tbuckley/cabot-search huggingface dataset:
Secondary Myeloid Leukemia and Myelodysplastic Syndromes in Patients Treated for Hodgkin’s Disease: A Report From the German Hodgkin’s Lymphoma Study Group
Authors: Andreas Josting, Sabine Wiedenmann, Jeremy Franklin, Michael May, Markus Sieber, Juergen Wolf, Andreas Engert, Volker Diehl
Journal: Journal of Clinical Oncology (2003)

To assess the incidence and outcome of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients with Hodgkin's disease (HD).Between 1981 and 1998, the GHSG conducted three trial generations for early, intermediate, and advanced HD involving a total of 5,411 patients (called HD1 through HD9).A total of 46 patients with secondary AML/MDS were identified. The median age at diagnosis of leukemia was 47 years (range, 22 to 79 years). Primary therapy was as follows: radiotherapy alone (n = 4); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; n = 1); cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/ABVD or similar (n = 30); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) baseline (n = 2); and BEACOPP escalated (n = 9). Twelve patients developed AML/MDS after salvage therapy, including four patients who developed AML/MDS after high-dose chemotherapy with autologous stem-cell transplantation. Thirty-six of the secondary malignancies were AML, and 10 malignancies were MDS. After a median observation time of 55 months, incidence of secondary AML/MDS was 1%. Treatment for secondary AML/MDS was as follows: cytarabine (Ara-C)-containing regimens (6-thioguanin, cytarabine, daunorubicin [TAD]/high-dose cytarabine, mitoxantrone [HAM], HAM, Ida-Ara-C (idarubicin + Ara-C), Ida-Flag (idarubicin, fludarabin, Ara-C, G-CSF), and idarubicin, cytarabine, etoposide [ICE]+HAM; n = 11), TAD-chemotherapy (n = 5), other regimens (n = 3), no treatment or supportive care (n = 24), palliative oral chemotherapy (n = 3), and allogeneic stem cell transplantation (n = 9). After 24 months of observation, no difference in freedom from treatment failure and overall survival (2% and 8%, respectively) was observed in patients who developed AML or MDS.The prognosis of patients with secondary AML/MDS after primary HD is poor. Thus, emphasis should be made to improve initial treatment in an attempt to prevent this complication.
Baicalein Overcomes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Resistance via Two Different Cell-Specific Pathways in Cancer Cells but not in Normal Cells
Authors: Hiroya Taniguchi, Tatsushi Yoshida, Mano Horinaka, Takashi Yasuda, Ahmed E. Goda, Masako Konishi, Miki Wakada, Keisho Kataoka, Toshikazu Yoshikawa, Toshiyuki Sakai
Journal: Cancer Research (2008)

Abstract Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for new cancer therapeutics. A current problem is that some cancers still remain resistant to TRAIL. We show for the first time that a naturally occurring flavonoid, baicalein, overcomes TRAIL resistance in cancer cells. The combination of baicalein and TRAIL effectively induced apoptosis in TRAIL-resistant colon cancer SW480 cells. Baicalein up-regulated the expression of death receptor 5 (DR5) among TRAIL receptors at the mRNA and protein levels. Suppression of this up-regulation with small interfering RNA (siRNA) efficiently reduced the apoptosis induced by TRAIL and baicalein, suggesting that the sensitization was mediated through DR5 induction. Moreover, baicalein also overcame TRAIL resistance with DR5 up-regulation in prostate cancer PC3 cells. Of note, the combination of TRAIL and baicalein hardly induced apoptosis in normal human cells, such as blood cells and hepatocytes. Baicalein increased DR5 promoter activity, and this enhanced activity was diminished by mutation of a CCAAT/enhancer-binding protein homologous protein (CHOP)–binding site in SW480 cells. In SW480 cells, CHOP siRNA blocked both functions of baicalein. CHOP expression was induced by baicalein in SW480 cells; however, in PC3 cells, baicalein scarcely induced CHOP and mutation of the CHOP-binding site did not abrogate the DR5 promoter activation by baicalein. Interestingly, baicalein induced reactive oxygen species (ROS) and a ROS scavenger prevented DR5 expression and TRAIL sensitization in PC3 but not SW480 cells. These results indicate that, using two different pathways, baicalein exposes cancer surveillance of TRAIL and overcomes TRAIL resistance in cancer cells. [Cancer Res 2008;68(21):8918–27]
Host Lymphodepletion Enhances the Therapeutic Activity of an Oncolytic Vaccinia Virus Expressing 4-1BB Ligand
Authors: Hong Sung Kim, Seunghee Kim-Schulze, Dae Won Kim, Howard L. Kaufman
Journal: Cancer Research (2009)

Abstract Oncolytic viral vectors have shown promise as antitumor therapeutic agents but their effectiveness is complicated by induction of antiviral antibody responses and rapid host clearance of recombinant vectors. We developed a recombinant oncolytic vaccinia virus expressing the 4-1BBL T-cell costimulatory molecule (rV-4-1BBL) and showed modest tumor regression in the poorly immunogenic B16 murine melanoma model. To improve the therapeutic potential of this vector, we tested the antitumor activity of local intratumoral injection in the setting of host lymphodepletion, which has been shown to augment vaccination and adoptive T-cell therapy. In this model, rV-4-1BBL injection in the setting of lymphodepletion promoted MHC class I expression, reduced antiviral antibody titers, promoted viral persistence, and rescued effector-memory CD8+ T cells, significantly improving the therapeutic effectiveness of the oncolytic vector. These data suggest that vaccination with rV-4-1BBL in the setting of host nonmyeloablative lymphodepletion represents a logical strategy for improving oncolytic vaccination in melanoma, and perhaps other cancers as well. [Cancer Res 2009;69(21):8516–25]
THE AMYGDALA MODULATES THE CONSOLIDATION OF MEMORIES OF EMOTIONALLY AROUSING EXPERIENCES
Authors: James L. McGaugh
Journal: Annual Review of Neuroscience (2004)

Converging findings of animal and human studies provide compelling evidence that the amygdala is critically involved in enabling us to acquire and retain lasting memories of emotional experiences. This review focuses primarily on the findings of research investigating the role of the amygdala in modulating the consolidation of long-term memories. Considerable evidence from animal studies investigating the effects of posttraining systemic or intra-amygdala infusions of hormones and drugs, as well as selective lesions of specific amygdala nuclei, indicates that (a) the amygdala mediates the memory-modulating effects of adrenal stress hormones and several classes of neurotransmitters; (b) the effects are selectively mediated by the basolateral complex of the amygdala (BLA); (c) the influences involve interactions of several neuromodulatory systems within the BLA that converge in influencing noradrenergic and muscarinic cholinergic activation; (d) the BLA modulates memory consolidation via efferents to other brain regions, including the caudate nucleus, nucleus accumbens, and cortex; and (e) the BLA modulates the consolidation of memory of many different kinds of information. The findings of human brain imaging studies are consistent with those of animal studies in suggesting that activation of the amygdala influences the consolidation of long-term memory; the degree of activation of the amygdala by emotional arousal during encoding of emotionally arousing material (either pleasant or unpleasant) correlates highly with subsequent recall. The activation of neuromodulatory systems affecting the BLA and its projections to other brain regions involved in processing different kinds of information plays a key role in enabling emotionally significant experiences to be well remembered.
Synergistic inhibition of the calcification of glutaraldehyde pretreated bovine pericardium in a rat subdermal model by FeCl3 and ethanehydroxydiphosphonate: pre-incubation and polymeric controlled release studies
Authors: Danielle Hirsch, Joelle Drader, Yashwant V. Pathak, Rebecca Yee, Frederick J. Schoen, Robert J. Levy
Journal: Biomaterials (1993)
Molecular Alterations in Tumors and Response to Combination Chemotherapy with Gefitinib for Advanced Colorectal Cancer
Authors: Shuji Ogino, Jeffrey A. Meyerhardt, Mami Cantor, Mohan Brahmandam, Jeffrey W. Clark, Chungdak Namgyal, Takako Kawasaki, Kate Kinsella, Ann L. Michelini, Peter C. Enzinger, Matthew H. Kulke, David P. Ryan, Massimo Loda, Charles S. Fuchs
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recently, activating mutations of the epidermal growth factor receptor (EGFR) gene were discovered in non–small cell lung cancers sensitive to gefitinib (ZD1839, an EGFR tyrosine kinase inhibitor) but not in gefitinib-resistant cancers. Abnormalities of EGFR and related pathways may have an effect on responsiveness of advanced colorectal cancer to combination chemotherapy with gefitinib. Experimental Design: We examined patients with previously untreated metastatic colorectal cancer, who were enrolled into two phase I/II trials of combination chemotherapy (irinotecan, leucovorin, and 5-fluorouracil) and daily oral gefitinib. We obtained paraffin tissue blocks of primary tumors from 31 patients, sequenced the EGFR, KRAS, and BRAF genes, and did immunohistochemistry for EGFR, phosphorylated AKT1, p53, p21, and p27. Results: Twelve (39%) of the 31 patients experienced a partial objective response to the therapy. A novel EGFR mutation in exon 18 (c.2170G&amp;gt;A, p.Gly724Ser) was identified in only one patient who did not experience an objective tumor response. EGFR immunohistochemistry was not predictive of responsiveness. In contrast, loss of p21 was associated with a higher response rate to therapy (P = 0.05). Moreover, the response rate among patients whose tumors maintained p21 expression and possessed a mutation in p53 was only 9% (1 of 11, P = 0.005). Overexpression of phosphorylated AKT1 also seemed to predict a trend towards resistance to the therapy. Conclusions: p21 expression in colorectal cancer, especially in combination with p53 mutation, is a predictor of resistance to the combination chemotherapy with gefitinib. Activating EGFR mutations are rare in colorectal cancer and do not seem to confer sensitivity to gefitinib and chemotherapy.
Targeted Regional Injection of Biocomposite Microspheres Alters Post–Myocardial Infarction Remodeling and Matrix Proteolytic Pathways
Authors: Jennifer A. Dixon, Robert C. Gorman, Robert E. Stroud, Rupak Mukherjee, Evan C. Meyer, Nathaniel L. Baker, Masato Morita, Hirotsugu Hamamoto, Liam P. Ryan, Joseph H. Gorman, Francis G. Spinale
Journal: Circulation (2011)

Although localized delivery of biocomposite materials, such as calcium hydroxyapatite (CHAM), have been demonstrated to potentially attenuate adverse left ventricular (LV) remodeling after myocardial infarction (MI), the underlying biological mechanisms for this effect remain unclear. This study tested the hypothesis that targeted CHAM injections would alter proteolytic pathways (matrix metalloproteinases [MMPs] and tissue inhibitors of MMPs [TIMPs]) and would be associated with parameters of post-MI LV remodeling.MI was induced in adult sheep followed by 20 targeted injections of a total volume of 1.3 mL (n=6) or 2.6 mL of CHAM (n=5) or saline (n=13) and LV end-diastolic volume (EDV) and MMP/TIMP profiles in the MI region were measured at 8 weeks after MI. LV EDV decreased with 2.6 mL CHAM versus MI only (105.4 ± 7.5 versus 80.6 ± 4.2 respectively, P<0.05) but not with 1.3 mL CHAM (94.5 ± 5.0, P=0.32). However, MI thickness increased by 2-fold in both CHAM groups compared with MI only (P<0.05). MMP-13 increased 40-fold in the MI only group (P<0.05) but fell by >6-fold in both CHAM groups (P<0.05). MMP-7 increased approximately 1.5-fold in the MI only group (P<0.05) but decreased to referent control values in both CHAM groups in the MI region (P<0.05). Collagen content was reduced by approximately 30% in the CHAM groups compared with MI only (P<0.05).Differential effects on LV remodeling and MMP/TIMP profiles occurred with CHAM. Thus, targeted injection of a biocomposite material can favorably affect the post-MI remodeling process and therefore holds promise as a treatment strategy in and of itself, or as a matrix with potentially synergistic effects with localized pharmacological or cellular therapies.
Oral Treatment of Pernicious Anaemia: First Fifty Cases
Authors: F. S. Mooney, J. G. Heathcote
Journal: BMJ (1966)

* Consultant Pathologist, St. Helens Hospital, St. Helens, t Reader in Biochemistry, Royal College of Advanced Technology, Salford. was 86%, the P.C.V. 38%, and the serum vitamin-Bi_ level 40 /^g./ ml. A marrow puncture at this time showed megaloblastic changes in approximately 40% of the red-cell series. No abnormal signs were detected. The daily dose was therefore increased to 40 /?g. of peptide complex, and by the 2,260th day the symptoms had disappeared, the blood picture had improved slightly, and the marrow had reverted to normal. The serum vitamin-Bi2 level,
Predictors of Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From Combined Analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27
Authors: Eleftherios P. Mamounas, Stewart J. Anderson, James J. Dignam, Harry D. Bear, Thomas B. Julian, Charles E. Geyer, Alphonse Taghian, D. Lawrence Wickerham, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

The limited information on predictors of locoregional recurrence (LRR) after neoadjuvant chemotherapy (NC) has resulted in controversy about the optimal use of adjuvant radiotherapy and the timing of sentinel lymph node biopsy.We examined patterns and predictors of LRR as first event in combined analysis of two National Surgical Adjuvant Breast and Bowel Project (NSABP) neoadjuvant trials. NC was either doxorubicin/cyclophosphamide (AC) alone or AC followed by neoadjuvant/adjuvant docetaxel. Lumpectomy patients received breast radiotherapy alone; mastectomy patients received no radiotherapy. Pathologic complete response was defined as the absence of invasive tumor in the breast. Multivariate analyses were used to identify independent predictors of LRR. The primary end point was time to LRR as first event.In 3,088 patients, 335 LRR events had occurred after 10 years of follow-up. The 10-year cumulative incidence of LRR was 12.3% for mastectomy patients (8.9% local; 3.4% regional) and 10.3% for lumpectomy plus breast radiotherapy patients (8.1% local; 2.2% regional). Independent predictors of LRR in lumpectomy patients were age, clinical nodal status (before NC), and pathologic nodal status/breast tumor response; in mastectomy patients, they were clinical tumor size (before NC), clinical nodal status (before NC), and pathologic nodal status/breast tumor response. By using these independent predictors, groups at low, intermediate, and high risk of LRR could be identified. Nomograms that incorporate these independent predictors were created.In patients treated with NC, age, clinical tumor characteristics before NC, and pathologic nodal status/breast tumor response after NC can be used to predict risk for LRR and to optimize the use of adjuvant radiotherapy.
Dietary History and Nutritional State in Treated Coeliac Patients
Authors: B J Collins, P M Bell, JM Thomson BSc, D B Fee BSc, E A Wilson, A H G Love
Journal: Journal of the Royal Society of Medicine (1986)

The gluten content and nutritional adequacy of the diet of a group of adult coeliac patients supposedly following a gluten-free diet for at least one year were assessed. Results were considered in relation to the nutritional state of these patients, determined by anthropometric measurement, and the histological appearance of jejunal biopsies taken at the time of nutritional assessment. Imperfect gluten avoidance, mild malnutrition and mild histological abnormalities on jejunal biopsy were frequent findings. A careful dietary and nutritional assessment when considered in light of histological findings at jejunal biopsy helps to identify the causes of persisting symptoms or malnutrition in treated coeliac patients. A normal jejunal biopsy in a malnourished patient whose dietary compliance is good should prompt a search for an alternative diagnosis.
Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet
Authors: Jordi Salas-Salvadó, Monica Bulló, Nancy Babio, Miguel Ángel Martínez-González, Núria Ibarrola-Jurado, Josep Basora, Ramon Estruch, Maria Isabel Covas, Dolores Corella, Fernando Arós, Valentina Ruiz-Gutiérrez, Emilio Ros
Journal: Diabetes Care (2010)

OBJECTIVE To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes. RESEARCH DESIGN AND METHODS This was a three-arm randomized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria. RESULTS After a median follow-up of 4.0 years, diabetes incidence was 10.1% (95% CI 5.1–15.1), 11.0% (5.9–16.1), and 17.9% (11.4–24.4) in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. Multivariable adjusted hazard ratios of diabetes were 0.49 (0.25–0.97) and 0.48 (0.24–0.96) in the MedDiet supplemented with olive oil and nuts groups, respectively, compared with the control group. When the two MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52% (27–86). In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity. CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk.
Ventilation and perfusion scans in the preoperative assessment of bronchial carcinoma.
Authors: D J Lipscomb, N B Pride
Journal: Thorax (1977)

Ventilation (krypton -81m) and perfusion (technetium -99m) lung scans were obtained in a consecutive series of 21 patients shortly before thoracotomy for proven or suspected carcinoma of the bronchus. In most patients ventilation and perfusion were impaired equally and the scan abnormality corresponded to the bronchoscopic and radiological findings. Unexpectedly large defects in the perfusion scan were seen in three patients, all of whom had extensive neoplastic involvement of the mediastinum at thoracotomy, but 11 other patients had mediastinal involvement which was not suspected from the scan. Ventilation scanning was useful in the prediction of postoperative ventilatory capacity in two patients who underwent pneumonectomy. We conclude that ventilation and perfusion scans are not sensitive indicators of neoplastic involvement of the mediastinum but they are valuable for the prediction of postoperative lung function.
Pancreatic Cancer: Steps in the Right Direction
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2012)

One of the most feared among cancer diagnoses, pancreatic ductal adenocarcinoma (PDA) has historically represented the worst of all worlds. Features include the following: a cancer with an insidious biology; diagnosis at an advanced stage in a previously asymptomatic patient; technically difficult surgery due to location often rendering small-volume disease inoperable; and drug-resistant disease making chemotherapy of little use. Progress has been hard to come by and has focused on chemotherapy options, given the advanced presentation of PDA or invariable recurrence after surgery. The first successful chemotherapy—with success defined as gaining regulatory approval for a PDA indication—was gemcitabine, approved in 1996 on the basis of its ability to improve survival and to provide “clinical benefit.” The latter was a novel descriptor including weight gain and pain reduction, important considerations given that gemcitabine improved survival by only 1.5 months. While a recent randomized trial reported that FOLFIRINOX compared with gemcitabine improved median overall survival by 4 months, everyone agrees we still have a long way to go.This CCR Focus series addresses progress in our understanding of the biology of the disease, identifying potential therapeutic targets. With an average of 63 genetic abnormalities per tumor, it seems unlikely that individual mutations will be individually targeted as in ALK-rearranged or EGFR-mutant lung cancer. However, as highlighted in the overview by Guest Editors Manuel Hidalgo and Daniel D. Von Hoff, there are multiple avenues to be explored. In addition to the search for a mutation that could be successfully targeted, experts point to the critical role of tumor stroma in determining drug resistance; the intratumoral heterogeneity of PDA cell types, including a subset with stem cell properties; and the altered metabolic pathways. Together these represent multiple approaches for discovery and clinical trial development.While progress is being made on many fronts in better understanding PDA, as evidenced from the articles in this CCR Focus section, one area that needs enhanced development is better strategies for early detection. Considering how very refractory PDA has been and is likely to remain once diagnosed, and given the evidence that the disease develops gradually over as many as 15 years, one could envision a strategy aimed at earlier detection when the disease could be more amenable to surgical resection. Admittedly, such a strategy is not risk free and would suffer from the problems all early detection strategies must contend with. But given the progress in genomic characterization of early lesions discussed in this CCR Focus section and the very large problem presented by PDA when detected in the clinic, early detection might be another way forward.As with every edition of CCR Focus, it is our hope that the articles will inform and intrigue both the expert in the field and the interested but nonexpert observer.
Update in Sleep Medicine 2014
Authors: Najib T. Ayas, Robert L. Owens, Leila Kheirandish-Gozal
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Update in Sleep Medicine 2014 Najib T. Ayas, Robert L. Owens, and Leila Kheirandish-Gozal Divisions of Respiratory and Critical Care Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, California; and Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, University of Chicago, Chicago, Illinois