tbuckley/cabot-search huggingface dataset:
American Society of Clinical Oncology Policy Statement: Disparities in Cancer Care
Authors: Elizabeth Goss, Ana Maria Lopez, Carol L. Brown, Dana S. Wollins, Otis W. Brawley, Derek Raghavan
Journal: Journal of Clinical Oncology (2009)

The American Society of Clinical Oncology (ASCO) has embarked on an intensive campaign to integrate elimination of cancer health disparities into the Society's overall mission and activities. Key components of this commitment are enhancing awareness of disparities; improving access to care; and supporting research on health disparities. Major objectives are to advance the education of the oncology community in the care of patients from underserved and minority populations; increase the diversity of the clinical oncology workforce as a requisite to improving access to cancer care for the underserved; and support research in the area of health disparities. Racial and ethnic disparities in cancer care are an issue of critical importance to ASCO, the oncology community, and our society at large. The health disparities initiative outlined herein enunciates ASCO's dedication to eliminating disparities in cancer care and discusses our multipronged approach for addressing disparities within the clinical oncology community. ASCO is committed to collaborating with the diverse community of stakeholders to undertake the following: develop policies to guarantee equal access to quality health care, with special emphasis on reducing insurance and economic barriers to cancer care; develop a comprehensive plan to increase awareness of racial and ethnic disparities in cancer care; execute a strategy to enhance the supply of minority physicians and to improve the training of the oncology workforce to meet the needs of racially and ethnically diverse cancer patients; increase prioritization of public and private research on cancer care disparities; develop mechanisms to increase participation of racially and ethnically diverse populations in cancer clinical trials; and support initiatives to enhance patients' involvement in their cancer care.
Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3
Authors: Ole E. Sørensen, Per Follin, Anders H. Johnsen, Jero Calafat, G. Sandra Tjabringa, Pieter S. Hiemstra, Niels Borregaard
Journal: Blood (2001)
Purification and characterization of mouse serum protein with specific binding affinity for C4 (Ss protein)
Authors: A Ferreira, M Takahashi, V Nussenzweig
Journal: The Journal of Experimental Medicine (1977)

A new component of the complement (C).system, with a specific binding affinity for the activated Ss-protein (C4) has been identified in mouse serum. This protein, named Ss- (or C4)-binding protein (Ss-bp), was purified about 200 times from mouse plasma. Ss-bp is a heat stable (56 degrees C, 60 rain) β-globulin with a sedimentation coefficient in sucrose density ultracentrifugation of 10s. Its concentration in serum of adult male and female mice is 160 and 60 μg/ml, respectively. In EDTA-plasma, Ss and Ss-bp are not associated and can be separated by chromatography in Sephadex G-200. However, in serum Ss-bp binds tightly to Ss. The bonds between these proteins cannot be reversed by chelation of divalent cations. As a consequence of the formation of Ss/Ss-bp complexes, the properties of Ss-bp appear to be quite different in serum of mice with high (Ss-H) or low (Ss-L) levels of Ss-protein. In Ss-H serum, all of Ss- bp is bound to Ss. In Ss-L serum, Ss-bp is mostly free. Because the electrophoretic mobilities of free and complexed Ss-bp are quite different, Ss-bp appears to be polymorphic in serum (but not in EDTA- plasma). The strict dependency of the apparent electrophoretic mobility of Ss-bp on the levels of Ss in serum was demonstrated in a series of congenic mice and among the progeny of a cross between Ss-H and Ss-L strains of mice. Without exception, the slow and fast varieties of Ss-bp were associated with the Ss-L and Ss-H traits. Ss-bp of the slow variety can be transformed into the fast variety by addition of pure human C4, or C4-sufficient guinea pig serum, to Ss-L serum. In both instances Ss-bp formed stable complexes with C4 or a C4- derived peptide. These findings highlight the binding specificity of Ss- bp for the fourth component of the complement system, and in addition they demonstrate a functional homology between the Ss-protein and C4 from two different species.
Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia.
Authors: C Sebban, E Lepage, J P Vernant, E Gluckman, M Attal, J Reiffers, L Sutton, E Racadot, M Michallet, D Maraninchi
Journal: Journal of Clinical Oncology (1994)

PURPOSE Optimal postremission therapy remains controversial in adult patients with acute lymphoblastic leukemia (ALL). In a large multicentric trial (LALA87), we compared allogeneic bone marrow transplantation (BMT) with other postremission therapies (chemotherapy or autologous transplantation) using the result of the human leukocyte antigen (HLA) typing as a random allocation. PATIENTS AND METHODS Patient eligibility requirements were as follows: (1) inclusion in LALA87 trial, (2) complete response to induction or salvage therapy, (3) age 15 to 40 years, and (4) at least one potential sibling donor. Patients with an HLA-identical sibling were assigned to the BMT group, while patients without a sibling donor constituted the control group. Allogeneic transplantation was scheduled for patients in the BMT group; in the control group, patients were randomly allocated to receive chemotherapy or autologous transplantation. RESULTS Of 284 eligible points, 257 entered the study: 116 were allocated to the BMT group and 141 to the control group. The 5-year survival rates were not statistically significantly different between the two groups. When only patients with high-risk ALL were considered (those with [1] Philadelphia chromosome [Ph1] ALL, [2] null or undifferentiated ALL, or [3] c-ALL with either age greater than 35 years or WBC count &gt; 30 x 10(9)/L or time to achieve complete remission &gt; 4 weeks), overall survival (P = .03) and disease-free-survival (P = .01) were better for the BMT group compared with the control group (5-year overall survival rates, 44% v 20%; 5-year disease-free survival rates, 39% v 14%). CONCLUSION Allogeneic transplantation does not improve survival in patients with standard-risk ALL and should be recommended only for patients with adverse prognostic factors.
The existence of geographical clusters of cases of inflammatory polyarthritis in a primary care based register
Authors: A. Silman
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To determine whether there is any evidence that there are spatial clusters of rheumatoid arthritis in particular, and inflammatory arthritis in general. <h3>METHODS</h3> Setting was a population based incidence register of inflammatory arthritis: the Norfolk Arthritis Register (NOAR). All cases identified between 1990–1995 were mapped to place of residence. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. <h3>RESULTS</h3> Three clusters were identified including one small area (population 85) where five unrelated cases developed during this time period. There was no obvious greater disease homogeneity within clusters and no common environmental factors were identified. <h3>CONCLUSION</h3> Rare clusters of inflammatory polyarthritis do occur. Their significance and cause remain to be elucidated.
Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial
Authors: Beatriz Grinsztejn, Mina C Hosseinipour, Heather J Ribaudo, Susan Swindells, Joseph Eron, Ying Q Chen, Lei Wang, San-San Ou, Maija Anderson, Marybeth McCauley, Theresa Gamble, Nagalingeshwaran Kumarasamy, James G Hakim, Johnstone Kumwenda, Jose H S Pilotto, Sheela V Godbole, Suwat Chariyalertsak, Marineide Gonçalves de Melo, Kenneth H Mayer, Susan H Eshleman, Estelle Piwowar-Manning, Joseph Makhema, Lisa A Mills, Ravindre Panchia, Ian Sanne, Joel Gallant, Irving Hoffman, Taha E Taha, Karin Nielsen-Saines, David Celentano, Max Essex, Diane Havlir, Myron S Cohen
Journal: The Lancet Infectious Diseases (2014)
Targeting TACE-dependent EGFR ligand shedding in breast cancer
Authors: P. A. Kenny, M. J. Bissell
Journal: Journal of Clinical Investigation (2007)

The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop that provides an oncogenic stimulus in the absence of proto-oncogene mutation. Targeting this protease, TNF-alpha-converting enzyme (TACE; also referred to as a disintegrin and metalloproteinase 17 [ADAM17]), with small molecular inhibitors or siRNAs reverted the malignant phenotype in a breast cancer cell line by preventing mobilization of 2 crucial growth factors, TGF-alpha and amphiregulin. We show that TACE-dependent ligand shedding was prevalent in a series of additional breast cancer cell lines and, in all cases examined, was amenable to inhibition. Using existing patient outcome data, we demonstrated a strong correlation between TACE and TGFA expression in human breast cancers that was predictive of poor prognosis. Tumors resulting from inappropriate activation of the EGFR were common in multiple tissues and were, for the most part, refractory to current targeted therapies. The data presented here delineate the molecular mechanism by which constitutive EGFR activity may be achieved in tumor progression without mutation of the EGFR itself or downstream pathway components and suggest that this important oncogenic pathway might usefully be targeted upstream of the receptor.
Repeat liposuction-curettage treatment of axillary hyperhidrosis is safe and effective
Authors: F.G. Bechara, M. Sand, N.S. Tomi, P. Altmeyer, K. Hoffmann
Journal: British Journal of Dermatology (2007)

Background Liposuction‐curettage (LC) is an effective surgical therapy option for axillary hyperhidrosis, with less scarring compared with radical excision of axillary skin. Although this method has proven to be effective, the treatment of nonresponders to minimally invasive surgery has not been previously defined. Whether these patients benefit from a second surgical procedure has not been evaluated so far. Objectives To investigate efficacy and side‐effects of a second LC with an aggressive rasping cannula in patients with insufficient prior surgery. Methods Nineteen nonresponders to prior LC (13 female and six male) underwent a second LC with a rasping cannula. Gravimetry was performed before and 8 months after surgery. Side‐effects, patient satisfaction, the surgeons' intraoperative evaluation and the Vancouver Scar Scale (VSS) before and after surgery were documented. Results Sweat rates showed a reduction of 69% in 17 (89%) patients. Two patients (11%) did not respond to surgery. Eighty‐four per cent of all patients were completely satisfied or satisfied with postoperative results. No severe side‐effects were observed. The surgeon reported slightly increased difficulties during dissection of dermis from subcutaneous fat in three patients. Assessment of scars showed an excellent aesthetic outcome (mean VSS 0·79 before vs. 1·1 after surgery). Conclusions LC using an aggressive cannula is an effective therapy option for patients with insufficient response to prior LC surgery, with a low risk of side‐effects.
Pleural atypical mesothelial hyperplasia: An early stage of pleural malignant mesothelioma?
Authors: Thomas Vandemoortele, Sophie Laroumagne, Olivier Bylicki, Sophie Giusiano, Hervé Dutau, Philippe Astoul
Journal: European Respiratory Journal (2012)

Mesothelioma is a neoplastic process most often secondary to asbestos exposure. Atypical mesothelial hyperplasia (AMH) is thought to be a benign process in reaction to various processes, including infectious pleurisy and recurring transudative pleural effusion. However, it is unknown if there might be a link between AMH and malignant pleural mesothelioma (MPM).  Herein, we present the case of a 69 year-old patient with documented asbestos exposure in whom MPM was diagnosed four months after a first diagnosis of AMH.  Thoracoscopy showed inflammation of the posterior parietal pleura and white lymphangitis of the anterior pleura, without nodule or any other suspicious lesion. Biopsies taken from the anterior pleura showed AMH.  Two months later, the patient returned with a recurring right sided effusion.  CT-scan revealed a subcarinal lymph node measuring 15x8mm and a pleural effusion with partial atelectasis of the right lower and middle lobes.  Repeat thoracoscopy was performed, four months after the initial one.  The pleura was dramatically changed, with numerous nodules and neoplastic lymphangitis. Multiple biopsies were performed on the diaphragmatic and posterior pleura. Histologic features were compatible with epithelioid MPM.  How MPM evolves from normal pleura is still debated, despite the acknowledgement of the causal relation with asbestos. Whether mesothelioma evolves from atypical hyperplasia, as epithelium-derived cancer of other origins, remains to be elucidated.  Conclusion  Diagnosis of MPM relies on pleural biopsy specimens. Thoracoscopy is particularly useful in guiding pleural biopsies and in symptomatic improvement if talc pleurodesis is performed.
Hotspot Mutation Panel Testing Reveals Clonal Evolution in a Study of 265 Paired Primary and Metastatic Tumors
Authors: Rashmi S. Goswami, Keyur P. Patel, Rajesh R. Singh, Funda Meric-Bernstam, E. Scott Kopetz, Vivek Subbiah, Ricardo H. Alvarez, Michael A. Davies, Kausar J. Jabbar, Sinchita Roy-Chowdhuri, Alexander J. Lazar, L. Jeffrey Medeiros, Russell R. Broaddus, Rajyalakshmi Luthra, Mark J. Routbort
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We used a clinical next-generation sequencing (NGS) hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. Experimental Design: A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single-nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Results: Of note, 227 of 265 (85.7%) tumor metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n = 20, 7.5%) than primary tumors (n = 12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Conclusions: Clinical NGS hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4, and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases. Clin Cancer Res; 21(11); 2644–51. ©2015 AACR.
Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein.
Authors: Y Nojima, D M Rothstein, K Sugita, S F Schlossman, C Morimoto
Journal: The Journal of Experimental Medicine (1992)

The VLA/integrins are a family of heterodimeric adhesion receptors shown to be involved in cell-to-cell and cell-to-extracellular matrix (ECM) interactions. Given recent evidence that VLA molecules can synergize with the CD3/T cell receptor (TCR) pathway to activate T cells, it is important to identify biochemical event(s) generated by these molecules. Here, we report that the engagement of VLA-4 on T cells with specific antibodies or its ligand activates protein-tyrosine kinase (PTK) activity as detected by antiphosphotyrosine immunoblotting. The crosslinking of VLA-beta 1 (CD29) with a specific monoclonal antibody (mAb) (anti-4B4) plus anti-mouse immunoglobulin resulted in the rapid tyrosine phosphorylation of a 105-kD protein (pp105) in the human T cell line H9, as well as in peripheral resting T cells. The increase in tyrosine phosphorylation of pp105 was specifically mediated by VLA-4, since mAbs against alpha 4, but not against other VLA alpha chains, could induce this phosphorylation. In addition, the binding of T cells with the CS1 alternatively spliced segment of fibronectin (the binding site recognized by VLA-4) induced pp105 tyrosine phosphorylation. Crosslinking the CD3 complex or VLA-4 molecules with mAbs demonstrated that each of these molecules stimulated the tyrosine phosphorylation of unique sets of proteins with different kinetics, suggesting that these two receptor systems are coupled to distinct PTKs. Since tyrosine phosphorylation of cellular proteins has been shown to be a crucial biochemical event in cell growth, our findings suggest that the induction of pp105 tyrosine phosphorylation via VLA-4 may play a role in the transduction of activation signals through this molecule.
Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice
Authors: F Dupic
Journal: Gut (2002)

Although much progress has been made recently in characterising the proteins involved in duodenal iron trafficking, regulation of intestinal iron transport remains poorly understood. It is not known whether the level of mRNA expression of these recently described molecules is genetically regulated. This is of particular interest however as genetic factors are likely to determine differences in iron status among mouse strains and probably also contribute to the phenotypic variability seen with disruption of the haemochromatosis gene.To investigate this issue, we examined concomitant variations in duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), hephaestin, stimulator of Fe transport (SFT), HFE, and transferrin receptor 1 (TfR1) transcripts in response to different dietary iron contents in the four mouse strains C57BL/6, DBA/2, CBA, and 129/Sv.Six mice of each strain were fed normal levels of dietary iron, six were subjected to the same diet supplemented with 2% carbonyl iron, and six were fed an iron deficient diet.Quantification of mRNAs isolated from the duodenum was performed using real time reverse transcription-polymerase chain reaction.There was a significant increase in mRNA expression of Dcytb, DMT1, FPN1, and TfR1 when mice were fed an iron deficient diet, and a significant decrease in mRNA expression of these molecules when mice were fed an iron supplemented diet. Strain to strain differences were observed not only in serum transferrin saturations, with C57BL/6 mice having the lowest values, but also in hepatic iron stores and in duodenal mRNA expression of Dcytb, DMT1, FPN1, hephaestin, HFE, and TfR1.The results favour some degree of genetic control of mRNA levels of these molecules.
Mitochondria and Mitophagy
Authors: Dieter A. Kubli, Åsa B. Gustafsson
Journal: Circulation Research (2012)

Mitochondria are primarily responsible for providing the contracting cardiac myocyte with a continuous supply of ATP. However, mitochondria can rapidly change into death-promoting organelles. In response to changes in the intracellular environment, mitochondria become producers of excessive reactive oxygen species and release prodeath proteins, resulting in disrupted ATP synthesis and activation of cell death pathways. Interestingly, cells have developed a defense mechanism against aberrant mitochondria that can cause harm to the cell. This mechanism involves selective sequestration and subsequent degradation of the dysfunctional mitochondrion before it causes activation of cell death. Induction of mitochondrial autophagy, or mitophagy, results in selective clearance of damaged mitochondria in cells. In response to stress such as ischemia/reperfusion, prosurvival and prodeath pathways are concomitantly activated in cardiac myocytes. Thus, there is a delicate balance between life and death in the myocytes during stress, and the final outcome depends on the complex cross-talk between these pathways. Mitophagy functions as an early cardioprotective response, favoring adaptation to stress by removing damaged mitochondria. In contrast, increased oxidative stress and apoptotic proteases can inactivate mitophagy, allowing for the execution of cell death. Herein, we discuss the importance of mitochondria and mitophagy in cardiovascular health and disease and provide a review of our current understanding of how these processes are regulated.
Signaling and Transcription in T Helper Development
Authors: Kenneth M. Murphy, Wenjun Ouyang, J. David Farrar, Jianfei Yang, Sheila Ranganath, Helene Asnagli, Maryam Afkarian, Theresa L. Murphy
Journal: Annual Review of Immunology (2000)

The recognition of polarized T cell subsets defined by cytokine production was followed by a search to define the factors controlling this phenomenon. Suitable in vitro systems allowed the development of cytokine “recipes” that induced rapid polarization of naïve T cells into Th1 or Th2 populations. The next phase of work over the past several years has begun to define the intracellular processes set into motion during Th1/Th2 development, particularly by the strongly polarizing cytokines IL-12 and IL-4. Although somewhat incomplete, what has emerged is a richly detailed tapestry of signaling and transcription, controlling an important T cell developmental switch. In addition several new mediators of control have emerged, including IL-18, the intriguing Th2-selective T1/ST2 product, and heterogeneity in dendritic cells capable of directing cytokine-independent Th development.
Macrophages retain hematopoietic stem cells in the spleen via VCAM-1
Authors: Partha Dutta, Friedrich Felix Hoyer, Lubov S. Grigoryeva, Hendrik B. Sager, Florian Leuschner, Gabriel Courties, Anna Borodovsky, Tatiana Novobrantseva, Vera M. Ruda, Kevin Fitzgerald, Yoshiko Iwamoto, Gregory Wojtkiewicz, Yuan Sun, Nicolas Da Silva, Peter Libby, Daniel G. Anderson, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf
Journal: The Journal of Experimental Medicine (2015)

Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)(+) macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE(-/-) mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques.