tbuckley/cabot-search huggingface dataset:
Phase II Study of Irinotecan and Temozolomide in Children With Relapsed or Refractory Neuroblastoma: A Children's Oncology Group Study
Authors: Rochelle Bagatell, Wendy B. London, Lars M. Wagner, Stephan D. Voss, Clinton F. Stewart, John M. Maris, Cynthia Kretschmar, Susan L. Cohn
Journal: Journal of Clinical Oncology (2010)

This phase II study was conducted to determine the response rate associated with use of irinotecan and temozolomide for children with relapsed/refractory neuroblastoma.Patients with relapsed/refractory neuroblastoma measurable by cross-sectional imaging (stratum 1) or assessable by bone marrow aspirate/biopsy or metaiodobenzylguanidine (MIBG) scan (stratum 2) received irinotecan (10 mg/m(2)/dose 5 days a week for 2 weeks) and temozolomide (100 mg/m(2)/dose for 5 days) every 3 weeks. Response was assessed after three and six courses using International Neuroblastoma Response Criteria. Of the first 25 evaluable patients on a given stratum, five or more patients with complete or partial responses were required to conclude that further study would be merited.Fifty-five eligible patients were enrolled. The objective response rate was 15%. Fourteen patients (50%) on stratum 1 and 15 patients (56%) on stratum 2 had stable disease. Objective responses were observed in three of the first 25 evaluable patients on stratum 1 and five of the first 25 evaluable patients on stratum 2. Less than 6% of patients experienced ≥ grade 3 diarrhea. Although neutropenia was observed, less than 10% of patients developed evidence of infection while neutropenic.The combination of irinotecan and temozolomide was well tolerated. The objective response rate of 19% in stratum 2 suggests that this combination may be effective for patients with neuroblastoma detectable by MIBG or marrow analysis. Although fewer objective responses were observed in patients with disease measurable by computed tomography/magnetic resonance imaging, patients in both strata seem to have derived clinical benefit from this therapy.
Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow.
Authors: M Chackal-Roy, C Niemeyer, M Moore, B R Zetter
Journal: Journal of Clinical Investigation (1989)

Malignant prostatic carcinoma, a major cause of cancer mortality in males, most often metastasizes to secondary sites in bone. Frequently, the growth rate of the secondary tumor in bone marrow is considerably greater than that of the slowly growing primary prostatic tumor. We now report that two lines of human prostatic carcinoma cells proliferate in response to conditioned media from unstimulated human, rat, or bovine bone marrow. Nonprostatic tumor cell lines showed little or no growth response to the same medium. The proliferative activity found in bone marrow was not duplicated by any of a variety of purified growth factors including epidermal growth factor (EGF), acidic or basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF) alpha or beta, interleukins 1, 2, 3, 4 or 6, granulocyte (G), macrophage (M) or granulocyte-macrophage (GM) colony stimulating factor (CSF). Whereas a mixture of G-CSF, M-CSF, and IL 3 produced a mitogenic response in the prostatic carcinoma cells, these three factors were not present in our bone marrow samples in sufficient quantities to promote the observed proliferative response. To further identify the cellular source of the proliferative activity present in bone marrow-conditioned medium, we tested conditioned media made from human bone marrow stromal cells. The stromal cell conditioned medium stimulated increased growth of the prostatic carcinoma cells to levels equivalent to those observed with the bone marrow conditioned medium. These results suggest that novel mitogenic factors that are produced by bone marrow stromal cells and remain in the bone marrow cavity may account, in part, for the preferential growth of prostatic metastases in bone.
Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial
Authors: P Mugyenyi, A S Walker, J Hakim, P Munderi, D M Gibb, C Kityo, A Reid, H Grosskurth, J H Darbyshire, F Ssali, D Bray, E Katabira, A G Babiker, C F Gilks, H Grosskurth, P Munderi, G Kabuye, D Nsibambi, R Kasirye, E Zalwango, M Nakazibwe, B Kikaire, G Nassuna, R Massa, K Fadhiru, M Namyalo, A Zalwango, L Generous, P Khauka, N Rutikarayo, W Nakahima, A Mugisha, J Todd, J Levin, S Muyingo, A Ruberantwari, P Kaleebu, D Yirrell, N Ndembi, F Lyagoba, P Hughes, M Aber, A Medina Lara, S Foster, J Amurwon, B Nyanzi Wakholi, J Whitworth, K Wangati, B Amuron, D Kajungu, J Nakiyingi, W Omony, K Fadhiru, D Nsibambi, P Khauka, P Mugyenyi, C Kityo, F Ssali, D Tumukunde, T Otim, J Kabanda, H Musana, J Akao, H Kyomugisha, A Byamukama, J Sabiiti, J Komugyena, P Wavamunno, S Mukiibi, A Drasiku, R Byaruhanga, O Labeja, P Katundu, S Tugume, P Awio, A Namazzi, G T Bakeinyaga, H Katabira, D Abaine, J Tukamushaba, W Anywar, W Ojiambo, E Angweng, S Murungi, W Haguma, S Atwiine, J Kigozi, L Namale, A Mukose, G Mulindwa, D Atwiine, A Muhwezi, E Nimwesiga, G Barungi, J Takubwa, S Murungi, D Mwebesa, G Kagina, M Mulindwa, F Ahimbisibwe, P Mwesigwa, S Akuma, C Zawedde, D Nyiraguhirwa, C Tumusiime, L Bagaya, W Namara, J Kigozi, J Karungi, R Kankunda, R Enzama, A Latif, J Hakim, V Robertson, A Reid, E Chidziva, R Bulaya-Tembo, G Musoro, F Taziwa, C Chimbetete, L Chakonza, A Mawora, C Muvirimi, G Tinago, P Svovanapasis, M Simango, O Chirema, J Machingura, S Mutsai, M Phiri, T Bafana, M Chirara, L Muchabaiwa, M Muzambi, J Mutowo, T Chivhunga, E Chigwedere, M Pascoe, C Warambwa, E Zengeza, F Mapinge, S Makota, A Jamu, N Ngorima, H Chirairo, S Chitsungo, J Chimanzi, C Maweni, R Warara, M Matongo, S Mudzingwa, M Jangano, K Moyo, L Vere, N Mdege, I Machingura, E Katabira, A Ronald, A Kambungu, F Lutwama, I Mambule, A Nanfuka, J Walusimbi, E Nabankema, R Nalumenya, T Namuli, R Kulume, I Namata, L Nyachwo, A Florence, A Kusiima, E Lubwama, R Nairuba, F Oketta, E Buluma, R Waita, H Ojiambo, F Sadik, J Wanyama, P Nabongo, J Oyugi, F Sematala, A Muganzi, C Twijukye, H Byakwaga, R Ochai, D Muhweezi, A Coutinho, B Etukoit, C Gilks, K Boocock, C Puddephatt, C Grundy, J Bohannon, D Winogron, D M Gibb, A Burke, D Bray, A Babiker, A S Walker, H Wilkes, M Rauchenberger, S Sheehan, C Spencer-Drake, K Taylor, M Spyer, A Ferrier, B Naidoo, D Dunn, R Goodall, J H Darbyshire, L Peto, R Nanfuka, C Mufuka-Kapuya, P Kaleebu, D Pillay, V Robertson, D Yirrell, S Tugume, M Chirara, P Katundu, N Ndembi, F Lyagoba, D Dunn, R Goodall, A McCormick, A Medina Lara, S Foster, J Amurwon, B Nyanzi Wakholi, J Kigozi, L Muchabaiwa, M Muzambi, I Weller, A Babiker, S Bahendeka, M Bassett, A Chogo Wapakhabulo, J H Darbyshire, B Gazzard, C Gilks, H Grosskurth, J Hakim, A Latif, C Mapuchere, O Mugurungi, P Mugyenyi, C Burke, S Jones, C Newland, G Pearce, S Rahim, J Rooney, M Smith, W Snowden, J-M Steens, A Breckenridge, A McLaren, C Hill, J Matenga, A Pozniak, D Serwadda, T Peto, A Palfreeman, M Borok, E Katabira
Journal: The Lancet (2009)
GSK690693 Delays Tumor Onset and Progression in Genetically Defined Mouse Models Expressing Activated Akt
Authors: Deborah A. Altomare, Lili Zhang, Jing Deng, Antonio Di Cristofano, Andres J. Klein-Szanto, Rakesh Kumar, Joseph R. Testa
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Akt plays a central role in regulating tumor cell survival and cell cycle progression and is regarded as a promising therapeutic target. We used genetically defined mouse models that develop spontaneous tumors exhibiting activated Akt to determine if Akt inhibition by GSK690693 is effective in the treatment of cancer. The broad long-term objective of this project was to use preclinical cancer models with precisely defined genetic lesions to elucidate the efficacy of targeting Akt with GSK690693. Experimental Design: We tested the in vivo effects of GSK690693 in Lck-MyrAkt2 transgenic mice that develop lymphomas, heterozygous Pten+/− knockout mice that exhibit endometrial tumors, and TgMISIIR-TAg-DR26 mice that develop ovarian carcinomas, all of which exhibit hyperactivation of Akt. In addition to standard disease onset and histology, tumors arising in treated animals were examined by immunohistochemistry to verify downregulated Akt signaling relative to placebo-treated mice. When possible, drug response was evaluated in tumor cell cultures by standard proliferation and apoptosis assays and by immunoblotting with various phosphospecific antibodies. Results: GSK690693 exhibited efficacy irrespective of the mechanism of Akt activation involved. Interestingly, GSK690693 was most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt. Both tumors and primary cell cultures displayed downregulation of the Akt pathway, increased apoptosis, and primarily decreased cell proliferation. Conclusion: These results suggest that GSK690693 or other Akt inhibitors might have therapeutic efficacy in human cancers with hyperactivated Akt and/or a dependence on Akt signaling for tumor progression. Clin Cancer Res; 16(2); 486–96
The Trace Deletion Hypothesis in relation to partial matching theory
Authors: David J. Murray
Journal: Behavioral and Brain Sciences (2000)

Grodzinsky has argued that the traces deleted in Broca's aphasia are “phonetically silent but syntactically active” (sect. 2.). If we assume such traces to be visuospatial in nature, and adopt the term “overwriting” from the author's partial matching theory (1998), we can account for the errors made by Broca's aphasics in comprehending Grodzinsky's Examples (5a), (5b), and (6).
Extrathoracic lymph node aspiration in bronchial carcinoma.
Authors: M S Phillips, V Barker
Journal: Thorax (1985)

Cytological examination of material obtained by percutaneous thin needle lymph node aspiration is an estab- lished diagnostic technique.'The method for obtaining such material has been well described,2 but there are no recent reports of its use in patients with bronchial car- cinoma who have enlarged peripheral lymph nodes at pre- sentation.We report our results of the past seven years to show the value of the technique in the diagnosis and man- agement of bronchial carcinoma.
The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review
Authors: A G Fraser
Journal: Gut (2002)

Background: There are limited data on factors predicting response to azathioprine and uncertainty regarding the optimal duration of treatment. Patients and methods: The notes of patients attending the Oxford IBD clinic from 1968 to 1999 were reviewed. Remission was defined as no need for oral steroids for at least three months and relapse was defined as active disease requiring steroids. Results: A total of 622 of 2205 patients were treated with azathioprine (272 Crohn9s disease, 346 ulcerative colitis, and four indeterminate colitis). Mean duration of the initial course of treatment was 634 days. The overall remission rates were 45% for Crohn9s disease and 58% for ulcerative colitis. For the 424 patients who received more than six months of treatment, remission rates were 64% and 87%, respectively. Factors favouring remission were ulcerative colitis (p=0.0001), lower white blood cell (WBC) or neutrophil count (p=0.0001), higher mean cell volume (p=0.0001), and older age (p=0.05). For Crohn9s disease, colonic disease favoured remission (p=0.03). Factors that were not significant were age, sex, lymphocyte count, and dose (mg/kg). The proportion of patients remaining in remission at one, three, and five years was 0.95, 0.69, and 0.55, respectively. The chance of remaining in remission was higher if WBC was less than 5×10<sup>9</sup> (p=0.03) and in male patients (p=0.01; Crohn9s disease only). There was no difference in relapse rates between Crohn9s disease and ulcerative colitis. After stopping azathioprine, the proportion of patients remaining in remission at one, three, and five years was 0.63, 0.44, and 0.35 (222 patients). Duration of azathioprine treatment did not affect the relapse rate after stopping treatment (p=0.68). Conclusions: Azathioprine is effective treatment for ulcerative colitis and Crohn9s disease. The efficacy of azathioprine is reasonably well sustained over five years.
Cases Resembling Encephalitis Lethargica occurring during the Influenza Epidemic
Authors: J. B. Alexander
Journal: BMJ (1919)

The sterno-hyoid and sterno-thyroid muscles, whichl are coitimronly greatly thinned and stretched, can readily be retracted inwards or outwards; there need, however, be no hesitation in dividing them if additional room is re(quired; division of the sterno-mastoid is never necessary.'r[he fascia over the gland is next cleared, the veins in it being at once picked up and ligatured.The gland in its
Determinants of Pain Severity Changes in Ambulatory Patients With Cancer: An Analysis From Eastern Cooperative Oncology Group Trial E2Z02
Authors: Fengmin Zhao, Victor T. Chang, Charles Cleeland, James F. Cleary, Edith P. Mitchell, Lynne I. Wagner, Michael J. Fisch
Journal: Journal of Clinical Oncology (2013)

Purpose To understand changes in pain severity over time and to explore the factors associated with pain changes in ambulatory patients with solid tumors. Patients and Methods We enrolled 3,106 patients with invasive cancer of the breast, prostate, colon/rectum, or lung from multiple sites. At baseline and 4 to 5 weeks later, patients rated their pain level on a 0 to 10 numerical rating scale. A 2-point change in pain score was defined as a clinically significant change in pain. Multivariable logistic models were fitted to examine the effects of pain management and demographic and clinical factors on change in pain severity. Results We analyzed 2,761 patients for changes in pain severity. At initial assessment, 53.0% had no pain, 23.5% had mild pain, 10.3% had moderate pain, and 13.2% had severe pain. Overall, one third of patients with initial pain had pain reduction within 1 month of follow-up, and one fifth had an increase, and the improvement and worsening of pain varied by baseline pain score. Of the patients without pain at initial assessment, 28.4% had pain (8.9% moderate to severe) at the follow-up assessment. Logistic regression analysis showed that inadequate pain management was significantly associated with pain deterioration, as were lower baseline pain level, younger age, and poor health status. Conclusion One third of patients have pain improvement and one fifth experience pain deterioration within 1 month after initial assessment. Inadequate pain management, baseline pain severity, and certain patient demographic and disease characteristics are associated with pain deterioration.
Increased energy expenditure in hemodialysis patients.
Authors: T A Ikizler, R L Wingard, M Sun, J Harvell, R A Parker, R M Hakim
Journal: Journal of the American Society of Nephrology (1996)

Malnutrition is prevalent in chronic hemodialysis patients and is related to multiple factors; the hemodialysis procedure itself has been suggested as a catabolic factor. To examine the possible role of hemodialysis on energy metabolism, resting energy expenditure and respiratory quotient in ten chronic hemodialysis patients was measured in this study, using a whole-room indirect calorimeter. Measurements were done continuously: for 2 h before hemodialysis, during 4 h of hemodialysis, for 2 h after hemodialysis, and separately on a nondialysis day after 12 h of fasting. Age-, sex-, and body mass index-matched healthy volunteers were used as control subjects. Chronic hemodialysis patients have a significantly higher resting energy expenditure on a nondialysis day (1.18 +/- 0.15 kcal/min; P < 0.01) as compared with control subjects (1.10 +/- 0.16 kcal/ min). Resting energy expenditure further increased significantly during the hemodialysis procedure (1.32 +/- 0.18 kcal/min, averaged over the 4 h of hemodialysis; P < 0.01 versus predialysis) and was also significantly higher compared with the postdialysis period and nondialysis day resting energy expenditure (P < 0.001 for both). This effect was most pronounced during the first (1.37 +/- 0.19 kcal/min) and second (1.33 +/- 0.18 kcal/min) hours of hemodialysis (P < 0.001 for both). Respiratory quotient was not significantly affected by hemodialysis. It was concluded that chronic hemodialysis patients have higher than normal resting energy expenditure levels, which is further increased during hemodialysis. This process may significantly potentiate the protein-calorie malnutrition seen in this patient population.
Chronic Tumor Necrosis Factor Alters T Cell Responses by Attenuating T Cell Receptor Signaling
Authors: Andrew P. Cope, Roland S. Liblau, Xiao-Dong Yang, Mauro Congia, Carlo Laudanna, Robert D. Schreiber, Lesley Probert, George Kollias, Hugh O. McDevitt
Journal: The Journal of Experimental Medicine (1997)

Repeated injections of adult mice with recombinant murine TNF prolong the survival of NZB/W F1 mice, and suppress type I insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. To determine whether repeated TNF injections suppress T cell function in adult mice, we studied the responses of influenza hemagglutinin-specific T cells derived from T cell receptor (HNT-TCR) transgenic mice. Treatment of adult mice with murine TNF for 3 wk suppressed a broad range of T cell responses, including proliferation and cytokine production. Furthermore, T cell responses of HNT-TCR transgenic mice also expressing the human TNF-globin transgene were markedly reduced compared to HNT-TCR single transgenic littermates, indicating that sustained p55 TNF-R signaling is sufficient to suppress T cell function in vivo. Using a model of chronic TNF exposure in vitro, we demonstrate that (a) chronic TNF effects are dose and time dependent, (b) TNF suppresses the responses of both Th1 and Th2 T helper subsets, (c) the suppressive effects of endogenous TNF produced in T cell cultures could be reversed with neutralizing monoclonal antibodies to TNF, and (d) prolonged TNF exposure attenuates T cell receptor signaling. The finding that anti-TNF treatment in vivo enhances T cell proliferative responses and cytokine production provides evidence for a novel regulatory effect of TNF on T cells in healthy laboratory mice. These effects are more pronounced in chronic inflammatory disease. In addition, our data provide a mechanism through which prolonged TNF exposure suppresses disease in animal models of autoimmunity.
Myocardial calcium-independent phospholipase A2 activity during global ischemia in isolated rabbit hearts
Authors: O. Vesterqvist, C. A. Sargent, G. J. Grover, M. L. Ogletree
Journal: Cardiovascular Research (1996)

To study calcium-independent phospholipase A2 activity during global ischemia in isolated rabbit hearts by measuring the hydrolysis of the endogenous choline phospholipids.Langendorff perfused rabbit hearts were exposed to global ischemia for 15 or 60 min, or control perfusion for the same length of time. The hearts were then rapidly frozen in liquid nitrogen and lyophilized. Calcium-independent phospholipase A2 activity in the lyophilized tissue was studied by measuring accumulation of lysophospholipids resulting from hydrolysis of both the choline diacylphospholipid and the choline plasmalogen pool.The calcium-independent phospholipase A2 activity showed the same pH, temperature and calcium sensitivity in control and ischemic (15 min of ischemia) lyophilized myocardial tissue. Incubation of control and ischemic tissue showed no difference in the rate of accumulation of lysophospholipids when the ischemic tissue was obtained from hearts exposed to 15 min of ischemia (107 +/- 4 vs 111 +/- 7 nmol/g dry wt x min, ischemia versus control, mean +/- s.e.m., n = 8), but a significant decrease was noticed in tissue from hearts that had been exposed to 60 min of ischemia (31 +/- 9 vs 86 +/- 18 nmol/g dry wt x min, P < 0.05, n = 4). The decreased phospholipase A2 activity in tissue exposed to 60 min of ischemia was not due to enhanced metabolism of the lysophospholipids (84 +/- 15 vs 79 +/- 8 nmol/g dry wt x min, n = 4). The calcium-independent phospholipase A2 activity was considerably lower in fresh myocardial tissue compared with lyophilized tissue, but comparison of control and ischemic fresh tissue gave results comparable to those found using lyophilized tissue. The myocardial calcium-independent phospholipase A2 activity showed no plasmalogen selectivity in either control or ischemic myocardium.In isolated perfused rabbit hearts we found no evidence for activation of calcium-independent phospholipase A2 activity during global ischemia. With prolonged time of ischemia there was a significant decrease in calcium-independent phospholipase A2 activity.
Copeptin Levels Associate with Cardiovascular Events in Patients with ESRD and Type 2 Diabetes Mellitus
Authors: Wiebke Fenske, Christoph Wanner, Bruno Allolio, Christiane Drechsler, Katja Blouin, Jürgen Lilienthal, Vera Krane
Journal: Journal of the American Society of Nephrology (2011)

In ESRD, the neurohormone arginine vasopressin (AVP) may act primarily through V1a and V1b receptors, which promote vasoconstriction, myocardial hypertrophy, and release of adrenocorticotropic hormone. The preanalytical instability of AVP limits the investigation of whether this hormone associates with cardiovascular events, but the stable glycopeptide copeptin may serve as a surrogate because it is co-secreted with AVP from the posterior pituitary. Here, we studied whether copeptin predicts cardiovascular risk and mortality in ESRD. We measured copeptin at baseline in 1241 hemodialysis patients with type 2 diabetes participating in the German Diabetes and Dialysis Study. The median copeptin level was 81 pmol/L (interquartile range, 81 to 122 pmol/L). In Cox regression analyses, compared with patients with copeptin levels in the lowest quartile (≤51 pmol/L), patients with copeptin levels in the highest quartile (>122 pmol/L) had a 3.5-fold increased risk for stroke (HR, 3.48; 95% CI: 1.71 to 7.09), a 73% higher risk for sudden death (HR, 1.73; 95% CI: 1.01 to 2.95), a 42% higher risk for combined cardiovascular events (HR, 1.42; 95% CI: 1.06 to 1.90), and a 48% higher risk for all-cause mortality (HR, 1.48; 95% CI: 1.15 to 1.90). In contrast, we did not detect significant associations between copeptin levels and risks for myocardial infarction or death caused by congestive heart failure. In conclusion, copeptin levels strongly associate with stroke, sudden death, combined cardiovascular events, and mortality in hemodialysis patients with type 2 diabetes. Whether vasopressin receptor antagonists will improve these outcomes requires further studies.
Clinical significance of cytogenetics and interphase fluorescence in situ hybridization analysis in newly diagnosed multiple myeloma in Taiwan
Authors: S.-Y. Huang, M. Yao, J.-L. Tang, W. Tsay, F.-Y. Lee, M.-C. Liu, C.-H. Wang, Y.-C. Chen, M.-C. Shen, H.-F. Tien
Journal: Annals of Oncology (2005)