraepithelial neoplasia (VIN) with superficially invasive carcinoma of the vulva (SICa). A retrospective study using information obtained from patient case notes. Twenty-six women found at presentation to have VIN in association with superficially invasive carcinoma were identified during a 15-year period. Pruritus vulvae was the most frequent presenting symptom in 18 patients (69%). Sixteen women (61.5%) had multiple symptoms. Features noted at vulvar examination were variable and none were pathognomonic of either VIN or of superficial invasion. All patients had VIN 3 in association with a superficially invasive carcinoma. Histological changes associated with human papillomavirus were found in 19 (73%) women. Half had a co-existent or previous abnormality of the lower genital tract. Local excision was the most frequent initial treatment (n = 9 [35%]). Mean follow up time was 65 months (range 12-174). Disease persisted after primary treatment in five women (19%). Both histological recurrence (of either VIN or SICa) or symptomatic recurrence occurred in 10 patients (38%). All patients who experienced recurrence did so within 36 months of treatment. Overall, 12 patients (46%) relapsed (histological or symptomatic recurrence); the mean time was 18 months. Fourteen patients (54%) were managed satisfactorily by their initial treatment. One patient died of recurrent cervical cancer. Three progressed to frankly invasive disease: two (aged 31 and 39 years) with carcinoma of the vulva and one aged 34 years with carcinoma of the perianal margin. All are alive and well after treatment. One patient had recurrence of superficially invasive carcinoma treated by local excision with no further problems. No episode of metastasis via lymphatic or vascular channels has been seen. Patients with superficially invasive carcinoma of the vulva may be safely treated by local excisional methods without recourse to

[Efficacy of the combination therapy in early stage of recurrent cholangio celluler carcinoma (CCC)].

PubMed

Fujiwara, Shinichi; Hasuike, Yasunori; Fukuchi, Nariaki; Hayashi, Nobuyasu; Kida, Hiroyuki; Tsujie, Masaki; Yoshida, Tetsuya; Ebisui, Chikara; Sakita, Isao; Fujimoto, Takayoshi

2005-10-01

We report a case of cholangio celluler carcinoma (CCC) with a good quality of life, in spite of the recurrence of peritoneum and portal hepatic lymph nodes (PHLN), due to the combination therapy that consisted of hepatic arterial infusion, systemic chemotherapy, radiation therapy and an insertion of a metallic stent into the bile duct. The patient was a 61-year-old man. Left hepatectomy was done due to multiple CCC. For the purpose of preventing the recurrence of CCC in residual liver, we performed an arterial infusion therapy. Ten months later, metastases to peritoneum and portal hepatic lymph nodes were found, so the resection of the peritoneum was performed, and cells in ascites were defined to be positive with cytology. After 2 years from the first operation, the size of portal hepatic lymph nodes had grown and both the billilbin and tumor marker levels had increased, so we started systemic chemotherapy, radiation therapy and insertion of a metallic stent into the bile duct. The tumor marker level decreased in a short time. Consequently, we inserted a metallic stent into the bile duct and radiation therapy was performed. Until the patient's death due to peritonitis carcinomatosa, the recurrence in residual liver occurred only once in three years after the first operation, and portal hepatic lymph nodes did not grow for two years after the recurrence.

Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression.

PubMed

Dong, Jianfeng; Cheng, Lijun; Zhao, Minchao; Pan, Xiangfeng; Feng, Zhiqiang; Wang, Dawei

2017-05-01

Oropharyngeal head and neck squamous cell carcinoma is a common malignant tumor in the oral cavity. High-risk human papillomavirus 16 infection is a major cause of oropharyngeal head and neck squamous cell carcinoma development. Strong antitumor immune responses, especially CD8 + T cell responses, are thought to be essential to effective cancer treatment and are associated with better prognosis in oropharyngeal head and neck squamous cell carcinoma. In this study, we examined the role of the Tim-3/Gal-9 pathway in oropharyngeal head and neck squamous cell carcinoma patients. We found that Gal-9 expression by CD4 + T cells was increased in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients, but not in human papillomavirus-negative oropharyngeal head and neck squamous cell carcinoma patients. Increased Gal-9 secretion by CD4 + T cells presented multiple immunosuppressive effects. Coculturing monocytes with high Gal-9-expressing CD4 + T cells resulted in the expansion of Tim-3 + monocytes, which suppressed interferon gamma production by activated CD8 + T cells. Subsequently, total monocytes incubated with exogenous Gal-9, or high Gal-9-expressing CD4 + T cells, suppressed the expression of interferon gamma by CD8 + T cells. Exogenous Gal-9 and high Gal-9-expressing CD4 + T cells also suppressed the secretion of both interleukin 10 and interleukin 12 by monocytes. These effects are Tim-3/Gal-9-dependent because blocking Tim-3 and/or Gal-9 could enhance the support of CD8 + T cell interferon gamma production and the interleukin 10 and interleukin 12 secretion by monocytes. Together, these data suggest that the high Tim-3 expression in monocytes could be utilized by tumor-promoting Gal-9 expression on CD4 + T cells. Immunotherapy in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients therefore faces an additional challenge posed by Tim-3 and Gal-9 and likely requires the blockade of these

Incidence of breast carcinoma in women with thyroid carcinoma.

PubMed

Vassilopoulou-Sellin, R; Palmer, L; Taylor, S; Cooksley, C S

1999-02-01

Breast carcinoma and differentiated thyroid carcinoma(the most common endocrine malignancy) occur predominantly in women. An association between the two tumors has been suggested by some investigators, but the potential impact of treatment of one of these diseases on the development of the other remains unclear. The authors examined the relation between the occurrence of these two tumors. There were 41,686 patients with breast carcinoma and 3662 with thyroid carcinoma who registered at The University of Texas M. D. Anderson Cancer Center between March 1944 and April 1997. Women who received both diagnoses since 1976 were identified and incidence rates and relative risks of secondary tumor development were calculated. Surveillance, Epidemiology and End Results (SEER) program data on the age-adjusted incidences of these diseases during the same time period were used for the expected incidences in the same population. Among 18,931 women with a diagnosis of breast carcinoma since 1976, 11 developed differentiated thyroid carcinoma > or = 2 years after the diagnosis of breast carcinoma. These breast carcinoma patients contributed 129,336 person-years of follow-up; the observed incidence of thyroid carcinoma in this group was not different from that in a similar age group of women in the SEER database. Among 1013 women with a diagnosis of thyroid carcinoma since 1976, 24 developed breast carcinoma > or = 2 years after the diagnosis of thyroid carcinoma. These thyroid carcinoma patients contributed 8380 person-years of follow-up; the observed incidence of breast carcinoma in women ages 40-49 years was significantly higher than the expected incidence for women in the same age group in the SEER database. Breast carcinoma developing after thyroid carcinoma was diagnosed more frequently than expected in young adult women seen at the study institution since 1976. This potential association and plausible mechanisms of breast carcinoma development after thyroid carcinoma should

Perineural Spread of Renal Cell Carcinoma: A Case Illustration with a Proposed Anatomic Mechanism and a Review of the Literature.

PubMed

Capek, Stepan; Krauss, William E; Amrami, Kimberly K; Parisi, Joseph E; Spinner, Robert J

2016-05-01

Perineural spread (PNS) is an unusual mechanism of tumor extension and has been typically reported in squamous cell carcinoma, adenocystic carcinoma, and desmoplastic melanoma. Our group has previously demonstrated PNS in rectal, prostate, bladder, and cervical cancer from the primary site along the autonomic nerves to the major somatic nerves and even intradurally. We believe similar principles apply to renal cell carcinoma (RCC) as well, despite the different anatomy. We performed a retrospective search to identify cases of intradural-extramedullary metastases of RCC caused by PNS. Strict anatomic and imaging inclusion criteria were defined: only lesions located between T6 and L3 were included, and PNS as a potential cause had to be supported by imaging evidence. Although 3 cases of spinal intradural metastases were identified, only one met our strict inclusion criteria. A 61-year-old woman developed a late intradural-extramedullary metastasis of RCC 16 years after the original diagnosis that we believe represents an example of visceral organ PNS. RCC can propagate via PNS from the primary tumor along the autonomic nerves to the aorticorenal, celiac, and mesenteric ganglia and then along the thoracic and lumbar splanchnic nerves to the corresponding spinal nerves and intradurally. We present radiologic evidence together with the review of the literature to support the premise that PNS of RCC not only occurs but goes unrecognized. Copyright © 2016 Elsevier Inc. All rights reserved.

Signal-on electrochemical assay for label-free detection of TdT and BamHI activity based on grown DNA nanowire-templated copper nanoclusters.

PubMed

Hu, Yufang; Zhang, Qingqing; Xu, Lihua; Wang, Jiao; Rao, Jiajia; Guo, Zhiyong; Wang, Sui

2017-11-01

Electrochemical methods allow fast and inexpensive analysis of enzymatic activity. Here, a simple and yet efficient "signal-on" electrochemical assay for sensitive, label-free detection of DNA-related enzyme activity was established on the basis of terminal deoxynucleotidyl transferase (TdT)-mediated extension strategy. TdT, which is a template-independent DNA polymerase, can catalyze the sequential addition of deoxythymidine triphosphate (dTTP) at the 3'-OH terminus of single-stranded DNA (ssDNA); then, the TdT-yield T-rich DNA nanowires can be employed as the synthetic template of copper nanoclusters (CuNCs). Grown DNA nanowires-templated CuNCs (noted as DNA-CuNCs) were attached onto graphene oxide (GO) surface and exhibited unique electrocatalytic activity to H 2 O 2 reduction. Under optimal conditions, the proposed biosensor was utilized for quantitatively monitoring TdT activity, with the observed LOD of 0.1 U/mL. It also displayed high selectivity to TdT with excellent stability, and offered a facile, convenient electrochemical method for TdT-relevant inhibitors screening. Moreover, the proposed sensor was successfully used for BamHI activity detection, in which a new 3'-OH terminal was exposed by the digestion of a phosphate group. Ultimately, it has good prospects in DNA-related enzyme-based biochemical studies, disease diagnosis, and drug discovery. Graphical Abstract Extraordinary TdT-generated DNA-CuNCs are synthesized and act as a novel electrochemical sensing platform for sensitive detection of TdT and BamHI activity in biological environments.

SU-E-T-503: Intensity Modulated Proton Therapy (IMPT) Versus Intensity Modulated X-Ray Therapy (IMRT) for Patient with Hepatocellular Carcinoma: A Dosimetric Comparison

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

Singh, H; Zhao, L; Prabhu, K

2015-06-15

Purpose This study compares the dosimetric parameters in treatment of unresectable hepatocellular carcinoma between intensity modulated proton therapy (IMPT) and intensity modulated x-ray radiation therapy (IMRT). Methods and Materials: We studied four patients treated at our institution. All patients were simulated supine with 4D-CT using a GE light speed simulator with a maximum slice thickness of 3mm. The average CT and an internal target volume to account for respiration motion were used for planning. Both IMRT and IMPT plans were created using Elekta’s CMSXiO treatment planning system (TPS). The prescription dose was 58.05 CGE in 15 fractions. The IMRT plansmore » had five beams with combination of co-planar and non-co-planar. The IMPT plans had 2 to 3 beams. Dose comparison was performed based on the averaged results of the four patients. Results The mean dose and V95% to PTV were 58.24CGE, 98.57% for IMPT, versus 57.34CGE and 96.68% for IMRT, respectively. The V10, V20, V30 and mean dose of the normal liver for IMPT were 23.10%, 18.61%, 13.75% and 9.78 CGE; and 47.19%, 37.55%, 22.73% and 17.12CGE for IMRT. The spinal cord didn’t receive any dose in IMPT technique, but received a maximum of 18.77CGE for IMRT. The IMPT gave lower maximum dose to the stomach as compared to IMRT (19.26 vs 26.35CGE). V14 for left and right kidney was 0% and 2.32% for IMPT and 3.89% and 29.54% for IMRT. The mean dose, V35, V40 and V45 for small bowl were similar in both techniques, 0.74CGE, 6.27cc, 4.85cc and 3.53 cc for IMPT, 3.47CGE, 9.73cc, 7.61cc 5.35cc for IMRT. Conclusion Based on this study, IMPT plans gave less dose to the critical structures such as normal liver, kidney, stomach and spinal cord as compared to IMRT plans, potentially leading to less toxicity and providing better quality of life for patients.« less

Impact of spontaneous tumor rupture on prognosis of patients with T4 hepatocellular carcinoma

PubMed Central

Chan, Wen‐Hui; Hung, Chien‐Fu; Pan, Kuang‐Tse; Lui, Kar‐Wai; Huang, Yu‐Ting; Lin, Shen‐Yen; Lin, Yang‐Yu; Wu, Tsung‐Han

2016-01-01

Background and objectives Compare the outcomes of three groups of patients with T4 hepatocellular carcinoma (HCC): tumor rupture with shock (RS group), tumor rupture without shock (R group), and no tumor rupture (NR group). Materials and Methods We retrospectively reviewed 221 patients with T4 HCC from 2010 to 2012. The clinical background and prognosis were analyzed. Results Overall in‐hospital mortality rate was 18.1%; overall median survival time was 4 months. The NR group were more likely to have multiple and infiltrative tumors (P < 0.001). Relative to the NR group, the R + RS group had better survival rates at 6 months (49.2% vs. 32.2%), 1 year (35.3% vs. 21.0%), 3 years (22.5% vs. 11.0%), and 5 years (17.7% vs. 5.5%) (P = 0.010). Patients in the RS group had a higher in‐hospital mortality rate, but significantly better long‐term survival than the NR and R group (P < 0.001). Multivariate analysis indicated that Child‐Pugh class B or C, presence of portal venous thrombosis, and absence of shock were significantly associated with poor survival. Conclusion Patients with tumor rupture and shock had worse in‐hospital survival. However, patients without decompensated liver cirrhosis and portal venous thrombosis, and eligible for curative treatment had favorable long‐term outcome. J. Surg. Oncol. 2016;113:789–795. © 2016 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc. PMID:27062288

[Poorly differentiated thyroid carcinomas: new therapeutic considerations].

PubMed

Graf, Hans

2005-10-01

For most differentiated thyroid carcinomas, as papillary and follicular carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant ablation, treatment with thyroid hormones to suppress TSH levels will reduce the growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation therapy will either cure or control the disease. Thyroid carcinomas are considered poorly differentiated when they start to lose such functions as iodine uptake and thyrotropin-dependence for growth and production of thyroid proteins like NIS, thyroglobulin and desiodases. One of the greatest challenges in the management of patients with follicular cell-derived thyroid cancer is the treatment of tumors that progressed despite surgery, (131)I and T4 suppression of TSH. With the better knowledge of the abnormal molecular signaling in thyroid cancer cells, actually known targeted cancer therapies, directed against molecules involved in neoplastic transformation, are being used. As the critical molecular requirements for tumor initiation, maintenance and progression are identified, combination therapies with targeted agents acting on each of them will improve the treatment of poorly differentiated thyroid carcinoma.

Salvage surgery in the treatment of local recurrences of nasopharyngeal carcinomas.

PubMed

Salom, María Cecilia; López, Fernando; Pacheco, Esteban; Muñoz, Gabriela; García-Cabo, Patricia; Fernández, Laura; Suárez, Vanessa; Llorente, José Luis

2018-04-03

Chemoradiotherapy is the treatment of choice for nasopharyngeal carcinoma. Local recurrences are one of the leading causes of death in these patients, and surgical salvage the treatment of choice. Our goal was to evaluate and compare the results of salvage surgery in the treatment of local recurrence of nasopharyngeal carcinomas comparing endoscopic to open approaches. Twenty patients with local recurrence of nasopharyngeal carcinomas underwent surgery: 12 patients underwent open surgery and 8 endoscopic endonasal transpterygoid nasopharyngectomy. One patient was classified as rT1; 3 as rT2;2 as rT3; and 6 as rT4 in the group of open approaches; in the endoscopic series, 2 patients were rT1, 5 rT2 and one rT3. In 3 patients (25%) operated by an open approach (one rT4, one rT3 and one rT2) a complete gross resection was not achieved. Gross total resection was achieved in patients operated by endoscopic surgery. The complication rate in the group operated by an open approach was 92% (5 minor complications, 5 moderate complications, and one serious complication) and in the group that underwent endoscopic surgery all patients had some complication (7 had minor complications and one patient developed a severe complication). Survival at 3 and 5 years was 53% and 42% with the open approach and 100% and 50% with the endoscopic approach, respectively. Endoscopic approaches decrease the morbidity associated with open approaches and allow for favourable oncological control. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma-Implications for Adoptive Cell Therapy.

PubMed

Andersen, Rikke; Westergaard, Marie Christine Wulff; Kjeldsen, Julie Westerlin; Müller, Anja; Pedersen, Natasja Wulff; Hadrup, Sine Reker; Met, Özcan; Seliger, Barbara; Kromann-Andersen, Bjarne; Hasselager, Thomas; Donia, Marco; Svane, Inge Marie

2018-02-01

In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCL) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared with those generated from metastatic melanoma. Immune recognition of autologous TCLs or fresh tumor digests was observed in CD8 + TILs from 82% of patients (18/22). Cytotoxicity assays confirmed the tumoricidal capacity of RCC-TILs. The overall expansion capacity of RCC-TILs was similar to MM-TILs. However, the magnitude, polyfunctionality, and ability to expand in classical expansion protocols of CD8 + T-cell responses was lower compared with MM-TILs. The RCC-TILs that did react to the tumor were functional, and antigen presentation and processing of RCC tumors was similar to MM-TILs. Direct recognition of tumors with cytokine-induced overexpression of human leukocyte antigen class II was observed from CD4 + T cells (6/12; 50%). Thus, TILs from primary RCC specimens could be isolated, expanded, and could recognize tumors. However, immune responses of expanded CD8 + RCC-TILs were typically weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select, enrich, and expand tumor-reactive polyfunctional T cells may be critical in developing effective ACT with TILs for RCC. In summary, TILs isolated from primary RCC specimens could recognize tumors. However, their immune responses were weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select and expand polyfunctional T cells may improve cell therapy for RCC. Cancer Immunol Res; 6(2); 222-35. ©2018 AACR

Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus.

PubMed

Miner, Andrew G; Patel, Rajiv M; Wilson, Deborah A; Procop, Gary W; Minca, Eugen C; Fullen, Douglas R; Harms, Paul W; Billings, Steven D

2015-04-01

Merkel cell carcinoma is a rare, highly aggressive cutaneous neuroendocrine carcinoma most commonly seen in sun-damaged skin. Histologically, the tumor consists of primitive round cells with fine chromatin and numerous mitoses. Immunohistochemical stains demonstrate expression of neuroendocrine markers. In addition, cytokeratin 20 (CK20) is expressed in ∼95% of cases. In 2008, Merkel cell carcinoma was shown to be associated with a virus now known as Merkel cell polyomavirus in ∼80% of cases. Prognostic and mechanistic differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel cell carcinoma may exist. There has been the suggestion that CK20-negative Merkel cell carcinomas less frequently harbor Merkel cell polyomavirus, but a systematic investigation for Merkel cell polyomavirus incidence in CK20-negative Merkel cell carcinoma has not been done. To test the hypothesis that Merkel cell polyomavirus is less frequently associated with CK20-negative Merkel cell carcinoma, we investigated 13 CK20-negative Merkel cell carcinomas from the files of the Cleveland Clinic and the University of Michigan for the virus. The presence or absence of Merkel cell polyomavirus was determined by quantitative PCR performed for Large T and small T antigens, with sequencing of PCR products to confirm the presence of Merkel cell polyomavirus. Ten of these (77%) were negative for Merkel cell polyomavirus and three (23%) were positive for Merkel cell polyomavirus. Merkel cell polyomavirus is less common in CK20-negative Merkel cell carcinoma. Larger series and clinical follow-up may help to determine whether CK20-negative Merkel cell carcinoma is mechanistically and prognostically unique.

Number of negative lymph nodes as a prognostic factor in esophageal squamous cell carcinoma.

PubMed

Ma, Mingquan; Tang, Peng; Jiang, Hongjing; Gong, Lei; Duan, Xiaofeng; Shang, Xiaobin; Yu, Zhentao

2017-10-01

The aim of this study is to investigate the number of negative lymph nodes (NLNs) as a prognostic factor for survival in patients with resected esophageal squamous cell carcinoma. A total of 381 esophageal squamous cell carcinoma patients who had underwent surgical resection as the primary treatment was enrolled into this retrospective study. The impact of number of NLNs on patient's overall survival was assessed and compared with the factors among the current tumor-nodes-metastasis (TNM) staging system. The number of NLNs was closely related to the overall survival, and the 5-year survival rate was 45.4% for number of NLNs of >20 (142 cases) and 26.4% for NLNs ≤ 20 (239 cases) (P = 0.001). In multivariate survival analysis, the number of NLNs remained an independent prognostic factor (P = 0.002) as did the other current TNM factors. For subgroup analysis, the predictive value of number of NLNs was significant in patients with T3 or T4 disease (P = 0.001) and patients with N1 and N2-3 disease (P = 0.025, 0.043), but not in patients with T1 or T2 disease or patients with N0 disease. The number of NLNs, which represents the extent of lymphadenectomy for esophageal squamous cell carcinoma, could impact the overall survival of patients with resected esophageal squamous cell carcinoma, especially among those with nodal-positive disease and advanced T-stage tumor. © 2016 John Wiley & Sons Australia, Ltd.

Structural and photoluminescence studies on europium-doped lithium tetraborate (Eu:Li2B4O7) single crystal grown by microtube Czochralski (μT-Cz) technique

NASA Astrophysics Data System (ADS)

A, Kumaresh; R, Arun Kumar; N, Ravikumar; U, Madhusoodanan; B, S. Panigrahi; K, Marimuthu; M, Anuradha

2016-05-01

Rare earth europium (Eu3+)-doped lithium tetraborate (Eu:Li2B4O7) crystal is grown from its stoichiometric melt by microtube Czochralski pulling technique (μT-Cz) for the first time. The grown crystals are subjected to powder x-ray diffraction (PXRD) analysis which reveals the tetragonal crystal structure of the crystals. UV-vis-NIR spectral analysis is carried out to study the optical characteristics of the grown crystals. The crystal is transparent in the entire visible region, and the lower cutoff is observed to be at 304 nm. The existence of BO3 and BO4 bonding structure and the molecular associations are analyzed by Fourier transform infrared (FTIR) spectroscopy. The results of excitation and emission-photoluminescence spectra of europium ion incorporated in lithium tetraborate (LTB) single crystal reveal that the observations of peaks at 258, 297, and 318 nm in the excitation spectra and peaks at 579, 591, 597, 613, and 651 nm are observed in the emission spectra. The chromaticity coordinates are calculated from the emission spectra, and the emission intensity of the grown crystal is characterized through a CIE 1931 (Commission International d’Eclairage) color chromaticity diagram. Project supported by the Department of Science and Technology-Science and Engineering Research Board (Grant No. SR/S2/LOP-0012/2011), the Government of India for Awarding Major Research Project, the University Grants Commission-Department of Atomic Research-Consortium for Scientific Research (Grant No. CSR-KN/CSR-63/2014-2015/503), and the Kalpakkam and Indore, India.

Metal-insulator transition characteristics of VO2 thin films grown on Ge(100) single crystals

NASA Astrophysics Data System (ADS)

Yang, Z.; Ko, C.; Ramanathan, S.

2010-10-01

Phase transitions exhibited by correlated oxides could be of potential relevance to the emerging field of oxide electronics. We report on the synthesis of high-quality VO2 thin films grown on single crystal Ge(100) substrates by physical vapor deposition and their metal-insulator transition (MIT) properties. Thermally triggered MIT is demonstrated with nearly three orders of magnitude resistance change across the MIT with transition temperatures of 67 °C (heating) and 61 °C (cooling). Voltage-triggered hysteretic MIT is observed at room temperature at threshold voltage of ˜2.1 V for ˜100 nm thickness VO2 films. Activation energies for electron transport in the insulating and conducting states are obtained from variable temperature resistance measurements. We further compare the properties of VO2 thin films grown under identical conditions on Si(100) single crystals. The VO2 thin films grown on Ge substrate show higher degree of crystallinity, slightly reduced compressive strain, larger resistance change across MIT compared to those grown on Si. Depth-dependent x-ray photoelectron spectroscopy measurements were performed to provide information on compositional variation trends in the two cases. These results suggest Ge could be a suitable substrate for further explorations of switching phenomena and devices for thin film functional oxides.

Bladder chondrosarcoma plus urothelial carcinoma in recurred transitional cell carcinoma of the upper urinary tract: a case report and literature review.

PubMed

Cho, Min Hyun; Kim, Sung Han; Park, Weon Seo; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Lee, Kang Hyun

2016-10-20

Sarcomatoid urothelial carcinoma (SUC) is a rare malignant neoplasm of the urinary bladder comprising 0.2-0.6 % of all histological bladder tumor subtypes. It presents as a high-stage malignancy and exhibits aggressive biological behavior, regardless of the treatment employed. It is defined as histologically indistinguishable from sarcoma and as a high-grade biphasic neoplasm with malignant epithelial and mesenchymal components. The mean age of patients presenting with SUC is 66 years, and the male-to-female ratio is 3:1. In addition, gross hematuria is usually present. The prognosis of SUC is poorer than that of typical urothelial carcinoma because of uncertainty concerning the optimal treatment regimen. We report the case of a 77-year-old woman with SUC containing a chondrosarcoma component who, 12 years previously, had undergone a nephroureterectomy for pT3N0M0 ureter cancer of the contralateral upper urinary tract. From the 4th year of follow-up after nephroureterectomy, multiple recurrent bladder tumors staged as Ta transitional cell carcinoma developed, and six transurethral resections of the bladder (TURB) with multiple intravesical instillations were performed without any evidence of metastases and upper tract recurrences. In 2015, a right partial distal ureterectomy and an additional TURB were performed due to a papillary mass at the right contralateral ureterovesical junction of the bladder, which was confirmed as a high-grade pT1 transitional cell carcinoma. After a further 2 years of follow-up, total pelvic exenteration with an ileal conduit diversion was performed to remove the mass, which was a pT4N0M0 tumor composed of carcinomatous and sarcomatous elements compatible with a sarcomatoid carcinoma including grade 3 transitional cell carcinoma and chondrosarcoma. Immunohistochemical examination showed that tumor cells were positive for vimentin and p63 and negative for NSE and Cd56 markers. In the first postoperative month, a metastatic lung nodule

Characterization of B61, the ligand for the Eck receptor protein-tyrosine kinase.

PubMed

Shao, H; Pandey, A; O'Shea, K S; Seldin, M; Dixit, V M

1995-03-10

B61 was originally described as a novel secreted tumor necrosis factor-alpha-inducible gene product in endothelial cells (Holzman, L. B., Marks, R. M., and Dixit, V. M. (1990) Mol. Cell. Biol. 10, 5830-5838). It was recently discovered that soluble recombinant B61 could serve as a ligand for the Eck receptor protein-tyrosine kinase, a member of the Eph/Eck subfamily of receptor protein-tyrosine kinases (Bartley, T.D., Hunt, R. W., Welcher, A. A., Boyle, W. J., Parker, V. P., Lindberg, R. A., Lu, H. S., Colombero, A. M., Elliott, R. L., Guthrie, R. A., Holst, P. L., Skrine, J. D., Toso, R. J., Zhang, M., Fernandez, E., Trail, G., Yarnum, B., Yarden, Y., Hunter, T., and Fox, G. M. (1994) Nature 368, 558-560). We now show that B61 can also exist as a cell surface glycosylphosphatidyl-inositol-linked protein that is capable of activating the Eck receptor protein-tyrosine kinase, the first such report of a receptor protein-tyrosine kinase ligand that is glycosylphosphatidylinositol-linked. In addition, the expression patterns of B61 and Eck during mouse ontogeny were determined by in situ hybridization. Both were found to be highly expressed in the developing lung and gut, while Eck was preferentially expressed in the thymus. Finally, the gene for B61 was localized to a specific position on mouse chromosome 3 by interspecific back-cross analysis.

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

PubMed Central

2012-01-01

Background c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. Methods In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008–2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Results Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. Conclusions c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429 PMID:22640970

Do pure squamous cell carcinomas and urothelial carcinomas have similar prognosis after radical cystectomy?

PubMed

Balci, Ugur; Ozer, Kutan; Gorgel, Sacit Nuri; Sefik, Ertugrul; Girgin, Cengiz; Dincel, Cetin

2013-10-01

The purpose of this study was to evaluate the surgical treatment results of urothelial carcinoma (UC) and pure squamous cell carcinoma of the bladder (SCC). The records of 460 patients who have undergone radical cystectomy in our department between the years 1991 and 2011 were analyzed retrospectively, and 364 patients with UC and 60 patients with pure SCC were evaluated. Average ages of the patients with UC and SCC were 61.12 ± 8.9 and 59.38 ± 8.6 years, respectively (p = 0.902). UC group had 29 female patients, whereas SCC group had 9 female patients (p = 0.077). The mean follow-up periods were 26.09 ± 24.75 months for UC group and 22.23 ± 31.01 months for SCC group (p = 0.805). The incidence of organ-confined, extravesical, lymph node-positive diseases in UC and SCC cases was 48.9 and 32.2, 29.3 and 32.2 %, 21.8 and 35.6 %, respectively (p = 0.028). Five-year disease-specific survival (DSS) rates were 57.5 % in UC and 39.1 % in SCC group (p = 0.011). Five-year DSS rates were 81.2 % in UC and 75.0 % in SCC group in organ-confined disease (p = 0.534) and 28.2 % in UC and 40.9 % in SCC group in extravesical disease (p = 0.845). In lymph node-positive patients, DSS time was 20.9 ± 2.85 months in UC and 12.8 ± 2.07 months in SCC patients (p = 0.182). In multivariate analysis, pT stage (HR: 2.221; 95 % CI: 1.695-2.911) and lymph node involvement (HR: 2.863; 95 % CI: 1.819-4.509) were independently associated with DSS (p < 0.001), but histological subtype (HR: 1.423; 95 % CI: 0.798-2.538) was not a statistically significant factor (p = 0.232). Although pure SCC cases are diagnosed at advanced stages of the disease, UC and pure SCC cases have similar prognosis by stages. Lymph node involvement and stages are the most important prognostic factors after radical cystectomy.

47 CFR 61.151 - Scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Scope. 61.151 Section 61.151 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) TARIFFS Applications for Special Permission § 61.151 Scope. Sections 61.152 and 61.153 set forth the procedures to be followed by a...

Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link between the constitutional t(11;22) and cancer.

PubMed

Doyen, Jérôme; Carpentier, Xavier; Haudebourg, Juliette; Hoch, Benjamin; Karmous-Benailly, Houda; Ambrosetti, Damien; Fabas, Thibault; Amiel, Jean; Lambert, Jean-Claude; Pedeutour, Florence

2012-11-01

We observed a t(11;22)(q23-24;q11.2-12) and monosomy 3 in renal tumor cells from a 72-year-old man. The hypothesis of a primitive peripheral neuroectodermal tumor (PPNET) located in the kidney was promptly excluded: Histologically, the tumor was a clear cell renal cell carcinoma (RCC) and we did not observe an EWSR1 gene rearrangement. The constitutional origin of this alteration was established. We report on the second case of RCC in a patient with a constitutional t(11;22). The t(11;22)(q23;q11.2) is the main recurrent germline translocation in humans. Unbalanced translocation can be transmitted to the progeny and can cause Emanuel syndrome. Our observation alerts cancer cytogeneticists to the fortuitous discovery of the constitutional t(11;22) in tumor cells. This translocation appears grossly similar to the t(11;22)(q24;q12) of PPNET and should be evoked if present in all cells of a tumor other than PPNET. This is important when providing appropriate genetic counseling. Moreover, the potential oncogenic role of the t(11;22) and its predisposing risk of cancer are under debate. The family history of the patient revealed a disabled brother who died at an early age from colon cancer and a sister with breast cancer. This observation reopens the issue of a link between the constitutional t(11;22) and cancer, and the utility of cancer prevention workups for t(11;22) carriers. Copyright © 2012 Elsevier Inc. All rights reserved.

Renal cell carcinoma with t(6:11) (p21;q12). A case report highlighting distinctive immunohistologic features of this rare tumor.

PubMed

Arneja, Sarabjeet Kaur; Gujar, Neeraj

2015-01-01

Renal cell carcinoma (RCC) with t(6:11) (p21;q12) are extremely rare, fewer than 30 cases have been reported in literature. These tumors are characterized by specific chromosomal translocation involving TFEB, as against the more commonly known TFE3 (Xp11.2) translocation associated RCCs. The distinctive immnohistologic features are helpful in enabling a diagnosis of this rare tumor, otherwise diagnosed by fluorescence in situ hybridization assay, specific for detecting TFEB gene rearrangement. Herein, we report a case of this rare tumor in a 11 years old boy, with the objective of highlighting distinctive light microscopic and immuno-phenotypic features of this rare sub-type of translocation associated renal cell carcinoma, otherwise diagnosed by fluorescence in situ hybridization technique. Morphologically tumor showed distinctive biphasic population of cells, large epitheloid cells with voluminous eosinophillic cytoplasm and smaller cells with much lesser amount of cytoplasm and small rounded nuclei. The smaller cells at places clustered around hyaline pink material forming "pseudorosettes". population. Immunohistochemically both types of tumor cells showed negativity for pan CK (cytokeratin), EMA (epitheleal membrane antigen) and TFE3 (transcription factor E3). HMB 45 (human melanoma black 45) and Melan- A /MART 1 (melanoma antigen recognized by T cells) were moderate to strongly expressed. On review of literature, most RCCs with t(6;11) translocation have been reported to be negative for pan cytokeratins and EMA. Published literature also shows that the most distinctive immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for TFEB protein. Immunostains for TFE3 have always been negative in the reported cases. It is noteworthy that immunoreactivity for melanocytic markers HMB45 and Melan A and immunonegativity for epithelial markers pan CK and EMA may lead to misdiagnosis of angiomyolipoma to the unwary. Knowledge of distinctive

Specific blockade CD73 alters the 'exhausted' phenotype of T cells in head and neck squamous cell carcinoma.

PubMed

Deng, Wei-Wei; Li, Yi-Cun; Ma, Si-Rui; Mao, Liang; Yu, Guang-Tao; Bu, Lin-Lin; Kulkarni, Ashok B; Zhang, Wen-Feng; Sun, Zhi-Jun

2018-04-16

The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4 + and CD8 + T cells was associated with an 'exhausted' phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the 'exhausted' phenotype of CD4 + and CD8 + T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells. Whereas the population of CD4 + CD73 hi /CD8 + CD73 hi T cells expressed higher CTLA-4 and PD-1 as compared to untreated controls. In addition, the human tissue microarrays showed the expression of CD73 is upregulated on tumor infiltrating immune cells in patients with primary HNSCC. Moreover, CD73 expression is an independent prognostic factor for poor outcome in our cohort of HNSCC patients. Altogether, these findings highlight the immunoregulatory role of CD73 in the development of HNSCC and we propose that CD73 may prove to be a promising immunotherapeutic target for the treatment of HNSCC. This article is protected by copyright. All rights reserved. © 2018 UICC.

A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk.

PubMed

Wang, Dan; Qi, Xiaoying; Liu, Fang; Yang, Chuanhua; Jiang, Wenguo; Wei, Xiaodan; Li, Xuri; Mi, Jia; Tian, Geng

2017-07-25

Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls (P < 0.001), with the power to detect this significance of being over 99.9%. Moreover, the above two polymorphisms increased the risk of developing hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P < 0.001) and dominant (OR = 1.75; 95% CI: 1.23-2.50; P = 0.002) models after adjusting for body mass index, smoking and drinking. Haplotype analysis showed that the T-C-T haplotype (rs1045411-rs2249825-rs1415125) in HMGB1 gene was associated with a 2.47-fold (95% CI: 1.41-4.34; P = 0.002) increased risk of hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.

Epithelial-myoepithelial carcinoma of floor of mouth: A case report with cytological, histological and immunohistochemical correlation.

PubMed

Mohanty, Sujata; Pathak, Himani

2014-01-01

A 61-year-old female presented with a 3-year-old swelling in the right floor of mouth. Clinical examination and fine needle aspiration cytology suggested a benign lesion. The mass was excised locally along with the involved sublingual and deep part of submandibular gland and duct. Post-operative histopathological examination revealed features of pleomorphic adenoma. However, on revision of histological sections, features were predominantly of a rare malignancy of the salivary glands, epithelial-myoepithelial carcinoma (EMC), along with focal areas of adenoid cystic carcinoma (Ad CC). The tumor was p-63, s-100 and smooth muscle actin positive but C-kit was negative, which ruled out Ad CC and the possibility of a hybrid carcinoma. The aim of this article is to describe a rare case of EMC in the floor of mouth and the confusing cytological picture that it created.

Nuclear Data Sheets for A = 61

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

Zuber, Kazimierz; Singh, Balraj

2015-03-15

The evaluated spectroscopic data are presented for known nuclides of mass 61 (Sc,Ti,V,Cr,Mn,Fe,Co,Ni, Cu,Zn,Ga,Ge). Excited-state data are nonexistent for {sup 61}Sc, {sup 61}Ti, {sup 61}V, and {sup 61}Ge. Significant amounts of new data have been added since the previous NDS evaluation of A=61 nuclides (1999Bh04). {sup 61}Sc nuclide is now experimentally known, but without any knowledge of its half-life. The ground state half-lives of {sup 61}Ti and {sup 61}V are now determined. Excited-state data have become available for {sup 61}Cr, {sup 61}Mn and {sup 61}Ga, while for {sup 61}Ge, five excited states were erroneously assigned in the previous evaluation, thesemore » have been omitted here. Improved and extensive high-spin excitations are available for {sup 61}Fe, {sup 61}Cu and {sup 61}Zn, including several new superdeformed structures in {sup 61}Cu and {sup 61}Zn. Thermal neutron capture γ-ray data are available in detail from 2004Ra23. The radioactive decay schemes of {sup 61}Sc and {sup 61}Ti are not known, while those for {sup 61}V, {sup 61}Fe and {sup 61}Ge are poorly known. This work benefited from the earlier full evaluations of A=61 published by 1999Bh04, 1983Ek01 and 1975Au05 and the one published in an ‘update’ mode by 1992Zh31. The data and conclusions presented in the current work supersede those in all the previous evaluations.« less

Living Donor Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Experience of a Single Center.

PubMed

Chang, Cheng-Chih; Chen, Ying-Ju; Huang, Tzu-Hao; Chen, Chun-Han; Kuo, Fang-Ying; Eng, Hock-Liew; Yong, Chee-Chien; Liu, Yueh-Wei; Lin, Ting-Lung; Li, Wei-Feng; Lin, Yu-Hung; Lin, Chih-Che; Wang, Chih-Chi; Chen, Chao-Long

2017-02-28

BACKGROUND Because the outcome of liver transplantation for cholangiocarcinoma is often poor, cholangiocarcinoma is a contraindication for liver transplantation in most centers. Combined hepatocellular carcinoma and cholangiocarcinoma is a rare type of primary hepatic malignancy containing features of hepatocellular carcinoma and cholangiocarcinoma. Diagnosing combined hepatocellular carcinoma and cholangiocarcinoma pre-operatively is difficult. Because of sparse research presentations worldwide, we report our experience with living donor liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma. MATERIAL AND METHODS A total of 710 patients underwent living donor liver transplantation at our institution from April 2006 to June 2014; 377 of them received transplantation because of hepatocellular carcinoma with University of California San Francisco (UCSF) staging criteria fulfilled pre-operatively. Eleven patients (2.92%) were diagnosed with combined hepatocellular carcinoma and cholangiocarcinoma confirmed pathologically from explant livers; we reviewed these cases retrospectively. Long-term survival was compared between patients diagnosed with combined hepatocellular carcinoma and cholangiocarcinoma and patients diagnosed with hepatocellular carcinoma. RESULTS The mean age of the patients in our series was 60.2 years, and the median follow-up period was 23.9 months. Four patients were diagnosed with a recurrence during the follow-up period, including one intra-hepatic and three extra-hepatic recurrences. Four patients died due to tumor recurrence. Except for patients with advanced-stage cancer, disease-free survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma compared with that of patients with hepatocellular carcinoma was 80% versus 97.2% in 1 year, and 46.7% versus 92.5% in 3 years (p<0.001), and overall survival was 90% versus 97.2% in 1 year, and 61.7% versus 95.1% in 3 years (p<0.001). CONCLUSIONS

Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma.

PubMed

Skala, Stephanie L; Liu, Tzu-Ying; Udager, Aaron M; Weizer, Alon Z; Montgomery, Jeffrey S; Palapattu, Ganesh S; Siddiqui, Javed; Cao, Xuhong; Fields, Kristina; Abugharib, Ahmed E; Soliman, Moaaz; Hafez, Khaled S; Miller, David; Lee, Cheryl T; Alva, Ajjai; Chinnaiyan, Arul M; Morgan, Todd M; Spratt, Daniel E; Jiang, Hui; Mehra, Rohit

2017-10-01

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Upper tract (renal pelvis and ureter) urothelial carcinomas (UTUC) account for approximately 5% of UCs but a significant subset are invasive and associated with poor clinical outcomes. To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC. UTUC cases from 1997-2016 were retrospectively identified from the surgical pathology database at a single large academic institution. The cohort included 149 cases: 27 low-grade and 24 high-grade pathologic T (pT)a, 29 pT1, 23 pT2, 38 pT3, and eight pT4. PD-L1 immunohistochemistry (IHC) was performed on representative whole tumor sections using anti-PD-L1 primary antibody clone 5H1. PD-L1 expression was evaluated using a previously established cut-off for positivity (≥ 5% membranous staining). Association between PD-L1 IHC expression and clinicopathologic parameters was examined with Fisher's exact test; the effect of PD-L1 expression on cancer-specific mortality was assessed using the Cox proportional hazard model. Approximately one-third (32.7%) of invasive primary UTUC and 23.5% of all primary UTUC (invasive and noninvasive tumors) demonstrated positive PD-L1 expression. Positive PD-L1 expression was associated with high histologic grade, high pathologic stage, and angiolymphatic invasion. Cancer-specific survival was not significantly associated with positive PD-L1 expression using a 5% cut-off. Study limitations include the retrospective nature and the fact that PD-L1 expression by IHC is an imperfect surrogate for response to therapy. Positive PD-L1 expression in approximately one-third of primary invasive UTUC and association with high-risk clinicopathologic features provide a rational basis for further investigation of PD-L1-based immunotherapeutics in these patients. Upper tract urothelial carcinoma is often associated with poor clinical outcome. While current treatment options for advanced upper tract urothelial carcinoma are

Somatic alterations of the serine/threonine kinase LKB1 gene in squamous cell (SCC) and large cell (LCC) lung carcinoma.

PubMed

Strazisar, Mojca; Mlakar, Vid; Rott, Tomaz; Glavac, Damjan

2009-05-01

Somatic LKB1 serine/threonine kinase alterations are rare in sporadic cancers, with the exception lung adenocarcinoma, but no mutations in squamous cell or large cell primary carcinoma were discovered. We screened the LKB1 gene in 129 primary nonsmall cell lung carcinomas, adjacent healthy lung tissue, and control blood samples. Forty-five percent of nonsmall cell lung tumors harbored either intron or exon alterations. We identified R86G, F354L, Y272Y and three polymorphisms: 290+36G/T, 386+156G/T, and 862+145C/T (novel). R86G (novel) and F354L mutations were found in six squamous cell carcinomas and three large cell cancer carcinomas, but not in the adjacent healthy tissue or controls samples. The F354L mutation was found in advanced squamous cell carcinomas with elevated COX-2 expression, rare P53, and no K-RAS mutation. Results indicate that the LKB1 gene is changed in a certain proportion of nonsmall cell lung tumors, predominately in advanced squamous lung carcinoma. Inactivation of the gene takes place via the C-terminal domain and could be related to mechanisms influencing tumor initiation, differentiation, and metastasis.

Lymphoepithelial Carcinoma of the Nasolacrimal Duct: Clinical, Radiologic, and Immunopathologic Features.

PubMed

Jakobiec, Frederick A; Stagner, Anna M; Rubin, Peter A D

Undifferentiated lymphoepithelial carcinoma (exhibiting both begin lymphoid and malignant epithelial components) most commonly arises in the head and neck, especially in the nasopharynx. It may also be encountered in various ocular adnexal sites, including the nasolacrimal duct. A 63-year-old woman developed a swelling in the region of the right lacrimal sac accompanied by epiphora. CT scanning revealed an enlargement of the nasolacrimal duct from the lacrimal sac to the inferior nasal meatus. A biopsy during dacryocystorhinostomy for symptomatic epiphora revealed hypercellular sheets of small lymphocytes which were interpreted as evidence for a chronic dacryocystitis. Two years later the subtotally excised lesion had substantially grown in size. Repeat CT scans demonstrated an inferonasal anterior orbital mass with further enlargement of the nasolacrimal duct with a solid mass in its lumen, and bone erosion. The biopsy combined a rich background of lymphocytes within which were clusters of undifferentiated carcinoma cells that were cytokeratin and p63 positive. Critical review of the earlier biopsy led to the detection of the same cells, but in smaller numbers, that had been overlooked. An awareness of the possibility of lymphoepithelial carcinoma of the lacrimal sac/duct should improve diagnostic accuracy with the aid of immunohistochemistry. Radiation therapy is often successful in managing this highly sensitive malignant tumor.

Expression of E-cadherin and vimentin in oral squamous cell carcinoma

PubMed Central

Zhou, Jingping; Tao, Detao; Xu, Qing; Gao, Zhenlin; Tang, Daofang

2015-01-01

The aim of the study is to determine the levels of E-cadherin, vimentin expression in tumor tissues from patients with oral squamous cell carcinoma (OSCC), and the relationship between the expression of E-cadherin, vimentin and epithelial-mesenchymal transition, in order to explore its values for predicting the invasion and metastasis of oral squamous cell carcinoma, short survival of patients in many types of cancer. E-cadherin and vimentin expression of 10 benign and 42 OSCC tumor tissues was examined by immunohistochemical staining. E-cadherin is positively expressed in normal oral mucosa epithelium, but vimentin expression is not found in normal oral mucosa epithelia; the E-cadherin and vimentin were expressed in 26 of 42 (61.9%) and 16 of 42 (38.1%), respectively. No statistically difference was found for E-cadherin and vimentin expression in patients with different age, gender and tumor location, E-cadherin and vimentin expression was significantly associated with lymph node metastasis and tissue location (P < 0.05); E-cadherin expression was also significantly associated with tumor stage (P < 0.05); there are significantly difference between infiltrative margin and central area in patients with oral squamous cell carcinoma for E-cadherin and vimentin positive expression (P < 0.05). E-cadherin and vimentin positive expression was associated with tumor metastasis of oral squamous cell carcinoma. Our study preliminarily confirmed that EMT phenomenon is existed during the development of oral squamous cell carcinoma. Co-evaluation of E-cadherin and vimentin might be a valuable tool for predicting OSCC patient outcome. PMID:26045832

Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response.

PubMed

Smith, Corey; Lee, Victor; Schuessler, Andrea; Beagley, Leone; Rehan, Sweera; Tsang, Janice; Li, Vivian; Tiu, Randal; Smith, David; A Neller, Michelle; Matthews, Katherine K; Gostick, Emma; Price, David A; Burrows, Jacqueline; Boyle, Glen M; Chua, Daniel; Panizza, Benedict; Porceddu, Sandro V; Nicholls, John; Kwong, Dora; Khanna, Rajiv

2017-01-01

Adoptive T cell therapy has emerged as a powerful strategy to treat human cancers especially haematological malignancies. Extension of these therapies to solid cancers remains a significant challenge especially in the context of defining immunological correlates of clinical responses. Here we describe results from a clinical study investigating autologous Epstein-Barr virus (EBV)-specific T cells generated using a novel AdE1-LMPpoly vector to treat patients with nasopharyngeal carcinoma (NPC) either pre-emptively in at-risk patients with no or minimal residual disease (N/MRD) or therapeutically in patients with active recurrent/metastatic disease (ARMD). Tolerability, safety and efficacy, including progression-free survival (PFS) and overall survival (OS), were evaluated following adoptive T-cell immunotherapy. Twenty-nine patients, including 20 with ARMD and nine with N/MRD, successfully completed T-cell therapy. After a median follow-up of 18.5 months, the median PFS was 5.5 months (95% CI 2.1 to 9.0 months) and the median OS was 38.1 months (95% CI 17.2 months to not reached). Post-immunotherapy analyses revealed that disease stabilization in ARMD patients was significantly associated with the functional and phenotypic composition of in vitro -expanded T cell immunotherapy. These included a higher proportion of effector CD8 + T-cells and an increased number of EBV-specific T-cells with broader antigen specificity. These observations indicate that adoptive immunotherapy with AdE1-LMPpoly-expanded T cells stabilizes relapsed, refractory NPC without significant toxicity. Promising clinical outcomes in N/MRD patients further suggest a potential role for this approach as a consolidation treatment following first-line chemotherapy.

18F-FDG PET/CT Findings of Metastasis to Spongy Body of Penis From Urothelial Carcinoma of Bladder.

PubMed

Wang, Yan-li; Fang, Na; Zeng, Lei; Wu, Zeng-jie; Cui, Xin-jian

2016-05-01

The spongy body of the penis metastasis from other primary sites is a rare clinical entity. It is frequently associated with widespread metastatic disease and poor prognosis clinically. We report a case of a 61-year-old man with a previous history of cystectomy due to infiltrating urothelial carcinoma of the bladder 12 months ago and presented with penile shaft swelling pain and hematuria for 3 months. The restaging F-FDG PET/CT scan demonstrated a hypermetabolic mass at his penile shaft. This lesion was confirmed on phallectomy to be infiltrating urothelial carcinoma metastasis from the known primary bladder tumor.

Sarcomatoid carcinoma of the lung -  a case report.

PubMed

Szkorupa, M; Bohanes, T; Neoral, C; Vomackova, K; Chudacek, J

2015-01-01

Sarcomatoid carcinoma (SARC) of the lung is a very rare and aggressive type of nonsmall cell lung cancer. It belongs to a group of poorly differentiated carcinomas with partial sarcomatoid differentiation or with a direct sarcoma component. Characteristic findings include a large tumor with an invasive tendency, early recurrence and systemic metastases. The authors present a case of SARC in the 77-year-old patient. Preoperative staging confirmed sarcomatoid carcinoma of the lower lobe of the left lung without generalization on PET/CT. However, an infiltration of more than 2/3 of the diaphragm was ascertained. A resection was performed -  a left lower lobectomy with resection of the diaphragm and its replacement by a muscle flap made from the latissimus dorsi muscle with vascular pedicle. Histological findings confirmed the dia-gnosis of sarcomatoid (pleomorphic) carcinoma pT3N0M0. The patient underwent adjuvant chemotherapy; recurrence and systemic dissemination of the disease occurred after 20 months; the patient died 21 months after the surgery.

Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract.

PubMed

O'Connell, Fionnuala P; Wang, Helen H; Odze, Robert D

2005-03-01

Breast carcinoma often metastasizes to the gastrointestinal tract, especially the stomach, where it is frequently difficult to distinguish from a primary gastric carcinoma. To evaluate the utility of immunohistochemical stains in differentiating primary gastric carcinomas from metastatic breast carcinomas. Mucosal biopsy specimens from 47 adenocarcinomas involving the gastrointestinal tract (28 primary gastric carcinomas and 19 metastatic breast carcinomas) and 16 control cases of primary breast carcinomas without metastasis were immunohistochemically stained for estrogen receptor protein (ER), progesterone receptor protein (PR), gross cystic disease fluid protein (GCDFP), human epidermal growth factor receptor 2 protein, cytokeratin (CK) 5/6, CK/7, CK/20, a panel of mucin glycoprotein antigens (MUC2, MUC3, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox transcription factor CDX2 and compared between primary and metastatic adenocarcinomas. Highly significant proportions of metastatic breast carcinomas were positive for ER (72%), PR (33%), GCDFP (78%), and CK5/6 (61%) compared with primary gastric carcinomas (ER, 0%; PR, 0%; GCDFP, 0%; and CK5/6, 14%) (P < .001, P = .002, P < .001, and P = .004, respectively). Of these immunostains, ER, PR, and GCDFP were 100% specific. Primary breast tumors and their metastases showed a similar phenotypic profile. In contrast, primary gastric carcinomas showed significantly higher proportions of cases that stained with CK20 (50%), MUC2 (54%), MUC5AC (71%), MUC6 (39%), DAS-1 (43%), and CDX2 (67%) compared with metastatic breast carcinomas (CK20, 0%; MUC2, 24%; MUC5AC, 6%; MUC6, 0%; DAS-1, 0%; and CDX2, 0%) (P = .001, P = .01, P < .001, P = .02, P = .009, and P < .001, respectively). No significant differences were observed with regard to any of the other immunostains (human epidermal growth factor receptor 2 protein, CK7, and MUC3) between the patient groups. Estrogen receptor protein, PR, GCDFP, CK5/6, CK20

Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality.

PubMed

Anglesio, Michael S; Wang, Yi Kan; Maassen, Madlen; Horlings, Hugo M; Bashashati, Ali; Senz, Janine; Mackenzie, Robertson; Grewal, Diljot S; Li-Chang, Hector; Karnezis, Anthony N; Sheffield, Brandon S; McConechy, Melissa K; Kommoss, Friedrich; Taran, Florin A; Staebler, Annette; Shah, Sohrab P; Wallwiener, Diethelm; Brucker, Sara; Gilks, C Blake; Kommoss, Stefan; Huntsman, David G

2016-06-01

Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Long-Term Outcomes of Eye-Sparing Surgery for Adenoid Cystic Carcinoma of Lacrimal Gland.

PubMed

Han, Jisang; Kim, Yoon-Duck; Woo, Kyung In; Sobti, Deepak

This study's primary purpose is to assess the long-term outcomes of patients who have undergone eye-sparing surgery and adjuvant radiotherapy for adenoid cystic carcinoma of the lacrimal gland. In this retrospective analysis, clinical records were reviewed of all patients diagnosed with adenoid cystic carcinoma of the lacrimal gland, at a single institution, between March 1998 and November 2012. Ten patients were identified as having undergone eye-sparing surgery and adjuvant radiotherapy for adenoid cystic carcinoma of the lacrimal gland. Preoperative radiographic findings, treatment modalities, histological results, and patient outcomes were analyzed. There were 6 male and 4 female patients. The patients' tumors were staged according to the 8th American Joint Committee on Cancer staging system, and were as follows: 1 patient was classified as T1aN0M0; 6 patients were classified as T2aN0M0; 1 patient was classified as T2cN0M0; 2 patients were classified as T3aN0M0. All patients had a histologically confirmed diagnosis of lacrimal gland adenoid cystic carcinoma, which was confined to the orbit, and was without extension into adjacent bone marrow or other organs. All patients underwent eye-sparing tumor excision followed by postoperative radiotherapy, with a median dose of 6000 cGy (range: 5000-6600 cGy). At the last follow up, 8 patients were alive without evidence of disease. One patient was deceased at 58 months post-surgery, due to esophageal carcinoma; this was unrelated to the lacrimal gland tumor. The final patient experienced tumor recurrence in the medial orbit 53 months post-surgery, and exenteration was performed. This patient was alive, without disease recurrence, at 90 months following exenteration. The median follow-up time was 89.5 months (range: 37-217 months). Systemic metastasis did not occur in any patient. Eye-sparing surgery and adjuvant radiotherapy have demonstrated favorable local control and long-term survival outcomes in patients with orbit

B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma

PubMed Central

Hua, Dong; Sun, Jing; Mao, Yong; Chen, Lu-Jun; Wu, Yu-Yu; Zhang, Xue-Guang

2012-01-01

AIM: To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. METHODS: One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software. RESULTS: Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues. Among the total T cells, a variable amount of regulatory T cells with a clear Foxp3+ (forkhead box P3) staining could be detected in CRC tissues and patients’ blood. Interestingly, in the 33 samples (15 cases of B7-H1high CRC tissues and 18 cases of B7-H1low CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percentages of CD4+Foxp3+ and CD8+Foxp3+ regulatory T cells were found remarkably higher in B7-H1high CRC tissues than in B7-H1low CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell, which is expressed by activated T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells

B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma.

PubMed

Hua, Dong; Sun, Jing; Mao, Yong; Chen, Lu-Jun; Wu, Yu-Yu; Zhang, Xue-Guang

2012-03-07

To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software. Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues. Among the total T cells, a variable amount of regulatory T cells with a clear Foxp3⁺ (forkhead box P3) staining could be detected in CRC tissues and patients' blood. Interestingly, in the 33 samples (15 cases of B7-H1(high) CRC tissues and 18 cases of B7-H1(low) CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percentages of CD4⁺Foxp3⁺ and CD8⁺Foxp3⁺ regulatory T cells were found remarkably higher in B7-H1(high) CRC tissues than in B7-H1(low) CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell, which is expressed by activated T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells (CD4�

[Biological characteristics and management of familial papillary thyroid carcinoma].

PubMed

Zhao, Jing; Yu, Yang; Xia, Ting-ting; Liu, You-zhong; Wei, Song-feng; Zheng, Xiang-qian; Gao, Ming

2011-11-01

To analyze the clinical biological characteristics and investigate the managements of familial papillary thyroid carcinoma (FPTC). Clinical data of 36 patients with PTC from 15 families were retrospectively analyzed compared with 95 control cases taken randomly from the patients with sporadic PTC diagnosed and treated in Tianjin Cancer Hospital between January 2010 and August 2011. Of the 36 patients with FPTC, 15 (41.7%) were ≥45 years old, 12 (33.3%) had bilateral carcinoma, 20 (55.6%) were multifocality, 27 (75.0%) had neck lymph node metastases, 17 (47.2%) coexisted thyroid benign tumors. Of the 95 patients with SPTC, 60 (63.2%) were ≥45 years old, 12(12.6%)had bilateral carcinomas, 21 (22.1%) were multifocality, 51 (53.7%) had neck lymph node metastases, and 26(27.4%)coexisted thyroid benign tumors. Of the 36 patients with FPTC, 22 (61.1%) underwent total thyroidectomy and 14 (38.9%) with unilateral thyroidectomy plus isthmusectomy, 3 (8.3%) received unilateral or bilateral lateral neck dissection and central compartment neck dissection (CND), 7 (19.4%) received unilateral or bilateral posterolateral neck dissection and CND, 6 (16.6%) received posterolateral neck dissection and bilateral CND, and 20 (55.6%) received unilateral or bilateral CND. Age at disease presentation of FPTC was younger than that of SPTC. FPTC has higher rates of multifocality and bilateral carcinoma coexisting with thyroid benign tumor than those of SPTC. It necessary to take family history in detail and to evaluate diseases before operation.

Arterial chemoradiotherapy for carcinomas of the external auditory canal and middle ear.

PubMed

Fujiwara, Masayuki; Yamamoto, Satoshi; Doi, Hiroshi; Takada, Yasuhiro; Odawara, Soichi; Niwa, Yasue; Ishikura, Reiichi; Kamikonya, Norihiko; Terada, Tomonori; Uwa, Nobuhiro; Sagawa, Kosuke; Hirota, Shozo

2015-03-01

The purpose of this study was to estimate the efficacy of superselective arterial chemoradiotherapy for locally advanced carcinomas of the external auditory canal and middle ear. A retrospective study of clinical data for consecutive patients with locally advanced carcinomas of the external auditory canal and middle ear. Thirteen patients with locally advanced carcinomas of the external auditory canal and middle ear (T3: one patient, T4: 12 patients) were reviewed. The median follow-up duration in the living patients was 33 months. The total dose of radiation therapy was 60 Gy using conventional fractionation. Four, five, or six courses of a superselective arterial infusion (cisplatin 50 mg) were given weekly. The overall survival and progression-free survival rates at 2 years, calculated by the Kaplan-Meier method, were 58.7% and 53.8%, respectively. No late-phase adverse effects due to chemoradiation and no adverse effects due to catheterization were observed. These results suggest that superselective arterial chemoradiation can be a treatment option for locally advanced carcinomas of the external auditory canal and middle ear. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Chemical, computational and functional insights into the chemical stability of the Hedgehog pathway inhibitor GANT61.

PubMed

Calcaterra, Andrea; Iovine, Valentina; Botta, Bruno; Quaglio, Deborah; D'Acquarica, Ilaria; Ciogli, Alessia; Iazzetti, Antonia; Alfonsi, Romina; Lospinoso Severini, Ludovica; Infante, Paola; Di Marcotullio, Lucia; Mori, Mattia; Ghirga, Francesca

2018-12-01

This work aims at elucidating the mechanism and kinetics of hydrolysis of GANT61, the first and most-widely used inhibitor of the Hedgehog (Hh) signalling pathway that targets Glioma-associated oncogene homologue (Gli) proteins, and at confirming the chemical nature of its bioactive form. GANT61 is poorly stable under physiological conditions and rapidly hydrolyses into an aldehyde species (GANT61-A), which is devoid of the biological activity against Hh signalling, and a diamine derivative (GANT61-D), which has shown inhibition of Gli-mediated transcription. Here, we combined chemical synthesis, NMR spectroscopy, analytical studies, molecular modelling and functional cell assays to characterise the GANT61 hydrolysis pathway. Our results show that GANT61-D is the bioactive form of GANT61 in NIH3T3 Shh-Light II cells and SuFu -/- mouse embryonic fibroblasts, and clarify the structural requirements for GANT61-D binding to Gli1. This study paves the way to the design of GANT61 derivatives with improved potency and chemical stability.

[Results of surgical treatment in ampullary and pancreatic carcinoma and its prognostic parameters after R0-resection].

PubMed

Ridwelski, K; Meyer, F; Schmidt, U; Lippert, H

2005-08-01

Resection is currently the only established reasonable therapeutic option with curative potential in pancreatic and ampullary carcinoma. The aim of the study was i) to analyze value and results of surgical therapy and ii) to detect the prognostic parameters, which determine significantly higher survival rates. Two-hundred-twenty patients with pancreatic and ampullary carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery. Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201 ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found, in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was determined according to the method by Kaplan/Meier. Survival was compared using log-rank test. Association of several or multiple parameters with survival was tested using Cox model. Hundred-ten patients underwent tumor resection with primary curative intention (50 %): 96 resections of the pancreatic head, 2 total pancreatectomies and 12 left resections of the pancreas. R0-resection was achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10 and R2 in 6 cases. In addition, 60 palliative interventions (28 gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites) and 50 explorative laparotomies were performed. In 42.3 % of patients, postoperative complications were found, but only 12/220 individuals died (overall letality, 5.4 %). Postoperative letality of curative pancreatic resections was 3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was 73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months, respectively). Taken together all other interventions, median survival time ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No patient survived 5 years. Therefore, the most relevant prognostic

Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus.

PubMed

Onozawa, Masakatsu; Nihei, Keiji; Ishikura, Satoshi; Minashi, Keiko; Yano, Tomonori; Muto, Manabu; Ohtsu, Atsushi; Ogino, Takashi

2009-08-01

There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer. Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI. One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence. In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

PubMed

Takano, Toru; Miyauchi, Akira; Ito, Yasuhiro; Amino, Nobuyuki

2006-06-01

We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.

Epithelial-myoepithelial carcinoma of floor of mouth: A case report with cytological, histological and immunohistochemical correlation

PubMed Central

Mohanty, Sujata; Pathak, Himani

2014-01-01

A 61-year-old female presented with a 3-year-old swelling in the right floor of mouth. Clinical examination and fine needle aspiration cytology suggested a benign lesion. The mass was excised locally along with the involved sublingual and deep part of submandibular gland and duct. Post-operative histopathological examination revealed features of pleomorphic adenoma. However, on revision of histological sections, features were predominantly of a rare malignancy of the salivary glands, epithelial-myoepithelial carcinoma (EMC), along with focal areas of adenoid cystic carcinoma (Ad CC). The tumor was p-63, s-100 and smooth muscle actin positive but C-kit was negative, which ruled out Ad CC and the possibility of a hybrid carcinoma. The aim of this article is to describe a rare case of EMC in the floor of mouth and the confusing cytological picture that it created. PMID:25937734

Voice handicap and health-related quality of life after treatment for small laryngeal carcinoma.

PubMed

Killguss, Helen; Gottwald, Frank; Haderlein, Tino; Maier, Andreas; Rosanowski, Frank; Iro, Heinrich; Psychogios, Georgios; Schuster, Maria

2011-01-01

Treatment of small carcinoma of the larynx may lead to voice handicap and restricted quality of life. The relationship between the two is revealed. Sixty-five patients aged 62.1 ± 10.0 years rated their voice handicap and quality of life after treatment of T1 (n = 35) or T2 (n = 30) laryngeal carcinoma during regular out-patient examinations. For the self-assessment of the voice, the Voice Handicap Index (VHI) and the disease-independent Short Form-36 Health Survery (SF-36) questionnaires were used. Voice handicap (total score 38.9 ± 26.0) did not differ in the two tested groups, T1 and T2, and the data of SF-36 (physical score 43.0 ± 10.7; mental score 50.2 ± 9.1) showed significant differences for the mental score. Patients rated their voice handicap worse than healthy persons did after treatment of laryngeal carcinoma. VHI and SF-36 data were strongly correlated. Voice handicap is significantly related to the quality of life, especially affecting the mental domain. Thus, the rehabilitation of voice disorders should have a beneficial impact on quality of life. Copyright © 2010 S. Karger AG, Basel.

Comparison of T stage, N stage, multifocality, and bilaterality in papillary thyroid carcinoma patients according to the presence of coexisting lymphocytic thyroiditis.

PubMed

Park, Jin Young; Kim, Dong Wook; Park, Ha Kyung; Ha, Tae Kwun; Jung, Soo Jin; Kim, Do Hun; Bae, Sang Kyun

2015-01-01

This study aimed to assess the relationship between coexisting lymphocytic thyroiditis and T-N stages of papillary thyroid carcinoma (PTC) by histopathological analysis. The study included 653 patients who underwent thyroid surgery for PTC at our hospital. Each case was classified as either Hashimoto's thyroiditis (HT), non-Hashimoto type of lymphocytic thyroiditis (NHLT), or normal according to the histopathology of thyroid parenchyma. Patient age, gender, surgical modality, location, T stage, N stage, multifocality and bilaterality were compared according to the histopathology. The prevalence of coexisting lymphocytic thyroiditis was 25.8% (169/653); HT (7.5%, 49/653) and NHLT (18.3%, 120/653). There were no significant differences in T stage, N stage, multifocality and bilaterality with regard to coexisting lymphocytic thyroiditis, regardless of whether HT and NHLT were considered collectively or discretely. Primary tumor size (p < 0.0001), location (p = 0.0011), N stage (p < 0.0001), multifocality (p < 0.0001) and bilaterality (p < 0.0001) differed significantly according to T stage, and gender (p = 0.0193), primary tumor size (p < 0.0001), T stage (p < 0.0001), multifocality (p < 0.0001) and bilaterality (p < 0.0001) differed significantly according to N stage. PTC patients with coexisting lymphocytic thyroiditis did not differ from those with normal parenchyma in terms of T stage, N stage, multifocality and bilaterality.

Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model.

PubMed

Suarez, Eloah Rabello; Chang, De Kuan; Sun, Jiusong; Sui, Jianhua; Freeman, Gordon J; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A

2016-06-07

Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50-80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.

Uniformity of dc and rf performance of MBE-grown AlGaN/GaN HEMTS on HVPE-grown buffers

NASA Astrophysics Data System (ADS)

Gillespie, J. K.; Fitch, R. C.; Moser, N.; Jenkins, T.; Sewell, J.; Via, D.; Crespo, A.; Dabiran, A. M.; Chow, P. P.; Osinsky, A.; Mastro, M. A.; Tsvetkov, D.; Soukhoveev, V.; Usikov, A.; Dmitriev, V.; Luo, B.; Pearton, S. J.; Ren, F.

2003-10-01

AlGaN/GaN high electron mobility transistors (HEMTs) were grown by molecular beam epitaxy (MBE) on 2 in. diameter GaN buffer layers grown by hydride vapor epitaxy (HVPE) on sapphire substrates. HEMTs with 1 μm gate length displayed excellent dc and rf performance uniformity with up to 258 separate devices measured for each parameter. The drain-source saturation current was 561 mA with a standard deviation of 1.9% over the 2 in. diameter, with a corresponding transconductance of 118 ± 3.9 mS/mm. The threshold voltage was -5.3 ± 0.07 V. The rf performance uniformity was equally good, with an fT of 8.6 ± 0.8 GHz and fmax of 12.8 ± 2.5 GHz. The results show the excellent uniformity of the MBE technique for producing AlGaN/GaN HEMTs and also the ability of HVPE to provide high quality buffers at low cost.

An Unusual Clinical Presentation of Gastrointestinal Metastasis From Invasive Lobular Carcinoma of Breast.

PubMed

Balakrishnan, Bathmapriya; Shaik, Sufiya; Burman-Solovyeva, Irina

2016-01-01

Introduction. We present an unusual case of metastatic lobular breast carcinoma. Typical areas of metastasis include bone, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract, in order of frequency. With regard to GI metastasis, extrahepatic represents a rare site. Case. Two years after being diagnosed with invasive lobular breast carcinoma, a 61-year-old female complained of 3 months of nonspecific abdominal pain and diarrhea. A colonoscopy revealed 5 tubular adenomatous polyps in the ascending and transverse colon. Contrast computed tomography (CT) of the abdomen and pelvis was done 7 months after the colonoscopy to further evaluate persistent diarrhea. The CT results were consistent with infectious or inflammatory enterocolitis. Despite conservative management, symptoms failed to improve and a repeat diagnostic colonoscopy was obtained. Random colonic biopsies revealed metastatic high-grade adenocarcinoma of the colon. Discussion. Metastatic lobular breast carcinoma to the GI tract can distort initial interpretation of endoscopic evaluation with lesions mimicking inflammation. The interval between discovery of GI metastasis and diagnosis of lobular breast cancer can vary widely from synchronous to 30 years; however, progression is most often much sooner. Nonspecific symptoms and subtle appearance of metastatic lesions may confound the diagnosis. A high index of suspicion is needed for possible metastatic spread to the GI tract in patients with a history of invasive lobular breast carcinoma. Perhaps, patients with nonspecific GI symptoms should have an endoscopic examination with multiple random biopsies as invasive lobular carcinoma typically mimics macroscopic changes consistent with colitis.

Identification of a FOXP3+CD3+CD56+ population with immunosuppressive function in cancer tissues of human hepatocellular carcinoma

PubMed Central

Li, Xiaofeng; Peng, Jirun; Pang, Yanli; Yu, Sen; Yu, Xin; Chen, Pengcheng; Wang, Wenzhen; Han, Wenling; Zhang, Jun; Yin, Yanhui; Zhang, Yu

2015-01-01

The liver resident lymphoid population is featured by the presence of a large number of CD3+CD56+ cells referred as natural T cells. In human hepatocellular carcinoma (HCC) patients, the natural T cells were found to be sharply decreased in tumor (5.871 ± 3.553%) versus non-tumor (14.02 ± 6.151%) tissues. More intriguingly, a substantial fraction of the natural T cells (22.76 ± 18.61%) assumed FOXP3 expression. These FOXP3-expressing CD3+CD56+ cells lost the expression of IFN-γ and perforin, which are critical for the effector function of natural T cells. On the other hand, they acquired surface expression of CD25 and CTLA-4 typically found in regulatory T (Treg) cells. Consistent with the phenotypic conversion, they imposed an inhibitory effect on anti-CD3-induced proliferation of naive T cells. Further studies demonstrated that transforming growth factor β1 (TGF-β1) could effectively induce FOXP3 expression in CD3+CD56+ cells and the cells were thus endowed with a potent immunosuppressive capacity. Finally, Kaplan-Meier analysis revealed that the relative abundance of FOXP3-expressing CD3+CD56+ cells in tumor tissues was significantly correlated with the survival of HCC patients. In conclusion, the present study identified a new type of regulatory immune cells whose emergence in liver cancer tissues may contribute to tumor progression. PMID:26437631

SU-F-T-27: A Comparative Case Study Among Four Modalities for the Superficial Treatment of Squamous Cell Carcinoma

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

Ashenafi, M; Koch, N; Peng, J

Purpose: We performed a comparative planning study among High Dose Rate (HDR) brachytherapy, superficial electrons, Volume Modulated Arc Therapy (VMAT), and Helical IMRT (Tomotherapy) for squamous cell carcinoma of the abdominal wall with consideration for the underlining bowel. Methods: A 69-year old female presented with squamous cell carcinoma protruding 8mm beyond the anterior skin surface of the midabdomen was considered for treatment. The patient had a ventral hernia which resulted in the reduction of the abdominal wall thickness and the adjacent small bowel being the dose limiting structure. Four plans were generated using different treatment modalities: a) an enface electronmore » field (eMC, Eclipse v. 11), b) Tomotherapy (HI-Art II v.5.0.5), c) VMAT (Acuros, Eclipse v. 11), and d) HDR using a Freiburg applicator (Oncentra v. 4.3). The following plan objectives were used for all four plans: for the CTV target, V90% ≥90% (61.8Gy2/2).For the small bowel, D0.1cc < 56.2 Gy2/2 was a hard constraint and expressed as a percentage of the prescription for comparison to demonstrate the dose fall-off achieved among the modalities.For HDR, V200% <0.1cc was an additional constraint. Multiple dosimetric parameters, including those listed above, were compared among the four modalities. Results: The HDR plan showed comparable target coverage compared to the Tomotherapy plan and better coverage compared to the electron plan. Small bowel doses (D0.1cc) were lower in HDR plan compared to Tomotherapy, electron, & VMAT plans (88.8%, 89.6%, 90.9%, & 96.6%). Integral dose to the whole body (V5%) was much higher for HDR, VMAT, and Tomotherapy when compared to electron plan by factors of seven, eight, and ten, respectively. After reviewing all treatment modalities, the physician selected HDR owing to better control of the small bowel dose while maintaining adequate target coverage. Conclusion: This case study demonstrated HDR can successfully treat superficial lesions with

Genetic diversity in cassava landraces grown on farms in Alta Floresta-MT, Brazil.

PubMed

Tiago, A V; Rossi, A A B; Tiago, P V; Carpejani, A A; Silva, B M; Hoogerheide, E S S; Yamashita, O M

2016-09-02

Brazil is considered one of the domestication centers of cassava (Manihot esculenta), containing a large part of the biological diversity and traditional knowledge of the species. The aim of the present study was to evaluate the genetic diversity of cassava landraces grown by farmers in the north of Mato Grosso State, Brazil, using inter simple sequence repeat (ISSR) molecular markers. The study was carried out in the municipality of Alta Floresta, MT, on farms located in two rural areas. Seventeen cassava landraces were selected. The DNA was extracted and polymerase chain reaction amplifications were performed using 15 ISSR primers. Genetic similarity estimates were calculated using Jaccard's index and the generated matrix was used for clustering the genotypes by using UPGMA and Tocher's methods. The 15 ISSR primers amplified 120 fragments, revealing 61.67% polymorphism. The polymorphism information content ranged from 0.04 to 0.61, averaging 0.39. The most similar genotypes were AF5 and AF8, whereas the least similar were AF1 and AF16. The UPGMA clustering method formed five groups. Group I included twelve landraces, Group II contained two, and the other groups contained one landrace each. Tocher's method resulted in six groups: 12 landraces clustered in one group, and the other groups each contained one landrace. The ISSR markers proved efficient in revealing genetic diversity among the cassava landraces. The landraces grown by farmers in the two rural areas of Alta Floresta have a great variability and, thus, can be exploited in programs for breeding and preservation of the species.

T-cell receptor BV gene usage in colorectal carcinoma patients immunised with recombinant Ep-CAM protein or anti-idiotypic antibody.

PubMed

Mosolits, Szilvia; Markovic, Katja; Fagerberg, Jan; Frödin, Jan-Erik; Rezvany, Mohammad-Reza; Kiaii, Shahryar; Mellstedt, Håkan; Jeddi-Tehrani, Mahmood

2005-06-01

The tumour-associated antigen, Ep-CAM, is over-expressed in colorectal carcinoma (CRC). In the present study, a recombinant Ep-CAM protein or a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM, either alone or in combination, was used for vaccination of CRC patients (n=9). GM-CSF was given as an adjuvant cytokine. A cellular immune response was assessed by measuring anti-Ep-CAM lymphoproliferation, IFN-gamma production (ELISPOT) and by analysing the TCR BV gene usage within the CD4+ and CD8+ T-cell subsets followed by CDR3 fragment analysis. A proliferative and/or IFN-gamma T-cell response was induced against the Ep-CAM protein in eight out of nine patients, and against Ep-CAM-derived peptides in nine out of nine patients. Analysis of the TCR BV gene usage showed a significantly higher usage of BV12 family in CD4+ T cells of patients both before and after immunisation than in those of healthy control donors (p<0.05). In the CD8+ T-cell subset, a significant (p<0.05) increase in the BV19 usage was noted in patients after immunisation. In individual patients, a number of TCR BV gene families in both CD4+ and CD8+ T cells were over-expressed mainly in post-immunisation samples. Analysis of the CDR3 length polymorphism revealed a higher degree of clonality in post-immunisation samples than in pre-immunisation samples. In vitro stimulation with Ep-CAM protein confirmed the expansion of anti-Ep-CAM T-cell clones. The results indicate that immunisation with the Ep-CAM protein and/or anti-Id entails the induction of an anti-Ep-CAM T-cell response in CRC patients, and suggest that BV19+ CD8+ T cells might be involved in a vaccine-induced immune response.

[Thyroid carcinoma--differentiated, poorly differentiated and anaplastic carcinoma].

PubMed

Kakudo, Kennichi; Bai, Yanhua; Li, Yaqiong; Wakasa, Tomoko; Mori, Ichiro

2007-11-01

The poorly differentiated carcinoma was first added as a new member in the lists of classification of thyroid carcinomas in the WHO 2004 edition. However its histological criteria include necrosis and increased mitoses in addition to the original definition by Sakamoto's proposal, solid, trabecular and schirrhous growth. This modification creates a significant change in the incidence and prognosis of this carcinoma. This carcinoma, defined by the new WHO classification, is about 1-5% of all thyroid malignancy and has more aggressive outcome than the previous definition.

The extended leukocyte differential count using the Cytodiff flow cytometric system reveals that higher CD16+ cytotoxic NK+T lymphocyte levels predict superior survival outcomes in patients with metastatic carcinoma.

PubMed

Park, Borae G; Park, Chan-Jeoung; Yoon, Chan-Hee; Jang, Seongsoo; Chi, Hyun-Sook; Ryu, Min-Hee; Kim, Sang-We

2013-05-01

The recently developed Cytodiff flow cytometric system (Beckman Coulter, Miami, FL) enables leukocyte analysis using a single immunophenotyping panel tube composed of six markers and five colors and that can detect 16 leukocyte subpopulations. We performed a preliminary investigation of whether changes in any of 16 leukocyte differentials were associated with survival and treatment outcomes in patients with metastatic carcinoma or not. We measured 16 leukocyte differential counts using the Cytodiff flow cytometric system in peripheral blood samples from 40 patients with metastatic malignancy (27 stomach cancer and 13 lung cancer) before chemotherapy and at 15 day intervals after chemotherapy for 2 months. A higher percentage of CD16+ cytotoxic NK+T lymphocytes was found to be the only significant prognostic factor among by Cox regression analysis and a higher percentage of CD16+ cytotoxic NK+T lymphocytes (>5.0%) showed significantly longer survival outcomes by Kaplan-Meier analysis (P = 0.003). The Cytodiff system enables 16 leukocyte subpopulations in a one tube assay and also can operate with only small amounts of sample, although it cannot differentiate NK cells from T lymphocytes. Hence, the monitoring of all leukocyte subpopulations using Cytodiff flow cytometry may be a helpful prognostic tool for patients with metastatic carcinoma. Copyright © 2012 International Clinical Cytometry Society.

Basal Cell Carcinoma with Myoepithelial Differentiation: Case Report and Literature Review.

PubMed

Cohen, Philip R

2018-01-17

Basal cell carcinoma is the most common skin cancer. Myoepithelial cells are specialized epithelial cells. Basal cell carcinoma with myoepithelial differentiation is a rare tumor. A 71-year-old man with a basal cell carcinoma with myoepithelial differentiation that presented as an asymptomatic red papule of two months duration on his forehead is described. Including the reported patient, this variant of basal cell carcinoma has been described in 16 patients: 11 men and five women. The patients ranged in age at diagnosis from 43 years to 83 years; the median age at diagnosis was 66 years. All of the tumors were located on the face-most were papules or nodules of less than 10 x 10 mm. Their pathology demonstrated two components: one was that of a typical basal cell carcinoma and the other was myoepithelioma-like in which the tumor cells were plasmacytoid or signet ring in appearance and contained abundant eosinophilic cytoplasm or hyaline inclusions or both. The myoepithelial tumor cells had variable immunohistochemical expression that included not only cytokeratin but also actin, glial fibrillary acid protein, S100, and vimentin. The most common clinical impression, prior to biopsy, was a basal cell carcinoma. The pathologic differential diagnosis included cutaneous mixed sweat gland tumor of the skin, myoepithelioma, myoepithelial carcinoma, and tumors that contain a prominent signet ring cell component (such as metastatic gastrointestinal and breast carcinoma, melanoma, plasmacytoid squamous cell carcinoma, and T-cell lymphoma). Mohs micrographic surgical excision, with complete removal of the tumor, was recommended for treatment of the carcinoma.

Basal Cell Carcinoma with Myoepithelial Differentiation: Case Report and Literature Review

PubMed Central

2018-01-01

Basal cell carcinoma is the most common skin cancer. Myoepithelial cells are specialized epithelial cells. Basal cell carcinoma with myoepithelial differentiation is a rare tumor. A 71-year-old man with a basal cell carcinoma with myoepithelial differentiation that presented as an asymptomatic red papule of two months duration on his forehead is described. Including the reported patient, this variant of basal cell carcinoma has been described in 16 patients: 11 men and five women. The patients ranged in age at diagnosis from 43 years to 83 years; the median age at diagnosis was 66 years. All of the tumors were located on the face—most were papules or nodules of less than 10 x 10 mm. Their pathology demonstrated two components: one was that of a typical basal cell carcinoma and the other was myoepithelioma-like in which the tumor cells were plasmacytoid or signet ring in appearance and contained abundant eosinophilic cytoplasm or hyaline inclusions or both. The myoepithelial tumor cells had variable immunohistochemical expression that included not only cytokeratin but also actin, glial fibrillary acid protein, S100, and vimentin. The most common clinical impression, prior to biopsy, was a basal cell carcinoma. The pathologic differential diagnosis included cutaneous mixed sweat gland tumor of the skin, myoepithelioma, myoepithelial carcinoma, and tumors that contain a prominent signet ring cell component (such as metastatic gastrointestinal and breast carcinoma, melanoma, plasmacytoid squamous cell carcinoma, and T-cell lymphoma). Mohs micrographic surgical excision, with complete removal of the tumor, was recommended for treatment of the carcinoma. PMID:29560294

Laryngeal adenoid cystic carcinoma: A population-based perspective.

PubMed

Dubal, Pariket M; Svider, Peter F; Folbe, Adam J; Lin, Ho-Sheng; Park, Richard C; Baredes, Soly; Eloy, Jean Anderson

2015-11-01

Adenoid cystic carcinoma (ACC) occurs infrequently in the larynx. Consequently, no large samples describing its clinical behavior are available in the literature. Our objective was to use a nationally representative population-based resource to evaluate clinical behavior, patient demographics, and outcomes among patients diagnosed with laryngeal ACC (LACC). Retrospective database analysis. The National Cancer Institute's Surveillance, Epidemiology, and End Results database was analyzed for patients diagnosed with LACC between 1973 and 2011. Patient demographics, incidence, treatment, and survival between LACC and other laryngeal malignancies were compared. Of 69 LACC patients, 63.8% were female, 78.2% Caucasian, and the median age was 54 years. LACC patients were much more likely to have subglottic lesions (44.9%) than individuals with other malignancies (1.6%). The incidence of LACC was 0.005/100,000 individuals. The majority of patients with LACC harbored T4 lesions at initial diagnosis, although 87.9% had N0 disease, and only 6.1% had distant metastasis at diagnosis. Disease-specific survival (DSS) was greater at 1 year for LACC compared to other laryngeal malignancies, but not at 5 or 10 years. Five-year DSS was greater for LACC patients who underwent surgery versus those who did not undergo surgery. This analysis notes that LACC has a low incidence with no significant change in incidence over the study period. Compared to other laryngeal malignancies, LACC has a female preponderance, is much more common in the subglottis, presents at a younger age, and more often presents with T4 disease. Surgery was noted to confer a survival advantage in LACC. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Successful Total En Bloc Spondylectomy of T7 Vertebra for Hepatocellular Carcinoma Metastasis After Living Donor Liver Transplantation.

PubMed

Kimura, Hiroaki; Fujibayashi, Shunsuke; Shimizu, Takayoshi; Otsuki, Bungo; Murakami, Hideki; Kaido, Toshimi; Uemoto, Shinji; Matsuda, Shuichi

2015-08-15

Case report. We report a patient who was successfully treated with total en bloc spondylectomy (TES) for T7 metastasis after living donor liver transplantation for hepatocellular carcinoma (HCC). Spinal metastasis from HCC has a poor prognosis. There are only a few studies on surgical outcomes of spinal metastasis from HCC. Because of the high surgical morbidity and short life expectancy in patients with HCC with spinal metastasis, TES is not considered in these patients, although several studies have reported satisfactory results for TES for some types of metastatic spinal tumors. Liver transplantation (LT) is the curative treatment option for early HCC. However, the recurrence of HCC is a possible problem after LT, although no reports on surgery for spinal metastasis following LT for HCC have been published. We report on the first case of a patient who was successfully treated with TES for T7 metastasis after living donor LT for HCC. The patient was a 65-year-old man, who had undergone living donor LT for HCC 2 years before. His main symptom was progressive gait disturbance because of the spinal cord compression by the tumor at T7. Radiology and pathology examinations revealed a solitary metastasis at T7 with neither recurrence in the liver nor metastasis in the other organs. We performed TES using a pedicle screw system and a mesh cage filled with frozen autografts. After surgery, the patient showed clear improvement in neurological symptoms. At 3 months after surgery, a T4 metastasis was detected with magnetic resonance imaging, and the patient was treated with heavy ion radiotherapy. He could walk without a cane and there was no evidence of recurrence at 1.5 years after surgery. Solitary spinal metastasis of HCC may become an indication for TES if liver function improves after LT. 5.

Stage Presentation, Care Patterns, and Treatment Outcomes for Squamous Cell Carcinoma of the Penis

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

Burt, Lindsay M.; Shrieve, Dennis C.; Tward, Jonathan D., E-mail: Jonathan.Tward@hci.utah.edu

Purpose: Penile squamous cell carcinoma (SCC) is a rare entity, with few published series on outcomes. We evaluated the stage distributions and outcomes for surgery and radiation therapy in a U.S. population database. Methods and Materials: Subjects with SCC of the penis were identified using the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program database between 1988 and 2006. Descriptive statistics were performed, and cause-specific survival (CSS) was estimated using Kaplan-Meier analysis. Comparisons of treatment modalities were analyzed using multivariate Cox regression. Subjects were staged using American Joint Committee on Cancer, sixth edition, criteria. Results: There were 2458more » subjects identified. The median age was 66.8 years (range, 17-102 years). Grade 2 disease was present in 94.5% of cases. T1, T2, T3, T4, and Tx disease was present in 64.8%, 17.1%, 9.5%, 2.1%, and 6.5% of cases, respectively. N0, N1, N2, N3, and Nx disease was noted in 61.6%, 6.9%, 4.0%, 3.7%, and 23.8% of cases, respectively. M1 disease was noted in 2.5% of subjects. Individuals of white ethnicity accounted for 85.1% of cases. Lymphadenectomy was performed in 16.7% of cases. The CSS for all patients at 5 and 10 years was 80.8% and 78.6%. By multivariable analysis grades 2 and 3 disease, T3 stage, and positive lymph nodes were adverse prognostic factors for CSS. Conclusion: SCC of the penis often presents as early-stage T1, N0, M0, grade 1, or grade 2 disease. The majority of patients identified were treated with surgery, and only a small fraction of patients received radiation therapy alone or as adjuvant therapy.« less

The translocon protein Sec61 mediates antigen transport from endosomes in the cytosol for cross-presentation to CD8(+) T cells.

PubMed

Zehner, Matthias; Marschall, Andrea L; Bos, Erik; Schloetel, Jan-Gero; Kreer, Christoph; Fehrenschild, Dagmar; Limmer, Andreas; Ossendorp, Ferry; Lang, Thorsten; Koster, Abraham J; Dübel, Stefan; Burgdorf, Sven

2015-05-19

The molecular mechanisms regulating antigen translocation into the cytosol for cross-presentation are under controversial debate, mainly because direct data is lacking. Here, we have provided direct evidence that the activity of the endoplasmic reticulum (ER) translocon protein Sec61 is essential for endosome-to-cytosol translocation. We generated a Sec61-specific intrabody, a crucial tool that trapped Sec61 in the ER and prevented its recruitment into endosomes without influencing Sec61 activity and antigen presentation in the ER. Expression of this ER intrabody inhibited antigen translocation and cross-presentation, demonstrating that endosomal Sec61 indeed mediates antigen transport across endosomal membranes. Moreover, we showed that the recruitment of Sec61 toward endosomes, and hence antigen translocation and cross-presentation, is dependent on dendritic cell activation by Toll-like receptor (TLR) ligands. These data shed light on a long-lasting question regarding antigen cross-presentation and point out a role of the ER-associated degradation machinery in compartments distinct from the ER. Copyright © 2015 Elsevier Inc. All rights reserved.

Low Temperature Grown and Highly Non-Stoichiometric GaAs and Related Materials

DTIC Science & Technology

1994-08-03

Ser. No. 67 (1983), p. 285.attributed to the nonuniformity of crystal growth 2T. Figielski, T. Wonsinski and A. Mokosa, Phys. Stat. Solidi (a) condition...1.75 pyramidal defect distribution was nonuniform in this pm; sample C, 1.6 pm; and sample D, 0.95 prm. Each sample, the defects being separated...the layers grown on [0011 oriented substrates whereas growth on the near [1101 substrates resulted in compositional nonuniformities , macrosteps for

Expression of cancer/testis antigens in salivary gland carcinomas with reference to MAGE-A and NY-ESO-1 expression in adenoid cystic carcinoma.

PubMed

Beppu, Shintaro; Ito, Yohei; Fujii, Kana; Saida, Kosuke; Takino, Hisashi; Masaki, Ayako; Murase, Takayuki; Kusafuka, Kimihide; Iida, Yoshiyuki; Onitsuka, Tetsuro; Yatabe, Yasushi; Hanai, Nobuhiro; Hasegawa, Yasuhisa; Ijichi, Kei; Murakami, Shingo; Inagaki, Hiroshi

2017-08-01

Cancer/testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins, and thus represent ideal targets for cytotoxic T-lymphocyte-mediated specific immune therapy. The aim of this study was to screen CTA expression in various types of salivary gland carcinoma and to clarify clinicopathological significance of MAGE-A and NY-ESO-1 expression in adenoid cystic carcinomas (AdCCs) of the salivary gland, which is one of the most common salivary gland carcinomas, and usually has a fatal outcome. We used immunohistochemistry to examine the expression of four CTAs (MAGE-A, NY-ESO-1, CT7, and GAGE7) in various types of salivary gland carcinoma (n = 95). When carcinoma cases were divided into low-grade and intermediate/high-grade types, NY-ESO-1 and CT7 were expressed more frequently in intermediate/high-grade carcinomas. We then focused on MAGE-A and NY-ESO-1 expression in a large cohort of adenoid cystic carcinomas (AdCCs) (n = 46). MAGE-A and NY-ESO-1 were frequently expressed in AdCC; specifically, MAGE-A was expressed in >60% of the AdCC cases. MAGE-A expression and tumour site (minor salivary gland) were identified as independent risk factors for locoregional tumour recurrence. These findings suggest that CTAs may be expressed in a variety of salivary gland carcinomas, especially in those with higher histological grades. In addition, MAGE-A, which is frequently expressed in AdCC cases, may be a useful prognostic factor for poorer locoregional recurrence-free survival. © 2017 John Wiley & Sons Ltd.

Clinicopathologic Features of Submucosal Esophageal Squamous Cell Carcinoma.

PubMed

Emi, Manabu; Hihara, Jun; Hamai, Yoichi; Furukawa, Takaoki; Ibuki, Yuta; Okada, Morihito

2017-12-01

The prognoses of submucosal esophageal squamous cell carcinoma patients vary. Patients with favorable prognoses may receive less invasive or nonsurgical interventions, whereas patients with poor prognoses or advanced esophageal cancer may require aggressive treatments. We sought to identify prognostic factors for patients with submucosal esophageal squamous cell carcinoma, focusing on lymph node metastasis and recurrence. We included 137 submucosal esophageal squamous cell carcinoma patients who had undergone transthoracic esophagectomy with systematic extended lymph node dissection. Submucosal tumors were classified as SM1, SM2, and SM3 according to the depth of invasion. Prognostic factors were determined by univariable and multivariable analyses. Lymph node metastasis was observed in 18.8%, 30.5%, and 50.0% of SM1, SM2, and SM3 cases, respectively. The overall 5-year recurrence rate was 21.9%; the rates for SM1, SM2, and SM3 tumors were 9.4%, 18.6%, and 34.8%, respectively. The SM1 tumors all recurred locoregionally; distant metastasis occurred in SM2 and SM3 cases. The 5-year overall survival rates were 83%, 77%, and 59% for SM1, SM2, and SM3 cases, respectively. On univariable analysis, lymph node metastasis, depth of submucosal invasion (SM3 versus SM1/2), and tumor location (upper thoracic versus mid/lower thoracic) were poor prognostic factors for overall survival. Multivariable Cox regression analyses identified depth of submucosal invasion (hazard ratio 2.51, 95% confidence interval: 1.37 to 4.61) and tumor location (hazard ratio 2.43, 95% confidence interval: 1.18 to 4.63) as preoperative prognostic factors. Tumor location (upper thoracic) and infiltration (SM3) are the worse prognostic factors of submucosal esophageal squamous cell carcinoma, but lymph node metastasis is not a predictor of poorer prognosis. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Functional Outcomes after Salvage Transoral Laser Microsurgery for Laryngeal Squamous Cell Carcinoma.

PubMed

Fink, Daniel S; Sibley, Haley; Kunduk, Melda; Schexnaildre, Mell; Sutton, Collin; Kakade-Pawar, Anagha; McWhorter, Andrew J

2016-10-01

Transoral laser microsurgery (TLM) has been increasingly used in lieu of total laryngectomy to treat malignancy after definitive radiation. There are few data in the literature regarding functional outcomes. We retrospectively reviewed voice and swallowing outcomes in patients who underwent TLM for recurrent laryngeal carcinoma. Case series with chart review. Tertiary care center. Forty-two patients were identified with recurrent squamous cell carcinoma of the larynx after definitive radiation therapy from 2001 to 2013: 28 patients with glottic recurrence and 14 with supraglottic recurrence. Swallowing outcomes were evaluated by gastrostomy tube dependence, the MD Anderson Dysphagia Inventory, and the Functional Oral Intake Scale. Voice outcomes were evaluated by the Voice Handicap Index and observer-rated perceptual analysis. No significant difference was noted between mean pre- and postoperative MD Anderson Dysphagia Inventory scores: 78.25 and 74.9, respectively (P = .118, t = 1.6955). Mean Functional Oral Intake Scale scores after TLM for supraglottic and glottic recurrences were 6.4 and 6.6, respectively. Of 42 patients, 17 (40.5%) required a gastrostomy tube either during radiation or in conjunction with the salvage procedure. Of 17 patients, 15 resumed sufficient oral diet for tube removal. Patients' mean Voice Handicap Index score did increase from 34.3 to 51.5 (P = .047), and their mean perceptual score did decrease from 60.0 to 45.3 (P = .005). However, at 1-year follow-up, there was no significant difference in perceptual score: 61.1 to 57.1 (P = .722). TLM is a successful surgical option for recurrent laryngeal cancer with acceptable functional outcomes. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

High-intensity focused ultrasound ablation for treatment of hepatocellular carcinoma and hypersplenism: preliminary study.

PubMed

Zhu, Jing; Zhu, Hui; Mei, Zhechuan; Jin, Chengbing; Ran, Lifeng; Zhou, Kun; Yang, Wei; Zhang, Lian; She, Chaokun

2013-10-01

The purpose of this work was to preliminarily investigate the efficacy and safety of high-intensity focused ultrasound treatment of hepatocellular carcinoma and hypersplenism. Nine patients with hepatocellular carcinoma complicated by hypersplenism (5 male and 4 female; median age, 56 years; range, 51-66 years) were treated with ultrasound-guided high-intensity focused ultrasound. Complications were recorded. Laboratory examination and magnetic resonance imaging were used to evaluate the efficacy. After high-intensity focused ultrasound treatment, mean spleen ablation ± SD of 28.76% ± 6.1% was discovered; meanwhile, the white blood cell count, platelet count, and liver function of the patients were substantially improved during the follow-up period. In addition, symptoms such as epistaxis and gingival bleeding were ameliorated or even eliminated, and the quality of life was improved. Follow-up imaging showed a nonperfused volume in the spleen and an absence of a tumor blood supply at the treated lesions in the liver. For the first time to our knowledge, high-intensity focused ultrasound ablation was used to treat hepatocellular carcinoma complicated by hypersplenism. High-intensity focused ultrasound may be an effective and safe alternative for treatment of hepatocellular carcinoma complicated by hypersplenism, but further studies are necessary to clarify the mechanisms.

HPV-negative penile squamous cell carcinoma: disruptive mutations in the TP53 gene are common.

PubMed

Kashofer, Karl; Winter, Elke; Halbwedl, Iris; Thueringer, Andrea; Kreiner, Marisa; Sauer, Stefan; Regauer, Sigrid

2017-07-01

The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16 ink4a overexpression and for TP53 mutations by ion torrent next-generation sequencing. Library preparation failed in 32/108 squamous cell carcinomas. Institutional review board approval was obtained. Thirty of 76 squamous cell carcinomas (43%; average 63 years) were HPV-negative with 8/33 squamous cell carcinomas being TP53 wild-type (24%; average 63 years). Twenty-five of 33 squamous cell carcinomas (76%; average 65 years) showed 32 different somatic TP53 mutations (23 missense mutations in exons 5-8, 6 nonsense, 1 frameshift and 2 splice-site mutations). Several hotspot mutations were detected multiple times (R175H, R248, R282, and R273). Eighteen of 19 squamous cell carcinomas with TP53 expression in immunohistochemistry had TP53 mutations. Fifty percent of TP53-negative squamous cell carcinomas showed mostly truncating loss-of-function TP53 mutations. Patients without mutations had longer survival (5 years: 86% vs 61%; 10 years: 60% vs 22%), but valid clinically relevant conclusions cannot be drawn due to different tumor stages and heterogeneous treatment of the cases presented in this study. Somatic TP53 mutations are a common feature in HPV-negative penile squamous cell carcinomas and offer an explanation for HPV-independent penile carcinogenesis. About half of HPV-negative penile cancers are driven by oncogenic activation of TP53, while a quarter is induced by loss of TP53 tumor suppressor function. Detection of TP53 mutations should be carried out by sequencing, as immunohistochemical TP53 staining could not identify all squamous cell carcinomas with TP53 mutations.

Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma

ClinicalTrials.gov

2018-04-20

Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Nasopharyngeal Undifferentiated Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7

40 CFR Appendix A to Part 61 - Appendix A to Part 61

Code of Federal Regulations, 2010 CFR

2010-07-01

...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS Pt. 61, App. A Appendix A to Part 61 EC01MY92.015... awarded; or date by which orders will be issued for the purchase of the component parts to accomplish...

40 CFR Appendix A to Part 61 - Appendix A to Part 61

Code of Federal Regulations, 2011 CFR

2011-07-01

...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS Pt. 61, App. A Appendix A to Part 61 EC01MY92.015... awarded; or date by which orders will be issued for the purchase of the component parts to accomplish...

Bronchoalveolar carcinoma of lung masquerading as iodine avid metastasis in a patient with minimally invasive follicular carcinoma of thyroid.

PubMed

Malhotra, Gaurav; Nair, Narendra; Menon, Hari; Gujral, Sumit; Abhyankar, Amit; Baghel, Nawab S; Awasare, Sushama; Nabar, Swapna J; Abhyankar, Suman; Kand, Purushottam G

2008-01-01

A 52-year-old man with follicular thyroid carcinoma was administered 182 mCi of radioiodine (I-131) a month after total thyroidectomy. Post-therapy scan revealed diffuse uptake of radioiodine in the apical left lung. CT-guided biopsy of this mass revealed mucinous bronchoalveolar carcinoma. Immunohistochemistry for thyroglobulin was negative. An FDG PET scan showed avid uptake in the lung mass. Surgery was ruled out, so he was given chemotherapy, without benefit. The lesion continued to show I-131 uptake even while on daily T3 substitution, suggesting that the mass was thyroid stimulating hormone-independent. Because the mass showed I-131 uptake and chemotherapy was not beneficial, it was decided to treat with I-131. He was continued on T3 substitution therapy and was given 209 mCi of I-131. Follow-up CT scan a few weeks later reported a 1-cm all round reduction of the mass. I-131 scan showed avid tracer uptake in the mass. This case suggests the possibility of this therapeutic option in nonthyroidal tumors that may concentrate radioiodine.

Radiation therapy for gastric wall metastasis from esophageal carcinoma.

PubMed

Hashimoto, Naoko; Iwazawa, Jin; Abe, Hisashi; Mitani, Takashi; Kagawa, Kazufumi

2010-04-01

An 86-year-old man with dysphagia underwent gastrointestinal fiberscopy (GIF) and was found to have a circumferential type 3 advanced carcinoma in the upper thoracic esophagus and a type 2 tumor in the posterior wall of the gastric body. Microscopic examination of biopsy specimens of both tumors demonstrated moderately differentiated squamous cell carcinoma. He was diagnosed as having stage IVb (T3N0M1b) esophageal carcinoma with gastric wall metastasis. A total of 60 Gy in 30 fractions of three-dimensional conformal radiation therapy (3D-CRT) was first administered to the esophageal carcinoma, next to the gastric wall metastasis. Concurrent chemotherapy was not given because of the patient's refusal. No subjective morbidity was observed during the treatment. In the GIF study immediately after 3D-CRT, both esophageal and gastric wall tumors had attained a complete response. The dysphagia dissolved as the esophageal tumor shrunk. The patient has been doing well for 17 months after the start of 3D-CRT. No local recurrence was observed in either the esophagus or the stomach during follow-up GIF. Considering the dismal prognosis of esophageal carcinoma patients with intramural metastasis to the stomach, a watchful follow-up is needed.

Effect of increasing the flip angle during the hepatocyte phase of gadobenate dimeglumine-enhanced 1.5T MRI in cirrhotic patients with hepatocellular carcinoma.

PubMed

Lee, Eun Jung; Kim, Dae Jung; Cho, Eun-Suk; Kim, Kyoung Ah

2016-03-01

To evaluate the effects of increasing the flip angle during the hepatocyte phase of gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) in cirrhotic patients with hepatocellular carcinoma (HCC). Sixty-three patients with liver cirrhosis underwent gadobenate dimeglumine-enhanced 1.5T MRI with 90-minute delayed hepatocyte phase with flip angles of 10°, 20°, 30°, consecutively. Relative enhancement and signal-to-noise ratio (SNR) of liver parenchyma at hepatocyte phase according to flip angle were calculated. The liver-to-lesion (low signal intensity HCCs, n = 63; ≥1 cm) and contrast-to-noise ratio (CNR) at the hepatocyte phase according to flip angle were calculated. Two radiologists independently assessed the presence of HCCs using a 5-point scale, and detection sensitivity of HCCs was calculated according to flip angle. The relative enhancement of hepatic parenchyma differed significantly according to flip angle (10°, mean relative enhancement = 0.69 ± 0.46; 20°, mean relative enhancement = 0.63 ± 0.47; 30°, mean relative enhancement = 0.49 ± 0.45; P = 0.043). The SNR of hepatic parenchyma was significantly different according to flip angle (10°, mean SNR = 26.2 ± 5.6; 20°, mean SNR = 25.3 ± 5.7; 30°, mean SNR = 22.8 ± 6.1; P = 0.004). The CNR of lesion was not significantly different according to flip angle (10°, mean CNR = 7.5 ± 6.6; 20°, mean CNR = 10.2 ± 6.9; 30°, mean CNR = 10.1 ± 7.1; P = 0.051). The sensitivities with 10° and 20° for HCCs were significantly higher than those with 30° for one reader (P < 0.05). In patients with cirrhosis, hepatocyte phase gadobenate dimeglumine-enhanced 1.5T MRI with 20° flip angle should be recommended rather than 10° and 30° flip angle. © 2015 Wiley Periodicals, Inc.

Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer

DTIC Science & Technology

2006-07-01

Davies S, Gibbs P, Morris LS, Coleman N and Alexander GJ. Compromised lymphocytes infiltrate hepatocellular carcinoma : the role of T-regulatory...cells in peripheral blood of patients with hepatocellular carcinoma . Cancer Res., 65: 2457-2464, 2005. (8) Casares N, Arribillaga L, Sarobe P, Dotor J

46 CFR 221.61 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Purpose. 221.61 Section 221.61 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING MARITIME CARRIERS AND RELATED ACTIVITIES REGULATED TRANSACTIONS INVOLVING DOCUMENTED VESSELS AND OTHER MARITIME INTERESTS Civil Penalties § 221.61...

14 CFR 61.323 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false [Reserved] 61.323 Section 61.323 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: PILOTS, FLIGHT INSTRUCTORS, AND GROUND INSTRUCTORS Sport Pilots § 61.323 [Reserved] ...

14 CFR 61.319 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false [Reserved] 61.319 Section 61.319 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: PILOTS, FLIGHT INSTRUCTORS, AND GROUND INSTRUCTORS Sport Pilots § 61.319 [Reserved] ...

40 CFR 420.61 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 420.61 Section 420.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Continuous Casting Subcategory § 420.61 [Reserved] ...

40 CFR 440.61 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false [Reserved] 440.61 Section 440.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORE MINING AND DRESSING POINT SOURCE CATEGORY Tungsten Ore Subcategory § 440.61 [Reserved] ...

40 CFR 440.61 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false [Reserved] 440.61 Section 440.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORE MINING AND DRESSING POINT SOURCE CATEGORY Tungsten Ore Subcategory § 440.61 [Reserved] ...

7 CFR 923.61 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Compliance. 923.61 Section 923.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... COUNTIES IN WASHINGTON Order Regulating Handling Miscellaneous Provisions § 923.61 Compliance. Except as...

7 CFR 922.61 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Compliance. 922.61 Section 922.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... IN WASHINGTON Order Regulating Handling Miscellaneous Provisions § 922.61 Compliance. Except as...

7 CFR 923.61 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Compliance. 923.61 Section 923.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... COUNTIES IN WASHINGTON Order Regulating Handling Miscellaneous Provisions § 923.61 Compliance. Except as...

7 CFR 922.61 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Compliance. 922.61 Section 922.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... IN WASHINGTON Order Regulating Handling Miscellaneous Provisions § 922.61 Compliance. Except as...

Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck.

PubMed

van Weert, Stijn; Reinhard, Rinze; Bloemena, Elisabeth; Buter, Jan; Witte, Birgit I; Vergeer, Marije R; Leemans, C René

2017-03-01

We examined the assumption in conventional teaching about metastatic adenoid cystic carcinoma (ACC) being an indolent type of disease. A single center analysis of 105 cases of ACC was performed. Radiographs were reviewed and tumor response to chemotherapy was measured. Distant disease-free survival (DDFS) and time to death since distant metastases diagnosis were analyzed. Forty-two percent of the patients were diagnosed with distant metastases. DDFS showed significant negative associations with advanced T classification, N+ classification, solid type tumor, and positive surgical margins. Distant metastases (91%) developed in the first 5 years after presentation. Median distant metastatic survival was 13.8 months. The most frequent organ sited was the lung. Solid type ACC showed a preponderance for multiorgan metastases (17/28; 61%). Distant metastases seemed not to occur in case of clear surgical margins. Solid type ACC had a significant poorer survival after development of distant metastases. Metastatic ACC is not always an indolent disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 456-463, 2017. © 2016 Wiley Periodicals, Inc.

CD 10 expression intensity in various grades and stages of urothelial carcinoma of urinary bladder.

PubMed

Atique, Muhammad; Abbasi, Muhammad Sajjad; Jamal, Shahid; Khadim, Muhammad Tahir; Akhtar, Farhan; Jamal, Nighat

2014-05-01

To evaluate CD10 expression in urothelial carcinoma of the urinary bladder and the association of immunohistochemical (IHC) CD10 expression intensity with grade and stage. Descriptive cross-sectional analytical study. Armed Forces Institute of Pathology, Rawalpindi, from January to December 2011. Fifty consecutive cases of urothelial bladder carcinomas, obtained through transurethral resections, were included in this study. Hematoxylin-eosin (HE) stained sections from each case were re-evaluated histopathologically according to WHO 2004 grading system. The TNM system was used for pathologic staging. On selected slides IHC CD10 marker was applied and a semiquantitative scoring for its expression based on the percentage of positive cells and intensity was performed. Data was entered and analysed on SPSS version 17. Fisher's exact test was used to compare grades, stages of urothelial carcinoma with CD 10 expression and age groups. P < 0.05 was taken as level of significance. Urothelial carcinoma was more common in males. The male to female ratio was 9:1. The older patients > 50 years had higher grade and stage as compared to the younger patients. All cases of high grade urothelial carcinoma showed higher positivity for CD 10. Twenty cases (86.95%) of high grade urothelial carcinoma were positive with +2 immunostaining while 3 cases (13.04 %) were positive with +1 staining. None of the tumors of stage pTa was positive for CD 10 expression. Of all patients with stage pT 1 tumor, 1 case (5.3%) was CD 10 negative and 17 cases (89.9%) were CD 10 positive having +1 staining with 5 - 50% staining and 1 case (5.3%) had +2 staining with more then 50% expression. Out of all patients with stage pT 2, no tumor was CD 10 negative, 3 (13.6%) patients were CD 10 positive with +1 staining and 19 (86.4%) with stage pT 2 tumor had stained positive with +2 staining. CD 10 expression was greater in high grade and invasive urothelial carcinomas; it may be associated with tumor progression

Glasgow Prognostic Score as a Prognostic Clinical Marker in T4 Esophageal Squamous Cell Carcinoma.

PubMed

Ohira, Masaichi; Kubo, Naoshi; Masuda, Go; Yamashita, Yoshito; Sakurai, Katsunobu; Toyokawa, Takahiro; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

2015-09-01

Patients with clinical T4 esophageal squamous cell carcinoma (ESCC) have an unfavorable prognosis, mainly indicated by the response to chemoradiotherapy (CRT), crucial to estimating long-term survival. Other prognostic measures include systemic inflammatory or immunonutritional indices such as the Glasgow Prognostic Score (GPS) and Prognostic Nutritional Index (PNI) that have not been sufficiently documented. This study retrospectively evaluated 91 patients with T4 ESCC treated at our Hospital between 2000 and 2013. All patients initially received CRT, including 5-fluorouracil (5FU) and cisplatin or nedaplatin with concurrent 2-Gy/fraction radiation (total dose, 40-60 Gy). Curative tumor resection was undertaken in suitable patients on completing CRT. Patients were classified as GPS0, GPS1, or GPS2 based on C-reactive protein (CRP) ≤ 10 mg/l and albumin ≥ 35 g/l, CRP >10 mg/l or albumin <35 g/l, or CRP >10 mg/l and albumin <35 g/l, respectively. PNI was calculated as 10-times the serum albumin (g/dl)+0.005 × total lymphocyte count (/mm(3)). The impact of the pre-treatment GPS and PNI on the prognosis of patients with T4 ESCC was investigated in univariate and multivariate analyses. Sixty (67%) patients responded to CRT (9 complete responses and 51 partial responses). Forty-one (45%) patients also underwent surgical resection of the residual tumor. The overall 5-year survival rate and median survival time were 27.0% and 11.8 months, respectively. In the cohort of CRT-plus-surgical resection, the 5-year survival rate was significantly higher than in the groups treated with CRT-alone (51.1% vs. 6.5%; p < 0.01). On multivariate analysis, good response to CRT [hazard ratio (HR) =0.449, p<0.01], GPS1/2 (HR=2.151, p=0.015), and surgical resection (HR=0.282, p<0.01) were significant prognostic factors, whereas PNI was not. The GPS is a useful, simple survival marker for patients with T4 ESCC undergoing multimodal therapy. Copyright© 2015 International Institute of

Urothelial carcinoma involving the distal penis.

PubMed

Dason, Shawn; Sheikh, Adeel; Wang, Jing Gennie; Tauqir, Syeda; Davies, Timothy O; Shayegan, Bobby

2012-04-01

Urothelial carcinoma (UC) rarely metastasizes to the penis and skin. We report the case of a 73-year-old man with UC metastases to the corpus spongiosum and dermis of the distal penis. We also review the clinicopathologic characteristics and management options for UC metastasizing to the penis. The patient presented with priapism and edema of the genital region. This follows a 5-year history of urothelial carcinoma in situ that progressed to invasive cancer despite intravesical immunotherapy. Seventeen months prior to presentation, the patient underwent a radical cystectomy with adjuvant chemotherapy. The cystectomy specimen demonstrated a pT4a N2 M0 G3 UC and margins were positive for carcinoma in situ. Follow-up had been negative for recurrence until his presentation with priapism. Incisional biopsy of the glans revealed UC and radical penectomy was performed with negative margins. The penile specimen demonstrated extensive involvement of the corpus spongiosum by UC with lymphovascular invasion and subepidermal involvement. Three months after penectomy, the patient presented with inguinal nodal recurrence. Palliative radiotherapy was administered and the patient passed away eight months after surgery.

7 CFR 30.61 - Administration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Administration. 30.61 Section 30.61 Agriculture... AND STANDARDS Administration § 30.61 Administration. The Director, Tobacco Division, Agricultural... the Division and the performance of all duties assigned thereto in the administration of the Tobacco...

7 CFR 30.61 - Administration.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Administration. 30.61 Section 30.61 Agriculture... AND STANDARDS Administration § 30.61 Administration. The Director, Tobacco Division, Agricultural... the Division and the performance of all duties assigned thereto in the administration of the Tobacco...

7 CFR 30.61 - Administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Administration. 30.61 Section 30.61 Agriculture... AND STANDARDS Administration § 30.61 Administration. The Director, Tobacco Division, Agricultural... the Division and the performance of all duties assigned thereto in the administration of the Tobacco...

40 CFR 440.61 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false [Reserved] 440.61 Section 440.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ORE MINING AND DRESSING POINT SOURCE CATEGORY Tungsten Ore Subcategory § 440.61 [Reserved] ...

40 CFR 440.61 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false [Reserved] 440.61 Section 440.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ORE MINING AND DRESSING POINT SOURCE CATEGORY Tungsten Ore Subcategory § 440.61 [Reserved] ...

40 CFR 440.61 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false [Reserved] 440.61 Section 440.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ORE MINING AND DRESSING POINT SOURCE CATEGORY Tungsten Ore Subcategory § 440.61 [Reserved] ...

42 CFR 61.34 - Qualifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Qualifications. 61.34 Section 61.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.34 Qualifications. Scholastic and other qualifications shall be...

42 CFR 61.12 - Accountability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Accountability. 61.12 Section 61.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.12 Accountability. Payments shall be subject to such requirements...

42 CFR 61.18 - Publications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Publications. 61.18 Section 61.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.18 Publications. Publication, distribution, and disposition of all...

42 CFR 61.34 - Qualifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Qualifications. 61.34 Section 61.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.34 Qualifications. Scholastic and other qualifications shall be...

42 CFR 61.12 - Accountability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Accountability. 61.12 Section 61.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.12 Accountability. Payments shall be subject to such requirements...

42 CFR 61.12 - Accountability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Accountability. 61.12 Section 61.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.12 Accountability. Payments shall be subject to such requirements...

42 CFR 61.18 - Publications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Publications. 61.18 Section 61.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.18 Publications. Publication, distribution, and disposition of all...

42 CFR 61.18 - Publications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Publications. 61.18 Section 61.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.18 Publications. Publication, distribution, and disposition of all...

42 CFR 61.34 - Qualifications.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Qualifications. 61.34 Section 61.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.34 Qualifications. Scholastic and other qualifications shall be...

42 CFR 61.18 - Publications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Publications. 61.18 Section 61.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.18 Publications. Publication, distribution, and disposition of all...

42 CFR 61.34 - Qualifications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Qualifications. 61.34 Section 61.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.34 Qualifications. Scholastic and other qualifications shall be...

42 CFR 61.34 - Qualifications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Qualifications. 61.34 Section 61.34 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.34 Qualifications. Scholastic and other qualifications shall be...

42 CFR 61.12 - Accountability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Accountability. 61.12 Section 61.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.12 Accountability. Payments shall be subject to such requirements...

42 CFR 61.12 - Accountability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Accountability. 61.12 Section 61.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.12 Accountability. Payments shall be subject to such requirements...

42 CFR 61.18 - Publications.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Publications. 61.18 Section 61.18 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.18 Publications. Publication, distribution, and disposition of all...

44 CFR 61.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Definitions. 61.2 Section 61.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program INSURANCE COVERAGE AND RATES § 61...

44 CFR 61.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Definitions. 61.2 Section 61.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program INSURANCE COVERAGE AND RATES § 61...

44 CFR 61.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 61.2 Section 61.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program INSURANCE COVERAGE AND RATES § 61...

44 CFR 61.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Definitions. 61.2 Section 61.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program INSURANCE COVERAGE AND RATES § 61...

14 CFR 158.61 - General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false General. 158.61 Section 158.61 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.61 General. This subpart contains the...

14 CFR 158.61 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false General. 158.61 Section 158.61 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.61 General. This subpart contains the...

14 CFR 158.61 - General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false General. 158.61 Section 158.61 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.61 General. This subpart contains the...

14 CFR 158.61 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false General. 158.61 Section 158.61 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.61 General. This subpart contains the...

14 CFR 158.61 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false General. 158.61 Section 158.61 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS PASSENGER FACILITY CHARGES (PFC'S) Reporting, Recordkeeping and Audits § 158.61 General. This subpart contains the...

10 CFR 61.5 - Interpretations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Interpretations. 61.5 Section 61.5 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.5 Interpretations. Except as specifically authorized by the Commission in writing, no...

10 CFR 61.5 - Interpretations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Interpretations. 61.5 Section 61.5 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.5 Interpretations. Except as specifically authorized by the Commission in writing, no...

10 CFR 61.5 - Interpretations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Interpretations. 61.5 Section 61.5 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.5 Interpretations. Except as specifically authorized by the Commission in writing, no...

10 CFR 61.4 - Communications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Communications. 61.4 Section 61.4 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.4 Communications. Except where otherwise specified, all communications and reports concerning...

10 CFR 61.4 - Communications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Communications. 61.4 Section 61.4 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.4 Communications. Except where otherwise specified, all communications and reports concerning...

10 CFR 61.4 - Communications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Communications. 61.4 Section 61.4 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.4 Communications. Except where otherwise specified, all communications and reports concerning...

10 CFR 61.4 - Communications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Communications. 61.4 Section 61.4 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.4 Communications. Except where otherwise specified, all communications and reports concerning...

10 CFR 61.5 - Interpretations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Interpretations. 61.5 Section 61.5 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.5 Interpretations. Except as specifically authorized by the Commission in writing, no...

10 CFR 61.5 - Interpretations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Interpretations. 61.5 Section 61.5 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.5 Interpretations. Except as specifically authorized by the Commission in writing, no...

10 CFR 61.4 - Communications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Communications. 61.4 Section 61.4 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.4 Communications. Except where otherwise specified, all communications and reports concerning...

7 CFR 915.61 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Compliance. 915.61 Section 915.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Miscellaneous Provisions § 915.61 Compliance. Except as provided in this part, no person...

7 CFR 916.61 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Compliance. 916.61 Section 916.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Miscellaneous Provisions § 916.61 Compliance. Except as provided in this part, no person...

7 CFR 925.61 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Compliance. 925.61 Section 925.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... SOUTHEASTERN CALIFORNIA Miscellaneous Provisions § 925.61 Compliance. Except as provided in this part, no...

7 CFR 916.61 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Compliance. 916.61 Section 916.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Miscellaneous Provisions § 916.61 Compliance. Except as provided in this part, no person...

7 CFR 925.61 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Compliance. 925.61 Section 925.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... SOUTHEASTERN CALIFORNIA Miscellaneous Provisions § 925.61 Compliance. Except as provided in this part, no...

7 CFR 915.61 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Compliance. 915.61 Section 915.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Miscellaneous Provisions § 915.61 Compliance. Except as provided in this part, no person...

Immune repertoire: A potential biomarker and therapeutic for hepatocellular carcinoma.

PubMed

Han, Yingxin; Li, Hongmei; Guan, Yanfang; Huang, Jian

2016-09-01

The immune repertoire (IR) refers to the sum of B cells and T cells with functional diversity in the circulatory system of one individual at any given time. Immune cells, which reside within microenvironments and are responsible for protecting the human body, include T cells, B cells, macrophages, and dendritic cells. These dedicated immune cells have a characteristic structure and function. T and B cells are the main lymphocytes and are responsible for cellular immunity and humoral immunity, respectively. The T cell receptor (TCR) and B cell receptor (BCR) are composed of multiple peptide chains with antigen specificity. The amino acid composition and sequence order are more diverse in the complementarity-determining regions (including CDR1, CDR2 and CDR3) of each peptide chain, allowing a vast library of TCRs and BCRs. IR research is becoming increasingly focused on the study of CDR3 diversity. Deep profiling of CDR3s using high-throughput sequencing is a powerful approach for elucidating the composition and distribution of the CDR3s in a given sample, with in-depth information at the sequence level. Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. To identify novel biomarkers for diagnosis and drug targets for therapeutic interventions, several groups attempted to describe immune repertoire characteristics of the liver in the physiological environment or/and pathological conditions. This paper reviews the recent progress in IR research on human diseases, including hepatocellular carcinoma, attempting to depict the relationships between hepatocellular carcinogenesis and the IR, and discusses the possibility of IR as a potential biomarker and therapeutic for hepatocellular carcinoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinicopathologic Characteristics and Prognosis of Xp11.2 Translocation Renal Cell Carcinoma: Multicenter, Propensity Score Matching Analysis.

PubMed

Choo, Min Soo; Jeong, Chang Wook; Song, Cheryn; Jeon, Hwang Gyun; Seo, Seong Il; Hong, Sung Kyu; Byun, Seok-Soo; Chung, Jin Soo; Hong, Sung-Hoo; Hwang, Eu Chang; Kim, Hyeon Hoe; Kwak, Cheol

2017-10-01

We evaluated the clinicopathologic characteristics and prognosis of Xp11.2 translocation (Xp11.2t) renal cell carcinoma (RCC) from a multicenter study and compare them with clear-cell RCC using a propensity score matching analysis. Between 2004 and 2013, 8384 consecutive patients from 7 institutions who were diagnosed with RCC were reviewed, and the pathologically confirmed Xp11.2t cases were enrolled. The oncological outcomes of Xp11.2t were compared with those of clear-cell RCC by selecting matched cases using 1:3 propensity score matching methods in a precollected clear-cell RCC data set from our hospital. The patients were divided into 2 subgroups on the basis of age of onset, either before (early) or after (late) 45 years old. Xp11.2t was found in 61 cases, corresponding to 0.72% of RCC cases for the 10 years. The mean age was 38.2 ± 19.4 years, and the mean tumor size was 6.2 ± 3.9 cm. The Xp11.2t cases were at more advanced stages and showed tendencies to involve lymph nodes at diagnosis. After the matching, there were no significant differences in recurrence-free and overall survival compared with clear-cell RCC. The age of incidence for Xp11.2t had a bimodal distribution, which was most common in the 30s and smaller peak in the 60s. Xp11.2t corresponded to a significantly worse prognosis for overall survival in late onset (after 45 years) subgroup (P = .038; hazard ratio, 3.199; 95% confidence interval, 1.065-9.609). This neoplasm has more aggressive clinicopathologic features at diagnosis. In older patients with onset age > 45 years, Xp11.2t showed a significantly worse prognosis than clear-cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

7 CFR 3550.61 - Insurance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Insurance. 3550.61 Section 3550.61 Agriculture... DIRECT SINGLE FAMILY HOUSING LOANS AND GRANTS Section 502 Origination § 3550.61 Insurance. (a) Borrower... furnish and continually maintain hazard insurance on the security property, with companies, in amounts...

45 CFR 605.61 - Procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Procedures. 605.61 Section 605.61 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Procedures § 605.61...

42 CFR 61.31 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Applicability. 61.31 Section 61.31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.31 Applicability. The regulations in this part apply to the establishment...

42 CFR 61.2 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Applicability. 61.2 Section 61.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.2 Applicability. The regulations in this subpart apply to the...

42 CFR 61.31 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Applicability. 61.31 Section 61.31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.31 Applicability. The regulations in this part apply to the establishment...

42 CFR 61.5 - Qualifications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Qualifications. 61.5 Section 61.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.5 Qualifications. In order to qualify for a regular fellowship, an...

42 CFR 61.2 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Applicability. 61.2 Section 61.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.2 Applicability. The regulations in this subpart apply to the...

42 CFR 61.5 - Qualifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Qualifications. 61.5 Section 61.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.5 Qualifications. In order to qualify for a regular fellowship, an...

42 CFR 61.2 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Applicability. 61.2 Section 61.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.2 Applicability. The regulations in this subpart apply to the...

42 CFR 61.2 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Applicability. 61.2 Section 61.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.2 Applicability. The regulations in this subpart apply to the...

42 CFR 61.5 - Qualifications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Qualifications. 61.5 Section 61.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.5 Qualifications. In order to qualify for a regular fellowship, an...

42 CFR 61.2 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Applicability. 61.2 Section 61.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.2 Applicability. The regulations in this subpart apply to the...

42 CFR 61.31 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Applicability. 61.31 Section 61.31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.31 Applicability. The regulations in this part apply to the establishment...

42 CFR 61.31 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Applicability. 61.31 Section 61.31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.31 Applicability. The regulations in this part apply to the establishment...

42 CFR 61.31 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Applicability. 61.31 Section 61.31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.31 Applicability. The regulations in this part apply to the establishment...

42 CFR 61.5 - Qualifications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Qualifications. 61.5 Section 61.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.5 Qualifications. In order to qualify for a regular fellowship, an...

42 CFR 61.5 - Qualifications.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Qualifications. 61.5 Section 61.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.5 Qualifications. In order to qualify for a regular fellowship, an...

44 CFR 61.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Definitions. 61.2 Section 61.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program INSURANCE COVERAGE AND RATES § 61.2...

14 CFR 294.61 - Waivers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Waivers. 294.61 Section 294.61 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CANADIAN CHARTER AIR TAXI OPERATORS Authorizations and Waivers § 294.61 Waivers. The Department...

14 CFR 294.61 - Waivers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Waivers. 294.61 Section 294.61 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS CANADIAN CHARTER AIR TAXI OPERATORS Authorizations and Waivers § 294.61 Waivers. The Department...

38 CFR 4.61 - Examination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Examination. 4.61 Section 4.61 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.61 Examination. With any form of arthritis...

38 CFR 4.61 - Examination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Examination. 4.61 Section 4.61 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.61 Examination. With any form of arthritis...

38 CFR 4.61 - Examination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Examination. 4.61 Section 4.61 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.61 Examination. With any form of arthritis...

38 CFR 4.61 - Examination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Examination. 4.61 Section 4.61 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.61 Examination. With any form of arthritis...

7 CFR 920.61 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Compliance. 920.61 Section 920.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Miscellaneous Provisions § 920.61 Compliance. (a) Except as provided in this part, no person shall handle...

7 CFR 920.61 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Compliance. 920.61 Section 920.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Miscellaneous Provisions § 920.61 Compliance. (a) Except as provided in this part, no person shall handle...

7 CFR 924.61 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Compliance. 924.61 Section 924.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... § 924.61 Compliance. Except as provided in this part, no person shall handle prunes, the shipment of...

7 CFR 924.61 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Compliance. 924.61 Section 924.61 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... § 924.61 Compliance. Except as provided in this part, no person shall handle prunes, the shipment of...

Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

PubMed

Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

2016-08-01

Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

10 CFR 39.61 - Training.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Training. 39.61 Section 39.61 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Radiation Safety Requirements § 39.61... handling tools, and radiation survey instruments by a field evaluation; and (4) Has demonstrated...

10 CFR 39.61 - Training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Training. 39.61 Section 39.61 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Radiation Safety Requirements § 39.61... handling tools, and radiation survey instruments by a field evaluation; and (4) Has demonstrated...

10 CFR 39.61 - Training.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Training. 39.61 Section 39.61 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Radiation Safety Requirements § 39.61... handling tools, and radiation survey instruments by a field evaluation; and (4) Has demonstrated...

10 CFR 39.61 - Training.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Training. 39.61 Section 39.61 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Radiation Safety Requirements § 39.61... handling tools, and radiation survey instruments by a field evaluation; and (4) Has demonstrated...

10 CFR 39.61 - Training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Training. 39.61 Section 39.61 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Radiation Safety Requirements § 39.61... handling tools, and radiation survey instruments by a field evaluation; and (4) Has demonstrated...

45 CFR 61.16 - Immunity.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Immunity. 61.16 Section 61.16 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HEALTHCARE INTEGRITY AND PROTECTION DATA BANK... Information by the Healthcare Integrity and Protection Data Bank § 61.16 Immunity. Individuals, entities or...

45 CFR 61.16 - Immunity.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Immunity. 61.16 Section 61.16 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HEALTHCARE INTEGRITY AND PROTECTION DATA BANK... Information by the Healthcare Integrity and Protection Data Bank § 61.16 Immunity. Individuals, entities or...

45 CFR 61.16 - Immunity.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Immunity. 61.16 Section 61.16 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HEALTHCARE INTEGRITY AND PROTECTION DATA BANK... Information by the Healthcare Integrity and Protection Data Bank § 61.16 Immunity. Individuals, entities or...

33 CFR 159.61 - Vents.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Vents. 159.61 Section 159.61 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION MARINE SANITATION DEVICES Design, Construction, and Testing § 159.61 Vents. Vents must be designed and constructed...

42 CFR 61.30 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Definitions. 61.30 Section 61.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.30 Definitions. As used in this part: Continental United States does not...

42 CFR 61.21 - Interest.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Interest. 61.21 Section 61.21 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.21 Interest. Any interest earned through deposit or investment by the sponsoring...

42 CFR 61.21 - Interest.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Interest. 61.21 Section 61.21 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.21 Interest. Any interest earned through deposit or investment by the sponsoring...

42 CFR 61.21 - Interest.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Interest. 61.21 Section 61.21 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.21 Interest. Any interest earned through deposit or investment by the sponsoring...

42 CFR 61.21 - Interest.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Interest. 61.21 Section 61.21 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.21 Interest. Any interest earned through deposit or investment by the sponsoring...

42 CFR 61.21 - Interest.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Interest. 61.21 Section 61.21 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.21 Interest. Any interest earned through deposit or investment by the sponsoring...

42 CFR 61.30 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Definitions. 61.30 Section 61.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.30 Definitions. As used in this part: Continental United States does not...

42 CFR 61.30 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Definitions. 61.30 Section 61.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.30 Definitions. As used in this part: Continental United States does not...

42 CFR 61.30 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Definitions. 61.30 Section 61.30 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Service Fellowships § 61.30 Definitions. As used in this part: Continental United States does not...

10 CFR 61.83 - Violations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Violations. 61.83 Section 61.83 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Records, Reports, Tests, and Inspections § 61.83 Violations. (a) The Commission may obtain an injunction or other court order...

10 CFR 61.25 - Changes.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Changes. 61.25 Section 61.25 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.25 Changes... land disposal facility or procedures described in the license application. The license will include...

10 CFR 61.6 - Exemptions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Exemptions. 61.6 Section 61.6 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.6 Exemptions. The Commission may, upon application by any interested person, or upon its own...

10 CFR 61.25 - Changes.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Changes. 61.25 Section 61.25 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.25 Changes... land disposal facility or procedures described in the license application. The license will include...

10 CFR 61.25 - Changes.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Changes. 61.25 Section 61.25 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.25 Changes... land disposal facility or procedures described in the license application. The license will include...

10 CFR 61.83 - Violations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Violations. 61.83 Section 61.83 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Records, Reports, Tests, and Inspections § 61.83 Violations. (a) The Commission may obtain an injunction or other court order...

10 CFR 61.83 - Violations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Violations. 61.83 Section 61.83 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Records, Reports, Tests, and Inspections § 61.83 Violations. (a) The Commission may obtain an injunction or other court order...

10 CFR 61.25 - Changes.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Changes. 61.25 Section 61.25 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.25 Changes... land disposal facility or procedures described in the license application. The license will include...

10 CFR 61.25 - Changes.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Changes. 61.25 Section 61.25 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Licenses § 61.25 Changes... land disposal facility or procedures described in the license application. The license will include...

10 CFR 61.6 - Exemptions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Exemptions. 61.6 Section 61.6 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.6 Exemptions. The Commission may, upon application by any interested person, or upon its own...

10 CFR 61.6 - Exemptions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Exemptions. 61.6 Section 61.6 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.6 Exemptions. The Commission may, upon application by any interested person, or upon its own...

10 CFR 61.6 - Exemptions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Exemptions. 61.6 Section 61.6 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.6 Exemptions. The Commission may, upon application by any interested person, or upon its own...

10 CFR 61.6 - Exemptions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Exemptions. 61.6 Section 61.6 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE General Provisions § 61.6 Exemptions. The Commission may, upon application by any interested person, or upon its own...

Measurements of π ^± differential yields from the surface of the T2K replica target for incoming 31 GeV/ c protons with the NA61/SHINE spectrometer at the CERN SPS

NASA Astrophysics Data System (ADS)

Abgrall, N.; Aduszkiewicz, A.; Ajaz, M.; Ali, Y.; Andronov, E.; Antićić, T.; Antoniou, N.; Baatar, B.; Bay, F.; Blondel, A.; Blümer, J.; Bogomilov, M.; Brandin, A.; Bravar, A.; Brzychczyk, J.; Bunyatov, S. A.; Busygina, O.; Christakoglou, P.; Ćirković, M.; Czopowicz, T.; Davis, N.; Debieux, S.; Dembinski, H.; Deveaux, M.; Diakonos, F.; Di Luise, S.; Dominik, W.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Feofilov, G. A.; Fodor, Z.; Garibov, A.; Gaździcki, M.; Golubeva, M.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Haesler, A.; Hasegawa, T.; Hervé, A. E.; Hierholzer, M.; Igolkin, S.; Ivashkin, A.; Johnson, S. R.; Kadija, K.; Kapoyannis, A.; Kaptur, E.; Kisiel, J.; Kobayashi, T.; Kolesnikov, V. I.; Kolev, D.; Kondratiev, V. P.; Korzenev, A.; Kowalik, K.; Kowalski, S.; Koziel, M.; Krasnoperov, A.; Kuich, M.; Kurepin, A.; Larsen, D.; László, A.; Lewicki, M.; Lyubushkin, V. V.; Maćkowiak-Pawłowska, M.; Maksiak, B.; Malakhov, A. I.; Manić, D.; Marcinek, A.; Marino, A. D.; Marton, K.; Mathes, H.-J.; Matulewicz, T.; Matveev, V.; Melkumov, G. L.; Messerly, B.; Mills, G. B.; Morozov, S.; Mrówczyński, S.; Nagai, Y.; Nakadaira, T.; Naskręt, M.; Nirkko, M.; Nishikawa, K.; Panagiotou, A. D.; Paolone, V.; Pavin, M.; Petukhov, O.; Pistillo, C.; Płaneta, R.; Popov, B. A.; Posiadała-Zezula, M.; Puławski, S.; Puzović, J.; Rauch, W.; Ravonel, M.; Redij, A.; Renfordt, R.; Richter-Wąs, E.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rumberger, B. T.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Sarnecki, R.; Schmidt, K.; Sekiguchi, T.; Selyuzhenkov, I.; Seryakov, A.; Seyboth, P.; Sgalaberna, D.; Shibata, M.; Słodkowski, M.; Staszel, P.; Stefanek, G.; Stepaniak, J.; Ströbele, H.; Šuša, T.; Szuba, M.; Tada, M.; Taranenko, A.; Tefelska, A.; Tefelski, D.; Tereshchenko, V.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberič, D.; Vechernin, V. V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Włodarczyk, Z.; Wojtaszek-Szwarc, A.; Wyszyński, O.; Yarritu, K.; Zambelli, L.; Zimmerman, E. D.; Friend, M.; Galymov, V.; Hartz, M.; Hiraki, T.; Ichikawa, A.; Kubo, H.; Matsuoka, K.; Murakami, A.; Nakaya, T.; Suzuki, K.; Tzanov, M.; Yu, M.

2016-11-01

Measurements of particle emission from a replica of the T2K 90 cm-long carbon target were performed in the NA61/SHINE experiment at CERN SPS, using data collected during a high-statistics run in 2009. An efficient use of the long-target measurements for neutrino flux predictions in T2K requires dedicated reconstruction and analysis techniques. Fully-corrected differential yields of π ^± -mesons from the surface of the T2K replica target for incoming 31 GeV/ c protons are presented. A possible strategy to implement these results into the T2K neutrino beam predictions is discussed and the propagation of the uncertainties of these results to the final neutrino flux is performed.

Does elimination of planned postoperative radiation to the primary bed in p16-positive, transorally-resected oropharyngeal carcinoma associate with poorer outcomes?

PubMed

Sinha, Parul; Pipkorn, Patrik; Thorstad, Wade L; Gay, Hiram A; Haughey, Bruce H

2016-10-01

The purpose of our study is to compare oncologic and functional outcomes of p16-positive oropharyngeal squamous cell carcinoma (OPSCC) patients, in the presence and absence of planned radiation to the primary bed following transoral surgery (TOS), stratified by T-classification. Retrospective cohort study of 261, T1-T4, consecutively TOS-treated OPSCC patients. At a median follow-up of 61months, local recurrence (LR) occurred in 6 (2.3%)patients (3 each in T1-T2 and T3-T4 groups), of which 5 had tumors in the tongue base and one in the tonsil. Of patients not receiving planned primary bed radiation, LR occurred in 3% of T1-T2s versus 17% of T3-T4s. In patients with T1-T2 tumors, Absolute Risk Reduction of LR with primary bed radiation was 3.26% (95% CI: -0.37%, 7%); Number Needed to Treat to prevent one LR was 31 (95% CI: 14.5, 271). Absolute Risk Increase for gastrostomy-tube with primary bed radiation was 34.4% (95% CI: 24%, 45%); Number Needed to Harm was 3 (95% CI: 2.2, 4.2), i.e., for every three patients with T1-T2 tumors receiving primary bed radiation, one had a gastrostomy-tube. Elimination of primary bed radiation in margin-negative resected, T1-T2 p16-positive OPSCC was not associated with significant compromise of local control, and correlated with superior swallowing preservation, assessed using gastrostomy rate as a surrogate. Lack of primary bed radiation in T3-T4 tumors associated with significantly increased LR rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Downregulation of Extracellular Matrix Metalloproteinase Inducer by scFv-M6-1B9 Intrabody Suppresses Cervical Cancer Invasion Through Inhibition of Urokinase-Type Plasminogen Activator.

PubMed

Panich, Tipattaraporn; Tragoolpua, Khajornsak; Pata, Supansa; Tayapiwatana, Chatchai; Intasai, Nutjeera

2017-02-01

Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) accelerates tumor invasion and metastasis via activation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) expression. The authors were interested in whether the scFv-M6-1B9 intrabody against EMMPRIN that retains EMMPRIN in endoplasmic reticulum could be a potential tool to suppress cervical cancer invasion through inhibition of uPA. The chimeric adenoviral vector Ad5/F35-scFv-M6-1B9 was transferred into human cervical carcinoma HeLa cells to produce the scFv-M6-1B9 intrabody against EMMPRIN. Cell surface expression of EMMPRIN, the membrane-bound uPA, the enzymatic activity of secreted uPA, and the invasion ability were analyzed. The scFv-M6-1B9 intrabody successfully diminished the cell surface expression of EMMPRIN and the membrane-bound uPA on HeLa cells. uPA activity from tissue culture media of EMMPRIN-downregulated HeLa cells was decreased. The invasion ability of HeLa cells harboring scFv-M6-1B9 intrabody was also suppressed. These results suggested that the scFv-M6-1B9 intrabody might represent a potential approach for invasive cervical cancer treatment. The application of scFv-M6-1B9 intrabody in animal experiments and preclinical studies would be investigated further.

The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy.

PubMed

Tian, Yun-Ming; Huang, Wei-Zeng; Yuan, Xia; Bai, Li; Zhao, Chong; Han, Fei

2017-06-27

Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed. The 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3-T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

Penile warty mucoepidermoid carcinoma with features of stratified mucin-producing intra-epithelial lesion and invasive stratified mucin-producing carcinoma.

PubMed

Yorita, Kenji; Kuroda, Naoto; Naroda, Takushi; Tamura, Masato; Ohe, Chisato; Divatia, Mukul; Amin, Mahul B; Cubilla, Antonio L; Kazakov, Dimitry V; Hes, Ondrej; Michal, Michael; Michal, Michal

2018-04-01

Stratified mucin-producing intra-epithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features. A 62-year-old Japanese man had a glans penis lesion of one-and-a-half years' duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in-situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease-free 26 months after surgery. The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE-like penile lesion as 'mucinous penile intra-epithelial neoplasia'. © 2017 John Wiley & Sons Ltd.

A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature.

PubMed

Mirfakhraee, Sasan; Mathews, Dana; Peng, Lan; Woodruff, Stacey; Zigman, Jeffrey M

2013-05-04

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant "hot" nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases of benign hyperfunctioning nodules. A literature review of surgical patients with solitary hyperfunctioning thyroid nodules managed by thyroid resection revealed an estimated 3.1% prevalence of malignancy. A separate literature search uncovered 76 cases of reported malignant hot thyroid nodules, besides the present case. Of these, 78% were female and mean age at time of diagnosis was 47 years. Mean nodule size was 4.13 ± 1.68 cm. Laboratory assessment revealed T3 elevation in 76.5%, T4 elevation in 51.9%, and subclinical hyperthyroidism in 13% of patients. Histological diagnosis was papillary thyroid carcinoma (PTC) in 57.1%, follicular thyroid carcinoma (FTC) in 36.4%, and Hurthle cell carcinoma in 7.8% of patients. Thus, hot thyroid nodules harbor a low but non-trivial rate of malignancy. Compared to individuals with benign hyperfunctioning thyroid nodules, those with malignant hyperfunctioning nodules are younger and more predominantly female. Also, FTC and Hurthle cell carcinoma are found more frequently in hot nodules than in general. We were unable to find any specific characteristics that could be used to distinguish between malignant and benign hot nodules.

A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature

PubMed Central

2013-01-01

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant “hot” nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases of benign hyperfunctioning nodules. A literature review of surgical patients with solitary hyperfunctioning thyroid nodules managed by thyroid resection revealed an estimated 3.1% prevalence of malignancy. A separate literature search uncovered 76 cases of reported malignant hot thyroid nodules, besides the present case. Of these, 78% were female and mean age at time of diagnosis was 47 years. Mean nodule size was 4.13 ± 1.68 cm. Laboratory assessment revealed T3 elevation in 76.5%, T4 elevation in 51.9%, and subclinical hyperthyroidism in 13% of patients. Histological diagnosis was papillary thyroid carcinoma (PTC) in 57.1%, follicular thyroid carcinoma (FTC) in 36.4%, and Hurthle cell carcinoma in 7.8% of patients. Thus, hot thyroid nodules harbor a low but non-trivial rate of malignancy. Compared to individuals with benign hyperfunctioning thyroid nodules, those with malignant hyperfunctioning nodules are younger and more predominantly female. Also, FTC and Hurthle cell carcinoma are found more frequently in hot nodules than in general. We were unable to find any specific characteristics that could be used to distinguish between malignant and benign hot nodules. PMID:23641736

10 CFR 40.61 - Records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Records. 40.61 Section 40.61 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL Records, Reports, and Inspections § 40.61 Records. (a) Each person who receives source or byproduct material pursuant to a license issued pursuant to the regulations...

7 CFR 900.61 - Depositions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Depositions. 900.61 Section 900.61 Agriculture... Governing Proceedings on Petitions To Modify or To Be Exempted From Marketing Orders § 900.61 Depositions. (a) Procedure in lieu of deposition. Before any party may have testimony taken by deposition, said...

7 CFR 900.61 - Depositions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 8 2011-01-01 2011-01-01 false Depositions. 900.61 Section 900.61 Agriculture... Governing Proceedings on Petitions To Modify or To Be Exempted From Marketing Orders § 900.61 Depositions. (a) Procedure in lieu of deposition. Before any party may have testimony taken by deposition, said...

7 CFR 985.61 - Records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Records. 985.61 Section 985.61 Agriculture Regulations... SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Reports and Records § 985.61 Records. Each handler shall maintain such records pertaining to all oil handled as will substantiate the required...

7 CFR 985.61 - Records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 8 2013-01-01 2013-01-01 false Records. 985.61 Section 985.61 Agriculture Regulations... SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Reports and Records § 985.61 Records. Each handler shall maintain such records pertaining to all oil handled as will substantiate the required...