tbuckley/cabot-search huggingface dataset:
Abstract 4908: Antennapedia "trojan" peptide delivers p21 protein resulting in tumor eradication
Authors: Christina Kousparou, Mahendra Deonarain, Spyros Stylianou, Agamemnon Epenetos
Journal: Cancer Research (2008)

Abstract The purpose of this study is to utilize the “trojan horse” approach to deliver an effector function to cancer cells in vitro and in vivo. Many cell-translocating trojan peptides have been studied in the context of therapeutic protein delivery, including the homeodomain region of the Drosophila Antennapedia protein. The mechanism of transduction of this peptide relies on the presence of basic aminoacids arranged in helical conformations, which are important for lipid interactions and for penetration of the membrane. The tumor-suppressor protein p21 is important in many key cell division processes including G1 arrest leading to apoptosis of damaged cells. Restoring p21 protein to tumor cells lacking functional p21 could lead to tumor cells regaining higher chemosensitivity and the ability to die upon genotoxic insult. Our experiments investigate the tumor inhibitory and therapeutic potential of a fusion protein comprising of the ‘trojan’ peptide Antennapedia and p21. The effects of administration of Antennapedia-p21 on the growth of cultured cancer cells and on tumors implanted into nude mice were evaluated. In vitro studies showed that nuclear localization of p21 protein could be achieved using the Antennapedia carrier. The efficacy of this treatment on cells was also determined in combination with conventional chemotherapy. Treatment with Antp-p21 induced cell-cycle arrest leading to the inhibition of tumor cell growth. Intra-venous administration of the fusion protein to tumor-bearing mice inhibited tumor growth and prolonged overall survival. Furthermore, co-administration of the fusion protein with conventional chemotherapeutic agents resulted in enhanced growth inhibitory effects, tumor eradication in 40% of animals and significant reduction in tumor burden in 100% of animals. In conclusion, our findings show that we can utilize the “trojan horse” approach to deliver an effector function to cancer cells in vitro and in vivo and achieve tumor eradication. The efficacy of our anti-tumor growth modality in combination with conventionally used anti-neoplastic medication suggests that it can be considered as a promising therapeutic drug for the management of a wide range of carcinomas.
Overproduction of soluble α2β1 integrin in a guinea-pig model of chronic asthma
Authors: Patricia Ramos-Ramírez, Diana García-Trejo, Blanca Bazán-Perkins
Journal: European Respiratory Journal (2014)

Background: The extracellular domains of some membrane proteins can be cleaved and shed from the cell. In chronic asthma model, the shedded ectodomains of α1β1 and α2β1 integrins are accumulated in airway wall, but it is unknown if soluble integrins are expressed during asthma. Aims: We evaluated the levels of α1β1 and α2β1 integrins in serum and bronchoalveolar lavage fluid (BALF) in an experimental model of chronic asthma. Methods : Sensitized guinea pigs were intermittently challenged with ovalbumin (OVA; applied every 10 days). At twelfth OVA challenge, the airway hyperresponsiveness (AHR) to histamine and the levels of cytosolic and extracellular domains of α1β1 and α2β1 integrins in serum and BALF were evaluated ( n =6). Controls received saline solution instead of OVA ( n =6). Results : From the first challenge on, OVA induced acute transient bronchoobstruction followed by development of AHR. The levels of extracellular and cytosolic domains of α1β1 integrin in BALF and serum in asthma model guinea pigs were similar between groups. The expression of cytosolic domain of α1β1 integrin in BALF and serum was similar in both groups; nevertheless, the extracellular domain of α2β1 integrin increase in serum and BALF of asthma model guinea pigs in comparison to controls. Conclusions : We suggest that the soluble ectodomain of α2β1 integrin, an integrin involved in matrix organization andcell adhesion, might be a putative molecular marker of chronic asthma.
Acquired bilateral naevus of Ota-like macules: an immunohistological analysis of dermal melanogenic paracrine cytokine networks
Authors: J.Y. Lee, E.H. Kim, K.H. Kim, H.Y. Kang, E-S. Lee, Y.C. Kim
Journal: British Journal of Dermatology (2010)

Acquired bilateral naevus of Ota-like macules (ABNOM) is similar to melasma with regard to their clinical features, including female predominance, acquired onset, and predominant involvement of the malar area. The similar clinical features suggest the possibility of a shared pathogenesis. Dermal factors including vascularity and melanogenic paracrine networks such as the stem cell factor (SCF)/c-kit pathway have recently been suggested to play an important role in the pathogenesis of melasma. However, the role of dermal factors in ABNOM remains unknown.To provide a novel view on the pathogenesis of ABNOM, we studied the expression of melanogenic paracrine cytokines such as SCF/c-kit, and assessed dermal vascularity.Thirty-seven patients with ABNOM and 20 patients with melasma were enrolled in this study. Skin samples were obtained from lesional and perilesional normal skin. Immunohistochemistry was performed.Solar elastosis was slightly more intense in the lesional skin of ABNOM. In contrast to dermal pigmentation and melanocytes, the amounts of epidermal pigmentation and melanocytes were not increased in the lesional skin of patients with ABNOM. The expression of dermal SCF and c-kit was increased; however, the expression of epidermal SCF and c-kit and dermal factor VIII-related antigen was not increased in the lesional skin of ABNOM.These results suggest that the increased expression of the SCF/c-kit pathway between dermal fibroblasts and dermal melanocytes may play an important role in the pathogenesis of ABNOM.
Phase I first-in-human study of the PI3 kinase inhibitor GSK2126458 (GSK458) in patients with advanced solid tumors (study P3K112826).
Authors: P. N. Munster, R. van der Noll, E. E. Voest, E. C. Dees, A. R. Tan, J. M. Specht, G. S. Falchook, A. Daud, M. P. Lolkema, J. E. Grilley-Olson, E. Y. Yu, S. Fu, E. K. Bergsland, J. Kleha, S. Peng, D. A. Smith, T. A. Lampkin, J. H. M. Schellens, S. R. Morris, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

3018 Background: Phosphatidylinositol 3-kinase (PI3K) is critical to cancer cell growth, survival, and metabolism. GSK458 is an oral, potent inhibitor of PI3K (α, β, γ, δ), mTORC1, and mTORC2. Preclinically, GSK458 has demonstrated broad anti-tumor activity against solid tumors and hematologic malignancies in vitro and in vivo. Cell lines with common activating mutations of PIK3CA are particularly sensitive to GSK458. Methods: Adult patients (pts) with relapsed or refractory advanced solid tumors received GSK458 by mouth daily until disease progression or toxicity. Dose escalation used a modified accelerated titration scheme. Expansion cohorts further evaluated pharmacodynamics (PD), pharmacokinetics and clinical activity in specific target populations. Results: Preliminary data reveal that 78 pts (51% female) with mean age of 57 (25-85) yrs received ≥1 dose of GSK458. Doses ranged from 0.1 to 3 mg. Maximum tolerated dose was 2.5 mg daily. AUC and Cmax increased with dose. Across doses: median Tmax was 2 hrs and mean t½ 10 hrs. Grade 3 diarrhea was dose-limiting in 2 pts at 3 mg and 1 pt at 1.5 mg. The incidence of grade 3 diarrhea was 7% (1/14) at 1.5 mg and 44% (4/9) at 3 mg. Grade 1 or 2 rash was reported in 22% (2/9) of patients at 3 mg. The most commonly (≥10%) reported drug-related adverse events were: fatigue (15%; G3/4 1%), nausea (15%; G3/4 1%), and diarrhea (12%; G3/4 6%). The change from baseline for fasting glucose values 1 and 2h post-dose after a single dose of GSK458 and at steady state increased with respect to dose and exposure, suggesting an on-target effect. Analysis of pre- and post-dose biopsy tissue for pAKT is ongoing. Partial response was observed in two pts, one with RCC at 0.4 mg (11+ mo), and one with bladder cancer at 2 mg (1+ mo). Conclusions: The MTD of GSK458 when administered daily is 2.5 mg. Dose-limiting toxicity is diarrhea. PD effects suggest on-target inhibition of PI3K. Two patients have experienced PR.
A phase III randomised trial comparing sequential to standard chemotherapy in advanced non-small cell lung cancer (NSCLC)
Authors: J. Sculier, J. Lafitte, J. Lecomte, C. Alexopoulos, O. Van Cutsem, V. Giner, A. Efremidis, A. Scherpereel, M. Paesmans, T. Berghmans
Journal: Journal of Clinical Oncology (2006)

7012 Background: Cisplatin-based chemotherapy and taxans are effective treatments for advanced NSCLC. We performed a phase III randomised trial to determine if the sequential administration of cisplatin-based chemotherapy followed by paclitaxel is superior to a cisplatin-based standard chemotherapy, with the use of paclitaxel as salvage treatment. Methods: Untreated advanced NSCLC with adequate PS, hematological, hepatic, cardiac and renal functions were treated by 3 courses of GIP (cisplatin 50 mg/m 2 , ifosfamide 3 g/m 2 , gemcitabine 1 g/m 2 ). Patients with a non-progressing tumour were randomised between 3 further courses of GIP or 3 courses of paclitaxel (225 mg/m 2 ). To detect an increase in the survival rates (primary endpoint) from 20% in the GIP arm to 35% in the sequential arm, with 80% probability using a two-sided logrank test with a significance level of 5%, we needed to observe 178 events, requiring to randomise 123 patients in each arm. Results: From January 2000 to February 2004, 485 patients received 3 courses of induction GIP of which 140 were randomised in the GIP arm and 141 in the paclitaxel arm. Median survival times were 14.1 (95% CI: 12.0–16.3) and 16.4 (95% CI: 14.0–18.8) months for the paclitaxel and the GIP arms, respectively (p = 0.17). When treatment comparison was adjusted for the two independent prognostic factors (sex and haemoglobin) revealed by a Cox multivariate analysis, the observed HR was 0.81 (95% CI: 0.63–1.09) in favour of the GIP arm (p = 0.10). There were more grades III/IV thrombopenia with GIP (p&lt; 0.01) and more alopecia with paclitaxel (p = 0.04). Conclusion: Sequential cisplatin-based chemotherapy by paclitaxel does not result in better survival than standard chemotherapy, with the use of paclitaxel as salvage treatment. No significant financial relationships to disclose.
Abstract 16993: Thrombospondin 1/CD36 Signaling Promotes Vascular Smooth Muscle Cell Proliferation and Contributes to Neointimal Hyperplasia
Authors: Wei Li, Phil A Klenotic, Roy Silverstein
Journal: Circulation (2012)

Dysregulated vascular smooth muscle cell (VSMC) proliferation contributes to neointima formation during pathogenesis of obstructive vascular diseases. The matricellular protein thrombospondin-1 (TS...
Non‐<scp>H</scp>odgkin lymphoma subtype distribution, geodemographic patterns, and survival in the <scp>US</scp>: A longitudinal analysis of the <scp>N</scp>ational <scp>C</scp>ancer <scp>D</scp>ata <scp>B</scp>ase from 1998 to 2011
Authors: Mohammed Al‐Hamadani, Thomas M. Habermann, James R. Cerhan, William R. Macon, Matthew J. Maurer, Ronald S. Go
Journal: American Journal of Hematology (2015)

The World Health Organization classification of non-Hodgkin lymphoma (NHL) was introduced in 2001. However, its incorporation into clinical practice is not well-described. We studied the distribution of NHL subtypes in adults diagnosed from 1998 to 2011, evaluated time trends, geo-demographic correlates, and changes in 5-year overall survival (OS). We obtained data prospectively collected by the National Cancer Data Base, which covers 70% of US cancer cases. There were 596,476 patients diagnosed with NHL. The major subtypes were diffuse large B-cell (32.5%), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 18.6%), follicular (17.1%), marginal zone (8.3%), mantle cell (4.1%), peripheral T-cell not-otherwise-specified (1.7%), Burkitt (1.6%), hairy cell (1.1%), lymphoplasmacytic (1.1%), and NHL not-otherwise-specified (10.8%). Over the study period, the proportion of NHL not-otherwise-specified declined by half, while marginal zone lymphoma doubled. The distribution of major and rare NHL subtypes varied according to demographics but less so geographically or by type of treatment facility. We noted several novel findings among Hispanics (lower proportion of CLL/SLL, but higher Burkitt lymphoma and nasal NK/T-cell lymphoma), Asians (higher enteropathy-associated T-cell and angioimmunoblastic T-cell lymphomas), Blacks (higher hepatosplenic T-cell lymphoma), and Native Americans (similar proportions of CLL/SLL and nasal NK/T-cell lymphoma as Asians). With the exception of peripheral T-cell not-otherwise-specified and hairy cell leukemia, 5-year OS has improved for all the major NHL subtypes.
Helmet Use and Injury Patterns in Motorcycle-Related Trauma
Authors: Jeff Lastfogel, Tahereh Soleimani, Roberto Flores, Adam Cohen, William A. Wooden, Imtiaz Munshi, Sunil S. Tholpady
Journal: JAMA Surgery (2015)

Wearing a motorcycle helmet has been shown to decrease the number of injuries and the mortality rate associated with motorcycle-related trauma. 1 Once almost universal, many states have regressed to partial or no helmet laws. 2 This changing leg-Table.
Discovery and Validation of Biomarkers That Distinguish Mucinous and Nonmucinous Pancreatic Cysts
Authors: Jisook Park, Hwan Sic Yun, Kwang Hyuck Lee, Kyu Taek Lee, Jong Kyun Lee, Soo-Youn Lee
Journal: Cancer Research (2015)

Abstract The use of advanced imaging technologies for the identification of pancreatic cysts has become widespread. However, accurate differential diagnosis between mucinous cysts (MC) and nonmucinous cysts (NMC) consisting of pseudocysts (NMC1) and nonmucinous neoplastic cysts (NMC2) remains a challenge. Thus, it is necessary to develop novel biomarkers for the differential diagnosis of pancreatic cysts. An integrated proteomics approach yielded differentially expressed proteins in MC that were verified subsequently in 99 pancreatic cysts (21 NMC1, 41 NMC2, and 37 MC) using a method termed GeLC-stable isotope dilution-multiple reaction monitoring-mass spectrometry (GeLC-SID-MRM-MS) along with established immunoassay techniques. We identified 223 proteins by nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC/MS-MS). Nine candidate biomarkers were identified, including polymeric immunoglobulin receptor (PIGR), lipocalin 2 (LCN2), Fc fragment of IgG-binding protein (FCGBP), lithostathine-1-alpha (REG1A), afamin (AFM), chymotrypsin C (caldecrin; CTRC), amylase, alpha 2B (pancreatic; AMY2B), lectin, galactoside-binding, soluble, 3 binding protein (LGALS3BP), and chymotrypsin-like elastase family, member 3A (CELA3A), which were established as biomarker candidates for MC. In particular, we have shown that a biomarker subset, including AFM, REG1A, PIGR, and LCN2, could differentiate MC not only from NMC (including NMC1) but also from NMC2. Overall, the MS-based comprehensive proteomics approach used in this study established a novel set of candidate biomarkers that address a gap in efforts to distinguish early pancreatic lesions at a time when more successful therapeutic interventions may be possible. Cancer Res; 75(16); 3227–35. ©2015 AACR.
Tuberculosis among children with cystic fibrosis
Authors: Ioana Ciuca, Liviu Pop, Zagorca Popa, Voicu Tudorache, Simona Turcu, Ioan Popa
Journal: European Respiratory Journal (2012)

Background: Cystic fibrosis patients are predisposed to pulmonary infections. Conditions associated with CF like underweight, diabetes mellitus (CFRD), liver disease(CFLD) are favoring factors for tuberculosis(TB). The hypothesis of a potential comorbidity of TB in CF children occurred. The aim of the paper was to evaluate the prevalence of TB in children with complicated CF. Methods: Thirty-two patients(pts) with typical CF, associating complication like CFLD(27 pts), diabetes(3 pts) and 2 with both complication were considered for a prospective five years study. Biannual bacteriologic exam (TB specific also) were included, in addition to clinical examination and annual CT, to the patients evaluation. Results: Tuberculosis occurred in 6.25 %(2 patients), both F508 del homozygous, with CFLD and poor nutritional status; one patient had also CFRD. His evolution was unfavorable; he developed portal hypertension and died from respiratory failure. The other patient was diagnosed with active TB,  Pseudomonas  positive and poor nutritional status, but good evolution after treatment. The rest of CFLD patients had a stationary evolution, except 4 of them (15.38%) developed diabetes. Tuberculin skin test was positive in 4 patients (12.5%), 3 of them received TB vaccine. Despite the mandatory vaccination for TB in our country, only 84% pts were vaccinated. 18.75% of patients (6 pts) were considered and treated as TB cases, without bacteriological confirmation, before being diagnosed with CF. Conclusion: Although TB is a frequent condition in our area, the prevalence among CF children is not as high as expected. It is possible that other factors, unknown so far, are implicated.
Hound of the Baskervilles effect
Authors: J. H Glaser
Journal: BMJ (2002)

# What about the good days? {#article-title-2} EDITOR—Phillips et al have uncovered a fascinating relation between the day of the month and the mortality rate for Chinese Americans and Japanese Americans.1 There clearly is an increase in chronic heart disease deaths of Chinese and Japanese on the fourth day of the month. Phillips et al attribute this to the similarity in the Chinese and Japanese languages of the spoken words “death” and “four.” Have Phillips et al considered whether days with a pleasurable association might have a beneficial impact? Their analysis shows a decrease in mortality for Chinese and Japanese on days 20, 26, and possibly 12. Is there any resemblance, either spoken or pictorially, between the words for those days and words evoking feelings of relaxation, wellness, or happiness? 1. 1.↵1. Phillips DP, 2. Liu GC, 3. Kwok K, 4. Jarvinen JR, 5. Zhang W, 6. Abramson IS .The Hound of the Baskervilles effect: natural experiment on the influence of psychological stress on timing of death.BMJ2001; 323:1443–1446. (22-29 December 2001.) [OpenUrl][1][Abstract/FREE Full Text][2] # Bad4U? {#article-title-4} EDITOR—In a large observational study Phillips et al noted an increase in cardiac mortality on the fourth of the month among Chinese and Japanese Americans that does not occur in white matched controls.1 This increase is particularly marked for inpatient deaths from chronic heart disease in California (figure 3). Phillips et al link this observation to their cultural and linguistic association of the number 4 with death. This effect may well be real, but some important issues remain unaddressed. Phillips et al have addressed a … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DPhillips%26rft.auinit1%253DD.%2BP%26rft.volume%253D323%26rft.issue%253D7327%26rft.spage%253D1443%26rft.epage%253D1446%26rft.atitle%253DThe%2BHound%2Bof%2Bthe%2BBaskervilles%2Beffect%253A%2Bnatural%2Bexperiment%2Bon%2Bthe%2Binfluence%2Bof%2Bpsychological%2Bstress%2Bon%2Btiming%2Bof%2Bdeath%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.323.7327.1443%26rft_id%253Dinfo%253Apmid%252F11751347%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=323/7327/1443&atom=%2Fbmj%2F324%2F7345%2F1098.atom
MRI signal hyperintensities in geriatric depression
Authors: B S Greenwald, E Kramer-Ginsberg, R R Krishnan, M Ashtari, P M Aupperle, M Patel
Journal: American Journal of Psychiatry (1996)

The authors rated periventricular and subcortical signal hyperintensities on magnetic resonance imaging (MRI) scans in elderly patients with depression and in normal subjects with similar demographic features to examine whether such changes discriminate patients with depression from normal subjects and whether they are associated with any clinical variables.Two established hyperintensity rating systems were used to compare the MRI brain scans of 48 elderly patients with depression diagnosed according to DSM-III-R with the scans of 39 normal elderly subjects.Elderly depressed patients manifested significantly more severe hyperintensity ratings in the subcortical gray matter than age-matched comparison subjects. Significant differences were not identified between patients with similar current ages and cerebrovascular disease risk who had early-onset or late-onset depression.These findings support those of neuroimaging studies implicating the basal ganglia in depression and geriatric depression. The data suggest that the relationship observed in some reports between late-onset depression and MRI hyperintensities is most likely a function of cerebrovascular disease risk and age.
Total colourblindness is caused by mutations in the gene encoding the α-subunit of the cone photoreceptor cGMP-gated cation channel
Authors: Susanne Kohl, Tim Marx, Ian Giddings, Herbert Jägle, Samuel G. Jacobson, Eckhart Apfelstedt-Sylla, Eberhart Zrenner, Lindsay T. Sharpe, Bernd Wissinger
Journal: Nature Genetics (1998)
Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial
Authors: M-J. Ko, J-Y. Yang, H-Y. Wu, F-C. Hu, S-I. Chen, P-J. Tsai, S-H. Jee, H-C. Chiu
Journal: British Journal of Dermatology (2011)

Background Pruritus is very common in uraemic patients, but the treatment remains challenging. Studies regarding narrowband ultraviolet B (NB-UVB) phototherapy for uraemic pruritus are rare. Objectives To investigate whether or not NB-UVB phototherapy is an effective treatment for uraemic pruritus. Methods We conducted a single-blind, randomized, controlled trial for patients with refractory uraemic pruritus. The treatment group received NB-UVB phototherapy three times per week for 6 weeks. The dose of NB-UVB started from 210 mJ cm−2 and was increased by 10% each time. The control group received time-matched exposures to long-wave UVA radiation. A visual analogue scale (VAS) score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6 weeks of phototherapy. Results Both the NB-UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared with the control group, the NB-UVB group showed a significant improvement in the involved body surface area affected by pruritus (P = 0·006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity scores at week 6, week 10 and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal. Conclusions NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared with a control group for refractory uraemic pruritus. Further studies are warranted.
Statement of intent needed
Authors: J S Hopkins
Journal: BMJ (1994)

EDITOR,—The debate about the core values of our profession seems to rest on a series of isolated notions and objectives.1 Would it be helpful to attempt to draw these ideas together in a single statement of intent? If so, I offer my version of what such a statement should encompass in its description of a doctor's obligations and rights.

To care for sick, old, frail, and weak people. To respect their privacy and their …