Browne A.S.,Emory University |
Yu J.,Emory University |
Yu J.,Medical Center Boulevard |
Huang R.-P.,Emory University |
And 7 more authors.
Fertility and Sterility | Year: 2012
Objective: To evaluate neurotrophin (NT) expression in the endometrium of women with and without endometriosis. Design: Prospective, cross-sectional, translational study. Setting: Academic hospital. Patient(s): Thirty-three reproductive-age women undergoing laparoscopy for infertility, pelvic pain, intramural fibroids, or tubal ligation. Intervention(s): Endometrial biopsies, protein microarrays, reverse transcriptase-polymerase chain reaction, ELISAs, and Western blotting. Main Outcome Measure(s): Neurotrophin proteins and mRNAs in eutopic endometrial biopsies. Result(s): Among seven neurotrophic proteins detected on the antibody microarrays, reverse transcriptase-polymerase chain reaction analysis confirmed nerve growth factor, NT-4/5, and brain-derived neurotrophic factor mRNAs in endometrial tissue. Quantitative ELISAs revealed that NT-4/5 (806 ± 701 vs. 256 ± 190 pg/100 mg protein) and brain-derived neurotrophic factor (121 ± 97 vs. 14 ± 11 ng/100 mg protein) concentrations were significantly higher in women with endometriosis. Nerve growth factor (100 ± 74 vs. 93 ± 83 pg/100 mg protein) levels did not differ between cases and controls. Conclusion(s): Neurotrophins are synthesized in situ within the endometrium. NT-4/5 and brain-derived neurotrophic factor proteins were more concentrated in biopsies from endometriosis cases than controls, whereas nerve growth factor levels were similar. We hypothesize that the local production of NTs induces sensory innervation of endometrium of women with endometriosis. These NTs represent novel targets for the diagnosis and treatment of endometriosis. © 2012 by American Society for Reproductive Medicine.
Jones V.S.,Raybiotech, Inc. |
Huang R.-Y.,Raybiotech, Inc. |
Chen L.-P.,Guangzhou University |
Chen Z.-S.,St. Johns University |
And 3 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2016
The development of oncoprotein-targeted anticancer drugs is an invaluable weapon in the war against cancer. However, cancers do not give up without a fight. They may develop multiple mechanisms of drug resistance, including apoptosis inhibition, drug expulsion, and increased proliferation that reduce the effectiveness of the drug. The collective work of researchers has highlighted the role of cytokines in the mechanisms of cancer drug resistance, as well as in cancer cell progression. Furthermore, recent studies have described how specific cytokines secreted by cancer stromal cells confer resistance to chemotherapeutic treatments. In order to gain a better understanding of mechanism of cancer drug resistance and a prediction of treatment outcome, it is imperative that correlations are established between global cytokine profiles and cancer drug resistance. Here we discuss the recent discoveries in this field of research and discuss their implications for the future development of effective anti-cancer medicines. © 2016.
Shi Z.,Raybiotech, Inc. |
Shi Z.,South China Biochip Research Center |
Yang W.-M.,Wuxi Maternal and Child Health Hospital |
Chen L.-P.,Guangzhou University |
And 8 more authors.
Breast Cancer Research and Treatment | Year: 2012
Drug resistance remains a major hurdle to successful cancer treatment. Many mechanisms such as overexpression of multidrug-resistance related proteins, increased drug metabolism, decreased apoptosis, and impairment of signal transduction pathway can contribute multidrug resistance (MDR). Recent studies strongly suggest a close link between cytokines and drug resistance. To identify new targets involved in drug resistance, we established a multidrug-resistant human breast cancer cell line MCF-7/R and examined the cytokine profile using cytokine antibody array technology. Among 120 cytokines/ chemokines screened, IL-6, IL-8, and 13 other proteins were found to be markedly increased in drug-resistant MCF-7/R cell line as compared to sensitive MCF-7/S cell line, while 7 proteins were specifically reduced in drugresistant MCF-7/R cells. Neutralizing antibodies against IL-6 and IL-8 partially reversed the drug resistance of MCF-7/R to paclitaxel and doxorubicin, while a neutralizing antibody against MCP-1 had no significant effect. Inhibition of endogenous IL-6 or IL-8 by siRNA technology significantly enhanced drug sensitivity of MCF-7/R cells. Furthermore, overexpression of IL-6 or IL-8 expression by transfection increased the ADM resistance in MCF-7/S cells. Our data suggest that increased expression levels of IL-6 and IL-8 may contribute to MDR in human breast cancer cells. © Springer Science+Business Media, LLC. 2012.
Burgess R.,Raybiotech, Inc. |
Burgess R.,University of Texas at Dallas |
Huang R.-P.,Raybiotech, Inc. |
Huang R.-P.,South China Biochip Research Center
Advances in Clinical Chemistry | Year: 2015
Cancer is a complex disease involving hundreds of pathways and numerous levels of disease progression. In addition, there is a growing body of evidence that the origins and growth rates of specific types of cancer may involve "cancer stem cells," which are defined as "cells within a tumor that possess the capacity to self-renew and to cause the development of heterogeneous lineages of cancer cells that comprise the tumor. 1 1American Association of Cancer Research consensus panel definition." Many types of cancer are now thought to harbor cancer stem cells. These cells themselves are thought to be unique in comparison to other cells types present within the tumor and to exhibit characteristics that allow for the promotion of tumorigenesis and in some cases metastasis. In addition, it is speculated that each type of cancer stem cell exhibits a unique set of molecular and biochemical markers. These markers, alone or in combination, may act as a signature for defining not only the type of cancer but also the progressive state. These biomarkers may also double as signaling entities which act autonomously or upon neighboring cancer stem cells or other cells within the local microenvironment to promote tumorigenesis. This review describes the heterogeneic properties of cancer stem cells and outlines the identification and application of biomarkers and signaling molecules defining these cells as they relate to different forms of cancer. Other examples of biomarkers and signaling molecules expressed by neighboring cells in the local tumor microenvironment are also discussed. In addition, biochemical signatures for cancer stem cell autocrine/paracrine signaling, local site recruitment, tumorigenic potential, and conversion to a stem-like phenotype are described. © 2016 Elsevier Inc.
Jiang W.,Raybiotech, Inc. |
Huang R.,Raybiotech, Inc. |
Duan C.,Sun Yat Sen University |
Fu L.,Sun Yat Sen University |
And 7 more authors.
PLoS ONE | Year: 2013
Background:Protein and antibody arrays have emerged as a promising technology to study protein expression and protein function in a high-throughput manner. These arrays also represent a new opportunity to profile protein expression levels in cancer patients' samples and to identify useful biosignatures for clinical diagnosis, disease classification, prediction, drug development and patient care. We applied antibody arrays to discover a panel of proteins which may serve as biomarkers to distinguish between patients with ovarian cancer and normal controls.Methodology/Principal Findings:Using a case-control study design of 34 ovarian cancer patients and 53 age-matched healthy controls, we profiled the expression levels of 174 proteins using antibody array technology and determined the CA125 level using ELISA. The expression levels of those proteins were analyzed using 3 discriminant methods, including artificial neural network, classification tree and split-point score analysis. A panel of 5 serum protein markers (MSP-alpha, TIMP-4, PDGF-R alpha, and OPG and CA125) was identified, which could effectively detect ovarian cancer with high specificity (95%) and high sensitivity (100%), with AUC =0.98, while CA125 alone had an AUC of 0.87.Conclusions/Significance:Our pilot study has shown the promising set of 5 serum markers for ovarian cancer detection. © 2013 Jiang et al.