tbuckley/cabot-search huggingface dataset:
Evaluation of the effect of TRU-016, an anti-CD37 directed SMIP in combination with other therapeutic drugs in models of non-Hodgkin's lymphoma
Authors: P. R. Baum, C. Cerveny, B. Gordon, C. Nilsson, J. Wiens, S. Rafiq, R. Lapalombella, N. Muthusamy, J. C. Byrd, A. Wahl
Journal: Journal of Clinical Oncology (2009)

8571 Background: TRU-016, a single chain anti-CD37 Fc fusion molecule has been shown to display pro-apoptotic and Fc-dependent cellular cytotoxicity activities against primary CLL cells and NHL cell lines. The pro-apoptotic signal generated by TRU-016 binding to CD37 on CLL cells has been shown to be caspase-independent and distinct from the signal generated by many other therapeutics including rituximab. We have tested drug combinations using the mantle cell lymphoma line Rec-1 and diffuse large B-cell lymphoma line SU-DHL-6 in vitro and extended these results to in vivo settings using the follicular lymphoma cell line DOHH2 treated with the combination of TRU-016 and bendamustine. Methods: To determine TRU-016 interactions with the established therapeutics rituximab, doxorubicin, rapamycin, and bendamustine, drugs were tested alone or in combination with TRU-016 and the anti-proliferative effects on cell lines measured after 96 hours. Combination index analysis was performed for drug combinations over the 20–90% effect levels using the Calcusyn software package. To determine if in vitro synergy could be recapitulated in vivo, SCID mice were implanted with DOHH2 cells and therapeutic treatment was initiated when tumor volumes reached 200 mm 3 . Treatments consisted of TRU-016, bendamustine, or the combination of TRU-016 and bendamustine. Results: Combination index analyses determined that TRU-016 is synergistic with rituximab, bendamustine, or rapamycin and additive with doxorubicin in NHL models. In vivo results show that treatment with the combination of TRU-016 and bendamustine resulted in increased efficacy compared to the efficacy attained with the individual drugs. This demonstrates that the in vitro synergy results were extendable to a more complex in vivo disease model. Conclusions: TRU-016 in combination with rituximab, rapamycin, or bendamustine increases cell killing of NHL cells. Furthermore, the combination of TRU-016 and bendamustine displayed greater in vivo anti-tumor activity than either agent alone against a follicular lymphoma tumor model. [Table: see text]
Two schedules of teniposide with or without cisplatin in advanced non-small-cell lung cancer: a randomized study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.
Authors: T A Splinter, T Sahmoud, J Festen, N van Zandwijk, S Sörenson, M Clerico, J Burghouts, B Dautzenberg, G S Kho, A Kirkpatrick, G Giaccone
Journal: Journal of Clinical Oncology (1996)

PURPOSE We conducted a randomized trial to investigate the value of the addition of cisplatin to teniposide (VM26) and to investigate the schedule dependence of the topoisomerase II inhibitor VM26, in advanced non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Two hundred twenty-five NSCLC patients were randomized to receive VM26 120 mg/m2 on days 1, 3, and 5 or 360 mg/m2 on day 1 only, either as a single drug or in combination with cisplatin 80 mg/m2 on day 1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. RESULTS The response rate of the two cisplatin-containing arms was superior to that of the two arms that contained VM26 only (22% v 6%, P &lt; .001); progression-free survival and survival times were also longer in the cisplatin-containing arms (median, 4.3 v 2.2 months, P = .003; median 7.2 v 5.9 months, P = .008, respectively). Toxicity was significantly higher in the cisplatin-containing arms; the most frequent side effects were leukopenia, nausea and vomiting, and alopecia. The schedule of VM26 did not significantly influence the response rate, progression-free survival interval, or survival duration. However, the response rate of the 1-day administration was significantly lower than that of the 3-day administration when given as single drugs. CONCLUSION The addition of cisplatin to VM26 improves the response rate, progression-free survival interval, and survival duration over VM26 alone, although at the cost of a significant increase in toxicity. Cisplatin should be considered as the basis for combination chemotherapies in advanced NSCLC.
Abstract 34: Statins Directly Activate Erk5 and Reduce Endothelial Dysfunction and Acute Allograft Rejection
Authors: Yuichiro Takei, Nhat-Tu Le, Hakjoo Lee, Kyung-Sun Heo, Cheryl Hurley, Alan V Smrcka, Benjamin Miller, Kyung Ae Ko, Craing Morrell, Keigi Fujiwara, Masashi Akaike, Jun-ichi Abe
Journal: Circulation Research (2012)

Rationale: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are principal therapeutic agents for the treatment of hypercholesteremia. Statins, however, appear to also exert cholesterol-independent pleiotropic effects, such as improvement of endothelial (EC) function, stabilization of fibrous plaques, and decrease vascular inflammation. It is now well established that statins are beneficial in the prevention of cardiovascular disease and also widely used for suppressing cardiac allograft rejection. Previously, we have reported anti-inflammatory effect of ERK5 kinase in ECs. Methods and Results: In this study, we screened small molecules that activate ERK5 using high throughput screening, and identified statins as strong activators of the transcriptional activity of ERK5. In particular, we have found that pitavastatin increases ERK5 transcriptional activity, KLF2 promoter activity, and eNOS mRNA expression in ECs. These effects are abolished by the depletion of ERK5, but not its direct upstream kinase, MEK5. In addition, pitavastatin directly and dose-dependently activates ERK5 kinase activity in an in vitro kinase reaction assay, suggesting that ERK5 is a direct target of this statin. To examine the functional role of EC ERK5 activation by the statin in vivo, we utilized inducible endothelial ERK5 knock out (EC-ERK5-KO) mice and evaluated the effect of pitavastatin on EC function and acute allograft rejection. Depletion of ERK5 in ECs resulted in significant EC inflammation and dysfunction in vivo. Although pitavastatin reduced leukocyte rolling and vascular reactivity in mesebteruc microvessels of diabetic mice and prolonged allograft survival in a full allomismatch combination model, these protective effects were lost in EC-ERK5-KO mice. Conclusion: These data suggest the crucial role of ERK5 in pleiotropic effects of statins on EC dysfunction and allograft rejection in vivo.
Abstract A27: Risk of hematopoietic cancer associated mortality among workers in the poultry slaughtering and processing industries.
Authors: Saritha Bangara, Martha J. Felini, Subhash Aryal, David Sterling, Eric S. Johnson
Journal: Clinical Cancer Research (2015)

Abstract Objectives: Previous occupational cohort studies among poultry workers have revealed an excess risk of cancer-related mortality, including deaths due to hematopoietic malignancies. However, specific occupational and non-occupational exposures contributing to this excess risk have yet to be identified. Poultry workers are particularly at high risk since an average of 175,000 chickens are killed daily in poultry plants in the United States. This brings poultry workers into intimate contact with their blood, organs, and secretions, which may harbor transmissible oncogenic viruses. Moreover, they are exposed to potentially carcinogenic chemicals that are emitted during packaging and preparation. Hence, our study was conducted to provide preliminary evidence of which specific poultry related and non-poultry related occupational tasks increase the risk of mortality from hematopoietic cancer among poultry workers. Methods: A pilot case-cohort study was conducted using a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects. Exposures pertaining to poultry and non-poultry related tasks were self-reported through telephone interviews from controls and next-of-kin for cases. Hematopoietic cancer mortality risk was assessed using logistic regression odds ratios (OR) and proportional hazard ratios (HR). Results: One hundred fifty-two cases of hematopoietic cancer occurred in this cohort between January 1, 1990 and December 31, 2003. Since this is a feasibility study, exhaustive attempts were not made to identify study subjects and their next of kin. Thus, we report here on the first 52 (69%) of the 75 cases whose next-of-kin were traced. Similarly, of the first 214 controls that were traced, 152 (71%) completed interviews. Preliminary analysis is currently underway to identify the specific task exposures contributing to this excess risk. Conclusion: We expect the results of our study will confirm known risk factors related to hematopoietic cancers, and uncover new risk exposures that have yet to be appreciated in the general population due to their low level exposures. Using high-risk unique populations offers an opportunity to better understand molecular mechanisms that investigators may explore to aid in future drug development. Citation Format: Saritha Bangara, Martha J. Felini, Subhash Aryal, David Sterling, Eric S. Johnson. Risk of hematopoietic cancer associated mortality among workers in the poultry slaughtering and processing industries. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A27.
EGFR, MAPK, and Akt status by immunohistochemistry (IHC) are not correlated with clinical outcome in HER2-positive (HER2+) metastatic breast cancer (MBC) patients (pts) treated with trastuzumab (T) with or without chemotherapy (CT)
Authors: S. Gori, A. Sidoni, M. Colozza, I. Ferri, C. Cioccoloni, D. Fenocchio, A. Mosconi, P. Anastasi, V. De Angelis, L. Crinò
Journal: Journal of Clinical Oncology (2007)

1090 Background: T alone or in combination with CT has been shown to be an active therapy in HER2-positive MBC pts. However, not all pts will benefit and mechanisms of resistance to T are still poorly understood. The aim of this study was to evaluate the IHC expression of EGFR and two downstream effectors of the EGFR family signaling pathway, MAPK and Akt and their correlation with clinical outcome in HER2-positive MBC pts treated with T ± CT. Methods: 133 consecutive HER2+ MBC pts were treated between 04/99 and 03/06 but tumor tissue was available for this analysis only from 45 pts. HER2 evaluated by CB11 was scored according to Herceptest. Tumors were considered EGFR positive if =1% positive tumor cells and MAPK positive and Akt positive if the percentage of positive tumor cells was =10%. Results: At median follow up of 57 months (range 5–229) from the start of T, 45 pts were evaluable for TTP and OS and 42 for response to T. Median age of pts was 53 years (23–77). Twenty seven objective responses (CR+PR) to T ± CT (64.28%) were observed; median TTP was 24 months (3.3–179.8). In 11 of the 27 responsive pts (40.7%), progression was observed in CNS ± other sites. Median OS from the start of T was 74 months. EGFR positive tumors were 10 (22.2%), MAPK positive tumors were 16 (35.5%) and Akt positive tumors were 23 (51.1%). We analyzed the correlation of HER2, EGFR, MAPK and Akt status with response to T, TTP and OS. HER2 was significantly correlated with response to T (p = 0.013): in HER2 3+ tumors we observed 22 (9 CR and 13 PR) out of 27 objective responses but, no significant correlation was found between HER2 status and TTP and OS. EGFR, MAPK and Akt status of tumor were not significantly associated with response to T, TTP and OS in this series of HER2+ MBC pts. Conclusions: We did not found any significant correlation between EGFR, MAPK, Akt status evaluated by IHC and clinical outcome in HER2+ MBC pts treated with T ± CT. Only HER2 status evaluated by IHC significantly correlated with response to T ± CT. No significant financial relationships to disclose.
Phase I Study of Anti-Pd-1 Antibody Ono-4538 and Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer
Authors: Shintaro Kanda, Ayako Tanaka, Hirofumi Utsumi, Kuniko Sunami, Hidenori Mizugaki, Hidehito Horinouchi, Yutaka Fujiwara, Hiroshi Nokihara, Noboru Yamamoto, Tomohide Tamura
Journal: Annals of Oncology (2014)
Role of Plasminogen in Matrix Breakdown by Neoplastic Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Emil Bogenmann, Peter A. Jones
 6
Journal: JNCI Journal of the National Cancer Institute (1983)

Destruction of the extracellular matrix is often observed during tumor invasion, and proteolytic enzymes may participate actively in the degradation of matrix proteins. The present report elucidates the role of plasminogen in the degradation by tumor cells of an in vitro elaborated extracellular matrix. Matrices produced by rat smooth muscle cells in the presence of [3H]proline or [3H]fucose were used as substrates for human fibrosarcoma cells (HT-1080), mouse melanoma cells (B16F1), or human rhabdomyosarcoma cells (RD). All three cell lines degraded part of the glycoprotein compartment of the matrix. HT-1080 cells digested the matrices in a density-dependent manner, and while matrix glycoprotein degradation was plasminogen-dependent at the beginning of the experiment and at low cell densities, the zymogen was not essential for further glycoprotein digestion at high cell densities. Depletion of plasminogen from the growth medium resulted in a threefold reduction of matrix degradation by B16F1 cells showing a distinct plasminogen dependency at low cell numbers. RD cells digested only matrix glycoproteins, and this degradation was completely dependent on the presence of plasminogen at all cell densities. These results suggested that plasmin generated from plasminogen by a tumor cell-associated plasminogen activator may be most important for matrix hydrolysis at low cell densities, and while certain tumor cell lines showed a definite plasminogenindependent matrix degradation with increased cell numbers, other neoplastic cells hydrolyzed the matrix only in the presence of the zymogen at all cell densities.
Immune Response to Melanoma Extracts In Three Melanoma-Prone Families&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A A Vandenbark, M H Greene, D R Burger, R M Vetto, R R Reimer
Journal: JNCI Journal of the National Cancer Institute (1979)

Immune reactivity to melanoma extracts was measured by the leukocyte adherence inhibition (LAI) test in 40 members of 3 melanoma-prone families. The melanoma patients had a wide range of responsiveness to the extract, the highest responder being a 10-year survivor. As a group, family members (including spouses) without disease had significantly elevated LAI responses compared to those of unrelated controls (P less than 0.01). Within the families, members with close exposure to melanoma patients for 10 years or more had a significantly higher response to melanoma antigen than did members with 0-5 years of close exposure (P less than 0.05). Responses of spouses and members at high risk of developing melanoma (B-K mole syndrome) also correlated with length of exposure to patients, which suggests that the elevated LAI response was not genetically determined. The high frequency of positive responses to melanoma antigens in these families, particularly in spouses, suggests the presence of transmissible melanoma-associated material capable of immunizing persons in contact with melanoma patients.
John Robey Cobbett
Authors: Tom Cochrane
Journal: BMJ (2016)

When John Robey Cobbett died, he had long been incapacitated through the ravages of Pick’s syndrome. His intention after qualifying, I understand, was to seek a career in general practice, for he had married his beautiful wife while still a student, and, in those days, training in almost any specialty demanded unaccompanied residence for long periods, with an outcome, in terms of employment, that was very uncertain. He applied for and was appointed to the post of house surgeon and casualty officer at the Queen Victoria Hospital, East Grinstead. This post would have served this ambition well since it included acting as assistant to Sir John Peel, Edward (later Sir Edward) Muir, and Leonard Cotton, who attended and operated at the hospital, from King’s, on a weekly basis. Regular clinics in ear, nose, and throat medicine and operating sessions were in the hands of John Musgrove. Dr Robertson was …
Programs for adult survivors of childhood cancer.
Authors: K C Oeffinger, D A Eshelman, G E Tomlinson, G R Buchanan
Journal: Journal of Clinical Oncology (1998)

PURPOSE The potential for late effects of treatment necessitates long-term monitoring of adult survivors of childhood cancer. The purpose of this study was to determine how institutions follow up young adult survivors of pediatric malignancy. Specifically, we were interested in the types of health care providers who follow up these patients, how the follow-up is administered, and what barriers to follow-up have been encountered. METHODS A 16-item questionnaire was mailed to the 219 members of the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG). The survey consisted of four categories of questions that asked for information regarding the existence of a program to follow up young adults, the setting of the program, routine activities of the program, and commonly encountered barriers to care. RESULTS One hundred eighty-two members returned the survey (83% response rate). Fifty-three percent of the respondents have a long-term follow-up clinic at their institution. Whereas 44% have a mechanism for following up adult survivors, only 15% of the programs have established a formal database for adults. Nearly all the programs (93%) use a pediatric oncologist. Although an adult oncologist assists in 13% of the programs, primary care physicians are uncommonly (8%) involved. CONCLUSION Few programs focus on the long-term health care needs of adult survivors of childhood cancer. The majority of existing programs are in pediatric institutions, without significant input from adult-oriented, generalist health care providers.
Apoptotic and anti-apoptotic signals in acute leukemias
Authors: S. Paydas, K. Tanriverdi, U. Disel, S. Yavuz, B. Sahin, F. Baslamisli
Journal: Journal of Clinical Oncology (2004)

6712 Background: Programmed cell death is an important factor in malignant disorders for two reasons: 1-Suppression of apoptosis is critical in cancer both in initiation and progression phases. 2-Most of the anti-cancer agents cause tumor regression, at least in part, by induction of the apoptosis. Although various genes are involved in apoptosis, the key mediators of apoptosis are caspases. However some signals, such as survivin and aven, inhibit apoptotic signals. In this study some apoptotic and anti-apoptotic signals have been studied in cases with acute leukemia Methods: 53 peripheral blood samples taken from patients with acute leukemia were used as study group and 30 samples taken from healthy subjects were used as control. APO-3, APO-3L, Caspase-8, Fas L, Survivin and Aven were studied as apoptotic and anti-apoptotic signals. Real time RT-PCR method was used to detect these signals. Results were evaluated as mRNA copy/10.000 cells Mann Whitney U, Wilcoxon W, Spearman correlation tests were used for statistical analysis. Results: Table shows the apoptotic and anti-apoptotic signals in patients and controls. Parameter Min-Max Mean±SD Median Patients APO-3 0–6225 690±1500 30.9 APO-3L 0–8920 437±1502 33.2 Casp-8 0–43233 14356±13410 9831 FasL 0–6350 410.6±1310 26.8 Survivin 0–8290 542.5±1398 72.1 Aven 0–8530 692.8±1515 124 Controls APO-3 6–138 33.3±36.8 15.2 APO-3L 38.5–657 160.6±127 117.5 Casp-8 112–532 308±95 296.5 FasL 0–45.7 16.56±13.9 16.75 Survivin 0–69.2 17±19.9 11.35 Aven 0–61.3 35.6±22.7 40.9 All the parameters, except APO-3, were different in cases and controls. There was an important correlation between APO-3 and APO-3L, APO-3 and Casp-8, APO-3 and Aven, APO-3L and Aven, Casp-8 and Survivin, Casp-8 and Aven, and Survivin and Aven Conclusions: Apoptotic and anti-apoptotic signals are found in different amounts in malign and benign cells. It has been found an important association between these signals. Although we did not find an important association among the clinical parameters and apoptotic signals, if these parameters can be studied in a large number of the patients and also the ratio between apoptotic and anti-apoptotic signals in each cell type may be more useful. No significant financial relationships to disclose.
Neuraminidase “Unmasking” and Failure of Trypsin to “Unmask” β- D -Galactose- Like Sites on Erythrocyte, Lymphoma, and Normal and Virus-Transformed Fibroblast Cell Membranes 2
Authors: Garth L. Nicolson
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Neuraminidase “Unmasking” and Failure of Trypsin to “Unmask” β-D-Galactose- Like Sites on Erythrocyte, Lymphoma, and Normal and Virus-Transformed Fibroblast Cell Membranes Get access Garth L. Nicolson Garth L. Nicolson Cancer Council Laboratory, Armand Hammer Center for Cancer Biology, The Salk Institute for Biological Studies, San Diego, Calilornia 92112 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 6, June 1973, Pages 1443–1451, https://doi.org/10.1093/jnci/50.6.1443 Published: 01 June 1973 Article history Received: 07 December 1972 Accepted: 14 February 1973 Published: 01 June 1973
In vivo tracking of dendritic cell therapy in patients with multiple myeloma
Authors: D. M. Wall, L. R. Mileshkin, H. M. Prince, B. E. Loveland, M. Thompson, J. Coverdale, J. Wong, P. X. Xing, R. Taylor, R. J. Hicks
Journal: Journal of Clinical Oncology (2004)

2568 Background: Dendritic cell (DC) immunotherapy is being actively studied in patients (pts) with multiple myeloma (MM). However, the best route of injection of these cells is unknown. The aim of this study was to determine the in vivo distribution of DC when given to pts with MM via varying routes of injection by using nuclear medicine imaging techniques. Methods: Eligible pts had stable or slowly progressive MM not requiring systemic treatment, with elevated serum MUC-1 or positive marrow plasma cell MUC-1 staining. DC were produced by in vitro culture of autologous monocytes collected from pts via apheresis. Cells were stimulated in culture by GM-CSF plus IL-13 and then pulsed with Mannan-MUC1 fusion protein, using the VacCell processor. Prior to injection, DC were labelled with either F-18 FDG or Indium-111 (In). Pts underwent serial PET and SPECT scans, respectively, to track the destination of injected cells which were given by subcutaneous (s.c.), intradermal (i.d.), intranodal (i.n.) or intravenous (i.v.) route. Results: 10 infusions of non-matured DC have been performed in 3 pts (Table 1). After i.v injection of In-labeled DC, cells were initially imaged within the lungs on SPECT. 24 hours post injection, most DC had cleared the lungs and were seen within the liver, spleen and axial and proximal appendicular skeleton. DC were still visible until 72 hours. Following s.c., i.n. and i.d. injection, tracking of a fraction of the DC to the draining lymph node was imaged (after s.c = 1 pt out of 3, after i.n = 1 pt, after i.d = 1pt). PET was not useful for tracking, as the FDG-labeling efficiency of DC was low with little retention of tracer in vivo. Future cohorts of pts will compare results for DC after maturation in vitro prior to injection using In labeling only. Conclusion: We have demonstrated that although FDG-labeling of non-matured DC was not feasible, it is possible to label DC with In and track their distribution in vivo. No significant financial relationships to disclose.