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Fibrosis and cancer

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https://www.readbyqxmd.com/read/28213277/fluorescence-and-computed-tomography-for-assessing-the-biodistribution-of-sirna-after-intratracheal-application-in-mice
#1
Antonia Geyer, Cornelia Lorenzer, Sebastian Gehrig, Manuela Simlinger, Johannes Winkler, Haider Sami, Manfred Ogris
Pulmonary delivery of nucleic acids opens the possibility for direct treatment of lung diseases, like fibrosis, cancer, and infections. Lung retention and biodistribution of nucleic acids remain important issues for the development of suitable therapeutic approaches. Moreover, monitoring the dynamic biodistribution processes of siRNA after aerosol delivery can help in identifying bottlenecks and optimising therapeutic concepts. We investigated dynamic biodistribution events after intratracheal application of chemically stabilised siRNA labeled with near infrared emitting dye AlexaFluor750 (AF750)...
February 14, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28212619/brain-and-liver-pathology-amyloid-deposition-and-interferon-responses-among-older-hiv-positive-patients-in-the-late-haart-era
#2
Isaac H Solomon, Umberto De Girolami, Sukrutha Chettimada, Vikas Misra, Elyse J Singer, Dana Gabuzda
BACKGROUND: HIV+ patients on highly active antiretroviral therapy (HAART) with suppressed viral loads have a low incidence of HIV-associated dementia, but increased prevalence of milder forms of HIV-associated neurocognitive disorders (HAND). These milder forms of HAND are often associated with minimal histological abnormalities, and their pathophysiology is unclear. Comorbidities, altered amyloid metabolism, accelerated brain aging, and activated interferon responses are suspected to play a role in HAND pathogenesis in HAART-treated persons...
February 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#3
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28209005/serum-iron-and-haemoglobin-estimation-in-oral-submucous-fibrosis-and-iron-deficiency-anaemia-a-diagnostic-approach
#4
Divya Bhardwaj, Ajit D Dinkar, Sujata K Satoskar, Sapna Raut Desai
INTRODUCTION: Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208047/targeted-therapy-for-chronic-respiratory-disease-a-new-paradigm
#5
Peter G Gibson, Matthew J Peters, Claire E Wainwright
Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes; however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28207963/nardilysin-promotes-hepatocellular-carcinoma-through-activation-of-signal-transducer-and-activator-of-transcription-3
#6
Yosuke Kasai, Kan Toriguchi, Etsuro Hatano, Kiyoto Nishi, Mikiko Ohno, Tomoaki Yoh, Keita Fukuyama, Takahiro Nishio, Masayuki Okuno, Keiko Iwaisako, Satoru Seo, Kojiro Taura, Masato Kurokawa, Makoto Kunichika, Shinji Uemoto, Eiichiro Nishi
Nardilysin (NRDC) is a metalloendopeptidase of the M16 family. We previously showed that NRDC activates inflammatory cytokine signaling, including interleukin-6-signal transducer and activator of transcription 3 (STAT3) signaling. NRDC has been implicated in the promotion of breast, gastric, and esophageal cancer, as well as the development of liver fibrosis. In this study, we investigated the role of NRDC in the promotion of hepatocellular carcinoma (HCC), both clinically and experimentally. We found that NRDC expression was up-regulated 3-fold in HCC tissue compared to the adjacent non-tumor liver tissue, which was confirmed by immunohistochemistry and western blotting...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28207528/idiopathic-retroperitoneal-fibrosis-causing-unilateral-ureteral-and-sigmoid-colon-obstruction-a-case-report
#7
Ting Yan, Yujuan Wang, Zhijun Liu, Xiaolei Zhang, Qian Wu, Mingrong Xi
OBJECTIVE: The present report aimed to present a unique case of idiopathic retroperitoneal fibrosis (RPF) presenting features of unilateral ureteral and sigmoid colon obstruction. RPF is a rare disorder with unclear etiology. CASE REPORT: A 43-year-old female had a 10-day history of lower right abdominal and lumbar pain. Gynecological examination, ultrasound, and computed tomography (CT) were all suggestive of right ovarian tumor. An enhanced CT showed right-sided hydronephrosis...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28199848/discoidin-domain-receptor-1-mediates-myosin-dependent-collagen-contraction
#8
Nuno M Coelho, Pamma D Arora, Sander van Putten, Stellar Boo, Petar Petrovic, Alyna Xue Lin, Boris Hinz, Christopher A McCulloch
Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced >30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28195363/liver-fibrosis-scores-predict-liver-disease-mortality-in-the-united-states-population
#9
Aynur Unalp-Arida, Constance E Ruhl
BACKGROUND AND RATIONALE: Fatty liver disease is common in the United States and worldwide due to changing lifestyles and can progress to fibrosis and cirrhosis contributing to premature death. We examined whether liver fibrosis scores were associated with increased overall and disease-specific mortality in a U.S. population-based prospective survey with up to 23 years of linked-mortality data. METHODS: Data were analyzed from 14,841 viral hepatitis negative adult participants in the third National Health and Nutrition Examination Survey, 1988-1994...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194432/bet-inhibitors-block-pancreatic-stellate-cell-collagen-i-production-and-attenuate-fibrosis-in-vivo
#10
Krishan Kumar, Brian T DeCant, Paul J Grippo, Rosa F Hwang, David J Bentrem, Kazumi Ebine, Hidayatullah G Munshi
The fibrotic reaction, which can account for over 70%-80% of the tumor mass, is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of collagen I production and fibrosis in vivo. In this report, we show that members of the bromodomain and extraterminal (BET) family of proteins are expressed in primary PSCs isolated from human PDAC tumors, with BRD4 positively regulating, and BRD2 and BRD3 negatively regulating, collagen I expression in primary cancer-associated PSCs...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28192371/somatic-mutations-in-telomerase-promoter-counterbalance-germline-loss-of-function-mutations
#11
Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A Newton, Cindy Barba, Nicolai S C van Oers, Richard C Wang, Christine Kim Garcia
Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function...
February 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28190633/novel-5-arylthio-5h-chromenopyridines-as-a-new-class-of-anti-fibrotic-agents
#12
Renukadevi Patil, Anandita Ghosh, Phoebus Sun Cao, Roger D Sommer, Kyle A Grice, Gulam Waris, Shivaputra Patil
Liver fibrosis is a critical wound healing response to chronic liver injury such as hepatitis C virus (HCV) infection. If persistent, liver fibrosis can lead to cirrhosis and hepatocellular carcinoma (HCC). The development of new therapies for preventing liver fibrosis and its progression to cancer associated with HCV infection remains a critical challenge. Identification of novel anti-fibrotic compounds will provide opportunities for innovative therapeutic intervention of HCV-mediated liver fibrosis. We designed and synthesized a focused set of 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28189065/the-pulmonary-fibrosis-associated-muc5b-promoter-polymorphism-is-prognostic-of-the-overall-survival-in-patients-with-non-small-cell-lung-cancer-nsclc-receiving-definitive-radiotherapy
#13
Ju Yang, Ting Xu, Daniel R Gomez, Melenda Jeter, Lawrence B Levy, Yipeng Song, Stephen Hahn, Zhongxing Liao, Xianglin Yuan
BACKGROUND: MUC5B is glycoprotein secreted by bronchial glands. A promoter variant in MUC5B, rs35705950, was previously found to be strongly associated with the incidence of idiopathic pulmonary fibrosis (IPF) and also the overall survival (OS) of such patients. Patients with IPF and patients with radiation pneumonitis (RP) have the similar pathologic process and clinical symptoms. However, the role of rs35705950 in patients receiving thoracic radiotherapy remains unclear. PATIENTS AND METHODS: In total, 664 patients with NSCLC receiving definitive radiotherapy (total dose ≥60 Gy) were included in our study...
February 8, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28188823/hepatic-stellate-cell-interferes-with-nk-cell-regulation-of-fibrogenesis-via-curcumin-induced-senescence-of-hepatic-stellate-cell
#14
Huanhuan Jin, Yan Jia, Zhen Yao, Jingjing Huang, Meng Hao, Shunyu Yao, Naqi Lian, Feng Zhang, Chenxi Zhang, Xingran Chen, Mianli Bian, Jiangjuan Shao, Li Wu, Anping Chen, Shizhong Zheng
Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis...
February 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28186091/topical-tacrolimus-for-the-treatment-of-secondary-lymphedema
#15
Jason C Gardenier, Raghu P Kataru, Geoffrey E Hespe, Ira L Savetsky, Jeremy S Torrisi, Gabriela D García Nores, Dawit K Jowhar, Matthew D Nitti, Ryan C Schofield, Dean C Carlow, Babak J Mehrara
Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28184272/treatment-of-radiation-induced-cystitis-and-vulvodynia-via-a-ganglion-impar-block-using-a-lateral-approach-under-computed-tomography-guidance-a-case-report
#16
Jeong-Eun Lee, Kyung-Hwa Kwak, Seong Wook Hong, Hoon Jung, Seung-Yeon Chung, Jun-Mo Park
Adjuvant radiation therapy (RT) after colorectal cancer surgery can prevent local recurrence, but has several side effects. Precise injection of drugs into the affected areas is complicated by radiation-induced fibrosis of soft or connective tissue. A 48-year-old woman experienced severe intractable perineal pain, dysuria, urinary urgency, and frequent urination after rectal cancer surgery and adjuvant RT, and was diagnosed with radiation-induced cystitis and vulvodynia. Her symptoms persisted despite two fluoroscopy-guided ganglion impar blocks...
February 2017: Korean Journal of Anesthesiology
https://www.readbyqxmd.com/read/28177155/a-chaperone-complex-formed-by-hsp47-fkbp65-and-bip-modulates-telopeptide-lysyl-hydroxylation-of-type-i-procollagen
#17
Ivan Duran, Jorge H Martin, Mary Ann Weis, Pavel Krejci, Peter Konik, Bing Li, Yasemin Alanay, Caressa Lietman, Brendan Lee, David Eyre, Daniel H Cohn, Deborah Krakow
Lysine hydroxylation of type I collagen telopeptides varies from tissue to tissue and these distinct hydroxylation patterns modulate collagen crosslinking to generate a unique extracellular matrix. Abnormalities in these patterns contribute to pathologies that include osteogenesis imperfecta (OI), fibrosis and cancer. Telopeptide procollagen modifications are carried out by lysyl hydroxylase 2 (LH2), however, little is known regarding how this enzyme regulates hydroxylation patterns. We identified an ER complex of resident chaperones that includes HSP47, FKBP65 and BiP regulating the activity of LH2...
February 8, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28168165/innate-immune-pathways-associated-with-lung-radioprotection-by-soy-isoflavones
#18
Lisa M Abernathy, Matthew D Fountain, Michael C Joiner, Gilda G Hillman
INTRODUCTION: Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radioprotection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury. METHODS: BALB/c mice (5-6 weeks old) received a single 10 Gy dose of thoracic irradiation and soy isoflavones were orally administrated daily before and after radiation at 1 mg/day...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28165859/exercise-induced-hypoxemia-in-juvenile-thyroid-carcinoma-with-lung-metastases
#19
Florian J Segerer, Johannes Biko, Christoph Reiners, Clemens Wirth, Helge Hebestreit
PURPOSE: Exercise-induced arterial hypoxemia (EIAH) has been reported in patients with juvenile thyroid cancer treated with radioiodine for lung metastases. This retrospective study tested the hypothesis that EIAH is due to ventilation-perfusion-mismatch in this rare pulmonary condition. METHOD: 50 patients (age 13 -23 years) treated for juvenile thyroid carcinoma and lung metastasis with 131I and 24 controls with thyroid cancer but without lung metastases and prior 131I-treatment were assessed in a state of acute hypothyroidism by computed tomography of the lungs, pulmonary function testing, cardiopulmonary exercise test with measurements of gas exchange, oxygen saturation, alveolar-arterial difference in pO2 (p(A-a)O2) and pCO2 (p(ET-a)CO2)...
February 6, 2017: Pediatric Exercise Science
https://www.readbyqxmd.com/read/28165027/potential-role-of-corneal-epithelial-cell-derived-exosomes-in-corneal-wound-healing-and-neovascularization
#20
Kyu-Yeon Han, Jennifer A Tran, Jin-Hong Chang, Dimitri T Azar, James D Zieske
Specific factors from the corneal epithelium underlying the stimulation of stromal fibrosis and myofibroblast formation in corneal wound healing have not been fully elucidated. Given that exosomes are known to transfer bioactive molecules among cells and play crucial roles in wound healing, angiogenesis, and cancer, we hypothesized that corneal epithelial cell-derived exosomes may gain access to the underlying stromal fibroblasts upon disruption of the epithelial basement membrane and that they induce signaling events essential for corneal wound healing...
February 6, 2017: Scientific Reports
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