tbuckley/cabot-search huggingface dataset:
Abstract 2864: RPS4X, a new prognostic and predictive biomarker of ovarian and breast cancer
Authors: Serges P. Tsofack, Liliane Meunier, Anne-Marie Mes-Masson, Michel Lebel
Journal: Cancer Research (2014)

Abstract Epithelial ovarian cancer (EOC) is a disease responsible for more cancer deaths among women in the Western world than all other gynecologic malignancies and breast cancer is leading cause of cancer death among the women worldwide. A major problem with such cancers is chemoresistance; hence the need to identify predictive biomarkers. Interestingly, overexpression of YB-1 in ovarian and breast cancer cells induces cisplatin resistance. Platinum coumpounds like cisplatin is often used in the treatments of these cancers. Y box-binding protein 1 (YB-1) is a multifunctional protein that affects transcription, splicing and translation of mRNA. In this study, we used a tagged YB-1 construct to identify by mass spectrometry the proteins that interacted with YB-1 and required for cisplatin resistance. Using the combination of two bioinformatics databases (Oncomine public microarray and genomic hybridization), we focused on the YB-1 protein partners that are potentially involved in cancer progression. We used the siRNA technique to screen different partners of YB-1 that are directly involve in the cisplatin resistance of MCF7 and MDA-MB-231 cells lines. From this analysis, we found that the RPS4X protein, a new partner of YB-1, would be a good marker of cisplatin resistance in breast cancer patients. Interestingly, the YB-1/RPS4X complex was also found in ovarian cancer cells. Like in the breast cancer cell lines, the depletion of RPS4X protein induced the cisplatin resistance of ovarian cancer cells lines (SKOV3 and OVCAR3). Finally, we used a validate antibodies to assess by immunohistochemistry the protein levels of RPS4X and YB-1 in tumor tissue samples from 192 high-grade serous epithelial ovarian cancer patients. We found that RPS4X correlated significantly with ovarian cancer patient outcome. Taken together, these results suggest that, the YB-1/RPS4X complex is a significant potential target to counteract cisplatin resistance in breast and ovarian cancers. Also, we have established that RPS4X is a new promising prognostic marker for patients with high-grade ovarian cancer. More importantly, RPS4X is shown to be predictive of cisplatin response. Additional immunohistochemistry studies on low-grade ovarian cancers and breast cancers are required to confirm the predictive value of RPS4X. Citation Format: Serges P. Tsofack, Liliane Meunier, Anne-Marie Mes-Masson, Michel Lebel. RPS4X, a new prognostic and predictive biomarker of ovarian and breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2864. doi:10.1158/1538-7445.AM2014-2864
PCR for diagnosis of tuberculosis and pulmonary mycoses in México
Authors: Rubén Garrido, Elisa Barrera, Karla Cabada
Journal: European Respiratory Journal (2011)

Introduction: Tuberculosis (TB) and pulmonary mycoses are a public health problem in the north of Mexico. We use polymerase chain reaction (PCR) for diagnosis of TB in patients with a negative baciloscopy. This method also allows us to differentiate between other Mycobacterium and microorganisms like the case of Histoplasma capsulatum, Coccidioides immitis and Aspergillus fumigatus. 

Objective: The identification of Mycobacterium tuberculosis in patients showing clinical and radiological findings with negative baciloscopies and its association with pulmonary mycosis.

Methods: Symptomatic patients with high pulmonary TB probability were selected by a complete physical exam, clinical history, thoracic x rays and baciloscopy. In patients with a negative baciloscopy an sputum sample was taken or a Bronchial-alveolar lavage to identify the presence of Mycobacterium, Histoplasma, Coccidioides and Aspergillus by PCR. Adequate treatment was administered according to the results obtained.

Results: A total of 23 patients were analyzed. The presence of Mycobacterium tuberculosis was found in 9 cases. In 5 subjects there was of Aspergillus fumigates and in 4 cases of both. In 2 cases the presence of Mycobacterium tuberculosis, Histoplsma capsulatum, Coccidioides immitis were associated. Three samples were negative for all those microorganisms.

Conclusions: PCR's sensibility and specificity increases the diagnosis of TB and mycoses cases. It is a magnificent tool when baciloscopy is negative generating the need for use in the everyday medical practice. The use of innovative techniques for early diagnosis and treatment of frequent pulmonary disease in this region is imperative.
Letter by Al-Atassi et al Regarding Article, “Cost-Effectiveness of Percutaneous Coronary Intervention With Drug-Eluting Stents Versus Bypass Surgery for Patients With 3-Vessel or Left Main Coronary Artery Disease: Final Results From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial”
Authors: Talal Al-Atassi, Maria Lorena Rodriguez, Marc Ruel
Journal: Circulation (2015)
Genetic control of hematoietic stem cell biology and leukemogenesis
Authors: Sylvie W. Shen, Alla Dolnikov, Toby Passioura, Geoff Symonds
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2789 

This work sought to identify genes that regulate hematopoietic stem cell (HSC) expansion and differentiation. GFP containing retroviral gene transfer into human cord blood CD34+ HSC was used to examine the effects of candidate gene over-expression in tissue culture and in engrafted immunocompromised NOD/SCID mice. We demonstrated that activation of ras signaling by retroviral transduction of mutant N-ras ( N-rasm) , a gene frequently mutated in AML, induced proliferation and differentiation of myeloid progenitor cells, associated with a reduced frequency of early lymphoid and erythroid progenitors. In addition a reduced frequency of early multipotential progenitor cells, as determined by limiting dilution of LTCIC, was observed. Increased engraftment and myeloid hyperproliferation at the expense of other lineages was also seen in NOD/SCID mice injected with N-rasm -transduced CD34+ HSC. The data indicates that paracrine mechanisms are likely to be involved in these effects of activated N-ras and that two responses are induced in HSC progenitor cells, namely proliferation and differentiation. By the use of cDNA array expression profiling in the human leukemic cell lines, K562, U937 and TF-1, which vary in their response to N-ras , we demonstrated that effects of ras on proliferation and differentiation are regulated by separate genetic programs. Three genes, namely - IRF-1, a member of the interferon regulatory factor family of transcription factors, known to be associated with myeloid differentiation; the transcriptional activator of CDK inhibitor p21Waf1, not previously identified as a ras target but shown to be involved in HSC regulation; and rac 2, a member of the Rho GTPases and a critical regulator of myeloid cell function and HSC migration were found to be associated with ras -mediated differentiation and inhibition of proliferation. Experiments are currently underway examining the involvement of these genes in the regulation of ras -induced proliferation and differentiation of human HSC.
Tropomyosin isoform 5b is expressed in human erythrocytes: implications of tropomodulin-TM5 or tropomodulin-TM5b complexes in the protofilament and hexagonal organization of membrane skeletons
Authors: Lanping Amy Sung, Ke-Ming Gao, Leland J. Yee, Constance J. Temm-Grove, David M. Helfman, Jim J.-C. Lin, Majid Mehrpouryan
Journal: Blood (2000)
Human Blood Coagulation, Haemostasis and Thrombosis.
Authors: Rosemary Biggs
Journal: Annals of Internal Medicine (1973)

Book reviews together within one cover a very wide range of ideas and concepts in the investi- gation of rheumatic diseases.It will be a useful starting point for those wishing to probe restricted aspects of these diseases in more depth.However, most articles in themselves do not give sufficient informa- tion to allow critical evaluation of the results which are given.Inevitably, a book of this type rapidly becomes out of date, and one cannot avoid commenting on the delay in publication of these proceedings.Over two years elapsed between the meet- ing and publication, and although the cover flap says that the contributions have been written and revised so as to ensure the book is up to date, the extremely sparse scattering of 1975 references qualifies one's interpretation of this statement.It is useful to compare this publication with that of the 2nd World Congress in Immunology, which was held in August
Abstract 2083: WNT5a/ROR1 axis in triple-negative breast cancer progression and potential therapy
Authors: Nicholas Borcherding, Magdalene Ameka, Ryan Kolb, Qing Xie, Weizhou Zhang
Journal: Cancer Research (2014)

Abstract Triple negative breast cancer (TNBC) accounts for 15-20% of total invasive breast cancer. These tumors are more aggressive and have a worse prognosis relative to other types of breast cancer, partially due to the lack of FDA-approved targeted therapy. Utilizing the RNA-seq data for invasive breast cancer specimens deposited in the Cancer Genome Atlas (TCGA), we found that the mRNA expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) decreased in the luminal A (n=231), luminal B (n=128) and Her2+ (n=58) subtypes relative to their corresponding normal controls. In contrast, ROR1 expression increased in all the pathologic stages of TNBC samples relative to normal specimens and ROR1 expression correlates positively with progression of TNBC (n=78). ROR1 is a receptor tyrosine kinase that is involved in embryonic patterning, but lacks expression in adult tissues. We undertook a series of mechanistic studies to understand the role of ROR1 in TNBC and evaluate ROR1 as a potential target for TNBC therapy. Using complex bioinformatics analysis, we found that ROR1 expression correlates with signature genes of TNBC, cancer stem cells, and TGFβ/SMAD pathways, which, in addition to recent observation of potential crosstalk between WNT5A/ROR1 signaling with TGFβ/SMAD, prompted us to examine if this crosstalk contributes to TNBC. Indeed, we found that WNT5a promotes SMAD2/3 activation in a ROR1- and TGFβR1-dependent manner. Inhibiting ROR1 by neutralizing antibody shifted cancer stem cells of TNBC to a more luminal-type, indicating a critical of ROR1 in self-renewal of cancer stem cells. SNAI1/2, master regulators of epithelial to mesenchymal transition (EMT), are potentially involved in the WNT5a/ROR1-mediated self-renewal of cancer stem cells. In agreement with these findings, TNBC cell lines with the highest surface expression of ROR1 had a greater cancer stem cell (CSC) population (CD24-CD44high). In collaboration with Speed Biosystems LLC, we developed an anti-ROR1 immunotoxin that specifically kills ROR1-high TNBC cells but not ROR1-low breast cancer cells or normal epithelial cells. Our findings suggest a role of WNT5a/ROR1 signaling in the progression of TNBC, through its role in potentiating TGFβ/SMAD/SNAI1/2 pathway thus promoting EMT and stem-like phenotype. ROR1 represents a novel therapeutic target for TNBC, especially for late-stage diseases. Citation Format: Nicholas Borcherding, Magdalene Ameka, Ryan Kolb, Qing Xie, Weizhou Zhang. WNT5a/ROR1 axis in triple-negative breast cancer progression and potential therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2083. doi:10.1158/1538-7445.AM2014-2083
Abstract B28: In vivo ERK1/2 pathway reporting during acquired resistance to combined RAF/MEK inhibition
Authors: Ileine Sanchez, Andrew Aplin
Journal: Cancer Research (2015)

Abstract The MEK-ERK1/2 signaling pathway is constitutively activated in BRAF V600E/K melanomas. Concurrent BRAF and MEK inhibitor treatment was recently FDA-approved for BRAF V600E melanoma; however, acquired resistance to the drug combination limits durable responses. Our lab has developed a luciferase reporter system that temporally and non-invasively quantitates ERK1/2 activity in mutant BRAF melanoma xenografts. We used this reporter system to examine the temporal kinetics of ERK1/2 activity in vivo upon treatment with combined BRAF/MEK inhibition. Using a 1205Lu reporter system, all established tumors regressed to levels that were not detectable visually. After prolonged treatment with BRAF and MEK inhibitors, only 2 out of 8 mice regrew resistant tumors. In similar experiments with A375 xenografts, only 1 out 12 tumors developed resistance. In 1205Lu tumors, re-activation of the ERK1/2 pathway was evident prior to re-growth. Additionally, cell lines generated from these resistant tumors exhibited elevated levels of ERK1/2 suggesting that resistance to BRAF + MEK inhibitors involves re-activation of ERK1/2 signaling. In comparison to parental cells, resistant cells in vitro displayed reduced levels of apoptosis, increased proliferation, and increased viability in the presence of BRAF plus MEK inhibitor. Furthermore, when removed from drugs, combination-resistant cells showed increased apoptosis and reduced proliferation and viability, suggesting that the resistant lines may be addicted to the dual therapy. RPPA analysis and whole exome sequencing to elucidate mechanisms of resistance are ongoing. Citation Format: Ileine Sanchez, Andrew Aplin. In vivo ERK1/2 pathway reporting during acquired resistance to combined RAF/MEK inhibition. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B28.
Bisphosphonate-induced depletion of geranylgeranyl pyrophosphate alters processing of Ras superfamily GTPases
Authors: Andrew J. Wiemer, Larry W. Shull, Jose S. Yu, Huaxiang Tong, David F. Wiemer, Raymond J. Hohl
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4728 

Chronic myeloid leukemia (CML) is a cancer of the bone marrow affecting thousands of people annually in the United States. Treatment with imatinib mesylate has been successful in some cases of CML, however other cases of CML appear to resist this drug through over-expression of the oncogenic bcr-abl fusion protein and subsequent signaling through the Ras superfamily of GTPases. Among the drugs that are used to inhibit Ras superfamily signaling are bisphosphonates, which are used clinically for treatment of bone metastasis as well as osteoporosis. Some bisphosphonates deplete cells of isoprenoid pyrophosphates which leads to inhibition of protein isoprenylation, a modification necessary for activation of Ras superfamily proteins. A previous study from our lab on the mechanism(s) of action of a series of dialkyl isoprenoid bisphosphonates of varying chain lengths showed that a ten carbon geranyl moiety was required to specifically inhibit geranylgeranylation of Rap1a and not farnesylation of Ras. For this study, we treated human CML derived K562 cells with various geranyl isoprenoid bisphosphonates. Levels of geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP) were measured through conjugation to dansylated peptides, separation by HPLC, and fluorescence detection. These results show that treatment of K562 cells with these bisphosphonates results in depletion of intercellular GGPP levels and a simultaneous increase in FPP levels. Interestingly, the olefin stereochemistry had little effect on the potency of the geranyl-containing bisphosphonates. The active compounds are more potent and specific for geranylgeranyl pyrophosphate depletion than pamidronate or zoledronate, two bisphosphonates commonly used in the clinical. This data suggests that a new generation of non-nitrogen bisphosphonates can be developed for improved treatment of imatinib mesylate resistant CML.
A Textbook of Family Medicine
Authors: Ian R. McWhinney, Thomas Freeman
Journal: Annals of Internal Medicine (1990)

PART I: BASIC PRINCIPLES 1. The Origins of Family Madicine 2. Principles of Family Medicine 3. Illness in the Community 4. A Profile of Family Pratice 5. Philosophical and Scientific Foundations of Family Medicine 6. Illness, Suffering, and Healing 7. Doctor-Patient Communication 8. Clinical Method 9. The Enhancement of Health and the Prevention of Disease 10. The Family in Health and Disease PART II: CLINICAL PROBLEMS 11. Acute Sore Throat 12. Headache 13. Fatigue 14. Hypertension 15. Diabetes PART III: THE PRACTICE OF FAMILY MEDICINE 16. Home Care 17. Consultation and Referral 19. The Health Profession 20. The Community Service Network 21. Alternative (Complementary) Medicine 22. Practice Management PART IV: EDUCATION AND RESEARCH 23. Continuing Self-Education 24. Research in Family Practice
DEATH DUE TO ADMINISTRATION OF TYPHUS VACCINE
Authors: Harold Rifkin
Journal: Annals of Internal Medicine (1946)

Case Reports1 August 1946DEATH DUE TO ADMINISTRATION OF TYPHUS VACCINEHAROLD RIFKINHAROLD RIFKINSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-25-2-346 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA recent editorial note in The United States Army Medical Bulletin states that a number of severe reactions due to typhus vaccine have been reported to the Surgeon General's Office, but that the number is negligible in comparison to the number of doses of egg vaccine administered. We have had occasion to observe all autopsied material in a South Pacific base. Only one case has come to autopsy as a result of typhus vaccine administration. Roth2has recently reviewed 32 cases of reactions to typhus vaccine. These reactions have been divided into two types. The first group consists chiefly of...Bibliography1. Editorial Note: U. S. Army Med. Bull., May 1945, No. 88, p. 111. Google Scholar2. ROTH VE: Reactions to typhus vaccine, U. S. Army Med. Bull., 1945, No. 88, pp. 111-113. Google Scholar3. TUFT L: Clinical allergy, 1937, W. B. Saunders Co., Philadelphia. Google Scholar4. Editorial Note: U. S. Army Med. Bull., 1945, No. 88, p. 112. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication September 10, 1945.†At present with the Dept. of Medicine, Montefiore Hospital, Gun Hill Road, New York City. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe safety of egg-containinq vaccines for egg-allergic patients 1 August 1946Volume 25, Issue 2Page: 346-350KeywordsAutopsyHospital medicineSurgeonsTyphusVaccines ePublished: 1 December 2008 Issue Published: 1 August 1946 PDF downloadLoading ...
Foreign-Body Tumorigenesis: Number, Distribution, and Cell Density of Preneoplastic Clones2
Authors: Mary Jane Thomassen, Lance C. Buoen, K. Gerhard Brand
Journal: JNCI Journal of the National Cancer Institute (1975)

Double 15×22-mm plastic films (two films on top of each other) were implanted subcutaneously in CBA/H-T6 mice. After 7.5,8.5, and 9.5 months the films were removed. Each interior film (next to the abdominal wall), covered by a cell monolayer on one side only, was cut in four 7×l0-mm segments. Wiping to 5×7, 4×4, 3×3, or 2×2 mm reduced the cell areas on three of them. They were then transferred to (CBA/H × CBA/Br)F1 or (CBA/H-T6 × CBA/Br)F1 recipient mice. Tumors arising from transferred film segments were analyzed as to chromosome number and morphology, sarcoma type, degree of anaplasticity, and posttransfer latency. We used these criteria to determine whether tumors originated from the same or different clones. From this information it was estimated that preneoplastic clones were present in limited numbers and that they were either widely disseminated or spatially restricted on the implant surfaces. The extent of clone dissemination appeared to be related to preneoplastic progression.
Abstract 4050: A central role for mTORC1 in CXCR4-mediated directional migration and metastasis
Authors: Patricia Dillenburg-Pilla, Vyomesh Patel, Constantinos M. Mikelis, Carlos Rodrigo Zarate-Blades, Panomwat Amornphimoltham, Zhiyong Wang, Daniel Martin, Kantima Leelahavanichkul, Colleen L. Doçi, Robert T. Dorsam, Andrius Masedunskas, Nijiro Nohata, Roberto Weigert, Alfredo A. Molinolo, J. Silvio Gutkind
Journal: Cancer Research (2014)

Abstract Tumor cells can co-opt the promigratory activity of chemokines and their cognate G protein-coupled receptors to disseminate to regional lymph nodes and distant organs. Indeed, the migration to SDF-1 of tumor cells expressing its receptor, CXCR4, is implicated in lymphatic and organ-specific metastasis in multiple human malignancies. However, the critical role of CXCR4 in bone marrow stem cell retention has hampered the development of CXCR4 inhibitors for metastasis prevention. Therefore the study of CXCR4 downstream signaling circuitry may provide new opportunities for the treatment of many human malignancies that depend on CXCR4 for their metastatic spread. The PI3K/mTOR pathway represents a major player in normal and aberrant cell growth. Consistently, mTOR inhibitors targeting its complex 1 (mTORC1) alone or mTORC1/mTORC2 have already shown promising therapeutic responses in many tumor types. Our data show that mTOR is activated upon SDF-1 stimulation of CXCR4 on epithelial-derived cancer cells, and that the disruption of mTORC1 or mTORC2 abrogates CXCR4-mediated directional migration. To study the CXCR4/mTOR axis in vivo we developed a simple and robust model for CXCR4-mediated spontaneous metastasis. Surprisingly, disruption of mTORC1 alone was sufficient to decrease tumor cell proliferation, angiogenesis, lymphangiogenesis, and CXCR4-mediated metastasis, whereas mTORC2 impairment had no effect on tumor dissemination or growth in vivo. Taken together, our data suggest that mTORC1 blockade could inhibit the migration of CXCR4 expressing cancer cells to their secondary sites, while disrupting the establishment of a permissive tumor microenvironment thereby halting the spread of highly aggressive tumors that require CXCR4 to metastasize. Citation Format: Patricia Dillenburg-Pilla, Vyomesh Patel, Constantinos M. Mikelis, Carlos Rodrigo Zarate-Blades, Panomwat Amornphimoltham, Zhiyong Wang, Daniel Martin, Kantima Leelahavanichkul, Colleen L. Doçi, Robert T. Dorsam, Andrius Masedunskas, Nijiro Nohata , Roberto Weigert, Alfredo A. Molinolo, J. Silvio Gutkind . A central role for mTORC1 in CXCR4-mediated directional migration and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4050. doi:10.1158/1538-7445.AM2014-4050