TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

DEFF Research Database (Denmark)

Loo, Suet K; Ch'ng, Ewe S; Md Salleh, Md Salzihan

2017-01-01

to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographic parameters and survival in DLBCL. METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared...... to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P ... immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly...

Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09).

Science.gov (United States)

Yoon, Dok Hyun; Sohn, Byeong Seok; Oh, Sung Yong; Lee, Won-Sik; Lee, Sang Min; Yang, Deok-Hwan; Huh, Jooryung; Suh, Cheolwon

2017-02-21

The appropriate number of chemotherapy cycles for limited stage diffuse large B-cell lymphoma (DLBCL) patients without gross residual lesions after complete resection, has not been specifically questioned. We performed a multicenter, single-arm, phase 2 study to investigate the feasibility of 3 cycles of abbreviated R-CHOP chemotherapy in low-risk patients with completely resected localized CD20+ DLBCL. Between December 2010 and May 2013, we recruited 23 patients. One was excluded due to ineligibility, and hence, 22 were included in the final analysis. The primary sites comprised the intestine (n = 15), cervical lymph nodes (n = 4), stomach (n = 1), tonsil (n = 1), and spleen (n = 1). All patients successfully completed the 3 cycles of planned R-CHOP chemotherapy. Over a median follow-up of 39.5 months (95% confidence interval, 29.9-47.1 months), both the estimated 2-year disease-free survival and overall survival rates was 95% confidence interval, 85.9-104.1%. Only one patient with an international prognostic index of 2 experienced relapse and died. The most common grade 3 or 4 toxicity condition included neutropenia (n = 8, 36.4%). Three patients experienced grade 3 febrile neutropenia, but no grade 3 or 4 non-hematologic toxicity was observed. DLBCL patients without residual lesions after resection were enrolled and R-CHOP chemotherapy was repeated at 3-week-intervals over 3 cycles. The primary endpoint was 2-year disease-free survival. Three cycles of abbreviated R-CHOP immunochemotherapy is feasible for completely resected low risk localized DLBCL.

Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy.

Science.gov (United States)

Park, Young Hoon; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo; Lim, Joo Han

2017-01-01

The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Patients were allocated to a low ALI group (n = 82, 38.7%) or a high ALI group (n = 130, 61.3%) according to an optimal pretreatment ALI cut-off value of 15.5 as determined by receiver operating curve analysis. The low ALI group displayed more adverse clinical characteristics, lower rates of complete remission (54.9 vs. 75.4%, p = 0.008), and poorer 5-year progression-free (PFS, 58.1 vs. 77.3%, p = 0.006) and overall (OS, 64.2 vs. 80.2%, p = 0.008) survival. Multivariate analysis showed that low ALI was found to independently predict shorter PFS and OS. Interestingly, a low ALI reverted to a high ALI during treatment in 58 patients (27.4%), and the 5-year OS of these patients was better than that of patients whose ALI remained low (n = 24, 72.5 vs. 24%, p ALI might be an easily available marker for predicting clinical outcomes in DLBCL patients treated with R-CHOP chemotherapy. © 2017 S. Karger AG, Basel.

A salvage chemotherapy of R-P-IMVP16/CBDCA consisting of rituximab, methylprednisolone, ifosfamide, methotrexate, etoposide, and carboplatin for patients with diffuse large B cell lymphoma who had previously received R-CHOP therapy as first-line chemotherapy.

Science.gov (United States)

Matsumoto, Takuro; Hara, Takeshi; Shibata, Yuhei; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Kito, Yusuke; Kasahara, Senji; Yamada, Toshiki; Sawada, Michio; Miyazaki, Tatsuhiko; Takami, Tsuyoshi; Takeuchi, Tamotsu; Moriwaki, Hisataka; Tsurumi, Hisashi

2017-09-01

We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R-CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m 2 on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m 2 for 5 days (from day 3 to day 7), methotrexate 30 mg/m 2 on day 5 and day 12, etoposide 80 mg/m 2 for 3 days (from day 3 to day 5), and carboplatin 300 mg/m 2 on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2-year overall survival rate was 55.3%. The 2-year progression free survival rate was 34.7%. The 2-year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p effects were mild and tolerable. The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

Science.gov (United States)

Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

2012-01-01

Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Frei, E; Visco, C; Xu-Monette, Z Y

2013-01-01

High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

Epstein-Barr virus (EBV) provides survival factors to EBV+ diffuse large B-cell lymphoma (DLBCL) lines and modulates cytokine induced specific chemotaxis in EBV+  DLBCL.

Science.gov (United States)

Wu, Liang; Ehlin-Henriksson, Barbro; Zhou, Xiaoying; Zhu, Hong; Ernberg, Ingemar; Kis, Lorand L; Klein, George

2017-12-01

Diffuse large B-cell lymphoma (DLBCL), the most common type of malignant lymphoma, accounts for 30% of adult non-Hodgkin lymphomas. Epstein-Barr virus (EBV) -positive DLBCL of the elderly is a newly recognized subtype that accounts for 8-10% of DLBCLs in Asian countries, but is less common in Western populations. Five DLBCL-derived cell lines were employed to characterize patterns of EBV latent gene expression, as well as response to cytokines and chemotaxis. Interleukin-4 and interleukin-21 modified LMP1, EBNA1 and EBNA2 expression depending on cell phenotype and type of EBV latent programme (type I, II or III). These cytokines also affected CXCR4- or CCR7-mediated chemotaxis in two of the cell lines, Farage (type III) and Val (type II). Further, we investigated the effect of EBV by using dominant-negative EBV nuclear antigen 1(dnEBNA1) to eliminate EBV genomes. This resulted in decreased chemotaxis. By employing an alternative way to eliminate EBV genomes, Roscovitine, we show an increase of apoptosis in the EBV-positive lines. These results show that EBV plays an important role in EBV-positive DLBCL lines with regard to survival and chemotactic response. Our findings provide evidence for the impact of microenvironment on EBV-carrying DLBCL cells and might have therapeutic implications. © 2017 John Wiley & Sons Ltd.

Commercial production of chopped firewood

International Nuclear Information System (INIS)

Jouhiaho, A.

2004-01-01

The aim of the reseach project was to improve the competitiveness of chopped firewood by producing information that can help to reduce production and distribution costs as well as increase the quality of chopped firewood produced. The sub-project 'New logistics solutions for the chopped firewood production process' studied current production and distribution efficiency of commerical chopped firewood and tried to find cost saving methods. The sub-project 'The current situation of the firewood trade in Europe' surveyed firewood trade volumes, operational methods and the firewood production equipment found on sale in European countries. Information about the chopped firewood trade and chopping device market was for the most part an estimate. This is because there is no research and statistical information available. Indicative information was obtained from Denmark, Germany, Norway, Spain, Sweden and Finland. The sub-project 'Productivity, costs and development targets of new chopped firewood machines' researched ten new firewood processing devices suitable for professional and domestic use by means of work-study methods. The research studied productivity and chopping costs, and analysed the quality of chopped firewood manufactured by the firewood processing devices. It also analysed the occupational safety and ergonomics of chopping work and suggestions were made for the device manufacturers on how to develop chopping devices. Sub-project 'The artificial drying and storage management for chopped firewood' carried out field tests on different types of cold and warm air dryers being used by chopped firewood entrepreneurs. The aim was to find the most promising dryer type according to its cost and operating efficiency. In addition, the suitability of resistance based electronic wood moisture meter for measuring the moisture content of single chopped firewood pieces was also studied. (orig.)

The chopped firewood trade in Finland

International Nuclear Information System (INIS)

Seppaenen, A.; Kaerhae, K.

2003-01-01

The TTS Institute studied the operations of chopped firewood merchants and described the cost structure of commercial chopped firewood production. The research material was collected via postal questionnaire in 2002 after being sent to those firewood merchants assumed to be selling chopped firewood. Acceptable responses were received from 244 firewood merchants. In addition, ten firewood merchants were interviewed. In 2001, the firewood merchants sold an average of 151 m 3 of chopped firewood. Half of the firewood merchants sold less than 51 m 3 of chopped firewood. The main source of income for the majority of chopped firewood merchants was agriculture and forestry. If approximately 300,000 m 3 of chopped firewood is sold annually, according to the research there are about 2,000 chopped firewood merchants in Finland. However, only a very few entrepreneurs get their main income from the chopped firewood trade. The majority of raw material for chopped firewood came from the merchant's own forest. Birch was the most commonly used species. 54% of the chopped firewood was made from pulpwood, 19% from pole size trees and 18% from split firewood. The drying methods for chopped firewood were most often natural drying outside in covered stocks or cages, natural drying in stacks or natural drying of mechanically debarked or debarked timber in stacks. Less than a tenth of the merchants dried their chopped, firewood using artificial cold air-drying. The share of packaged chopped firewood was 14% i.e. approximately 42,000 m 3 . Chopped firewood was packed mostly into small packages (about 10 kg). The chopped firewood trade is a local business: the average transport distance from the merchant's store to the customer was 25 km. The chopped firewood merchants delivered 73% of lie chopped firewood themselves. An agricultural tractor and a trailer were the most common transport method. The most important customer group is detached houses. The average production costs amongst the

ctDNA DLBCL Detection Lancet Oncology

Science.gov (United States)

Measurement of circulating tumor DNA in blood can be used to detect disease recurrence in patients with a curable form of cancer known as diffuse large B-cell lymphoma (DLBCL). In most patients, measurement of ctDNA enabled detection of microscopic diseas

P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma

International Nuclear Information System (INIS)

Vega, Gabriel G.; Avilés-Salas, Alejandro; Chalapud, J. Ramón; Martinez-Paniagua, Melisa; Pelayo, Rosana; Mayani, Héctor; Hernandez-Pando, Rogelio; Martinez-Maza, Otoniel; Huerta-Yepez, Sara; Bonavida, Benjamin; Vega, Mario I.

2015-01-01

The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients. Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed. Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38 − and 34 % for p38 + and for OS was 83 % for p38 − and 47 % for p38 + . The p-p38 + tissues expressed Bcl-2 and 90 % of p-p38 − where Bcl-2 − . The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB. The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors. The online version of this article (doi:10.1186/s12885-015-1778-8) contains supplementary material, which is available to authorized users

A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

Energy Technology Data Exchange (ETDEWEB)

Zhang, Qiao, E-mail: zhangqiao200824@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Yang, Zhe, E-mail: zheyang@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Wang, Weiping, E-mail: wwp@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Guo, Ting, E-mail: luckyguoting@bjmu.edu.cn [Department of Gastrointestinal Translation Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, 52 Fucheng Road, 100142 Beijing (China); Jia, Zhuqing, E-mail: zhuqingjia@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Ma, Kangtao, E-mail: makangtao11@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Zhou, Chunyan, E-mail: chunyanzhou@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China)

2014-07-04

Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.

A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

International Nuclear Information System (INIS)

Zhang, Qiao; Yang, Zhe; Wang, Weiping; Guo, Ting; Jia, Zhuqing; Ma, Kangtao; Zhou, Chunyan

2014-01-01

Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes

Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study.

NARCIS (Netherlands)

Visco, C.; Tzankov, A.; Xu-Monette, Z.Y.; Miranda, R.N.; Tai, Y.C.; Li, Y.; Liu, W.M.; d'Amore, E.S.; Li, Y.O.; Montes-Moreno, S.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Wang, H.Y.; Dunphy, C.H.; His, E.D.; Zhao, X.F.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Ai, W.; O'Neill, S.; Ponzoni, M.; Ferreri, A.J.; Kahl, B.S.; Winter, J.N.; Go, R.S.; Dirnhofer, S.; Piris, M.A.; Moller, M.B.; Wu, L.; Medeiros, L.J.; Young, K.H.

2013-01-01

Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has

Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers

DEFF Research Database (Denmark)

Pedersen, Mette Ølgod; Gang, Anne Ortved; Brown, Peter

2017-01-01

BACKGROUND: Double expression of MYC and BCL2 proteins (DE) and double-hit MYC+BCL2/BCL6 translocations (DH) were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL) by the 2016 revision of the World Health Organization classification of lymphoid neoplasms...... in situ hybridization (FISH). RESULTS: DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS) in patients treated with R-CHOP but not R-CHOEP (peffect of DE for response (PFS) to R...

Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP.

Science.gov (United States)

Gupta, Mamta; Maurer, Matthew J; Wellik, Linda E; Law, Mark E; Han, Jing Jing; Ozsan, Nazan; Micallef, Ivana N; Dogan, Ahmet; Witzig, Thomas E

2012-11-22

STAT3 regulates cell growth by up-regulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-α (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients.

Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

Science.gov (United States)

Lanic, Hélène; Kraut-Tauzia, Jerôme; Modzelewski, Romain; Clatot, Florian; Mareschal, Sylvain; Picquenot, Jean Michel; Stamatoullas, Aspasia; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

2014-04-01

Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.

Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

OpenAIRE

Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Link, Brian K.; Zou, Lihua

2012-01-01

To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include...

Producing chopped firewood with firewood processors

International Nuclear Information System (INIS)

Kaerhae, K.; Jouhiaho, A.

2009-01-01

The TTS Institute's research and development project studied both the productivity of new, chopped firewood processors (cross-cutting and splitting machines) suitable for professional and independent small-scale production, and the costs of the chopped firewood produced. Seven chopped firewood processors were tested in the research, six of which were sawing processors and one shearing processor. The chopping work was carried out using wood feeding racks and a wood lifter. The work was also carried out without any feeding appliances. Altogether 132.5 solid m 3 of wood were chopped in the time studies. The firewood processor used had the most significant impact on chopping work productivity. In addition to the firewood processor, the stem mid-diameter, the length of the raw material, and of the firewood were also found to affect productivity. The wood feeding systems also affected productivity. If there is a feeding rack and hydraulic grapple loader available for use in chopping firewood, then it is worth using the wood feeding rack. A wood lifter is only worth using with the largest stems (over 20 cm mid-diameter) if a feeding rack cannot be used. When producing chopped firewood from small-diameter wood, i.e. with a mid-diameter less than 10 cm, the costs of chopping work were over 10 EUR solid m -3 with sawing firewood processors. The shearing firewood processor with a guillotine blade achieved a cost level of 5 EUR solid m -3 when the mid-diameter of the chopped stem was 10 cm. In addition to the raw material, the cost-efficient chopping work also requires several hundred annual operating hours with a firewood processor, which is difficult for individual firewood entrepreneurs to achieve. The operating hours of firewood processors can be increased to the required level by the joint use of the processors by a number of firewood entrepreneurs. (author)

Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

Science.gov (United States)

Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

2016-06-01

There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures

DEFF Research Database (Denmark)

Hu, Shimin; Xu-Monette, Zijun Y; Tzankov, Alexander

2013-01-01

Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclo...

Novel disease targets and management approaches for diffuse large B-cell lymphoma.

Science.gov (United States)

Wilson, Wyndham H; Hernandez-Ilizaliturri, Francisco J; Dunleavy, Kieron; Little, Richard F; O'Connor, Owen A

2010-08-01

Diffuse large B-cell lymphoma (DLBCL) responds well to treatment with CHOP and the R-CHOP regimen, but a subset of patients still fail to achieve complete or durable responses. Recent advances in gene expression profiling have led to the identification of three different subtypes of DLBCL, and confirmed that patients with the activated B-cell (ABC) disease subtype are less likely to respond well to CHOP-based regimens than those with germinal centre B-cell-type (GCB) disease. This discovery could herald the use of gene expression profiling to aid treatment decisions in DLBCL, and help identify the most effective management strategies for patients. Treatment options for patients with relapsed or refractory DLBCL are limited and several novel agents are being developed to address this unmet clinical need. Novel agents developed to treat plasma cell disorders such as multiple myeloma have shown promising activity in patients with NHL. Indeed, the immunomodulatory agent lenalidomide and the proteasome inhibitors bortezomib and carfilzomib, as single agents or in combination with chemotherapy, have already demonstrated promising activity in patients with the ABC subtype of DLBCL. One should not be complacent however when applying these agents to new disease types, because dose and drug scheduling can have marked effects on the responses achieved with investigational agents. As more targeted agents are developed, the timing of administration with other agents in clinical trials will become increasingly important to ensure maximal efficacy while minimizing side effects.

An Oncogenic Role for Alternative NF-κB Signaling in DLBCL Revealed upon Deregulated BCL6 Expression

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Baochun Zhang

2015-05-01

Full Text Available Diffuse large B cell lymphoma (DLBCL is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-κB activity, a role for oncogenic lesions that activate the alternative NF-κB pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-κB pathway, occurs in ∼15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-κB pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-κB pathway in DLBCL development.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

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Niu, Mingshan [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Shen, Yangling; Xu, Xiaoyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Yao, Yao; Fu, Chunling [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Yan, Zhiling [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Wu, Qingyun [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Cao, Jiang; Sang, Wei [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Zeng, Lingyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Li, Zhenyu [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Liu, Xuejiao, E-mail: liuxuejiao0923@126.com [Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China); and others

2015-07-10

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

International Nuclear Information System (INIS)

Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao

2015-01-01

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys 38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy

Multiplex polymerase chain reaction-based prognostic models in diffuse large B-cell lymphoma patients treated with R-CHOP

DEFF Research Database (Denmark)

Green, Tina M; Jensen, Andreas K; Holst, René

2016-01-01

We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de...... models. The best model was validated in data from an online available R-CHOP treated cohort. With progression-free survival (PFS) as primary endpoint, the best performing IPI independent model incorporated the LMO2 and HLADQA1 as well as gene interactions for GCSAMxMIB1, GCSAMxCTGF and FOXP1xPDE4B....... This model assigned 33% of patients (n = 60) to poor outcome with an estimated 3-year PFS of 40% vs. 87% for low risk (n = 61) and intermediate (n = 60) risk groups (P model incorporated LMO2 and BCL2 and assigned 33% of the patients with a 3-year PFS of 35% vs...

Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy

DEFF Research Database (Denmark)

Ok, Chi Young; Xu-Monette, Zijun Y; Tzankov, Alexandar

2014-01-01

oncogene E3 ubiquitin protein ligase (MDM2), MDM4, and tumor protein 53 (TP53) were rare or absent. Gene expression profiling did not reveal any striking differences with respect to cyclin D1 in DLBCL. CONCLUSIONS: Compared with patients who had cyclin D1-negative DLBCL, men were more commonly affected......1-positive according to immunohistochemistry were also assessed for rearrangements of the cyclin D1 gene (CCND1) using fluorescence in situ hybridization. Gene expression profiling was performed to compare patients who had DLBCL with and without cyclin D1 expression. RESULTS: In total, 30 patients...... (2.1%) who had DLBCL that expressed cyclin D1 and lacked CCND1 gene rearrangements were identified. Patients with cyclin D1-positive DLBCL had a median age of 57 years (range, 16.0-82.6 years). There were 23 males and 7 females. Twelve patients (40%) had bulky disease. None of them expressed CD5. Two...

Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

Science.gov (United States)

Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Zou, Lihua; Gould, Joshua; Saksena, Gordon; Stransky, Nicolas; Rangel-Escareño, Claudia; Fernandez-Lopez, Juan Carlos; Hidalgo-Miranda, Alfredo; Melendez-Zajgla, Jorge; Hernández-Lemus, Enrique; Schwarz-Cruz y Celis, Angela; Imaz-Rosshandler, Ivan; Ojesina, Akinyemi I.; Jung, Joonil; Pedamallu, Chandra S.; Lander, Eric S.; Habermann, Thomas M.; Cerhan, James R.; Shipp, Margaret A.; Getz, Gad; Golub, Todd R.

2012-01-01

To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase–mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease. PMID:22343534

Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease

DEFF Research Database (Denmark)

Brauner, S; Zhou, W; Backlin, C

2015-01-01

OBJECTIVE: TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21...... in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. MATERIALS AND METHODS: TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated...... with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR...

Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma

DEFF Research Database (Denmark)

Czuczman, Myron S; Hess, Georg; Gadeberg, Ole V

2012-01-01

An international, Phase II trial was conducted to assess two doses of ofatumumab, a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m(2) ), doxorubicin (50 mg/m(2) ), prednisone (100 mg days 3-7) and vincristine (1·4 mg/m(2) ) (O-CHOP), as frontline treatment for follicular...... lymphoma (FL). 59 patients with previously untreated FL were randomized to ofatumumab 500 mg (n = 29) or 1000 mg (n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles. Median duration of FL was 0·1 years for both dose groups; 34% and 38% of patients had high-risk Follicular Lymphoma International...

The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

Science.gov (United States)

Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

2015-07-01

A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.

Science.gov (United States)

Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung

2014-01-01

The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

Full dose CHOP chemotherapy

International Nuclear Information System (INIS)

Tominaga, Shinichi; Kondo, Makoto; Ando, Yutaka; Yamashita, Shoji; Uematsu, Minoru; Shigematsu, Naoyuki; Nishiguchi, Iku; Hashimoto, Shozo

1985-01-01

Since 1982, we have performed 125 courses of CHOP chemotherapy for 27 patients of malignancy, adhering to the original regimen as strictly as possible. CHOP chemotherapy consisted of Cyclophosphamide 750 mg/m 2 , iv, on day 1; Adriamycin 50 mg/m 2 , iv, on day 1; Vincristine 1.4 mg/m 2 , iv, on day 1 (maximum single dose 2.0 mg) and Prednisolone 50 mg/m 2 , po, day 1 through 5. The cycle was repeated every 21 days. As side effects, myelosuppression, hair loss, fever, nausea, vomiting, liver dysfunction, stomatitis, neuropathy, herpes zoster, arrhythmia and hemorrhagic cystitis were seen. Due to myelosuppression, twenty patients experienced febrile episodes at each nadir of WBC counts on 40 courses. However, any febrile patient did not have life threatening infection. Other side effects were also reversible. The radiotherapy of most patients was carried out as initially scheduled, except for 3 patients in whom irradiation was interrupted due to severe stomatitis or herpes zoster. We consider that CHOP chemotherapy is excellent in feasibility even when combined with radiotherapy. (author)

Voltammetric detection of biological molecules using chopped carbon fiber.

Science.gov (United States)

Sugawara, Kazuharu; Yugami, Asako; Kojima, Akira

2010-01-01

Voltammetric detection of biological molecules was carried out using chopped carbon fibers produced from carbon fiber reinforced plastics that are biocompatible and inexpensive. Because chopped carbon fibers normally are covered with a sizing agent, they are difficult to use as an electrode. However, when the surface of a chopped carbon fiber was treated with ethanol and hydrochloric acid, it became conductive. To evaluate the functioning of chopped carbon fibers, voltammetric measurements of [Fe(CN)(6)](3-) were carried out. Redoxes of FAD, ascorbic acid and NADH as biomolecules were recorded using cyclic voltammetry. The sizing agents used to bundle the fibers were epoxy, polyamide and polyurethane resins. The peak currents were the greatest when using the chopped carbon fibers that were created with epoxy resins. When the electrode response of the chopped carbon fibers was compared with that of a glassy carbon electrode, the peak currents and the reversibility of the electrode reaction were sufficient. Therefore, the chopped carbon fibers will be useful as disposable electrodes for the sensing of biomolecules.

The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.

Science.gov (United States)

Pál, Ildikó; Illés, Árpád; Gergely, Lajos; Pál, Tibor; Radnay, Zita; Szekanecz, Zoltán; Zilahi, Erika; Váróczy, László

2018-04-01

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL. The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes. Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant. Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.

Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.

Science.gov (United States)

Akyurek, Nalan; Uner, Aysegul; Benekli, Mustafa; Barista, Ibrahim

2012-09-01

Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors. Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis. Copyright © 2011 American Cancer Society.

miR expression in MYC-negative DLBCL/BL with partial trisomy 11 is similar to classical Burkitt lymphoma and different from diffuse large B-cell lymphoma.

Science.gov (United States)

Zajdel, Michalina; Rymkiewicz, Grzegorz; Chechlinska, Magdalena; Blachnio, Katarzyna; Pienkowska-Grela, Barbara; Grygalewicz, Beata; Goryca, Krzysztof; Cieslikowska, Maria; Bystydzienski, Zbigniew; Swoboda, Pawel; Walewski, Jan; Siwicki, Jan Konrad

2015-07-01

Fast and reliable differential diagnosis of Burkitt lymphoma (BL) vs. diffuse large B cell lymphoma (DLBCL) is of major importance for therapeutic decisions and patient outcome. Aggressive B cell non-Hodgkin lymphomas (B-NHLs) that do not belong to the abovementioned entities were categorized by the current WHO lymphoma classification as "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (DLBCL/BL). We have recently described a DLBCL/BL subgroup with recurrent chromosome 11q aberrations, resembling BL (B-NHLs[11q]). Here, we analyzed 102 prospectively collected fine needle aspirates from patients with aggressive B-NHLs in order to investigate the potential of microRNA (miR)-155, its precursor BIC, as well as miR-21 and miR-26a to differentiate BL from DLBCL, and from DLBCL/BL that include B-NHLs[11q]. Both BL and DLBCL/BL cases, including B-NHLs[11q], demonstrated significantly lower expression levels of miR-155/BIC, miR-21, and miR-26a compared to primary DLBCL. In conclusion, the miRs expression in B-NHLs[11q] provides a new suggestion, in addition to pathomorphological and clinical similarities between classical, i.e., MYC translocation-positive BL, and B-NHLs[11q], to recognize the B-NHLs[11q] subgroup of DLBCL/BL category as a MYC translocation-negative variant of BL in most cases, and points to the potential utility of miR-155/BIC/miR-21/miR-26a for the differential diagnosis of a heterogeneous category of DLBCL/BL.

Correlation between compressive strength and ultrasonic pulse velocity of high strength concrete incorporating chopped basalt fibre

Science.gov (United States)

Shafiq, Nasir; Fadhilnuruddin, Muhd; Elshekh, Ali Elheber Ahmed; Fathi, Ahmed

2015-07-01

Ultrasonic pulse velocity (UPV), is considered as the most important test for non-destructive techniques that are used to evaluate the mechanical characteristics of high strength concrete (HSC). The relationship between the compressive strength of HSC containing chopped basalt fibre stands (CBSF) and UPV was investigated. The concrete specimens were prepared using a different ratio of CBSF as internal strengthening materials. The compressive strength measurements were conducted at the sample ages of 3, 7, 28, 56 and 90 days; whilst, the ultrasonic pulse velocity was measured at 28 days. The result of HSC's compressive strength with the chopped basalt fibre did not show any improvement; instead, it was decreased. The UPV of the chopped basalt fibre reinforced concrete has been found to be less than that of the control mix for each addition ratio of the basalt fibre. A relationship plot is gained between the cube compressive strength for HSC and UPV with various amounts of chopped basalt fibres.

FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas

DEFF Research Database (Denmark)

Brown, P J; Wong, K K; Felce, S L

2016-01-01

The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II......) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes......, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (PABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone...

A novel type of EWS-CHOP fusion gene in myxoid liposarcoma

International Nuclear Information System (INIS)

Matsui, Yoshito; Ueda, Takafumi; Kubo, Takahiro; Hasegawa, Tadashi; Tomita, Yasuhiko; Okamoto, Mina; Myoui, Akira; Kakunaga, Shigeki; Yasui, Natsuo; Yoshikawa, Hideki

2006-01-01

The cytogenetic hallmark of myxoid type and round cell type liposarcoma consists of reciprocal translocation of t(12;16)(q13;p11) and t(12;22)(q13;q12), which results in fusion of TLS/FUS and CHOP, and EWS and CHOP, respectively. Nine structural variations of the TLS/FUS-CHOP chimeric transcript have been reported, however, only two types of EWS-CHOP have been described. We describe here a case of myxoid liposarcoma containing a novel EWS-CHOP chimeric transcript and identified the breakpoint occurring in intron 13 of EWS. Reverse transcription-polymerase chain reaction and direct sequence showed that exon 13 of EWS was in-frame fused to exon 2 of CHOP. Genomic analysis revealed that the breaks were located in intron 13 of EWS and intron 1 of CHOP

The management and development of the chopped firewood production process

International Nuclear Information System (INIS)

Jouhiaho, A.; Kouki, J.; Kara, K.; Mutikainen, A.; Oksanen, E.; Seppaenen, A.; Vuorio, K.

2005-01-01

The main aim of the project was to improve competitiveness of chopped firewood by producing information that can help to reduce production and distribution costs as well as increase the quality of chopped firewood produced. The aim was to attain the goal through four subprojects: 1. Productivity, Costs and Development Targets of New Firewood Machines, 2. The Artificial Drying and Storage Management of Chopped Firewood, 3. New Logistics Solutions for the Chopped Firewood Production Process, and 4. The Current Situation of the Firewood Trade in Europe. The research project covered an analysis of the productivity of new firewood machines, and the costs and quality of produced chopped firewood. Suggestions were made to firewood machine manufacturers for developing firewood machines. Also, the cost-effectiveness of current chopped firewood production and distribution chains was studied. Field tests were carried out on different types of cold and warm air dryers being used by chopped firewood entrepreneurs. In addition, the suitability of resistance based electronic wood moisture meter for measuring the moisture content of single chopped firewood pieces was also studied. Furthermore, a survey was carried out on the volume of firewood sales and the firewood production equipment available for sale in Europe, and European firewood merchants' methods of operation was studied. (orig.)

An International Collaborative Study of Outcome and Prognostic Factors in Patients with Secondary CNS Involvement By Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

El-Galaly, Tarec Christoffer; Cheah, Chan Yoon; Bendtsen, Mette Dahl

2016-01-01

) determine prognostic factors after SCNS.Patients and methods: We performed a retrospective study of patients diagnosed with SCNS during or after frontline immunochemotherapy (R-CHOP or equivalently effective regimens). SCNS was defined as new involvement of the CNS (parenchymal, leptomeningeal, and/or eye......Background: Secondary CNS involvement (SCNS) is a detrimental complication seen in ~5% of patients with diffuse large B-cell lymphoma (DLBCL) treated with modern immunochemotherapy. Data from older series report short survival following SCNS, typically lt;6 months. However, data in patients...

Lymphoma Patients Treated without Anthracyclines Have Negligible Risk of Cardiotoxicity: A Nationwide Cohort Study

DEFF Research Database (Denmark)

bech, Joachim; Hansen, Steen Møller; Lund, Peter Enemark

Abstract Objective: For more than two decades, CHOP (and later R-CHOP) has been the standard frontline treatment for diffuse large b-cell lymphoma (DLBCL). However, anthracycline-based chemotherapy regimens increase risk of cardiotoxicity with congestive heart failure (HF) being the best document....... Patients treated without anthracyclines had a negligible risk of HF supporting the safety of these regimens in patients considered at substantial risk of cardiotoxicity....

Two kinds of manual chopping methods applied in small incision extracapsular cataract extraction

Directory of Open Access Journals (Sweden)

Xia Jiang

2016-02-01

Full Text Available AIM:To research clinical effect of two manual chopping methods for small incision extracapsular cataract extraction. METHODS: We observed 143 cases(184 eyeswith grade Ⅳ or higher taken the small incision cataract extraction and intraocular lens implantation. Patients were given randomly knifed chopping with closed hook(92 eyesor double knifed chopping(92 eyes. The intra-operative posterior capsule rupture was observed and compared. At 1d, 1wk and 1mo postoperatively, visual acuity, corneal edema and corneal astigmatism were observed and analyzed. RESULTS:There were 10 eyes in patients accepting knifed chopping with closed hook with intra-operative posterior capsule rupture and 1 eye in patients accepting double knifed chopping. The difference between the two groups was statistically significant. The visual acuity of patients accepting knifed chopping with closed hook(92 eyesat 1d postoperatively was 0.380±0.105, and that of patients accepting double knifed chopping(92 eyeswas 0.420±0.095; the difference between the two groups was statistically significant. The visual acuity of patients accepting knifed chopping with closed hook(84 eyesat 1wk postoperatively was 0.480±0.123, and that of patients accepting double knifed chopping(86 eyeswas 0.520±0.085; the difference between the two groups was statistically significant. The visual acuity of patients accepting knifed chopping with closed hook(60 eyesat 1mo postoperatively was 0.610±0.083, and that of patients accepting double knifed chopping(52 eyeswas 0.643±0.072; the difference between the two groups was not statistically significant. The differences on corneal edema and corneal astigmatism between the two methods at 1d, 1wk and 1mo postoperatively were not statistically significant. CONCLUSION:The application of knifed chopping with closed hook and double knifed chopping in small incision extracapsular cataract extraction and intraocular lens implantation can effectively treat with

Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Science.gov (United States)

Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Lee, Hyang Rae; Kim, Yire; Kim, Rock Bum; Lee, Soon Il; Lee, Gyeong-Won

2016-12-01

Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). Treatment-related mortality (21.7 vs. 5.0%, P  = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P  = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group ( P  Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P  = 0.009; revised-IPI, 0.74, P  Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort.

Science.gov (United States)

Wang, Han-I; Smith, Alexandra; Aas, Eline; Roman, Eve; Crouch, Simon; Burton, Cathy; Patmore, Russell

2017-03-01

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma. Previous studies examining the cost of treating DLBCL have generally focused on a specific first-line therapy alone; meaning that their findings can neither be extrapolated to the general patient population nor to other points along the treatment pathway. Based on empirical data from a representative population-based patient cohort, the objective of this study was to develop a simulation model that could predict costs and life expectancy of treating DLBCL. All patients newly diagnosed with DLBCL in the UK's population-based Haematological Malignancy Research Network ( www.hmrn.org ) in 2007 were followed until 2013 (n = 271). Mapped treatment pathways, alongside cost information derived from the National Tariff 2013/14, were incorporated into a patient-level simulation model in order to reflect the heterogeneities of patient characteristics and treatment options. The NHS and social services perspective was adopted, and all outcomes were discounted at 3.5 % per annum. Overall, the expected total medical costs were £22,122 for those treated with curative intent, and £2930 for those managed palliatively. For curative chemotherapy, the predicted medical costs were £14,966, £23,449 and £7376 for first-, second- and third-line treatments, respectively. The estimated annual cost for treating DLBCL across the UK was around £88-92 million. This is the first cost modelling study using empirical data to provide 'real world' evidence throughout the DLBCL treatment pathway. Future application of the model could include evaluation of new technologies/treatments to support healthcare decision makers, especially in the era of personalised medicine.

The presence of Epstein-Barr virus (EBV) in diffuse large B-cell lymphomas (DLBCLs) in Turkey: special emphasis on 'EBV-positive DLBCL of the elderly'.

Science.gov (United States)

Uner, Aysegul; Akyurek, Nalan; Saglam, Arzu; Abdullazade, Samir; Uzum, Nuket; Onder, Sevgen; Barista, Ibrahim; Benekli, Mustafa

2011-04-01

Accumulated evidence has shown the importance of Epstein-Barr virus in the pathogenesis of various lymphomas. This study aimed to determine the prevalence of Epstein-Barr virus expression and its effect on survival amongst diffuse large B-cell lymphoma (DLBCL) cases from two large tertiary care centres in Turkey with a particular interest in identifying cases of 'Epstein-Barr virus-positive DLBCL of the elderly'. Diffuse large B-cell lymphoma cases diagnosed between 1999 and 2009 were retrieved and 340 cases were used to construct tissue microarrays. The presence of Epstein-Barr virus small ribonucleic acids was examined by in situ hybridization using Epstein-Barr virus (EBV)-encoded small RNA (EBER) oligonucleotides. A total of 18 cases (5.3%) showed Epstein-Barr virus expression. Twelve cases were classified as Epstein-Barr virus-positive DLBCL of the elderly. Epstein-Barr virus-positive DLBCL cases showed a significantly inferior overall survival as compared with Epstein-Barr virus-negative cases (p < 0.001). In our study group Epstein-Barr virus expression is not prevalent in DLBCLs. Epstein-Barr virus-positive DLBCL of the elderly is also rare in the Turkish population. The presence of Epstein-Barr virus, however, is associated with poor prognosis. © 2011 The Authors. APMIS © 2011 APMIS.

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

Science.gov (United States)

Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

2014-08-12

Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

Lenalidomide combined with R-GDP in a patient with refractory CD5-positive diffuse large B-cell lymphoma: A promising response and review.

Science.gov (United States)

Zhang, Yaping; Wang, Xinfeng; Liu, Yifei; Sun, Chunfeng; Shi, Wenyu; Huang, Hongming

2018-07-03

CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is associated with poor survival compared with CD5-negative DLBCL. The clinical characteristics of CD5+ DLBCL are different from both CD5-negative DLBCL and other CD5+ B cell lymphomas. There is currently no promising chemotherapy for CD5+ DLBCL. Herein, we report a 49-year-old Asian male with refractory CD5+ DLBCL. He complained of aggravated abdominal pain and weight loss. Computed tomography scan revealed abdominal masses, widespread lymphadenopathy, splenomegaly, and intussusception of the ileocecal junction with bowel wall thickening. Core needle aspiration biopsy of an abdominal mass was performed and immunohistochemistry revealed DLBCL of nongerminal center type. In this report, the dose-intensified R-Hyper CVAD (A) regimen as salvage therapy was introduced but failed to result in substantial improvement over the initially standard R-CHOP regimen. Next, the R-GDP regimen was administered as second-line treatment, but only resulted in a partial response. However, the addition of lenalidomide to R-GDP (R2-GDP) resulted in complete remission. The clinical features, pathogenesis, and possible mechanism of action of lenalidomide in CD5+ DLBCL have been described in the literature. The results of the present case report and literature searches indicate that CD5+ DLBCL may share a common pathway with activated B-cell like (ABC) DLBCL as determined by gene expression profiling. Lenalidomide is expected to induce favorable responses in patients with CD5+ DLBCL.

Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin.

Science.gov (United States)

Rink, Jonathan S; Yang, Shuo; Cen, Osman; Taxter, Tim; McMahon, Kaylin M; Misener, Sol; Behdad, Amir; Longnecker, Richard; Gordon, Leo I; Thaxton, C Shad

2017-11-06

Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1). As we previously reported, GC DLBCL are exquisitely sensitive to HDL NP as monotherapy, while ABC DLBCL are less sensitive. Herein, we report that enhanced BCR signaling and resultant de novo cholesterol synthesis in ABC DLBCL drastically reduces the ability of HDL NPs to reduce cellular cholesterol and induce cell death. Therefore, we combined HDL NP with the BCR signaling inhibitor ibrutinib and the SYK inhibitor R406. By targeting both cellular cholesterol uptake and BCR-associated de novo cholesterol synthesis, we achieved cellular cholesterol reduction and induced apoptosis in otherwise resistant ABC DLBCL cell lines. These results in lymphoma demonstrate that reduction of cellular cholesterol is a powerful mechanism to induce apoptosis. Cells rich in cholesterol require HDL NP therapy to reduce uptake and molecularly targeted agents that inhibit upstream pathways that stimulate de novo cholesterol synthesis, thus, providing a new paradigm for rationally targeting cholesterol metabolism as therapy for cancer.

A comparison between hominy chop and defatted maize germ meal ...

African Journals Online (AJOL)

Defatted maize germ meal (DMG) is arbitrarily rated at a lower economic value than maize meal or hominy chop (HC). Five treatments with 15 steers each were fed different inclusion levels of DMG (0%, 25%, 50%, 75% and 100%), replacing hominy chop during the fattening period. Slaughter data were collected for carcass ...

Alisertib added to rituximab and vincristine is synthetic lethal and potentially curative in mice with aggressive DLBCL co-overexpressing MYC and BCL2.

Directory of Open Access Journals (Sweden)

Daruka Mahadevan

Full Text Available Pearson correlation coefficient for expression analysis of the Lymphoma/Leukemia Molecular Profiling Project (LLMPP demonstrated Aurora A and B are highly correlated with MYC in DLBCL and mantle cell lymphoma (MCL, while both Auroras correlate with BCL2 only in DLBCL. Auroras are up-regulated by MYC dysregulation with associated aneuploidy and resistance to microtubule targeted agents such as vincristine. Myc and Bcl2 are differentially expressed in U-2932, TMD-8, OCI-Ly10 and Granta-519, but only U-2932 cells over-express mutated p53. Alisertib [MLN8237 or M], a highly selective small molecule inhibitor of Aurora A kinase, was synergistic with vincristine [VCR] and rituximab [R] for inhibition of cell proliferation, abrogation of cell cycle checkpoints and enhanced apoptosis versus single agent or doublet therapy. A DLBCL (U-2932 mouse model showed tumor growth inhibition (TGI of ∼ 10-20% (p = 0.001 for M, VCR and M-VCR respectively, while R alone showed ∼ 50% TGI (p = 0.001. M-R and VCR-R led to tumor regression [TR], but relapsed 10 days after discontinuing therapy. In contrast, M-VCR-R demonstrated TR with no relapse >40 days after stopping therapy with a Kaplan-Meier survival of 100%. Genes that are modulated by M-VCR-R (CENP-C, Auroras play a role in centromere-kinetochore function in an attempt to maintain mitosis in the presence of synthetic lethality. Together, our data suggest that the interaction between alisertib plus VCR plus rituximab is synergistic and synthetic lethal in Myc and Bcl-2 co-expressing DLBCL. Alisertib plus vincristine plus rituximab [M-VCR-R] may represent a new strategy for DLBCL therapy.

Alisertib added to rituximab and vincristine is synthetic lethal and potentially curative in mice with aggressive DLBCL co-overexpressing MYC and BCL2.

Science.gov (United States)

Mahadevan, Daruka; Morales, Carla; Cooke, Laurence S; Manziello, Ann; Mount, David W; Persky, Daniel O; Fisher, Richard I; Miller, Thomas P; Qi, Wenqing

2014-01-01

Pearson correlation coefficient for expression analysis of the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) demonstrated Aurora A and B are highly correlated with MYC in DLBCL and mantle cell lymphoma (MCL), while both Auroras correlate with BCL2 only in DLBCL. Auroras are up-regulated by MYC dysregulation with associated aneuploidy and resistance to microtubule targeted agents such as vincristine. Myc and Bcl2 are differentially expressed in U-2932, TMD-8, OCI-Ly10 and Granta-519, but only U-2932 cells over-express mutated p53. Alisertib [MLN8237 or M], a highly selective small molecule inhibitor of Aurora A kinase, was synergistic with vincristine [VCR] and rituximab [R] for inhibition of cell proliferation, abrogation of cell cycle checkpoints and enhanced apoptosis versus single agent or doublet therapy. A DLBCL (U-2932) mouse model showed tumor growth inhibition (TGI) of ∼ 10-20% (p = 0.001) for M, VCR and M-VCR respectively, while R alone showed ∼ 50% TGI (p = 0.001). M-R and VCR-R led to tumor regression [TR], but relapsed 10 days after discontinuing therapy. In contrast, M-VCR-R demonstrated TR with no relapse >40 days after stopping therapy with a Kaplan-Meier survival of 100%. Genes that are modulated by M-VCR-R (CENP-C, Auroras) play a role in centromere-kinetochore function in an attempt to maintain mitosis in the presence of synthetic lethality. Together, our data suggest that the interaction between alisertib plus VCR plus rituximab is synergistic and synthetic lethal in Myc and Bcl-2 co-expressing DLBCL. Alisertib plus vincristine plus rituximab [M-VCR-R] may represent a new strategy for DLBCL therapy.

The effect of long or chopped straw on pig behaviour.

Science.gov (United States)

Lahrmann, H P; Oxholm, L C; Steinmetz, H; Nielsen, M B F; D'Eath, R B

2015-05-01

In the EU, pigs must have permanent access to manipulable materials such as straw, rope, wood, etc. Long straw can fulfil this function, but can increase labour requirements for cleaning pens, and result in problems with blocked slatted floors and slurry systems. Chopped straw might be more practical, but what is the effect on pigs' behaviour of using chopped straw instead of long straw? Commercial pigs in 1/3 slatted, 2/3 solid pens of 15 pigs were provided with either 100 g/pig per day of long straw (20 pens) or of chopped straw (19 pens). Behavioural observations were made of three focal pigs per pen (one from each of small, medium and large weight tertiles) for one full day between 0600 and 2300 h at each of ~40 and ~80 kg. The time spent rooting/investigating overall (709 s/pig per hour at 40 kg to 533 s/pig per hour at 80 kg), or directed to the straw/solid floor (497 s/pig per hour at 40 kg to 343 s/pig per hour at 80 kg), was not affected by straw length but reduced with age. Time spent investigating other pigs (83 s/pig per hour at 40 kg), the slatted floor (57 s/pig per hour) or pen fixtures (21 s/pig per hour) was not affected by age or straw length. Aggressive behaviour was infrequent, but lasted about twice as long in pens with chopped straw (2.3 s/pig per hour at 40 kg) compared with pens with long straw (1.0 s/pig per hour at 40 kg, P=0.060). There were no significant effects of straw length on tail or ear lesions, but shoulders were significantly more likely to have minor scratches with chopped straw (P=0.031), which may reflect the higher levels of aggression. Smaller pigs showed more rooting/investigatory behaviour, and in particular directed towards the straw/solid floor and the slatted floor than their larger pen-mates. Females exhibited more straw and pen fixture-directed behaviour than males. There were no effects of pig size or sex on behaviour directed towards other pigs. In summary, pigs spent similar amounts of time interacting with straw

Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL)

International Nuclear Information System (INIS)

Griffiths, Robert; Gleeson, Michelle; Knopf, Kevin; Danese, Mark

2010-01-01

Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL. Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality. Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1

CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

NARCIS (Netherlands)

Doorduijn, JK; van der Holt, B; van Imhoff, GW; van der Hem, KG; Kramer, MHH; van Oers, MHJ; Ossenkoppele, GJ; Verdonck, LF; Verhoef, GEG; Steijaert, MMC; Buijt, I.; Uyl-de Groot, CA; van Agthoven, M; Mulder, AH; Sonneveld, P; Schaafsma, M.

2003-01-01

Purpose : To investigate whether the relative close-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

NARCIS (Netherlands)

Doorduijn, J. K.; van der Holt, B.; van Imhoff, G. W.; van der Hem, K. G.; Kramer, M. H. H.; van Oers, M. H. J.; Ossenkoppele, G. J.; Schaafsma, M. R.; Verdonck, L. F.; Verhoef, G. E. G.; Steijaert, M. M. C.; Buijt, I.; Uyl-de Groot, C. A.; van Agthoven, M.; Mulder, A. H.; Sonneveld, P.

2003-01-01

PURPOSE: To investigate whether the relative dose-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

Effect of grass silage chop length on chewing activity and digestibility

DEFF Research Database (Denmark)

Garmo, T.H.; Randby, Å.T.; Eknæs, M.

2008-01-01

Round bale grass silage harvested early (D-value 757 g kg-1 DM) or at a normal (D-value 696 g kg-1 DM) time was used to study the effect of harvesting time, chop length and their interaction on chewing activity and digestibility by dairy cows. Six early lactating Norwegian Red cows were used in a 6...... due to reduced ET, CT = 45, 41 and 39 min kg-1 DM for rations with long, coarsely and finely chopped silage, respectively. Grass silage chop length did not influence diet digestibility, but there was a significant effect of harvesting time on digestibility. No interaction between harvesting time...

Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach

NARCIS (Netherlands)

de Jong, Mathilde R. W.; Visser, Lydia; Huls, Gerwin; Diepstra, Arjan; van Vugt, Marcel; Ammatuna, Emanuele; van Rijn, Rozemarijn S.; Vellenga, Edo; van den Berg, Anke; Fehrmann, Rudolf S. N.; van Meerten, Tom

2018-01-01

Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs

A comparison of pectoralis versus lumbar skeletal muscle indices for defining sarcopenia in diffuse large B-cell lymphoma - two are better than one.

Science.gov (United States)

Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Kang, Jung Hun; Kim, Hye Ree; Lee, Gyeong-Won

2017-07-18

Sarcopenia is known to be associated with poor clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). There is no consensus concerning the optimal method to define sarcopenia in DLBCL. We retrospectively reviewed 193 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Sarcopenia was classified by the region where the pretreatment skeletal muscle index (SMI) was measured. Both the sarcopenia-L3 and sarcopenia-pectoralis muscle (PM) groups had increased incidences of severe treatment-related toxicities and treatment discontinuation compared with the non-sarcopenia-L3 and non-sarcopenia-PM groups, respectively. The sarcopenia-L3 and non-sarcopenia-L3 groups had 5-year overall survival (OS) rates of 40.5% and 67.8% (p sarcopenia-PM and non-sarcopenia-PM groups had 5-year OS rates of 35.9% and 69.0% (p sarcopenia-L3 alone and sarcopenia-PM alone groups were compared, there were no differences in baseline characteristics, treatment toxicity, or survival. In multivariate analysis, when compared with the non-sarcopenia-both group, OS was significantly worse in the sarcopenia-both group (HR, 2.480; 95% CI, 1.284 - 4.792; p = 0.007), but not in patients with either sarcopenia-L3 alone or sarcopenia-PM alone (p = 0.151). L3- and PM-SMIs are equally useful to define sarcopenia, which is related to intolerance to R-CHOP therapy and to worse survival in patients with DLBCL. More prognostic information can be obtained when these two SMIs are combined to define sarcopenia.

Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL.

Science.gov (United States)

Pilichowska, Monika; Pittaluga, Stefania; Ferry, Judith A; Hemminger, Jessica; Chang, Hong; Kanakry, Jennifer A; Sehn, Laurie H; Feldman, Tatyana; Abramson, Jeremy S; Kritharis, Athena; Hernandez-Ilizaliturri, Francisco J; Lossos, Izidore S; Press, Oliver W; Fenske, Timothy S; Friedberg, Jonathan W; Vose, Julie M; Blum, Kristie A; Jagadeesh, Deepa; Woda, Bruce; Gupta, Gaurav K; Gascoyne, Randy D; Jaffe, Elaine S; Evens, Andrew M

2017-12-12

Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20 + , 83%; PAX5 + , 100%; BCL6 + , 20%; MUM1 + , 100%; CD30 + , 92%; EBV + , 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV + DLBCL, n = 3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n = 1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P = .038) and less likely more than 1 extranodal site (0% vs 25%; P = .019). With a 44-month median follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases ( P = .19 and P = .15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P = .01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP±R) was associated with improved 3-year PFS (70% vs 20%; P = .03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.

FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures

DEFF Research Database (Denmark)

Wong, Kah Keng; Gascoyne, Duncan M; Soilleux, Elizabeth J

2016-01-01

frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which...

Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan.

Science.gov (United States)

Inano, Shojiro; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Arima, Nobuyoshi

2014-02-01

High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17-110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting.

Intrinsic stress of bismuth oxide thin films: effect of vapour chopping and air ageing

International Nuclear Information System (INIS)

Patil, R B; Puri, R K; Puri, V

2008-01-01

Bismuth oxide thin films of thickness 1000 A 0 have been prepared by thermal oxidation (in air) of vacuum evaporated bismuth thin films (on glass substrate) at different oxidation temperatures and duration. Both the vapour chopped and nonchopped bismuth oxide thin films showed polycrystalline and polymorphic structure. The monoclinic bismuth oxide was found to be predominant in both the cases. The effect of vapour chopping and air exposure for 40 days on the intrinsic stress of bismuth oxide thin films has been studied. The vapour chopped films showed low (3.92 - 4.80 x 10 9 N/m 2 ) intrinsic stress than those of nonchopped bismuth oxide thin films (5.77 - 6.74 x 10 9 N/m 2 ). Intrinsic stress was found to increase due to air ageing. The effect of air ageing on the vapour chopped films was found low. The vapour chopped films showed higher packing density. Higher the packing density, lower the film will age. The process of chopping vapour flow creates films with less inhomogenety i.e. a low concentration of flaws and non-planar defects which results in lower intrinsic stress

Baked Pork Chops With Apple Cranberry Sauce

Science.gov (United States)

... bakedporkchopswithapplecranberrysauce.html Baked Pork Chops With Apple Cranberry Sauce To use the sharing features on this page, ... minutes Number of Servings: 4 A wonderful fruit sauce adds the perfect touch to these pork chops— ...

Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

Science.gov (United States)

Kilickap, Saadettin; Yavuz, Bunyamin; Aksoy, Sercan; Sahiner, Levent; Dincer, Murat; Harputluoglu, Hakan; Erman, Mustafa; Aytemir, Kudret; Tokgozoglu, Lale; Barista, Ibrahim

2008-01-01

The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P 0.05). Conventional Doppler echocardiography yielded consistent findings. Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

Effect of meat appearance on consumer preferences for pork chops in Greece and Cyprus.

Science.gov (United States)

Fortomaris, P; Arsenos, G; Georgiadis, M; Banos, G; Stamataris, C; Zygoyiannis, D

2006-04-01

The effect of meat appearance on consumers' preferences for pork chops was assessed using images manipulated for appearance characteristics. Data were collected from 412 consumers in Greece and Cyprus. Consumers were asked for their preference for pork chops from a book of computer-modified images and then completed a questionnaire of socio-demographic information, including eating and purchasing behaviour. Consumers under the age of 35 years showed preferences for dark red, lean pork, while consumers aged 35 years and older preferred either dark or light red pork. Gender appeared to be an important selection factor as men showed an increased preference for dark red pork while women preferred the light red. Consumers who stated that they like pork for its taste (91%) preferred either dark or light red pork chops while those who like pork for reasons other than taste preferred dark red, lean pork. Urban consumers preferred light red, fatty pork chops while the rural consumers preferred the dark red pork chops.

Etching radical controlled gas chopped deep reactive ion etching

Science.gov (United States)

Olynick, Deidre; Rangelow, Ivo; Chao, Weilun

2013-10-01

A method for silicon micromachining techniques based on high aspect ratio reactive ion etching with gas chopping has been developed capable of producing essentially scallop-free, smooth, sidewall surfaces. The method uses precisely controlled, alternated (or chopped) gas flow of the etching and deposition gas precursors to produce a controllable sidewall passivation capable of high anisotropy. The dynamic control of sidewall passivation is achieved by carefully controlling fluorine radical presence with moderator gasses, such as CH.sub.4 and controlling the passivation rate and stoichiometry using a CF.sub.2 source. In this manner, sidewall polymer deposition thicknesses are very well controlled, reducing sidewall ripples to very small levels. By combining inductively coupled plasmas with controlled fluorocarbon chemistry, good control of vertical structures with very low sidewall roughness may be produced. Results show silicon features with an aspect ratio of 20:1 for 10 nm features with applicability to nano-applications in the sub-50 nm regime. By comparison, previous traditional gas chopping techniques have produced rippled or scalloped sidewalls in a range of 50 to 100 nm roughness.

Development of disassembly and pin chopping technology for FBR spent fuels

International Nuclear Information System (INIS)

Kobayashi, Tsuguyuki; Namba, Takashi; Kawabe, Yukinari; Washiya, Tadahiro

2008-01-01

Japan Atomic Power Company (JAPC) and Japan Atomic Energy Agency (JAEA) have been developing fuel disassembly and fuel pin chopping systems for a future Japanese commercial FBR. At first, the wrapper tube is cut by the slit-cut to pull it out, then the fuel pins are cut by the crop-cut at their end-plugs to separate them from the entrance nozzle. The pins are transferred to the magazine of the chopping machine. A series of tests were performed to develop this procedure. As the result of mechanical cutting tests, the CBN wheel was selected. The slit-cut tests were carried out to evaluated the cutting performance of the wheel. The wrapper tube is normally slit-cut in the circumferential direction. One CBN wheel could cut more than 5 fuel assemblies in this direction. The slit-cut in the axial direction is prepared as provision when the tube is difficult to put out. More work is needed to cut 5mm thick PNC-FMS plate in this direction without damaging the pins beneath it. As the result of the crop-cut tests of end-plugs made of ODS steel, the CBN wheel could cut the 61 pin bundle by two strokes. More work is needed to cut the 217 pin bundle. Fuel pin handling tests were performed to transfer them from the disassembly machine to the chopping machine. The Saucer tray was selected to receive the disassembled pins. All the pins were transferred and loaded into a magazine of the chopping machine. Fuel pin loading tests were conducted to optimize the magazine configuration to make the chopping length within 1.0±0.5 cm. In order to decrease the disturbance during chopping, the width of the magazine was adjusted to be 12 cm and installation of a height adjuster is favourable to control the free space above the pins. (author)

Modeling wormhole growth and wormhole networks in unconsolidated sand media using the BP CHOPS model

Energy Technology Data Exchange (ETDEWEB)

Vanderheyden, W.B. [BP America, Inc. Exploration and Production Technology Unconventional Oil Flagship (United States); Zhang, D. Z.; Jayaraman, B. [Los Alamos National Laboratory Theoretical Division Solid and Fluid Dynamics Group (United States)

2011-07-01

Cold Heavy Oil Production with Sand (CHOPS) is a recovery method used in unconsolidated sands to produce heavy oil. During the use of the CHOPS method, wormholes originating from production wells are generated. The aim of this paper is to present 2 modeling tools developed by BP in order to improve reservoir simulation of CHOPS operations with wormholes. The first tool developed is a CHOPS modeling framework representing wormhole networks through reservoir simulation and its wellbore model. The second one consists of the application of advanced fluid-structure interaction modeling into the simulation of wormhole and its network growth. Experiments were carried out and a qualitative agreement was achieved with the model. In addition the BP CHOPS model can predict probable oil production without calibration. This paper presented an improved model for reservoir simulation with wormholes but further work is required to predict wormhole shape in a more accurate manner.

Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma

Directory of Open Access Journals (Sweden)

Peroja Pekka

2012-03-01

Full Text Available Abstract Background Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL, although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx, manganese superoxide dismutase (MnSOD and glutamate-cysteine ligase (GCL via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL. Results Strong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002, a high International Prognostic Index (p = 0.002 and strong Trx (p = 0.011 and GCL (p = 0.0003 expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046 and poor disease-specific survival (p = 0.015. Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049. Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003 and disease-specific survival (p = 0.031 compared with the other patients. Conclusions The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.

Dimension and quality requirements for chopped firewood; Pilkkeen mitta- ja laatuvaatimukset

Energy Technology Data Exchange (ETDEWEB)

Tuomi, S [Work Efficiency Inst., Rajamaeki (Finland)

1997-12-01

Over the heating season of 1992-1993 in total 5.6 million m{sup 3} of firewood was used for heating one-family houses in Finland. Major part consisted of chopped firewood. Two-thirds of firewood was acquired from consumers` own forests. The proportion of purchased wood was less than a fifth, about one million m{sup 3}. More than half, i.e. 750 000 house-owners consider the use of purchased firewood possible. Chopped firewood is the most favoured type of wood. A crucial problem of firewood sales is the lack of dimension and quality requirements. The measuring practice of chopped firewood has neither been standardised. These problems hamper the development of the commercial firewood market and prevents the increase of firewood use in particular in one-family houses, in which stoves and fireplaces are presently under-used. The aim of the project is to promote firewood sales and to protect consumers by preparing a proposal for the measurement and dimension and quality requirements for chopped firewood. The work is carried out on the basis of material based on field and laboratory measurements and on a literature survey. The most important results will be published as a guide book for firewood entrepreneurs and buyers. (orig.)

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

Energy Technology Data Exchange (ETDEWEB)

Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

2015-03-15

Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

Does the presence of tumor-induced cortical bone destruction at CT have any prognostic value in newly diagnosed diffuse large B-cell lymphoma?

Energy Technology Data Exchange (ETDEWEB)

Adams, Hugo J.A.; Nievelstein, Rutger A.J.; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Fijnheer, Rob [Meander Medical Center, Department of Hematology, Amersfoort (Netherlands); Heggelman, Ben G.F. [Meander Medical Center, Department of Radiology, Amersfoort (Netherlands); Dubois, Stefan V. [Meander Medical Center, Department of Pathology, Amersfoort (Netherlands)

2015-05-01

To determine the prognostic value of tumor-induced cortical bone destruction at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 105 patients with newly diagnosed DLBCL who had undergone CT and bone marrow biopsy (BMB) before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemo-immunotherapy. Cox regression analyses were used to determine the associations of cortical bone status at CT (absence vs. presence of tumor-induced cortical bone destruction), BMB findings (negative vs. positive for lymphomatous involvement), and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) strata (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). Univariate Cox regression analysis indicated that cortical bone status at CT was no significant predictor of either PFS or OS (p = 0.358 and p = 0.560, respectively), whereas BMB findings (p = 0.002 and p = 0.013, respectively) and dichotomized NCCN-IPI risk strata (p = 0.002 and p = 0.003, respectively) were significant predictors of both PFS and OS. In the multivariate Cox proportional hazards model, only the dichotomized NCCN-IPI score was an independent predictive factor of PFS and OS (p = 0.004 and p = 0.003, respectively). The presence of tumor-induced cortical bone destruction at CT was not found to have any prognostic implications in newly diagnosed DLBCL. (orig.)

MYC-rearranged lymphomas other than Burkitt: Comparison between R-CHOP and Burkitt-type immunochemotherapy.

Science.gov (United States)

Baptista, Maria Joao; Tapia, Gustavo; Hernández-Rivas, José-Ángel; Martínez-Trillos, Alejandra; Mate, José-Luis; Navarro, José-Tomás

2017-10-23

MYC-rearranged (MYC-R) lymphomas other than Burkitt lymphoma (BL) are very aggressive, with poor prognosis when treated with standard regimens. We aimed to study the characteristics and outcome of a series of MYC-R lymphomas comparing the treatment results between R-CHOP based and a specific intensive regimen for BL (BURKIMAB). Retrospective study of patients diagnosed with MYC-R. Translocations of MYC, BCL2 and BCL6 were evaluated by fluorescent in situ hybridization. Patients were treated with either, R-CHOP based immunochemotherapy or the Burkitt type regimen, BURKIMAB. Thirty-four MYC-R lymphoma cases were studied: 21 treated with R-CHOP and 13 treated with BURKIMAB. There were no differences in CR rate; 45% (9/20) for R-CHOP and 42% (5/12) for BURKIMAB (P=.99). Although overall survival (OS) and progression free survival (PFS) of BURKIMAB-treated patients were better than those of R-CHOP-treated (3y-OS: 46 vs. 24%; 3y-PFS: 46 vs. 10%), the differences were not statistically significant. MYC-R lymphomas show poor outcomes even when treated with intensive immunochemotherapy for BL. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

76 FR 76890 - Nutrition Labeling of Single-Ingredient Products and Ground or Chopped Meat and Poultry Products...

Science.gov (United States)

2011-12-09

.... FSIS-2005-0018] Nutrition Labeling of Single-Ingredient Products and Ground or Chopped Meat and Poultry... major cuts of single-ingredient, raw meat and poultry products and ground or chopped meat and poultry... Ground or Chopped Meat and Poultry Products'' in the Federal Register (75 FR 82148) that, among other...

RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

DEFF Research Database (Denmark)

Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

2012-01-01

Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase L(-/-)-MEFs, maintaining preadipocyte state while impairing their terminal differentiation. RNase L(-/-)-MEFs have decreased lipids storage capacity, insulin sensitivity and glucose uptake. Expression of ectopic...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

Primary Diffuse Large B-Cell Lymphoma Localized to the Lacrimal Sac: A Case Presentation and Review of the Literature

Directory of Open Access Journals (Sweden)

Kevin Zarrabi

2016-01-01

Full Text Available We report a rare case of diffuse large B-cell lymphoma (DLBCL of the lacrimal sac in a 50-year-old male. The incidence of primary ocular lymphoma is low and it is considered a rare disease. Moreover, reports of ocular DLBCL are uncommon and the disease remains poorly characterized. Our patient presented for management of osteomyelitis and was incidentally found to have a painless swelling and cyst around his right eye. A PET/CT scan revealed hypermetabolic activity within the lacrimal sac and a subsequent excisional biopsy of the mass yielded histopathology consistent with DLBCL. Consequently, the patient underwent treatment with R-CHOP therapy. The patient responded well to chemotherapy with a substantial shrinkage in tumor burden and the disease remained localized. Herein, we present a rare case of primary ocular lymphoma, highlight the importance of early diagnosis, and review current treatment modalities.

Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

Energy Technology Data Exchange (ETDEWEB)

Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

2016-07-15

The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy

DEFF Research Database (Denmark)

Xu-Monette, Zijun Y; Møller, Michael B; Tzankov, Alexander

2013-01-01

MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab, cycloph...

Dose-dense chemoimmunotherapy and CNS prophylaxis in patients with high-risk DLBCL: a comparison of Nordic CRY-04 and CHIC studies

DEFF Research Database (Denmark)

Leppä, Sirpa; Jørgensen, Judit Meszaros; Brown, Peter De Nully

Background: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression relatively high. We investigated the efficacy of dose-dense chemoimmunotherapy and systemic CNS prophylaxis in two completed Nordic trials...... including patients less than 65 years with high-risk DLBCL. We combined individual patient data from these studies to compare clinical outcome and prognostic factors in patients treated with CNS prophylaxis given in the beginning (CHIC) vs at the end (CRY-04) of therapy. Patients and methods: Inclusion...... proliferation index (Ki67 expression available PET data, Deauville score 5 at the end of treatment was associated with increased rate of progression and death in both trials (p=0.012). Only one out of 17 biopsies from PET positive...

Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B mutations.

Science.gov (United States)

Cao, Xin-Xin; Li, Jian; Cai, Hao; Zhang, Wei; Duan, Ming-Hui; Zhou, Dao-Bin

2017-11-01

This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

Application of phaco prechop with phaco chop technique in phacoemulsification

Directory of Open Access Journals (Sweden)

Wei Liu

2014-03-01

Full Text Available AIM:To compare two phaco techniques, namely phaco prechop with phaco chop and divide and conquer, and to discuss the technical advantages of phaco prechop with phaco chop METHODS:The study included 131 patients(156 eyeswith age-related cataract eyes divided into 2 groups, group A including 68 patients(82 eyes, in which phaco prechop with phaco chop was performed, and group B including 63 patients(74 eyes, in which divide and conquer was performed. The mean parameters including average power(AP, U/S time, accumulated energy complex parameter(AECP, mean endothelial cell count, mean endothelial cell loss, intraoperative complications, postoperative uncorrected visual acuity(UCVAat 1d and 1wk, and corneal edema were reported in the two groups both preoperative and postoperative.RESULTS:The subgroups with same grade of lens nucleus hardness were compared. Parameters such as AP, U/S time, AECP in group A were significantly less than those in group B. Postoperative corneal clarity and UCVA at 1d in group A was better than that in group B. No significant difference was found in UCVA at 1wk after operation between the two groups. The difference in mean endothelial cell count at 3mo postoperative between the two groups was statistically insignificant(P>0.05, however the difference in endothelial cell loss at 3mo postoperatively between the two groups was statistically significant(PCONCLUSION:Compare with divide and conquer, phaco prechop with phaco chop utilized less phaco time, energy, and the rate of endothelial cell loss at 3mo postoperatively, and better early postoperative uncorrected visual acuity.

Cyclophilin B is involved in p300-mediated degradation of CHOP in tumor cell adaptation to hypoxia.

Science.gov (United States)

Jeong, K; Kim, H; Kim, K; Kim, S-J; Hahn, B-S; Jahng, G-H; Yoon, K-S; Kim, S S; Ha, J; Kang, I; Choe, W

2014-03-01

The regulation of CCAAT/enhancer-binding protein-homologous protein (CHOP), an endoplasmic reticulum (ER) stress-response factor, is key to cellular survival. Hypoxia is a physiologically important stress that induces cell death in the context of the ER, especially in solid tumors. Although our previous studies have suggested that Cyclophilin B (CypB), a molecular chaperone, has a role in ER stress, currently, there is no direct information supporting its mechanism under hypoxia. Here, we demonstrate for the first time that CypB is associated with p300 E4 ligase, induces ubiquitination and regulates the proteasomal turnover of CHOP, one of the well-known pro-apoptotic molecules under hypoxia. Our findings show that CypB physically interacts with the N-terminal α-helix domain of CHOP under hypoxia and cooperates with p300 to modulate the ubiquitination of CHOP. We also show that CypB is transcriptionally induced through ATF6 under hypoxia. Collectively, these findings demonstrate that CypB prevents hypoxia-induced cell death through modulation of ubiquitin-mediated CHOP protein degradation, suggesting that CypB may have an important role in the tight regulation of CHOP under hypoxia.

Characterization of methane emissions from five cold heavy oil production with sands (CHOPS) facilities.

Science.gov (United States)

Roscioli, Joseph R; Herndon, Scott C; Yacovitch, Tara I; Knighton, W Berk; Zavala-Araiza, Daniel; Johnson, Matthew R; Tyner, David R

2018-03-07

Cold heavy oil production with sands (CHOPS) is a common oil extraction method in the Canadian provinces of Alberta and Saskatchewan that can result in significant methane emissions due to annular venting. Little is known about the magnitude of these emissions, nor their contributions to the regional methane budget. Here the authors present the results of field measurements of methane emissions from CHOPS wells and compare them with self-reported venting rates. The tracer ratio method was used not only to analyze total site emissions but at one site it was also used to locate primary emission sources and quantify their contributions to the facility-wide emission rate, revealing the annular vent to be a dominant source. Emissions measured from five different CHOPS sites in Alberta showed large discrepancies between the measured and reported rates, with emissions being mainly underreported. These methane emission rates are placed in the context of current reporting procedures and the role that gas-oil ratio (GOR) measurements play in vented volume estimates. In addition to methane, emissions of higher hydrocarbons were also measured; a chemical "fingerprint" associated with CHOPS wells in this region reveals very low emission ratios of ethane, propane, and aromatics versus methane. The results of this study may inform future studies of CHOPS sites and aid in developing policy to mitigate regional methane emissions. Methane measurements from cold heavy oil production with sand (CHOPS) sites identify annular venting to be a potentially major source of emissions at these facilities. The measured emission rates are generally larger than reported by operators, with uncertainty in the gas-oil ratio (GOR) possibly playing a large role in this discrepancy. These results have potential policy implications for reducing methane emissions in Alberta in order to achieve the Canadian government's goal of reducing methane emissions by 40-45% below 2012 levels within 8 yr.

Serum lactate dehydrogenase with a systemic inflammation score is useful for predicting response and survival in patients with newly diagnosed diffuse large B-cell lymphoma.

Science.gov (United States)

Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

2015-01-01

We evaluated the relationship between serum lactate dehydrogenase (LDH) level with systemic inflammation score and survival in 213 patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. The patients were classified into 3 groups based on LDH with the Glasgow Prognostic Score (L-GPS). A score of 2 was assigned to patients with elevated C-reactive protein, hypoalbuminemia and elevated LDH, a score of 1 to those with one or two abnormalities and a score of 0 to those with no abnormality. In multivariate analysis, independent poor prognostic factors for progression-free survival were L-GPS 2 [hazard ratio (HR) 5.415, p = 0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.504, p = 0.001) and bulky lesion (HR 2.030, p = 0.039). Independent poor prognostic factors for overall survival were L-GPS 2 (HR 5.898, p = 0.001) and ECOG PS ≥2 (HR 3.525, p = 0.001). The overall response rate for the R-CHOP chemotherapy decreased according to the L-GPS; it was 96.7% at L-GPS 0, 87% at L-GPS 1 and 75% at L-GPS 2 (p = 0.009). L-GPS based on systemic inflammatory indicators may be a useful clinical prognostic indicator for survival, and predicts the response for R-CHOP chemotherapy in patients with newly diagnosed DLBCL. © 2014 S. Karger AG, Basel.

An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

Science.gov (United States)

Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

2018-01-02

Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

ATF4- and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress

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Xiao-shan Wan

2014-01-01

Full Text Available Fibroblast growth factor 21 (FGF21 is an important endogenous regulator involved in the regulation of glucose and lipid metabolism. FGF21 expression is strongly induced in animal and human subjects with metabolic diseases, but little is known about the molecular mechanism. Endoplasmic reticulum (ER stress plays an essential role in metabolic homeostasis and is observed in numerous pathological processes, including type 2 diabetes, overweight, nonalcoholic fatty liver disease (NAFLD. In this study, we investigate the correlation between the expression of FGF21 and ER stress. We demonstrated that TG-induced ER stress directly regulated the expression and secretion of FGF21 in a dose- and time-dependent manner. FGF21 is the target gene for activating transcription factor 4 (ATF4 and CCAAT enhancer binding protein homologous protein (CHOP. Suppression of CHOP impaired the transcriptional activation of FGF21 by TG-induced ER stress in CHOP−/− mouse primary hepatocytes (MPH, and overexpression of ATF4 and CHOP resulted in FGF21 promoter activation to initiate the transcriptional programme. In mRNA stability assay, we indicated that ER stress increased the half-life of mRNA of FGF21 significantly. In conclusion, FGF21 expression is regulated by ER stress via ATF- and CHOP-dependent transcriptional mechanism and posttranscriptional mechanism, respectively.

development of oscillating classifiers for forage chop length ...

African Journals Online (AJOL)

Dr Obe

1987-09-01

Sep 1, 1987 ... 6.Calculation of Forage Chop Size. Particle size distribution is characterised by the parameters that measure the central tendency of the distribution and the dispersion about the central tendency. Most fine particle systems obey the logarithmic normal distribution function [4]. This means that the distribution.

Chop Suey as Imagined Authentic Chinese Food: The Culinary Identity of Chinese Restaurants in the United States

OpenAIRE

Haiming Liu

2009-01-01

At least until the 1960s, chop suey was synonymous with Chinese food in the United States, where most Chinese restaurants were called chop suey houses. By uncovering the history of chop suey, this article analyzes the development of Chinese cuisine in the U.S. as an example of transnational cultural exchange. The authenticity and culinary identity of Chinese food in America often rested on its real or imagined Chinese roots while its popularity depended on how well Chinese restaurant...

Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

Science.gov (United States)

Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

2016-11-20

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

Lipopolysaccharide preconditioning protects hepatocytes from ischemia/reperfusion injury (IRI through inhibiting ATF4-CHOP pathway in mice.

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Jianhua Rao

Full Text Available BACKGROUND: Low-dose lipopolysaccharide (LPS preconditioning-induced liver protection has been demonstrated during ischemia-reperfusion injury (IRI in several organs but has not been sufficiently elucidated underlying causal mechanism. This study investigated the role of low-dose LPS preconditioning on ATF4-CHOP pathway as well as the effects of the pathway on tissue injury and inflammation in a mouse model of liver partial-warm IRI. METHODS: LPS (100 µg/kg/d was injected intraperitoneally two days before ischemia. Hepatic injury was evaluated based on serum alanine aminotransferase levels, histopathology, and caspase-3 activity. The ATF4-CHOP pathway and its related apoptotic molecules were investigated after reperfusion. The role of LPS preconditioning on apoptosis and ATF4-CHOP pathway was examined in vitro. Moreover, the effects of the ATF4-CHOP pathway on apoptosis, Caspase-12, and Caspase-3 were determined with ATF4 small interfering RNA (siRNA. Inflammatory cytokine expression was also checked after reperfusion. Inflammatory cytokines and related signaling pathways were analyzed in vitro in macrophages treated by LPS preconditioning or ATF4 siRNA. RESULTS: LPS preconditioning significantly attenuated liver injury after IRI. As demonstrated by in vitro experiments, LPS preconditioning significantly reduced the upregulation of the ATF4-CHOP pathway and inhibited Caspase-12 and Caspase-3 activation after IRI. Later experiments showed that ATF4 knockdown significantly suppressed CHOP, cleaved caspase-12 and caspase-3 expression, as well as inhibited hepatocellular apoptosis. In addition, in mice pretreated with LPS, TNF-α and IL-6 were inhibited after reperfusion, whereas IL-10 was upregulated. Similarly, low-dose LPS significantly inhibited TNF-α, IL-6, ATF4-CHOP pathway, NF-κB pathway, and ERK1/2 in high-dose LPS-stimulated macrophages, whereas IL-10 and cytokine signaling (SOCS-3 suppressor were induced. Importantly, ATF4 siRNA is

Role of intrinsic search cues in the formation of consumer preferences and choice for pork chops.

Science.gov (United States)

Verbeke, Wim; De Smet, Stefaan; Vackier, Isabelle; Van Oeckel, Monique J; Warnants, Nathalie; Van Kenhove, Patrick

2005-02-01

This study investigates the role of drip, colour, marbling and fat cover as intrinsic search cues in the formation of pork chop preferences and individual determinants. Data are collected from a sample of 443 pork consumers in Belgium through using repeated selection of chops from randomised photobooks and questionnaires including socio-demographic, attitudinal and behavioural variables. Data analysis includes mixture regression analysis, bivariate descriptive statistics and the estimation of multivariate probit models. Consumers sampled in this study prefer pork chops without fat cover. Preference for fat cover is stronger among male, 35+ aged consumers with lower levels of awareness of the relation between food and health and who like pork for other reasons than taste and nutritional value (all p<0.05). Preference for colour is equally consistent within an individual, though fifty-fifty light-dark, with dark chops being more preferred by 35+ aged consumers (p<0.05). Preferences for marbling and drip are not consistent and not determined by joint socio-demographic, attitudinal and behavioural factors. Preferences for cue levels are not correlated, except a weak relation between preference for dark chops without drip (r=0.116). Preferences are apparently formed by deductions with the use of single cues as key information, mainly based on fat cover or colour, and random choice on marbling and drip.

Electron beam sub-harmonics chopping system for linear accelerator injector

International Nuclear Information System (INIS)

Bourat, Christophe

1988-01-01

The need of a 100 % duty cycle electron accelerator for use in nuclear physics, has led in 1981 the CEN Saclay Linear Accelerator Group, to study a machine using the existing linac associated with a pulse stretcher ring. The production of electron bunches at the ring RF frequency (600 MHz) requires the design of a new injector including a chopping beam System with a deflecting electromagnetic cavity and a collimator. A comparison between four transverse magnetic modes, led to choose a TM110 parallelepiped chopper. The construction of a prototype and of a vacuum-tight cavity followed by microwave measurements has permitted to solve several mechanical problems and to specify the cavity electrical properties. In a first step, the beam line, including - focusing, offset deflection coils, chopping with a rectangular collimator - has been studied, for zero intensity beam current, on the basis of a matrix model. An experimental 40 keV beam line, has been assembled to measure the bunch length. The method was based on a spectral analysis of the signal delivered by a large band, 50 ohms adapted beam collector. The bunch shape in the time domain was reconstructed by inverse Fourier transform. The beam dynamics has been studied with a 3D space charge model which has been introduced into the PARMELA tracking code. Simulations showed that a 150 keV, 2 A beam could be chopped with the same deflecting lay-out. (author) [fr

Effect of chopping time and heating on 1 H nuclear magnetic resonance and rheological behavior of meat batter matrix.

Science.gov (United States)

Zhou, Fen; Dong, Hui; Shao, Jun-Hua; Zhang, Jun-Long; Liu, Deng-Yong

2018-04-01

The effect of chopping time and heating on physicochemical properties of meat batters was investigated by low-field nuclear magnetic resonance and rheology technology. Cooking loss and L* increased while texture profile analysis index decreased between chopping 5 and 6 min. The relaxation time T 21 (bound water) and its peak area ratio decreased, while the ratio of T 22 peak area (immobilized water) in raw meat batters gradually increased with the extension of chopping time. However, T 22 was opposite after being heated and a new component T 23 (free water) appeared (T 2i is the spin - spin relaxation time for the ith component.). The initial damping factor (Tan δ) gradually decreased and there were significant difference between 4 and 5 min of chopping time. There were significantly positive correlations between the ratio of peak area of T 22 and chopping time, the storage modulus (G'), cooking loss, and L*, respectively. Continued chopping time could improve the peak area proportion of T 22 in raw meat batters. Further, the higher the peak area proportion of T 22 in raw meat batters, the cooking loss of heated meat gel was higher. Also, the stronger the mobility of immobilized water in meat batter, the higher the L* of the fresh meat batters. Thus, it is revealed that the physicochemical properties of meat batter are significantly influenced by chopping time which further affects the water holding capacity and the texture of emulsification gel. © 2017 Japanese Society of Animal Science.

Combined reservoir simulation and seismic technology, a new approach for modeling CHOPS

Energy Technology Data Exchange (ETDEWEB)

Aghabarati, H.; Lines, L.; Settari, A. [Calgary Univ., AB (Canada); Dumitrescu, C. [Sensor Geophysical Ltd., Calgary, AB (Canada)

2008-10-15

One of the primary recovery schemes for developing heavy oil reservoirs in Canada is cold heavy oil production with sand (CHOPS). With the introduction of progressive cavity pumps, CHOPS can be applied in unconsolidated or weakly consolidated formations. In order to better understand reservoir properties and recovery mechanism, this paper discussed the use of a combined reservoir simulation and seismic technology that were applied for a heavy oil reservoir situated in Saskatchewan, Canada. Using a seismic survey acquired in 1989, the study used geostatistical methods to estimate the initial reservoir porosity. Sand production was then modeled using an erosional velocity approach and the model was run based on oil production. The paper also compared the results of true porosity derived from simulation against the porosity estimated from a second seismic survey acquired in 2001. Last, the extent and the shape of the enhanced permeability region was modelled in order to estimate porosity distribution. It was concluded that the performance of the CHOPS wells depended greatly on the rate of creation of the high permeability zone around the wells. 9 refs., 2 tabs., 18 figs., 1 appendix.

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

Science.gov (United States)

Bascuas, Thais; Moreno, María; Grille, Sofía; Chabalgoity, José A.

2018-01-01

We have previously shown that Salmonella immunotherapy is effective to treat B-cell non-Hodgkin lymphoma (B-NHL) in mice. However, this model involves animals with high tumor burden, whereas in the clinics B-NHL patients are usually treated with chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy prior to immunotherapy. Recently, we have described a NHL-B preclinical model using CHOP chemotherapy to achieve MRD in immunocompetent animals that closely resemble patients’ conditions. In this work, we assessed the efficacy of Salmonella immunotherapy in B-NHL-bearing mice undergoing chemotherapy. Salmonella administration significantly delayed tumor growth and prolonged survival of chemotherapy-treated NHL-bearing animals. Mice receiving the CHOP–Salmonella combined therapy showed increased numbers of tumor-infiltrating leukocytes and a different profile of cytokines and chemokines expressed in the tumor microenvironment. Further, Salmonella immunotherapy in CHOP-treated animals also enhanced NK cells cytotoxic activity as well as induced systemic lymphoma-specific humoral and cellular responses. Chemotherapy treatment profoundly impacted on the general health status of recipient animals, but those receiving Salmonella showed significantly better overall body condition. Altogether, the results clearly demonstrated that Salmonella immunotherapy could be safely used in individuals under CHOP treatment, resulting in a better prognosis. These results give strong support to consider Salmonella as a neoadjuvant therapy in a clinical setting. PMID:29410666

Ocular Adnexal Diffuse Large B-cell LymphomaA Multicenter International Study

DEFF Research Database (Denmark)

Munch-Petersen, Helga D; Rasmussen, Peter K; Coupland, Sarah E

2015-01-01

: This retrospective international cooperative study involved 6 eye cancer centers. During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded from the study. The median follow-up period was 52 months. MAIN OUTCOMES AND MEASURES: Overall survival, disease-specific survival (DSS), and progression...

Effect of packaging type during postmortem aging and degree of doneness on pork chop sensory traits of loins selected to vary in color and marbling.

Science.gov (United States)

Klehm, B J; King, D A; Dilger, A C; Shackelford, S D; Boler, D D

2018-05-04

The objective was to determine the interactions between packaging type and degree of doneness on sensory traits of pork loins classified based on the newly proposed USDA quality grades. A total of 144 loins were selected from 2 groups of pigs (lean growth or meat quality production focus) to represent as much variation in visual color and marbling as possible. Selection was achieved with a VQG grading camera. The ventral surface of the loins was evaluated for loin quality traits at 1 d postmortem. At 2 d postmortem loins were sliced into 28-mm-thick chops. Chop within each loin was randomly assigned to either individual vacuum packages or to individual Styrofoam trays and overwrapped in polyvinyl chloride (PVC) oxygen permeable film. Overwrapped PVC packages were then placed in bulk packages and flushed with a gas mixture that contained approximately 0.4% carbon monoxide, 30% carbon dioxide, and 80% nitrogen. Vacuum-packaged chops were aged until 14 d postmortem. Chops packaged in PVC overwrap were aged until 9 d postmortem in the bulk packages, then placed on simulated retail display until 14 d postmortem. Chops from each packaging type were cooked to an internal temperature of either 63 °C or 71 °C for the evaluation of slice shear force (SSF) or for evaluation of tenderness, juiciness, and flavor by a trained panel. Data were analyzed as split-split plot design with production focus of the pigs, proposed USDA quality grade, packaging type, and degree of doneness as fixed effects. While there were main effect differences between production focuses, there were no interactions with production focus. There were also no 3-way (P ≥ 0.19) interactions and only one 2-way interaction among quality grade, packaging type, or degree of doneness. There were no differences in sensory tenderness (P = 0.30), juiciness (P = 0.49), flavor (P = 0.89), SSF (P = 0.13), or cook loss (P = 0.06) among USDA quality grades. There were no differences in sensory tenderness (P = 0

Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature

Directory of Open Access Journals (Sweden)

Yang Qing-Xu

2012-01-01

Full Text Available Abstract Only a few cases of extranodal Epstein-Barr virus (EBV-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone, but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1197421158639299

Primary Breast Mucosa-Associated Lymphoid Tissue (MALT Lymphoma Transformation to Diffuse Large B-cell Lymphoma: A Case Report

Directory of Open Access Journals (Sweden)

Şerife Hülya Arslan

2012-09-01

Full Text Available Primary non-Hodgkin’s lymphoma (NHL of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL. A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3 × 3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.

Chop Suey as Imagined Authentic Chinese Food: The Culinary Identity of Chinese Restaurants in the United States

Directory of Open Access Journals (Sweden)

Haiming Liu

2009-02-01

Full Text Available At least until the 1960s, chop suey was synonymous with Chinese food in the United States, where most Chinese restaurants were called chop suey houses. By uncovering the history of chop suey, this article analyzes the development of Chinese cuisine in the U.S. as an example of transnational cultural exchange. The authenticity and culinary identity of Chinese food in America often rested on its real or imagined Chinese roots while its popularity depended on how well Chinese restaurant proprietors adapted the flavors, ingredients, and cooking methods of Chinese cuisine to the tastes and markets of local American communities. The dynamic interaction between Chinese food and American customers functioned as a complex cultural negotiation. While Chinese restaurants helped shape the American diet, Chinese food was at the same time being shaped and transformed by American popular taste. By appealing to a wide range of American diners, chop suey eventually evolved into a popular American ethnic food and a central component in the culinary identity of Chinese restaurants. Chop suey generated numerous jobs for Chinese immigrants and established a culinary bond between Chinese food and American customers. Also, as an imagined authentic Chinese dish, it represented a type of affordable exoticism in the eyes of American consumers, meeting not only American tastes but also their social expectations of Chinese culture.

Chop Suey as Imagined Authentic Chinese Food: The Culinary Identity of Chinese Restaurants in the United States

Directory of Open Access Journals (Sweden)

Haiming Liu

2009-02-01

Full Text Available

At least until the 1960s, chop suey was synonymous with Chinese food in the United States, where most Chinese restaurants were called chop suey houses. By uncovering the history of chop suey, this article analyzes the development of Chinese cuisine in the U.S. as an example of transnational cultural exchange. The authenticity and culinary identity of Chinese food in America often rested on its real or imagined Chinese roots while its popularity depended on how well Chinese restaurant proprietors adapted the flavors, ingredients, and cooking methods of Chinese cuisine to the tastes and markets of local American communities. The dynamic interaction between Chinese food and American customers functioned as a complex cultural negotiation. While Chinese restaurants helped shape the American diet, Chinese food was at the same time being shaped and transformed by American popular taste. By appealing to a wide range of American diners, chop suey eventually evolved into a popular American ethnic food and a central component in the culinary identity of Chinese restaurants. Chop suey generated numerous jobs for Chinese immigrants and established a culinary bond between Chinese food and American customers. Also, as an imagined authentic Chinese dish, it represented a type of affordable exoticism in the eyes of American consumers, meeting not only American tastes but also their social expectations of Chinese culture.

Effects of oil-water mixed frying and pure-oil frying on the quality characteristics of soybean oil and chicken chop

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Ruixue MA

2016-01-01

Full Text Available Abstract The effects of oil-water mixed frying (OWF and pure-oil frying (POF on changes in quality characteristics of soybean oil and chicken chop during six days of frying were comparatively investigated. The results showed that the changes in specific extinction coefficients, p-anisidine value, carbonyl value, viscosity and color of soybean oil were more pronounced in the case of POF, indicating that oil oxidative and polymeric degradation was retarded by OWF. Concerning fat content of chicken chop, lower (p<0.05 values were observed in the last three days in the case of OWF than POF. Meanwhile, OWF led to lower acrylamide formation in chops during the six days. Sensory evaluation showed that OWF provided chops with five attributes similar to those of chops fried by POF on the first day. As frying days increased, the decreases in scores for color, odor, flavor and overall acceptability were less in the case of OWF. In conclusion, OWF could be a worthwhile alternative for retarding oil deterioration and producing healthier and higher quality fried meat products.

Resultados quirúrgicos de la facoemulsificación por técnicas de Pre Chop Surgical results of phacoemulsification by Pre Chop techniques

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Juan R. Hernández Silva

2004-12-01

Full Text Available Este estudio se propuso determinar los resultados obtenidos con la técnica de Pre-Chop en la cirugía de catarata por facoemulsificación en el Centro de Microcirugía Ocular del Hospital Oftalmológico Docente "Ramón Pando Ferrer" en el 2001. El universo de trabajo estuvo constituido por todos los pacientes (ojos con diagnóstico de catarata presenil y senil y recibieron tratamiento quirúrgico con la técnica de Pre-Chop por facoemulsificación. Se analizaron como variables: edad, sexo, agudeza visual con corrección, microscopia endotelial y cilindro refractivo, todos en el pre y posoperatorio, así como el tiempo de ultrasonido y complicaciones más frecuentes. Estos datos se analizaron a través de tablas de contingencia con frecuencias absolutas y relativas, medias y se utilizó la prueba T de Student para su comparación. Se encontró que la catarata predominó en el sexo masculino entre los 46 y los 60 años; la agudeza visual con corrección mejoró a 0.64 (20/40 como promedio, el cilindro refractivo apenas se modificó, el tiempo de ultrasonido aplicado estuvo dentro de valores normales, la pérdida de células endoteliales no fue importante y la complicación transoperatoria más frecuente fue rotura de cápsula posterior con salida de vítreo y queratitis.The aim of this paper was to determine the results obtained with the Pre Chop technique in the cataract surgery by phacoemulsification at the Center of Ocular Microsurgery of "Ramón Pando Ferrer" Ophthalmological Teaching Hospital in 2001. All the patients (eyes with diagnosis of presenile and senile cataract that received surgical treatment with the Pre Chop technique by phacoemulsification were included in the study. Variables such as age, sex, visual acuity with correction, endothelial microscopy, refractive cylinder in the pre- and postoperative, time of ultrasound and the most frequent complications, were analyzed through contingency tables with mean absolute and relative

Kaempferol induces hepatocellular carcinoma cell death via endoplasmic reticulum stress-CHOP-autophagy signaling pathway.

Science.gov (United States)

Guo, Haiqing; Lin, Wei; Zhang, Xiangying; Zhang, Xiaohui; Hu, Zhongjie; Li, Liying; Duan, Zhongping; Zhang, Jing; Ren, Feng

2017-10-10

Kaempferol is a flavonoid compound that has gained widespread attention due to its antitumor functions. However, the underlying mechanisms are still not clear. The present study investigated the effect of kaempferol on hepatocellular carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells, which was evidenced by the significant increase of autophagy-related genes. Inhibition of autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished kaempferol-induced apoptosis. We further hypothesized that kaempferol can induce autophagy via endoplasmic reticulum (ER) stress pathway. Indeed, blocking ER stress by 4-phenyl butyric acid (4-PBA) or knockdown of CCAAT/enhancer-binding protein homologous protein (CHOP) with siRNA alleviated kaempferol-induced HepG2 or Huh7 cells autophagy; while transfection with plasmid overexpressing CHOP reversed the effect of 4-PBA on kaempferol-induced autophagy. Our results demonstrated that kaempferol induced hepatocarcinoma cell death via ER stress and CHOP-autophagy signaling pathway; kaempferol may be used as a potential chemopreventive agent for patients with hepatocellular carcinoma.

Chopped or Long Roughage: What Do Calves Prefer? Using Cross Point Analysis of Double Demand Functions

Science.gov (United States)

Webb, Laura E.; Bak Jensen, Margit; Engel, Bas; van Reenen, Cornelis G.; Gerrits, Walter J. J.; de Boer, Imke J. M.; Bokkers, Eddie A. M.

2014-01-01

The present study aimed to quantify calves'(Bos taurus) preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were trained to work for roughage rewards from two simultaneously available panels. The cost (number of muzzle presses) required on the panels varied in each session (left panel/right panel): 7/35, 14/28, 21/21, 28/14, 35/7. Demand functions were estimated from the proportion of rewards achieved on one panel relative to the total number of rewards achieved in one session. Cross points (cp) were calculated as the cost at which an equal number of rewards was achieved from both panels. The deviation of the cp from the midpoint (here 21) indicates the strength of the preference. Calves showed a preference for long versus chopped hay (cp  = 14.5; P  = 0.004), and for hay versus straw (cp  = 38.9; P = 0.004), both of which improve rumen function. Long hay may stimulate chewing more than chopped hay, and the preference for hay versus straw could be related to hedonic characteristics. No preference was found for chopped versus long straw (cp  = 20.8; P = 0.910). These results could be used to improve the welfare of calves in production systems; for example, in systems where calves are fed hay along with high energy concentrate, providing long hay instead of chopped could promote roughage intake, rumen development, and rumination. PMID:24558426

Chopped or long roughage: what do calves prefer? Using cross point analysis of double demand functions.

Directory of Open Access Journals (Sweden)

Laura E Webb

Full Text Available The present study aimed to quantify calves' (Bos taurus preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were trained to work for roughage rewards from two simultaneously available panels. The cost (number of muzzle presses required on the panels varied in each session (left panel/right panel: 7/35, 14/28, 21/21, 28/14, 35/7. Demand functions were estimated from the proportion of rewards achieved on one panel relative to the total number of rewards achieved in one session. Cross points (cp were calculated as the cost at which an equal number of rewards was achieved from both panels. The deviation of the cp from the midpoint (here 21 indicates the strength of the preference. Calves showed a preference for long versus chopped hay (cp = 14.5; P = 0.004, and for hay versus straw (cp = 38.9; P = 0.004, both of which improve rumen function. Long hay may stimulate chewing more than chopped hay, and the preference for hay versus straw could be related to hedonic characteristics. No preference was found for chopped versus long straw (cp = 20.8; P = 0.910. These results could be used to improve the welfare of calves in production systems; for example, in systems where calves are fed hay along with high energy concentrate, providing long hay instead of chopped could promote roughage intake, rumen development, and rumination.

Chopping and webbing control saw-palmetto in south Florida

Science.gov (United States)

Clifford E. Lewis

1972-01-01

Saw-palmetto is one of the more troublesome plants growing in south Florida, and its control is often desirable in programs of range and timber management. Both cross-chopping and webbing (root plowing) proved to be effective control measures, but webbing appeared to be less effective on a moist site. Many other shrubs were also effectively reduced by these treatments...

[Use of archival formalin-fixed, paraffin-embedded (FFPE) tissue samples for molecular genetic analysis in diffuse large B-cell lymphoma (DLBCL)].

Science.gov (United States)

Jarošová, Marie; Kučerová, Jana; Flodr, Patrik; Mikešová, Michaela; Procházka, Vít; Papajík, Tomáš

2014-04-01

The currently valid molecular genetic subclassification of patients with diffuse large B-cell lymphoma (DLBCL) into three prognostic subgroups based on expression profiling has been the objective of numerous genetic studies. In routine clinical practice, however, expression profiling technology remains unavailable for the most of centers. Apart from the technology, in some cases molecular genetic laboratories have problems obtaining high-quality material, i.e. fresh tissues, for RNA isolation to determine gene expression. One possibility is to determine the gene expression from RNA obtained by isolation from formalin-fixed, paraffin-embedded (FFPE) tissue. This pilot study aimed at isolating RNA from FFPE in patients diagnosed with DLBCL and verifying the potential use of such RNA for the expression analysis of 7 selected genes. Although the study showed that it is possible to isolate RNA and determine the expression of the selected genes from archival material, the values of relative expression of some genes in the set were too variable to be used for unambiguous prognostic classification. It was confirmed that retrospective analyses of selected genes may be performed with sufficient material obtained, and that properly archived blocks may be used for molecular biology analyses even after 8 years.

Comparison of gemcitabin, cisplatin, and dexamethasone (GDP), CHOP, and CHOPE in the first-line treatment of peripheral T-cell lymphomas.

Science.gov (United States)

Jia, Bo; Hu, Shaoxuan; Yang, Jianliang; Zhou, Shengyu; Liu, Peng; Qin, Yan; Gui, Lin; Yang, Sheng; Lin, Hua; Zhang, Changgong; Xing, Puyuan; Wang, Lin; Dong, Mei; Zhou, Liqiang; Sun, Yan; He, Xiaohui; Shi, Yuankai

2016-10-01

Optimal chemotherapy regimen for peripheral T-cell lymphomas (PTCL) has not been fully defined. This study aimed to evaluate the optimal chemotherapy regimen in the first-line treatment for PTCL patients. Between 2003 and 2014, 93 consecutive patients with PTCL were enrolled in this study. Of 93 patients, 42 patients received CHOPE, 40 patients with CHOP, and 11 patients with GDP regimen. Response could be evaluated in 88 of 93 patients at the end of primary treatment. The CR rate for patients received CHOP (n = 38), CHOPE (n = 39), and GDP (n = 11) were 28.9, 51.3, and 45.5%, respectively, (P = 0.132) with an ORR of 65.8, 76.9, and 90.9%, respectively, (P = 0.210). The median follow-up time was 17.1 (1.4-108.3) months. Median progression-free survival (PFS) in CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) groups were 6.0, 15.3, and 9.7 months (P = 0.094) with 1-year PFS of 35.0, 54.8, and 45.5%, respectively, (P = 0.078). One-year OS for patients received CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) were 65.0, 83.3, and 100%, respectively, (P = 0.013) (CHOP vs CHOPE, P = 0.030; CHOP vs GDP, P = 0.024; CHOPE vs GDP, P = 0.174). CHOPE has a trend to improve CR rate, 1-year PFS and OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies. Clinical experience presented in this study may serve as reference for future large cohort studies.

4-Phenylbutyrate inhibits tunicamycin-induced acute kidney injury via CHOP/GADD153 repression.

Directory of Open Access Journals (Sweden)

Rachel E Carlisle

Full Text Available Different forms of acute kidney injury (AKI have been associated with endoplasmic reticulum (ER stress; these include AKI caused by acetaminophen, antibiotics, cisplatin, and radiocontrast. Tunicamycin (TM is a nucleoside antibiotic known to induce ER stress and is a commonly used inducer of AKI. 4-phenylbutyrate (4-PBA is an FDA approved substance used in children who suffer from urea cycle disorders. 4-PBA acts as an ER stress inhibitor by aiding in protein folding at the molecular level and preventing misfolded protein aggregation. The main objective of this study was to determine if 4-PBA could protect from AKI induced by ER stress, as typified by the TM-model, and what mechanism(s of 4-PBA's action were responsible for protection. C57BL/6 mice were treated with saline, TM or TM plus 4-PBA. 4-PBA partially protected the anatomic segment most susceptible to damage, the outer medullary stripe, from TM-induced AKI. In vitro work showed that 4-PBA protected human proximal tubular cells from apoptosis and TM-induced CHOP expression, an ER stress inducible proapoptotic gene. Further, immunofluorescent staining in the animal model found similar protection by 4-PBA from CHOP nuclear translocation in the tubular epithelium of the medulla. This was accompanied by a reduction in apoptosis and GRP78 expression. CHOP(-/- mice were protected from TM-induced AKI. The protective effects of 4-PBA extended to the ultrastructural integrity of proximal tubule cells in the outer medulla. When taken together, these results indicate that 4-PBA acts as an ER stress inhibitor, to partially protect the kidney from TM-induced AKI through the repression of ER stress-induced CHOP expression.

Immunohistochemical Expression of CD-10, BCL-6 and MUM-1 Antibodies and Immediate Clinical Response in Patients of Diffuse Large B-Cell Lymphomas after Six Cycles of Chemotherapy

International Nuclear Information System (INIS)

Hassan, U.; Ishtiaq, S.; Hussain, M.

2014-01-01

Objective: To determine the expression of CD-10, BCL-6 and MUM-1 in patients with diffuse large B-cell lymphoma (DLBCL) and its association with immediate clinical response after six cycles of CHOP chemotherapy. Study Design: Analytical study. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Nuclear medicine, Oncology and Radiotherapy Institute (NORI), Islamabad from September 2010 to September 2011. Methodology: CD-10, BCL-6 and MUM-1 antibodies were applied on cases diagnosed as DLBCL. Immediate clinical response was noted after 6 cycles of chemotherapy with the help of oncologist and divided into complete response, partial response, stable disease and relapse/ progression. Patient's age, results of expression of CD-10, BCL-6 and MUM-1 and results of immediate clinical response to chemotherapy were noted. Regarding analysis of prognostic markers (CD-10, BCL-6 and MUM-1), chi-square test was used for immediate clinical response to chemotherapy in DLBCL. Results: CD-10 was positive in 40% cases, BCL-6 in 58.7% cases and MUM-1 was positive in 46.7% cases. About 41.3% of patients showed complete response, 10.6% partial response, 17.3% stable disease and 30.8% showed relapse/progression. CD-10 expression in DLBCL was associated with better immediate clinical response (p = 0.011) whereas MUM-1 expression in DLBCL was associated with poor immediate clinical response (p < 0.0001). However, there was no statistically significant association of BCL-6 with immediate clinical response (p = 0.22). Conclusion: DLBCL shows expression of CD-10, BCL-6 and MUM-1 in nearly fifty percent of the cases. CD-10 is associated with good whereas MUM is associated with poor response. However, there was no association of BCL-6 with immediate clinical response. (author)

Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

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A León-Suárez

2016-12-01

Full Text Available Non-Hodgkin lymphoma (NHL is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS. However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI. A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction.

Activating transcription factor 6 mediates oxidized LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating CHOP expression.

Science.gov (United States)

Yao, Shutong; Zong, Chuanlong; Zhang, Ying; Sang, Hui; Yang, Mingfeng; Jiao, Peng; Fang, Yongqi; Yang, Nana; Song, Guohua; Qin, Shucun

2013-01-01

This study was to explore whether activating transcription factor 6 (ATF6), an important sensor to endoplasmic reticulum (ER) stress, would mediate oxidized low-density lipoprotein (ox-LDL)- induced cholesterol accumulation and apoptosis in cultured macrophages and the underlying molecular mechanisms. Intracellular lipid droplets and total cholesterol levels were assayed by oil red O staining and enzymatic colorimetry, respectively. Cell viability and apoptosis were determined using MTT assay and AnnexinV-FITC apoptosis detection kit, respectively. The nuclear translocation of ATF6 in cells was detected by immunofluorescence analysis. Protein and mRNA levels were examined by Western blot analysis and real time-PCR, respectively. ATF6 siRNA was transfected to RAW264.7 cells by lipofectamin. Exposure of cells to ox-LDL induced glucose-regulated protein 78 (GRP78). C/EBP homologous protein (CHOP), a key-signaling component of ER stress-induced apoptosis, was up-regulated in ox-LDL-treated cells. ATF6, a factor that positively regulates CHOP expression, was activated by ox-LDL in a concentration- and time- dependent manner. The role of the ATF6-mediated ER stress pathway was further confirmed through the siRNA-mediated knockdown of ATF6, which attenuated ox-LDL-induced upregulation of CHOP, cholesterol accumulation and apoptosis in macrophages. In addition, the phosphorylation of double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK), another factor that positively regulates CHOP expression, was induced in the presence of ox-LDL, and PERK-specific siRNA also inhibited the ox-LDL-induced upregulation of CHOP and apoptosis in RAW264.7 cells. These results demonstrate that ER stress-related proteins, particularly ATF6 and its downstream molecule CHOP, are involved in ox-LDL-induced cholesterol accumulation and apoptosis in macrophages.

FUS-CHOP Promotes Invasion in Myxoid Liposarcoma through a SRC/FAK/RHO/ROCK-Dependent Pathway

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Juan Tornin

2018-01-01

Full Text Available Deregulated SRC/FAK signaling leads to enhanced migration and invasion in many types of tumors. In myxoid and round cell liposarcoma (MRCLS, an adipocytic tumor characterized by the expression of the fusion oncogene FUS-CHOP, SRC have been found as one of the most activated kinases. Here we used a cell-of-origin model of MRCLS and an MRCLS cell line to thoroughly characterize the mechanisms of cell invasion induced by FUS-CHOP using in vitro (3D spheroid invasion assays and in vivo (chicken chorioallantoic membrane model approaches. FUS-CHOP expression activated SRC-FAK signaling and increased the invasive ability of MRCLS cells. In addition, FAK expression was found to significantly correlate with tumor aggressiveness in sarcoma patient samples. The involvement of SRC/FAK activation in FUS-CHOP–mediated invasion was further confirmed using the SRC inhibitor dasatinib, the specific FAK inhibitor PF-573228, and FAK siRNA. Notably, dasatinib and PF573228 could also efficiently block the invasion of cancer stem cell subpopulations. Downstream of SRC/FAK signaling, we found that FUS-CHOP expression increases the levels of the RHO/ROCK downstream effector phospho-MLC2 (T18/S19 and that this activation was prevented by dasatinib or PF573228. Moreover, the ROCK inhibitor RKI-1447 was able to completely abolish invasion in FUS-CHOP–expressing cells. These data uncover the involvement of SRC/FAK/RHO/ROCK signaling axis in FUS-CHOP–mediated invasion, thus providing a rationale for testing inhibitors of this pathway as potential novel antimetastatic agents for MRCLS treatment.

Fludarabine-based versus CHOP-like regimens with or without rituximab in patients with previously untreated indolent lymphoma: a retrospective analysis of safety and efficacy

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Xu XX

2013-10-01

Full Text Available Xiao-xiao Xu,1 Bei Yan,2 Zhen-xing Wang,3 Yong Yu,1 Xiao-xiong Wu,2 Yi-zhuo Zhang11Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, 2Department of Hematology, First Affiliated Hospital of Chinese People's Liberation Army General Hospital, Beijing, 3Department of Stomach Oncology, TianJin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of ChinaAbstract: Fludarabine-based regimens and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone-like regimens with or without rituximab are the most common treatment modalities for indolent lymphoma. However, there is no clear evidence to date about which chemotherapy regimen should be the proper initial treatment of indolent lymphoma. More recently, the use of fludarabine has raised concerns due to its high number of toxicities, especially hematological toxicity and infectious complications. The present study aimed to retrospectively evaluate both the efficacy and the potential toxicities of the two main regimens (fludarabine-based and CHOP-like regimens in patients with previously untreated indolent lymphoma. Among a total of 107 patients assessed, 54 patients received fludarabine-based regimens (FLU arm and 53 received CHOP or CHOPE (doxorubicin, cyclophosphamide, vincristine, prednisone, or plus etoposide regimens (CHOP arm. The results demonstrated that fludarabine-based regimens could induce significantly improved progression-free survival (PFS compared with CHOP-like regimens. However, the FLU arm showed overall survival, complete response, and overall response rates similar to those of the CHOP arm. Grade 3–4 neutropenia occurred in 42.6% of the FLU arm and 7.5% of the CHOP arm (P 60 years and presentation of grade 3–4 myelosuppression were the independent factors to infection, and the FLU arm had significantly

Mars Science Laboratory Launch-Arrival Space Study: A Pork Chop Plot Analysis

Science.gov (United States)

Cianciolo, Alicia Dwyer; Powell, Richard; Lockwood, Mary Kae

2006-01-01

Launch-Arrival, or "pork chop", plot analysis can provide mission designers with valuable information and insight into a specific launch and arrival space selected for a mission. The study begins with the array of entry states for each pair of selected Earth launch and Mars arrival dates, and nominal entry, descent and landing trajectories are simulated for each pair. Parameters of interest, such as maximum heat rate, are plotted in launch-arrival space. The plots help to quickly identify launch and arrival regions that are not feasible under current constraints or technology and also provide information as to what technologies may need to be developed to reach a desired region. This paper provides a discussion of the development, application, and results of a pork chop plot analysis to the Mars Science Laboratory mission. This technique is easily applicable to other missions at Mars and other destinations.

Effect of the type of frying culinary fat on volatile compounds isolated in fried pork loin chops by using SPME-GC-MS.

Science.gov (United States)

Ramírez, María Rosario; Estévez, Mario; Morcuende, David; Cava, Ramón

2004-12-15

The effect of the type of frying culinary fat (olive oil, sunflower oil, butter, and pig lard) on volatile compounds isolated from fried pork loin chops (m. Longissimus dorsi) was measured by SPME-GC-MS. Frying modified the fatty acid composition of lipids from pork loin chops, which tended to be similar to that of the culinary fat used to fry. Volatile compounds formed from the oxidation of fatty acids increased, such as aldehydes, ketones, alcohols, and hydrocarbons. Besides, each culinary fat used modified the volatile profiles in fried meat differently. Sunflower oil-fried pork loin chops presented the highest aldehyde aliphatic content, probably due to their highest content of polyunsaturated acids. Hexanal, the most abundant aldehyde in fried samples, presented the most elevated content in sunflower oil-fried pork loin chops. In addition, these samples presented more heterocyclic compounds from the Maillard reaction than other fried samples. Volatiles detected in olive oil-fried pork loin chops were mainly lipid-derived compounds such as pentan-1-ol, hexanal, hept-2-enal, nonanal, decanal, benzaldehyde, and nonan-2-one. Butter-fried pork loins were abundant in ketones with a high number of carbons (heptan-2-one, nonan-2-one, undecan-2-one, tridecanone, and heptadecan-2-one). Pig lard-fried pork loin chops presented some Strecker aldehydes isolated in only these samples, such as 2-methylbutanal and 3-(methylthio)propanal, and a sulfur compound (dimethyl disulfide) related to Strecker aldehydes.

Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma : Systematic review and meta-analysis

NARCIS (Netherlands)

Adams, Hugo J A; Kwee, Thomas C.

2016-01-01

This study aimed to systematically review and meta-analyze the prognostic value of interim 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone

Mechanical and abrasive wear characterization of bidirectional and chopped E-glass fiber reinforced composite materials

International Nuclear Information System (INIS)

Siddhartha,; Gupta, Kuldeep

2012-01-01

Highlights: ► Bi-directional and chopped E-glass fiber reinforced epoxy composites are fabricated. ► Three body abrasive wear behavior of fabricated composites has been assessed. ► Results are validated against existing microscopic models of Lancaster and Wang. ► Tensile strength of bi-directional E-glass fiber reinforced composites increases. ► Chopped glass fiber composites are found better in abrasive wear situations. -- Abstract: Bi-directional and chopped E-glass fiber reinforced epoxy composites are fabricated in five different (15, 20, 25, 30 and 35) wt% in an epoxy resin matrix. The mechanical characterization of these composites is performed. The three body abrasive wear behavior of fabricated composites has been assessed under different operating conditions. Abrasive wear characteristics of these composites are successfully analysed using Taguchi’s experimental design scheme and analysis of variance (ANOVA). The results obtained from these experiments are also validated against existing microscopic models of Ratner-Lancaster and Wang. It is observed that quite good linear relationships is held between specific wear rate and reciprocal of ultimate strength and strain at tensile fracture of these composites which is an indicative that the experimental results are in fair agreement with these existing models. Out of all composites fabricated it is found that tensile strength of bi-directional E-glass fiber reinforced composites increases because of interface strength enhancement. Chopped glass fiber reinforced composites are observed to perform better than bi-directional glass fiber reinforced composites under abrasive wear situations. The morphology of worn composite specimens has been examined by scanning electron microscopy (SEM) to understand about dominant wear mechanisms.

Effects of chopping time, meat source and storage temperature on the colour of New Zealand type fresh beef sausages.

Science.gov (United States)

Boles, J A; Mikkelsen, V L; Swan, J E

1998-05-01

The colour stability of finely chopped fresh sausages made from post-rigor, pre-rigor salt added (1.5% w/w) or pre-rigor no salt added beef mince was evaluated using a Hunter Miniscan (L (∗) a (∗) b (∗)) and sensory colour panel. Batters were chopped for various times and sausages stored at -1.5 °, + 4.0 ° and + 8.0 °C. Regardless of meat source or chopping time, colour stability was greatest at -1.5 °C. Panellists found the colour of all sausages stored at -1.5 °C acceptable for at least six days. Sausages made from unsalted pre-rigor mince had markedly better colour stability than those made from the other meats, especially when stored at 4 °C or 8 °C.

Analysis of the first CHOPS pilot for heavy oil production in Kuwait

Energy Technology Data Exchange (ETDEWEB)

Sanyal, Tirtharenu; Al-Sammak, Ibrahim [Kuwait Oil Company (Kuwait)

2011-07-01

Cold heavy oil production with sand (CHOPS) is a technique for extracting difficult heavy crude oil by simply pumping it out of the sands, often using progressive cavity pumps. This technique was tested in a pilot heavy oil production project at one of the fields in Kuwait. The pilot performance of three wells is presented in this paper as is an analysis of the pilot results, which provide important clues for understanding the reservoir description issues as well as sand production characteristics. This process found an intimate relationship between rock mechanics and the fluid viscosity and flow potential of the formation. The wells seemed to develop an enlarged well bore around them, giving a high negative skin factor. Moreover, the lower viscosity of the oil and absence of any strong directional geomechanical trend could be possible reasons for the absence of wormhole development, which has often been observed in other CHOPS operations. The initial burst of sand production needs to be addressed by optimizing the perforation policy.

Extremely decreased release of prostaglandin E-like activity from chopped lung of ethyl linolenate-supplemented rats

DEFF Research Database (Denmark)

Hansen, Harald S.; Jensen, B.; Fjalland, B.

1983-01-01

Three groups of weanling male rats were reared on a fat-free diet for 13 weeks. One group received only the fat-free diet (FF rats), the other 2 groups received the fat-free diet and a daily supplement of 2 energy% ethyl linoleate ([n-6] rats), or 2 energy% ethyl linolenate ([n-3] rats). The chop......). The chopped lung preparation was used to illustrate an in vitro prostaglandin formation. PGE-like activity was quantified on rat stomach strip. The release of PGE-like activity expressed as ng PGE-equivalent per g lung tissue (mean±SD) was 23±7,...

study on the chopping and mixing of cotton stalks with soil | Sa glam ...

African Journals Online (AJOL)

-type, splined-type and vertical-blade rotating dredge). Field experiments were conducted with each type to determine the proportion of non-uprooted cotton stalks; mean “post-chopping height” of the stalks, measured from soil surface; and the ...

Validation of the Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) Model.

Science.gov (United States)

Binenbaum, Gil; Ying, Gui-Shuang; Tomlinson, Lauren A

2017-08-01

The Children's Hospital of Philadelphia Retinopathy of Prematurity (CHOP ROP) model uses birth weight (BW), gestational age at birth (GA), and weight gain rate to predict the risk of severe retinopathy of prematurity (ROP). In a model development study, it predicted all infants requiring treatment, while greatly reducing the number of examinations compared with current screening guidelines. To validate the CHOP ROP model in a multicenter cohort that is large enough to obtain a precise estimate of the model's sensitivity for treatment-requiring ROP. This investigation was a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study. The setting was 30 hospitals in the United States and Canada between January 1, 2006, and June 30, 2012. The dates of analysis were September 28 to October 5, 2015. Participants were premature infants at risk for ROP with a known ROP outcome. Sensitivity for Early Treatment of Retinopathy of Prematurity type 1 ROP and potential reduction in the number of infants requiring examinations. In the primary analysis, the CHOP ROP model was applied weekly to predict the risk of ROP. If the risk was above a cut-point level (high risk), examinations were indicated, while low-risk infants received no examinations. In a secondary analysis, low-risk infants received fewer examinations rather than no examinations. Participants included 7483 premature infants at risk for ROP with a known ROP outcome. Their median BW was 1070 g (range, 310-3000 g), and their median GA was 28 weeks (range, 22-35 weeks). Among them, 3575 (47.8%) were female, and their race/ethnicity was 3615 white (48.3%), 2310 black (30.9%), 233 Asian (3.1%), 93 Pacific Islander (1.2%), and 40 American Indian/Alaskan native (0.5%). The original CHOP ROP model correctly predicted 452 of 459 infants who developed type 1 ROP (sensitivity, 98.5%; 95% CI, 96.9%-99.3%), reducing the number of infants requiring examinations by 34.3% if only high

Processing of chopped mussel meat in retort pouch

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Giustino TRIBUZI

2015-01-01

Full Text Available Abstract Chopped mussel meat packaged in retort pouches was processed in a laboratory-scale water immersion retort, adapted for processing under overpressure conditions. Retort temperature effects on product yield and on cook value were evaluated by setting the F0 at 7 min. The effects of different pre-treatments (salting and marination on the characteristics of mussels were evaluated after processing at retort temperature of 118 °C and during a whole year of storage at 25 °C. The salted samples showed better yield during storage, while no differences were found for the other physicochemical parameters.

Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy.

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Fournier, Q; Serra, J-C; Handel, I; Lawrence, J

2018-01-01

Prechemotherapy absolute neutrophil count (ANC) cutoffs are arbitrary and vary across institutions and clinicians. Similarly, subjective guidelines are utilized for the administration of prophylactic antibiotics in neutropenic dogs. To evaluate the impact of various ANC cutoffs on chemotherapy administration in dogs with lymphoma treated with CHOP chemotherapy and to determine whether an association between prechemotherapy ANC and subsequent toxicity exists. The secondary objective was to evaluate a currently used ANC cutoff to indicate prescription of prophylactic antibiotics. Dogs diagnosed with lymphoma treated with CHOP chemotherapy (n = 64). Six hundred and fifteen ANCs were stratified into 6 classes. The 3 ANC cutoffs 1.5 × 10 3 /μL, 2.0 × 10 3 /μL, and 2.5 × 10 3 /μL were assessed. The presence of an association between prechemotherapy ANC class and toxicity was determined. Afebrile neutropenic dogs with ANC ANC cutoff of 1.5 × 10 3 /μL; chemotherapy would not have been administered in 10% and 16% of visits with an ANC cutoff of 2.0 × 10 3 /μL or 2.5 × 10 3 /μL, respectively. There was no association among the 3 lower prechemotherapy ANC classes and toxicity. All dogs with ANC 0.75-1.5 × 10 3 /μL recovered spontaneously without medical intervention. The number of dose delays was minimized with a prechemotherapy ANC cutoff of 1.5 × 10 3 /μL, and the prechemotherapy ANC class 1.5-1.99 × 10 3 /μL was not associated with an increased toxicity. Further investigation of an ANC cutoff near 0.75 × 10 3 /μL in which to prescribe prophylactic antibiotics is indicated. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effect of Different Tumbling Marination Methods and Time on the Water Status and Protein Properties of Prepared Pork Chops

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Tian Gao

2015-07-01

Full Text Available The combined effect of tumbling marination methods (vacuum continuous tumbling marination, CT; vacuum intermittent tumbling marination, IT and effective tumbling time (4, 6, 8, and 10 h on the water status and protein properties of prepared pork chops was investigated. Results showed that regardless of tumbling time, CT method significantly decreased the muscle fiber diameter (MD and significantly increased the total moisture content, product yield, salt soluble proteins (SSP solubility, immobilized water component (p<0.05 compared with IT method. With the effective tumbling time increased from 4 h to 10 h, the fat content and the MD were significantly decreased (p<0.05, whereas the SSP solubility of prepared pork chops increased firstly and then decreased. Besides, an interactive effect between CT method and effective tumbling time was also observed for the chemical composition and proportion of immobilized water (p<0.05. These results demonstrated that CT method of 8 h was the most beneficial for improving the muscle structure and water distribution status, increasing the water-binding capacity and accelerating the marinade efficiency of pork chops; and thus, it should be chosen as the most optimal treatment method for the processing production of prepared pork chops.

EBV-positive immunodeficiency lymphoma after alemtuzumab-CHOP therapy for peripheral T-cell lymphoma

NARCIS (Netherlands)

Kluin-Nelemans, Hanneke C.; Coenen, Jules L.; Boers, James E.; van Imhoff, Gustaaf W.; Rosati, Stefano

2008-01-01

Chemotherapy with alemtuzumab and the combination of cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP) has become experimental trial therapy for aggressive T-cell lymphoma. Several multicenter phase 3 trials; will incorporate this scheme. As part of an ongoing phase 2 trial in which we

A Comparative study of two RVE modelling methods for chopped carbon fiber SMC

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Chen, Zhangxing; Li, Yi; Shao, Yimin; Huang, Tianyu; Xu, Hongyi; Li, Yang; Chen, Wei; Zeng, Danielle; Avery, Katherine; Kang, HongTae; Su, Xuming

2017-04-06

To achieve vehicle light-weighting, the chopped carbon fiber sheet molding compound (SMC) is identified as a promising material to replace metals. However, there are no effective tools and methods to predict the mechanical property of the chopped carbon fiber SMC due to the high complexity in microstructure features and the anisotropic properties. In this paper, the Representative Volume Element (RVE) approach is used to model the SMC microstructure. Two modeling methods, the Voronoi diagram-based method and the chip packing method, are developed for material RVE property prediction. The two methods are compared in terms of the predicted elastic modulus and the predicted results are validated using the Digital Image Correlation (DIC) tensile test results. Furthermore, the advantages and shortcomings of these two methods are discussed in terms of the required input information and the convenience of use in the integrated processing-microstructure-property analysis.

Resultados de la técnica stop and chop en la facoemulsificación Results of stop and chop technique in phacoemulsification

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Juan Raúl Hernández Silva

2010-06-01

Full Text Available OBJETIVOS: Describir los resultados morfofuncionales alcanzados con la técnica stop and chop en la cirugía de catarata por facoemulsificación (faco, en el Centro de Microcirugía Ocular del Instituto Cubano de Oftalmología "Ramón Pando Ferrer" entre Junio de 2006 y Marzo de 2009. MÉTODOS: Se realizó un estudio descriptivo, transversal en el cual el universo y la muestra del trabajo lo constituyeron todos los pacientes con diagnóstico de catarata presenil y senil, quienes cumplían con los criterios de selección y aceptaron someterse a la técnica quirúrgica señalada, lo cual correspondió a 201 ojos operados. Estos datos se analizaron a través de tablas de contingencia con frecuencias absolutas y relativas; además se emplearon medias con el uso del programa de procesamiento de datos SPSS versión 11.1, donde se aplicó la prueba t de student para su comparación. RESULTADOS: Se encontró que la catarata predominó en mayores de 70 años en el 33,4 % de los pacientes. La mejor agudeza visual con corrección obtenida se incrementó hasta siete líneas en la escala de Snellen en el 93,0 % de los casos; el cilindro refractivo apenas se modificó en 0,15 dioptrías; la pérdida de células endoteliales fue de 8,2 % y las complicaciones operatorias fueron de 1,5 %. CONCLUSIONES: La edad de los pacientes sometidos a cirugía de catarata por la técnica de stop and chop fue en su mayoría de más de 70 años. La MAVC posoperatoria ganó hasta siete líneas en la escala de Snellen; el astigmatismo que se indujo en la cirugía fue menor de media dioptría; la pérdida celular y las complicaciones posoperatorias no fueron significativas.OBJECTIVES: To describe the morphofunctional results of the stop and chop technique in cataract surgery in phacoemulsification at the Eye Microsurgery Center of "Ramón Pando Ferrer" Cuban Institute of Ophthalmology from June 2006 to March 2009. METHODS: A cross-sectional descriptive study was conducted. The

Rituximab and chemotherapy in diffuse large B-cell lymphoma.

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Sonet, Anne; Bosly, André

2009-06-01

Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell Non-Hodgkin’s Lymphoma: Results of the FAB/LMB 96 international study

Science.gov (United States)

Poirel, HA; Cairo, MS; Heerema, NA; Swansbury, J; Aupérin, A; Launay, E; Sanger, WG; Talley, P; Perkins, SL; Raphaël, M; McCarthy, K; Sposto, R; Gerrard, M; Bernheim, A; Patte, C

2010-01-01

Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event free survival (EFS) in pediatric mature B-NHL treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt Lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature-B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24 associated chromosomal aberrations were +1q [29%], +7q and del(13q) [14% each]. The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 [34%] was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS [HR: 6.1 (p=0.030), 2.5 (p=0.015), 4.0 (p=0.0003), respectively]. The adverse prognosis of R8q24 was observed only in DLBCL while del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk adapted therapy in childhood mature-B-NHL. PMID:19020548

Straight and chopped DC performance data for a reliance EV-250AT motor with a General Electric EV-1 controller

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Edie, P. C.

1981-01-01

Straight and chopped DC motor performances for a Reliance EV-250AT motor with an EV-1 controller were examined. Effects of motor temperature and operating voltage are shown. It is found that the maximum motor efficiency is approximately 85% at low operating temperatures in the straight DC mode. Chopper efficiency is 95% under all operating conditions. For equal speeds, the motor operated in the chopped mode develops slightly more torque and draws more current than it does in the straight DC mode.

Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type: 13-year follow-up in 135 patients.

Science.gov (United States)

Wang, Liang; Xia, Zhong-jun; Huang, Hui-qiang; Lu, Yue; Zhang, Yu-jing

2012-11-01

We conducted a retrospective study of 135 patients of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction chemotherapy to find some valuable prognostic factors and analyze the usefulness of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in predicting prognosis. Most of the patients were in the low-risk group (IPI score 0-1). Complete remission (CR) after induction chemotherapy was achieved in 31.8 % of the patients, which increased to 69.6 % after radiotherapy. The 2-, 5-, and 10-year overall survival (OS) rates were 60, 48, and 43 %, respectively. Patients with better performance status (ECOG 0-1), normal serum LDH level, without local invasiveness, low KPI scores, and IPI score of 0 had significantly better overall survival (P KPI score systems should be improved further to classify patients into different groups, and should be validated in larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL, CHOP is no longer the state of art and novel drugs should be incorporated into future treatments.

Durability-Based Design Criteria for a Chopped-Glass-Fiber Automotive Structural Composite; TOPICAL

International Nuclear Information System (INIS)

Battiste, R.L.; Corum, J.M.; Ren, W.; Ruggles, M.B.

1999-01-01

This report provides recommended durability-based design criteria for a chopped-glass-fiber reinforced polymeric composite for automotive structural applications. The criteria closely follow the framework of an earlier criteria document for a continuous-strand-mat (CSM) glass-fiber reference composite. Together these design criteria demonstrate a framework that can be adapted for future random-glass-fiber composites for automotive structural applications

Consumer choice of pork chops in Taiwan.

Science.gov (United States)

Chen, M T; Guo, H L; Tseng, T F; Roan, S W; Ngapo, T M

2010-07-01

Digital photographs of pork chops varying systematically in appearance were presented to 716 Taiwanese consumers in a study that aimed to identify the most important characteristics of fresh pork which determine consumer choice in Taiwan. Relationships between consumer segmentation in choice and socio-demographic and cultural differences were also investigated. Colour and fat cover were the most frequently chosen of the four characteristics studied. Dark red colour was preferred by 64% of consumers and lean fat cover by 44%. Marbling and drip were less important in the decision making process being used by less than a half of consumers. The four preference-based clusters of consumers showed no correlation with socio-demographic-based consumer clusters, but did show significant links with possession of a refrigerator, age at which schooling was completed, liking pork for its price and gender of consumer. Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.

CHOP THERAPY INDUCED MITOCHONDRIAL REDOX STATE ALTERATION IN NON-HODGKIN'S LYMPHOMA XENOGRAFTS

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H. N. XU

2013-04-01

Full Text Available We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and survival. The redox state can be imaged by the redox scanner that collects the fluorescence signals from both the oxidized-flavoproteins (Fp and the reduced form of nicotinamide adenine dinucleotide (NADH in snap-frozen tissues and has been previously employed to study tumor aggressiveness and treatment responses. Here, with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large B-cell lymphoma cell line (DLCL2. The mice were treated with CHOP therapy, i.e., cyclophosphamide (C + hydroxydoxorubicin (H + Oncovin (O + prednisone (P with CHO administration on day 1 and prednisone administration on days 1–5. The Fp content of the treated group was significantly decreased (p = 0.033 on day 5, and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group (p = 0.048. The decrease of the Fp heterogeneity (measured by the mean standard deviation had a border-line statistical significance (p = 0.071. The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOP therapy.

Efficacy on chopping with lens loop-pad in the small incision extracapsular cataract surgery with intraocular lens implantation

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Xiao-Ning Peng

2014-04-01

Full Text Available AIM: To study the clinical effects of chopping with lens loop-pad in the small incision extracapsular cataract surgery with intraocular lens implantation.METHODS:A total of 75 cases(80 eyes, in which loop-pad and chop knife were performed to chop nucleus before implanting intraocular lens. Visual acuity, postoperative astigmatism degree, intraoperative and postoperative complications were observed. The post-operative follow-up periods ranged from 3 to 12mo.RESULTS: The visual acuity was 0.3-0.5 in 37 eyes and 0.6 or better in 21 eyes at 1d, while was respectively in 43 eyes and in 26 eyes at 1mo. Compared with preoperative astigmatism(0.85±0.29D, there were significant difference at postoperative 1wk(1.75±0.55D(PP>0.05. Intraoperative posterior capsule rupture occurred in 4 eyes, which implantation was successful in 1 eye and 3 eyes was managed viaciliary sulcus. Two eyes had dermatoglyphic pattern edema in corneal endothelium which recovered after about 3d. Two eyes had local patchy opacities which recovered in 2wk. Two eyes had transient high intraocular pressure.CONCLUSION: The surgery is efficient, low cost, easy process and less complications, it is worth to be popularized.

Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression

International Nuclear Information System (INIS)

Li Xi; Huang Haiyan; Chen Jiegen; Jiang Lin; Liu Honglei; Liu Deguo; Song Tanjing; He Qun; Ma Chungu; Ma Duan; Song Houyan; Tang Qiqun

2006-01-01

Hormonal induction triggers a cascade leading to the expression of CCAAT/enhancer-binding protein(C/EBP)α and peroxisome proliferator-activated receptor (PPAR) γ, C/EBPα, and PPARγ turns on series of adipocyte genes that give rise to the adipocyte phenotype. Previous findings indicate that C/EBPβ, a transcriptional activator of the C/EBPα and PPARγ genes, is rapidly expressed after induction, but lacks DNA-binding activity and therefore cannot activate transcription of the C/EBPα and PPARγ genes early in the differentiation program. Acquisition of DNA-binding activity of C/EBPβ occurs when CHOP-10, a dominant-negative form of C/EBP family members, is down-regulated and becomes hyperphosphorylated as preadipocytes traverse the G 1 -S checkpoint of mitotic clonal expansion. Evidences are presented in this report that lactacystin, a proteasome inhibitor, up-regulated the CHOP-10 expression, blocked the DNA-binding activity of C/EBPβ, and subsequently inhibited MCE as well as adipocyte differentiation

The antimicrobial effects of chopped garlic in ground beef and raw meatball (ciğ köfte).

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Aydin, Ali; Bostan, Kamil; Erkan, Mehmet Emin; Bingöl, Bariş

2007-03-01

This study was carried out to investigate the antimicrobial effects of chopped garlic in ground beef and raw meatball (çig köfte), which is a traditional food product eaten raw. Fresh minced ground beef and raw meatball batter prepared with traditional methods were separated into groups. Chopped and crushed garlic was added to each batch in order to reach various concentrations from 0% to 10%. The ground beef samples were stored at refrigerator and ambient temperatures. The raw meatball samples were only stored at room temperature. All samples were analyzed in order to determine the microbial counts at the 2(nd), 6(th), 12(th), and 24(th) hours of storage. Garlic addition decreased the microbial growth in some ground beef samples kept either at room temperature or in the refrigerator. However, microbial growth increased in some ground beef samples kept in similar conditions. The difference was found in samples kept in the refrigerator for 24 hours in terms of total aerobic mesophilic bacteria and coliform bacteria when garlic used at 10%. The effects of garlic on the microbial growth of both coliforms and Staphylococcus/Micrococcus in the samples kept at room temperature were increased. The yeast and mold counts in ground beef samples kept in any condition were not affected by garlic addition. However, the addition of garlic to the raw meatball mix decreased the microbial count, in terms of total aerobic mesophilic bacteria and yeast and mold counts, when the garlic was added at 5% or 10% (P meatball caused a permanent decrease in yeast and mold count, unlike in ground beef. The results of this study indicate that the chopped garlic has a slowing-down effect on microbiological growth in ground meat depending on the garlic concentration, but this effect was not at an expected level even at the highest concentration, because potential antimicrobial agents in chopped garlic were probably insufficiently extracted.

9 CFR 319.311 - Chow mein vegetables with meat, and chop suey vegetables with meat.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chow mein vegetables with meat, and chop suey vegetables with meat. 319.311 Section 319.311 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY...

Standardized uptake value for (18)F-fluorodeoxyglucose is correlated with a high International Prognostic Index and the presence of extranodal involvement in patients with diffuse large B-cell lymphoma.

Science.gov (United States)

Akkas, B E; Vural, G U

2014-01-01

The aim of this study was to evaluate whether the maximum standardized uptake value (SUVmax) of (18)F-fluorodeoxyglucose (FDG) correlates with the International Prognostic Index (IPI) and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma (DLBCL). 77 patients (age: 57.2±18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for initial staging were included. SUVmax of the predominant lesions were compared to Ann Arbor stage, IPI scores, the presence of extranodal involvement and the number extranodal sites. PET/CT detected nodal (n:25) and extranodal involvement (n:52) in all the patients. In 27 patients, extranodal disease could only be detected by PET. SUVmax of the predominant lesion in patients with extranodal disease was significantly higher than that of the patients who had only nodal disease (25±12 vs. 15.3±10 respectively, p=0.001). SUVmax significantly correlated with IPI scores; the average SUVmax was significantly correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9±9.5 in patients with low risk (IPI=0-1), 14.2±8.8 in low-intermediate risk group (IPI=2) whereas 26.6±9.5 in high-intermediate risk group (IPI=3) and 25±13.6 in high risk group patients (IPI=4-5) (p=0.002). SUVmax was not correlated with clinical stage, the number of extranodal sites and serum LDH levels. FDG uptake correlates with IPI and the presence of extranodal involvement in DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The correlation of SUVmax with these prognostic factors may highlight the importance of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients with DLBCL. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

DEFF Research Database (Denmark)

Xu-Monette, Zijun Y; Dabaja, Bouthaina S; Wang, Xiaoxiao

2015-01-01

MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about...

Diffraction, chopping, and background subtraction for LDR

Science.gov (United States)

Wright, Edward L.

1988-01-01

The Large Deployable Reflector (LDR) will be an extremely sensitive infrared telescope if the noise due to the photons in the large thermal background is the only limiting factor. For observations with a 3 arcsec aperture in a broadband at 100 micrometers, a 20-meter LDR will emit 10(exp 12) per second, while the photon noise limited sensitivity in a deep survey observation will be 3,000 photons per second. Thus the background subtraction has to work at the 1 part per billion level. Very small amounts of scattered or diffracted energy can be significant if they are modulated by the chopper. The results are presented for 1-D and 2-D diffraction calculations for the lightweight, low-cost LDR concept that uses an active chopping quaternary to correct the wavefront errors introduced by the primary. Fourier transforms were used to evaluate the diffraction of 1 mm waves through this system. Unbalanced signals due to dust and thermal gradients were also studied.

Prognostic value of negative interim 2-["1"8F]-fluoro-2-deoxy-D-glucose PET/CT in diffuse large B-cell lymphoma

International Nuclear Information System (INIS)

Kwon, S.H.; Kang, D.R.; Kim, J.; Yoon, J.-K.; Lee, S.J.; Jeong, S.H.; Lee, H.W.; An, Y.-S.

2016-01-01

Aim: To assess the prognostic value of negative interim combined 2-["1"8F]-fluoro-2-deoxy-D-glucose ("1"8F-FDG) positron-emission tomography/computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods: Ninety-two patients with histologically proven DLBCL were enrolled. All of the patients underwent "1"8F-FDG PET/CT at diagnosis, and interim PET/CT after the second cycle of chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R-CHOP). Negative interim PET/CT was defined as the disappearance of all abnormal "1"8F-FDG uptake compared to the pretreatment PET/CT image, as determined by visual assessment. The clinical outcome of patients was estimated as progression-free survival (PFS), and the prognostic significance of clinicopathological and imaging parameters were assessed using the Cox proportional hazards model. Results: Thirty-six patients (39.1%) showed lymphoma progression within a median follow-up of 30.8 months. According to univariate analysis, Ann Arbor stage, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group scale, International Prognostic Index (IPI) score, and maximum standardised uptake values on initial PET/CT were significant prognostic factors for PFS (all p<0.05). Among these parameters, only the IPI score was an independent predictor for PFS (p=0.044). Survival of patients with a high IPI score (≥3) was poorer than those with a low IPI score (0–2; p<0.001). Conclusion: Despite a negative interim "1"8F-FDG PET/CT, approximately 39% of DLBCL patients showed progression during follow-up. Although the negative PET/CT was obtained during chemotherapy, it is important to closely follow-up patients, especially those with a high IPI score. - Highlights: • About 39% of patients showed progression after negative interim PET/CT. • The IPI score was an independent predictor for PFS. • It is important to closely follow-up with high IPI score

Application of the gravimetric method to closing the material balance around the chop-leach cell of a spent-fuel reprocessing plant

International Nuclear Information System (INIS)

Fishbone, L.G.

1985-01-01

For a spent-fuel reprocessing plant handling commercial light-water-reactor fuel, plutonium accounting is traditionally done for the material balance area (MBA) extending from the input accountability tank to the product accountability tank - the process MBA. Consider an MBA comprising the chop-leach cell, with an inward flow consisting of the intact spent-fuel assemblies and outward flows consisting of leached hulls and dissolver solution. Given knowledge of the original uranium mass in the fuel and a measurement of the uranium-plutonium concentration ratio in the dissolver solution, the gravimetric method can be used to determine the amount of plutonium in the spent-fuel assemblies. A measurement of residual plutonium in the leached hulls would then permit the determination of a plutonium material balance for the chop-leach cell alone, since the volumetrically determined plutonium in the input accountability tank yields the plutonium in the flow leaving the chop-leach cell for the process MBA. The uncertainty in the balance can be estimated given the individual measurement uncertainties

Mechanical characterization of glass fiber (woven roving/chopped strand mat E-glass fiber) reinforced polyester composites

Science.gov (United States)

Bhaskar, V. Vijaya; Srinivas, Kolla

2017-07-01

Polymer reinforced composites have been replacing most of the engineering material and their applications become more and more day by day. Polymer composites have been analyzing from past thirty five years for their betterment for adapting more applications. This paper aims at the mechanical properties of polyester reinforced with glass fiber composites. The glass fiber is reinforced with polyester in two forms viz Woven Rovings (WRG) and Chopped Strand Mat (CSMG) E-glass fibers. The composites are fabricated by hand lay-up technique and the composites are cut as per ASTM Standard sizes for corresponding tests like flexural, compression and impact tests, so that flexural strength, compression strength, impact strength and inter laminar shear stress(ILSS) of polymer matrix composites are analyzed. From the tests and further calculations, the polyester composites reinforced with Chopped Strand Mat glass fiber have shown better performance against flexural load, compression load and impact load than that of Woven Roving glass fiber.

Determination of salt content in various depth of pork chop by electrical impedance spectroscopy

International Nuclear Information System (INIS)

Kaltenecker, P; Szöllösi, D; Vozáry, E; Friedrich, L

2013-01-01

The salt concentration was determined inside of pork chop both by electrical impedance spectroscopy and by a conventional chemical method (according to Mohr). The pork chop in various depths (4 mm, 10 mm, 20 mm and 25 mm) was punctured with two stainless steel electrodes. The length of electrodes was 60 mm, and they were insulated along the length except 1 cm section on the end, so the measurement of impedance was realized in various depths. The magnitude and phase angle of impedance were measured with a HP 4284A and a HP 4285A LCR meters from 30 Hz up to 1 MHz and from 75 kHz up to 30 MHz frequency range, respectively at 1 V voltage. The distance between the electrodes was 1 cm. The impedance magnitude decreased as the salt concentration increased. The magnitude of open-short corrected impedance values at various frequencies (10 kHz, 100 kHz, 125 kHz, 1.1 MHz and 8 MHz) showed a good correlation with salt content determined by chemical procedure. The electrical impedance spectroscopy seems a prospective method for determination the salt concentration inside the meat in various depths during the curing procedure.

Chopped or long roughage: what do calves prefer? Using cross point analysis of double demand functions

NARCIS (Netherlands)

Webb, L.E.; Bak Jensen, M.; Engel, B.; Reenen, van C.G.; Gerrits, W.J.J.; Boer, de I.J.M.; Bokkers, E.A.M.

2014-01-01

The present study aimed to quantify calves'(Bos taurus) preference for long versus chopped hay and straw, and hay versus straw, using cross point analysis of double demand functions, in a context where energy intake was not a limiting factor. Nine calves, fed milk replacer and concentrate, were

The effect of metformin treatment on endoplasmic reticulum (ER stress induced by status epilepticus (SE via the PERK-eIF2α-CHOP pathway

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Jing Chen

2018-02-01

Full Text Available Status epilepticus (SE is defined as continuous seizure activity lasting more than 5 minutes. It results in neuronal cell death, mediated by endoplasmic reticulum (ER stress response. Previously, metformin demonstrated neuroprotective effects in primary cortical neurons. In this study, we analyzed the effect of metformin on ER stress via the pro-apoptotic protein kinase RNA-like endoplasmic reticulum kinase (PERK-eukaryotic initiation factor 2α (eIF2α-C/EBP homologous protein (CHOP pathway. SE was induced in rats by pentylenetetrazole. Following SE, the rats were treated with salubrinal, GSK2656157, or metformin. In a control group (normal saline SE was not induced. CHOP, eIF2α, and PERK expression was determined by Western blot; apoptosis was analyzed by TUNEL assay. CHOP expression was significantly increased at 6 and 24 hours following SE. At both time points, eIF2α and PERK levels were also increased. At 6 hours, CHOP expression was significantly reduced in salubrinal, GSK2656157 and metformin groups versus SE group. eIF2α and PERK levels were decreased in metformin compared to SE group. eIF2α expression was markedly decreased in salubrinal versus SE group, while PERK expression was markedly reduced in GSK2656157 versus SE group. At 6 and 24 hours, the apoptosis rate was significantly increased in SE versus control group, while it was significantly reduced in salubrinal, GSK2656157, and metformin groups compared to SE group. The apoptosis rate also decreased in salubrinal group at 24 hours, although not to the extent observed in metformin group. Overall, CHOP expression and apoptosis induced by SE in rats were reduced with metformin. Further studies are required to evaluate the clinical relevance of metformin for patients with SE.

Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma.

Science.gov (United States)

Dranitsaris, G; Altmayer, C; Quirt, I

1997-06-01

Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

Science.gov (United States)

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Tamura, Miho; Sawada, Takeshi; Omuro, Yasushi; Hishima, Tsunekazu; Maeda, Yoshiharu

2018-02-01

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (BMI (BMI (≥25 kg/m 2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age. Copyright © 2017 John Wiley & Sons, Ltd.

Chopped hemp: Logistics, compaction and financial viability; Logistik, komprimering och ekonomi angaaende hackad hampa

Energy Technology Data Exchange (ETDEWEB)

Soederstroem, Yvonne

2010-05-15

In this project compaction and logistics experiments were conducted using chopped hemp. The aim was to reduce the hemp to 250 kg/m3, as well as to identify the best possible logistical system for compaction and subsequent transportation to the end-user in terms of cost and environmental impact. The project primarily focused on landowners and power companies. Other stakeholders are industries, universities and other ongoing projects in related fields. These studies have shown that it is possible to compact chopped hemp from a density of 60 kg dm/m3 (0.30 MWh/m3) when harvesting directly into the container, to a density of 202 kg dm/m3 (1.01 MWh/m3) using the baler. The original compaction target was a volumetric weight of 250 kg/m3. It was determined that straw and hemp react similarly to compaction. This project has demonstrated that the transport rig system has the best potential for large-scale use as compared with the alternate systems used. According to our calculations, the transport rig was the most cost-effective system measured in kronor per energy content. In addition, this system is also flexible. From an environmental standpoint, however, the energy balance showed that the container system was slightly superior

Utilization of gum tragacanth as bind enhancing agent in extended restructured mutton chops

OpenAIRE

Sharma, Heena; Sharma, B. D.; Talukder, S.; Ramasamy, Giriprasad

2013-01-01

Use of extenders in meat products is not only health promoting but can also increase the economic worth of the products. Extension of the meat product is generally associated with poor binding and texture. Thus, the present study was envisaged to solve this problem by the incorporation of gum tragacanth (GT) as bind enhancing agent, used at three different levels viz., 0.1, 0.15 and 0.2 % in a pre standardized formulation of extended restructured mutton chops (ERMC), by replacing the lean mea...

Prognosis of localized diffuse large B-cell lymphoma in younger patients

DEFF Research Database (Denmark)

Møller, Michael B; Christensen, Bjarne E; Pedersen, Niels T

2003-01-01

BACKGROUND: The International Prognostic Index (IPI) is widely used as a predictive model in diffuse large B-cell lymphoma (DLBCL) patients of all ages and stages. To determine the optimal IPI-based prognostic system at the time of diagnosis in younger patients with limited-stage DLBCL, the authors...

Time-Dependent Deformation Modelling for a Chopped-Glass Fiber Composite for Automotive Durability Design Criteria

Energy Technology Data Exchange (ETDEWEB)

Ren, W

2001-08-24

Time-dependent deformation behavior of a polymeric composite with chopped-glass-fiber reinforcement was investigated for automotive applications, The material under stress was exposed to representative automobile service environments. Results show that environment has substantial effects on time-dependent deformation behavior of the material. The data were analyzed and experimentally-based models developed for the time-dependent deformation behavior as a basis for automotive structural durability design criteria.

[Fever, atrial fibrillation, and angina pectoris in a 58-year-old man].

Science.gov (United States)

Groebner, M; Südhoff, T; Doering, M; Kirmayer, M; Nitsch, T; Prügl, L; Römer, W; Wolf, H; Tacke, J; Massoudy, P; Nüsse, T; Elsner, D

2014-05-01

Primary cardiac lymphoma (PCL) respresents a very rare type of cardiac tumour. This report illustrates a case of PCL in an immunocompetent 58-year-old man presenting with atrial fibrillation and febrile syndrome. Comprehensive imaging [computer tomography (CT), cardiac magnetic resonance imaging (cMRI), 3-dimensional transesophageal echocardiography (3D-TEE)] identified a large right atrial tumour, leading to pericardial effusion. Isolated cardiac involvement was confirmed by positron emission tomography (PET)-CT. A diffuse large B-cell lymphoma (DLBCL) was diagnosed based on the results of a TEE-guided biopsy. A normalized PET scan (PETAL study) indicated complete remission following R-CHOP 14 immunochemotherapy. Thus, an interdisciplinary and multimodal approach avoided unnecessary cardiac surgery.

Finite element analysis of interface stress between neutron absorption coating and chop disk

International Nuclear Information System (INIS)

Tang Changliang; Zhang Xiaozhang; Jiang Lei; Dai Xingjian

2012-01-01

The performance of disk chopper is directly affected by bond strength between neutron absorption coating and chop disk. Based on the finite element analysis software ANSYS, the interface stress distribution under high speed centrifugal load was calculated, which was to investigate the effects of coating's elastic modulus, poisson ratio and coating thickness on the interfacial stress distribution. The results show that soft and tough coating can reduce the peak stress effectively, and coating thickness reducing is helpful to avoid the plastic failure of opening in the disk under high speed centrifugal load. (authors)

Straight and chopped DC performance data for a General Electric 5BY436A1 DC shunt motor with a General Electric EV-1 controller

Science.gov (United States)

Edie, P. C.

1981-01-01

Both straight and chopped dc motor performance data for a General Electric 5BY436A1 motor with a General Electric EV-1 controller is presented in tabular and graphical formats. Effects of motor temperature and operating voltage are also shown. The maximum motor efficiency is approximately 85% at low operating temperatures in the straight dc mode. Chopper efficiency can be assumed to be 95% under all operating conditions. For equal speeds, the motor operated in the chopped mode develops slightly more torque and draws more current than it does in the straight mode.

Fatigue Characteristic of Chopped Strand Mat/Polyester Composite

Directory of Open Access Journals (Sweden)

I Made Astika

2012-11-01

Full Text Available The application of composite as an alternatif material to substitute of metal has better properties than metal such as light, high elasticity, corrosion and fatigue resistance. Some components in its application are subjected to millions of varying stress cycles that initiated to fatigue failure such as crack, delamination and fracture. The strength of composite is influenced by construction, fiber type, orientation and fiber fraction. The objective of this experiment is to investigate the fatigue characteristic on SCM composite. Material composite to be used is glass fiber with chopped strand mat (CSM as fiber and Yukalac 157 BQTN-EX with 1% hardener (Mexpox as matrix. The mold process was built with hand lay-up. Fiber volume fractions in composite are 40, 32 and 24 %. The tests to be done on composite are fatigue and tensile test. The research show that the increasing of fiber fraction in composite affects increasing of fatigue life, endurance limit and tensile strength. Fatigue failure modes of composite are debonding, matrix cracking, delamination and fiber fracture.

A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification

DEFF Research Database (Denmark)

Gang, Anne O.; Pedersen, Michael; d'Amore, Francesco

2015-01-01

The introduction of rituximab and generally improved health among elderly patients have increased the survival of patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) from 1992 is based on pre-rituximab data from clinical trials including several lymphoma ...... dehydrogenase (LDH), stage and albumin level, and (2) a separate age-adjusted DLBCL-PI for patients 1 extranodal lesion, however excluding stage....... subtypes. We applied IPI factors to a population-based rituximab-treated cohort of 1990 patients diagnosed 2000-2010 and explored new factors and the optimal prognostic age cut-off for DLBCL. Multivariate-analyses (MVA) confirmed the prognostic value of all IPI factors except the presence of > 1 extranodal...... lesion. The optimal age cut-off was 70 years. In a MVA of albumin, lymphocyte count, sex, immunoglobulin G, bulky disease, hemoglobin and B-symptoms, only albumin was prognostic. We propose: (1) a modified DLBCL prognostic index (DLBCL-PI) including: age (70 years), performance status (PS), lactate...

Time-Dependent Deformation Modelling for a Chopped-Glass Fiber Composite for Automotive Durability Design Criteria; FINAL

International Nuclear Information System (INIS)

Ren, W

2001-01-01

Time-dependent deformation behavior of a polymeric composite with chopped-glass-fiber reinforcement was investigated for automotive applications, The material under stress was exposed to representative automobile service environments. Results show that environment has substantial effects on time-dependent deformation behavior of the material. The data were analyzed and experimentally-based models developed for the time-dependent deformation behavior as a basis for automotive structural durability design criteria

Thermo-Mechanical Properties of Unsaturated Polyester Reinforced with SiliconCarbide Powder And with Chopped Glass Fiber

Directory of Open Access Journals (Sweden)

Bushra Hosnie Musa

2018-02-01

Full Text Available The work studied the effectoffine silicon carbide (SiC powder with (0,3,5,7wt % on the thermal conductivity and mechanical properties of unsaturated polyester composite in the presence of a fixed amount of chopped glass fiber. The hand lay-up technique was employed to preparethe required samples. Results showed that tensile, impact strength and thermal conductivity increased with increasing the weight fraction of reinforced materials.

Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

Science.gov (United States)

Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

2017-05-01

Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity

Energy Technology Data Exchange (ETDEWEB)

Yin, Li [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Dai, Yanlin [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Medical Laboratory Technology Department, Chuxiong Medical College, Yunnan 675005 (China); Cui, Zhihong; Jiang, Xiao; Liu, Wenbin; Han, Fei; Lin, Ao; Cao, Jia [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China); Liu, Jinyi, E-mail: jinyiliutmmu@163.com [Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038 (China)

2017-01-01

Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the environment, wildlife, and humans. Evidence from past studies suggests that BPA is associated with decreased semen quality. However, the molecular basis for the adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we explored the potential mechanism of its action. The results showed that BPA inhibited cell proliferation and increased the apoptosis rate. The testes from BPA-treated mice showed fewer spermatogenic cells and sperm in the seminiferous tubules. In addition, BPA caused reactive oxygen species (ROS) accumulation. Previous study has verified that mitochondrion was the organelle affected by the BPA-triggered ROS accumulation. We found that BPA induced damage to the endoplasmic reticulum (ER) in addition to mitochondria, and most ER stress-related proteins were activated in cellular and animal models. Knocking down of the PERK/EIF2α/chop pathway, one of the ER stress pathways, partially recovered the BPA-induced cell apoptosis. In addition, an ROS scavenger attenuated the expression of the PERK/EIF2α/chop pathway-related proteins. Taken together, these data suggested that the ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced male reproductive toxicity. - Highlights: • BPA exposure caused the damage of the endoplasmic reticulum. • BPA exposure activated ER stress related proteins in male reproductive system. • ROS regulated PERK/EIF2α/chop pathway played a vital role in BPA-induced toxicity.

Febrile Neutropenia Risk Assessment and Granulocyte-Colony Stimulating Factor Support in Patients with Diffuse Large B Cell Lymphoma Receiving R-CHOP Regimens

DEFF Research Database (Denmark)

Salar, Antonio; Haioun, Corinne; Rossi, Francesca Gaia

2009-01-01

BACKGROUND: ASCO and EORTC guidelines recommend granulocyte colony-stimulating factor (G-CSF) primary prophylaxis for cancer patients with a ≥20% overall risk of febrile neutropenia (FN), and to support delivery of dose-dense regimens. CHOP-like regimens (with rituximab [R]) are the current...... standard of care for the management of aggressive non-Hodgkin lymphoma (NHL), but they are often associated with significant myelosuppression. Neutropenic events, particularly febrile neutropenia (FN), can be life-threatening and may lead to dose delays or reductions that compromise the efficacy......-CSF primary prophylaxis. Across all cycles, 29% of R-CHOP-21 patients had an unplanned hospitalization, with neutropenia/FN being the main reason. Subsequently, 67% of patients achieved a relative dose intensity (RDI) of ≥90% of their planned treatment (with respect to cyclophosphamide, doxorubicin...

Investigation on Stress-Rupture Behavior of a Chopped-Glass-Fiber Composite for Automotive Durability Design Criteria

Energy Technology Data Exchange (ETDEWEB)

Ren, W

2001-08-24

Practical and inexpensive testing methods were developed to investigate stress-rupture properties of a polymeric composite with chopped glass fiber reinforcement for automotive applications. The material was tested in representative automotive environments to generate experimental data. The results indicate that environments have substantial effects on the stress-rupture behavior. The data were analyzed and developed into stress-rupture design criteria to address one of the durability aspects of the material for automotive structural applications.

Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

Directory of Open Access Journals (Sweden)

Vadim Gorodetskiy

2016-01-01

Full Text Available Sjögren’s syndrome (SS has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL. To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

Primary testicular diffuse large B-cell lymphoma: A case report

Directory of Open Access Journals (Sweden)

Muhammad Sadiq

2017-12-01

Full Text Available Primary testicular diffuse large-B cell lymphoma (DLBCL is an uncommon and aggressive disease with predominant manifestation in the older age. Herein, we report a case of 47-year-old male patient who presented with three months history of left testis swelling. The patient underwent unilateral (left radical orchiectomy. Histopathological examination revealed extensive involvement and replacement of testicular parenchyma by a tumor composed of large discohesive sheets of cells with pleomorphic, hyperchromatic nuclei and prominent nucleoli. Immunohistochemical (IHC staining showed reactivity for LCA & Pan B (CD20 and negativity for OCT 3/4, SALL4 and Inhibin. Moreover, Pan T (CD3 highlighted reactive T-cells. These features rendered the diagnosis of DLBCL of testis. The hybrid 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG positron emission tomography/computed tomography (PET/CT demonstrated two para-aortic FDG avid lymph nodes on the left side at the level of L2 vertebra. Presently, the patient has been planned for doxorubicin-based chemotherapy (i.e., cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP along with intrathecal Methroxate (MTX, which would presumably improve the prognosis. Our study would expand the pool of this uncommon tumor towards its better understanding. Keywords: Primary testicular lymphoma, Diffuse large-B cell lymphoma, Orchiectomy, Doxorubicin-based chemotherapy

Ascites as the initial characteristic manifestation in a patient with primary gastric CD8-positive diffuse large B-cell lymphoma.

Science.gov (United States)

Zhao, K-X; Dai, G-Z; Zhu, J-F

2016-05-01

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and the most common type of non-Hodgkin's lymphomas, the stomach is the most common extranodal site. Gastric DLBCL is often characterized by epigastric pain and vomiting. We report a case of a 78-year-old female patient with gastric diffuse large B-cell lymphoma (DLBCL) with high CD8 level which was initially manifested with ascites of unknown origin. The patient was admitted with a chief complaint of abdominal distension and scanty urine over the last twenty days, while without anorexia and fatigue until 15 March. She had no history of viral hepatitis, tuberculosis, schistosomiasis. Laboratory data revealed normal aminotransferases and bilirubin levels, but serum lactate dehydrogenase, CA125, ascitic fluid lactate dehydrogenase, ascitic fluid lymphocytes increased. The ascitic fluid was yellow-colored with 98.5% lymphocytes. Stool occult blood test was positive. Upper gastrointestinal endoscopy performed a few days later revealed multiple gastric crateriform ulcers, and Helicobacter pylori was detected in the biopsy specimen. Peripheral blood CD8+ was increased by 51%. Pathology test showed lymphocytes with atypical hyperplasia, and immunohistochemistry test resulted CD20+, CD10-, CD79α+, κ+, bcl-6+, Ki-67+ (approximately 95%), λ-, bcl-2-, CD3-, CD43-. Immunoglobulin gene (Ig) clonal rearrangement showed IgH: FR1 (+), FR2 (+), FR3(-), Igk: VJ(+), Vkde (+) in lymphoma tissue. The features of histopathology and immunohistochemistry of the tissue confirmed diffuse large B-cell lymphoma (DLBL). The patient received an uncompleted CHOP program combined with H. pylori eradication. However, the patient deceased due to disease development sixteen days later after the diagnosis.

Comparison between Antiemetic Effects of Palonosetron and Granisetron on Chemotherapy-Induced Nausea and Vomiting in Japanese Patients Treated with R-CHOP.

Science.gov (United States)

Uchida, Mayako; Mori, Yasuo; Nakamura, Tsutomu; Kato, Koji; Kamezaki, Kenjiro; Takenaka, Katsuto; Shiratsuchi, Motoaki; Kadoyama, Kaori; Miyamoto, Toshihiro; Akashi, Koichi

2017-01-01

In the present study, the antiemetic effect of palonosetron, not combined with dexamethasone and aprepitant, on chemotherapy-induced nausea and vomiting was evaluated in patients with malignant lymphoma receiving first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, and was compared to that of granisetron. A total of 74 patients with non-Hodgkin lymphoma were included in this study (April 2007 to December 2015). Palonosetron (0.75 mg) or granisetron (3 mg) was intravenously administered before R-CHOP therapy. The proportions of patients with complete response (CR) during the overall (0-120 h after the start of R-CHOP therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CR was defined as no vomiting and no use of antiemetic rescue medication. A total of 32 and 42 patients were treated with palonosetron and granisetron, respectively. The CR rate in the palonosetron group was significantly higher than that in the granisetron group during the delayed phase (90.6 and 61.9%, respectively; p=0.007). Logistic regression analysis showed that use of palonosetron improved the CR rate during the delayed phase, compared to use of granisetron. Female sex, age less than 60 years, no habitual alcohol intake, and Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 1 were significant risk factors associated with non-CR. The findings of this study suggested the superiority of palonosetron to granisetron, without accompanying dexamethasone and aprepitant, for chemotherapy-induced nausea and vomiting in patients with malignant lymphoma.

Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

Science.gov (United States)

Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

2017-07-01

The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

International preferences for pork appearance: I. Consumer choices

NARCIS (Netherlands)

Ngapo, T.M.; Martin, J.F.; Dransfield, E.

2007-01-01

Using the same digital photographs of pork chops varying systematically in fat cover, colour, marbling and drip, 12,590 consumers from 23 countries each selected their preferred chop. Preferences differed considerably between individuals, between groups and between countries when comparing

Investigation on Stress-Rupture Behavior of a Chopped-Glass-Fiber Composite for Automotive Durability Design Criteria; FINAL

International Nuclear Information System (INIS)

Ren, W

2001-01-01

Practical and inexpensive testing methods were developed to investigate stress-rupture properties of a polymeric composite with chopped glass fiber reinforcement for automotive applications. The material was tested in representative automotive environments to generate experimental data. The results indicate that environments have substantial effects on the stress-rupture behavior. The data were analyzed and developed into stress-rupture design criteria to address one of the durability aspects of the material for automotive structural applications

R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience.

Science.gov (United States)

Widmer, Fabienne; Balabanov, Stefan; Soldini, Davide; Samaras, Panagiotis; Gerber, Bernhard; Manz, Markus G; Goede, Jeroen S

2018-02-01

Standard of care for untreated mantle cell lymphoma (MCL) is still debated. At the University Hospital Zurich, advanced MCL in physically fit patients is treated either with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone induction followed by consolidating high-dose chemotherapy and autologous stem cell support (R-CHOP/HD-ASCT), or with rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate-cytarabine (R-hyper-CVAD/MTX-AraC) without consolidating HD-ASCT upon physicians' and patients' choice. We retrospectively analysed the outcome and therapy tolerance in patients with MCL treated with R-CHOP/HD-ASCT or R-hyper-CVAD/MTX-AraC at the University Hospital Zurich between January 1996 and January 2016. Forty-three patients were included; 29 patients received R-CHOP/HD-ASCT and 14 patients R-hyper-CVAD/MTX-AraC. Mean age at diagnosis was 54.4 years (range 38-68 years). Thirty-five patients (81.4%) completed the entire first-line therapy (n = 24 in the R-CHOP/HD-ASCT group, n = 11 in the R-hyper-CVAD group). Of those, all patients responded and 97% achieved a complete remission (CR). With a mean follow-up of 5.7 years 10-year progression-free survival (PFS) for all patients was 32% and overall survival (OS) was 76%, with no difference between the two therapy groups. Complication-induced hospitalisation rate, haematological toxicity and economic burden were significantly higher in the R-hyper-CVAD therapy group. In contrast, quality of life and global health state were better in the R-hyper-CVAD therapy group. Both first-line therapies showed similar outcome with a median OS longer than 10 years. Due to significantly lower haematological toxicity and lower economic burden, we recommend R-CHOP/HD-ASCT as first-line therapy in fit adult patients with advanced MCL.

Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation

International Nuclear Information System (INIS)

Fuller, Lillian M.; Krasin, Matthew J.; Velasquez, William S.; Allen, Pamela K.; McLaughlin, Peter; Rodriguez, M. Alma; Hagemeister, Fredrick B.; Swan, Forrest; Cabanillas, Fernando; Palmer, Judy L.; Cox, James D.

1995-01-01

Purpose: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). Methods and Materials: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or ≥ 40 Gy and (b) relapse patterns. Results: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of ≥ 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. Conclusion: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients

Drug: D02994 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D02994 Drug Rituximab (USAN/INN); Rituximab (genetical recombination) (JAN); Ritux...imab (genetical recombination) [Rituximab biosimilar 1] (JAN); Rituxan (TN) ... Therapeutic category: 429

Subamolide B Isolated from Medicinal Plant Cinnamomum subavenium Induces Cytotoxicity in Human Cutaneous Squamous Cell Carcinoma Cells through Mitochondrial and CHOP-Dependent Cell Death Pathways

Directory of Open Access Journals (Sweden)

Shu-Yi Yang

2013-01-01

Full Text Available Subamolide B is a butanolide isolated from Cinnamomum subavenium, a medicinal plant traditionally used to treat various ailments including carcinomatous swelling. We herein reported for the first time that subamolide B potently induced cytotoxicity against diverse human skin cancer cell lines while sparing nonmalignant cells. Mechanistic studies on human cutaneous squamous cell carcinoma (SCC cell line SCC12 highlighted the involvement of apoptosis in subamolide B-induced cytotoxicity, as evidenced by the activation of caspases-8, -9, -4, and -3, the increase in annexin V-positive population, and the partial restoration of cell viability by cotreatment with the pan-caspase inhibitor z-VAD-fmk. Additionally, subamolide B evoked cell death pathways mediated by FasL/Fas, mitochondria, and endoplasmic reticulum (ER stress, as supported by subamolide B-induced FasL upregulation, BCL-2 suppression/cytosolic release of cytochrome c, and UPR activation/CHOP upregulation, respectively. Noteworthy, ectopic expression of c-FLIPL or dominant-negative mutant of FADD failed to impair subamolide B-induced cytotoxicity, whereas BCL-2 overexpression or CHOP depletion greatly rescued subamolide B-stimulated cells. Collectively, these results underscored the central role of mitochondrial and CHOP-mediated cell death pathways in subamolide B-induced cytotoxicity. Our findings further implicate the potential of subamolide B for cutaneous SCC therapy or as a lead compound for developing novel chemotherapeutic agents.

Ku70 acetylation and modulation of c-Myc/ATF4/CHOP signaling axis by SIRT1 inhibition lead to sensitization of HepG2 cells to TRAIL through induction of DR5 and down-regulation of c-FLIP

DEFF Research Database (Denmark)

Kim, Mi-Ju; Hong, Kyung-Soo; Kim, Hak-Bong

2013-01-01

In this study, we investigated the role of c-Myc/ATF4/CHOP signaling pathway in sensitization of human hepatoma HepG2 cells to TRAIL. Knockdown of SIRT1 or treatment with SIRT1 inhibitor caused the up-regulation of DR5 and down-regulation of c-FLIP through modulation of c-Myc/ATF4/CHOP pathway, a...

The γ-secretase cleavage product of Polycystin-1 regulates TCF and CHOP-mediated transcriptional activation through a p300-dependent mechanism

Science.gov (United States)

Merrick, David; Chapin, Hannah; Baggs, Julie E.; Yu, Zhiheng; Somlo, Stefan; Sun, Zhaoxia; Hogenesch, John B.; Caplan, Michael

2011-01-01

Summary Mutations in Pkd1, encoding polycystin-1 (PC1), cause Autosomal Dominant Polycystic Kidney Disease (ADPKD). We show that the carboxy-terminal tail (CTT) of PC1 is released by γ-secretase-mediated cleavage and regulates the Wnt and CHOP pathways by binding the transcription factors TCF and CHOP, disrupting their interaction with the common transcriptional co-activator p300. Loss of PC1 causes increased proliferation and apoptosis, while reintroducing PC1-CTT into cultured Pkd1 null cells reestablishes normal growth rate, suppresses apoptosis, and prevents cyst formation. Inhibition of γ-secretase activity impairs the ability of PC1 to suppress growth and apoptosis, and leads to cyst formation in cultured renal epithelial cells. Expression of the PC1-CTT is sufficient to rescue the dorsal body curvature phenotype in zebrafish embryos resulting from either γ-secretase inhibition or suppression of Pkd1 expression. Thus, γ-secretase-dependent release of the PC1-CTT creates a protein fragment whose expression is sufficient to suppress ADPKD-related phenotypes in vitro and in vivo. PMID:22178500

[Bendamustine-rituximab therapy is effective for transformed follicular lymphoma with significant expression of p53].

Science.gov (United States)

Kuroda, Hiroyuki; Jomen, Wataru; Miura, Shogo; Arihara, Yohei; Yamada, Michiko; Hirako, Tasuku; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Okagawa, Yutaka; Hoki, Toshifumi; Kato, Junji

2013-08-01

We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

The CHOP postnatal weight gain, birth weight, and gestational age retinopathy of prematurity risk model.

Science.gov (United States)

Binenbaum, Gil; Ying, Gui-Shuang; Quinn, Graham E; Huang, Jiayan; Dreiseitl, Stephan; Antigua, Jules; Foroughi, Negar; Abbasi, Soraya

2012-12-01

To develop a birth weight (BW), gestational age (GA), and postnatal-weight gain retinopathy of prematurity (ROP) prediction model in a cohort of infants meeting current screening guidelines. Multivariate logistic regression was applied retrospectively to data from infants born with BW less than 1501 g or GA of 30 weeks or less at a single Philadelphia hospital between January 1, 2004, and December 31, 2009. In the model, BW, GA, and daily weight gain rate were used repeatedly each week to predict risk of Early Treatment of Retinopathy of Prematurity type 1 or 2 ROP. If risk was above a cut-point level, examinations would be indicated. Of 524 infants, 20 (4%) had type 1 ROP and received laser treatment; 28 (5%) had type 2 ROP. The model (Children's Hospital of Philadelphia [CHOP]) accurately predicted all infants with type 1 ROP; missed 1 infant with type 2 ROP, who did not require laser treatment; and would have reduced the number of infants requiring examinations by 49%. Raising the cut point to miss one type 1 ROP case would have reduced the need for examinations by 79%. Using daily weight measurements to calculate weight gain rate resulted in slightly higher examination reduction than weekly measurements. The BW-GA-weight gain CHOP ROP model demonstrated accurate ROP risk assessment and a large reduction in the number of ROP examinations compared with current screening guidelines. As a simple logistic equation, it can be calculated by hand or represented as a nomogram for easy clinical use. However, larger studies are needed to achieve a highly precise estimate of sensitivity prior to clinical application.

EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity?

Science.gov (United States)

Hong, J Y; Yoon, D H; Suh, C; Huh, J; Do, I-G; Sohn, I; Jo, J; Jung, S-H; Hong, M E; Yoon, H; Ko, Y H; Kim, S J; Kim, W S

2015-03-01

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined only in adults older than 50 years. However, EBV-positive DLBCL can affect younger patients. We investigated the prevalence, clinical characteristics and survival outcomes of EBV-positive DLBCL in young adults. We analyzed patients with de novo DLBCL who were registered in the Samsung Medical Center (SMC) retrospective lymphoma cohort and prospective SMC Lymphoma Cohort Study I (ClinicalTrials.gov: NCT00822731). A total of 571 cases were included in the analysis. The prevalence of EBV positivity was 6.7% (13/195) and 9.3% (35/376) in the young group (≤50 years) and in the elderly group (>50 years), respectively. EBV status was closely associated with unique unfavorable clinical characteristics [older age, more advanced stage, two or more sites of extranodal involvement, higher International Prognostic Index (IPI), and age-adjusted IPI risk] only in the elderly group. Poor prognostic impact of EBV positivity on overall survival was observed only in the elderly group [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.83-4.47; P young group (HR 1.17; 95% CI 0.35-3.89; P = 0.801). A substantial proportion of EBV-positive DLBCL of the elderly can occur in young adults. EBV positivity of DLBCL in young adults was not associated with unfavorable clinical characteristics or worse outcomes. We suggest that EBV-positive DLBCL should not be confined only in the elderly and 'EBV-positive DLBCL in young adults' needs to be considered as a clinically distinct disease entity. ClinicalTrials.gov: NCT02060435. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Consumer visual appraisal and shelf life of leg chops from suckling kids raised with natural milk or milk replacer.

Science.gov (United States)

Ripoll, Guillermo; Alcalde, María J; Argüello, Anastasio; Córdoba, María G; Panea, Begoña

2018-05-01

The use of milk replacers to feed suckling kids could affect the shelf life and appearance of the meat. Leg chops were evaluated by consumers and the instrumental color was measured. A machine learning algorithm was used to relate them. The aim of this experiment was to study the shelf life of the meat of kids reared with dam's milk or milk replacers and to ascertain which illuminant and instrumental color variables are used by consumers as criteria to evaluate that visual appraisal. Meat from kids reared with milk replacers was more valuable and had a longer shelf life than meat from kids reared with natural milk. Consumers used the color of the whole surface of the leg chop to assess the appearance of meat. Lightness and hue angle were the prime cues used to evaluate the appearance of meat. Illuminant D65 was more useful for relating the visual appraisal with the instrumental color using a machine learning algorithm. The machine learning algorithms showed that the underlying rules used by consumers to evaluate the appearance of suckling kid meat are not at all linear and can be computationally schematized into a simple algorithm. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

9 CFR 319.105 - “Ham patties,” “Chopped ham,” “Pressed ham,” “Spiced ham,” and similar products.

Science.gov (United States)

2010-01-01

... MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Cured Meats, Unsmoked and Smoked § 319.105 “Ham patties,” “Chopped ham... of cured pork product Minimum meat PFF percentage 1 Product name and qualifying statements “Ham...

Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

Science.gov (United States)

Hayashi, K; Joko, H; Koirala, T R; Onoda, S; Jin, Z-S; Munemasa, M; Ohara, N; Oda, W; Tanaka, T; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yamada, M; Akagi, T

2003-10-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious

Energy Saving by Chopping off Peak Demand Using Day Light

Directory of Open Access Journals (Sweden)

Ashok Kumar Maitra

2011-08-01

Full Text Available An artificial intelligent technique has been implemented in this research using real time datas to calculate how much energy can be chopped from peak load demand. The results are based on real time data that are taken from power delivering centers. These datas do reflect the present condition of power and a solution to those critical conditions during the peak period. These are done in such a way such that helps in judicious scheduling of load. The time based load scheduling has been done so as to understand the basic criteria for solving power crisis during morning peak and early evening peak. The sunray availability and percentage of load that will use day light saving (DLS technique has been taken into account in this work. The results shows that about 0.5% to 1% of load can be shedded off from the peak load period which otherwise is reduction of power. Thus it otherwise also means that an equivalent amount of energy is saved which amounts to a large saving of national money. This result is obtained on monthly and even daily basis. Thus this paper justifies DLS gives a new renewable technique to save energy.

Study Suggests New Treatment Option for Some Lymphomas

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Updated findings from a large European clinical trial indicate that patients with some types of lymphoma could initially be treated with the chemotherapy drug bendamustine (Treanda) and the targeted agent rituximab (Rituxan).

Kaempferol Sensitizes Human Ovarian Cancer Cells-OVCAR-3 and SKOV-3 to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis via JNK/ERK-CHOP Pathway and Up-Regulation of Death Receptors 4 and 5.

Science.gov (United States)

Zhao, Yingmei; Tian, Binqiang; Wang, Yong; Ding, Haiying

2017-10-26

BACKGROUND Ovarian cancer is the most common gynecological malignancies in women, with high mortality rates worldwide. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) superfamily which preferentially induces apoptosis of cancer cells. However, acquired resistance to TRAIL hampers its therapeutic application. Identification of compounds that sensitize cancer cells to TRAIL is vital in combating resistance to TRAIL. The effect of kaempferol, a flavonoid enhancing TRAIL-induced apoptosis in ovarian cancer cells, was investigated in this study. MATERIAL AND METHODS The cytotoxic effects of TRAIL (25 ng/mL) and kaempferol (20-100 µM) on human ovarian cancer cells OVCAR-3 and SKOV-3 were assessed. Effect of kaempferol on the expression patterns of cell survival proteins (Bcl-xL, Bcl-2, survivin, XIAP, c-FLIP) and apoptotic proteins (caspase-3, caspase-8, caspase-9, Bax) were studied. The influence of kaempferol on expression of DR4 and DR5 death receptors on the cell surface and protein and mRNA levels was also analyzed. Apoptosis following silencing of DR5 and CHOP by small interfering RNA (siRNA), and activation of MAP kinases were analyzed as well. RESULTS Kaempferol enhanced apoptosis and drastically up-regulated DR4, DR5, CHOP, JNK, ERK1/2, p38 and apoptotic protein expression with decline in the expression of anti-apoptotic proteins. Further transfection with siRNA specific to CHOP and DR5 indicated the involvement of CHOP in DR5 up-regulation and also the contribution of DR5 in kaempferol-enhanced TRAIL-induced apoptosis. CONCLUSIONS Kaempferol sensitized ovarian cancer cells to TRAIL-induced apoptosis via up-regulation of DR4 and DR5 through ERK/JNK/CHOP pathways.

PROPERTIES OF NR AND NR/ENR BASED RUBBER COMPOUNDS REINFORCED WITH CHOPPED AND SIZED CARBON FIBER

Directory of Open Access Journals (Sweden)

Bağdagül Karaağaç

2016-12-01

Full Text Available High elasticity, mechanical resistance and antivibration characteristics of natural rubber (NR are essential issue in the main area of vehicle tyres and high modulus demanding bearing applications. In this study, especially in bearing applications, where natural rubber modulus properties are limited, natural rubber has been reinforced with chopped and hydrocarbon sized carbon fiber to get improved tensile modulus. Besides, epoxidized natural rubber (ENR, which was produced by chemical modification of natural rubber, blended with NR and the compounds have been reinforced with epoxy sized carbon fiber. NR and NR/ENR based rubber compounds’ rheological, mechanical, and aging properties have been systematically investigated and evaluated.

Energy Absorption in Chopped Carbon Fiber Compression Molded Composites

International Nuclear Information System (INIS)

Starbuck, J.M.

2001-01-01

In passenger vehicles the ability to absorb energy due to impact and be survivable for the occupant is called the ''crashworthiness'' of the structure. To identify and quantify the energy absorbing mechanisms in candidate automotive composite materials, test methodologies were developed for conducting progressive crush tests on composite plate specimens. The test method development and experimental set-up focused on isolating the damage modes associated with the frond formation that occurs in dynamic testing of composite tubes. Quasi-static progressive crush tests were performed on composite plates manufactured from chopped carbon fiber with an epoxy resin system using compression molding techniques. The carbon fiber was Toray T700 and the epoxy resin was YLA RS-35. The effect of various material and test parameters on energy absorption was evaluated by varying the following parameters during testing: fiber volume fraction, fiber length, fiber tow size, specimen width, profile radius, and profile constraint condition. It was demonstrated during testing that the use of a roller constraint directed the crushing process and the load deflection curves were similar to progressive crushing of tubes. Of all the parameters evaluated, the fiber length appeared to be the most critical material parameter, with shorter fibers having a higher specific energy absorption than longer fibers. The combination of material parameters that yielded the highest energy absorbing material was identified

Archaeal community dynamics and abiotic characteristics in a mesophilic anaerobic co-digestion process treating fruit and vegetable processing waste sludge with chopped fresh artichoke waste.

Science.gov (United States)

Ros, M; Franke-Whittle, I H; Morales, A B; Insam, H; Ayuso, M; Pascual, J A

2013-05-01

This study evaluated the feasibility of obtaining methane in anaerobic digestion (AD) from the waste products generated by the processing of fruit and vegetables. During the first phase (0-55 d) of the AD using sludge from fruit and vegetable processing, an average value of 244±88 L kg(-1) dry matter d(-1)of biogas production was obtained, and methane content reached 65% of the biogas. Co-digestion with chopped fresh artichoke wastes in a second phase (55-71 d) enhanced biogas production, and resulted in an average value of 354±68 L kg(-1) dry matter d(-1), with higher methane content (more than 70%). The archaeal community involved in methane production was studied using the ANAEROCHIP microarray and real-time PCR. Results indicated that species of Methanosaeta and Methanosarcina were important during the AD process. Methanosarcina numbers increased after the addition of chopped fresh artichoke, while Methanosaeta numbers decreased. Copyright © 2013 Elsevier Ltd. All rights reserved.

Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

Science.gov (United States)

Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

2017-06-01

The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulator considerations for beam chopping in the low energy beam transport at the SSC Laboratory

International Nuclear Information System (INIS)

Anderson, D.; Pappas, G.

1991-06-01

Beam chopping in the low energy transport line at the Superconducting Super Collider Laboratory is accomplished using an electrostatic deflection system. LINAC requirements dictate the design of two modulators operating at 10 Hz with rise and fall times (as measured from approximately 10--99%) of ∼100 ns. Design of the first pulser, normally at 10 kV and pulsed to ground potential, utilizes a transformer-coupled diode-clamped solid state circuit to achieve the 2--35 μs pulse width range required. The second pulser, which pulses from ground to approximately 7 kV, relies on a series vacuum tube circuit. The current designs, as well as recent test results and other circuit topologies considered, will be presented. 6 refs

Chemical decontamination and melt densification of chop-leach fuel hulls

International Nuclear Information System (INIS)

Dillon, R.L.; Griggs, B.; Kemper, R.S.; Nelson, R.G.

1976-01-01

This paper reports on decontamination and densification studies of chop-leach fuel hull residues designed to minimize the transuranic element (TRU) contaminated waste stream. Decontamination requirements have been established from studies of TRU element distribution in the fuel hull residues. Effective surface decontamination of Zircaloy requires removal of zirconium oxide corrosion products. Good decontamination factors have been achieved with aqueous solutions following high temperature HF conditioning of oxide films. Molten fluoride salt mixtures are effective decontaminants, but pose problems in metal loss and salt dragout. Molten metal decontamination methods are highly preliminary, but may be required to reduce TRU originating from tramp uranium in Zircaloy. Low melting (1300 0 C) alloy of Zircaloy, stainless steel, and Inconel have been prepared in induction heated graphite crucibles. High quality ingots of Zircaloy-2 have been prepared directly from short sections of descaled fuel clad tubing using the Inductoslag process. This material is readily capable of refabrication. Inductoslag melts have also been prepared from heavily oxidized Zircaloy tubing demonstrating melt densification without prior decontamination is technically feasible. Hydrogen absorption kinetics have been demonstrated with cast Zircaloy-2 and cast Zircaloy-stainless steel-Inconel alloys. Metallic fuel hull residues have been proposed as a storage medium for tritium released from fuel during reprocessing. (author)

Electron-beam induced current characterization of back-surface field solar cells using a chopped scanning electron microscope beam

Science.gov (United States)

Luke, K. L.; Cheng, L.-J.

1984-01-01

A chopped electron beam induced current (EBIC) technique for the chacterization of back-surface field (BSF) solar cells is presented. It is shown that the effective recombination velocity of the low-high junction forming the back-surface field of BSF cells, in addition to the diffusion length and the surface recombination velocity of the surface perpendicular to both the p-n and low-high junctions, can be determined from the data provided by a single EBIC scan. The method for doing so is described and illustrated. Certain experimental considerations taken to enhance the quality of the EBIC data are also discussed.

Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.

Science.gov (United States)

Chapuy, Bjoern; Stewart, Chip; Dunford, Andrew J; Kim, Jaegil; Kamburov, Atanas; Redd, Robert A; Lawrence, Mike S; Roemer, Margaretha G M; Li, Amy J; Ziepert, Marita; Staiger, Annette M; Wala, Jeremiah A; Ducar, Matthew D; Leshchiner, Ignaty; Rheinbay, Ester; Taylor-Weiner, Amaro; Coughlin, Caroline A; Hess, Julian M; Pedamallu, Chandra S; Livitz, Dimitri; Rosebrock, Daniel; Rosenberg, Mara; Tracy, Adam A; Horn, Heike; van Hummelen, Paul; Feldman, Andrew L; Link, Brian K; Novak, Anne J; Cerhan, James R; Habermann, Thomas M; Siebert, Reiner; Rosenwald, Andreas; Thorner, Aaron R; Meyerson, Matthew L; Golub, Todd R; Beroukhim, Rameen; Wulf, Gerald G; Ott, German; Rodig, Scott J; Monti, Stefano; Neuberg, Donna S; Loeffler, Markus; Pfreundschuh, Michael; Trümper, Lorenz; Getz, Gad; Shipp, Margaret A

2018-04-30

Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.

Prognostic Value of FDG-PET, Based on the Revised Response Criteria, in Patients with Malignant Lymphoma: A Comparison with CT/MRI Evaluations, Based on the International Working Group/Cotswolds Meeting Criteria

International Nuclear Information System (INIS)

Isohashi, Kayako; Tatsumi, Mitsuaki; Kato, Hiroki; Fukushima, Kentaro; Maeda, Tetsuo; Watabe, Tadashi; Shimosegawa, Eku; Kanakura, Yuzuru; Hatazawa, Jun

2015-01-01

Post-treatment evaluations by CT/MRI (based on the International Working Group/Cotswolds meeting guidelines) and PET (based on Revised Response Criteria), were examined in terms of progression-free survival (PFS) in patients with malignant lymphoma (ML). 79 patients, undergoing CT/MRI for the examination of suspected lesions and whole-body PET/CT before and after therapy, were included in the study during April 2007-January 2013. The relationship between post-treatment evaluations (CT/MRI and PET) and PFS during the follow-up period was examined, using Kaplan-Meier survival analysis. The patients were grouped according to the histological type into Hodgkin’s lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and other histological types. The association between post-treatment evaluations (PET or PET combined with CT/MRI) and PFS was examined separately. Moreover, the relationship between disease recurrence and serum soluble interleukin-2 receptor, lactic dehydrogenase, and C-reactive protein levels was evaluated before and after the treatment. Patients with incomplete remission on both CT/MRI and PET had a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET and those exhibiting incomplete remission on CT/MRI and complete remission on PET (P<0.001). Post-treatment PET evaluations were strongly correlated with patient outcomes in cases with HL or DLBCL (P<0.01) and other histological types (P<0.001). In patients with HL or DLBCL, incomplete remission on both CT/MRI and PET was associated with a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET (P<0.05) and those showing incomplete remission on CT/MRI and complete remission on PET (P<0.01). In patients with other histological types, incomplete remission on both CT/MRI and PET was associated with a significantly shorter PFS, compared to cases with complete remission on both CT/MRI and PET (P<0.001). None of the serum parameters

Prediction of Central Nervous System Relapse of Diffuse Large B-Cell Lymphoma Using Pretherapeutic [18F]2-Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography/Computed Tomography.

Science.gov (United States)

Song, Yoo Sung; Lee, Won Woo; Lee, Jong Seok; Kim, Sang Eun

2015-11-01

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare complication, but has a poor prognosis with unknown pathophysiology. Recent trials of CNS prophylaxis have shown to be ineffective, despite patient's selection using several known clinical risk factors. In this study, the authors evaluated the value of pretreatment [F]2-Fluoro-2-deoxyglucose positron emission tomography in predicting CNS relapse in DLBCL patients.The authors analyzed 180 pathologically confirmed DLBCL patients, retrospectively. Patients underwent [F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography before first line rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Clinical characteristics were evaluated and total lesion glycolysis (TLG) with a threshold margin of 50% was calculated.Among age, sex, Ann Arbor stage, International Prognostic Index, revised International Prognostic Index, high serum lactate dehydrogenase level, presence of B symptoms, bulky disease (≥10 cm), extranodal lesion involvement, bone marrow involvement, high metabolic tumor volume ( >450 mL), and high TLG50 (>2000), the high TLG50 was the only significant prognostic factor for predicting CNS relapse in a multivariate analysis (P = 0.04). Kaplan-Meir survival analysis between high TLG50 (>2000) and low TLG50 (≤2000) groups revealed significantly different mean progression free survival (PFS) of 1317.2 ± 134.3 days and 1968.6 ± 18.3 days, respectively (P positron emission tomography/computed tomography is the most significant predictor of CNS relapse in un-treated DLBCL patients.

Resultados facodinámicos del chopping inverso en la cirugía de catarata 2009 Phacodynamic outcomes of the reversed chopping technique in the cataract surgery in 2009

Directory of Open Access Journals (Sweden)

Abel Plasencia Blanco

2011-12-01

Full Text Available Objetivo: Evaluar los resultados facodinámicos alcanzados con la técnica de cirugía de catarata por facoemulsificación chopping inverso en el Instituto Cubano de Oftalmología “Ramón Pando Ferrer” en 2009. Métodos: Se realizó un estudio descriptivo y prospectivo en 182 pacientes (ojos con diagnóstico de catarata presenil y senil, que aceptaron someterse a la técnica quirúrgica. Los resultados facodinámicos de la técnica se evaluaron según las siguientes variables: dureza del cristalino, mejor agudeza visual con y sin corrección, poder de ultrasonido, tiempo de facoemulsificación, tiempo efectivo de facoemulsificación, densidad de células endoteliales y complicaciones. Estos datos se analizaron a través de tablas de contingencia con frecuencias absolutas y relativas, se aplicó la prueba t de Student para su comparación. Resultados: La agudeza visual con corrección obtenida significó cinco líneas en la escala de Snellen. El tiempo de ultrasonido aplicado estuvo dentro de valores normales en relación con la dureza del núcleo. La pérdida de células endoteliales no fue importante. La complicación operatoria no fue significativa. Conclusión: La técnica se consideró efectiva con resultados muy favorables. Es perfectamente aplicable para todos los grados de dureza de la catarata, evitándose con ella un gran número de complicaciones. Esto le permite al paciente una rápida incorporación a su vida social.Objectives: To assess the phacodynamic outcomes of the reversed chopping phacoemulsification technique applied in cataract surgery at “Ramon Pando Ferrer” Cuban Institute of Ophthalmology between January and December, 2009. Methods: A prospective and descriptive study was performed on 182 patients (eyes diagnosed with pre-senile and senile cataract, who agreed to be operated on with this procedure. The phacodynamic outcomes were evaluated according to the following variables: lens hardness, best visual acuity with

Effects of alfalfa hay and its physical form (chopped versus pelleted) on performance of Holstein calves.

Science.gov (United States)

Jahani-Moghadam, M; Mahjoubi, E; Hossein Yazdi, M; Cardoso, F C; Drackley, J K

2015-06-01

Inclusion of forage and its physical form in starter may affect rumen development, average daily gain (ADG), and dry matter intake (DMI) of dairy calves. To evaluate the effects of forage and its physical form (chopped vs. pelleted) on growth of calves under a high milk feeding regimen, 32 Holstein calves (38.8±1.1kg) were assigned at birth to 1 of 3 treatments in a completely randomized block design. Dietary treatments (% of dry matter) were (1) 100% semi-texturized starter (CON); (2) 90% semi-texturized starter + 10% chopped alfalfa hay (mean particle size=5.4mm) as a total mixed ration (TMR; CH); and (3) 90% semi-texturized starter + 10% pelleted alfalfa (mean=5.8mm) hay as a TMR (PH). Data were subjected to mixed model analysis with contrasts used to evaluate effect of forage inclusion. Calves were weaned at 76 d of age and the experiment finished 2 wk after weaning. Individual milk and solid feed consumption were recorded daily. Solid feed consumption and ADG increased as age increased (effect of week), but neither forage inclusion nor physical form of forage affected these variables pre- or postweaning. Plasma urea N was affected by treatments such that the CON group had a lower concentration than forage-fed groups. Forage inclusion, but not physical form, resulted in increased total protein in plasma. Although days with elevated rectal temperature, fecal score, and general appearance were not affected by dietary treatments, calves fed alfalfa hay during the first month of life had fewer days with respiratory issues, regardless of physical form of hay. We concluded that provision of forage does have some beneficial effects in calves fed large amounts of milk replacer, but pelleted alfalfa hay did not result in any improvement in calf performance or health. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

B-Zell-Lymphome der Haut - Pathogenese, Diagnostik und Therapie.

Science.gov (United States)

Nicolay, Jan P; Wobser, Marion

2016-12-01

Primär kutane B-Zell-Lymphome (PCBCL) beschreiben reifzellige lymphoproliferative Erkrankungen der B-Zell-Reihe, die primär die Haut betreffen. Die Biologie und der klinische Verlauf der einzelnen PCBCL-Subtypen variieren untereinander stark und unterscheiden sich grundsätzlich von primär nodalen und systemischen B-Zell-Lymphomen. Primär kutane Marginalzonenlymphome (PCMZL) und primäre kutane follikuläre Keimzentrumslymphome (PCFCL) werden auf Grund ihres unkomplizierten Verlaufs und ihrer exzellenten Prognose zu den indolenten PCBCL gezählt. Demgegenüber stellen die diffus großzelligen B-Zell-Lymphome, hauptsächlich vom Beintyp (DLBCL, LT) die aggressiveren PCBCL-Varianten mit schlechterer Prognose dar. Für die Ausbreitungsdiagnostik und die Therapieentscheidung sind eine genaue histologische und immunhistochemische Klassifizierung sowie der Ausschluss einer systemischen Beteiligung in Abgrenzung zu nodalen oder systemischen Lymphomen notwendig. Die Diagnostik sollte dabei durch molekularbiologische Untersuchungen unterstützt werden. Therapeutisch stehen für die indolenten PCBCL primär operative und radioonkologische Maßnahmen im Vordergrund sowie eine Systemtherapie mit dem CD20-Antikörper Rituximab bei disseminiertem Befall. Die aggressiveren Varianten sollten in erster Linie mit Kombinationen aus Rituximab und Polychemotherapieschemata wie z. B. dem CHOP-Schema oder Modifikationen davon behandelt werden. Auf Grund der in allen seinen Einzelheiten noch nicht vollständig verstandenen Pathogenese und Biologie sowie des begrenzten Therapiespektrums der PCBCL besteht hier, speziell beim DLBCL, LT, noch erheblicher Forschungsbedarf. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

3-Bromopyruvate enhances TRAIL-induced apoptosis in human nasopharyngeal carcinoma cells through CHOP-dependent upregulation of TRAIL-R2.

Science.gov (United States)

Can, Zhou; Lele, Song; Zhirui, Zhang; Qiong, Pan; Yuzhong, Chen; Lingling, Liu; Surong, Zhao; Yiming, Sun; Pei, Zhang; Chenchen, Jiang; Liu, Hao

2017-08-01

Past reports have shown that the sensitivity of cancer cells to TRAIL-induced apoptosis is related to their expression of TRAIL-death receptors on the cell surface. However, the level of TRAIL-death receptors expression on cancer cells is always low. Our previous research showed that nasopharyngeal carcinoma (NPC) cells have a poor sensitivity to low doses of TRAIL. Here, we evaluated combined treatment with the energy inhibitor 3-bromopyruvate (3BP) and TRAIL as a method to produce an increased apoptotic response in NPC cells. The results showed that 3BP and TRAIL together produced higher cytotoxicity and increased TRAIL-R2 expression in NPC cells compared with the effects of either 3BP or TRAIL alone. These findings led us to hypothesize that 3BP may sensitize NPC cells to TRAIL. 3BP is a metabolic blocker that inhibits hexokinase II activity, suppresses ATP production, and induces endoplasmic reticulum (ER) stress. Our results showed that 3BP also activated AMP-activated protein kinase, which we found to play an important role in the induction of ER stress by 3BP. Furthermore, the induction of TRAIL-R2 expression and the sensitization of the NPC cells to TRAIL by 3BP were reduced when we inhibited the expression of CHOP. Taken together, our results showed that a low dose of 3BP sensitized NPC cells to TRAIL-induced apoptosis by the upregulation of CHOP, which was mediated by the activation of AMP-activated protein kinase and ER stress. The results showed that 3BP is a promising candidate agent for enhancing the therapeutic response to TRAIL in NPC.

Changes in the positron-electron momentum distribution in GaAs brought about by chopped light

International Nuclear Information System (INIS)

Li, S.; Fung, S.; Beling, C.D.; Ling, C.C.

2001-01-01

We report on an attempt to observe the EL2→ EL2 * transition in semi-insulating GaAs using Doppler broadening of annihilation radiation spectroscopy. Unlike the original observation of this transition using positron annihilation spectroscopy, the present method has sought to observe the production of EL2 * through a light chopping experiment, where on the half cycle of illumination the EL2 * state is formed and on the second half cycle the EL2 * thermally quenches back to EL2. While results are at a preliminary state we have obtained evidence for the production of EL2 * from the broad-band emission of a Xenon lamp. While calculations suggest that we should be able to see the EL2 * from the IR emission (1.3eV) of GaAs light emitting diodes we have not yet been able to achieve this. Reasons why are discussed. (orig.)

Three Point Bending of Top-Hat Stiffened Chopped Short Fibre Ramie/HDPE Thermoplastic Composite Beam

Science.gov (United States)

Hadi, Bambang K.; Nuril, Yogie S.

2018-04-01

The use of natural fibre and thermoplastic matrices in composite materials increased significantly during the last decade especially in the automotive industries. Ramie is one of these potential natural fibres. In this paper, a three point bending of top-hat beam made of ramie/HDPE (High-Density-Polyethylene) composites was performed. Top-hat stiffened structures were common structures found in the aerospace industries. Nevertheless, these structures are beginning to be applied in automotive structures in the forms of chassis and bumpers. The ramie/HDPE composite was manufactured using hot-press technique. The temperature was set to be 135°C and the pressure was 6 bars. Chopped short ramie fibre was used, due to good drape ability characteristics. The experiments showed that the beams produced a large non-linearity. Linear Finite Element Analysis was carried out to be compared with the experimental data. The differences are reasonable.

The role of FDG-PET imaging as a prognostic marker of outcome in primary mediastinal B-cell lymphoma

International Nuclear Information System (INIS)

Nagle, Sarah J; Chong, Elise A; Chekol, Seble; Shah, Nirav N; Nasta, Sunita D; Glatstein, Eli; Plastaras, John P; Torigian, Drew A; Schuster, Stephen J; Svoboda, Jakub

2015-01-01

Primary mediastinal B-cell lymphoma (PMBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that arises in the mediastinum from B-cells of thymic origin. Optimal management of patients with PMBL remains controversial. The present study evaluates outcomes of 27 PMBL patients treated with R-CHOP with or without radiation therapy (RT). It investigates the role of both interim and posttreatment fluorodeoxyglucose-positron emission tomography (FDG-PET) as prognostic markers of outcome. Additionally, it assesses postprogression therapies in the six patients who had progressive disease. At a median follow-up of 41.5 months (range: 6.1–147.2 months), OS was 95.5% (95% CI = 71.9–99.4) and progression-free survival (PFS) was 70.4% (95% CI = 49.4–83.9) for the entire cohort. The negative predictive values of interim and posttreatment FDG-PET scans were both 100%. Patients who failed initial therapy and were treated with salvage regimens and autologous stem cell transplantation (ASCT) all achieved and maintained CR. PMBL patients can achieve excellent outcomes with minimal toxicities when treated with R-CHOP with or without RT. Negative interim and negative posttreatment FDG-PET results identified PMBL patients who achieve long-term remission. However, the significance of both positive interim and positive posttreatment FDG-PET results needs to be better defined. Those who failed initial therapy were successfully treated with salvage regimens and ASCT

PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro.

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Lina Quan

Full Text Available Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1 antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL.

Patterns of failure of diffuse large B-cell lymphoma patients after involved-site radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Holzhaeuser, Eva; Berlin, Maximilian; Bezold, Thomas; Mayer, Arnulf; Schmidberger, Heinz [University Medical Center Mainz, Department of Radiation Oncology and Radiotherapy, Mainz (Germany); Wollschlaeger, Daniel [University Medical Center Mainz, Institute for Medical Biostatistics, Epidemiology and Informatics, Mainz (Germany); Hess, Georg [University Medical Center Mainz, Department of Internal Medicine, Mainz (Germany)

2017-12-15

Radiotherapy (RT) in combination with chemoimmunotherapy is highly efficient in the treatment of diffuse large B-cell lymphoma (DLBCL). This retrospective analysis evaluated the efficacy of the treatment volume and the dose concept of involved-site RT (ISRT). We identified 60 histologically confirmed stage I-IV DLBCL patients treated with multimodal cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005-2015. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate analyses were performed by log-rank test and Mann-Whitney U-test. After initial chemoimmunotherapy (mostly R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 19 (36%) patients achieved complete response (CR), 34 (64%) partial response (PR) or less. Excluded were 7 (12%) patients with progressive disease after chemoimmunotherapy. All patients underwent ISRT with a dose of 40 Gy. After a median follow-up of 44 months, 79% of the patients remained disease free, while 21% presented with failure, progressive systemic disease, or death. All patients who achieved CR after chemoimmunotherapy remained in CR. Of the patients achieving PR after chemotherapy only 2 failed at the initial site within the ISRT volume. No marginal relapse was observed. Ann Arbor clinical stage I/II showed significantly improved PFS compared to stage III/IV (93% vs 65%; p ≤ 0.021). International Prognostic Index (IPI) score of 0 or 1 compared to 2-5 has been associated with significantly increased PFS (100% vs 70%; p ≤ 0.031). Postchemoimmunotherapy status of CR compared to PR was associated with significantly increased PFS (100% vs 68%; p ≤ 0.004) and OS (100% vs 82%; p ≤ 0.026). Only 3 of 53 patients developed grade II late side effects, whereas grade III or IV side effects have not been observed. These data suggest that a reduction of the RT treatment volume from involved-field (IF) to involved-site (IS) is sufficient because

Chopped basalt fibres: A new perspective in reinforcing poly(lactic acid to produce injection moulded engineering composites from renewable and natural resources

Directory of Open Access Journals (Sweden)

P. Tamas

2013-02-01

Full Text Available This paper focuses on the reinforcing of Poly(lactic acid with chopped basalt fibres by using silane treated and untreated basalt fibres. Composite materials with 5–10–15–20–30–40 wt% basalt fibre contents were prepared from silane sized basalt fibres using extrusion, and injection moulding, while composites with 5–10–15 wt% basalt fibre contents were also prepared by using untreated basalt fibres as control. The properties of the injection moulded composites were extensively examined by using quasi-static (tensile, three-point bending and dynamic mechanical tests (notched and unnotched Charpy impact tests, dynamic mechanical analysis (DMA, differential scanning calorimetry (DSC, heat deflection temperature (HDT analysis, dimensional stability test, as well as melt flow index (MFI analysis and scanning electron microscopic (SEM observations. It was found that silane treated chopped basalt fibres are much more effective in reinforcing Poly(lactic acid than natural fibres; although basalt fibres are not biodegradable but they are still considered as natural (can be found in nature in the form of volcanic rocks and biologically inert. It is demonstrated in this paper that by using basalt fibre reinforcement, a renewable and natural resource based composite can be produced by injection moulding with excellent mechanical properties suitable even for engineering applications. Finally it was shown that by using adequate drying of the materials, composites with higher mechanical properties can be achieved compared to literature data.

A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy.

Science.gov (United States)

Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

2016-08-01

Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

Effect of gamma irradiation on the B vitamins of pork chops and chicken breasts

International Nuclear Information System (INIS)

Fox, J.B. Jr.; Thayer, D.W.; Jenkins, R.K.; Phillips, J.G.; Ackerman, S.A.; Beecher, G.R.; Holden, J.M.; Morrow, F.D.; Quirbach, D.M.

1989-01-01

A study was made of the effect of low-dose gamma irradiation on the content of thiamine (B 1 ), riboflavin (B 2 ), niacin, pyridoxine (B 6 ) and cobalamin (B 12 ) in pork chops, and thiamine, riboflavin and niacin in chicken breasts. Over the range of dose and temperature studied (0.49-6.65 kGy from -20 to 20 0 C) it was possible to derive a mathematical expression for predicting losses. A calculation was made of the effect of the loss of thiamine, riboflavin and niacin due to irradiation on overall loss of these vitamins in the American diet. Losses of riboflavin and niacin were of the order of a fraction of a per cent. The calculated loss at 1.0kGy of thiamine in cooked pork was only 1.5%. There were initial increases with radiation doses up to 2-4 kGy in measured concentrations of riboflavin and niacin in pork and chicken. Increases were highly significant, and of concern to the study of radiation effects and the chemical method of determination of these vitamins. (author)

Carriers of a VEGFA enhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone

DEFF Research Database (Denmark)

Ahluwalia, Tarun Veer Singh; Troelsen, Jesper Thorvald; Balslev-Harder, Marie

2017-01-01

BACKGROUND: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (VEGFA) gene are associated with TSH levels. The aim of this study was to characterise...... levels (p=0.0014). The SNP rs881858 is located in a binding site for CHOP (C/EBP homology protein) and c/EBPβ (ccaat enhancer binding protein β). Reporter-gene analysis showed increased basal enhancer activity of the rs881858 A-allele versus the G-allele (34.5±9.9% (average±SEM), p=0.0012), while co...

Chop Shop and Foreign Parts settle on the fuzzy boundary between fiction and documentary: new representations of New York City in Contemporary Cinema.

Directory of Open Access Journals (Sweden)

Fernando Canet

2013-06-01

Full Text Available Capturing reality has been a constant aim of different movements throughout the history of the cinema. Historically, this challenge has been taken up by makers of both documentaries and fiction, through hybrid proposals that blended strategies from both fields. Even though these proposals have been ignored by traditional film historians, they constitute a persistent tendency from the cinema’s earliest times, as Rhodes and Springer pointed out in their book Docufictions: Essay on the intersection of documentary and fictional filmmaking (2006. There are good examples of these proposals in contemporary cinema that have even won awards at leading international film festivals, including the two movies referred to in this paper: the fictional Chop Shop made by Ramin Bahrani in 2007 and the documentary Foreign Parts by Verena Paravel and J.P. Sniadecki in 2010. Both movies try to portray the same reality in the form of the little known Willets Point (Queens, New York City. Both films aim to show the truth behind the reality portrayed by its inhabitants in real life situations. The main goal of this paper is to reveal their manner of doing this and to show how both movies, even though belonging to different genres, share the same strategies to such an extent that their images could be interchangeable.

Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma

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Hannah ePhipps-Yonas

2013-12-01

Full Text Available The MHC class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4+ T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL, the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT, an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for MHC class II binding and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics.

Bullet Design and Fabrication of Dual Mode Pyroelectric Sensor: High Sensitive Energymeter for Nd: YAG Laser and Detector for Chopped He-Ne Laser

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S. SATAPATHY

2008-05-01

Full Text Available Pyroelectric sensor using TGS has been designed and fabricated which can be operated in laser energy meter mode as well as pyroelectric detector mode. The amplifying circuit configuration has very good signal to noise ratio, very high input impedance and low drift. The pyroelectric sensor has been tested using Q-switched Nd: YAG laser and chopped He-Ne laser. The sensitivity of pyroelectric sensor in energymeter mode is 421.7V/J and the voltage responsivity of the pyroelectric sensor is 3.27 V/W in detector mode.

Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

Energy Technology Data Exchange (ETDEWEB)

Miao, Xiaobing; Wu, Yaxun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Wang, Yuchan [Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Zhu, Xinghua; Yin, Haibing [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Yunhua [Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Xu, Xiaohong, E-mail: xuxiaohongnantong@126.com [Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China)

2016-08-15

YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1{sup S102} were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1{sup S102} nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. - Highlights: • The expression statuses of YB-1 and pYB-1{sup S102} are reversely correlated with outcomes of DLBCL patients. • YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL. • YB-1 confers drug resistance to mitoxantrone in DLBCL.

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

Science.gov (United States)

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Hishima, Tsunekazu; Omuro, Yasushi

2018-06-01

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies.

Science.gov (United States)

Seelig, Davis M; Ito, Daisuke; Forster, Colleen L; Yoon, Una A; Breen, Matthew; Burns, Linda J; Bachanova, Veronika; Lindblad-Toh, Kerstin; O'Brien, Timothy D; Schmechel, Stephen C; Rizzardi, Anthony E; Modiano, Jaime F; Linden, Michael A

2017-07-01

Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

Science.gov (United States)

Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

2017-02-01

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

International Nuclear Information System (INIS)

Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

2017-01-01

Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

Increased expression of IRF8 in tumor cells inhibits the generation of Th17 cells and predicts unfavorable survival of diffuse large B cell lymphoma patients.

Science.gov (United States)

Zhong, Weijie; Xu, Xin; Zhu, Zhigang; Du, Qinghua; Du, Hong; Yang, Li; Ling, Yanying; Xiong, Huabao; Li, Qingshan

2017-07-25

The immunological pathogenesis of diffuse large B cell lymphoma (DLBCL) remains elusive. Searching for new prognostic markers of DLBCL is a crucial focal point for clinical scientists. The aim of the present study was to examine the prognostic value of interferon regulatory factor 8 (IRF8) expression and its effect on the development of Th17 cells in the tumor microenvironment of DLBCL patients. Flow cytometry, immunohistochemistry, and quantitative real-time PCR were used to detect the distribution of Th17 cells and related cytokines and IRF8 in tumor tissues from DLBCL patients. Two DLBCL cell lines (OCI-LY10 and OCI-LY1) with IRF8 knockdown or overexpression and two human B lymphoblast cell lines were co-cultured with peripheral blood mononuclear cells (PBMCs) in vitro to determine the effect of IRF8 on the generation of Th17 cells. Quantitative real-time PCR and Western blotting were used to investigate the involvement of retinoic acid receptor-related orphan receptor gamma t (RORγt) in the effect of IRF8 on Th17 cell generation. The survival of 67 DLBCL patients was estimated using the Kaplan-Meier method and log-rank analysis. The percentage of Th17 cells was lower in DLBCL tumor tissues than in PBMCs and corresponding adjacent benign tissues. Relative expression of interleukin (IL)-17A was lower, whereas that of interferon (IFN)-γ was higher in tumor tissues than in benign tissues. Co-culture with DLBCL cell lines inhibited the generation of Th17 cells in vitro. IRF8 upregulation was detected in DLBCL tumor tissues, and it was associated with decreased DLBCL patient survival. Investigation of the underlying mechanism suggested that IRF8 upregulation in DLBCL, through an unknown mechanism, inhibited Th17 cell generation by suppressing RORγt in neighboring CD4+ T cells. Tumor cells may express soluble or membrane-bound factors that inhibit the expression of RORγt in T cells within the tumor microenvironment. Our findings suggest that IRF8 expression could

Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Biccler, Jorne Lionel; Eloranta, Sandra; Brown, Peter de Nully

2018-01-01

The international prognostic index (IPI) and similar models form the cornerstone of clinical assessment in newly diagnosed diffuse large B-cell lymphoma (DLBCL). While being simple and convenient to use, their inadequate use of the available clinical data is a major weakness. In this study, we co...

Uterine, but not ovarian, female reproductive organ involvement at presentation by diffuse large B-cell lymphoma is associated with poor outcomes and a high frequency of secondary CNS involvement

DEFF Research Database (Denmark)

El-Galaly, Tarec Christoffer; Cheah, Chan Y; Hutchings, Martin

2016-01-01

progression-free survival and overall survival compared to those without reproductive organ involvement, whereas ovarian DLBCL was not predictive of outcome. Secondary central nervous system (CNS) involvement (SCNS) occurred in 7/17 (41%) women with uterine DLBCL (two patients with concomitant ovarian DLBCL...

Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

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Cha, Zhanshan [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Qian, Guangfang [Department of Endocrinology, Zhangqiu Municipal Hospital of Traditional Chinese Medicine, Zhangqiu, Shandong 250200 (China); Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Song, Haihan [Emergency Center, East Hospital, Shanghai 200120 (China); Qian, Baohua, E-mail: qianbhl963@163.com [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

2017-01-01

Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5{sup +} CD4{sup +} T cells, in DLBCL. Data showed that compared to CXCR5{sup -} CD4{sup +} T cells, CXCR5{sup +} CD4{sup +} T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5{sup +} CD4{sup +} T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5{sup -} CD4{sup +} T cells, while the level of IL-10 secretion was significant elevated in the CXCR5{sup +} compartment compared to the CXCR5{sup -} compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5{sup +} CD4{sup +} T cell coculture compromised the CXCR5{sup +} CD4{sup +} T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5{sup +} compartment also contained significantly lower frequencies of cytotoxic CD4{sup +} T cells than the CXCR5{sup -} compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4{sup +} T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature

Directory of Open Access Journals (Sweden)

Tirado Carlos A

2012-09-01

Full Text Available Abstract Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH, as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS. The advent of microarray-based studies (chromosome, RNA, gene expression, etc has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1 array based CGH; 2 classical CGH; and 3 gene expression profiling studies. The aims of this review were three-fold: (1 to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2 to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3 to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such

Survival of Listeria monocytogenes and Salmonella typhimurium and quality attributes of cooked pork chops and cured ham after irradiation

International Nuclear Information System (INIS)

Fu, A.H.; Sebranek, J.G.; Murano, E.A.

1995-01-01

Cooked pork chops (pumped with salt/polyphosphate brine or untreated) and cured hams were inoculated with Listeria monocytogenes and Salmonella typhimurium. The samples were irradiated at low (0.75 to 0.90 kGy) or medium doses (1.8 to 2.0 kGy), and each dose was delivered at either a low (2.5 M/min conveyor speed) or high (5.4 M/min) dose rate. Low-dose irradiation reduced L. monocytogenes by more than 2 log and S. typhimurium by 1 to 3 log. Pathogen populations and total plate counts (TPC) were reduced to undetectable levels by medium doses. No meat quality attributes were affected, and no dose rate effect was observed. Nitrite reduced (P 0.05) both pathogens and TPC during 7 degrees C storage in ham, especially when combined with low-dose irradiation

Analysis of the microbiota of refrigerated chopped parsley after treatments with a coating containing enterocin AS-48 or by high-hydrostatic pressure.

Science.gov (United States)

Grande Burgos, María José; López Aguayo, María Del Carmen; Pérez Pulido, Rubén; Galvez, Antonio; Lucas, Rosario

2017-09-01

Parsley can be implicated in foodborne illness, yet chopped parsley is used as an ingredient or garnish for multiple dishes. The aim of the present study was to determine the effect of two different treatments on the bacterial diversity of parsley: (i) coating with a pectin-EDTA solution containing the circular bacteriocin enterocin AS-48, and (ii) treatment by high hydrostatic pressure (HHP) at 600MPa for 8min. Control and treated parsley were stored in trays at 5°C for 10days. Both treatments reduced viable counts by 3.7 log cycles and retarded growth of survivors during storage. The bacterial diversity of the chopped parsley was studied by high throughput sequencing (Illumina Miseq). Bacterial diversity of control samples mainly consists of Proteobacteria (96.87%) belonging to genera Pseudomonas (69.12%), Rheinheimera (8.56%) and Pantoea (6.91%) among others. During storage, the relative abundance of Bacteroidetes (mainly Flavobacterium and Sphingobacterium) increased to 26.66%. Application of the pectin-bacteriocin-EDTA coating reduced the relative abundance of Proteobacteria (63.75%) and increased that of Firmicutes (34.70%). However, the relative abundances of certain groups such as Salmonella, Shigella and Acinetobacter increased at early storage times. Late storage was characterized by an increase in the relative abundance of Proteobacteria, mainly Pseudomonas. Upon application of HHP treatment, the relative abundance of Proteobacteria was reduced (85.88%) while Actinobacteria increased (8.01%). During early storage of HHP-treated samples, the relative abundance of Firmicutes increased. Potentially-pathogenic bacteria (Shigella) only increased in relative abundance by the end of storage. Results of the present study indicate that the two treatments had different effects on the bacterial diversity of parsley. The HHP treatment provided a safer product, since no potentially-pathogenic bacteria were detected until the end of the storage period. Copyright �

Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK/ERK signaling pathway.

Science.gov (United States)

Wang, Yingjun; Zhang, Mingzhi; Xu, Huanan; Wang, Yifei; Li, Zhaoming; Chang, Yu; Wang, Xinhuan; Fu, Xiaorui; Zhou, Zhiyuan; Yang, Siyuan; Wang, Bei; Shang, Yufeng

2017-09-22

Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Recent studies have shown that long non-coding RNAs (lncRNAs) play an important role in the development of cancer. By using the next generation HiSeq sequencing assay, we determined lncRNAs exhibiting differential expression between DLBCL patients and healthy controls. Then, RT-qPCR was performed for identification in clinical samples and cell materials, and lncRNA PANDA was verified to be down-regulated in DLBCL patients and have considerable diagnostic potential. In addition, decreased serum PANDA level was correlated to poorer clinical outcome and lower overall survival in DLBCL patients. Subsequently, we determined the experimental role of lncRNA PANDA in DLBCL progression. Luciferase reporter assay and chromatin immunoprecipitation assay suggested that lncRNA PANDA was induced by p53 and p53 interacts with the promoter region of PANDA. Cell functional assay further indicated that PANDA functioned as a tumor suppressor gene through the suppression of cell growth by a G0/G1 cell cycle arrest in DLBCL. More importantly, Cignal Signal Transduction Reporter Array and western blot assay showed that lncRNA PANDA inactivated the MAPK/ERK signaling pathway. In conclusion, our integrated approach demonstrates that PANDA in DLBCL confers a tumor suppressive function through inhibiting cell proliferation and silencing MAPK/ERK signaling pathway. Thus, PANDA may be a promising therapeutic target for patients with DLBCL.

Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

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Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

2014-11-15

We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries

DEFF Research Database (Denmark)

Ok, Chi Young; Li, Ling; Xu-Monette, Zijun Y

2014-01-01

PURPOSE: Epstein-Barr virus-positive (EBV(+)) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV(+) DLBCL, independent of age...

ACCELEROMETERS IN FLOW FIELDS: A STRUCTURAL ANALYSIS OF THE CHOPPED DUMMY INPILE TUBE

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Howard, T. K.; Marcum, W. R.; Latimer, G. D.; Weiss, A.; Jones, W. F.; Phillips, A. M.; Woolstenhulme, N.; Holdaway, K.; Campbell, J.

2016-06-01

Four tests characterizing the structural response of the Chopped-Dummy In-Pile tube (CDIPT) experiment design were measured in the Hydro-Mechanical Fuel Test Facility (HMFTF). Four different test configurations were tried. These configurations tested the pressure drop and flow impact of various plate configurations and flow control orifices to be used later at different reactor power levels. Accelerometers were placed on the test vehicle and flow simulation housing. A total of five accelerometers were used with one on the top and bottom of the flow simulator and vehicle, and one on the outside of the flow simulator. Data were collected at a series of flow rates for 5 seconds each at an acquisition rate of 2 kHz for a Nyquist frequency of 1 kHz. The data were then analyzed using a Fast Fourier Transform (FFT) algorithm. The results show very coherent vibrations of the CDIPT experiment on the order of 50 Hz in frequency and 0.01 m/s2 in magnitude. The coherent vibrations, although small in magnitude pose a potential design problem if the frequencies coincide with the natural frequency of the fueled plates or test vehicle. The accelerometer data was integrated and combined to create a 3D trace of the experiment during the test. The merits of this data as well as further anomalies and artifacts are also discussed as well as their relation to the instrumentation and experiment design.

Utilization of gum tragacanth as bind enhancing agent in extended restructured mutton chops.

Science.gov (United States)

Sharma, Heena; Sharma, B D; Talukder, S; Ramasamy, Giriprasad

2015-03-01

Use of extenders in meat products is not only health promoting but can also increase the economic worth of the products. Extension of the meat product is generally associated with poor binding and texture. Thus, the present study was envisaged to solve this problem by the incorporation of gum tragacanth (GT) as bind enhancing agent, used at three different levels viz., 0.1, 0.15 and 0.2 % in a pre standardized formulation of extended restructured mutton chops (ERMC), by replacing the lean meat. The products were subjected to analysis for physico-chemical, sensory and textural properties. There was no significant difference (P > 0.05) in any of the physicochemical property parameters of product incorporated with different levels of GT except fat percent and shear force value. Mean scores for binding, texture and overall acceptability of ERMC incorporated with 0.1 % GT recorded significantly higher value (P < 0.05) than control and other treatment products. On the basis of sensory scores and physico-chemical properties, the optimum incorporation level of GT was adjudged as 0.1 %. Hardness and adhesiveness values were significantly higher (P < 0.05) in product with 0.1 % GT level. The product with optimum level of GT was also assessed for water activity (aw) and microbiological characteristics. It was found that treatment as well as control products were quite acceptable up to 15th day of storage period without any marked differences in sensory quality.

Single agent and synergistic combinatorial efficacy of first-in-class small molecule imipridone ONC201 in hematological malignancies.

Science.gov (United States)

Prabhu, Varun V; Talekar, Mala K; Lulla, Amriti R; Kline, C Leah B; Zhou, Lanlan; Hall, Junior; Van den Heuvel, A Pieter J; Dicker, David T; Babar, Jawad; Grupp, Stephan A; Garnett, Mathew J; McDermott, Ultan; Benes, Cyril H; Pu, Jeffrey J; Claxton, David F; Khan, Nadia; Oster, Wolfgang; Allen, Joshua E; El-Deiry, Wafik S

2018-01-01

ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1-8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma, anaplastic large cell lymphoma (ALCL), cutaneous T-cell lymphoma (CTCL), Hodgkin's lymphoma (nodular sclerosis) and multiple myeloma (MM) cell lines including cells resistant to standard of care (dexamethasone in MM) and primary samples. ONC201 induced caspase-dependent apoptosis that involved activation of the integrated stress response (ATF4/CHOP) pathway, inhibition of Akt phosphorylation, Foxo3a activation, downregulation of cyclin D1, IAP and Bcl-2 family members. ONC201 synergistically reduced cell viability in combination with cytarabine and 5-azacytidine in AML cells. ONC201 combined with cytarabine in a Burkitt's lymphoma xenograft model induced tumor growth inhibition that was superior to either agent alone. ONC201 synergistically combined with bortezomib in MM, MCL and ALCL cells and with ixazomib or dexamethasone in MM cells. ONC201 combined with bortezomib in a Burkitt's lymphoma xenograft model reduced tumor cell density and improved CHOP induction compared to either agent alone. These results serve as a rationale for ONC201 single-agent trials in relapsed/refractory acute leukemia, non-Hodgkin's lymphoma, MM and combination trial with dexamethasone in MM, provide pharmacodynamic biomarkers and identify further synergistic combinatorial regimens that can be explored in the clinic.

Effect of ensiling time and exogenous protease addition to whole-plant corn silage of various hybrids, maturities, and chop lengths on nitrogen fractions and ruminal in vitro starch digestibility.

Science.gov (United States)

Ferraretto, L F; Crump, P M; Shaver, R D

2015-12-01

The objective of this study was to evaluate the effects of ensiling time and exogenous protease addition on soluble CP (% of CP), ammonia-N (% of N), and ruminal in vitro starch digestibility (ivSD) of whole-plant corn silage (WPCS) from 3 hybrids, 2 maturities, and 2 chop lengths. Samples from 3 nonisogenic hybrids [brown midrib containing the bm3 gene mutation (BM3), dual-purpose (DP), or floury-leafy (LFY)] at 2 harvest maturities [2/3 kernel milk line (early) or 7d later (late)] with 2 theoretical lengths of cut settings (0.64 or 1.95cm) on a forage harvester were collected at harvest, treated with or without exogenous protease, and ensiled in triplicate in vacuum heat-sealed plastic bags for 0, 30, 60, 120, and 240d. Thus, the experiment consisted of 120 treatments (3 hybrids × 2 maturities × 2 chop lengths × 2 protease treatments × 5 time points) and 360 mini-silos (3 replications per treatment). Vitreousness, measured by dissection on unfermented kernels on the day of harvest, averaged 66.8, 65.0, and 59.0% for BM3, DP, and LFY, respectively. A protease × maturity interaction was observed with protease increasing ivSD in late but not early maturity. Ensiling time × hybrid interactions were observed for ammonia-N and soluble CP concentrations with greater values for FLY than other hybrids only after 120d of ensiling. Ensiling time × hybrid or protease × hybrid interactions were not observed for ivSD. Measurements of ivSD were greatest for FLY and lowest for BM3. Length of the ensiling period did not attenuate negative effects of kernel vitreousness or maturity on ivSD in WPCS. Results suggest that the dosage of exogenous protease addition used in the present study may reduce but not overcome the negative effects of maturity on ivSD in WPCS. No interactions between chop length and ensiling time or exogenous protease addition were observed for ivSD. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Straight and chopped dc performance data for a Prestolite MTC-4001 motor and a general electric EV-1 controller

Science.gov (United States)

Edie, P. C.

1981-01-01

Performance data on the Prestolite MTC-4001 series wound dc motor and General Electric EV-1 Chopper Controller is supplied for the electric vehicle manufacturer. Data are provided for both straight and chopped dc input to the motor, at 2 motor temperature levels. Testing was done at 6 voltage increments to the motor, and 2 voltage increments to the controller. Data results are presented in both tabular and graphical forms. Tabular information includes motor voltage and current input data, motor speed and torque output data, power data and temperature data. Graphical information includes torque-speed, motor power output-speed, torque-current, and efficiency-speed plots under the various operating conditions. The data resulting from this testing show the speed-torque plots to have the most variance with operating temperature. The maximum motor efficiency is between 76% and 82%, regardless of temperature or mode of operation.

Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

Science.gov (United States)

Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

2015-08-15

Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

Science.gov (United States)

Sorigue, Marc; Garcia, Olga; Baptista, Maria Joao; Sancho, Juan-Manuel; Tapia, Gustavo; Mate, José Luis; Feliu, Evarist; Navarro, José-Tomás; Ribera, Josep-Maria

2017-03-22

The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Immunoglobulin gene repertoire diversification and selection in the stomach – from gastritis to gastric lymphomas

Directory of Open Access Journals (Sweden)

Miri eMichaeli

2014-06-01

Full Text Available Chronic gastritis is characterized by gastric mucosal inflammation due to autoimmune responses or infection, frequently with Helicobacter pylori. Gastritis with H. pylori background can cause gastric mucosa-associated lymphoid tissue lymphoma (MALT-L, which sometimes further transforms into diffuse large B cell lymphoma (DLBCL. However, gastric DLBCL can also be initiated de novo. The mechanisms underlying transformation into DLBCL are not completely understood. We analyzed immunoglobulin repertoires and clonal trees to investigate whether and how immunoglobulin gene repertoires, clonal diversification and selection in gastritis, gastric MALT-L and DLBCL differ from each other and from normal responses. The two gastritis types (positive or negative for H. pylori had similarly diverse repertoires. MALT-L dominant clones presented higher diversification and longer mutational histories compared with all other conditions. DLBCL dominant clones displayed lower clonal diversification, suggesting the transforming events are triggered by similar responses in different patients. These results are surprising, as we expected to find similarities between the dominant clones of gastritis and MALT-L and between those of MALT-L and DLBCL.

Histone deacetylase 1, 2, 6 and acetylated histone H4 in B- and T-cell lymphomas

DEFF Research Database (Denmark)

Marquard, L.; Poulsen, C.B.; Gjerdrum, L.M.

2009-01-01

AIMS: Histone deacetylase (HDAC) inhibitors are novel therapeutics in the treatment of peripheral T-cell lymphoma, unspecified (PTCL) and diffuse large B-cell lymphoma (DLBCL), where, for unknown reasons, T-cell malignancies appear to be more sensitive than B-cell malignancies. The aim was to det......AIMS: Histone deacetylase (HDAC) inhibitors are novel therapeutics in the treatment of peripheral T-cell lymphoma, unspecified (PTCL) and diffuse large B-cell lymphoma (DLBCL), where, for unknown reasons, T-cell malignancies appear to be more sensitive than B-cell malignancies. The aim...... was to determine HDAC expression in DLBCL and PTCL which has not previously been investigated. METHODS AND RESULTS: The expression of HDAC1, HDAC2, HDAC6 and acetylated histone H4 was examined immunohistochemically in 31 DLBCL and 45 PTCL. All four markers showed high expression in both DLBCL and PTCL compared...

Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

Directory of Open Access Journals (Sweden)

Azhar R Hussain

Full Text Available BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL. In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene, a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS. Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

Synchronous Microscopic Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Adrenal and Lymphoplasmacytic Lymphoma: De Novo Disease or Transformation?

Science.gov (United States)

Moonim, Mufaddal T; Nasir, Alia; Hubbard, Jonathan; Ketley, Nicholas; Fields, Paul

2017-06-01

Lymphomas arising in the adrenal are rare, and to our knowledge, 2 cases of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (DLBCL) in an adrenal pseudocyst have been reported. We report an incidental EBV-positive DLBCL arising in an adrenal pseudocyst in a 58-year-old man with a 7-year history of lymphoplasmacytic lymphoma (LPL). The DLBCL was present in the fibrinous exudate, while the LPL resided in the cyst wall. The patient underwent de-roofing of the same cyst 3 years previously; review of histology revealed foci of LPL in the cyst wall, but not of DLBCL. There have been reports of similar microscopic EBV-positive DLBCLs within enclosed cystic spaces. However, all these cases were incidental extranodal primary DLBCLs. Since residual LPL was present alongside DLBCL, with similar light chain restriction, we propose that this may represent transformation, rather than a de novo primary EBV-driven lymphoma.

Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era.

Science.gov (United States)

Howlader, Nadia; Mariotto, Angela B; Besson, Caroline; Suneja, Gita; Robien, Kim; Younes, Naji; Engels, Eric A

2017-09-01

Survival after the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long-term outcomes for these patients in the modern treatment era are still unknown. Using Surveillance, Epidemiology, and End Results data, this study first assessed factors associated with DLBCL-specific mortality during 2002-2012. An epidemiologic risk profile, based on clinical and demographic characteristics, was used to stratify DLBCL cases into low-, medium-, and high-risk groups. The proportions of DLBCL cases that might be considered cured in these 3 risk groups was estimated. Risks of death due to various noncancer causes among DLBCL cases versus the general population were also calculated with standardized mortality ratios (SMRs). Overall, 8274 deaths were recorded among 18,047 DLBCL cases; 76% of the total deaths were attributed to DLBCL, and 24% were attributed to noncancer causes. The 10-year survival rates for the low-, medium-, and high-risk groups were 80%, 60%, and 36%, respectively. The estimated cure proportions for the low-, medium-, and high-risk groups were 73%, 49%, and 27%, respectively; however, these cure estimates were uncertain because of the need to extrapolate the survival curves beyond the follow-up time. Mortality risks calculated with SMRs were elevated for conditions including vascular diseases (SMR, 1.3), infections (SMR, 3.1), gastrointestinal diseases (SMR, 2.5), and blood diseases (SMR, 4.6). These mortality risks were especially high within the initial 5 years after the diagnosis and declined after 5 years. Some DLBCL patients may be cured of their cancer, but they continue to experience excess mortality from lymphoma and other noncancer causes. Cancer 2017;123:3326-34. © 2017 American Cancer Society. © 2017 American Cancer Society.

Straight and chopped dc performance data for a General Electric 5BT 2366C10 motor and an EV-1 controller

Science.gov (United States)

Edie, P. C.

1981-01-01

Performance data on the General Electric 5BT 2366C10 series wound dc motor and EV-1 Chopper Controller is supplied for the electric vehicle manufacturer. Data is provided for both straight and chopped dc input to the motor, at 2 motor temperature levels. Testing was done at 6 voltage increments to the motor, and 2 voltage increments to the controller. Data results are presented in both tabular and graphical forms. Tabular information includes motor voltage and current input data, motor speed and torque output data, power data and temperature data. Graphical information includes torque-speed, motor power output-speed, torque-current, and efficiency-speed plots under the various operating conditions. The data resulting from this testing shows the speed-torque plots to have the most variance with operating temperature. The maximum motor efficiency is between 86% and 87%, regardless of temperature or mode of operation. When the chopper is utilized, maximum motor efficiency occurs when the chopper duty cycle approaches 100%.

International trade in meat: the tip of the pork chop.

Science.gov (United States)

Galloway, James N; Burke, Marshall; Bradford, G Eric; Naylor, Rosamond; Falcon, Walter; Chapagain, Ashok K; Gaskell, Joanne C; McCullough, Ellen; Mooney, Harold A; Oleson, Kirsten L L; Steinfeld, Henning; Wassenaar, Tom; Smil, Vaclav

2007-12-01

This paper provides an original account of global land, water, and nitrogen use in support of industrialized livestock production and trade, with emphasis on two of the fastest-growing sectors, pork and poultry. Our analysis focuses on trade in feed and animal products, using a new model that calculates the amount of "virtual" nitrogen, water, and land used in production but not embedded in the product. We show how key meat-importing countries, such as Japan, benefit from "virtual" trade in land, water, and nitrogen, and how key meat-exporting countries, such as Brazil, provide these resources without accounting for their true environmental cost. Results show that Japan's pig and chicken meat imports embody the virtual equivalent of 50% of Japan's total arable land, and half of Japan's virtual nitrogen total is lost in the US. Trade links with China are responsible for 15% of the virtual nitrogen left behind in Brazil due to feed and meat exports, and 20% of Brazil's area is used to grow soybean exports. The complexity of trade in meat, feed, water, and nitrogen is illustrated by the dual roles of the US and The Netherlands as both importers and exporters of meat. Mitigation of environmental damage from industrialized livestock production and trade depends on a combination of direct-pricing strategies, regulatory approaches, and use of best management practices. Our analysis indicates that increased water- and nitrogen-use efficiency and land conservation resulting from these measures could significantly reduce resource costs.

The conditions for use of reed canary grass briquettes and chopped reed canary grass in small heating plants; Foerutsaettningar foer anvaendning av roerflensbriketter och hackad roerflen i mindre vaermecentraler

Energy Technology Data Exchange (ETDEWEB)

Paulrud, Susanne; Davidsson, Kent; Holmgren, Magnus A. (Swedish National Testing and Research Inst., Boraas (Sweden)); Hedman, Henry; Oehman, Rikard; Leffler, Joel (ETC, Piteaa (Sweden))

2010-09-15

The aim of this study was to test fuel blends of briquettes and chopped reed canary grass in three existing heating plants (50 kW - 500 kW) and elucidate the requirements for good performance and low emissions. In addition, the study investigated production of reed canary grass briquettes using a Polish screw press developed for straw. Some tests with a bale shredder were also undertaken. The screw press technique is of interest for reed canary grass because it is a simple technique, easy to handle, developed for small scale production, and for straw. The test with reed canary grass in this study showed that the technique worked well but that further adjustments and a longer test period are needed in order to achieve higher bulk density and mechanical strength. The test with chopped reed canary grass shows that a system with a forage harvester is slightly more effective than baling and cutting in a bale shredder. The study concluded that few existing heating plants of size 50 kW-1 MW that currently use wood fuels will be able to use reed canary grass without adjustment, conversion or replacement of the combustion equipment. Reed canary grass has 15-20 times higher ash content than wood briquettes and 2-3 times higher ash content than forest residue; the combustion equipment must be able to handle these properties. The boiler must be equipped with a continuously operating ashing system and it must be possible to move the ash bed mechanically. There is a risk of high content of unburned matter if the residence time in the boiler is too short, due to the structure and low bulk density of the reed canary grass ash. Using a blend of wood briquettes and reed canary briquettes results in lower ash content, but also affects the ash chemistry and tends to lower the initial ash fusion temperature compared to using 100 % reed canary grass. Blending chopped reed canary grass and wood chips in an existing small scale heating plant also requires measures to achieve an even fuel

CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature

DEFF Research Database (Denmark)

Hu, Shimin; Xu-Monette, Zijun Y; Balasubramanyam, Aarthi

2013-01-01

CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD3...... value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL....

[A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

Science.gov (United States)

Gorgidze, L A; Vorob'ev, I A

2009-01-01

To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma.

Science.gov (United States)

Battistello, Elena; Katanayeva, Natalya; Dheilly, Elie; Tavernari, Daniele; Donaldson, Maria C; Bonsignore, Luca; Thome, Margot; Christie, Amanda L; Murakami, Mark A; Michielin, Olivier; Ciriello, Giovanni; Zoete, Vincent; Oricchio, Elisa

2018-05-24

In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR) promotes multiple oncogenic signals, which are essential for tumor proliferation. Inhibition of the Bruton's tyrosine kinase (BTK), a BCR downstream target, is therapeutically effective only in a subgroup of patients with DLBCL. Here, we used lymphoma cells isolated from patients with DLBCL to measure the effects of targeted therapies on BCR signaling and to anticipate response. In lymphomas resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor dependencies from alternative oncogenic signals downstream of the BCR, converging on MYC upregulation. To completely ablate the activity of the BCR, we genetically and pharmacologically repressed the activity of the SRC kinases LYN, FYN, and BLK, which are responsible for the propagation of the BCR signal. Inhibition of these kinases strongly reduced tumor growth in xenografts and cell lines derived from patients with DLBCL independent of their molecular subtype, advancing the possibility to be relevant therapeutic targets in broad and diverse groups of DLBCL patients. © 2018 by The American Society of Hematology.

Optimisation of metabolic criteria in the prognostic assessment in patients with lymphoma. A multicentre study.

Science.gov (United States)

Del Puig Cózar-Santiago, M; García-Garzón, J R; Moragas-Freixa, M; Soler-Peter, M; Bassa Massanas, P; Sánchez-Delgado, M; Sanchez-Jurado, R; Aguilar-Barrios, J E; Sanz-Llorens, R; Ferrer-Rebolleda, J

To compare sensitivity, specificity and predictive value of Deauville score (DS) vs. ΔSUVmax in interim-treatment PET (iPET) and end-treatment PET (ePET), in patients with diffuse large B cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and follicular lymphoma (FL). Retrospective longitudinal multicentre study including 138 patients (46 DLBCL, 46 HL, 46 FL), on whom 3 18 F-FDG PET/CT were performed: baseline, iPET, and ePET. Visual (DS) and semi-quantitative (ΔSUVmax) parameters were determined for iPET and ePET. Predictive value was determined in relation to disease-free interval. Statistical analysis. iPET for DLBCL, HL, and FL: 1) sensitivity of DS: 76.92/83.33/61.53%; specificity: 78.78/85/81.81%; 2) sensitivity of ΔSUVmax: 53.84/83.33/61.53%; specificity: 87.87/87.50/78.78%. ePET for DLBCL, HL and FL: 1) sensitivity of DS: 61.53/83.33/69.23%; specificity: 90.90/85/87.87%; 2) sensitivity of ΔSUVmax: 69.23/83.33/69.23%; specificity: 90.90/87.50/84.84%. Predictive assessment. iPET study: in DLBCL, DS resulted in 10.3% recurrence of negative iPET, and 17.1% in ΔSUVmax at disease-free interval; in HL, both parameters showed a 2.8% recurrence of negative iPET; in FL, DS resulted in 15.6% recurrence of negative iPET, and 16.1% in ΔSUVmax, with no statistical significance. ePET study: in DLBCL, DS resulted in 14.3% recurrence of negative ePET, and 11.8% in ΔSUVmax at disease-free interval; in HL and FL, both methods showed 2.8 and 12.5% recurrence in negative ePET, respectively. DS and ΔSUVmax did not show significant differences in DLBCL, HL and FL. Their predictive value also did not show significant differences in HL and FL. In DLBCL, DS was higher in iPET, and ΔSUVmax in ePET. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Medicinal therapy of malignant lymphomas; Medikamentoese Therapie maligner Lymphome

Energy Technology Data Exchange (ETDEWEB)

Aul, C.; Schroeder, M.; Giagounidis, A. [Medizinische Klinik II, St.-Johannes-Hospital Duisburg (Germany)

2002-12-01

Chemotherapy represents the most important therapeutic option in malignant lymphomas. Low to intermediate risk Hodgkin's disease is treated by a combination of chemotherapy and radiation. The new chemotherapy protocol BEACOPP has improved the outcome of advanced stages in comparison with the internationally accepted standard protocol COPP/ABVD. Dependent on the initial staging, cure rates between 50 and 95% can be achieved. Indolent non-Hodgkin's lymphomas usually present in advanced stages of disease. Chemotherapy in these cases has palliative character and aims at improving patients'quality of life and at avoiding complications due to the disease. In aggressive and very aggressive non-Hodgkin's lymphoma chemotherapy is curative and must be initiated immediately irrespective of the staging results. The efficacy of the standard protocol CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone), that was established in the 1970s, has recently been improved by shortening of the therapy interval (CHOP-14 vs.CHOP-21),addition of etoposide (CHOEP) and combination with the monoclonal antibody rituximab (R-CHOP). The value of high dose chemotherapy with stem cell transplantation has been shown unequivocally only for aggressive non-Hodgkin lymphoma and relapsed Hodgkin's disease responsive to chemotherapy. The therapeutic strategy of malignant lymphomas is likely to be improved within the next years due to the introduction of novel cytostatic agents, the broadening application of monoclonal antibodies,upcoming new transplantation procedures and the development of substances with molecular targets.To rapidly increase our current knowledge on the topic it is mandatory to include patients into the large national and international multicenter studies. (orig.) [German] Die Chemotherapie stellt die wichtigste Behandlungsoption maligner Lymphome dar. Bei Hodgkin-Lymphomen niedrigen bzw. intermediaeren Risikoprofils wird eine kombinierte Behandlung

The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity.

Directory of Open Access Journals (Sweden)

Ryan C Thompson

Full Text Available BACKGROUND: Diffuse large B-cell lymphoma (DLBCL is a genetically heterogeneous disease and this variation can often be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi's as monotherapy or in combination with other agents. METHODOLOGY/PRINCIPAL FINDINGS: We have used a variety of cell-based and molecular/biochemical assays to show that two pan-HDAC inhibitors, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Consistent with previous reports implicating the BCL-2 family in regulating HDACi-induced apoptosis, ectopic over-expression of anti-apoptotic proteins BCL-2 and BCL-XL or pro-apoptotic protein BIM in these cell lines conferred further resistance or sensitivity, respectively, to HDACi treatment. Additionally, BCL-2 family antgonist ABT-737 increased the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including one cell line (SUDHL6 that is resistant to vorinostat alone. Moreover, two variants of the HDACi-sensitive SUDHL4 cell line that have decreased sensitivity to vorinostat showed up-regulation of BCL-2 family anti-apoptotic proteins such as BCL-XL and MCL-1, as well as decreased sensitivity to ABT-737. These results suggest that the regulation and overall balance of anti- to pro-apoptotic BCL-2 family protein expression is important in defining the sensitivity of DLBCL to HDACi-induced apoptosis. However, the sensitivity of DLBCL cell lines to HDACi treatment does not correlate with expression of any individual BCL-2 family member. CONCLUSIONS/SIGNIFICANCE: These studies indicate that the sensitivity of DLBCL to treatment with HDACi's is dependent on the complex regulation of BCL-2 family members and that BCL-2 antagonists may enhance the response of a subset of DLBCL patients to HDACi treatment.

Similar chemokine receptor profiles in lymphomas with central nervous system involvement - possible biomarkers for patient selection for central nervous system prophylaxis, a retrospective study.

Science.gov (United States)

Lemma, Siria A; Pasanen, Anna Kaisa; Haapasaari, Kirsi-Maria; Sippola, Antti; Sormunen, Raija; Soini, Ylermi; Jantunen, Esa; Koivunen, Petri; Salokorpi, Niina; Bloigu, Risto; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi

2016-05-01

Central nervous system (CNS) relapse occurs in around 5% of diffuse large B-cell lymphoma (DLBCL) cases. No biomarkers to identify high-risk patients have been discovered. We evaluated the expression of lymphocyte-guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi-square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of Candidate B-Lymphoma Genes by Cross-Species Gene Expression Profiling

Science.gov (United States)

Tompkins, Van S.; Han, Seong-Su; Olivier, Alicia; Syrbu, Sergei; Bair, Thomas; Button, Anna; Jacobus, Laura; Wang, Zebin; Lifton, Samuel; Raychaudhuri, Pradip; Morse, Herbert C.; Weiner, George; Link, Brian; Smith, Brian J.; Janz, Siegfried

2013-01-01

Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as a gene discovery tool in liver, breast, lung, prostate and other cancers, but has been largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We used global gene expression profiles of DLBCL-like tumors that arose spontaneously in Myc-transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the human DLBCL transcriptome. The human and mouse lymphomas were found to have 60 concordantly deregulated genes in common, including 8 genes that Cox hazard regression analysis associated with overall survival in a published landmark dataset of DLBCL. Genetic network analysis of the 60 genes followed by biological validation studies indicate FOXM1 as a candidate DLBCL and BL gene, supporting a number of studies contending that FOXM1 is a therapeutic target in mature B cell tumors. Our findings demonstrate the value of the “mouse filter” for genomic studies of human B-lineage neoplasms for which a vast knowledge base already exists. PMID:24130802

Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation.

Science.gov (United States)

Gupta, Mamta; Han, Jing Jing; Stenson, Mary; Maurer, Matthew; Wellik, Linda; Hu, Guangzhen; Ziesmer, Steve; Dogan, Ahmet; Witzig, Thomas E

2012-03-22

Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.

Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

International Nuclear Information System (INIS)

Paone, Gaetano; Itti, Emmanuel; Lin, Chieh; Meignan, Michel; Haioun, Corinne; Dupuis, Jehan; Gaulard, Philippe

2009-01-01

To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher's exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement. (orig.)

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

NARCIS (Netherlands)

Bernatsky, Sasha; Velásquez García, Héctor A; Spinelli, John; Gaffney, Patrick; Smedby, Karin E; Ramsey-Goldman, Rosalind; Wang, Sophia S.; Adami, Hans-Olov; Albanes, Demetrius; Angelucci, Emanuele; Ansell, Stephen M.; Asmann, Yan W.; Becker, Nikolaus; Benavente, Yolanda; Berndt, Sonja I.; Bertrand, Kimberly A.; Birmann, Brenda M.; Boeing, Heiner; Boffetta, Paolo; Bracci, Paige M.; Brennan, Paul; Brooks-Wilson, Angela R.; Cerhan, James R.; Chanock, Stephen J.; Clavel, Jacqueline; Conde, Lucia; Cotenbader, Karen H; Cox, David G; Cozen, Wendy; Crouch, Simon; De Roos, Anneclaire J.; De Sanjose, Silvia; Di Lollo, Simonetta; Diver, W. Ryan; Dogan, Ahmet; Foretova, Lenka; Ghesquières, Hervé; Giles, Graham G.; Glimelius, Bengt; Habermann, Thomas M.; Haioun, Corinne; Hartge, Patricia; Hjalgrim, Henrik; Holford, Theodore R.; Holly, Elizabeth A.; Jackson, Rebecca D.; Kaaks, Rudolph; Kane, Eleanor; Kelly, Rachel S.; Klein, Robert J.; Kraft, Peter; Kricker, Anne; Lan, Qing; Lawrence, Charles; Liebow, Mark; Lightfoot, Tracy; Link, Brian K.; Maynadie, Marc; McKay, James; Melbye, Mads; Molina, Thierry Jo; Monnereau, Alain; Morton, Lindsay M.; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Offit, Kenneth; Purdue, Mark P.; Rais, Marco; Riby, Jacques; Roman, Eve; Rothman, Nathaniel; Salles, Gilles; Severi, Gianluca; Severson, Richard K.; Skibola, Christine F.; Slager, Susan L.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Staines, Anthony; Teras, Lauren R.; Thompson, Carrie A.; Tilly, Hervé; Tinker, Lesley F.; Tjonneland, Anne; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C H; Vijai, Joseph; Vineis, Paolo; Virtamo, Jarmo; Wang, Zhaoming; Weinstein, Stephanie; Witzig, Thomas E.; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Yawei; Zheng, Tongzhang; Zucca, Mariagrazia; Clarke, Ann E

2017-01-01

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

DEFF Research Database (Denmark)

Yao, Zhilei; Deng, Lijuan; Xu-Monette, Z Y

2018-01-01

In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positiv...

Clinical features of patients with nodal marginal zone lymphoma compared to follicular lymphoma: similar presentation, but differences in prognostic factors and rate of transformation.

Science.gov (United States)

van den Brand, Michiel; van der Velden, Walter J F M; Diets, Illja J; Ector, Geneviève I C G; de Haan, Anton F J; Stevens, Wendy B C; Hebeda, Konnie M; Groenen, Patricia J T A; van Krieken, Han J M

2016-07-01

Nodal marginal zone lymphoma (NMZL) is a rare type of B-cell non-Hodgkin lymphoma. This study assessed the clinical features of 56 patients with NMZL in comparison to 46 patients with follicular lymphoma (FL). Patients with NMZL and FL had a largely similar clinical presentation, but patients with FL had a higher disease stage at presentation, more frequent abdominal lymphadenopathy and bone marrow involvement, and showed more common transformation into diffuse large B-cell lymphoma (DLBCL) during the course of disease. Overall survival and event-free survival were similar for patients with NMZL and FL, but factors associated with worse prognosis differed between the two groups. Transformation into DLBCL was associated with a significantly poorer outcome in both groups, but the phenotypes were different: DLBCL arising in FL was mainly of germinal center B-cell phenotype, whereas DLBCL arising in NMZL was mainly of non-germinal center B-cell phenotype.

Determining the correlation of Epstein-Barr virus with diffuse large B-cell lymphoma by chromogenic in situ hybridization

Directory of Open Access Journals (Sweden)

Kosari F

2012-09-01

Full Text Available Background: Diffuse large B-cell lymphoma (DLBCL is the most common type of lymphoma. There are various types of DLBCL including immunoblastic and centroblastic. Epstein-Barr virus (EBV is a member of Herpes virus family found in all human populations inducing different lymphoproliferative disorders. The role of EBV in the development of DLBCL is known. Multiple laboratory methods are available for detecting EBV. This study was conducted to determine the correlation of EBV with DLBCL in samples referred to pathology ward in Shariati and Sina Hospitals by chromogenic in situ hybridization (CISH method.Methods: In this case/control study, pathological specimens of 50 patients with DLBCL as well as 50 reactive lymph nodes and tonsils (control group were collected from archives of Shariati and Sina Hospitals and were evaluated for EBV encoded RNA (EBER expression based on CISH method. A peptide nucleic acid (PNA EBV probe (Dakocytomatin was used while all the processes were done in RNAase-free conditions using RNAase-free water, sterile gloves and samplers. Results: Out of fifty specimens in the case group, eight were positive for EBER in comparison with two in the control group (P=0.046. No statistically significant difference was observed between intranodal or extranodal samples (P=0.736 or between males and females (P=0.0746.Conclusion: Our study showed that EBV positivity for EBER in patient with DLBCL could be determined more effectively by CISH method than immunohistochemistry (IHC. Comparative analysis between CISH, PCR and IHC methods is recommended.

Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma.

Science.gov (United States)

Su, Yinghan; Sun, Bin; Lin, Xuejing; Zhao, Xinying; Ji, Weidan; He, Miaoxia; Qian, Haihua; Song, Xianmin; Yang, Jianmin; Wang, Jianmin; Chen, Jie

2016-08-02

In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.

Design and development of a chopping and deflecting system for the high current injector at IUAC

Science.gov (United States)

Kedia, Sanjay Kumar; Mehta, R.

2018-05-01

The Low Energy Beam Transport (LEBT) section of the High Current Injector (HCI) incorporates a Chopping cum Deflecting System (CDS). The CDS comprises of a deflecting system and a pair of slits that will remove dark current and produce time bunched beam of 60 ns at different repetition rates of 4, 2, 1, 0.5, 0.25 and 0.125 MHz. The distinguishing feature of the design is the use of a multi-plate deflecting structure with low capacitance to optimize the electric field, which in turn results in higher efficiency in terms of achievable ion current. To maximize the effective electric field and its uniformity, the gap between the deflecting plates has been varied and a semi-circular contour has been incorporated on the deflecting plates. Due to this the electric field variation is less than ±0.5% within the plate length. The length of deflecting plates was chosen to maximize the transmission efficiency. Since the velocity of the charged particles in the LEBT section is constant, therefore the separation between two successive sets of deflecting plates has been kept constant to match the ions transient time within the gap which is nearly 32 ns. A square pulse has been chosen, instead of a sinusoidal one, to increase the transmission efficiency and to decrease the tailing effect. The loaded capacitance of the structure was kept 90% transmission efficiency with in the bunch length. Various simulation codes like Solid Works, TRACE 3D, CST MWS and homebrew Python codes were used to validate the design.

Rolado de fachinales y calidad de suelos en el Chaco occidental, Argentina Roller-chopping of shrub-thickets and soil quality in the western Chaco, Argentina

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Analía Anriquez

2005-12-01

significativo de sitio.In the western Chaco region the suitability for cow-calf operations of areas dominated by shrub thickets of Acacia, Celtis and Prosopis ('fachinales' is reduced because of their low carrying capacity and poor accessibility. Our objective was to assess the effect of practices commonly used to increase the standing forage of 'fachinales' on some indicators of soil quality (bulk density, total soil organic carbon, respiration, particulate organic carbon, microbial biomass carbon and dehydrogenase activity at three range sites of the Chaco region: upland, midland and bottom. The treatments applied were roller chopping, roller chopping plus seeding of Panicum maximum cv trichoglume cv Green panic, roller chopping followed by prescribed fire and controls. Bulk density, total soil organic carbon, particulate organic carbon and microbial biomass carbon were not altered by the treatments. A higher dehydrogenase activity was observed in the bottom site, irrespective of treatments, probably due to a greater soil water content. Soil respiration increased in the upland site in all treatments, probably because of the modification of soil microbial activity, attributable to the stimulation produced by the root exudates of green panic, native grasses and forbs that appeared after the treatments. In general, soil quality indicators were not significantly affected by the treatments used, a fact attributed to their 'low' intensity of application. However, there was a significant effect of range site.

Combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation

International Nuclear Information System (INIS)

Weick, J.K.; Antunez, A.; Kraus, T.A.; Fabian, C.J.; Dixon, D.

1983-01-01

The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. Responses were seen in 8/11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3020 x 10 9 /μl (range 1.2 to 5.5) and a mean nadir platelet count of 188 x 10 9 /μl (range 016 to 270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients

Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: a prospective, multicentre, non-interventional study

International Nuclear Information System (INIS)

Wu, Jianqiu; Song, Yongping; Su, Liping; Xu, Li; Chen, Tingchao

2016-01-01

The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL. Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration. Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR. This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures

Effect of Chopped Basalt Fibers on the Mechanical Properties and Microstructure of High Performance Fiber Reinforced Concrete

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Tehmina Ayub

2014-01-01

Full Text Available This paper presents the mechanical properties and the microstructure of the high performance fiber reinforced concrete (HPFRC containing up to 3% volume fraction of chopped Basalt fibers. Three types of the concrete were prepared, out of which, the first type was prepared by utilizing 100% cement content. The other two types of the concrete were prepared by replacing 10% cement content with silica fume and the locally produced metakaolin. Using each concrete type, four mixes were prepared in which Basalt fibers were added in the range of 0–3%; that is, total twelve mixes of the HPFRC concrete were prepared. From each of the twelve concrete mixes, total twelve specimens were cast to determine the mechanical properties of the HPFRC including compressive strength (cube and cylinder, splitting tensile strength, and the flexural strength. In this way, a total of 108 specimens were cast and tested in this study. Test results showed that the addition of the Basalt fibers significantly increased the tensile splitting strength and the flexural strength of the HPFRC, while there was slight improvement in the compressive strength with the addition of Basalt fibers. The microstructure of HPFRC was examined to determine the interfacial transition zone (ITZ between the aggregates and the paste by using field emission scanning electron microscope (FESEM, which showed the improvement of the ITZ due to the addition of the Basalt fibers.

Primary diffuse large B cell lymphoma arising from a leiomyoma of the uterine corpus.

Science.gov (United States)

Zhao, Lianhua; Ma, Qiang; Wang, Qiushi; Zeng, Ying; Luo, Qingya; Xiao, Hualiang

2016-01-20

Primary diffuse large B cell lymphoma (DLBCL) of the uterus is rare, and primary DLBCL arising from a uterine leiomyoma (collision tumor) has not been reported in the literature. We describe the clinical, histological, immunohistochemical, and molecular features of primary DLBCL arising from a leiomyoma in the uterine corpus. A 73-year-old female patient had a uterine mass for 23 years. An ultrasound scan revealed marked enlargement of the uterus, measuring 18.2 × 13 × 16.3 cm, with a 17.6 × 10.9 × 11.6 cm hypoechoic mass in the uterine corpus. The tumors consisted of medium- to large-sized cells exhibiting a diffuse pattern of growth with a well-circumscribed leiomyoma. The neoplastic cells strongly expressed CD79α, CD20 and PAX5. Molecular analyses indicated clonal B-cell receptor gene rearrangement. To the best of our knowledge, no previous cases of primary DLBCL arising from a leiomyoma have been reported. It is necessary to differentiate a diagnosis of primary DLBCL arising from a leiomyoma from that of leiomyoma with florid reactive lymphocytic infiltration (lymphoma-like lesion). Careful analysis of clinical, histological, immunophenotypic, and genetic features is required to establish the correct diagnosis.

Medicinal therapy of malignant lymphomas

International Nuclear Information System (INIS)

Aul, C.; Schroeder, M.; Giagounidis, A.

2002-01-01

Chemotherapy represents the most important therapeutic option in malignant lymphomas. Low to intermediate risk Hodgkin's disease is treated by a combination of chemotherapy and radiation. The new chemotherapy protocol BEACOPP has improved the outcome of advanced stages in comparison with the internationally accepted standard protocol COPP/ABVD. Dependent on the initial staging, cure rates between 50 and 95% can be achieved. Indolent non-Hodgkin's lymphomas usually present in advanced stages of disease. Chemotherapy in these cases has palliative character and aims at improving patients'quality of life and at avoiding complications due to the disease. In aggressive and very aggressive non-Hodgkin's lymphoma chemotherapy is curative and must be initiated immediately irrespective of the staging results. The efficacy of the standard protocol CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone), that was established in the 1970s, has recently been improved by shortening of the therapy interval (CHOP-14 vs.CHOP-21),addition of etoposide (CHOEP) and combination with the monoclonal antibody rituximab (R-CHOP). The value of high dose chemotherapy with stem cell transplantation has been shown unequivocally only for aggressive non-Hodgkin lymphoma and relapsed Hodgkin's disease responsive to chemotherapy. The therapeutic strategy of malignant lymphomas is likely to be improved within the next years due to the introduction of novel cytostatic agents, the broadening application of monoclonal antibodies,upcoming new transplantation procedures and the development of substances with molecular targets.To rapidly increase our current knowledge on the topic it is mandatory to include patients into the large national and international multicenter studies. (orig.) [de

Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features

NARCIS (Netherlands)

de Jong, Daphne; Glas, Annuska M.; Boerrigter, Lucie; Hermus, Marie-Christine; Dalesio, Otilia; Willemse, Els; Nederlof, Petra M.; Kersten, Marie José

2003-01-01

Patients with diffuse large B-cell lymphoma (DLBCL) rarely show relapse after 4 years of complete remission (CR). In this study, we addressed the following questions: (1) Does late-relapsing DLBCL represent clonally related disease or a second malignancy; and (2) is there a characteristic biologic

Clinical and Biologic Significance of MYC Genetic Mutations in De Novo Diffuse Large B-cell Lymphoma

NARCIS (Netherlands)

Xu-Monette, Z.Y.; Deng, Q.; Manyam, G.C.; Tzankov, A.; Li, L; Xia, Y.; Wang, X.X.; Zou, D.; Visco, C.; Dybkaer, K.; Li, J.; Zhang, L.; Liang, H.; Montes-Moreno, S.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huh, J.; Ponzoni, M.; Ferreri, A.J.; Parsons, B.M.; Moller, M.B.; Wang, S.A.; Miranda, R.N.; Piris, M.A.; Winter, J.N.; Medeiros, L.J.; Li, Y.; Young, K.H.

2016-01-01

PURPOSE: MYC is a critical driver oncogene in many cancers, and its deregulation in the forms of translocation and overexpression has been implicated in lymphomagenesis and progression of diffuse large B-cell lymphoma (DLBCL). The MYC mutational profile and its roles in DLBCL are unknown. This study

Aberrant methylation of cell-free circulating DNA in plasma predicts poor outcome in diffuse large B cell lymphoma

DEFF Research Database (Denmark)

Sommer Kristensen, Lasse; Hansen, Jakob Werner; Kristensen, Søren Sommer

2016-01-01

BACKGROUND: The prognostic value of aberrant DNA methylation of cell-free circulating DNA in plasma has not previously been evaluated in diffuse large B cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant promoter DNA methylation can be detected in plasma from DLBCL patients...

AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

Wang, Jinfen; Xu-Monette, Zijun Y; Jabbar, Kausar J

2017-01-01

AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found that high levels of p-AKT...

Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

NARCIS (Netherlands)

Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

2014-01-01

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?

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İkbal Cansu Barış

2015-12-01

Full Text Available INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. METHODS: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. RESULTS: GADD45γ methylation was frequent (50.0% in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041. In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040. DISCUSSION AND CONCLUSION: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ.

Primary breast lymphoma: A single-institute experience in Taiwan

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Che-Wei Ou

2014-10-01

Full Text Available Background: Breast is an uncommon location of lymphoma involvement. The most common type of primary breast lymphoma (PBL is diffuse large B-cell lymphoma (DLBCL. Rituximab is the widely used monoclonal antibody against CD20+ B-cell lymphoma, especially DLBCL. We aimed to analyze the clinical features, prognostic factors, and treatment outcome with or without rituximab in primary breast DLBCL. Methods: We retrospectively analyzed patients diagnosed with PBL from October 1987 to March 2012 in our hospital, excluding metastasis by whole-body computed tomography and bone marrow study. Results: Twenty-three patients were diagnosed with PBL. All were females. Eighteen patients were stage IE and five were stage IIE according to the Ann Arbor staging system. Two patients had lymphoma other than DLBCL. The median age of primary breast DLBCL patients was 48 years (range 27-79. Two were excluded from the analysis due to refusal or ineligibility for chemotherapy. No significant prognostic factor was found. Patients receiving chemotherapy with (RC or without (C rituximab were not significantly different in the 5-year overall survival (RC: 57.1%; C: 58.3%; p = 0.457 or progression-free survival (RC: 57.1%; C: 50.0%; p = 0.456. A high incidence of relapse in the central nervous system (CNS (17.6% was observed. Conclusions: In accordance with prior literature reports, our Taiwanese cohort of primary breast DLBCL seemed younger than those reported in Japan, Korea, and Western societies. Relapse in the CNS was not uncommon. The benefit of rituximab in addition to chemotherapy was not statistically significant. Treatment modality remained to be defined by further large-scale studies.

Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma in the Elderly: A Matched Case-Control Analysis.

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Chen-Ge Song

Full Text Available Epstein-Barr virus (EBV-positive diffuse large B-cell lymphoma (DLBCL in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity.In situ hybridization (ISH analysis of Epstein-Barr virus (EBV and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3 was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly.A total of 16 patients (7.0% were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB subtypes (87.5% and high Ki67 (75% and CD30 expression (93.8%. For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8% had complete remission, 2 (12.5% had partial remission, 2 (12.5% had stable disease, and 5 (31.3% had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P<0.001.EBV-positive DLBCL of the elderly is associated with an inferior clinical course and inferior survival outcomes. The role of EBV in this disease and the optimal management of this subgroup warrants further investigation.

Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2α and inhibiting activation of pro-apoptotic CHOP

Energy Technology Data Exchange (ETDEWEB)

Barber, Claire; Netherton, Chris; Goatley, Lynnette [The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF (United Kingdom); Moon, Alice; Goodbourn, Steve [Institute for Infection and Immunity, St. George' s, University of London, London SW17 0RE (United Kingdom); Dixon, Linda, E-mail: linda.dixon@pirbright.ac.uk [The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF (United Kingdom)

2017-04-15

The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required. PP1 was co-precipitated with wild type DP71L and the mutant lacking residues 52- 66 or the LSAVL motif, but not with the PP1 binding motif mutant. The residues in the LSAVL motif play a critical role in DP71L function but do not interfere with binding to PP1. Instead we propose these residues are important for DP71L binding to eIF2α. - Highlights: •The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate translation initiation factor eIF2α (eIF2α). •The residues V{sup 16}, F{sup 18} of DP71L are required for binding to the α, β and γ isoforms of PP1 and for DP71L function. •The sequence LSAVL downstream from the PP1 binding site (residues 57–61) are also important for DP71L function. •DP71L mutants of the LSAVL sequence retain ability to co-precipitate with PP1 showing these sequences have a different role to PP1 binding.

Fluorine-18-fluorodeoxyglucose positron emission tomography for interim response assessment of advanced-stage Hodgkin's lymphoma and diffuse large B-cell lymphoma: a systematic review

DEFF Research Database (Denmark)

Terasawa, T.; Lau, J.; Bardet, S.

2009-01-01

. RESULTS: Thirteen studies involving 360 advanced-stage HL patients and 311 DLBCL patients met our inclusion criteria. Advanced-stage HL studies included few unfavorable-risk patients. DLBCL studies were heterogeneous. FDG-PET had an overall sensitivity of 0.81 (95% CI, 0.72 to 0.89) and a specificity of 0.......97 (95% CI, 0.94 to 0.99) for advanced-stage HL, and a sensitivity of 0.78 (95% CI, 0.64 to 0.87) and a specificity of 0.87 (95% CI, 0.75 to 0.93) for DLBCL. Meta-regression and subgroup analyses did not identify factors that affect prognostic accuracy. CONCLUSION: For low- to intermediate-risk advanced...

A novel antibody-drug conjugate targeting SAIL for the treatment of hematologic malignancies.

Science.gov (United States)

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D'Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-05-29

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody-drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.

Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma

International Nuclear Information System (INIS)

Caramuta, S; Lee, L; Özata, D M; Akçakaya, P; Georgii-Hemming, P; Xie, H; Amini, R-M; Lawrie, C H; Enblad, G; Larsson, C; Berglund, M; Lui, W-O

2013-01-01

Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL

Promoter methylation patterns in Richter syndrome affect stem-cell maintenance and cell cycle regulation and differ from de novo diffuse large B-cell lymphoma.

Science.gov (United States)

Rinaldi, Andrea; Mensah, Afua Adjeiwaa; Kwee, Ivo; Forconi, Francesco; Orlandi, Ester M; Lucioni, Marco; Gattei, Valter; Marasca, Roberto; Berger, Françoise; Cogliatti, Sergio; Cavalli, Franco; Zucca, Emanuele; Gaidano, Gianluca; Rossi, Davide; Bertoni, Francesco

2013-10-01

In a fraction of patients, chronic lymphocytic leukaemia (CLL) can transform to Richter syndrome (RS), usually a diffuse large B-cell lymphoma (DLBCL). We studied genome-wide promoter DNA methylation in RS and clonally related CLL-phases of transformed patients, alongside de novo DLBCL (of non-germinal centre B type), untransformed-CLL and normal B-cells. The greatest differences in global DNA methylation levels were observed between RS and DLBCL, indicating that these two diseases, although histologically similar, are epigenetically distinct. RS was more highly methylated for genes involved in cell cycle regulation. When RS was compared to the preceding CLL-phase and with untransformed-CLL, RS presented a higher degree of methylation for genes possessing the H3K27me3 mark and PRC2 targets, as well as for gene targets of TP53 and RB1. Comparison of the methylation levels of individual genes revealed that OSM, a stem cell regulatory gene, exhibited significantly higher methylation levels in RS compared to CLL-phases. Its transcriptional repression by DNA methylation was confirmed by 5-aza-2'deoxycytidine treatment of DLBCL cells, determining an increased OSM expression. Our results showed that methylation patterns in RS are largely different from de novo DLBCL. Stem cell-related genes and cell cycle regulation genes are targets of DNA methylation in RS. © 2013 John Wiley & Sons Ltd.

Food Safety While Hiking, Camping and Boating

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... veal steaks, chops, and roasts to a minimum internal temperature of 145 °F as measured with a food thermometer before removing meat from the heat source. For safety and quality, allow meat to rest for at least three ...

Salmonella Questions and Answers

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... veal steaks, chops, and roasts to a minimum internal temperature of 145 °F as measured with a food thermometer before removing meat from the heat source. For safety and quality, allow meat to rest for at least three ...

Parasites and Foodborne Illness

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... veal steaks, chops, and roasts to a minimum internal temperature of 145 °F as measured with a food thermometer before removing meat from the heat source. For safety and quality, allow meat to rest for at least three ...

High Altitude Cooking and Food Safety

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... veal steaks, chops, and roasts to a minimum internal temperature of 145 °F as measured with a food thermometer before removing meat from the heat source. For safety and quality, allow meat to rest for at least three ...

Food Safety Tips for College Students

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... veal steaks, chops, and roasts to a minimum internal temperature of 145 °F as measured with a food thermometer before removing meat from the heat source. For safety and quality, allow meat to rest for at least three ...

Combination of Bcl-2 and MYC protein expression improves high-risk stratification in diffuse large B-cell lymphoma

Directory of Open Access Journals (Sweden)

Wang J

2015-09-01

Full Text Available Jing Wang,* Min Zhou,* Jing-Yan Xu,* Bing Chen, Jian OuyangDepartment of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this work and should be considered as cofirst authorsPurpose: To evaluate whether the addition of two biological markers (MYC and BCL-2 protein overexpression improves the stratification of high-risk patients with diffuse large B-cell lymphoma (DLBCL.Method: Seven risk factors were identified at diagnosis, and a maximum of 7 points were assigned to each patient. The patients were classified according to four risk groups: low (0–1, low-intermediate (2–3, high-intermediate (4, and high (5–7. Only high-risk patients with DLBCL were included in this analysis. We retrospectively examined 20 cases from 2008 to 2013 at the Nanjing Drum Tower Hospital.Results: The median expression of MYC protein was 60%, and 17 of 20 (65% evaluable cases overexpressed MYC. The median expression of BCL-2 protein was also 60%. Eighteen of 20 (90% evaluable cases showed BCL-2 overexpression. Additionally, 12 out of 20 cases (60% demonstrated coexpression of MYC and BCL-2 proteins. The percentages of overall survival and progression-free survival at the median follow-up time (36 months were 33.3%±16.1% and 16.9%±13.5%, respectively. By comparison, nine, four, and 20 patients were classified as high risk based on the International Prognostic Index (IPI, National Comprehensive Cancer Network(NCCN-IPI, and revised IPI criteria, respectively. According to the IPI and NCCN-IPI stratification, the risk groups demonstrated closely overlapping survival curves. In addition, four out of 20 cases were identified as low-intermediate risk according to the NCCN-IPI criteria.Conclusion: The addition of MYC and BCL-2 protein expression to the IPI could identify a subset of DLBCL patients with high-risk clinicopathological characteristics and

Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH: revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma

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Lu Xin-Yan

2009-11-01

Full Text Available Abstract Background Plasmablastic lymphoma (PL is a subtype of diffuse large B-cell lymphoma (DLBCL. Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM. The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related and PCM using array-based comparative genomic hybridization. Results Examination of genomic data in PL revealed that the most frequent segmental gain (> 40% include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation. Conclusion To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.

Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia.

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García-Barchino, Maria J; Sarasquete, Maria E; Panizo, Carlos; Morscio, Julie; Martinez, Antonio; Alcoceba, Miguel; Fresquet, Vicente; Gonzalez-Farre, Blanca; Paiva, Bruno; Young, Ken H; Robles, Eloy F; Roa, Sergio; Celay, Jon; Larrayoz, Marta; Rossi, Davide; Gaidano, Gianluca; Montes-Moreno, Santiago; Piris, Miguel A; Balanzategui, Ana; Jimenez, Cristina; Rodriguez, Idoia; Calasanz, Maria J; Larrayoz, Maria J; Segura, Victor; Garcia-Muñoz, Ricardo; Rabasa, Maria P; Yi, Shuhua; Li, Jianyong; Zhang, Mingzhi; Xu-Monette, Zijun Y; Puig-Moron, Noemi; Orfao, Alberto; Böttcher, Sebastian; Hernandez-Rivas, Jesus M; Miguel, Jesus San; Prosper, Felipe; Tousseyn, Thomas; Sagaert, Xavier; Gonzalez, Marcos; Martinez-Climent, Jose A

2018-05-01

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV - tumours, EBV + DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV + DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV + DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2 -/- IL2γc -/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV + B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV + DLBCL in patients. Accordingly, clonally related and unrelated EBV + DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV + DLBCL. Copyright © 2018 Pathological

MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

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Landt Olfert

2008-04-01

Full Text Available Abstract Background SNP309 T/G (rs2279744 causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522 gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. Methods SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. Results The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. Conclusion In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.

CD4+ T cell-mediated cytotoxicity is associated with MHC class II expression on malignant CD19+ B cells in diffuse large B cell lymphoma.

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Zhou, Yong; Zha, Jie; Lin, Zhijuan; Fang, Zhihong; Zeng, Hanyan; Zhao, Jintao; Luo, Yiming; Li, Zhifeng; Xu, Bing

2018-01-15

Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with approximately 30% of patients present relapsed or refractory disease after first-line therapy. Research of further treatment options is needed. Cytotoxic CD4 + T cells express cytolytic molecules and have potential antitumor function. Here, we showed that the CD19 + cells from DLBCL patients presented significantly reduced expression of MHC II molecules than those from healthy controls. Three years after the first-line treatment, patients that presented relapsed disease had significantly lower MHC II expression on their CD19 + cells than patients who did not show recurrence. Examining cytotoxic CD4 + T cells show that DLBCL patients presented significantly elevated frequencies of granzyme A-, granzyme B-, and/or perforin-expressing cytotoxic CD4 + T cells. Also, frequency of cytotoxic CD4 + T cells in DLBCL patients was positively correlated with the MHC II expression level. Subsequently, the cytotoxic potential of CD4 + T cells against autologous CD19 + cells was investigated. We found that the cytotoxic potential of CD4 + T cells was highest in MHC II-high, intermediate in MHC II-mid, and lowest in MHC II-low patients. The percentage of MHC II-expressing viable CD19 + cells presented a significant reduction after longer incubation with cytotoxic CD4 + T cells, suggesting that cytotoxic CD4 + T cells preferentially eliminated MHC II-expressing CD19 + cells. Blocking MHC II on CD19 + cells significantly reduced the cytolytic capacity of CD4 + T cells. Despite these discoveries, the frequency of cytotoxic CD4 + T cells did not predict the clinical outcome of DLBCL patients. Together, these results demonstrated that cytotoxic CD4 + T cells presented an MHC II-dependent cytotoxic potential against autologous CD19 + cells and could potentially represent a future treatment option for DLBCL. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

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Schmitz, Roland; Wright, George W; Huang, Da Wei; Johnson, Calvin A; Phelan, James D; Wang, James Q; Roulland, Sandrine; Kasbekar, Monica; Young, Ryan M; Shaffer, Arthur L; Hodson, Daniel J; Xiao, Wenming; Yu, Xin; Yang, Yandan; Zhao, Hong; Xu, Weihong; Liu, Xuelu; Zhou, Bin; Du, Wei; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Connors, Joseph M; Campo, Elias; Lopez-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa M; Tay Kuang Wei, Kevin; Zelenetz, Andrew D; Leonard, John P; Bartlett, Nancy L; Tran, Bao; Shetty, Jyoti; Zhao, Yongmei; Soppet, Dan R; Pittaluga, Stefania; Wilson, Wyndham H; Staudt, Louis M

2018-04-12

Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88 L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

Routine imaging for diffuse large B-cell lymphoma in first remission is not associated with better survival

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El-Galaly, Tarec; Jakobsen, Lasse Hjort; Hutchings, Martin

2015-01-01

Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients-two neighbour......Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients...... are fully publicly funded. Follow-up (FU) for Swedish patients included symptom assessment, clinical examinations, and blood tests with 3-month intervals for 2 years and with longer intervals later in follow-up. Imaging was only performed in response to suspected relapse. FU for Danish patients...... was equivalent but included additional routine surveillance imaging (usually half-yearly CT for 2 years as a minimum). Clinico-pathological features were retrieved from the national lymphoma registries, and vital status was updated using the civil registries. OS was defined as the time from end of treatment...

Metabolic fingerprinting of fresh lymphoma samples used to discriminate between follicular and diffuse large B-cell lymphomas.

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Barba, Ignasi; Sanz, Carolina; Barbera, Angels; Tapia, Gustavo; Mate, José-Luis; Garcia-Dorado, David; Ribera, Josep-Maria; Oriol, Albert

2009-11-01

To investigate if proton nuclear magnetic resonance ((1)H NMR) spectroscopy-based metabolic profiling was able to differentiate follicular lymphoma (FL) from diffuse large B-cell lymphoma (DLBCL) and to study which metabolites were responsible for the differences. High-resolution (1)H NMR spectra was obtained from fresh samples of lymph node biopsies obtained consecutively at one center (14 FL and 17 DLBCL). Spectra were processed using pattern-recognition methods. Discriminant models were able to differentiate between the two tumor types with a 86% sensitivity and a 76% specificity; the metabolites that most contributed to the discrimination were a relative increase of alanine in the case of DLBCL and a relative increase of taurine in FL. Metabolic models had a significant but weak correlation with Ki67 expression (r(2)=0.42; p=0.002) We have proved that it is possible to differentiate between FL and DLBCL based on their NMR metabolic profiles. This approach may potentially be applicable as a noninvasive tool for diagnostic and treatment follow-up in the clinical setting using conventional magnetic resonance systems.

Sending the Right Signals | Center for Cancer Research

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Diffuse large B-cell lymphomas (DLBCL), the most common type of non-Hodgkin’s lymphoma, causes about 10,000 deaths every year in the United States, even though about half of all patients are cured with current regimens. There are different subtypes of DLBCL that vary biologically and have significantly different rates of patient survival following chemotherapy, with the

Campylobacter Questions and Answers

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... veal steaks, chops, and roasts to a minimum internal temperature of 145 °F (62.8 °C) as measured with a food thermometer before removing meat from the heat source. For safety and quality, allow meat to rest for at least three ...

Patients with primary diffuse large B-cell lymphoma of female genital tract have high risk of central nervous system relapse.

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Cao, Xin-xin; Li, Jian; Zhang, Wei; Duan, Ming-hui; Shen, Ti; Zhou, Dao-bin

2014-06-01

The objective of this study was to evaluate retrospectively the clinical characteristics, treatments, and outcomes of patients with primary diffuse large B-cell lymphoma (DLBCL) of the female genital tract. The basic characteristics, treatments, and outcomes of six patients diagnosed with primary DLBCL of the female genital tract, including the ovary, uterine cervix, and vagina, treated in our hospital between 2000 and 2012, were analyzed retrospectively. Seven of 323 (2.2 %) newly diagnosed DLBCLs were diagnosed as primary female genital tract DLBCL. Six patients with complete medical data were included in the analysis. The median age at diagnosis was 52.5 years (range 20-65). The presenting symptoms included abnormal vaginal bleeding, increased vaginal discharge, abdominal fullness, and abdominal pain. Two patients had stage IE disease and four patients had stage IIE disease. Treatment included chemotherapy only in five patients, and combined chemotherapy and localized radiation in one patient. After a median follow-up of 58 months, four patients showed relapse in the central nervous system and two had died from progressive disease. The median progression-free survival was 27 months and the median overall survival for this group has not been reached. Patients with primary female genital tract DLBCL may have poor outcomes and a high risk of central nervous system relapse. Central nervous system prophylaxis might be considered in addition to systemic chemotherapy for DLBCL of the female genital tract.

PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro

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Cui W

2017-04-01

Full Text Available Wenli Cui,1–4,* Shutao Zheng,5,6,* Zebing Liu,1–3 Weige Wang,1–3 Ying Cai,1–3 Rui Bi,1–3 Bing Cao,1–3 Xiaoyan Zhou1–3 1Department of Pathology, Shanghai Cancer Center, Fudan University, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Institute of Pathology, Fudan University, Shanghai, 4Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, 5Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 6State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL. In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan–Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8 and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS

CCR investigators use liquid biopsies to uncover cancer in the blood of lymphoma patients | Center for Cancer Research

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CCR investigators are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma. are using circulating tumor DNA (ctDNA) as a type of noninvasive liquid biopsy for patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin

Diffuse large B-cell lymphoma in the era of precision oncology: How imaging is helpful

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Shah, Hina J.; Keraliya, Abhishek R.; Lele, Vikram R.; Tirumani, Sree Harsha; DiPiro, Pamela J.; Jagannathan, Jyothi P. [Dept. of Imaging, Dana Farber Cancer Institute, Harvard Medical School, Boston (United States)

2017-01-15

Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of Non-Hodgkin's lymphoma. As treatments continues to evolve, so do imaging strategies, and positron emission tomography (PET) has emerged as the most important imaging tool to guide oncologists in the diagnosis, staging, response assessment, relapse/recurrence detection,and therapeutic decision making of DLBCL. Other imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and conventional radiography are also used in the evaluation of lymphoma. MRI is useful for nervous system and musculoskeletal system involvement and is emerging as a radiation free alternative to PET/CT. This article provides a comprehensive review of both the functional and morphological imaging modalities, available in the management of DLBCL.

Community health outreach program of the Chad-Cameroon petroleum development and pipeline project.

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Utzinger, Jürg; Wyss, Kaspar; Moto, Daugla D; Tanner, Marcel; Singer, Burton H

2004-02-01

A critical appraisal has been presented of the CHOP for a large-scale energy infrastructure development project that was implemented in two of the world's poorest countries. The project is under close scrutiny from various independent monitoring groups, civil society organizations, and human rights groups. Reviewing the achievements and shortcomings permits the extraction of important lessons that will be critical for the future adoption of the CHOP in the current setting and for the implementation of additional CHOPs elsewhere in the developing world. The authors believe that the design must be flexible, efficient, and innovative so that a CHOP promptly can address pressing public health issues as they arise (eg, epidemic outbreak) and include the needs and demands of the concerned communities. An innovative feature of the current project is the high degree and mix of public-private partnerships. The project's CHOP also relies on partnerships. As elaborated elsewhere, public-private partnerships should be seen as a social experiment--they reveal promise but are not the solution for every problem. For this CHOP, the focus is on partnerships between a multinational consortium, government agencies, and international organizations. The partnerships also include civil society organizations for monitoring and evaluation and local NGOs designated for the implementation of the selected public health interventions within the CHOP. The governments and their respective health policies often form the umbrella under which the partnerships operate. With the increase in globalization, however, the importance and capacities of governments have diminished, and there is growing private-sector involvement. Private enterprise is seen as an efficient, innovative, pragmatic, and powerful means to achieve environmental and social sustainability. Experiences with the partnership configurations in the current CHOP are of importance for tackling grand challenges in global health by

Central nervous system prophylaxis in diffuse large B-cell lymphoma.

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Zahid, Mohammad Faizan; Khan, Nadia; Hashmi, Shahrukh K; Kizilbash, Sani Haider; Barta, Stefan K

2016-08-01

Central nervous system (CNS) involvement with diffuse large B-cell lymphoma (DLBCL) is a relatively uncommon manifestation; with most cases of CNS involvement occuring during relapse after primary therapy. CNS dissemination typically occurs early in the disease course and is most likely present subclinically at the time of diagnosis in many patients who later relapse in the CNS. CNS relapse in these patients is associated with poor outcomes. Based on a CNS relapse rate of 5% in DLBCL and weighing the benefits against the toxicities, universal application of CNS prophylaxis is not justified. The introduction of rituximab has significantly reduced the incidence of CNS relapse in DLBCL. Different studies have employed other agents for CNS prophylaxis, such as intrathecal chemotherapy and high-dose systemic agents with sufficient CNS penetration. If CNS prophylaxis is to be given, it should be preferably administered during primary chemotherapy. However, there is no strong evidence that supports any single approach for CNS prophylaxis. In this review, we outline different strategies of administering CNS prophylaxis in DLBCL patients reported in literature and discuss their advantages and drawbacks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma.

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Loo, Suet Kee; Ab Hamid, Suzina Sheikh; Musa, Mustaffa; Wong, Kah Keng

2018-01-01

Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) 0.8) with DNMT1 expression and significantly downregulated (log fold-change <-1.35; p<0.05) following DNMT1 silencing in HT cells. These results suggest the involvement of DNMT1 in the activation of cell cycle and DNA replication in DLBCL cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

International Nuclear Information System (INIS)

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C

2015-01-01

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC 50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

Science.gov (United States)

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D‘Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-01-01

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs. PMID:26024286

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma.

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Afshin Beheshti

Full Text Available Extensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA signatures in the host influence diffuse large B cell lymphoma (DLBCL development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach. We harnessed a novel murine model of spontaneous DLBCL initiation (Smurf2-deficient at two age groups: 3 and 15 months old. All Smurf2-deficient mice develop visible DLBCL tumor starting at 15 months of age. Total miRNA was isolated from serum, bone marrow and spleen and were collected for all age groups for Smurf2-deficient mice and age-matched wild-type C57BL/6 mice. Using systems biology techniques, we identified a list of 10 circulating miRNAs being regulated in both the spleen and bone marrow that were present in DLBCL forming mice starting at 3 months of age that were not present in the control mice. Furthermore, this miRNA signature was found to occur circulating in the blood and it strongly impacted JUN and MYC oncogenic signaling. In addition, quantification of the miRNA signature was performed via Droplet Digital PCR technology. It was discovered that a key miRNA signature circulates throughout a host prior to the formation of a tumor starting at 3 months old, which becomes further modulated by age and yielded calculation of a 'carcinogenic risk score'. This novel age-based circulating miRNA signature may potentially be leveraged as a DLBCL risk profile at a young age to predict future lymphoma development or disease progression as well as for potential innovative miRNA-based targeted therapeutic strategies in lymphoma.

De Novo Nodal Diffuse Large B-Cell Lymphoma: Identification of Biologic Prognostic Factors

International Nuclear Information System (INIS)

Abd El-Hameed, A.

2005-01-01

Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL). Although combination chemotherapy has improved the outcome, long-term cure is now possible for approximately 50% of all patients. making the search for parameters identifying patients at high risk particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic significance of t( 14; 18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo nodal DLBCL who where uniformly evaluated and treated. Material and Methods: A total of 40 patients with de novo nodal DLBCL treated at National Cancer Institute (NCI), Cairo University were investigated. Formal infixed, paraffin-embedded sections were analyzed for: I) bcl-2 gene rearrangement including major break point region (mbr) and minor cluster region (mcr) by polymerase chain reaction (PCR). and 2) bcl-2 protein expression by immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and subsequent clinical course. Bcl-2 gene rearrangement was detected in 8 cases (20%). 2 cases at mbr, and 6 cases at mcr. Bcl-2 protein (> I 0%) was expressed in 24 cases (60%), irrespective of the presence of t( 14; 18) translocation. The t( 14; 18), and bcl-2 protein overexpression were more frequently associated with failure to achieve a complete response to therapy (ρ=0.008. and 0.04. respectively). DLBCL patients with t(14;18), and bcl-2 protein expression had a significantly reduced 5-year disease free survival (ρ=0.04, and 0.01, respectively). The t( 14; 18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches. Geographic differences in t(14;18) may be related to the

Th1/2 Immune Response Signature Predicts Outcome after Dose-Dense Immunochemotherapy in Patients with High Risk Diffuse Large B-Cell Lymphoma – Results from Nordic Lymphoma Group Trials

DEFF Research Database (Denmark)

M, Autio; Jørgensen, Judit Meszaros; SK, Leivonen

treatment-specific roles in diffuse large B-cell lymphoma. For the high risk DLBCL patients treated with dose-dense immunochemotherapy, high expression of type 1/2 immune response signature genes predicts a poor outcome. A detailed characterization of immune cell composition in the tumor microenvironment......Introduction: Despite better therapeutic options and improved survival of diffuse large B-cell lymphoma (DLBCL), 30-40% of the patients still relapse and have dismal prognosis. Recently, the impact of genomic aberrations, allowing lymphoma cells to escape immune recognition on DLBCL pathogenesis...... has been recognized. However, whether immune related signatures could be used as determinants for treatment outcome has not been rigorously evaluated. Here, our aim was to elucidate the immunologic characteristics of the tumor microenvironment, and associate the findings with outcome in patients...

Internal dose evaluation from actinide intakes during nuclear power reactor spent fuel reprocessing

International Nuclear Information System (INIS)

Pawar, S.K.; Kumar, Ranjeet; Gamre, Rupali; Purohit, R.G.

2011-01-01

Full text: Indian PHWR reactors are using natural uranium as fuel. After use they are discharged from the core and send for fuel reprocessing to extract the unused uranium and plutonium. Plutonium and other actinides are formed by activation of 238 U with neutrons and subsequent decay. During reprocessing of the spent fuel, major long lived actinides (Pu, Am and U) may become radiological safety hazard. Actinides intakes are more probable during declading and chopping of spent fuel. During routine plant operation in reprocessing, exposure to Pu is a major concern along with Am and U in working environment due to its higher radiological hazard and occupational workers are likely to get exposed to plutonium, Americium and Uranium mostly through inhalation. Internally deposited Pu-isotopes, Am-isotope and U-isotopes are estimated using techniques such as lung counting (in-vivo) and urine and faecal bioassay (in-vitro). Evaluation of internal dose of actinides is dependent upon urinary excreted activity. To estimate the internally deposited Pu, U and Am at an intake level of about one ALI (ICRP-78, 1997) of occupational workers, urine bioassay is the preferred technique due to high detection sensitivity, ease of sample handling and economical method. A small and measurable fraction of internally deposited Pu, Am and U are excreted through urine whose content is dependent on time of inhalation, quantity and type of chemical form of inhaled material (S and M class). A standardized radiochemical analysis method for separation and estimation of Pu, Am and U is used to evaluate the urinary excreted activity and internal dose. Several measurements techniques are employed for the estimation of plutonium, Americium and Uranium for example, Alpha Spectrometry, Gamma Spectrometry, Neutron Activation Analysis, Mass Spectrometry and Fission Track Analysis. The radiochemical separation followed by alpha counting and/or spectrometry is chosen due to its ease of handling and

Vav-1 expression correlates with NFkappaB activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines

DEFF Research Database (Denmark)

Hollmann, Annette; Aloyz, Raquel; Baker, Kristi

2010-01-01

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with a variable response to therapy. We have previously shown that DLBCL cell lines differ in their susceptibility to CD40-mediated cell death, and that resistance to CD40-targeted antibodies correlated with increased expression...... as a potential marker to identify tumours likely to respond to CD40-targeted therapies. Copyright (c) 2010 John Wiley & Sons, Ltd....

The rGel/BLyS Fusion Toxin Inhibits Diffuse Large B-cell Lymphoma Growth In Vitro and In Vivo

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Mi-Ae Lyu

2010-05-01

Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-κB (NF-κB are expected to be of therapeutic value in those tumors where NF-κB seems to play a unique survival role such as activated B-cell (ABC-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-κB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-κB (IκB-α, inhibition of NF-κB DNA-binding activity, and accumulation of IκB-α. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-κB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05 in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-κB and are resistant to conventional chemotherapeutic regimens.

Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.

Science.gov (United States)

Kuo, Hsu-Ping; Ezell, Scott A; Schweighofer, Karl J; Cheung, Leo W K; Hsieh, Sidney; Apatira, Mutiah; Sirisawad, Mint; Eckert, Karl; Hsu, Ssucheng J; Chen, Chun-Te; Beaupre, Darrin M; Versele, Matthias; Chang, Betty Y

2017-07-01

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy. Mol Cancer Ther; 16(7); 1246-56. ©2017 AACR . ©2017 American Association for Cancer Research.

81 - 88_Salim et al.,,

African Journals Online (AJOL)

pc

2017-06-01

Jun 1, 2017 ... conventional drugs in terms of how they functi. This enables herbal medicines ... oderate sinusoidal lymphocytosis with prominent kupfer cells and fo he test groups. ... decoction of the chopped stem barks and leaf of ..... cells being stable cells heal by regeneration and mild ... Internal Medicine: 19(1):40-45.

Occurrence and prognostic relevance of CD30 expression in post-transplant lymphoproliferative disorders

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Vase, Maja Ølholm; Maksten, Eva Futtrup; Bendix, Knud

2015-01-01

Post-transplant lymphoproliferative disorders (PTLDs) are potentiallyfatal, often Epstein-Barr virus (EBV)-driven neoplasias developing in immunocompromised hosts. Initial treatment usually consists of a reduction in immunosuppressive therapy and/or rituximab with or without chemotherapy. However...... favorable outcome. For diffuse large B-cell lymphoma (DLBCL)-type PTLD this was regardless of EBV status, and remained significant in multivariate analysis. Cell-of-origin had no independent prognostic value in our series of DLBCL PTLD....

A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma

OpenAIRE

Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

2015-01-01

Background Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. Case presentation A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3?months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinica...

CD7 Positive Diffuse Large B-Cell Lymphoma Arising in a Background of Follicular Lymphoma: A Case Report and Review of the Literature

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Elham Vali Betts

2016-01-01

Full Text Available Diffuse large B-cell lymphoma (DLBCL is a neoplasm of large B-lymphocytes with a diffuse growth pattern. The neoplastic cells express B-cell markers such as CD20 and PAX-5 and there may be coexpression of BCL-2, BCL-6, CD10, and MUM-1. With the exception of CD5, other T-cell markers are not commonly expressed in this neoplasm. Here, we describe the first reported case of a DLBCL with abnormal expression CD7 arising in a background of follicular lymphoma in an 81-year-old male who presented with a nontender left axillary mass. Additionally, no other T-cell antigens were expressed in this B-cell lymphoma. Expression of CD7 in DLBCL is exceptionally rare and its prognostic significance is unknown. Here, we describe this rare case with review of literature of known DLBCLs with expression of T-cell antigens.

Hepatitis C virus positive diffuse large B-cell lymphomas have distinct molecular features and lack BCL2 translocations

DEFF Research Database (Denmark)

Visco, Carlo; Wang, Jinfen; Tisi, Maria Chiara

2017-01-01

apoptotic pathways, have higher proliferative index, and lack BCL2 translocations. CONCLUSIONS: HCV-positive DLBCL have distinct molecular and pathological features compared to the HCV-negative counterparts.British Journal of Cancer advance online publication, 26 September 2017; doi:10.1038/bjc.2017.345 www.bjcancer.com....... in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas. METHODS: We performed a case-control study including 44 HCV-positive cases of de novo DLBCL, comparing them with 132 HCV-negative patients as controls (ratio 3 to 1). Cases and controls were...... for MYC, BCL2 and BCL6, TP53 mutations, and diagnostic specimens reviewed to exclude transformation from low-grade lymphoma. RESULTS: Compared to the HCV-negative controls, patients with HCV-positive de novo DLBCL had differential expression of genes that regulate innate immune response and modulate...

Microarray-based classification of diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Poulsen, Christian Bjørn; Borup, Rehannah; Nielsen, Finn Cilius

2005-01-01

on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL. METHODS AND RESULTS: First, three previously published gene lists were converted to the HG-U133A probe sets and used......OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation...... for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1...

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

Science.gov (United States)

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-05-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

Science.gov (United States)

Uccini, Stefania; Al-Jadiry, Mazin F; Scarpino, Stefania; Ferraro, Daniela; Alsaadawi, Adel R; Al-Darraji, Amir F; Moleti, Maria Luisa; Testi, Anna Maria; Al-Hadad, Salma A; Ruco, Luigi

2015-05-01

Pediatric Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare disease in nonimmunocompromised hosts. In a review of 231 cases of malignant lymphoma (87 Hodgkin lymphoma and 144 non-Hodgkin lymphoma) occurring in Iraqi children, 7 cases (5% of NHLs) were classified as EBV+ DLBCL. Six children presented with nodal disease, and 1 presented with extranodal localization (bone). In all cases, the disease was at an advanced clinical stage (III/IV). Evidence of immunodeficiency (Evans syndrome and selective IgA deficiency) was observed in a single case. Two cases were "monomorphic" with immunoblastic histology, and 5 cases were "polymorphic" with histologic aspects reminiscent of nodular lymphocyte-predominant Hodgkin lymphoma (2 cases) and of CD30+ classical Hodgkin lymphoma (3 cases). In all cases, tumor cells were EBV infected (EBER+/LMP-1+), were medium-large B-cells (CD20+/CD79a+/PAX-5+/BOB-1+/OCT-2+) of non-germinal center (non-GC) origin (CD10-/MUM-1+), and had high proliferative activity (50%-70%). Chromosomal translocations involving BCL2, MYC, and IGH genes were not observed. IGH monoclonality could be demonstrated in 3 of 3 investigated cases. Six cases of EBV-negative DLBCL (4% of NHL) were present in the same series. All had monomorphic histology with centroblastic/immunoblastic morphology; 3 cases were of GC type and 3 of non-GC type. Our findings indicate that in Iraq, DLBCLs are 9% of NHLs. Moreover, 2 different types of the disease do exist; the EBV-positive cases, with strong histologic and immunohistochemical resemblance with EBV+ DLBCL of the elderly, and the EBV-negative cases, which are similar to the pediatric DLBCL usually observed in Western populations. Copyright © 2015 Elsevier Inc. All rights reserved.

Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

Science.gov (United States)

Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

2017-06-01

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

Subsequent primary malignancies after diffuse large B-cell lymphoma in the modern treatment era.

Science.gov (United States)

Tao, Li; Clarke, Christina A; Rosenberg, Aaron S; Advani, Ranjana H; Jonas, Brian A; Flowers, Christopher R; Keegan, Theresa H M

2017-07-01

With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated. We found that the incidence of acute myeloid leukaemia (AML) nearly doubled in the post-rituximab era [SIR (95% CI) 4·39 (2·51-7·13) pre- (1989-2000) and 8·70 (6·62-11·22) post-rituximab (2001-2012)]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 (0·08-2·37) vs. 2·27(1·44-3·41)]. The 5-year CMI for all SPMs (4·77% pre- vs. 5·41% post-rituximab, P = 0·047), AML (0·15% vs. 0·41%, P = 0·003), thyroid cancer (0·03% vs. 0·15%, P = 0·003) and melanoma (0·25% vs. 0·42%, P = 0·020) were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients. © 2017 John Wiley & Sons Ltd.

Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Science.gov (United States)

Noujima-Harada, Mai; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sakurai, Hiroaki; Igarashi, Kazuhiko; Ito, Etsuro; Nagakita, Keina; Taniguchi, Kohei; Ohnishi, Nobuhiko; Omote, Shizuma; Tabata, Tetsuya; Sato, Yasuharu; Yoshino, Tadashi

2017-05-01

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-β-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

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Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian; Liu, Yue-Ping; Wang, Wei-Hu; Jin, Jing; Song, Yong-Wen; Ren, Hua; Fang, Hui [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); He, Xiao-Hui; Dong, Mei [Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Chen, Bo; Lu, Ning-Ning; Li, Ning; Tang, Yuan; Tang, Yu; Dai, Jian-Rong [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Li, Ye-Xiong, E-mail: yexiong12@163.com [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

2016-10-01

Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating very good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.

The Predictive Value of Interim and Final [18F] Fluorodeoxyglucose Positron Emission Tomography after Rituximab-Chemotherapy in the Treatment of Non-Hodgkin's Lymphoma: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Yuyuan Zhu

2013-01-01

Full Text Available Background and Purpose. The aim of this study is to determine the prognostic value of interim and final FDG-PET in major histotypes of B-cell NHL patients treated with rituximab containing-chemotherapy. Methods. We searched for articles published in English, limited to lymphoma, rituximab, and FDG-PET, and dedicated to deal with the impact on progression and survival. The log hazard ratios (HR and their variances were estimated. Results. A PubMed and Scopus review of published trials identified 13 studies of Progression-free survival (PFS and overall survival (OS which were set as the main outcome measures. The combined HRs of I-PET for PFS and OS in DLBCL were 4.4 (P=0.11 and 3.99 (P=0.46, respectively. The combined HRs of F-PET for PFS and OS in DLBCL were 5.91 (P=0.39 and 6.75 (P=0.92, respectively. Regarding to non-DLBCL with F-PET, the combined HRs of F-PET for PFS and OS were 4.05 (P=0.79 and 5.1 (P=0.51, respectively. No publication bias existed. Conclusion. In DLBCL, both I-PET and F-PET can be performed for survival and progression analysis. But in other B-cell subtypes such as follicular lymphoma (FL and mantle cell lymphoma (MCL, it would be necessary to perform F-PET for predictive purposes.

IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

Science.gov (United States)

Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

2010-01-01

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine

Energy Technology Data Exchange (ETDEWEB)

Chen, Jiann-Hwa [Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Department of Emergency Medicine, Cathay General Hospital, Taipei, Taiwan (China); Kuo, Hsing-Chun [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Taiwan (China); Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China); Lee, Kam-Fai [Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Taiwan (China); Tsai, Tung-Hu, E-mail: thtsai@ym.edu.tw [Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China)

2014-09-15

Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30 mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. - Graphical abstract: Schematic presentation of the signaling pathways involved in magnolol inhibited transient global ischemia brain apoptosis and inflammation in rats. The effect of magnolol on the scavenger of ROS, which inhibits p38 MAPK and CHOP protein inactivation

Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine

International Nuclear Information System (INIS)

Chen, Jiann-Hwa; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

2014-01-01

Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30 mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. - Graphical abstract: Schematic presentation of the signaling pathways involved in magnolol inhibited transient global ischemia brain apoptosis and inflammation in rats. The effect of magnolol on the scavenger of ROS, which inhibits p38 MAPK and CHOP protein inactivation

Efficacy of Flaxseed Flour as Bind Enhancing Agent on the Quality of Extended Restructured Mutton Chops

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Heena Sharma

2014-02-01

Full Text Available Consumers have become very conscious about their nutrition and well being due to changes in their socio-economic lifestyle and rapid urbanization. Therefore, development of technology for production of low cost and functional meat products is urgently required. One such approach is innovative restructuring technology in which binding of meat pieces still remains the main challenge and extension of product is generally associated with poor binding and texture. Thus, the present study was envisaged as an attempt to solve this problem by the incorporation of flaxseed flour (FF as bind enhancing agent. The FF was used at three different levels viz., 0.5%, 1%, and 1.5% to replace lean meat in pre-standardized restructured mutton chops formulation. The products were subjected to analysis for physico-chemical, sensory and textural properties. Cooking yield, moisture percentage and fat percentage increased with increase in the level of incorporation of FF, however, protein percent and pH decreased with increase in the level of incorporation. Shear force value of product incorporated with 1.5% FF was significantly higher (p<0.01 than control and product containing 0.5% FF level. Among the sensory attributes, product with 1% flaxseed flour showed significantly higher values (p<0.05 for general appearance, binding, texture and overall acceptability. Hardness showed significant increasing (p<0.01 values with increasing levels of incorporation of flaxseed flour, however all other parameters of texture profile analysis showed a decreasing trend. On the basis of sensory scores and physico-chemical properties, the optimum incorporation level of FF was adjudged as 1%. Products incorporated with optimum level of flaxseed flour (1% were also assessed for water activity and microbiological quality during the storage period of 15 days. It was found that the extended restructured product could be safely stored under refrigeration (4°C±1°C in low density

Simultaneous dual pathology in lymph node

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Prakas Kumar Mandal

2014-05-01

Full Text Available [Abstract] Tubercuous lymphadenitis and Non Hodgkins’ Lymphoma are common in India. As both diseases can occur in elderly persons there is a definite chance of co-existence of both diseases; but that coexistence has not been reported. Here we present a unique case in an elderly woman who had synchronous double pathology of tuberculosis (TB and Diffuse Large B cell Lymphoma (DLBCL of the lymph nodes.     Key words:- lymph nodes, tuberculosis (TB, Diffuse Large B cell Lymphoma (DLBCL.

Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

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Taskinen, M.; Louhimo, R.; Koivula, S.

2014-01-01

Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment...... tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein...

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

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Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

2016-01-01

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

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Anastasiadou, Eleni; Stroopinsky, Dina; Alimperti, Stella; Jiao, Alan L; Pyzer, Athalia R; Cippitelli, Claudia; Pepe, Giuseppina; Severa, Martina; Rosenblatt, Jacalyn; Etna, Marilena P; Rieger, Simone; Kempkes, Bettina; Coccia, Eliana M; Sui, Shannan J Ho; Chen, Christopher S; Uccini, Stefania; Avigan, David; Faggioni, Alberto; Trivedi, Pankaj; Slack, Frank J

2018-06-26

Cancer cells subvert host immune surveillance by altering immune checkpoint (IC) proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs in the context of its preferred host, the B lymphocyte and in derived lymphomas. Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III-expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancers, our findings may have important implications for combinatorial immunotherapy, which include IC inhibiting antibodies and miR-34a, for EBV-associated cancers.

Adult non Hodgkin's lymphoma patients: experience from a tertiary care cancer centre in north east India.

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Hazarika, Munlima; Iqbal, Asif; Krishnatreya, Manigreeva; Sharma, Jagannath Dev; Bhuyan, Chidananda; Saikia, Bhargab Jyoti; Roy, Partha Sarathi; Das, Rashmi; Nandy, Pintu; Kataki, Amal Chandra

2015-01-01

There is paucity of data on non Hodgkin's lymphoma (NHL) from our population in North-East India. In this retrospective study, patients were consecutively followed-up to see the clinic-pathological pattern of NHL, various responses, and pattern of relapses to first line treatment with chemotherapy. All patients in the present study received standard regimen of cyclophosphamde, doxorubicin, vincristine, prednisolone (CHOP) with or without rituximab (R-CHOP) as per our institutional protocol as first line therapy. Our study has shown that, in our adult population, the majority of NHL cases present with stage II and stage III disease and extra nodal involvement, B-cell lymphomas and diffuse large cell lymphomas being the most common subtypes. International prognostic index was a significant factor for varied responses to treatment. The majority of relapses after complete remission occurred in the first year.

Fluorine-18-fluorodeoxyglucose Positron Emission Tomography in Diffuse Large B-cell Lymphoma

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Mylam, Karen Juul; Nielsen, Anne Lerberg; Pedersen, Lars Møller

2014-01-01

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and potentially curable type of lymphoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is part of clinical routine for DLBCL in most hospitals and also recommended for staging and end-of-therapy evaluation. FDG......-PET/computed tomography (CT) is able to identify nodal and extranodal sites with greater accuracy than CT alone. Little evidence supports the use of surveillance FDG-PET imaging in the follow-up setting because of high rates of false-positive scans and because most studies are retrospective. This article discusses FDG...

Komplet remission af højmalignt lymfom i ventriklen efter eradikation af Helicobacter pylori

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Høeg, Rasmus Tetens; Skau, Anne-Marie; Nørgaard, Peter

2011-01-01

. The recommended treatment of DLBCL is chemotherapy followed by involved-field irradiation. However, small prospective trials have shown high rates of complete remission after eradication of H. pylori alone and this treatment is an option in patients of advanced age or with severe co-morbidities.......A 91 year-old man was found to have diffuse large cell B-cell lymphoma (DLBCL), localized to the stomach. Because of his age, his only treatment was anti-Helicobacter pylori therapy. He achieved a complete remission, and six months after the initial presentation, there were no signs of recurrence...

Global hypomethylation is an independent prognostic factor in diffuse large B cell lymphoma

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Wedge, Eileen; Hansen, Jakob Werner; Garde, Christian

2017-01-01

Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure...... for global methylation, was measured in DNA from 67 tumor biopsies. Additionally, cell-free circulating DNA (cfDNA) in plasma samples from 74 patients was tested to assess the feasibility of global hypomethylation as a biomarker in liquid biopsies. LINE1 methylation was assessed using a commercially...

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

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Kai Qing

2016-08-01

Full Text Available Abstract We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.

Assessment of Correlation Between Early and Late Efficacy Endpoints to Identify Potential Surrogacy Relationships in Non-Hodgkin Lymphoma: a Literature-Based Meta-analysis of 108 Phase II and Phase III Studies.

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Zhu, Rui; Lu, Dan; Chu, Yu-Waye; Chai, Akiko; Green, Michelle; Zhang, Nancy; Jin, Jin Yan

2017-05-01

Correlations between early and late efficacy endpoints were assessed to identify potential surrogate endpoints for overall survival (OS) or progression-free survival (PFS) with clinical trial-level data in three non-Hodgkin lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). One hundred and eight phase II-III trials (129 trial arms) in DLBCL, FL, and MCL were identified and included in the database. Correlations between efficacy endpoints were analyzed using weighted linear regression and Pearson's coefficient of determination (R 2 ). In newly diagnosed DLBCL, 6-month PFS was strongly correlated with 2-year OS (R 2  = 0.81, 95% confidence interval [CI] 0.51-0.96). Six-month PFS was strongly correlated with 3-year PFS (R 2  = 0.89, 95% CI 0.62-0.96) in FL and was moderately correlated with 2-year OS (R 2  = 0.69, 95% CI 0.40-0.91) in MCL trials. Linear regression determined that a 10% increase in 6-month PFS would yield a 13% ± 1.2% increase in 2-year OS in DLBCL, a 23% ± 1.1% increase in 3-year PFS in FL, or a 6.7% ± 1.0% increase in 2-year OS in MCL. Both 6-month PFS and complete response (CR) rate were moderately correlated with median PFS in FL trials with R 2  = 0.66 (95% CI 0.52-0.98) and R 2  = 0.69 (95% CI 0.22-0.89), respectively. Six-month PFS is a potential surrogate endpoint for 2-year OS in newly diagnosed DLBCL and MCL and for 3-year PFS in FL. Both 6-month PFS and CR rate are potential surrogate endpoints for median PFS in FL patients. Confirmation and validation of these correlations may facilitate early interpretation of NHL trials.

Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

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Kung-Chao Chang

Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

Prognostic Value of FDG-PET, Based on the Revised Response Criteria, in Patients with Malignant Lymphoma: A Comparison with CT/MRI Evaluations, Based on the International Working Group/ Cotswolds Meeting Criteria

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Kayako Isohashi

2015-07-01

Full Text Available Objective(s: Post-treatment evaluations by CT/MRI (based on the International Working Group/ Cotswolds meeting guidelines and PET (based on Revised Response Criteria, were examined in terms of progression-free survival (PFS in patients with malignant lymphoma (ML. Methods: 79 patients, undergoing CT/MRI for the examination of suspected lesions and whole-body PET/CT before and after therapy, were included in the study during April 2007-January 2013. The relationship between post-treatment evaluations (CT/MRI and PET and PFS during the follow-up period was examined, using Kaplan-Meier survival analysis. The patients were grouped according to the histological type into Hodgkin’s lymphoma (HL, diffuse large B-cell lymphoma (DLBCL, and other histological types. The association between post-treatment evaluations (PET or PET combined with CT/ MRI and PFS was examined separately. Moreover, the relationship between disease recurrence and serum soluble interleukin-2 receptor, lactic dehydrogenase, and C-reactive protein levels was evaluated before and after the treatment. Results: Patients with incomplete remission on both CT/MRI and PET had a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET and those exhibiting incomplete remission on CT/MRI and complete remission on PET (P

Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBV association

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Castro Juan

2010-07-01

Full Text Available Abstract Background In Tanzania, the International Working Formulation [WF] rather than the WHO Classification is still being used in diagnosing malignant lymphomas (ML and the biological characterization including the HIV/EBV association is sketchy, thus restraining comparison, prognostication and application of established therapeutic protocols. Methods Archival, diagnostic ML biopsies (N = 336, available sera (N = 35 screened by ELISA for HIV antibodies and corresponding clinical/histological reports at Muhimbili National Hospital (MNH in Tanzania between 1996 and 2006 were retrieved and evaluated. A fraction (N = 174 were analyzed by histopathology and immunohistochemistry (IHC. Selected biopsies were characterized by flow-cytometry (FC for DNA ploidy (N = 60 and some by in-situ hybridization (ISH for EBV-encoded RNA (EBER, N = 37. Results A third (38.8%, 109/281 of the ML patients with available clinical information had extranodal disease presentation. A total of 158 out of 174 biopsies selected for immunophenotyping were confirmed to be ML which were mostly (84. 8%, 134/158 non-Hodgkin lymphoma (NHL. Most (83.6%, 112/134 of NHL were B-cell lymphomas (BCL (CD20+, of which 50.9%, (57/112 were diffuse large B-cell (DLBCL. Out of the 158 confirmed MLs, 22 (13.9% were T-cell [CD3+] lymphomas (TCL and 24 (15.2% were Hodgkin lymphomas (HL [CD30+]. Furthermore, out of the 60 FC analyzed ML cases, 27 (M:F ratio 2:1 were DLBCL, a slight majority (55.6%, 15/27 with activated B-cell like (ABC and 45% (12/27 with germinal center B-cell like (GCB immunophenotype. Overall, 40% (24/60 ML were aneuploid mostly (63.0%, 17/27 the DLBCL and TCL (54.5%, 6/11. DNA index (DI of FC-analyzed ML ranged from 1.103-2.407 (median = 1.51 and most (75.0% aneuploid cases showed high (>40% cell proliferation by Ki-67 reactivity. The majority (51.4%, 19/37 of EBER ISH analyzed lymphoma biopsies were positive. Of the serologically tested MLs, 40.0% (14/35 were HIV positive

Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBV association

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2010-01-01

Background In Tanzania, the International Working Formulation [WF] rather than the WHO Classification is still being used in diagnosing malignant lymphomas (ML) and the biological characterization including the HIV/EBV association is sketchy, thus restraining comparison, prognostication and application of established therapeutic protocols. Methods Archival, diagnostic ML biopsies (N = 336), available sera (N = 35) screened by ELISA for HIV antibodies and corresponding clinical/histological reports at Muhimbili National Hospital (MNH) in Tanzania between 1996 and 2006 were retrieved and evaluated. A fraction (N = 174) were analyzed by histopathology and immunohistochemistry (IHC). Selected biopsies were characterized by flow-cytometry (FC) for DNA ploidy (N = 60) and some by in-situ hybridization (ISH) for EBV-encoded RNA (EBER, N = 37). Results A third (38.8%, 109/281) of the ML patients with available clinical information had extranodal disease presentation. A total of 158 out of 174 biopsies selected for immunophenotyping were confirmed to be ML which were mostly (84. 8%, 134/158) non-Hodgkin lymphoma (NHL). Most (83.6%, 112/134) of NHL were B-cell lymphomas (BCL) (CD20+), of which 50.9%, (57/112) were diffuse large B-cell (DLBCL). Out of the 158 confirmed MLs, 22 (13.9%) were T-cell [CD3+] lymphomas (TCL) and 24 (15.2%) were Hodgkin lymphomas (HL) [CD30+]. Furthermore, out of the 60 FC analyzed ML cases, 27 (M:F ratio 2:1) were DLBCL, a slight majority (55.6%, 15/27) with activated B-cell like (ABC) and 45% (12/27) with germinal center B-cell like (GCB) immunophenotype. Overall, 40% (24/60) ML were aneuploid mostly (63.0%, 17/27) the DLBCL and TCL (54.5%, 6/11). DNA index (DI) of FC-analyzed ML ranged from 1.103-2.407 (median = 1.51) and most (75.0%) aneuploid cases showed high (>40%) cell proliferation by Ki-67 reactivity. The majority (51.4%, 19/37) of EBER ISH analyzed lymphoma biopsies were positive. Of the serologically tested MLs, 40.0% (14/35) were HIV

A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma.

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Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

2015-03-25

Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3 months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinical stage IV in the Ann Arbor staging classification). The first course of chemotherapy improved anasarca remarkably and the patient's body weight returned to what it was 3 months before. We experienced a patient with remarkable anasarca caused by DLBCL infiltration of the pituitary gland. A pituitary gland lesion with central hypothyroidism should be considered as one of the differential diagnoses of edema. This case was very valuable because we could assess it by following the time course of symptoms (edema and delayed relaxation time of the Achilles tendon reflex), laboratory data, and imaging findings (swelling anterior pituitary lobe).

CD79B limits response of diffuse large B cell lymphoma to ibrutinib.

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Kim, Joo Hyun; Kim, Won Seog; Ryu, Kyungju; Kim, Seok Jin; Park, Chaehwa

2016-01-01

Blockage of B cell receptor signaling with ibrutinib presents a promising clinical approach for treatment of B-cell malignancies. However, many patients show primary resistance to the drug or develop secondary resistance. In the current study, cDNA microarray and Western blot analyses revealed CD79B upregulation in the activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) that display differential resistance to ibrutinib. CD79B overexpression was sufficient to induce resistance to ibrutinib and enhanced AKT and MAPK activation, indicative of an alternative mechanism underlying resistance. Conversely, depletion of CD79B sensitized primary refractory cells to ibrutinib and led to reduced phosphorylation of AKT or MAPK. Combination of the AKT inhibitor or the MAPK inhibitor with ibrutinib resulted in circumvention of both primary and acquired resistance in ABC-DLBCL. Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.

Change of CD20 Expression in Diffuse Large B-Cell Lymphoma Treated with Rituximab, an Anti-CD20 Monoclonal Antibody: A Study of the Osaka Lymphoma Study Group

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Naoki Wada

2009-10-01

Full Text Available Change of CD20 expression was examined in cases of diffuse large B-cell lymphoma (DLBCL. CD20 expression after treatment with anti-CD20 antibody (rituximab, Rx for DLBCL was examined in 23 cases who received serial biopsy by immunohistochemistry (IHC and flow cytometry (FCM. CD20– by IHC and/or FCM was defined as CD20–. Four cases were CD20– at initial biopsy but became CD20+ after chemotherapy with Rx (CH-R (group A. Recurrent tumors in three group A cases became resistant to CH-R. Initial and recurrent tumors were CD20+ before and after CH-R in 17 cases (group B. Tumors before CH-R were CD20– in two cases (group C and continued to be CD20– in one and turned CD20+ in the other with survival time after the relapse of 8 and 23 months, respectively. Evaluation of CD20 expression with immunohistochemical and flow cytometric methods is used for the prediction of responsiveness of relapsed DLBCL for CH-R.

Relationship between pretreatment FDG-PET and diffusion-weighted MRI biomarkers in diffuse large B-cell lymphoma

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de Jong, Antoinette; Kwee, Thomas C; de Klerk, John MH; Adam, Judit A; de Keizer, Bart; Fijnheer, Rob; Kersten, Marie José; Ludwig, Inge; Jauw, Yvonne WS; Zijlstra, Josée M; den Bos, Indra C Pieters - Van; Stoker, Jaap; Hoekstra, Otto S; Nievelstein, Rutger AJ

2014-01-01

The purpose of this study was to determine the correlation between the 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) and the diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Pretreatment FDG-PET and diffusion-weighted MRI of 21 patients with histologically proven DLBCL were prospectively analyzed. In each patient, maximum, mean and peak standardized uptake value (SUV) was measured in the lesion with visually highest FDG uptake and in the largest lesion. Mean ADC (ADCmean, calculated with b-values of 0 and 1000 s/mm2) was measured in the same lesions. Correlations between FDG-PET metrics (SUVmax, SUVmean, SUVpeak) and ADCmean were assessed using Pearson’s correlation coefficients. In the lesions with visually highest FDG uptake, no significant correlations were found between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.498, P=0.609 and P=0.595, respectively). In the largest lesions, there were no significant correlations either between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.992, P=0.843 and P=0.894, respectively). The results of this study indicate that the glycolytic rate as measured by FDG-PET and changes in water compartmentalization and water diffusion as measured by the ADC are independent biological phenomena in newly diagnosed DLBCL. Further studies are warranted to assess the complementary roles of these different imaging biomarkers in the evaluation and follow-up of DLBCL. PMID:24795837

Application of Translational Medicine Theory in Chinese Materia Medica: Effect and Mechanism of Mahuang and Wuweizi on Pulmonary Fibrosis

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Hai-zhi QIN

2015-06-01

Full Text Available Objective: To explore the clinical efficacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL. Methods: A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efficacy and related adverse reactions of 2 groups were observed. Results: The rate of complete remission (CR in observational group was significantly higher than in control group (χ2=4.6589, P=0.0309. However, there was no significant difference in objective remission rate (ORR between 2 groups (P=0.3651. The rates of 3-year overall survival (OS, progression-free survival (PFS and disease-free survival (DFS were 80.30% (53/66, 69.70% (46/66 and 59.09% (39/66 in observational group, and 61.29% (19/31, 58.06% (18/31 and 58.06% (18/31 in control group, respectively. The OS in observational group was significantly longer than in control group (P=0.035. However, there was no significant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089; P=0.438; χ2=0.1562, P=0.6927. Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the first-line treatment for DLBCL, thus deserving to be widely applied in clinic.

Recent discoveries in high energy physics

CERN Multimedia

Schopper, Herwig

1975-01-01

At the 14th International Cosmic Ray Conference at Munich in August, Professor S chop per, Director of the DESY Laboratory, reviewed the recent findings. This is an abridged version of his talk. It is a little more specialised than we normally include but, for those who recall some of their physics education, it adds background to the arguments that we have been sketching in recent articles.

Effects of chopping, and soaking in water, hydrochloric acidic and calcium hydroxide solutions on the nutritional value of Acacia villosa for goats

International Nuclear Information System (INIS)

Wina, E.; Tangendjaja, B.; Susana, I.W.R.

2005-01-01

Acacia villosa, a thornless shrub legume, has potential as a feed supplement for ruminants if anti-nutritional factors, especially tannins, can be overcome. The effects of chopping and soaking the leaves on the amounts of tannin in the extracting solution and that left in the recovered leaves were studied. The tannin and non-tannin phenolics were solubilized in the extracting solution and the amount was increased with the soaking time. Soaking in calcium hydroxide solution, hydrochloric acid or water removed 41-76% of tannin and total phenolics removed from the recovered leaves. Soaking of the leaves also removed fermentable materials and reduced the gas production. In the first of two digestibility experiments, three groups of goats received one of these diets, those were: (1) sugar cane tops: unsoaked Acacia leaves (7:3), (2) sugar cane tops: water soaked Acacia leaves (7:3) and (3) sugar cane tops: water soaked Acacia leaves (7:3) + 100 g/day of cassava flour. Live weight of goats was measured every 2 weeks and a large increase in average daily gain was obtained for goats fed diet containing water soaked leaves and cassava flour (71 g/day) compared to those fed diet containing unsoaked leaves and water soaked leaves (38.9 and 44.7 g/day, respectively) (P 0.05) found in intake or digestibility between unsoaked and soaked leaves. In conclusion, soaking reduced tannin in Acacia leaves, improved digestibility and intake of Acacia leaves. In the presence of cassava flour, soaking improved average daily gain. Diets supplemented with water soaked Acacia leaves probably also need an energy supplement and cassava flour is one of the feed ingredients that is satisfactory. (author)

Diffuse large B-cell lymphoma with combined TP53 mutation and MIR34A> methylation

DEFF Research Database (Denmark)

Asmar, Fazila; Hother, Christoffer; Kulosman, Gorjan

2014-01-01

and MIR34A methylation ("double hit") and these patients have an exceedingly poor prognosis with a median survival of 9.4 months (Phit") influence on survival. The TP53/MIR34A "double-hit" is an independent...... negative prognostic factor for survival (P=0.0002). In 2 DLBCL-cell lines with both TP53 mutation and promoter methylation of MIR34A, miR34A-5p is upregulated by 5-aza-2'deoxycytidine. Thus, the TP53/MIR34A "double hit" characterizes a very aggressive subgroup of DLBCL, which may be treatable...

Minimal Loss of Lifetime for Patients With Diffuse Large B-Cell Lymphoma in Remission and Event Free 24 Months After Treatment

DEFF Research Database (Denmark)

Jakobsen, Lasse Hjort; Bøgsted, Martin; Brown, Peter de Nully

2017-01-01

Purpose The general outlook for patients with diffuse large B-cell lymphoma (DLBCL) in first remission is important information for patients and for planning post-treatment follow-up. The purpose of this study was to evaluate the survival of patients with DLBCL in remission compared with a matched......). During the first 8 years after pEFS24, the average loss of lifetime was 0.31 mo/y (95% CI, 0.11 to 0.50 mo/y). Excess mortality diminished when analyzing death from lymphoma as competing event to death from other causes, suggesting that early and late relapse is responsible for increased mortality...

Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

Science.gov (United States)

Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

2018-02-01

We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

International Nuclear Information System (INIS)

Pan, Mu-Yun; Shen, Yuh-Chiang; Lu, Chien-Hsing; Yang, Shu-Yi; Ho, Tsing-Fen; Peng, Yu-Ta; Chang, Chia-Che

2012-01-01

Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified as an

Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Pan, Mu-Yun [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Shen, Yuh-Chiang [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); National Research Institute of Chinese Medicine, Taipei, Taiwan (China); Lu, Chien-Hsing [Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yang, Shu-Yi [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Ho, Tsing-Fen [Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Peng, Yu-Ta [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chang, Chia-Che, E-mail: chia_che@dragon.nchu.edu.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China)

2012-12-15

Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified

Process optimization for enhancing production of cis-4-hydroxy-L-proline by engineered Escherichia coli.

Science.gov (United States)

Chen, Kequan; Pang, Yang; Zhang, Bowen; Feng, Jiao; Xu, Sheng; Wang, Xin; Ouyang, Pingkai

2017-11-22

Understanding the bioprocess limitations is critical for the efficient design of biocatalysts to facilitate process feasibility and improve process economics. In this study, a proline hydroxylation process with recombinant Escherichia coli expressing L-proline cis-4-hydroxylase (SmP4H) was investigated. The factors that influencing the metabolism of microbial hosts and process economics were focused on for the optimization of cis-4-hydroxy-L-proline (CHOP) production. In recombinant E. coli, SmP4H synthesis limitation was observed. After the optimization of expression system, CHOP production was improved in accordance with the enhanced SmP4H synthesis. Furthermore, the effects of the regulation of proline uptake and metabolism on whole-cell catalytic activity were investigated. The improved CHOP production by repressing putA gene responsible for L-proline degradation or overexpressing L-proline transporter putP on CHOP production suggested the important role of substrate uptake and metabolism on the whole-cell biocatalyst efficiency. Through genetically modifying these factors, the biocatalyst activity was significantly improved, and CHOP production was increased by twofold. Meanwhile, to further improve process economics, a two-strain coupling whole-cell system was established to supply co-substrate (α-ketoglutarate, α-KG) with a cheaper chemical L-glutamate as a starting material, and 13.5 g/L of CHOP was successfully produced. In this study, SmP4H expression, and L-proline uptake and degradation, were uncovered as the hurdles for microbial production of CHOP. Accordingly, the whole-cell biocatalysts were metabolically engineered for enhancing CHOP production. Meanwhile, a two-strain biotransformation system for CHOP biosynthesis was developed aiming at supplying α-KG more economically. Our work provided valuable insights into the design of recombinant microorganism to improve the biotransformation efficiency that catalyzed by Fe

PET/CT before autologous stem cell transplantation predicts outcome in refractory/relapsed follicular lymphoma

Energy Technology Data Exchange (ETDEWEB)

Alcantara, Marion; Tilly, Herve [Universite de Rouen, Service d' Hematologie, Centre Henri Becquerel, Rouen (France); Dupuis, Jehan; Haioun, Corinne [CHU Henri Mondor et Universite Paris-Est, Assistance Publique - Hopitaux de Paris, Unite Hemopathies Lymphoides, Marechal de Lattre de Tassigny (France); Mareschal, Sylvain; Dubois, Sydney [Centre Henri Becquerel, IRIB, Unite Inserm U918, Rouen (France); Julian, Anne [CHU Purpan, Service de Medecine Nucleaire, Toulouse (France); Cottereau, Anne Segolene; Becker, Stephanie [Centre Henri Becquerel, Service de Medecine Nucleaire, Rouen (France); Oberic, Lucie; Huynh, Anne; Laurent, Guy; Ysebaert, Loic [IUCT-Oncopole, Departement d' Hematologie, Toulouse (France); Meignan, Michel [CHU Henri-Mondor, Service de Medecine Nucleaire, Paris (France)

2014-09-20

Salvage of young patients with follicular lymphoma (FL) after R-CHOP includes salvage immunochemotherapy followed by autologous stem cell transplantation (ASCT). Previous studies dealing with relapsed Hodgkin lymphoma have shown the prognostic value of PET/CT prior to ASCT. We retrospectively analysed 59 patients with refractory/relapsed FL after first-line R-CHOP who were chemosensitive (as evaluated by CT) to the salvage treatment and who proceeded to ASCT. The role of PET/CT in this setting to define chemosensitivity is not definitely established. So we focused on the prognostic value of PET/CT performed after salvage treatment, before ASCT. The estimated 3-year progression-free survival (PFS) and overall survival were 63.1 % (50.9-78.3 %) and 90.5 % (82.8 - 98.8 %), respectively, and did not differ significantly according to their Follicular Lymphoma International Prognostic Index at relapse, conditioning regimen, or type of salvage. PFS was significantly lower in PET/CT-positive patients, according to the International Harmonization Project revised response criteria, with a 3-year PFS of 45.5 % (26.6 - 77.8 %) versus 72.6 % (58.5 - 90.0 %; p = 0.039). To better refine prognosis, we applied two types of thresholds: a Deauville five-point scale positive threshold of ≥3 (3-year PFS of 74.9 %, range 61.0 - 92.1 % %, versus 42.8 %, range 24.7 - 74.4 %; p = 0.02), and a ≥70 % ∇SUV{sub max} threshold between presalvage and pre-ASCT PET/CT (3-year PFS of 72.4 %, range 57.5 - 91.3 % versus 13.3 %, 2.2 - 81.7 %; p < 10{sup -3}). The PET/CT findings before ASCT were independently correlated with PFS in our series. PET/CT negativity before ASCT is a desirable and achievable goal in the management of chemosensitive FL relapsing after first-line R-CHOP. (orig.)

Assessment of different dietary fibers (tomato fiber, beet root fiber, and inulin) for the manufacture of chopped cooked chicken products.

Science.gov (United States)

Cava, Ramón; Ladero, Luis; Cantero, V; Rosario Ramírez, M

2012-04-01

Three dietary fibers (tomato fiber [TF], beet root fiber [BRF], and inulin) at 3 levels of addition (1%, 2%, and 3%) were assessed for the manufacture of chopped, cooked chicken products and compared with a control product without fiber added. The effect of fiber incorporation on (i) batters, (ii) cooked (30 min at 70 °C), and (iii) cooked and stored (for 10 d at 4 °C) chicken products were studied. The addition of the fiber to chicken meat products reduced the pH of chicken batters in proportional to the level of fiber addition. Fiber incorporation increased water-holding capacity but only the addition of TF reduced cook losses. The color of batters and cooked products was significantly modified by the type and level of fiber added. These changes were more noticeable when TF was added. Texture parameters were affected by the incorporation of TF and BRF; they increased the hardness in proportional to the level of addition. The addition of tomato and BRF to chicken meat products reduced lipid oxidation processes. These changes were dependent on the level of fiber added. The reduction of lipid oxidation processes was more marked in TF meat products than in products with other types of fibers. In contrast, the addition level of inulin increased TBA-RS numbers in chicken meat products. Although the addition of TF increased the redness of the meat products, the use of this fiber was more suitable as it reduced the extent of lipid oxidation processes. INDUSTRIAL APPLICATION: Nowadays, the reduction of fat and the increase of fiber content in meat products is one of the main goals of meat industry. Numerous sources of fiber can be added to the meat products; however, before that it is necessary to study their technological effect on raw and cooked meat products in order to evaluate their suitability for meat products manufacture. In addition, some of them could have beneficial effect on meat products conservation that could also increase their shelf life. © 2012

Distribution of medium-to-coarse glass beads in slurry pipe flow: evaluation of measured concentration profiles

Czech Academy of Sciences Publication Activity Database

Matoušek, Václav; Krupička, Jan; Pěník, Vojtěch

2014-01-01

Roč. 32, č. 2 (2014), s. 186-196 ISSN 0272-6351. [7th International Conference for Conveying and Handling of Particulate Solids (CHoPS). Friedrichshafen, 10.09.2013-13.09.2012] R&D Projects: GA ČR GA103/09/0383 Institutional support: RVO:67985874 Keywords : concentration distribution * high concentrated slurry * pipeline flow * slurry flow experiment Subject RIV: BK - Fluid Dynamics Impact factor: 0.523, year: 2014

Fully stratified particle-laden flow in horizontal circular pipe

Czech Academy of Sciences Publication Activity Database

Vlasák, Pavel; Kysela, Bohuš; Chára, Zdeněk

2014-01-01

Roč. 32, č. 2 (2014), s. 179-185 ISSN 0272-6351. [7th International Conference for Conveying and Handling of Particulate Solids (CHoPS). Friedrichshafen, 10.09.2013-13.09.2012] R&D Projects: GA ČR GAP105/10/1574 Institutional support: RVO:67985874 Keywords : coarse-grained slurry * flow structure * liquid local velocity * particle velocity * PIV Subject RIV: BK - Fluid Dynamics Impact factor: 0.523, year: 2014

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

International Nuclear Information System (INIS)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

2005-01-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20∼70 mg) immediately prior to administration of therapeutic dose (51.4∼152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

Energy Technology Data Exchange (ETDEWEB)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

2005-07-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma

International Nuclear Information System (INIS)

Nishi, Tatsuya; Takahashi, Hiroyuki; Hashimura, Miki; Yoshida, Tsutomu; Ohta, Yasutaka; Saegusa, Makoto

2015-01-01

FilGAP, a Rho GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK (Rho-associated protein kinase)-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focus on the possible roles of FilGAP expression in normal and malignant lymphocytes. Eighty-three cases of follicular lymphoma (FL), 84 of diffuse large B-cell lymphoma (DLBCL), and 25 of peripheral T-cell lymphoma (PTCL), as well as 10 of normal lymph nodes, were immunohistochemically investigated. In normal lymph nodes, FilGAP immunoreactivity was significantly higher in lymphocytes in the mantle zone as compared to those in the germinal center and paracortical areas. In contrast, the expression levels of both cytoplasmic and perinuclear Rac1 were significantly lower in the germinal center as compared to paracortical regions, suggesting that changes in the FilGAP/Rac axis may occur in B-cell lineages. In malignant lymphomas, FilGAP expression was significantly higher in B-cell lymphomas than PTCL, and the immunohistochemical scores were positively correlated with cytoplasmic Rac1 scores in FL and DLBCL, but not in PTCL. Patients with FL and germinal center B-cell-like (GCB)-type DLBCL showing high FilGAP scores had poor overall survival rates as compared to the low-score patients. Moreover, multivariate Cox regression analysis showed that a high FilGAP score was a significant and independent unfavorable prognostic factor in FL, but not in DLBCL. In conclusion, FilGAP may contribute to change in cell motility of B-lymphocytes. In addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular FL

Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

Energy Technology Data Exchange (ETDEWEB)

Dhakal, Sughosh; Bates, James E. [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Casulo, Carla; Friedberg, Jonathan W.; Becker, Michael W.; Liesveld, Jane L. [Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Constine, Louis S., E-mail: louis_constine@urmc.rochester.edu [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States)

2016-10-01

Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from further analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.

EBV-positive diffuse large B-cell lymphoma in a patient with primary Sjögren’s syndrome and membranous glomerulonephritis

Directory of Open Access Journals (Sweden)

Kim Chang

2012-11-01

Full Text Available Abstract Background Sjögren’s syndrome is a systemic autoimmune disease in which lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is thought to be a rare occurrence in primary Sjögren’s syndrome. Furthermore, concurrent glomerular involvement and lymphoma in patients with Sjögren’s syndrome has seldom been reported. Case presentation A 52-year-old woman with primary Sjögren’s syndrome developed membranous glomerulonephritis and Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL. She was diagnosed with Sjögren’s syndrome based on the dry eyes, dry mouth, positive anti-nuclear antibody test, anti-Ro (SS-A antibody, salivary gland biopsy, and salivary scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous glomerulonephritis. Three months later, her small bowel was perforated with pneumoperitoneum, and the biopsy revealed Epstein-Barr virus-positive DLBCL. Conclusions We observed the first case of primary Sjögren’s syndrome associated with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because of the possibility of malignancy-associated membranous glomerulonephritis in patients with primary Sjögren’s syndrome, we should be careful and examine such patients for hidden malignancy.

Clinical significance of post-treatment {sup 18}F-fluorodeoxyglucose uptake in cervical lymph nodes in patients with diffuse large B-cell lymphoma

Energy Technology Data Exchange (ETDEWEB)

An, Young-Sil; Yoon, Joon-Kee; Lee, Su Jin [Ajou University School of Medicine, Department of Nuclear Medicine and Molecular Imaging, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon-si (Korea, Republic of); Jeong, Seong Hyun; Lee, Hyun Woo [Ajou University School of Medicine, Department of Hematology-Oncology, Woncheon-dong, Yeongtong-gu, Gyeonggi-do, Suwon (Korea, Republic of)

2016-12-15

We assessed the clinical significance of FDG uptake in cervical lymph nodes after treatment of patients with DLBCL. In total, 87 patients with DLBCL were enrolled. All patients had newly appeared FDG uptake in cervical lymph nodes on PET/CT during follow-up after cessation of therapy. Cervical lymph nodes were finally diagnosed as benign or malignant according to histopathological findings or follow-up PET. Clinical characteristics and PET findings were compared between groups and factors associated with malignant lesions were evaluated. Only 8 (9.2 %) patients with cervical lymph nodes with FDG uptake ultimately had malignancy. FDG uptake lymph nodes appeared significantly earlier in the malignant group than in patients with benign FDG uptake (p = 0.013). Primary nodal lymphoma was more frequent in patients with cancer spread than in those with benign FDG uptake in lymph nodes (p < 0.001). Most cervical lymph nodes with FDG uptake (about 91 %) appearing after treatment of malignant DLBCL were ultimately benign. The elapsed time between the end of therapy and the appearance of cervical lymph nodes with FDG uptake and the primary sites of lymphomas are helpful clues in determining which cases are malignant. (orig.)

Formation of toroidal pre-heat plasma without residual magnetic field for high-beta pinch experiments

International Nuclear Information System (INIS)

Ikeda, Nagayasu; Tamaru, Ken; Nagata, Akiyoshi.

1979-01-01

Formation of toroidal pre-heat plasma was studied. The pre-heat plasma without residual magnetic field was made by chopping the current for pre-heat, A small toroidal-pinch system was used for the experiment. The magnetic field was measured with a magnetic probe. One turn loop was used for the measurement of the toroidal one-turn electric field. A pair of Rogoski coil was used for the measurement of plasma current. The dependence of residual magnetic field on chopping time was measured. By fast chopping of the primary current in the pre-heating circuit, the poloidal magnetic field was reduced to several percent within 5 microsecond. After chopping, no instability was observed in the principal discharge plasma produced within several microsecond. As the conclusion, it can be said that the control of residual field can be made by current chopping. (Kato, T.)

The mantle cells lymphoma: a proposed treatment

International Nuclear Information System (INIS)

Chavez Martinez, Marlene Elizabeth

2012-01-01

A literature review was performed on mantle cells lymphoma in the therapeutic schemes. The literature that has been used is published in journals of medicine specializing in hematology, oncology, radiation therapy, molecular biology and internal medicine. The literature review was performed to propose a scheme of treatment according to Costa Rica. Epigenetic alterations have been revealed in patients with mantle lymphoma on current researches. The mantle lymphoma pathology has been described in various forms of clinical and histological presentation, stressing the importance of detailing the different methods and diagnostic reports. Working groups have proposed and developed various chemotherapy regimens and concluded that CHOP alone is without effect in mantle cell lymphoma unlike R-hyper-CVAD, CHOP / DHAP, high-dose Ara-C. Researchers have tried to develop new treatments based vaccines, use of modified viruses, specific monoclonal antibodies. The classic treatment has been triple intrathecal therapy. The central nervous system has been one of the most momentous sites of mantle cell lymphoma infiltration because poorer patient prognosis [es

Measurements of transient electromagnetic propagation through concrete and sand

Energy Technology Data Exchange (ETDEWEB)

Aurand, J.F.

1996-09-01

This is the final report of a one-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). If a beam-chopping system could be developed for the Los Alamos Meson Physics Facility low-energy beam line, there would be potential to operate the Los Alamos Neutron Scattering Center (LANSCE) at much higher power and duty factor and enable such operation with a radio-frequency quadrapole (RFQ) injector. This would greatly extend the capability of the facility. To accommodate LANSCE operation in the new configuration, a chopped beam must be created in the low-energy transport line before the RFQ. Chopping in this region has never been demonstrated and constitutes the major uncertainty of the proposal and determines the critical path for project completion. This study produces a better understanding of the physics involved in chopping an H-beam in a dilute plasma background, and in transporting a chopped H-beam through a neutralized or partially neutralized plasma channel, as well as an estimate for the optimum neutralization strategy for the beam chopping and transport between the ion source and the RFQ.

Conditional survival of patients with diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Møller, Michael Boe; Pedersen, Niels Tinggaard; Christensen, Bjarne E

2006-01-01

BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survive...... survival probability provides more accurate prognostic information than the conventional survival rate estimated from the time of diagnosis.......BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survived...... a period of time after treatment. Conditional survival data have not been reported for lymphoma patients. METHODS: Conditional survival was estimated for 1209 patients with diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of the Danish Lymphoma Group. The Kaplan-Meier method...

The role of lipooligosaccharide phosphorylcholine in colonization and pathogenesis of Histophilus somni in cattle

Directory of Open Access Journals (Sweden)

Elswaifi Shaadi F

2012-06-01

Full Text Available Abstract Histophilus somni is a Gram-negative bacterium and member of the Pasteurellaceae that is responsible for respiratory disease and other systemic infections in cattle. One of the bacterium’s virulence factors is antigenic phase variation of its lipooligosaccharide (LOS. LOS antigenic variation may occur through variation in composition or structure of glycoses or their substitutions, such as phosphorylcholine (ChoP. However, the role of ChoP in the pathogenesis of H. somni disease has not been established. In Haemophilus influenzae ChoP on the LOS binds to platelet activating factor on epithelial cells, promoting bacterial colonization of the host upper respiratory tract. However, ChoP is not expressed in the blood as it also binds C-reactive protein, resulting in complement activation and killing of the bacteria. In order to simulate the susceptibility of calves with suppressed immunity due to stress or previous infection, calves were challenged with bovine herpes virus-1 or dexamethazone 3 days prior to challenge with H. somni. Following challenge, expression of ChoP on the LOS of 2 different H. somni strains was associated with colonization of the upper respiratory tract. In contrast, lack of ChoP expression was associated with bacteria recovered from systemic sites. Histopathology of cardiac tissue from myocarditis revealed lesions containing bacterial clusters that appeared similar to a biofilm. Furthermore, some respiratory cultures contained substantial numbers of Pasteurella multocida, which were not present on preculture screens. Subsequent biofilm experiments have shown that H. somni and P. multocida grow equally well together in a biofilm, suggesting a commensal relationship may exist between the two species. Our results also showed that ChoP contributed to, but was not required for, adhesion to respiratory epithelial cells. In conclusion, expression of ChoP on H. somni LOS contributed to colonization of the bacteria to the

Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

Science.gov (United States)

Hodson, Daniel J; Shaffer, Arthur L; Xiao, Wenming; Wright, George W; Schmitz, Roland; Phelan, James D; Yang, Yandan; Webster, Daniel E; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A; Staudt, Louis M

2016-04-05

The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.

A phase I/II trial to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor Temsirolimus added to standard therapy of Rituximab and DHAP for the treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma – the STORM trial

International Nuclear Information System (INIS)

Witzens-Harig, Mathias; Memmer, Marie Luise; Dreyling, Martin; Hess, Georg

2013-01-01

The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches. The STORM study is a prospective, multicentre phase I/II study to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to the standard therapy rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. The primary objective of the phase I of the trial is to establish the maximum tolerated dose (MTD) of temsirolimus in combination with rituximab and DHAP. The secondary objective is to demonstrate that stem cells can be mobilized during this regimen in patients scheduled to proceed to high dose therapy. In phase II, the previously established maximum tolerated dose of temsirolimus will be used. The primary objective is to evaluate the overall response rate (ORR) in patients with relapsed DLBCL. The secondary objective is to evaluate progression free survival (PFS), overall survival (OS) and toxicity. The study will be accompanied by an analysis of lymphoma subtypes determined by gene expression analysis (GEP). The STORM trial evaluates the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to standard therapy of rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. It also might identify predictive markers for this treatment modality. ClinicalTrials.gov http

Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas.

Science.gov (United States)

Islam, Shariful; Qi, Wenqing; Morales, Carla; Cooke, Laurence; Spier, Catherine; Weterings, Eric; Mahadevan, Daruka

2017-10-01

Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2 , which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan-Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083-93. ©2017 AACR . ©2017 American Association for Cancer Research.

Proceedings of ITOHOS 2008 : The 2008 SPE/PS/CHOA International Thermal Operations and Heavy Oil Symposium : Heavy Oil : Integrating the Pieces

International Nuclear Information System (INIS)

2008-10-01

This multi-disciplinary conference and exhibition combined the Society of Petroleum Engineers (SPE) and the Petroleum Society's (PS) international thermal operations and heavy oil symposium, and the Canadian Heavy Oil Association's (CHOA) annual business meeting. The conference provided a forum to examine emerging technologies and other critical issues affecting the global heavy oil and bitumen industry. The most current technologies from around the world that enhance the recovery of heavy oil and bitumen from oil sand deposits were also showcased. The technical program encompassed the economic, technical, and environmental challenges that the petroleum industry is currently facing. The sessions of the conference were entitled: artificial lift; mining, extraction and cold production; simulation; solvent processes; reservoir characterization; steam generation and water treatment; and, in-situ combustion in Canada. The conference also featured a series of short courses and tutorials on heavy oil wellbore completions and design; drilling horizontal heavy oil wells and steam assisted gravity drainage (SAGD) wells; geomechanical based reservoir monitoring; thermal well design; fiber optic thermal monitoring; heavy oil thermal recovery and economics; wellbore slotting; advanced geomechanics; and, an overview of cold heavy oil production with sand (CHOPS). All 91 presentations from the conference have been catalogued separately for inclusion in this database. refs., tabs., figs

Proceedings of ITOHOS 2008 : The 2008 SPE/PS/CHOA International Thermal Operations and Heavy Oil Symposium : Heavy Oil : Integrating the Pieces

Energy Technology Data Exchange (ETDEWEB)

NONE

2008-10-15

This multi-disciplinary conference and exhibition combined the Society of Petroleum Engineers (SPE) and the Petroleum Society's (PS) international thermal operations and heavy oil symposium, and the Canadian Heavy Oil Association's (CHOA) annual business meeting. The conference provided a forum to examine emerging technologies and other critical issues affecting the global heavy oil and bitumen industry. The most current technologies from around the world that enhance the recovery of heavy oil and bitumen from oil sand deposits were also showcased. The technical program encompassed the economic, technical, and environmental challenges that the petroleum industry is currently facing. The sessions of the conference were entitled: artificial lift; mining, extraction and cold production; simulation; solvent processes; reservoir characterization; steam generation and water treatment; and, in-situ combustion in Canada. The conference also featured a series of short courses and tutorials on heavy oil wellbore completions and design; drilling horizontal heavy oil wells and steam assisted gravity drainage (SAGD) wells; geomechanical based reservoir monitoring; thermal well design; fiber optic thermal monitoring; heavy oil thermal recovery and economics; wellbore slotting; advanced geomechanics; and, an overview of cold heavy oil production with sand (CHOPS). All 91 presentations from the conference have been catalogued separately for inclusion in this database. refs., tabs., figs.

RNA-binding protein VICKZ is expressed in a germinal center associated pattern among lymphoma subtypes

DEFF Research Database (Denmark)

Natkunam, Y.; Vainer, G.; Zhao, S.C.

2005-01-01

and tumorigenesis/metastasis. We generated an antibody that recognizes all three isoforms of VICKZ protein and characterized its expression in normal lymphoid tissue and in lymphoma subtypes. In normal tonsils, VICKZ protein showed a germinal center-specific pattern of expression with staining localized...... to the cytoplasm. Among 868 non-Hodgkin and Hodgkin lymphomas tested by immunohistochemistry on tissue microarrays, staining for VICKZ protein was present in 76% (126/165) of follicular lymphoma, 78% (155/200) of DLBCL, 90% (9/10) of mediastinal large B-cell lymphoma, and 100% (2/2) of Burkitt lymphoma. A subset...... protein in lymphoma subtypes suggests a potential utility for VICKZ in the identification of subgroups of DLBCL associated with different prognoses....

STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

Science.gov (United States)

Mizowaki, Takashi; Sasayama, Takashi; Tanaka, Kazuhiro; Mizukawa, Katsu; Takata, Kumi; Nakamizo, Satoshi; Tanaka, Hirotomo; Nagashima, Hiroaki; Nishihara, Masamitsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

2015-09-01

Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

A Case Report of Nongerminal Center B-Cell Type Diffuse Large B-Cell Lymphoma Treated to Complete Response with Rituximab and Ibrutinib

Directory of Open Access Journals (Sweden)

Geoffrey Shouse

2018-01-01

Full Text Available Diffuse large B-cell lymphoma (DLBCL is a molecularly heterogeneous disease consisting of different subtypes with varying clinical behaviors. For example, the activated B-cell-like (ABC type of DLBCL has lower cure rates with traditional chemotherapy regimens. The molecular pathway promoting tumorigenic growth of the ABC type includes a dependence on intracellular signaling by Bruton’s agammaglobulinemia tyrosine kinase (BTK. This specific pathway has led to the investigation of the utility of ibrutinib in treatment of this type of lymphoma at relapse or in combination with standard chemotherapy. In elderly patients stricken with this disease, standard combination chemotherapy can pose significant toxicity. Some reduced intensity regimens have activity but significantly less favorable long-term outcomes and still pose significant toxicity to elderly patients. In the following case, we demonstrate induction of complete response in an elderly patient with significant comorbidities with nongerminal center B-cell type (NGCB DLBCL treated with rituximab, ibrutinib, and prednisone. Toxicity included atrial fibrillation that ultimately led to heart failure as well as sepsis which ultimately led to the patient’s demise. Despite this fact, the response to treatment appeared durable. This case illustrates the utility and limitations of molecularly targeted therapies to treat aggressive lymphoma in frail elderly patients.

Radiotherapy of primary gastric malignant lymphoma

International Nuclear Information System (INIS)

Monzen, Yoshio; Mutsukura, Masahide; Moriuchi, Yukiyoshi

2017-01-01

Fifteen patients with primary gastric malignant lymphoma who underwent radiotherapy were examined. Median age was 68 years, and male to female ratio was 1:2. All the cases were stage I including 7 cases of diffuse large B-cell lymphoma (DLBCL), 7 cases of MALT lymphoma, and 1 case of follicular lymphoma. Therapy methods were as follows. For DLBCL, 30 Gy of radiotherapy was performed after chemotherapy. For six cases of MALT lymphomas, 30 Gy of radiotherapy was performed. For one patient diagnosed as high-grade gastric MALT lymphoma was treated in the same way as DLBCL. For one patient with follicular lymphoma, 30 Gy of radiotherapy was performed. The radiotherapy was applied with 3-dimensional fixed multi-portal irradiation, with the reduced irradiation of the liver and kidney. There was no recurrence of disease in all cases, and all patients have been alive, and no-recurrence living periods are 20 to 120 months. There was no harmful adverse event, and the tumor had disappeared with 30 Gy of radiation therapy in all cases. Considering the occurrence of secondary cancer, it was considered that a dosage of more than 30 Gy was not necessary for primary gastric malignant lymphoma. (J.P.N.)

Hypomethylation and Over-Expression of the Beta Isoform of BLIMP1 is Induced by Epstein-Barr Virus Infection of B Cells; Potential Implications for the Pathogenesis of EBV-Associated Lymphomas

Directory of Open Access Journals (Sweden)

Katerina Vrzalikova

2012-10-01

Full Text Available B-lymphocyte-induced maturation protein 1 (BLIMP1 exists as two major isoforms, α and β, which arise from alternate promoters. Inactivation of the full length BLIMP1α isoform is thought to contribute to B cell lymphomagenesis by blocking post-germinal centre (GC B cell differentiation. In contrast, the shorter β isoform is functionally impaired and over-expressed in several haematological malignancies, including diffuse large B cell lymphomas (DLBCL. We have studied the influence on BLIMP1β expression of the Epstein-Barr virus (EBV, a human herpesvirus that is implicated in the pathogenesis of several GC-derived lymphomas, including a subset of DLBCL and Hodgkin’s lymphoma (HL. We show that BLIMP1β expression is increased following the EBV infection of normal human tonsillar GC B cells. We also show that this change in expression is accompanied by hypomethylation of the BLIMP1β-specific promoter. Furthermore, we confirmed previous reports that the BLIMP1β promoter is hypomethylated in DLBCL cell lines and show for the first time that BLIMP1β is hypomethylated in the Hodgkin/Reed-Sternberg (HRS cells of HL. Our results provide evidence in support of a role for BLIMP1β in the pathogenesis of EBV-associated B cell lymphomas.

Analysis of treatment outcomes for primary tonsillar lymphoma

Energy Technology Data Exchange (ETDEWEB)

Lee, Yun Hee [Dept. of Radiation Oncology, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju (Korea, Republic of); Cho, Seok Goo; Jung, Seung Eun; Kim, Sung Hoon; O, Joo Hyun; Park, Gyeong Sin; Yang, Suk Woo; Lee, In Seok; Rhee, Chin; Kook; Choi, Byung Ock [Catholic University Lymphoma Group (CULG), Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

2016-12-15

Although each Waldeyer’s ring sub-site is considered an independent prognostic factor, few studies have assessed the prognosis and treatment of tonsillar lymphoma. Treatment outcomes were analyzed in patients with primary tonsillar lymphoma who were treated with chemotherapy and radiotherapy (RT). Nineteen patients with diffuse large B-cell lymphoma were evaluated, with a median follow-up of 53 months. Age, sex, and histology, amongst other factors, were reviewed. Progression-free survival (PFS) and overall survival (OS) rates were analyzed. Most patients had Ann Arbor stage I-II (94.7%), IPI score of 0 (89.5%), and complete remission after chemotherapy (89.5%). The 5-year PFS and OS rates were 74.6% and 80%, respectively. In univariate analysis, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen resulted in a better PFS than the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (88.9% vs. 50.0%; p = 0.053). RT dose was related to the survival outcome (p = 0.010 for PFS, p = 0.044 for OS). Patients were classified into the CHOP + RT (>40 Gy) group and R-CHOP + RT (≤40 Gy) group. The 5-year PFS rates were 50% in the CHOP + RT group, and 100 % in the R-CHOP + RT group (p = 0.018). The 5-year OS rates were 66.7% and 100%, respectively (p = 0.087). Primary tonsillar lymphoma patients typically have favorable outcomes. Chemotherapy (R-CHOP) combined with relatively lower dose consolidative RT may be safe and effective for primary tonsillar lymphoma.

Ki-67 is a valuable prognostic predictor of lymphoma but its utility varies in lymphoma subtypes: evidence from a systematic meta-analysis

International Nuclear Information System (INIS)

He, Xin; Chen, Zhigang; Fu, Tao; Jin, Xueli; Yu, Teng; Liang, Yun; Zhao, Xiaoying; Huang, Liansheng

2014-01-01

Ki-67 is a nuclear protein involved in cell proliferation regulation, and its expression has been widely used as an index to evaluate the proliferative activity of lymphoma. However, its prognostic value for lymphoma is still contradictory and inconclusive. PubMed and Web of Science databases were searched with identical strategies. The impact of Ki-67 expression on survival with lymphoma and various subtypes of lymphoma was evaluated. The relationship between Ki-67 expression and Diffuse Large B Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL) was also investigated after the introduction of a CD-20 monoclonal antibody rituximab. Furthermore, we evaluated the association between Ki-67 expression and the clinical-pathological features of lymphoma. A total of 27 studies met the inclusion criteria, which comprised 3902 patients. Meta-analysis suggested that high Ki-67 expression was negatively associated with disease free survival (DFS) (HR = 1.727, 95% CI: 1.159-2.571) and overall survival (OS) (HR = 1.7, 95% CI: 1.44-2) for lymphoma patients. Subgroup analysis on the different subtypes of lymphoma suggested that the association between high Ki-67 expression and OS in Hodgkin Lymphoma (HR = 1.511, 95% CI: 0.524-4.358) was absent, while high Ki-67 expression was highly associated with worse OS for Non-Hodgkin Lymphoma (HR = 1.777, 95% CI: 1.463-2.159) and its various subtypes, including NK/T lymphoma (HR = 4.766, 95% CI: 1.917-11.849), DLBCL (HR = 1.457, 95% CI: 1.123-1.891) and MCL (HR = 2.48, 95% CI: 1.61-3.81). Furthermore, the pooled HRs for MCL was 1.981 (95% CI: 1.099-3.569) with rituximab and 3.123 (95% CI: 2.049-4.76) without rituximab, while for DLBCL, the combined HRs for DLBCL with and without rituximab was 1.459 (95% CI: 1.084-2.062) and 1.456 (95% CI: 0.951-2.23) respectively. In addition, there was no correlation between high Ki-67 expression and the clinical-pathological features of lymphoma including the LDH level, B symptoms, tumor stage

New proposal for the treatment of poor prognosis young patients with advanced stage diffuse large B-cell lymphoma Nova proposta de tratamento no linfoma difuso de grandes células B no paciente jovem de mau prognóstico em estágio avançado

Directory of Open Access Journals (Sweden)

Sergio Cortelazzo

2008-06-01

Full Text Available Patients with DLBCL now have a better outcome with a longer survival because of two major developments: 1 increasing the dose of active drugs with shortening the time between cycles, resulting in dose-dense or dose-intense regimens; and 2 combining rituximab with chemotherapy. Both strategies were associated with a better clinical outcome, particularly in patients without adverse prognostic factors. Poor risk patients in the age range of 60 to 65 years may benefit from a combination of dose-dense or dose-intense regimens plus rituximab. Young patients with poor risk DLBCL defined by an aaIPI of 2 or 3 and age younger than 60 years, are characterized by truly refractory disease, evidenced by progression during or early after treatment, or later relapse. Attempts to modify treatment including immunotherapy to improve the response rate and reduce the proportion of patients with progressive disease have been only partially successful: to date: the best progression-free survival was 51%. In contrast, some attempts to decrease the high resistant and relapse rate with sequential high-dose chemotherapy with rituximab (R-HDS and autologous stem cell transplantation (ASCT have succeeded. On the basis of these promising results, GITIL launched a prospective phase III randomized trial comparing the efficacy and safety of dose-dense CHOP plus rituximab with R-HDS and ASCT. Preliminary data show that intensive programs such as dose-dense chemo-immunotherapy and R-HDS with ASCT are feasible until 65 years with a manageable toxic profile, also on multi-centre basis.Os pacientes com linforma de grande células B agora apresentam uma melhor evolução e longa sobrevida por causa de dois grandes desenvolvimentos: 1- Aumento da dose de drogas ativas e o espaço de tempo mais curto entre os ciclos, resultando deste fato uma dose mais consistente ou um regime com dose mais intensa. 2- Combinação da quimioterapia com o rituximab. Estas duas estratégias s

Accidents in making fireworks. Tapaturmat polttopuun teossa

Energy Technology Data Exchange (ETDEWEB)

Solmio, H

1991-01-01

The accidents and the trends in the number of accidents and their causes were analyzed in a study conducted by the Forestry Department of the Work Efficiency Institute. The study was funded by the Finnish Agricultural Enterpreneurs' Pension Fund (MELA). The study material was selected from MELA's accident stage work and cause code. Altogether, the material comprised the following accidents that occurred while making and using firewood: 671 accidents in 1987 and 596 accidents in 1988. The amount of accidents caused by the working environment and hand tools was clearly higher in 1987 than in 1988. The number of accidents occurred while chopping wood was 20 % higher in 1987 than in 1988. April was the most accident-prone month both in 1987 and in 1988. Chopping of firewood was the most dangerous work stage in terms of the number of accidents. In 1988, the number of accidents in chopping firewood was 336, in sawing using circular saw 97 cases and other mechanized chopping led to 93 accidents. Heating with wood caused 33 accidents. In 1988 there were 10 (2 %) accidents involving loss of limbs and 9 of them occurred in the mechanized chopping of firewood. Nine accidents of these involved the loss of one or more fingers. Serious accidents, leading to inability to work for more than 3 months, were most frequent in chopping and in storing firewood.

Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

Directory of Open Access Journals (Sweden)

Georg Lenz

2015-05-01

Full Text Available Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

Energy Technology Data Exchange (ETDEWEB)

Lenz, Georg [Translational Oncology, Department of Medicine A, Albert-Schweitzer Campus 1, University Hospital Münster, 48149 Münster (Germany); Cluster of Excellence EXC 1003, Cells in Motion, 48149 Münster (Germany)

2015-05-22

Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma.

Science.gov (United States)

Nijland, Marcel; Jansen, Anne; Doorduijn, Jeanette K; Enting, Roelien H; Bromberg, Jacoline E C; Kluin-Nelemans, Hanneke C

2017-09-01

Central nervous system (CNS) involvement in systemic B-cell non-Hodgkin lymphoma (B-NHL) at diagnosis (sysCNS) is rare. We investigated the outcome of 21 patients with sysCNS, most commonly diffuse large B-cell lymphoma, treated with high dose methotrexate (HD-MTX) and R-CHOP. The median number of cycles of HD-MTX and R-CHOP was 4 (range 1-8) and 6 (range 0-8), respectively. Consolidative whole brain radiotherapy (WBRT) was given to 33% (7/21) patients. With a median follow-up of 44 months the 3-year progression free survival (PFS) and overall survival (OS) were 45% (95%CI 34-56%) and 49% (95%CI 38-60%), respectively. Over 90% of patients had an unfavorable international prognostic index score, reflected by treatment-related mortality of 19% (4/21) and relapse-related mortality of 28% (6/21). The outcome of these patients was, however, unexpectedly good when compared to secondary CNS relapses. Prospective studies are needed to define the optimal treatment for patients with sysCNS, but its rarity might be challenging.

Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort.

Science.gov (United States)

Schinasi, Leah H; De Roos, Anneclaire J; Ray, Roberta M; Edlefsen, Kerstin L; Parks, Christine G; Howard, Barbara V; Meliker, Jaymie R; Bonner, Matthew R; Wallace, Robert B; LaCroix, Andrea Z

2015-11-01

Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of US women. In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers. The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% confidence interval [CI] = 0.95-1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% CI = 1.15-2.38). Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL (95% CI = 1.13-3.09). Insecticide exposures may contribute to risk of CLL/SLL and DLBCL. Future studies should examine relationships of LH subtypes with specific types of household insecticides. Copyright © 2015 Elsevier Inc. All rights reserved.

Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women’s Health Initiative (WHI) observational study cohort

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Schinasi, L; De Roos, AJ; Ray, RM; Edlefsen, KL; Parks, CG; Howard, BV; Meliker; Bonner, MR; Wallace, RB; LaCroix, AZ

2017-01-01

Purpose Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of United States women. Methods In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers. Results The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% CI: 0.95–1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% CI: 1.15–2.38). Women younger than 65 who ever applied insecticides had 87% higher risk of DLBCL (95% CI: 1.13–3.09). Conclusions Insecticide exposures may contribute to risk of CLL/SLL and DLBCL. Future studies should examine relationships of LH subtypes with specific types of household insecticides. PMID:26365305

A clinicopathological study of primary central nervous system lymphomas & their association with Epstein-Barr virus

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Mehar Chand Sharma

2016-01-01

Results: During a period of 10 years, 65 PCNSL were diagnosed which comprised 0.69 per cent (65/9476 of all intracranial tumours. The mean age of presentation was 49 yr with sex ratio (M:F of 1.4:1. Most common location was supratentorial region with predominant involvement of frontal lobe. Single lesions were seen in 38 (58.4% and multifocal lesions in 27 (41.5% patients. None of the patients were immunocompromised. All cases were B cell immunophenotype and were DLBCL except one case of follicular lymphoma. According to Hans classification, majority of them were NGC (n=51, 79.6% and 13 (20.3% were GC type. Bcl-2 expression was noted in 34 (52.3% tumours. EBV was positive in three (4.6% cases; two were detected both by IHC and CISH and one case by CISH only. Interpretation & conclusions: In Indian population, PCNSL occurs mainly in immunocompetent patients, and a decade earlier than in western population. Immunophenotyping revealed that all cases were DLBCL with predominance of NGC type. No prognostic difference was seen between GC and NGC DLBCL. Association of EBV was rare and this virus was possibly not involved in the pathogenesis of PCNSL in immunocompetent individuals. CISH was an easy, economical and less cumbersome method for detection of EBV in PCNSL.

Interleukin 10 gene promoter polymorphism and risk of diffuse large ...

African Journals Online (AJOL)

Roba M. Talaat

2013-10-09

Oct 9, 2013 ... chain reaction (SSP-PCR) in 100 Egyptian DLBCL patients and 119 normal controls. Circulating .... One hundred nineteen unrelated healthy blood donors ..... patients and were correlated with adverse disease features and.

Food processing and structure impact the metabolizable energy of almonds.

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Gebauer, Sarah K; Novotny, Janet A; Bornhorst, Gail M; Baer, David J

2016-10-12

The measured metabolizable energy (ME) of whole almonds has been shown to be less than predicted by Atwater factors. However, data are lacking on the effects of processing (roasting, chopping or grinding) on the ME of almonds. A 5-period randomized, crossover study in healthy individuals (n = 18) was conducted to measure the ME of different forms of almonds (42 g per day), as part of a controlled diet: whole, natural almonds; whole, roasted almonds; chopped almonds; almond butter; and control (0 g per day). After 9 days of adaptation to each diet, participants collected all urine and fecal samples for 9 days. Diets, urine, and feces were analyzed to determine ME. Fracture force and fracture properties of whole and chopped almonds were measured. Measured ME (kcal g -1 ) of whole natural almonds (4.42), whole roasted almonds (4.86), and chopped almonds (5.04) was significantly lower than predicted with Atwater factors (P almond butter (6.53 kcal g -1 ) was similar to predicted (P = 0.08). The ME of whole roasted and chopped almonds was lower than almond butter (P almonds was lower than whole roasted almonds (P almonds (345 ± 1.6 N) (P almonds fracturing into fewer, larger particles, thus inhibiting the release of lipids. Atwater factors overestimate the ME of whole (natural and roasted) and chopped almonds. The amount of calories absorbed from almonds is dependent on the form in which they are consumed.

NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients

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Prochazka, Katharina T; Melchardt, Thomas; Posch, Florian; Schlick, Konstantin; Deutsch, Alexander; Beham-Schmid, Christine; Weiss, Lukas; Gary, Thomas; Neureiter, Daniel; Klieser, Eckhard; Greil, Richard; Neumeister, Peter; Egle, Alexander; Pichler, Martin

2016-01-01

Background: Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. Methods: The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. Results: Five-year OS and PFS were 50.4% (95% CI: 39.2–60.6) and 44.0% (33.4–54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl−1), and 66.2% (60.4–71.5) and 59.6% (53.7–65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10–1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16–2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17–9.23, Puric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index. PMID:27764838

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

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Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium

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Kane, Eleanor; Skibola, Christine F.; Bracci, Paige M.; Cerhan, James R.; Costas, Laura; Smedby, Karin Ekström; Holly, Elizabeth A.; Maynadié, Marc; Novak, Anne J.; Lightfoot, Tracy J.; Ansell, Stephen M.; Smith, Alex G.; Liebow, Mark; Melbye, Mads; Morton, Lindsay; de Sanjosé, Silvia; Slager, Susan L.; Wang, Sophia S.; Zhang, Yawei; Zheng, Tongzhang; Roman, Eve

2015-01-01

Background Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported. Method Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI). Results Obesity (BMI≥30kg m−2) was associated with DLBCL risk (OR=1.33, 95%CI 1.02–1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07–1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27–2.94), with a RERI of 0.41 (95%CI −0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected. Conclusions Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk. Impact Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma. PMID:25962811

Advances in the molecular diagnosis of diffuse large B-cell lymphoma in the era of precision medicine.

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Araf, Shamzah; Korfi, Koorosh; Rahim, Tahrima; Davies, Andrew; Fitzgibbon, Jude

2016-10-01

The adoption of high-throughput technologies has led to a transformation in our ability to classify diffuse large B-cell lymphoma (DLBCL) into unique molecular subtypes. In parallel, the expansion of agents targeting key genetic and gene expression signatures has led to an unprecedented opportunity to personalize cancer therapies, paving the way for precision medicine. Areas covered: This review summarizes the key molecular subtypes of DLBCL and outlines the novel technology platforms in development to discriminate clinically relevant subtypes. Expert commentary: The application of emerging diagnostic tests into routine clinical practise is gaining momentum following the demonstration of subtype specific activity by novel agents. Co-ordinated efforts are required to ensure that these state of the art technologies provide reliable and clinically meaningful results accessible to the wider haematology community.

Effects of chopping, and soaking in water, hydrochloric acidic and calcium hydroxide solutions on the nutritional value of Acacia villosa for goats

Energy Technology Data Exchange (ETDEWEB)

Wina, E. [Research Institute for Animal Production, Bogor (Indonesia)]. E-mail: winabudi@yahoo.com; Tangendjaja, B.; Susana, I.W.R. [Research Institute for Animal Production, Bogor (Indonesia)

2005-08-19

Acacia villosa, a thornless shrub legume, has potential as a feed supplement for ruminants if anti-nutritional factors, especially tannins, can be overcome. The effects of chopping and soaking the leaves on the amounts of tannin in the extracting solution and that left in the recovered leaves were studied. The tannin and non-tannin phenolics were solubilized in the extracting solution and the amount was increased with the soaking time. Soaking in calcium hydroxide solution, hydrochloric acid or water removed 41-76% of tannin and total phenolics removed from the recovered leaves. Soaking of the leaves also removed fermentable materials and reduced the gas production. In the first of two digestibility experiments, three groups of goats received one of these diets, those were: (1) sugar cane tops: unsoaked Acacia leaves (7:3), (2) sugar cane tops: water soaked Acacia leaves (7:3) and (3) sugar cane tops: water soaked Acacia leaves (7:3) + 100 g/day of cassava flour. Live weight of goats was measured every 2 weeks and a large increase in average daily gain was obtained for goats fed diet containing water soaked leaves and cassava flour (71 g/day) compared to those fed diet containing unsoaked leaves and water soaked leaves (38.9 and 44.7 g/day, respectively) (P < 0.05). In the second digestibility experiment, the three diets were: (1) sugar cane tops: unsoaked Acacia (7:3), (2) sugar cane tops water soaked Acacia (7:3), (3) sugar cane tops: calcium hydroxide soaked Acacia (7:3). A supplement of 100 g/day of cassava flour was added to each of these three diets. In both digestibility experiments, soaking improved intake and digestibility of Acacia leaves, and cassava flour increased the intake, but when all the diets contained cassava flour, there was no significant difference (P > 0.05) found in intake or digestibility between unsoaked and soaked leaves. In conclusion, soaking reduced tannin in Acacia leaves, improved digestibility and intake of Acacia leaves. In the

Retrospective analysis of first-line treatment for follicular lymphoma based on outcomes and medical economics.

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Muneishi, Manaka; Nakamura, Ayaka; Tachibana, Katsumi; Suemitsu, Junko; Hasebe, Shinji; Takeuchi, Kazuto; Yakushijin, Yoshihiro

2018-04-01

Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients' QOL and medical economics.

40 CFR 761.79 - Decontamination standards and procedures.

Science.gov (United States)

2010-07-01

.... (b) Decontamination standards. Chopping (including wire chopping), distilling, filtering, oil/water... burned and marketed in accordance with the requirements for used oil in § 761.20(e), disposed of in... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Decontamination standards and...

Study Identifies New Lymphoma Treatment Target

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NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

Study on Mechanical and Physical Behaviour of Hybrid GFRP

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Nor Bahiyah Baba

2015-01-01

Full Text Available The paper discusses the mechanical and physical behaviour of hybrid glass fibre reinforced plastic (GFRP. Hybrid GFRP was fabricated by three different types of glass fibre, namely, 3D, woven, and chopped, which were selected and combined with mixture of polyester resin and hardener. The hybrid GFRP was investigated by varying three parameters which were the composite volume fractions, hybrid GFRP arrangement, and single type fibre. The hybrid GFRP was fabricated by using open mould hand lay-up technique. Mechanical testing was conducted by tensile test for strength and stiffness whereas physical testing was performed using water absorption and hardness. These tests were carried out to determine the effect of mechanical and physical behaviour over the hybrid GFRP. The highest volume fraction of 0.5 gives the highest strength and stiffness of 73 MPa and 821 MPa, respectively. Varying hybrid fibre arrangement which is the arrangement of chopped-woven-3D-woven-chopped showed the best value in strength of 66.2 MPa. The stiffness is best at arrangement of woven-chopped-woven-chopped-woven at 690 MPa. This arrangement also showed the lowest water absorption of 4.5%. Comparing the single fibre type, woven had overtaken the others in terms of both mechanical and physical properties.

Resultados de la cirugía de cataratas por la técnica de facoemulsificación Results of cataract surgery using quick chop phacoemulsification

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Luis Curbelo Cunill

2007-12-01

Full Text Available La catarata, en la mayoría de los casos, se considera una causa remediable de disminución de agudeza visual. A través del tiempo se han conseguido mejoras tecnológicas que hacen que la cirugía de catarata sea relativamente fácil, segura y la rehabilitación visual usualmente exitosa sobre todo cuando esta se acompaña de implante de lente intraocular. Varias alternativas para dividir el núcleo del cristalino surgieron desde entonces, pero pocas son realmente necesarias. Este trabajo tiene como objetivo describir los resultados funcionales y anatómicos alcanzados con la técnica de facoemulsificación con quick chop, las edades de los pacientes, la agudeza visual corregida preoperatoria y posoperatoria, el astigmatismo preoperatorio y posoperatorio, la microscopia endotelial preoperatorio y posoperatoria, el tiempo de ultrasonido aplicado y las complicaciones presentadas. Realizamos un estudio descriptivo, prospectivo, de corte transversal, en 146 pacientes (ojos operados entre enero de 2004 y enero de 2006 en el Centro de Microcirugía Ocular del Instituto Cubano de Oftalmología “Ramón Pando Ferrer” El universo de trabajo lo constituyeron todos los pacientes con diagnóstico de catarata presenil y senil que cumplían con los criterios de selección y que aceptaron someterse a la técnica quirúrgica señalada. Con el fin de evaluar la eficacia de la técnica, se analizaron como variables: edad, sexo, agudeza visual con corrección (AVCC, y cilindro refractivo, así como microscopia endotelial, tiempo de ultrasonido, y complicaciones más frecuentes. Estos datos se analizaron a través de tablas de contingencia con frecuencias absolutas y relativas además con medias; se utilizó la prueba t de Student para compararlos. Se encontró que la catarata predominó en el sexo masculino en mayores de 60 años, la agudeza visual con corrección obtenida como promedio fue mejor que en el preoperatorio, el cilindro refractivo apenas se

EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies

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Marshall Williams

2018-05-01

Full Text Available The Epstein-Barr virus (EBV, which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase modulates innate and adaptive immune responses by engaging the Toll-Like Receptor 2 (TLR2, which leads to the modulation of downstream genes involved in oncogenesis, chronic inflammation, and in effector T-cell function. Furthermore, examination of serum samples from diffuse large B-cell lymphoma (DLBCL and chronic lymphocytic leukemia patients revealed the presence of increased levels of anti-dUTPase antibodies in both cohorts compared to controls with the highest levels (3.67-fold increase observed in DLBCL female cases and the lowest (2.12-fold increase in DLBCL males. Using computer-generated algorithms, dUTPase amino acid sequence alignments, and functional studies of BLLF3 mutants, we identified a putative amino acid motif involved with TLR2 interaction. These findings suggest that the EBV-dUTPase: TLR2 interaction is a potential molecular target that could be used for developing novel therapeutics (small molecules/vaccines.

Epstein-Barr virus EBNA2 directs doxorubicin resistance of B cell lymphoma through CCL3 and CCL4-mediated activation of NF-κB and Btk.

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Kim, Joo Hyun; Kim, Won Seog; Hong, Jung Yong; Ryu, Kung Ju; Kim, Seok Jin; Park, Chaehwa

2017-01-17

Epstein-Barr virus (EBV)-encoded nuclear antigen, EBNA2, expressed in EBV-infected B lymphocytes is critical for lymphoblastoid cell growth. Microarray profiling and cytokine array screening revealed that EBNA2 is associated with upregulation of the chemokines CCL3 and CCL4 in lymphoma cells. Depletion or inactivation of CCL3 or CCL4 sensitized DLBCL cells to doxorubicin. Our results indicate that EBV influences cell survival via an autocrine mechanism whereby EBNA2 increases CCL3 and CCL4, which in turn activate the Btk and NF-κB pathways, contributing to doxorubicin resistance of B lymphoma cells. Western blot data further confirmed that CCL3 and CCL4 direct activation of Btk and NF-κB. Based on these findings, we propose that a pathway involving EBNA2/Btk/NF-κB/CCL3/CCL4 plays a key role in doxorubicin resistance, and therefore, inhibition of specific components of this pathway may sensitize lymphoma cells to doxorubicin. Evaluation of the relationship between CCL3 expression and EBV infection revealed high CCL3 levels in EBV-positive patients. Our data collectively suggest that doxorubicin treatment for EBNA2-positive DLBCL cells may be effectively complemented with a NF-κB or Btk inhibitor. Moreover, evaluation of the CCL3 and CCL4 levels may be helpful for selecting DLBCL patients likely to benefit from doxorubicin treatment in combination with the velcade or ibrutinib.

Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients.

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Culpin, Rachel E; Sieniawski, Michal; Angus, Brian; Menon, Geetha K; Proctor, Stephen J; Milne, Paul; McCabe, Kate; Mainou-Fowler, Tryfonia

2013-12-01

To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients. The prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival (OS; P = 0.033, P = 0.010 and P = 0.008, respectively). High Bcl-2 (≥80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival (PFS; P = 0.001, P = 0.048, P = 0.045 and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS (P = 0.022, P = 0.037 and P = 0.011) and PFS (P = 0.021, P = 0.020 and P = 0.004). The Choi, Choi* and Tally were associated with PFS (P = 0.049, P = 0.009 and P = 0.023). In multivariate analysis, the International Prognostic Index (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P < 0.001 and PFS; HR: 2.91, P < 0.001). Results highlight the controversy surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized. © 2013 John Wiley & Sons Ltd.

Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting

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Zhao Jiangning

2012-08-01

Full Text Available Abstract Indolent lymphoma (IL, the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone remains the standard frontline regimen for diffuse Large B –cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial, R-CHOP was compared with R-CVP (cyclophosphamide, vincristine, prednisone and R-FM (fludarabine, mitoxantrone. The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.

Primary Type3 (Non-ABC, Non-GCB Subtype of Extranodal Diffuse Large B-Cell Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization

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Yukiko Nishi

2017-06-01

Full Text Available Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of mostly neoplastic transformation of germinal center-like B cells (GCB or memory B cells. Other B-cell-type malignancies arising primarily in the thyroid have rarely been described. Immunohistochemical examination of autopsied primary malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL without the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B-cell (ABC subtype, and the detection of an extremely aggressive yet local clinical phenotype demonstrated that the present case was an exceptional entity of the type3 (non-GCB and non-ABC subtype.

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

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Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

2016-08-01

Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

Induction of the unfolded protein response by cigarette smoke is primarily an activating transcription factor 4-C/EBP homologous protein mediated process

Directory of Open Access Journals (Sweden)

Geraghty P

2011-06-01

Full Text Available Patrick Geraghty, Alison Wallace, Jeanine M D'ArmientoDepartment of Medicine, Divisions of Molecular and Pulmonary Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USAPurpose: Cigarette smoke is the major risk factor associated with the development of chronic obstructive pulmonary disease (COPD. Recent studies propose a link between endoplasmic reticulum (ER stress and emphysema, demonstrated by increased ER stress markers under smoking conditions. Here, we investigate whether cigarette smoke-induced ER stress is cell specific and correlates with acute and chronic cigarette smoke exposure.Methods: Gene and protein expression changes in human primary lung cell cultures following cigarette smoke extract (CSE exposure were monitored by qPCR and Western blot analysis. Mice and guinea pigs were exposed to cigarette smoke and ER stress markers examined in whole lung homogenates. Inflammatory cells from the bronchoalveolar lavage fluid of 10 days smoke exposed mice were also examined.Results: Cigarette smoke induced a trend increase in the ER stress response through an activating transcription factor 4 (ATF4 mediated induction of C/EBP homologous protein (CHOP in primary small airway epithelial cells. Bronchial epithelial cells and macrophages responded similarly to CSE. Wild-type mice and guinea pigs exposed to acute levels of cigarette smoke exhibited increased levels of CHOP but not at significant levels. However, after long-term chronic cigarette smoke exposure, CHOP expression was reduced. Interestingly, inflammatory cells from smoke exposed mice had a significant increase in CHOP/ATF4 expression.Conclusion: A trend increase in CHOP levels appear in multiple human lung cell types following acute cigarette smoke exposure in vitro. In vivo, inflammatory cells, predominately macrophages, demonstrate significant cigarette smoke-induced ER stress. Early induction of CHOP in cigarette smoke may play a pivotal role in early

Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines

Science.gov (United States)

Hirasawa, Kazuhiro; Moriya, Shota; Miyahara, Kana; Kazama, Hiromi; Hirota, Ayako; Takemura, Jun; Abe, Akihisa; Inazu, Masato; Hiramoto, Masaki; Tsukahara, Kiyoaki

2016-01-01

Autophagy, a self-digestive system for cytoplasmic components, is required to maintain the amino acid pool for cellular homeostasis. We previously reported that the macrolide antibiotics azithromycin (AZM) and clarithromycin (CAM) have an inhibitory effect on autophagy flux, and they potently enhance the cytocidal effect of various anticancer reagents in vitro. This suggests that macrolide antibiotics can be used as an adjuvant for cancer chemotherapy. Since cancer cells require a larger metabolic demand than normal cells because of their exuberant growth, upregulated autophagy in tumor cells has now become the target for cancer therapy. In the present study, we examined whether macrolides exhibit cytotoxic effect under an amino acid-starving condition in head and neck squamous cancer cell lines such as CAL 27 and Detroit 562 as models of solid tumors with an upregulated autophagy in the central region owing to hypovascularity. AZM and CAM induced cell death under the amino acid-depleted (AAD) culture condition in these cell lines along with CHOP upregulation, although they showed no cytotoxicity under the complete culture medium. CHOP knockdown by siRNA in the CAL 27 cells significantly suppressed macrolide-induced cell death under the AAD culture condition. CHOP-/- murine embryonic fibroblast (MEF) cell lines also attenuated AZM-induced cell death compared with CHOP+/+ MEF cell lines. Using a tet-off atg5 MEF cell line, knockout of atg5, an essential gene for autophagy, also induced cell death and CHOP in the AAD culture medium but not in the complete culture medium. This suggest that macrolide-induced cell death via CHOP induction is dependent on autophagy inhibition. The cytotoxicity of macrolide with CHOP induction was completely cancelled by the addition of amino acids in the culture medium, indicating that the cytotoxicity is due to the insufficient amino acid pool. These data suggest the possibility of using macrolides for “tumor-starving therapy”. PMID

Epidemiological studies on salmonella in a certain area ("Walcheren project") III. The presence of salmonella in man, insects, seagulls and in foods, chopping-block scrapings from butcher's shops, effluent of sewage treatment plants and drains of butcher's shops.

Science.gov (United States)

Edel, W; van Schothorst, M; van Leusden, F M; Kampelmacher, E H

1978-12-01

For a period of three months in a relatively small area (Walcheren), various materials (meat and meat products, insects, seagull droppings, chopping-block scrapings from butcher's shops, effluent of sewage treatment plants, drains from butcher's shops and stools of patients) were examined again for the presence of Salmonella as a continuation of previous investigations. As had been the case in previous studies, S. typhimurium (27.5%), S. panama (22.2%) and S. brandenburg (9.2%) were the three most frequently isolated serotypes. The three most frequently isolated phage types of S. typhimurium were II 505 (62.1%) II 502 (5.3%) and I 650 (4.2%). The serotypes and phage types were present in almost all the materials examined which again emphasizes the fact that there are contamination cycles of Salmonella. These studies show that the route of contamination divides in the butcher's shops. Salmonella organisms carried with the meat from the slaughter-house find their way into the drains on the one hand, and through meat and meat products, to the consumer on the other. Moreover, the high degree of contamination of effluent is not in accordance with the small number of cases of salmonellosis in man.

Features and performance of PCa board which cuts off the electromagnetic wave. Electromagnetic shield building using the carbon fiber contamination PCa board; Denjiha wo shadansuru PCa ban no tokucho to seino. Tanso sen'i konnyu PCa ban wo mochiita denji shirudobiru

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Katsuo; Kasai, Yasuaki [Obayashi Corp., Osaka (Japan); Okada, Shin' ichiro; Sakamoto, Shin [Osaka Gas Corp., Osaka (Japan)

1999-03-10

With the rapid popularization of public radio information communication equipment, portable telephones, wireless LAN, etc., the interception (building shield) of the electromagnetic wave internal and external the building becomes large problem. As process equal to the convention and the method in which the cost is possible, they did do not shield the whole building, and also ensure the comfort as an office, and PCa board which mixed the carbon fiber into the mortar was developed. They described the survey result of the electromagnetic shield performance of the building which constructed by using this in external wall. They explained electromagnetism characteristics of the contamination mortar and application to the PCa board and method. They carried out the measurement in the electromagnetic shield room laboratory, and they obtained next result. 1) There is seldom on the effect both only the concrete and only by the carbon fiber mesh. 2) They considered the effect that carbon fiber chop 1% are mixed into the concrete. 3) The effect became a maximum, when carbon fiber chop and carbon fiber mesh were mixed, and they confirmed being excellent cost-concerned. (NEDO)

Nordic scepticism towards health claims

DEFF Research Database (Denmark)

Pedersen, Susanne; Grunert, Klaus G.

2008-01-01

Imagine that you are shopping in a supermarket and find a package of pork chops labelled "omega-3 added" or that the yogurt "contains phosphatidylserine, which can improve your memory"; would you buy these pork chops or this yogurt? Most Nordic consumers would choose products without health claims....

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

The expression patterns of CHOP and glucose-regulated protein (GRP) 78, a good marker of ER stress, were assessed by Western blotting, real-time PCR, Hoechst and immunohistochemistry in the hippocampus, cortex and striatum on a status epilepticus (SE) model. Double-fluorescent staining of CHOP and the terminal ...

The amount of food ingested in a single meal by rainbow trout offered chopped herring, dry and wet diets

Science.gov (United States)

Ruohonen; Grove; McIlroy

1997-07-01

Two-year-old 1·5-kg rainbow trout were held in cages and conditioned by feeding either on low-fat chopped herring (H trout) or dry pellets (P trout) for 15 weeks. Their satiation amounts were then determined under standard conditions. On a wet weight basis H trout ate 2·5-3·5 times more food than P trout; this was sufficient to compensate for the high water content of herring and thereby maintain the dry matter intake. When P trout were offered herring (PH trout) they consumed more food than when offered dry pellets but not as much as H trout. Stomach capacity restricted the intake and their dry matter intake was reduced by c. 40%. When H trout were offered dry pellets (HP trout) they adjusted their intake immediately close to the level of P trout although their larger stomachs could have accommodated more than twice this volume of dry food. The return of appetite after a satiation meal was almost linear with time. Appetite increased at c. 556 mg g-1 body weight h-1 for H trout and at 142 mg g-1 bw h-1 for P trout. The return of appetite in PH trout was significantly slower (c. 370 mg g-1 bw h-1) than in H trout; the previous dietary history of the PH trout limited their capacity to process larger volumes of wet food in a single meal. Fish offered dry diet (P and HP trout) had similar rates of appetite return despite their previous feeding history suggesting that the property of the dry feed itself might limit meal size. The total gastric emptying time of diets of similar dry matter content (with and without large amounts of water) was similar, but the delay time before gastric emptying starts tended to be longer for dry diets. Dry pellets appear to impose a demand for water that prolongs the gastric delay. This water demand is met partly by drinking since the trout fed on dry pellets drank significantly more (436±189 mg kg-1 h-1) than unfed and herring-fed trout which drank little or not at all (65±113 and 70±66 mg kg-1 h-1 respectively). Dietary water

Whole-brain radiotherapy and high-dose methylprednisolone for elderly patients with primary central nervous system lymphoma: Results of North Central Cancer Treatment Group (NCCTG) 96-73-51

International Nuclear Information System (INIS)

Laack, Nadia N.; Ballman, Karla V.; Brown, Paul B.; O'Neill, Brian Patrick

2006-01-01

Purpose: The aim of this study was to evaluate the efficacy, toxicity, and survival of whole-brain radiotherapy-treated (WBRT) and high-dose methylprednisolone (HDMP)-treated in elderly patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients with PCNSL who were 70 years and older received 1 g of methylprednisolone daily for 5 days, 30 days after WBRT. Patients then received 1 g of methylprednisolone every 28 days until progression. The primary endpoint was overall survival (OS) at 6 months. Results were compared with those in patients on the previous North Central Cancer Treatment Group (NCCTG) trial who received pre-WBRT cytoxan, adriamycin, vincristine, prednisone (CHOP) and high-dose cytarabine (CHOP-WBRT). A planned interim analysis was performed. The current regimen would be considered inactive if survival was not improved from patients treated with CHOP-WBRT. Results: Nineteen patients were accrued between 1998 and 2003. Median age was 76 years. Interim analysis revealed a 6-month survival of 33%, resulting in closure of the trial. Toxicity, OS, and event-free survival (EFS) were similar to those in patients more than 70 years of age who received CHOP-WBRT. The subgroup of patients who received HDMP had longer OS (12.1 vs. 7.0 months, p = 0.76) and EFS (11.7 vs. 4.0 months, p = 0.04) compared with the CHOP-WBRT patients alive 60 days after the start of treatment. Conclusions: Patients on-study long enough to receive HDMP had prolongation of OS and EFS compared to patients receiving CHOP-WBRT. Although the numbers of patients are too small for statistical conclusions, the HDMP regimen deserves further study

Mmu-miR-615-3p regulates lipoapoptosis by inhibiting C/EBP homologous protein.

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Yasuhiro Miyamoto

Full Text Available Lipoapoptosis occurring due to an excess of saturated free fatty acids such as palmitate is a key pathogenic event in the initiation of nonalcoholic fatty liver disease. Palmitate loading of cells activates the endoplasmic reticulum stress response, including induction of the proapoptotic transcription factor C/EBP homologous protein (CHOP. Furthermore, the loss of microRNAs is implicated in regulating apoptosis under conditions of endoplasmic reticulum (ER stress. The aim of this study was to identify specific microRNAs regulating CHOP expression during palmitate-induced ER stress. Five microRNAs were repressed under palmitate-induced endoplasmic reticulum stress conditions in hepatocyte cell lines (miR-92b-3p, miR-328-3p, miR-484, miR-574-5p, and miR-615-3p. We identified miR-615-3p as a candidate microRNA which was repressed by palmitate treatment and regulated CHOP protein expression, by RNA sequencing and in silico analyses, respectively. There is a single miR-615-3p binding site in the 3'untranslated region (UTR of the Chop transcript. We characterized this as a functional binding site using a reporter gene-based assay. Augmentation of miR-615-3p levels, using a precursor molecule, repressed CHOP expression; and under these conditions palmitate- or tunicamycin-induced cell death were significantly reduced. Our results suggest that palmitate-induced apoptosis requires maximal expression of CHOP which is achieved via the downregulation of its repressive microRNA, miR-615-3p. We speculate that enhancement of miR-615-3p levels may be of therapeutic benefit by inhibiting palmitate-induced hepatocyte lipoapoptosis.

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

2017-01-01

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

Clinical Implications of Phosphorylated STAT3 Expression in de novo Diffuse Large B-cell Lymphoma

DEFF Research Database (Denmark)

Ok, Chi Y; Chen, Jiayu; Xu-Monette, Ziju

2014-01-01

PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of...

Effect of Litter on Development and Severity of Foot-Pad Dermatitis and Behavior of Broiler Chickens

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D Zikic

Full Text Available ABSTRACT This study was conducted to evaluate the impact of litter type and litter treatment with enzymatic-bacterial production incidence and severity of footpad dermatitis and consequently on behavior of broiler chickens. A total of 1,200 one day-old Ross 308 broilers were randomly allocated to 4 treatments with 4 replicates in 2 x 2 factorial design. The first factor was the physical form of the straw (chopped on approximately 2 cm or un-chopped and the second factor was addition of enzymatic-bacterial product applied directly on the straw. Each replicate consisted of 75 as-hatched birds per pen. Occurrence and severity of the footpad dermatitis and histological evaluation of the scores was done at the end of the trial (42 days of age. During the trial, at 3 and 6 weeks of age, broiler behavior was observed by Scan Sampling Method. The results showed that chopped straw significantly lowered the incidence of footpad dermatitis. Chopped straw in combination with enzymatic-bacterial product showed the lowest footpad dermatitis score in broilers. Histological procedures confirmed the macroscopic evaluation of the footpad dermatitis severity. The chopped straw had a significant effect on some behavioral patterns of broiler chickens. Differences were observed for dust bathing and scratching. Correlation between footpad dermatitis and birds locomotor activity was not confirmed.

Lymphoma of the Eyelid

DEFF Research Database (Denmark)

Svendsen, Frederik Holm; Rasmussen, Peter Kristian; Coupland, Sarah E.

2017-01-01

Purpose To document subtype-specific clinical features of lymphoma of the eyelid, and their effect on patient outcome. Design Retrospective observational case series. Methods Patient data were collected from 7 international eye cancer centers from January 1, 1980 through December 31, 2015....... The cases included primary and secondary lymphomas affecting the eyelid. Overall survival, disease-specific survival (DSS), and progression-free survival were the primary endpoints. Results Eighty-six patients were included. Mean age was 63 years and 47 (55%) were male. Non-Hodgkin B-cell lymphomas...... constituted 83% (n = 71) and T-cell lymphomas constituted 17% (n = 15). The most common subtypes were extranodal marginal-zone lymphoma (EMZL) (37% [n = 32]), follicular lymphoma (FL) (23% [n = 20]), diffuse large B-cell lymphoma (DLBCL) (10% [n = 9]), mantle cell lymphoma (MCL) (8% [n = 7]), and mycosis...

Internal Audit Service | Internal Audit Service

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their internal auditing function in the areas of professional excellence, quality of service and Students and teachers Media Internal Audit Service Navbar Toggle Home About the Staff Risk Assessment and Planning Internal Audit Process Search for Search Home The mission of the Fermilab Internal Audit Service

CD3+/CD16+CD56+ cell numbers in peripheral blood are correlated with higher tumor burden in patients with diffuse large B-cell lymphoma

Directory of Open Access Journals (Sweden)

Anna Twardosz

2011-04-01

Full Text Available Diffuse large B-cell lymphoma is the commonest histological type of malignant lymphoma, andremains incurable in many cases. Developing more efficient immunotherapy strategies will require betterunderstanding of the disorders of immune responses in cancer patients. NKT (natural killer-like T cells wereoriginally described as a unique population of T cells with the co-expression of NK cell markers. Apart fromtheir role in protecting against microbial pathogens and controlling autoimmune diseases, NKT cells havebeen recently revealed as one of the key players in the immune responses against tumors. The objective of thisstudy was to evaluate the frequency of CD3+/CD16+CD56+ cells in the peripheral blood of 28 diffuse largeB-cell lymphoma (DLBCL patients in correlation with clinical and laboratory parameters. Median percentagesof CD3+/CD16+CD56+ were significantly lower in patients with DLBCL compared to healthy donors(7.37% vs. 9.01%, p = 0.01; 4.60% vs. 5.81%, p = 0.03, although there were no differences in absolute counts.The frequency and the absolute numbers of CD3+/CD16+CD56+ cells were lower in advanced clinical stagesthan in earlier ones. The median percentage of CD3+/CD16+CD56+ cells in patients in Ann Arbor stages 1–2 was5.55% vs. 3.15% in stages 3–4 (p = 0.02, with median absolute counts respectively 0.26 G/L vs. 0.41 G/L (p == 0.02. The percentage and absolute numbers of CD3+/CD16+CD56+ cells were significantly higher in DL-BCL patients without B-symptoms compared to the patients with B-symptoms, (5.51% vs. 2.46%, p = 0.04;0.21 G/L vs. 0.44 G/L, p = 0.04. The percentage of CD3+/CD16+CD56+ cells correlated adversely with serumlactate dehydrogenase (R= –445; p < 0.05 which might influence NKT count. These figures suggest a relationshipbetween higher tumor burden and more aggressive disease and decreased NKT numbers. But it remains tobe explained whether low NKT cell counts in the peripheral blood of patients with DLBCL are the result

Profiling of diffuse large B-cell lymphoma by immunohistochemistry

DEFF Research Database (Denmark)

Sjö, Lene Dissing; Poulsen, Christian Bjørn; Hansen, Mads

2007-01-01

Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed...

Role of Radiation Therapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

Ng, Andrea K; Yahalom, Joachim; Goda, Jayant S

2018-01-01

Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with a...

The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT

DEFF Research Database (Denmark)

Alzahrani, M; El-Galaly, T C; Hutchings, M

2016-01-01

BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing positron emission tomography combined with computed tomography (PET/CT) staging is controversial. PATIENTS AND METHODS: Patients with newly d...

Chopped filter for nuclear spectroscopy

International Nuclear Information System (INIS)

Koyama, J.

1980-12-01

Some of the theoretical and practical factors affecting the energy resolution of a spectrometry system are considered, specially those related to t he signal-to-noise ratio, and a time-variant filter with the transfer function of the theoretical optimum filter, during its active time, is proposed. A prototype has been tested and experimental results are presented. (Author) [pt

Multifocal Gastric Ulcers Caused by Diffuse Large B Cell Lymphoma in a Patient With Significant Weight Loss

Directory of Open Access Journals (Sweden)

Mark A. Gromski MD

2016-12-01

Full Text Available Primary gastrointestinal (GI lymphoma is a heterogeneous disease with varied clinical presentations. The stomach is the most common GI site and accounts for 70% to 75% of GI lymphomas. We present a patient with gastric diffuse large B cell lymphoma (DLBCL who presented with significant weight loss, early satiety, and multifocal ulcerated gastric lesions. Esophagoduodenoscopy should be performed in patients presenting with warning symptoms as in our case. Diagnosis is usually made by endoscopic biopsies. Multiple treatment modalities including surgery, radiotherapy, and chemotherapy have been used. Advancements in endoscopic and pathologic technology decrease turnaround time for diagnosis and treatment initiation, thus reducing the need for surgery. Health care providers should maintain a high level of suspicion and consider gastric DLBCL as part of the differential diagnosis, especially in those with warning symptoms such as weight loss and early satiety with abnormal endoscopic findings.

International Trade. International Business

OpenAIRE

Мохнюк, А. М.; Mokhniuk, A. M.

2015-01-01

Work programme of the study course “International Trade. International Business” was prepared in accordance with educational and vocational training program for bachelors of training direction 6.030601 “Management”.

241 244

Indian Academy of Sciences (India)

tribpo

et al. 1994) or by using high frequency chopping mechanism (like the ZIMPOL, Povel. 1995) which eliminates seeing induced spurious polarisation signals. In an earlier attempt at the KTT (Ananth et al. 1994), a chopping scheme was utilised with a peltier cooled CCD detector achieving a rate of 0.5 Hz. However, this CCD ...

"Slow-scanning" in Ground-based Mid-infrared Observations

Science.gov (United States)

Ohsawa, Ryou; Sako, Shigeyuki; Miyata, Takashi; Kamizuka, Takafumi; Okada, Kazushi; Mori, Kiyoshi; Uchiyama, Masahito S.; Yamaguchi, Junpei; Fujiyoshi, Takuya; Morii, Mikio; Ikeda, Shiro

2018-04-01

Chopping observations with a tip-tilt secondary mirror have conventionally been used in ground-based mid-infrared observations. However, it is not practical for next generation large telescopes to have a large tip-tilt mirror that moves at a frequency larger than a few hertz. We propose an alternative observing method, a "slow-scanning" observation. Images are continuously captured as movie data, while the field of view is slowly moved. The signal from an astronomical object is extracted from the movie data by a low-rank and sparse matrix decomposition. The performance of the "slow-scanning" observation was tested in an experimental observation with Subaru/COMICS. The quality of a resultant image in the "slow-scanning" observation was as good as in a conventional chopping observation with COMICS, at least for a bright point-source object. The observational efficiency in the "slow-scanning" observation was better than that in the chopping observation. The results suggest that the "slow-scanning" observation can be a competitive method for the Subaru telescope and be of potential interest to other ground-based facilities to avoid chopping.

Plasma Epstein-Barr virus and Hepatitis B virus in non-Hodgkin lymphomas: Two lymphotropic, potentially oncogenic, latently occurring DNA viruses.

Science.gov (United States)

Sinha, Mahua; Rao, Clementina Rama; Premalata, C S; Shafiulla, Mohammed; Lakshmaiah, K C; Jacob, Linu Abraham; Babu, Govind K; Viveka, B K; Appaji, L; Subramanyam, Jayshree R

2016-01-01

There is a need to study potential infective etiologies in lymphomas. Lymphocyte-transforming viruses can directly infect lymphocytes, disrupt normal cell functions, and promote cell division. Epstein-Barr virus (EBV) is known to be associated with several lymphomas, especially Hodgkin lymphomas (HLs). And recently, the lymphocyte-transforming role of hepatitis B virus (HBV) has been emphasized. The aim of this study was to elucidate the association of two potentially oncogenic, widely prevalent latent DNA viruses, EBV and HBV, in non-HL (NHL). In this prospective study, we estimated plasma EBV and HBV DNA in NHL patients. Peripheral blood was obtained from newly diagnosed, treatment na ïve, histologically confirmed NHL patients. Plasma EBV DNA was quantified by real-time polymerase chain reaction (PCR) targeting Epstein-Barr Nucleic acid 1 while the plasma HBV DNA was detected using nested PCR targeting HBX gene. In a small subset of patients, follow-up plasma samples post-anticancer chemotherapy were available and retested for viral DNA. Of the 110 NHL patients, ~79% were B-cell NHL and ~21% were T-cell NHL. Plasma EBV-DNA was detected in 10% NHLs with a higher EBV association in Burkitt lymphoma (33.3%) than other subtypes. Pretherapy HBV DNA was detected in 21% NHLs; most of them being diffuse large B-cell lymphoma (DLBCL). Moreover, 42% of DLBCL patients had HBV DNA in plasma. Since all patients were HBV surface antigen seronegative at diagnosis, baseline plasma HBV-DNAemia before chemotherapy was indicative of occult hepatitis B infection. Our findings indicate a significant association of HBV with newly diagnosed DLBCL.

Ectopic Expression of Homeobox Gene NKX2-1 in Diffuse Large B-Cell Lymphoma Is Mediated by Aberrant Chromatin Modifications

Science.gov (United States)

Nagel, Stefan; Ehrentraut, Stefan; Tomasch, Jürgen; Quentmeier, Hilmar; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A. F.

2013-01-01

Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies. PMID:23637834

Performance of a 14.9-kW laminated-frame dc series motor with chopper controller

Science.gov (United States)

Schwab, J. R.

1979-01-01

Traction motor using two types of excitation: ripple free dc from a motor generator set for baseline data and chopped dc as supplied by a battery and chopper controller was tested. For the same average values of input voltage and current, the power output was independent of the type of excitation. At the same speeds, motor efficiency at low power output (corresponding to low duty cycle of the controller) was 5 to 10 percentage points less on chopped dc than on ripple-free dc. This illustrates that for chopped waveforms, it is incorrect to calculate input power as the product of average voltage and average current. Locked-rotor torque, no load losses, and magnetic saturation data were so determined.

Impact of virtual reality simulation on learning barriers of phacoemulsification perceived by residents.

Science.gov (United States)

Ng, Danny Siu-Chun; Sun, Zihan; Young, Alvin Lerrmann; Ko, Simon Tak-Chuen; Lok, Jerry Ka-Hing; Lai, Timothy Yuk-Yau; Sikder, Shameema; Tham, Clement C

2018-01-01

To identify residents' perceived barriers to learning phacoemulsification surgical procedures and to evaluate whether virtual reality simulation training changed these perceptions. The ophthalmology residents undertook a simulation phacoemulsification course and proficiency assessment on the Eyesi system using the previously validated training modules of intracapsular navigation, anti-tremor, capsulorrhexis, and cracking/chopping. A cross-sectional, multicenter survey on the perceived difficulties in performing phacoemulsification tasks on patients, based on the validated International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR), using a 5-point Likert scale (1 = least and 5 = most difficulty), was conducted among residents with or without prior simulation training. Mann-Whitney U tests were carried out to compare the mean scores, and multivariate regression analyses were performed to evaluate the association of lower scores with the following potential predictors: 1) higher level trainee, 2) can complete phacoemulsification most of the time (>90%) without supervisor's intervention, and 3) prior simulation training. The study was conducted in ophthalmology residency training programs in five regional hospitals in Hong Kong. Of the 22 residents, 19 responded (86.3%), of which 13 (68.4%) had completed simulation training. Nucleus cracking/chopping was ranked highest in difficulty by all respondents followed by capsulorrhexis completion and nucleus rotation/manipulation. Respondents with prior simulation training had significantly lower difficulty scores on these three tasks (nucleus cracking/chopping 3.85 vs 4.75, P = 0.03; capsulorrhexis completion 3.31 vs 4.40, P = 0.02; and nucleus rotation/manipulation 3.00 vs 4.75, P = 0.01). In multivariate analyses, simulation training was significantly associated with lower difficulty scores on these three tasks. Residents who had completed Eyesi simulation training had higher

Hunger in pregnant sows: Effects of a fibrous diet and free access to straw

DEFF Research Database (Denmark)

Jensen, Margit Bak; Pedersen, Lene Juul; Theil, Peter Kappel

2015-01-01

of metabolites and hormones in pregnant sows. Ten groups of three pregnant sows were housed in pens with concrete floor where a limited amount of chopped straw (approx. 330 g/sow) was provided daily. In 5 of the 10 groups sows had free access to uncut straw in racks in addition to the chopped straw (Ad libitum...

The SAT Protein of Porcine Parvovirus Accelerates Viral Spreading through Induction of Irreversible Endoplasmic Reticulum Stress.

Science.gov (United States)

Mészáros, István; Tóth, Renáta; Olasz, Ferenc; Tijssen, Peter; Zádori, Zoltán

2017-08-15

The SAT protein (SATp) of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER), and SAT deletion induces the slow-spreading phenotype. The in vitro comparison of the wild-type Kresse strain and its SAT knockout (SAT - ) mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT - virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences in the quantity and the localization of CHOP were detected, suggesting a role of SATp in the induction of irreversible ER stress in infected cells. The involvement of the induction of irreversible ER stress in porcine testis (PT) cell necrosis and viral egress was confirmed by treatment of infected cells by ER stress-inducing chemicals (MG132, dithiothreitol, and thapsigargin), which accelerated the egress and spreading of both the wild-type and the SAT - viruses. UV stress induction had no beneficial effect on PPV infection, underscoring the specificity of ER stress pathways in the process. However, induction of CHOP and its nuclear translocation cannot alone be responsible for the biological effect of SAT, since nuclear CHOP could not complement the lack of SAT in a coexpression experiment. IMPORTANCE SATp is encoded by an alternative open reading frame of the PPV genome. Earlier we showed that SATp of the attenuated PPV NADL-2 strain accumulates in the ER and accelerates virus release and spreading. Our present work revealed that slow spreading is a general feature of SAT - PPVs and is the consequence of prolonged cell integrity. PPV infection induced ER stress in infected cells regardless of the presence of SATp, as demonstrated by the morphological changes of the ER and expression of the stress response proteins Xbp1 and CHOP. However, the presence of SATp made the ER stress more severe and

Metallothionein-I plus II and receptor megalin are altered in relation to oxidative stress in cerebral lymphomas

DEFF Research Database (Denmark)

Pedersen, M.O.; Hansen, P.B.; Nielsen, Signe Ledou

2010-01-01

Primary central nervous system lymphoma (PCNSL) in immunocompetent patients is highly malignant and has a poor prognosis. The PCNSL molecular features are reminiscent to some degree of diffuse large B-cell lymphoma (DLBCL), yet PCNSL shows unique molecular profiles and a distinct clinical behavior...

Metallothionein-I plus II and receptor megalin are altered in relation to oxidative stress in cerebral lymphomas

DEFF Research Database (Denmark)

Pedersen, M.O.; Hansen, P.B.; Nielsen, Signe Ledou

2010-01-01

. This article characterizes the histopathology and expression profiles of metallothionein-I + II (MT-I + II) and their receptor megalin along with proliferation, oxidative stress, and apoptosis in PCNSL and in central nervous system (CNS) lymphomas due to relapse from DLBCL (collectively referred to as CNS...

Case report

African Journals Online (AJOL)

abp

2017-11-01

Nov 1, 2017 ... Non-Hodgkin's lymphomas (NHL) with intracranial origin are very rare and constitutes ... Diffuse large B cell lymphoma (DLBCL) is the most common subtype of NHL ... revealed grossly normal complete blood count (CBC) with slightly .... of chemotherapeutic drugs and autologous stem cell transplantation.

Bacteroides fragilis Enterotoxin Induces Formation of Autophagosomes in Endothelial Cells but Interferes with Fusion with Lysosomes for Complete Autophagic Flux through a Mitogen-Activated Protein Kinase-, AP-1-, and C/EBP Homologous Protein-Dependent Pathway.

Science.gov (United States)

Ko, Su Hyuk; Jeon, Jong Ik; Myung, Hyun Soo; Kim, Young-Jeon; Kim, Jung Mogg

2017-10-01

Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3 protein II (LC3-II) conversion from LC3-I and protein expression of p62, Atg5, and Atg12. In addition, BFT-exposed ECs showed increased indices of autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2 (LAMP2) colocalization and the percentage of red vesicles monitored by the expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP homologous protein (CHOP), and inhibition of CHOP significantly increased indices of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription factor, in which suppression of AP-1 activity significantly downregulated CHOP and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) significantly inhibited the AP-1 and CHOP signals, leading to an increase in autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest that BFT induced accumulation of autophagosomes in ECs, but activation of a signaling pathway involving JNK, AP-1, and CHOP may interfere with complete autophagy. Copyright © 2017 American Society for Microbiology.

Nuclear fuel cycle: international market, international constraints and international cooperation

International Nuclear Information System (INIS)

Imai, R.

1977-01-01

Some of the constraints on the nuclear fuel cycle are ones arising from economic and financial reasons, those caused by uranium resources and their distribution, those arising from technical reasons, issues of public acceptance, and those quite independent of normal industrial considerations, but caused by elements of international politics. The nuclear fuel cycle and the international market, matters of nuclear non-proliferation, and international cooperation are discussed

Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Xia, Yi; Xu-Monette, Z Y; Tzankov, A

2017-01-01

PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBC...

EBV-positive diffuse large B-cell lymphoma of the elderly

NARCIS (Netherlands)

C.Y. Ok (Chi Young); T.G. Papathomas (Thomas); L.J. Medeiros (L. Jeffrey); K.H. Young (Ken)

2013-01-01

textabstractEpstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in

Clinical, immunophenotypic, and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma

NARCIS (Netherlands)

Haralambieva, E; Boerma, EJ; van Imhoff, GW; Rosati, S; Schuuring, E; Muller-Hermelink, HK; Kluin, PM; Ott, G

A prompt distinction of Burkitt lymphoma (BL) versus diffuse large B cell lymphomas (DLBCL) has important clinical implications; however, this distinction can be difficult. We analyzed 74 adult gray zone and 10 reference pediatric BL using immunohistochemistry (Ki-67, CD10, bcl2, bcl6) and

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

NARCIS (Netherlands)

Mihajlović, J.; Bax, P.; Van Breugel, E.; Blommestein, H.M.; Hoogendoorn, M.; Hospes, W.; Postma, M.J.

2015-01-01

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will

Flavour development in pork. Influence of flavour precursor concentrations in longissimus dorsi from pigs with different raw meat qualities

DEFF Research Database (Denmark)

Meinert, Lene; Tikk, Kaja; Tikk, Meelis

2009-01-01

Flavour development and overall eating quality of pan-fried pork chops of longissimus dorsi from eight different raw meat qualities aged for 4 and IS days were assessed by a trained sensory panel. The raw meat qualities were obtained through combinations of strategic feeding/fasting (control vs...... the differences in sensory perception of the pan-fried pork chops. Overall, the differences were small....

ROMI 4.0: Rough mill simulator 4.0 users manual

Science.gov (United States)

R. Edward Thomas; Timo Grueneberg; Urs. Buehlmann

2015-01-01

The Rough MIll simulator (ROMI Version 4.0) is a computer software package for personal computers (PCs) that simulates current industrial practices for rip-first, chop-first, and rip and chop-first lumber processing. This guide shows how to set up the software; design, implement, and execute simulations; and examine the results. ROMI 4.0 accepts cutting bills with as...

International Criminalization of International Terrorizm

Directory of Open Access Journals (Sweden)

Alexander Grigoryevich Volevodz

2014-01-01

Full Text Available Analysis and studying of the terrorism in all its facets is a complex entangled problem with less clear legal regulation that it might seem at first glance, especially after its transformation from local phenomenon into a world threat. Hitherto terrorism and actions connected to it have been criminalized by the majority of states. There are in modern criminal law whole systems of rules on criminal liability for terrorism which differs considerably from country to country. Terrorism has been criminalized in numerous international regional and universal antiterrorist legal instruments. The author notes that differences in definitions that are enshrined in them hinders international cooperation in criminal matters with respect to terrorist cases. Difficulties reside in the necessity to meet the dual criminality requirement and in the political offense exception. These difficulties can only be overcome through elaboration of a universally recognized definition of the notion of international terrorism and making it legally binding via its inclusion into a universal convention. The issue of definition of international terrorism is an important part of an efficient mutual assistance among states in fight against this crime. In this article the author accounts of actual ways of tackling by the international community of the issue of criminalization of international terrorism and of factors influencing them.

Conjunctival Lymphoma

DEFF Research Database (Denmark)

Kirkegaard, Marina M; Rasmussen, Peter K; Coupland, Sarah E

2016-01-01

IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS...... age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse...... large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were...

Transformation of a Cutaneous Follicle Center Lymphoma to a Diffuse Large B-Cell Lymphoma—An Unusual Presentation

Directory of Open Access Journals (Sweden)

J. Dias Coelho

2010-01-01

Full Text Available Primary cutaneous follicle center lymphoma (PCFCL is characterized by a proliferation of follicle center cells in the skin. A definitive diagnosis is frequently delayed because of difficulties in interpretation of the histopathologic findings. It has an excellent prognosis with a 5-year survival over 95% and its risk of transformation has not been established. We describe a case report of man with a gastric diffuse large B-cell lymphoma (DLBCL referred to our clinic because of nodules in the back that had gradually developed over a period of 10 years. A biopsy performed 3 years before was interpreted as reactive follicular hyperplasia. A new skin biopsy revealed a diffuse large B-cell lymphoma and immunoglobulin heavy chain gene rearrangements from the initial skin biopsy (PCBCL and the DLBCL gastric biopsy were studied by polymerase chain reaction and an identical clonal rearrangement was detected which was highly suggestive of a transformation lymphoma.

Mutagenicity of basic fractions derived from lamb and beef cooked by common household methods.

Science.gov (United States)

Barrington, P J; Baker, R S; Truswell, A S; Bonin, A M; Ryan, A J; Paulin, A P

1990-03-01

Mutagen production was examined in lamb and beef in relation to certain common household cooking methods. Mutagenicity was assessed, after extraction of the basic fraction of cooked meat samples, using Salmonella typhimurium strain TA1538 with added rat-liver S-9 homogenate. Little or no mutagenicity was found in barbecued lamb chops, in microwave-cooked lamb chops, sirloin steak, leg of lamb, or rolled beef loaf, in roasted leg of lamb or rolled beef loaf, in stewed blade steak or in boiled chuck steak. However, the basic fraction from well-done, edible fried or grilled meat contained mutagenic activity equivalent to approximately 30,000 TA1538 revertants/100 g cooked meat. It was found tht the mutagenic activity of grilled lamb chops, sirloin and rump steaks was directly related to the average surface temperatures attained during cooking. Use of butter as a frying medium was particularly associated with higher mutagenicity in meat samples. Fried meats (rump and fillet steaks) generally yielded higher mutagenic activity than did grilled meats (rump steak, lamb chops) at comparable temperatures of the cooking medium. Using similar cooking procedures, lamb did not differ markedly from beef in mutagenic activity.

Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

DEFF Research Database (Denmark)

Reddy, Anupama; Zhang, Jenny; Davis, Nicholas S

2017-01-01

Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed...

Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway.

Science.gov (United States)

Guo, Haiqing; Ren, Feng; Zhang, Li; Zhang, Xiangying; Yang, Rongrong; Xie, Bangxiang; Li, Zhuo; Hu, Zhongjie; Duan, Zhongping; Zhang, Jing

2016-03-01

Kaempferol is a flavonoid compound that has gained importance due to its antitumor properties; however, the underlying mechanisms remain to be fully understood. The present study aimed to investigate the molecular mechanisms of the antitumor function of kaempferol in HepG2 hepatocellular carcinoma cells. Kaempferol was determined to reduce cell viability, increase lactate dehydrogenase activity and induce apoptosis in a concentration‑ and time‑dependent manner in HepG2 cells. Additionally, kaempferol‑induced apoptosis possibly acts via the endoplasmic reticulum (ER) stress pathway, due to the significant increase in the protein expression levels of glucose‑regulated protein 78, glucose‑regulated protein 94, protein kinase R‑like ER kinase, inositol‑requiring enzyme 1α, partial activating transcription factor 6 cleavage, caspase‑4, C/EBP homologous protein (CHOP) and cleaved caspase‑3. The pro‑apoptotic activity of kaempferol was determined to be due to induction of the ER stress‑CHOP pathway, as: i) ER stress was blocked by 4‑phenyl butyric acid (4‑PBA) pretreatment and knockdown of CHOP with small interfering RNA, which resulted in alleviation of kaempferol‑induced HepG2 cell apoptosis; and ii) transfection with plasmid overexpressing CHOP reversed the protective effect of 4‑PBA in kaempferol‑induced HepG2 cells and increased the apoptotic rate. Thus, kaempferol promoted HepG2 cell apoptosis via induction of the ER stress‑CHOP signaling pathway. These observations indicate that kaempferol may be used as a potential chemopreventive treatment strategy for patients with hepatocellular carcinoma.

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

Science.gov (United States)

Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

2016-09-13

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

Increasing physically effective fiber content of dairy cow diets through forage proportion versus forage chop length: chewing and ruminal pH.

Science.gov (United States)

Yang, W Z; Beauchemin, K A

2009-04-01

A study was conducted to evaluate whether the risk of acidosis in dairy cows can be lowered by increasing the physically effective fiber (peNDF) concentration of the diet, either through increased theoretical chop length of alfalfa silage or higher proportion of forage in the diet. The experiment was designed as a replicated 4 x 4 Latin square using 8 ruminally cannulated lactating dairy cows. Treatments were arranged in a 2 x 2 factorial design; 2 forage particle lengths (FPL) of alfalfa silage (short and long) were combined with low (35:65) and high (60:40) forage:concentrate (F:C) ratios [dry matter (DM) basis]. Dietary peNDF concentration (DM basis) was determined from the sum of the proportion of dietary DM retained either on the 2 sieves (8 and 19 mm) or on the 3 sieves (1.18, 8, and 19 mm) of the Penn State Particle Separator multiplied by the neutral detergent fiber concentration of the diet. The dietary peNDF concentrations were altered by changing the F:C or the FPL, and ranged from 10.7 to 17.5% using 2 sieves, or from 23.1 to 28.2% using 3 sieves. Intake of peNDF was increased by increasing FPL but not by increasing F:C ratio because of the reduction of DM intake at the higher F:C ratio. Chewing activity, including number of chews and chewing time, increased with increasing F:C ratio or FPL. Mean ruminal pH was elevated by 0.4 and 0.2 units with increasing F:C ratio and FPL, respectively. Lowering the F:C ratio decreased the duration that ruminal pH was below 5.8 (1.2 vs. 8 h/d). Increased F:C ratio or FPL reduced ruminal volatile fatty acids concentration from 137 to 122 or from 133 to 126 mM, respectively, whereas acetate:propionate ratio was increased from 2.55 to 3.46 with increasing F:C ratio. Dietary peNDF concentration measured using 2 sieves was correlated to chewing time (r = 0.57) and mean ruminal pH (r = 0.75), whereas dietary peNDF concentration measured using 3 sieves was correlated to mean ruminal pH (r = 0.83) and negatively correlated to

Molecular characterization of phosphorylcholine expression on the lipooligosaccharide of Histophilus somni

Science.gov (United States)

Elswaifi, Shaadi F.; St. Michael, Frank; Sreenivas, Avula; Cox, Andrew; Carman, George M.; Inzana, Thomas J.

2013-01-01

Histophilus somni (Haemophilus somnus) is an important pathogen of cattle that is responsible for respiratory disease, septicemia, and systemic diseases such as thrombotic meningoencephalitis, myocarditis, and abortion. A variety of virulence factors have been identified in H. somni, including compositional and antigenic variation of the lipooligosaccharide (LOS). Phosphorylcholine (ChoP) has been identified as one of the components of H. somni LOS that undergoes antigenic variation. In this study, five genes (lic1ABCDHs and glpQ) with homology to genes responsible for ChoP expression in Haemophilus influenzae LOS were identified in the H. somni genome. An H. somni open reading frame (ORF) with homology to H. influenzae lic1A (lic1AHi) contained a variable number of tandem repeats (VNTR). However, whereas the tetranucleotide repeat 5′-CAAT-3′ is present in lic1AHi, the VNTR in H. somni lic1A (lic1AHs) consisted of 5′-AACC-3′. Due to the propensity of VNTR to vary during replication and cause the ORF to shift in and out of frame with the upstream start codon, the VNTR were deleted from lic1AHs to maintain the gene constitutively on. This construct was cloned into Escherichia coli, and functional enzyme assays confirmed that lic1AHs encoded a choline kinase, and that the VNTR were not required for expression of a functional gene product. Variation in the number of VNTR in lic1AHs correlated with antigenic variation of ChoP expression in H. somni strain 124P. However, antigenic variation of ChoP expression in strain 738 predominately occurred through variable extension/truncation of the LOS outer core. These results indicated that the lic1Hs genes controlled expression of ChoP on the LOS, but that in H. somni there are two potential mechanisms that account for antigenic variation of ChoP. PMID:19682567

The Development of Customary International Law by International Organizations

DEFF Research Database (Denmark)

Odermatt, Jed

2017-01-01

In his Fourth Report on the Identification of Customary International Law (2016), Special Rapporteur Michael Wood confirmed that ‘[i]n certain cases, the practice of international organizations also contributes to the expression, or creation, of rules of customary international law.......’ That the practice of international organizations can be relevant when identifying customary international law is relatively uncontroversial. The practice of states within international organizations such as the UN General Assembly, for example, may contribute to the development of custom. Yet, there is little...... discussion about whether and how the practice of international organizations as such may contribute to the development of customary international law. This contribution discusses the organization that is the most capable of contributing to the development of customary international law in its own right...

The international law commission and international environmental law

International Nuclear Information System (INIS)

Ramcharan, B.G.

1975-01-01

If the oceans are destroyed through pollution there will be nothing left to manage. Protection against pollution is thus a fundamental aspect of ocean management. What legal principles are available for the protection of the oceans. This paper brings together the relevant practice of the foremost international body responsible for the codification and development of international law: the International Law Commission. It describes the work of the Commission concerning: 1) pollution of the high seas; 2) pollution of international watercourses; and 3) international responsibility for environmental hazards. It concludes by expressing the hope that the Commission will further study, codify and develop international environmental law

Internationalism and Globalization as Contexts for International Education

Science.gov (United States)

Cambridge, James; Thompson, Jeff

2004-01-01

A problem with the construction of an inclusive definition of international education is that the word 'international' has a variety of connotations. It is proposed that the term 'international education' is ambiguous because it appears to refer to contrasting usages in educational studies. International education is frequently discussed in the…

From Public International to International Public Law: Translating World Public Opinion into International Public Authority

NARCIS (Netherlands)

von Bogdandy, A.; Goldmann, M.; Venzke, I.

This article argues that increasing demands in world public opinion for legitimate and effective international institutions require a paradigm shift in public international law. There is a part of public international law that should be better understood as international public law because it

Nanosecond electron beam generation and instrumentation at SLAC

International Nuclear Information System (INIS)

Koontz, R.F.; Miller, R.H.

1975-01-01

The present SLAC injector system, including the latest beam chopping equipment, is discussed, and an updated diagram is given. The present equipment can produce almost any mix of chopped and single bunch beams for experimenters with a high degree of multiple beam compatibility. Topics covered include the grid pulsers, the pulse isolation transformers, the resonant choppers, the nonresonant chopper, the synchronization system, and the fast beam monitors. (PMA)

RF trapping and acceleration in CSNS/RCS

International Nuclear Information System (INIS)

Wei Tao; Fu Shinian; Qin Qing; Tang Jingyu

2008-01-01

In this paper, two injection scenarios with different chopping rate are discussed. The waveforms of the RF voltage are studied and optimized, respectively. Some suggestions are made, concerning chopping and momentum painting of the injected beam. Furthermore, the momentum spread and transverse tune shift are calculated so that the beam aperture and the beam loss can be estimated. Finally, the beam loss with magnet field error is analyzed. (authors)

Determining optimum age of Holstein dairy calves when adding chopped alfalfa hay to meal starter diets based on measures of growth and performance.

Science.gov (United States)

Hosseini, S M; Ghorbani, G R; Rezamand, P; Khorvash, M

2016-04-01

The present study was conducted to determine the optimum age of Holstein dairy calves for an effective inclusion of alfalfa hay (AH) in starter feed on performance, apparent digestibility and feeding behavior. A total of 40 Holstein dairy calves (20 female and 20 male) were used in a completely randomized design in which calves were randomly assigned to one of four different dietary treatments including control (CON) calves fed starter feed without any forage and three treatments consisting of the same starter feed plus 15% chopped AH fed when calves were at the 2nd (AH2), 4th (AH4) or 6th (AH6) week of age. Calves were individually housed and bedded with sand that was replaced every other day. Feed and water were available ad libitum throughout the experiment. Calves were fed milk at 10% of birth BW twice daily until d 57. The study concluded when calves were 73 days old. Starter intake was recorded daily and BW was measured weekly. Data were analyzed as a complete randomized design by MIXED procedures of SAS. Results demonstrate that calves receiving AH treatments numerically consumed more starter feed (0.62 v. 0.78, 0.71 and 0.65 kg/day for CON, AH2, AH4 and AH6, respectively) and had greater average daily gain (ADG) compared with CON (0.48 v. 0.57, 0.49 and 0.49 kg/day for CON, AH2, AH4 and AH6), although the significant difference was observed only between AH2 and CON. Among AH treatments, calves in AH2 had better performance than AH6 in several cases including starter intake, ADG. No detectable differences were observed, however, in apparent dry matter, organic matter or CP digestibility among treatments. Ruminal pH and NH3 concentrations, measured on weeks 4, 6, 8 and 10, were lower for calves fed CON compared with other treatments, with ammonia concentrations decreasing over time. Calves in the AH treatments spent more time eating and ruminating compared with CON. Calves fed CON, however, spent more time on laying down compared with other treatments

Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Xu-Monette, Zijun Y; Li, Ling; Byrd, John C

2016-01-01

CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its...

Challenges imposed by International Environmental Law to Classical International Law

Directory of Open Access Journals (Sweden)

Fabian Augusto Cárdenas Castañeda

2010-05-01

Full Text Available The emergence of international environmental law has produced important challenges to the very foundations of public international law. Traditional concepts such as state sovereignty, subjects of international law, and the early perspectives of national security are being transformed. The needs of the contemporary international society differ from the ones of the Wesphalian conception, situations which clearly explains the raise of alternative views for the understanding of the current dynamics of international law, where concepts like res communis, common concerns and simply “commons” take a privileged place in the study of international law. The foregoing has been strengthened by the international development of the so called erga ommnes obligations, label which is being used by international environmental law as the perfect explanation of its own existence. This academic article presents and studies the abovementioned concepts trying to compare what international law used to be before the emergence of international environmental law and what it is and what it should be in order to attend the developments and challenges imposed by the contemporary international society, particularly by international environmental law, a new fi eld of the corpus juris of public international law.

International Ecohealth Forum 2008 | IDRC - International ...

International Development Research Centre (IDRC) Digital Library (Canada)

... the International Forum on Ecosystem Approaches to Human Health (Montreal, ... the International Association of Ecology and Health (IAEH), and a Brazilian ... Nutrition, health policy, and ethics in the age of public-private partnerships.

Effects of ubiquilin 1 on the unfolded protein response.

Science.gov (United States)

Lu, Alice; Hiltunen, Mikko; Romano, Donna M; Soininen, Hilkka; Hyman, Bradley T; Bertram, Lars; Tanzi, Rudolph E

2009-05-01

Previous studies have implicated the unfolded protein response (UPR) in the pathogenesis of Alzheimer's disease (AD). We previously reported that DNA variants in the ubiquilin 1 (UBQLN1) gene increase the risk for AD. Since UBQLN1 has been shown to play a role in the UPR, we assessed the effects of overexpression and downregulation of UBQLN1 splice variants during tunicamycin-induced ER stress. In addition to previously described transcript variants, TV1 and TV2, we identified two novel transcript variants of UBQLN1 in brain: TV3 (lacking exons 2-4) and TV4 (lacking exon 4). Overexpression of TV1-3, but not TV4 significantly decreased the mRNA induction of UPR-inducible genes, C/EBP homologous protein (CHOP), BiP/GRP78, and protein disulfide isomerase (PDI) during the UPR. Stable overexpression of TV1-3, but not TV4, also significantly decreased the induction of CHOP protein and increased cell viability during the UPR. In contrast, downregulation of UBQLN1 did not affect CHOP mRNA induction, but instead increased PDI mRNA levels. These findings suggest that overexpression UBQLN1 transcript variants TV1-3, but not TV4, exert a protective effect during the UPR by attenuating CHOP induction and potentially increasing cell viability.

Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

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Warissara Rongthong

2017-05-01

Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

True retention of nutrients on cooking of Australian retail lamb cuts of differing carcass classification characteristics.

Science.gov (United States)

Kosulwat, Somkiat; Greenfield, Heather; Buckle, Kenneth A

2003-12-01

The true retention of nutrients (proximate principles and cholesterol) on cooking of three retail cuts from lambs classified by weight, sex and fatness score was investigated. Fat retentions of the total cut and of the lean portion of lamb legs and mid-loin chops were not affected by carcass fatness, weight and sex or their interactions, however, the fat retention of the total cut and of the lean portion of forequarter chops was affected by fat score, with forequarter chops from fat score 1 retaining more fat than did chops of carcasses of higher fat score. Overall, fat was lost by all cuts (total cut) on cooking, with only 70-80% of fat being retained, but fat content of lean only increased on cooking (retention >100%), indicating the passage of fat into the lean portion from the external fat cover during the cooking process. Carcass factors and their interactions had little or no effect on the protein, water and ash retentions of the total cut or the lean portions of the three cuts. Cholesterol retention by the lean portion of three cooked lamb cuts was not affected by any carcass factors or their interactions. Cholesterol retentions were ∼99% for total cuts and tended to be ∼102% for the lean portions.

Endoplasmic Reticulum Stress-Mediated Hippocampal Neuron Apoptosis Involved in Diabetic Cognitive Impairment

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Xiaoming Zhang

2013-01-01

Full Text Available Poor management of DM causes cognitive impairment while the mechanism is still unconfirmed. The aim of the present study was to investigate the activation of C/EBP Homology Protein (CHOP, the prominent mediator of the endoplasmic reticulum (ER stress-induced apoptosis under hyperglycemia. We employed streptozotocin- (STZ- induced diabetic rats to explore the ability of learning and memory by the Morris water maze test. The ultrastructure of hippocampus in diabetic rats and cultured neurons in high glucose medium were observed by transmission electron microscopy and scanning electron microscopy. TUNEL staining was also performed to assess apoptotic cells while the expression of CHOP was assayed by immunohistochemistry and Western blot assay in these hippocampal neurons. Six weeks after diabetes induction, the escape latency increased and the average frequency in finding the platform decreased in diabetic rats (P<0.05. The morphology of neuron and synaptic structure was impaired; the number of TUNEL-positive cells and the expression of CHOP in hippocampus of diabetic rats and high glucose medium cultured neurons were markedly altered (P<0.05. The present results suggested that the CHOP-dependent endoplasmic reticulum (ER stress-mediated apoptosis may be involved in hyperglycemia-induced hippocampal synapses and neurons impairment and promote the diabetic cognitive impairment.

Development of the negative ion source at the National Laboratory for High Energy Physics

Energy Technology Data Exchange (ETDEWEB)

Takagi, Akira [National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan)

1997-02-01

On formation of direct high frequency chopped negative hydrogen ion beam from surface forming type negative hydrogen ion source, incident acceleration due to proton synchrotron was tried for a forming experiment and its application. By overlapping a high frequency pulse onto a bias DC voltage of convertor electrode, control of formation of negative hydrogen ion with high speed RF pulse of 2 MHz could be realized. And, incidence into 12 GeV proton accelerator to catch RF particles with waiting bucket system due to booster synchrotron, was effective for control of longitudinal emittance in the booster synchrotron. As a result, controls of the beam width and shape emitted from the booster synchrotron were possible. On application of high speed chopped negative hydrogen ion beam to accelerator, improvement of beam capture efficiency to the accelerated RF bucket, control of longitudinal emittance of accelerated beam, beam measurement at incidence into the accelerator and so forth were conducted. In this paper, results of the high speed chopped beam formation experiment using surface plasma forming type negative ion source and application of high speed beam chopping method synchronized with high frequency pulse at the National Laboratory of High Energy Physics are described. (G.K.)

A method for aggregating external operating conditions in multi-generation system optimization models

DEFF Research Database (Denmark)

Lythcke-Jørgensen, Christoffer Ernst; Münster, Marie; Ensinas, Adriano Viana

2016-01-01

This paper presents a novel, simple method for reducing external operating condition datasets to be used in multi-generation system optimization models. The method, called the Characteristic Operating Pattern (CHOP) method, is a visually-based aggregation method that clusters reference data based...... on parameter values rather than time of occurrence, thereby preserving important information on short-term relations between the relevant operating parameters. This is opposed to commonly used methods where data are averaged over chronological periods (months or years), and extreme conditions are hidden...... in the averaged values. The CHOP method is tested in a case study where the operation of a fictive Danish combined heat and power plant is optimized over a historical 5-year period. The optimization model is solved using the full external operating condition dataset, a reduced dataset obtained using the CHOP...

Effect of the callipyge phenotype and cooking method on tenderness of several major lamb muscles.

Science.gov (United States)

Shackelford, S D; Wheeler, T L; Koohmaraie, M

1997-08-01

We conducted three experiments to determine the effects of the callipyge phenotype on the tenderness of several major lamb muscles and to determine the effect of method of cookery on the tenderness of callipyge lamb at 7 d postmortem. In Exp. 1, chops from normal (n = 23) and callipyge (n = 16) carcasses were open-hearth-broiled. Warner-Bratzler shear force values of longissimus, gluteus medius, semimembranosus, biceps femoris, semitendinosus, adductor, and quadriceps femoris were 123, 44, 28, 26, 19, 16, and 13% greater, respectively, for callipyge (P lamb carcasses (n = 60). Callipyge chops were less tender than normal chops (P cooking method, callipyge samples were less juicy than normal samples (P < .05). These data demonstrate that the callipyge phenotype will likely reduce consumer satisfaction due to reduced tenderness and juiciness; however, reduced tenderness in callipyge leg muscles could be prevented by ovenroasting.

International opportunities and value creation in international entrepreneurship.

NARCIS (Netherlands)

Mainela, Tuija; Puhakka, Vesa; Wakkee, Ingrid; Marinova, Svetla; Larimo, Jorma; Nummela, Niina

2016-01-01

International entrepreneurship (IE) as a field of research has emerged at the intersection of internationalization and entrepreneurship theories. At this intersection it has come to emphasize the activities centered on international opportunities. International opportunities, then, are about value

REFLECTIONS ON PRODUCTION INTERNALIZATION AND ITS INTERNATIONAL TRADE IMPLICATIONS

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CLIPA RALUCA IRINA

2014-06-01

Full Text Available Vertically-integrated multinational companies place the different stages of production and marketing chain in different countries, looking for advantages such as low production costs, lower taxes, abundant resources and so on, while benefiting from the advantages of economies of scale, control of supplies or outlets. In fact, this vertical integration of multinational companies has led to the expansion of intra-firm trade and "internalized" operations, thus creating their own markets for the vertically-integrated production. Internationally active firms operate in a way that replaces the different functions of an open market with internal transactions, i.e. intra-firm transactions, whenever internal transaction costs are lower than the open-market ones. The direct consequence over international trade is the increase of intra-firm share of trade flows to one third of world trade, those companies making a suppression of international market segments that act in favour of an internal market. The creation of a multinational market and the enhancement of intra-firm trade have profound quantitative and qualitative implications on the composition, geographic orientation and dynamics of international trade. This paper deals with the issue of production internalization, with an overview of the main contributions made to the theory of internalization, while tackling its relative dimension. However, we intend to highlight the implications of this phenomenon on international trade. The work methodology falls within the range of qualitative approaches: logical argumentation, critical theoretical analysis.

Quantifying Nanoparticle Internalization Using a High Throughput Internalization Assay.

Science.gov (United States)

Mann, Sarah K; Czuba, Ewa; Selby, Laura I; Such, Georgina K; Johnston, Angus P R

2016-10-01

The internalization of nanoparticles into cells is critical for effective nanoparticle mediated drug delivery. To investigate the kinetics and mechanism of internalization of nanoparticles into cells we have developed a DNA molecular sensor, termed the Specific Hybridization Internalization Probe - SHIP. Self-assembling polymeric 'pHlexi' nanoparticles were functionalized with a Fluorescent Internalization Probe (FIP) and the interactions with two different cell lines (3T3 and CEM cells) were studied. The kinetics of internalization were quantified and chemical inhibitors that inhibited energy dependent endocytosis (sodium azide), dynamin dependent endocytosis (Dyngo-4a) and macropinocytosis (5-(N-ethyl-N-isopropyl) amiloride (EIPA)) were used to study the mechanism of internalization. Nanoparticle internalization kinetics were significantly faster in 3T3 cells than CEM cells. We have shown that ~90% of the nanoparticles associated with 3T3 cells were internalized, compared to only 20% of the nanoparticles associated with CEM cells. Nanoparticle uptake was via a dynamin-dependent pathway, and the nanoparticles were trafficked to lysosomal compartments once internalized. SHIP is able to distinguish between nanoparticles that are associated on the outer cell membrane from nanoparticles that are internalized. This study demonstrates the assay can be used to probe the kinetics of nanoparticle internalization and the mechanisms by which the nanoparticles are taken up by cells. This information is fundamental for engineering more effective nanoparticle delivery systems. The SHIP assay is a simple and a high-throughput technique that could have wide application in therapeutic delivery research.

Quasi-elastic measurements using neutron spin flippers

International Nuclear Information System (INIS)

Bleuel, M.; Fitzsimmons, M.R.; Lal, J.

2008-01-01

A method for low-resolution quasi-elastic measurements using commonly available components on a polarized neutron beam reflectometer is demonstrated. By amplitude modulation of the current in a neutron spin flipper placed between the neutron beam polarizer and polarization analyzer, the intensity of the neutron beam illuminating a sample is similarly modulated (or chopped). We show that the intensity contrast between subsequent chopped pulses is dramatically reduced by a sample that changes neutron velocity