tbuckley/cabot-search huggingface dataset:
NHS76/PEP2, a Fully Human Vasopermeability-Enhancing Agent to Increase The Uptake and Efficacy of Cancer Chemotherapy
Authors: Leslie A. Khawli, Peisheng Hu, Alan L. Epstein
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Previously, we have shown that the attachment of interleukin 2 (IL-2) to a tumor-targeting antibody can produce a 4-fold enhancement in the uptake of antibodies and drugs in tumors. More recently, we discovered that a 37-amino-acid linear sequence of IL-2 designated vasopermeability-enhancing peptide (PEP), contained the vasopermeability activity of IL-2, and could be used after linkage to tumor-targeting antibodies to produce the same enhancement of drugs and antibodies in tumors. We now describe the generation of a fully human antibody fusion protein, designated NHS76/PEP2, which can be used in patients to enhance the therapeutic potential of chemotherapy. Methods: NHS76/PEP2 was expressed in NS0 cells using the glutamine synthetase gene amplification system. To show its clinical potential as a pretreatment to chemotherapy, NHS76/PEP2 was given i.v. 2 hours before the injection of suboptimal doses of etoposide, doxorubicin, Taxol, Taxotere, 5-fluorouracil, or vinblastine in mice bearing established solid tumors. Results were recorded by measuring tumor volumes thrice per week. Results: Compared with drug treatment alone, NHS76/PEP2 pretreatment substantially improved the effectiveness of chemotherapeutic agents in solid tumor models. Tumor suppression was most pronounced in those groups of mice bearing tumors known to be sensitive to the specific drug under study. However, in certain instances, tumors previously known to be resistant to specific single chemotherapeutic agents were shown to respond by the addition of NHS76/PEP2 pretreatment. Conclusions: NHS76/PEP2 seems an excellent candidate to improve the value of standard chemotherapy drug treatment by virtue of its ability to increase the uptake of drugs in solid tumors selectively.
Plasma Levels of Cytokines and Soluble Cytokine Receptors During Treatment With Haloperidol
Authors: Thomas Pollmauml;cher, Dunja Hinze-Selch,, Thomas Fenzel, Thomas Kraus, Andreas Schuld, Janet Mullington
Journal: American Journal of Psychiatry (1997)

Clozapine increases the levels of cytokines and soluble cytokine receptors. The authors investigated whether haloperidol has similar effects.Rectal temperature, white blood cell counts, and plasma levels of cytokines and soluble cytokine receptors were assessed before and during 6 weeks of haloperidol treatment in 10 psychiatric patients.Haloperidol at mean doses of 7.0 mg/day (SD = 3.4), 6.9 mg/day (SD = 3.4), and 5.0 mg/day (SD = 3.1) at the end of the 1st, 2nd, and 6th weeks of treatment, respectively, did not affect rectal temperature, white blood cell counts, or plasma level of interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor p55 or p75, or soluble interleukin-2 receptor.Haloperidol is unlikely to confound the results of studies investigating disease-related alterations in the levels of a broad range of cytokines and soluble cytokine receptors in schizophrenia.
Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance
Authors: Michelle D. Williams, Dianna B. Roberts, Merrill S. Kies, Li Mao, Randal S. Weber, Adel K. El-Naggar
Journal: Clinical Cancer Research (2010)

Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2, although the underlying mechanisms remain undefined. Because of the potential utilization of these markers as treatment targets, we evaluated protein and gene status by several techniques to determine complementary value.A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquantitatively evaluated into a three-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status. Sequencing of exons 18, 19, and 21 of the EGFR gene for mutations was carried out.For EGFR, 46 (69.7%) of the 66 tumors showed some form of EGFR expression (17 at 3+, 17 at 2+, 12 at 1+) but none gene amplification. Five (9.4%) of 53 tumors showed mutations in exon 18 (n = 3) and exon 19 (n = 2). Polysomy of chromosome 7 (average >2.5 copies/cell) was detected in 15 (25.0%) of 60 tumors (6 at 3+, 5 at 2+, 2 at 1+, 2 at 0+ expression) and correlated with poor 3-year survival (P = 0.015). For HER-2, 17 (25.8%) of 66 tumors expressed HER-2 (10 at 3+, 3 at 2+, 4 at 1+). Eight tumors showed HER-2 gene amplification (6 at 3+, 1 at 1+, 1 at 0+ protein expression). Chromosome 17 polysomy was found in 8 (15.7%) of 51 tumors; two had HER-2 expression (3+, 1+).Our study shows that salivary duct carcinomas (a) harbor EGFR gene mutations in a subset of tumors that may guide therapy, (b) pursue an aggressive clinical course in cases with chromosome 7 polysomy and high EGFR expression, and (c) with HER-2 gene amplification and protein high expression, may be selected for targeted therapy.
Cigarette smoking has a dose-dependent impact on progression of structural damage in the spine in patients with axial spondyloarthritis: results from the GErman SPondyloarthritis Inception Cohort (GESPIC)
Authors: Denis Poddubnyy, Hildrun Haibel, Joachim Listing, Elisabeth Märker-Hermann, Henning Zeidler, Jürgen Braun, Joachim Sieper, Martin Rudwaleit
Journal: Annals of the Rheumatic Diseases (2013)

Recently, we demonstrated that smoking status itself is an independent predictor of radiographic spinal progression over 2 years in patients with axial SpA (axSpA).1 Here we report in more detail the relationship between tobacco smoking and development of structural damage in the spine in patients with axSpA with a focus on a dose-dependent association and a relationship between smoking and activity of systemic inflammation.

In total, 210 patients with axSpA (115 with ankylosing spondylitis (AS) and 95 with non-radiographic axSpA (nr-axSpA)) from the GErman SPondyloarthritis Inception Cohort (GESPIC)1 ,2 were included. Detailed description of the patients and radiographs scoring has been reported elsewhere.1 In the current analysis, we used an extended syndesmophytes count, which included lateral views of the cervical and lumbar spine, and also antero-posterior views of the lumbar spine. Significant radiographic spinal progression was defined as (1) worsening of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by ≥2 units after 2 years and (2) development of a new syndesmophyte or progression of existing syndesmophytes (formation of a bridging syndesmophyte from two single syndesmophytes) after 2 years. Smoking status and smoking intensity (non-smoker, 10 cigarettes a day and less, 11–20 cigarettes, and more than 20 cigarettes …
COMPETING DIETARY CLAIMS FOR WEIGHT LOSS: Finding the Forest Through Truculent Trees
Authors: David L. Katz
Journal: Annual Review of Public Health (2004)

In response to an accelerating obesity pandemic, competing weight-loss diets have propagated; those touting carbohydrate restriction are currently most in vogue. Evidence that sustainable weight loss is enhanced by means other than caloric restriction, however, is lacking. Whereas short-term weight loss is consistently achieved by any dietary approach to the restriction of choice and thereby calories, lasting weight control is not. Competing dietary claims imply that fundamental knowledge of dietary pattern and human health is lacking; an extensive literature belies this notion. The same dietary and lifestyle pattern conducive to health promotion is consistently associated with weight control. A bird's eye view of the literature on diet and weight reveals a forest otherwise difficult to discern through the trees. Competing diet claims are diverting attention and resources from what is actually and urgently needed: a dedicated and concerted effort to make the basic dietary pattern known to support both health and weight control more accessible to all.
Deregulated apoptosis is a hallmark of the Fanconi anemia syndrome.
Authors: A Ridet, C Guillouf, E Duchaud, E Cundari, M Fiore, E Moustacchi, F Rosselli
Journal: Cancer Research (1997)

Fanconi anemia (FA) is a genetic human disorder associated with bone marrow failure and predisposition to cancer. FA cells show poor growth capacity and spontaneous chromosomal anomalies as well as cellular and chromosomal hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). Because it is likely that disruption of the apoptotic control would lead to such a phenotype, we investigated the implication of apoptosis in the FA syndrome. It is shown that, although demonstrating a high frequency of spontaneous apoptosis, FA cells from four genetic complementation groups are deficient in gamma-ray-induced apoptosis and their MMC hypersensitivity is not due to apoptosis. Fas is a cell surface receptor belonging to the tumor necrosis factor receptor family and is involved in apoptosis. We show that, independently of DNA damage, the alteration in the control of apoptosis in FA concerns also the pathway initiated by Fas activation. Finally, ectopic expression of the wild-type FAC gene corrects the MMC hypersensitivity and anomalies in apoptosis and cell cycle response in FA cells. Altogether, these findings strongly implicate the FA genes as playing a major role in the control of apoptosis. Thus, further studies with FA syndrome will be instrumental toward molecularly dissecting the apoptotic pathways.
Gold Nanocage-Photosensitizer Conjugates for Dual-Modal Image-Guided Enhanced Photodynamic Therapy
Authors: Avinash Srivatsan, Samir V. Jenkins, Mansik Jeon, Zhijin Wu, Chulhong Kim, Jingyi Chen, Ravindra Pandey
Journal: Theranostics (2014)

We have demonstrated that gold nanocage-photosensitizer conjugates can enable dual image-guided delivery of photosensitizer and significantly improve the efficacy of photodynamic therapy in a murine model.The photosensitizer, 3-devinyl-3-(1'-hexyloxyethyl)pyropheophorbide (HPPH), was noncovalently entrapped in the poly(ethylene glycol) monolayer coated on the surface of gold nanocages.The conjugate is stable in saline solutions, while incubation in protein rich solutions leads to gradual unloading of the HPPH, which can be monitored optically by fluorescence and photoacoustic imaging.The slow nature of the release in turn results in an increase in accumulation of the drug within implanted tumors due to the passive delivery of gold nanocages.Furthermore, the conjugate is found to generate more therapeutic singlet oxygen and have a lower IC 50 value than the free drug alone.Thus the conjugate shows significant suppression of tumor growth as compared to the free drug in vivo.Short-term study showed neither toxicity nor phenotypical changes in mice at therapeutic dose of the conjugates or even at 100-fold higher than therapeutic dose of gold nanocages.
Partial gastrectomy for haemorrhage
Authors: J. R. Cocks, A. M. Desmond, B. F. Swynnerton, N. C. Tanner
Journal: Gut (1972)

An analysis was made of the results of 566 partial gastrectomies for haemorrhage from gastroduodenal ulceration between 1953 and 1962 with regard to mortality, morbidity, and long-term follow up. With rigid criteria for selection of patients for surgery, the overall mortality rate for ulcerative gastroduodenal haemorrhage was 8·6%. The actual operative mortality rate more than doubles if an emergency operation is performed later than four days after the patient9s admission with haemorrhage. Postoperative and later bleeding complications occurred in 5% of patients. Regardless of the length of ulcerative history, over 92% of patients have clinically satisfactory long-term results. Six per cent required further operation, after which, they too had clinically satisfactory results.
The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom
Authors: I D Johnston, S A Gomm, S Kalra, A A Woodcock, C C Evans, C R Hind
Journal: European Respiratory Journal (1993)

The case notes of 200 patients with cryptogenic fibrosing alveolitis, from three regions in the United Kingdom, were reviewed, in order to determine how physicians manage this uncommon condition. In the majority of cases (119), the diagnosis was based solely on clinical grounds, with no attempt at histological confirmation of the diagnosis. Transbronchial biopsy was attempted in 66 patients, but was unhelpful in confirming a diagnosis of pulmonary fibrosis in 30% of these patients. Thirty five patients underwent bronchoalveolar lavage, and 15 had an open lung biopsy. Of the 132 patients treated, 110 received prednisolone alone, and the rest a combination of other immunosuppressive agents. The doses and duration of therapy varied considerably. These results suggest that, in the late 1980s, there were wide variations of practice in the management of cryptogenic fibrosing alveolitis in the United Kingdom. This is likely to reflect a paucity of information on the optimum management of this uncommon condition.
RITZ-5: randomized intravenousTeZosentan (an endothelin-A/B antagonist)for the treatment of pulmonary edema
Authors: Edo Kaluski, Isaac Kobrin, Reuven Zimlichman, Alon Marmor, Oscar Krakov, Olga Milo, Aline Frey, Shoshana Kaplan, Rikardo Krakover, Avi Caspi, Zvi Vered, Gad Cotter
Journal: Journal of the American College of Cardiology (2003)
Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder
Authors: Chihiro Kakiuchi, Kazuya Iwamoto, Mizuho Ishiwata, Miki Bundo, Takaoki Kasahara, Ichiro Kusumi, Takahiro Tsujita, Yuji Okazaki, Shinichiro Nanko, Hiroshi Kunugi, Tsukasa Sasaki, Tadafumi Kato
Journal: Nature Genetics (2003)
Prognostic Significance of Truncating <i>TP53</i> Mutations in Head and Neck Squamous Cell Carcinoma
Authors: Marlon Lindenbergh-van der Plas, Ruud H. Brakenhoff, Dirk J. Kuik, Marijke Buijze, Elisabeth Bloemena, Peter J.F. Snijders, C. René Leemans, Boudewijn J.M. Braakhuis
Journal: Clinical Cancer Research (2011)

TP53 is a key gene in cellular homeostasis and is frequently mutated in head and neck squamous cell carcinoma (HNSCC). There is a variety of TP53 mutations, each with its own biological and clinical implication. Aim of the study was to assess the prognostic significance of TP53 mutations in HNSCCs and to identify the most relevant mutation.TP53 mutation status was investigated in 141 consecutive HNSCCs treated by surgery with radiotherapy when indicated and with a known human papilloma virus status. The type of mutation was correlated with overall and progression-free survival in a multivariate two-sided Cox regression analysis with wild type as reference.A TP53 mutation was found in 88 (62.4%) of the carcinomas and was not significantly associated with overall survival (HR = 1.65, P = 0.11). Patients with a mutation resulting in a truncated protein (n = 36, 25.5%) had a significantly worse overall survival (HR = 2.54, P = 0.008) and progression-free survival (HR = 2.65, P = 0.002). Four of these mutations were at a splice site, 13 were nonsense mutations (produces stop codon), and 19 were insertions or deletions resulting in a frameshift. After multivariate analysis, a truncating mutation remained a significant prognosticator. A missense (i.e., nontruncating) mutation did not influence prognosis. Other ways of classification (disruptive vs. nondisruptive, hotspot vs. nonhotspot, and DNA binding vs. non-DNA binding) were less discriminative.In HNSCCs, a truncating TP53 mutation is associated with a poor prognosis. This patient group seems as a target population for adjuvant therapy with chemoradiation or viral vector-mediated TP53 gene transfer.
Quality of life, major medical complications and hospital service utilization in patients with primary biliary cirrhosis after liver transplantation
Authors: Miquel Navasa, Xavier Forns, Victoria Sánchez, Hernán Andreu, Victoria Marcos, Joseph M. Boarràs, Antoni Rimola, Luis Grande, Juan-Carlos García-Valdecasas, Alicia Granados, Joan Rodés
Journal: Journal of Hepatology (1996)
Second Neoplasms After Wilms' Tumor in Childhood
Authors: Frederick P. Li, James Cai-jie Yan, Stephen Sallan, J. Robert Cassady, Jane Danahy, William Fine, Richard D. Gelber, Daniel M. Green
Journal: JNCI Journal of the National Cancer Institute (1983)

The frequency of second neoplasms was examined among 487 Wilms' tumor patients treated at the Dana-Farber Cancer Institute and Children's Hospital of Boston, 1927-81. Thirty study patients (6%) developed second primary tumors: 11 cancers, 16 benign tumors, and 3 borderline neoplasms. Cumulative probability of a second cancer was 18% (standard error, 6%) in 34 years after diagnosis of Wilms' tumor. The subgroup of 412 patients who had received radiotherapy for Wilms' tumor developed all 11 second cancers, which included 1 skin carcinoma, 1 acute leukemia, and 9 solid internal cancers (expected, 0.7 cancers other than skin carcinoma; P less than .001). After exclusion of the secondary leukemia, all but 1 second cancer arose within the radiotherapy field. Concurrent therapy with dactinomycin did not reduce the risk of a radiation-associated cancer. Second cancer was the cause of death in 7 patients.
Mutation-Selective Tumor Remission with Ras-Targeted, Whole Yeast-Based Immunotherapy
Authors: Yingnian Lu, Donald Bellgrau, Lori D. Dwyer-Nield, Alvin M. Malkinson, Richard C. Duke, Timothy C. Rodell, Alex Franzusoff
Journal: Cancer Research (2004)

Abstract Activating mutations in Ras oncoproteins represent attractive targets for cancer immunotherapy, but few vectors capable of generating immune responses required for tumor killing without vector neutralization have been described. Whole recombinant yeast heterologously expressing mammalian mutant Ras proteins were used to immunize mice in a carcinogen-induced lung tumor model. Therapeutic immunization with the whole recombinant yeast caused complete regression of established Ras mutation-bearing lung tumors in a dose-dependent, antigen-specific manner. In combination with the genomic sequencing of tumors in patients, the yeast-based immunotherapeutic approach could be applied to treat Ras mutation-bearing human cancers.
Mechanisms and Treatment of CKD
Authors: Piero Ruggenenti, Paolo Cravedi, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2012)

As CKD continues to increase worldwide, along with the demand for related life-saving therapies, the financial burden of CKD will place an increasing drain on health care systems. Experimental studies showed that glomerular capillary hypertension and impaired sieving function with consequent protein overload play a pathogenic role in the progression of CKD. Consistently, human studies show that proteinuria is an independent predictor of progression and that its reduction is renoprotective. At comparable BP control, inhibitors of the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), more effectively than non-RAS inhibitor therapy reduce proteinuria, slow progression to ESRD, and even improve the kidney function achieving disease regression in some cases. In participants with diabetes, RAS inhibitors delay the onset of microalbuminuria and its progression to macroalbuminuria, and ACE inhibitors may reduce the excess cardiovascular mortality associated with diabetic renal disease. In addition to RAS inhibitors, however, multimodal approaches including lifestyle modifications and multidrug therapy will be required in most cases to optimize control of the several risk factors for CKD and related cardiovascular morbidity. Whether novel medications may help further improve the cost-effectiveness of renoprotective interventions is a matter of investigation.
Update on the use of ciclosporin in immune-mediated dermatoses
Authors: C.E.M. Griffiths, A. Katsambas, B.A.C. Dijkmans, A.Y. Finlay, V.C. Ho, A. Johnston, T.A. Luger, U. Mrowietz, K. Thestrup-Pedersen
Journal: British Journal of Dermatology (2006)

Immune-mediated dermatoses, such as psoriasis and atopic dermatitis, affect a significant proportion of the population. Although most cases are not life threatening, these diseases can have a profound effect on the sufferer's quality of life and that of their family. Systemic therapy, such as ciclosporin, is often indicated for severe or recalcitrant disease. The efficacy of ciclosporin in the treatment of psoriasis and atopic dermatitis has been established and clinical data also demonstrate its efficacy in treating less common but equally challenging conditions such as pyoderma gangrenosum, lichen planus, autoimmune bullous disease, recalcitrant chronic idiopathic urticaria and chronic dermatitis of the hands and feet. The risk of potential adverse events associated with ciclosporin is greatly reduced if current treatment and monitoring guidelines are followed.
Preparation and Immunological Properties of Procaine‐Protein Conjugates
Authors: Athanasia Liakopoulou
Journal: Allergy (1981)

Procaine was conjugated to BSA and rat and rabbit Gf using the carbodiimide method and 14C-procaine as a tracer. The composition of the conjugates could be varied depending on the time of incubation and the concentration of procaine in the reaction mixture. Procaine-BSA conjugates were soluble in water or saline. However, procaine conjugates to rat or rabbit Gf were not readily soluble in saline. These conjugates were good for immunization purposes, but it was cumbersome to work with them when clear solutions were needed, as in the immunochemical procedures used in this study. The immunological properties of the conjugates were studied in rats and rabbits. Rats responded with production of IgGa and precipitating antibodies to the procaine group, but IgE antibodies to the immunogen could not be detected. Furthermore, precipitating antibodies towards the procaine group were raised in rabbits. When BSA was the protein carrier, antibodies to the carrier molecule were also detected in both rats and rabbits. The conjugates of procaine to rat or rabbit Gf did not elicit antibody response to the carrier molecular when used in the homologous species. Hapten inhibition studies suggested that, in the rabbit, antibodies were also produced with specificity directed towards the molecular configuration of the hapten-carrier bond.
Anti-self HLA may be clonally expressed.
Authors: E Goulmy, J D Hamilton, B A Bradley
Journal: The Journal of Experimental Medicine (1979)

A monolayer absorption technique was used to test the hypothesis that killer cells directed to self HLA-associated minor histocompatibility antigens (H-Y) were divisible into subsets. The results showed that sensitized killer cells, which recognized two combined antigens HLA-A2; H-Y and HLA-B7; H-Y could indeed be divided into two populations. One was directed to HLA-A2; H-Y and the other to HLA-B7; H-Y. These results can be interpreted in the context of the altered self hypothesis. However, when interpreted in the context of the dual recognition hypothesis, they strongly suggest that independant clones of killer T cells exist which are committed to the recognition of self HLA.