Predictive ability of DWI/ADC and DCE-MRI kinetic parameters in differentiating benign from malignant breast lesions and in building a prediction model.
Authors: Allarakha A, Gao Y, Jiang H, Wang GL, Wang PJ Abstract OBJECTIVES: To analyze DWI/ADC and DCE-MRI kinetic parameters on breast MRI between benign and malignant lesions, to obtain independent predictors of malignancy, and to build a possible future predictive model. METHODS: 121 patients (151 breast lesions) were evaluated by 3.0T breast MRI. Based on their post-operative histopathology, we divided them into two groups, benign and malignant. We processed their DCE-MRI images to obtain size of lesions and several kinetic parameters like Time Intensity Curve (TIC), Time To Peak (TTP), Area Under Curve (AU...
Source: Discovery Medicine - May 17, 2019 Category: Research Tags: Discov Med Source Type: research

Protective effects on age-related macular degeneration by activated autophagy induced by amyloid- β in retinal pigment epithelial cells.
This study was performed to detect the activation of autophagy in retinal pigment epithelial (RPE) cells treated with Aβ, aiming to investigate the potential protective mechanism of RPE cells against Aβ stress. Human ARPE-19 cells were treated with soluble Aβ1-42 oligomer. Transmission electron microscopy was used to assess the formation of autophagic compartments; immunofluorescence was used to detect the subcellular localization of LC3; and western blot was used to detect the conversion of LC3-I to LC3-II and the expression of p62. Activated autophagy in Aβ-treated ARPE-19 cells was detected by three ...
Source: Discovery Medicine - May 17, 2019 Category: Research Tags: Discov Med Source Type: research

The virology of breast cancer: viruses as the potential causative agents of breast tumorigenesis.
Authors: Lehrer S, Rheinstein PH Abstract Breast cancer is the most common form of cancer in women. The cause of sporadic cases is usually difficult to ascertain. Viruses that might be related to breast cancer are human papillomaviruses and herpes viruses. Mouse mammary tumor virus (MMTV) has also been a suspect. MMTV is a milk-transmitted beta retrovirus, a form of single-stranded positive-sense RNA virus that inserts a copy of its genome into the DNA of a host cell, thus altering the cell's genome. MMTV DNA sequences have been found in 36% of human breast tumor samples and 24% of non-cancerous breast tissue. The ...
Source: Discovery Medicine - May 17, 2019 Category: Research Tags: Discov Med Source Type: research

Molecular diagnostics and targeted therapies in non-small cell lung cancer (NSCLC): an update.
In this report, we discuss some of these updates. PMID: 31095926 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - May 17, 2019 Category: Research Tags: Discov Med Source Type: research

Stationary phase persister/biofilm microcolony of Borrelia burgdorferi causes more severe disease in a mouse model of Lyme arthritis: implications for understanding persistence, Post-treatment Lyme Disease Syndrome (PTLDS), and treatment failure.
Authors: Feng J, Li T, Yee R, Yuan Y, Bai C, Cai M, Shi W, Embers M, Brayton C, Saeki H, Gabrielson K, Zhang Y Abstract Although most patients with Lyme disease can be cured with a 2-4 week antibiotic therapy, about 10-20% of patients continue to suffer prolonged persistent symptoms, a condition called post-treatment Lyme disease syndrome (PTLDS). The cause for PTLDS is unclear and hotly debated. Borrelia burgdorferi develops morphological variants under stress conditions but their significance is not clear. Here we isolated the biofilm-like microcolony (MC) and planktonic (spirochetal form and round body) (SP) var...
Source: Discovery Medicine - April 6, 2019 Category: Research Tags: Discov Med Source Type: research

Genetic association and interaction of PD1 and TIM3 polymorphisms in susceptibility of chronic hepatitis B virus infection and hepatocarcinogenesis.
Authors: Li F, Fan X, Wang X, Deng H, Zhang X, Zhang K, Li N, Han Q, Lv Y, Liu Z Abstract The PD1 (rs2227982, rs41386349, rs6710479, rs7421861, and rs7565639) and TIM3 (rs11134551, rs11742259, rs246871, rs25855, and rs31223) polymorphisms were examined in 362 patients with chronic hepatitis B virus (HBV) infection, 91 HBV infection resolvers, and 158 healthy controls. Univariate logistic regression was carried out by SNPstats to detect the associations. Multifactor dimensionality reduction (MDR) analysis was performed to explore interactions between PD1 and TIM3 polymorphisms. Associations of polymorphisms with cli...
Source: Discovery Medicine - April 3, 2019 Category: Research Tags: Discov Med Source Type: research

Modulation of cancer immunotherapy efficacy by gut microbiota.
Authors: Huo S, Liu L, Liu J, Li Q, Wang J Abstract The microbial community is present abundantly in mucosal organs including the intestine, the oral cavity, and the vagina, and is referred to as the microbiota. The microbiota is composed of commensal bacteria and other microorganisms. Intestinal colonization by commensal microorganisms is essential for host physiological functions from the maintenance of barrier homeostasis locally to the regulation of metabolism, hematopoiesis, inflammation, immune development, and other functions systemically. Evidence is growing that the gut microbiota can modulate the host res...
Source: Discovery Medicine - April 3, 2019 Category: Research Tags: Discov Med Source Type: research

Hypertriglyceridemia-induced acute pancreatitis: progress on disease mechanisms and treatment modalities.
Authors: Guo YY, Li HX, Zhang Y, He WH Abstract Acute pancreatitis (AP) is a common and destructive inflammatory condition of the pancreas. Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has become the second major cause of AP. Although the association between HTG and AP is well established, HTG as a risk factor of AP in the general population is not well identified. In this review, we summarize recent progress in our understanding of the pathogenesis of HTG-AP and clinical management of this disease. The mechanism responsible for HTG-AP is related to high-level free fatty acid (FFA), microcirculatory dis...
Source: Discovery Medicine - April 3, 2019 Category: Research Tags: Discov Med Source Type: research

How thyroid hormone works depends upon cell type, receptor type, and hormone analogue: implications in cancer growth.
Authors: Davis PJ, Lin HY, Hercbergs AA, Keating KA, Mousa SA Abstract The classical molecular mechanism of thyroid hormone involves the intranuclear interaction of 3,5,3'-triiodo-L-thyronine (T3) with thyroid hormone-specific nuclear proteins and consequent specific gene expression. This mechanism prevails in normal cells. What we emphasize here is that how thyroid hormone acts depends upon the types of cell or cell-like structure, e.g., platelet, under consideration, and that cancer cells, dividing endothelial cells, phagocytes, and platelets respond to the liganding of L-thyroxine (T4) by plasma membrane integri...
Source: Discovery Medicine - April 3, 2019 Category: Research Tags: Discov Med Source Type: research

Epigallocatechin-3-gallate suppresses pain-related and proinflammatory mediators in the subacromial bursa in rotator cuff tendinopathy.
In this study, we first examined the histological features of subacromial bursa from patients with rotator cuff tendinopathy who had symptoms of pain, and investigated the expression of pain mediators, proinflammatory cytokines, metalloproteinases, growth factors, and alarmins in diseased tendon and bursa tissue by real-time PCR, western blot, and/or immunohistochemistry/immunofluorescence staining. Then we investigated whether epigallocatechin-3-gallate (EGCG) could reduce the expression of pain mediators and proinflammatory cytokines in human primary bursa cells and explored the paracrine effect of these EGCG-treated bur...
Source: Discovery Medicine - March 4, 2019 Category: Research Tags: Discov Med Source Type: research

Synovial fluid alpha-melanocyte-stimulating hormone may act as a protective biomarker for primary knee osteoarthritis.
CONCLUSIONS: Reduced SF α-MSH expression may be a characteristic of OA patients. Attenuated α-MSH level in SF may serve as a potential biomarker for disease severity of knee OA, and further studies are needed to identify its potential application for monitoring the course of the disease and the efficacy of therapies in OA patients. PMID: 30721648 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - February 7, 2019 Category: Research Tags: Discov Med Source Type: research

Targeting cyclin-dependent kinases in gastrointestinal cancer therapy.
Authors: Zhang J, Su G, Lin Y, Meng W, Lai JKL, Qiao L, Li X, Xie X Abstract Cyclin-dependent kinases (CDKs) play an important role in cell-cycle progression. CDKs are positively modulated by regulatory mitotic cyclins and negatively controlled by endogenous CDK inhibitors (CDKIs) cyclically as cells progress through different cell cycles of transitions. When activated by cyclins, cyclin-CDK complexes were able to facilitate the transition of cell cycle from one phase to the next, e.g., from G1 to S or from G2 to M. DNA damages may cause inhibition of CDKs leading to cell-cycle arrest, while unrepairable DNA damage...
Source: Discovery Medicine - February 7, 2019 Category: Research Tags: Discov Med Source Type: research

Transspinal delivery of drugs by transdermal patch back-of-neck for Alzheimer's disease: a new route of administration.
Authors: Lehrer S, Rheinstein PH Abstract NSAIDs may prevent Alzheimer's disease (AD) but have failed as a treatment, possibly because only 1-2% of an oral NSAID dose reaches the brain. This minuscule dose is enough to have a preventative effect on Alzheimer's disease but not to treat it. We propose a new route of administration for drugs to treat AD: transspinal delivery by transdermal patch over the back-of-neck/cervical spine. The drug would diffuse from the patch through the intervertebral spaces, penetrate the dura, enter the CSF, and reach the brain. For example, diclofenac from a transdermal patch over the b...
Source: Discovery Medicine - February 7, 2019 Category: Research Tags: Discov Med Source Type: research

Advances in the techniques and methodologies of cancer gene therapy.
Authors: Sun W, Shi Q, Zhang H, Yang K, Ke Y, Wang Y, Qiao L Abstract Cancer is the second leading cause of mortality worldwide after cardiovascular diseases, predominantly due to the lack of early symptoms and early diagnosis, and high relapse rate after radical surgery and conventional therapies. Therefore, novel approaches such as gene therapy have raised hope to significantly improve the survival rate of patients with cancers. This review aims to provide up-to-date information concerning gene therapy including improved vectors, suicide genes, cancer suppressor genes, anti-tumor angiogenesis, gene silencing, onc...
Source: Discovery Medicine - February 7, 2019 Category: Research Tags: Discov Med Source Type: research

Prediction and prognosis of biologically aggressive breast cancers by the combination of DWI/DCE-MRI and immunohistochemical tumor markers.
Authors: Allarakha A, Gao Y, Jiang H, Wang PJ Abstract Breast cancer (BC) research has been evolving tremendously on all fronts, whether it being for imaging, pathology, oncology, pharmacology, or genetics. Regarding medical imaging, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) are now both universally recognized and widely used modalities in multiparametric MRI (mp-MRI) to diagnose and stage BC, to assess post-chemotherapy response, and to differentiate between scar tissue and recurrent tumor. Meanwhile, pathologists have provided evidence of BC being heterogeneous and having severa...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

Application of high frequency ultrasound in dermatology.
Authors: Bhatta AK, Keyal U, Liu Y Abstract High frequency ultrasound (HFUS) refers to the ultrasound probe frequency of more than 10 MHz. HFUS has shorter wavelengths, is absorbed more easily, and is therefore not as penetrating. This explains its use for superficial structures and hence its increasing application in the field of dermatology. HFUS is a simple, reliable, and noninvasive technique that is being used along with the physical examination for the assessment, diagnosis, and management of many dermatologic conditions. In addition, it can also be used for the evaluation of normal skin structure. In the pre...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

Two novel heterozygous mutations in the CYP17A1 gene in a Chinese patient with 17 α-hydroxylase 17,20-lyase deficiency.
In conclusion, we discovered two novel heterozygous CYP17A1 mutations Ile381Thr (c.1142T>C) and Ser168del (c.503_505delCCT) in a Chinese patient with 17-OHD. PMID: 30695673 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

Modulation of aldosterone levels by aldosterone synthase promoter polymorphism and association with eGFR decline in patients with chronic kidney disease.
Authors: Qian J, Zhong J, Yan M, Shi H, Hao C, Gu Y, Lai L Abstract To determine whether -344T/C CYP11B2 promoter polymorphism affects serum aldosterone levels and whether this polymorphism is an indicator of eGFR decline in patients with chronic kidney disease. -344 C/T CYP11B2 gene polymorphism analysis was performed in 96 adults with stages 1-5 CKD by using polymerase chain reaction. Serum aldosterone levels were measured at baseline and at 1.5-year follow-up. The primary outcome was the annual eGFR decline and the secondary outcome was the occurrence of cardio-cerebrovascular events. The genotype distribution o...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

Bringing wearable devices into oncology practice: fitting smart technology in the clinic.
Authors: Menta AK, Subbiah IM, Subbiah V Abstract The new way of acquiring data is at its inception in our ever-changing world. There are now a plethora of opportunities to acquire data; from the data, trends can be calculated, validated, and utilized to solve current problems. Wearable technology has been widely adopted in our society, acquiring roles in many aspects of daily life. With each iteration of a wearable platform, devices are further miniaturized with greater integration of sensors that continually collect and store vast amounts of data. The commercialization of these wearable technologies brings to lig...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

MicroRNAs in peritoneal fibrosis: a systematic review.
Authors: Yanai K, Ishii H, Aomatsu A, Ishibashi K, Morishita Y Abstract Peritoneal fibrosis is a crucial complication of long-term peritoneal dialysis (PD). Peritoneal fibrosis contributes to the development of peritoneal membrane failure, which leads to withdrawal from PD. No specific biomarkers or therapies have yet been established for peritoneal fibrosis. MicroRNAs (miRNAs) are small noncoding RNAs that can inhibit the translation of target messenger RNAs. Previous studies have shown that miRNAs play pivotal roles in the development of peritoneal fibrosis, indicating that they may represent potential biomarkers...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

MiR-212-5p exerts a protective effect in chronic obstructive pulmonary disease.
In this study, the expression level of miR-212-5p and miR-223 decreased significantly in COPD patients compared to healthy controls. In vitro experiments showed that cigarette smoke extract (CSE) induced NCI-H292 cell apoptosis and inhibited cell proliferation. Inflammation and COPD related genes were also upregulated by CSE, while miR-212-5p inhibited the overexpression of these genes. Furthermore, miR-212-5p promoted cell proliferation and inhibited IGFBP3 expression which was induced by CSE. The expression of p-Akt was also inhibited by CSE, while miR-212-5p significantly promoted the phosphorylation of Akt. In summary,...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

Metabolic syndrome relates to high risk in hepatocellular carcinoma: a meta-analysis.
Authors: Li Y, Shi J, Liu X, Deng Q, Huang Y, Yang Z Abstract Metabolic syndrome (MetS) has been linked to the development of cancer. The relationship between MetS and hepatocellular carcinoma (HCC) remains controversial. Studies up to September 2017 of MetS and HCC were systematically identified and meta-analyzed. Ten studies (nine cohorts and one case-control) were included in this meta-analysis. It was found that MetS patients are significantly more likely to develop HCC (RR = 1.60, 95%CI = 1.12-2.28, P = 0.01). Additionally, when only cohort studies were included, MetS is a potential risk factor for HCC occurre...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

Clinical utility of the cold pressor test: evaluation of pain patients, treatment of opioid-induced hyperalgesia and fibromyalgia with low dose naltrexone.
CONCLUSIONS: CPT is an objective complement to the subjective FACES pain scale. It gives an objective measure of changes in pain sensitivity accompanying administration of LDN. Limitations of a case series report are noted. SIGNIFICANCE: CPT is shown to be an objective test of pain tolerance with clinical applications: evaluation of OIH, evaluation of fibromyalgia, reversal of OIH, protracted withdrawal with LDN, and amelioration of fibromyalgia with LDN. PMID: 30695679 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

The wet bridge transfer system: a novel tool to assess exogenous surfactant as a vehicle for intrapulmonary drug delivery.
The objective was to develop and test an in vitro system to rapidly assess surfactant based therapies prior to animal studies. The Wet Bridge Transfer System consisted of two connected wells in which drugs were instilled into a delivery well and function was tested in a remote well which mimicked the remote areas of the lung where drug activity would be required. The system was used to assess surfactant as a carrier for antibiotics (Gentamicin, Ciprofloxacin, and Colistin) by measuring their ability to kill Pseudomonas aeruginosa bacteria in the remote well. Anti-inflammatory agents (Budesonide and a host defense peptide, ...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

New developments in molecular targeted therapy of ovarian cancer.
Authors: Guan LY, Lu Y Abstract Ovarian cancer remains the most mortal gynecological cancer in the world. The standard treatment for ovarian cancer remains cytoreductive surgery followed by platinum-based chemotherapy. Although most patients are platinum-sensitive initially, the majority of them will develop platinum resistance after multiple relapses, and platinum-resistant patients have a low response to the second-line chemotherapy. Besides, ovarian cancer is considered to be a highly heterogeneous disease at the molecular level. Molecular targeted therapy is expected to be a more effective and less toxic therap...
Source: Discovery Medicine - January 31, 2019 Category: Research Tags: Discov Med Source Type: research

Characteristics of hepatitis B core antibody level in the natural history of chronic hepatitis B.
Authors: Wang J, Yan X, Chen Y, Liu Y, Wang L, Jia B, Wang G, Xiong Y, Song P, Wu W, Xia J, Lu S, Zhang Z, Huang R, Wu C Abstract OBJECTIVE: We aimed to analyze serum antibody to hepatitis B core antigen (anti-HBc) level during different immunological phases in the natural history of patients with chronic hepatitis B (CHB). METHODS: Serum anti-HBc levels in the immune tolerant (IT), immune clearance (IC), low replicative (LR), and HBeAg negative hepatitis (ENH) phases from 634 treatment-naïve CHB patients were measured and compared between phases and with other serum markers. RESULTS: Median serum anti...
Source: Discovery Medicine - December 27, 2018 Category: Research Tags: Discov Med Source Type: research

BDNF as a biomarker in diagnosis and evaluation of treatment for schizophrenia and depression.
This article presents a review of BDNF as a neurobiological marker for schizophrenia and depression and for the efficacy of rTMS treatments of these mental diseases. PMID: 30586536 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - December 27, 2018 Category: Research Tags: Discov Med Source Type: research

Classic challenges and emerging approaches to medication therapy in older adults.
Authors: Alagiakrishnan K, Mah D, Padwal R Abstract Prescribing medications safely and effectively in older adults is a complex process. This review discusses challenges with medication prescribing in older adults and outlines a holistic approach to medication management in older adults. Well-known challenges including the alterations in pharmacokinetics and pharmacodynamics that often occur with aging are discussed. Other classic concerns including polypharmacy, potentially inappropriate medication use, prescribing cascades, suboptimal prescribing, paradoxical harm and unintended consequences of medications, and d...
Source: Discovery Medicine - December 27, 2018 Category: Research Tags: Discov Med Source Type: research

The SORCS3 gene is mutated in brothers with infantile spasms and intellectual disability.
Authors: Alfadhel M, Albahkali S, Almuaysib A, Alrfaei BM Abstract The sortilin-related VPS10 domain-containing receptor 3 (SORCS3) is a type-I receptor transmembrane protein and a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined to have a vacuolar protein sorting 10 domain at the N-terminus. They play important roles as a sorting agency within the cells and transport a variety of intracellular proteins between the Golgi apparatus, endosome, lysosome, secretory granules, and plasma membrane. They are also involved in signal transduction. Clinically, they have been impli...
Source: Discovery Medicine - December 27, 2018 Category: Research Tags: Discov Med Source Type: research

The efficacy and safety of nivolumab, pembrolizumab, and arezolizumab in treatment of advanced non-small cell lung cancer.
Authors: Chen R, Tao Y, Xu X, Shan L, Jiang H, Yin Q, Pei L, Cai F, Ma L, Yu Y Abstract Currently, platinum-based chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) that is not driven by identifiable genetic events, such as sensitizing mutations of epidermal growth factor receptor (EGFR) and translocations of anaplastic lymphoma kinase (ALK). Immune checkpoint inhibitors, which unleash a patient's own T cells to attack tumors, are revolutionizing the treatment paradigm of lung cancer. Anti-programmed death 1 (anti-PD-1) antibodies, pembrolizumab and nivolumab, and anti...
Source: Discovery Medicine - December 27, 2018 Category: Research Tags: Discov Med Source Type: research

TNF-alpha is upregulated in subacute thyroiditis and stimulates expression of miR-155-5p in thyroid follicle cells.
Authors: Li H, Zhang X, Gao L, Min J, Zhang Y, Zhang R, Yang Y Abstract Tumor necrosis factor alpha (TNF-α) regulates the expression of proinflammatory cytokines and apoptosis in thyroids. miR-155-5p is upregulated in circulating microvesicles in patients with autoimmune thyroiditis. However, the function and molecular mechanisms of TNF-α and miR-155-5p in the initiation and progression of subacute thyroiditis are largely unknown. Herein, we determined serum TNF-α levels in subacute thyroiditis patients and normal healthy controls by ELISA assay. Proliferation and apoptosis of rat thyroid follicle...
Source: Discovery Medicine - November 8, 2018 Category: Research Tags: Discov Med Source Type: research

Hiding in plain sight: time to unlock autoimmune clues in human CD5+ B cells by using nextgen technology.
Authors: Ahmed R, Omidian Z, Donner T, Hamad ARA Abstract CD5+ B cells expand in many autoimmune diseases, including type 1 diabetes (T1D), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Furthermore, CD5+ B cells contain important subsets: IL-10-producing B-reg cells, FasL-expressing subset, and the majority of pre-naive B cells. In addition, they are major sources of natural autoantibodies, which are polyreactive and autoreactive. Thus, CD5+ B cells are clearly loaded with autoimmune clues that are yet to be unlocked and understood. We hypothesize that human CD5+ B cells are likely to yield eno...
Source: Discovery Medicine - November 8, 2018 Category: Research Tags: Discov Med Source Type: research

Promise and pitfalls of immune checkpoint inhibitors in hepato-pancreato-biliary malignancies.
Authors: McLoughlin KC, Brown ZJ, Shukla Y, Shukla V Abstract A growing understanding of the immune system and its anti-tumor functions has been imperative for the comprehension of malignant processes and beneficial in the pursuit of effective cancer treatments. To defend the body, immune cells must be able to differentiate between self and foreign cells using checkpoints, allowing the immune cells to attack foreign cells. Among the different types of immune target therapies recently developed, checkpoint inhibitors have come to the forefront in cancer treatment, encouraging their study in numerous different types ...
Source: Discovery Medicine - November 8, 2018 Category: Research Tags: Discov Med Source Type: research

Resident bacteria in breast cancer tissue: pathogenic agents or harmless commensals?
Authors: O'Connor H, MacSharry J, Bueso YF, Lindsay S, Kavanagh EL, Tangney M, Clyne M, Saldova R, McCann A Abstract Breast cancer is the second most common cancer in women. Recent evidence identifies a unique microbiome in breast tissue; a site previously thought to be sterile. The identification that this microbiome varies considerably from healthy subjects to cancer patients has prompted investigations into the role of specific bacterial species in oncogenesis. Indeed, certain bacteria have been shown to aid cancer development in vitro by promoting genomic instability, invasion, and chemotherapy resistance. Howe...
Source: Discovery Medicine - November 8, 2018 Category: Research Tags: Discov Med Source Type: research

TGF-beta signaling and its targeted therapy in gastrointestinal cancers.
Authors: Gotovac JR, Fujihara KM, Phillips WA, Clemons NJ Abstract The transforming growth factor β (TGFβ) signaling pathway governs physiological homeostasis in the gastrointestinal system and its deregulation can lead to a diverse range of human pathologies including juvenile polyposis syndrome and tumor initiation, progression, and metastasis. In gastrointestinal malignancies, tumor cells evade the known tumor suppressive effects of TGFβ signaling through frequent inactivation of the pathway. Paradoxically, tumor cells utilize TGFβ-mediated regulation of epithelial-mesenchymal transition and ...
Source: Discovery Medicine - November 8, 2018 Category: Research Tags: Discov Med Source Type: research

Clinical significance of increased urotensin II levels in acute myocardial infarction.
Authors: Zhang X, Ye Y, Yang C, Gong H, Li Y, Zhang G, Yuan J, Zou Y Abstract We aimed to study urotensin II (UII) in acute myocardial infarction (AMI) patients before and after percutaneous coronary intervention (PCI) and to investigate its interaction with angiotensin II (ATII) in post-AMI myocardial remodeling. In this clinical study, 63 AMI patients and 66 controls were included. Levels of UII, ATII, and NT-B-type natriuretic peptide (NT-BNP) were determined. Participants were followed up for 2 years to observe clinical outcomes. In cell biology experiments, ATII and UII were added into cardiomyocytes and fibro...
Source: Discovery Medicine - September 30, 2018 Category: Research Tags: Discov Med Source Type: research

Understanding molecular diagnostic technology in oncology through the lens of lung cancer.
Authors: Jonna S, Giaccone G, Subramaniam DS Abstract Historically, advanced lung cancer conferred a poor prognosis, and chemotherapy only improved outcomes in patients with good performance status. The identification of certain molecular subtypes of non-small cell lung cancer changed the treatment paradigm by incorporating tumor genomic information into clinical decision-making. To meet the demands of this emerging approach, genomic technology rapidly expanded in an effort to detect specific driver mutations. While polymerase-chain reaction testing, immunohistochemistry, and fluorescent-in-situ hybridization have ...
Source: Discovery Medicine - September 30, 2018 Category: Research Tags: Discov Med Source Type: research

Chemerin modulation of tumor growth: potential clinical applications in cancer.
Authors: Shin WJ, Pachynski RK Abstract Chemerin is a relatively newly described, yet increasingly studied multifunctional protein that mediates a variety of important biological functions. With significant roles in immune trafficking and adipo/angiogenesis, chemerin has gained traction in recent years for its potential functions in cancer, tumorigenesis, and immune surveillance. Chemerin's main chemotactic cellular receptor, CMKLR1, is expressed on both immune cells and malignant tumor cells, while a second non-signaling receptor, CCRL2, may act to help concentrate chemerin along activated endothelial cells and at...
Source: Discovery Medicine - September 30, 2018 Category: Research Tags: Discov Med Source Type: research

Mechanisms of resistance to HER2-targeted therapies in HER2-amplified uterine serous carcinoma, and strategies to overcome it.
This study presents a comprehensive review of the mechanisms of USC resistance to HER2-targeted therapies and potential strategies to overcome it. PMID: 30265854 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - September 30, 2018 Category: Research Tags: Discov Med Source Type: research

BRAF alterations in primary brain tumors.
Authors: Maraka S, Janku F Abstract Primary brain tumors can harbor v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene alterations. BRAF is a serine/threonine kinase protein and is a downstream effector of the Ras-Raf-MEK extracellular signal-regulated kinase (ERK) signaling pathway, which is responsible for cell division and differentiation. BRAF-V600E mutations are most commonly found in pleomorphic xanthoastrocytoma, ganglioglioma, epithelioid glioblastoma, and gliomas diagnosed at a younger age; BRAF-KIAA1549 fusion is the most common BRAF alteration in pilocytic astrocytoma. First-generation BRAF inhib...
Source: Discovery Medicine - September 30, 2018 Category: Research Tags: Discov Med Source Type: research

miR-212 and mTOR form a regulation loop to modulate autophagy in colorectal adenoma HT-29 cells.
This study warrants further investigation of miR-212 as an effective target of autophagy-based cancer therapeutic strategies. PMID: 30021100 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - July 19, 2018 Category: Research Tags: Discov Med Source Type: research

Dynamic testing of stimulative and suppressive biomarkers on peripheral blood cells at early stages of immunotherapy predicts response in advanced cancer patients.
CONCLUSION: Our work indicates that by testing biomarkers on patients' PBMCs at an early stage of treatment, the immunotherapeutic effect can be predicted, thus improving patient outcomes and cost efficiency. PMID: 30021101 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - July 19, 2018 Category: Research Tags: Discov Med Source Type: research

Applications of vitamin D in sepsis prevention.
Authors: Takeuti FAC, Guimaraes FSF, Guimaraes PSF Abstract Vitamin D (VD) is a steroid prohormone that regulates the body's calcium and phosphate levels in bone mineralization. It is also well described as a fat-soluble vitamin playing an important role in immunomodulation, regulation of cytokines, and cell proliferation. Thus, VD is a powerful hormone with pleiotropic effects, which acts to maintain optimal health. Recent studies demonstrate that VD deficiency is associated with the development of cardiovascular diseases, autoimmune disorders, and various types of cancer, each associated with increased mortality ...
Source: Discovery Medicine - July 19, 2018 Category: Research Tags: Discov Med Source Type: research

Re-framing the theory of autoimmunity in the era of the microbiome: persistent pathogens, autoantibodies, and molecular mimicry.
Authors: Proal AD, Marshall TG Abstract The theory of autoimmunity was developed at a time when the human body was regarded as largely sterile. Antibodies in patients with chronic inflammatory disease could consequently not be tied to persistent human pathogens. The concept of the "autoantibody" was created to reconcile this phenomenon. Today, however, the discovery of the human microbiome has revolutionized our understanding of human biology. Humans are superorganisms that harbor trillions of persistent microbial cells. Indeed, vast human microbiomes have been detected in human tissue and blood. These mi...
Source: Discovery Medicine - July 19, 2018 Category: Research Tags: Discov Med Source Type: research

Novel targeted therapies in ovarian and uterine carcinosarcomas.
This article reviews the genetic landscapes and explores novel targeted treatment modalities against this deadly gynecologic tumor. PMID: 30021104 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - July 19, 2018 Category: Research Tags: Discov Med Source Type: research

Collagen 1A1 (COL1A1) promotes metastasis of breast cancer and is a potential therapeutic target.
CONCLUSION: Cellular expression of COL1A1 could promote breast cancer metastasis. COL1A1 is a new prognostic biomarker and a potential therapeutic target for breast cancer, especially in ER+ patients. PMID: 29906404 [PubMed - in process] (Source: Discovery Medicine)
Source: Discovery Medicine - June 17, 2018 Category: Research Tags: Discov Med Source Type: research

Dermatologic manifestations of inflammatory bowel disease: a review.
Authors: Keyal U, Liu Y, Bhatta AK Abstract Inflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal tract with unknown etiology and pathogenesis. It includes Crohn's disease (CD) and ulcerative colitis (UC). Approximately one-third of the patients with IBD are seen to develop extraintestinal manifestations, among which cutaneous manifestations are the most common and should be managed in close collaboration with a dermatologist. Depending upon the nature of the association, skin conditions associated with IBD can be listed under 4 categories: specific, reactive, secondary to malnutri...
Source: Discovery Medicine - June 17, 2018 Category: Research Tags: Discov Med Source Type: research

The malignancy index in plasma samples as a prostate cancer biomarker.
In this study, we attempt to discriminate prostate cancer from non-cancer in a cohort of plasma samples, using the Imubind ELISA assay. In this cohort, PAI-1 levels are higher in prostate cancer patients than healthy donors; uPA levels are higher in healthy donors than prostate cancer patients; and the uPA/PAI-1 ratio is higher in healthy donors than in prostate cancer patients. To date, and across three prostate sample types, i.e. transurethral resection tissue, needle biopsies, and blood plasma, data have been disparate. Given the inconsistency, a malignancy index was created by dividing the product of three biomarkers [...
Source: Discovery Medicine - June 17, 2018 Category: Research Tags: Discov Med Source Type: research

Crosstalk between the immune system and neural pathways in interstitial cystitis/bladder pain syndrome.
We describe what is currently known about the immunological and neurological basis of this disease, focusing on the interactions between the immune and nervous system. Evidence for immune involvement in IC/BPS comes from its high co-occurrence with known autoimmune diseases, altered cytokine profiles, and immune cell infiltration in patients. These cytokines have the ability to cross-talk with the nervous system via NGF signaling, resulting in hyper-sensitization of pain receptors, causing them to release substance P and creating a positive feedback loop of neuroinflammation. While it seems that the crosstalk between the i...
Source: Discovery Medicine - June 17, 2018 Category: Research Tags: Discov Med Source Type: research

The potential for liquid biopsies in head and neck cancer.
Authors: Spector ME, Farlow JL, Haring CT, Brenner JC, Birkeland AC Abstract Head and neck cancers consist of a heterogeneous group of cancers that are difficult to treat successfully. Limited screening options result in patients being diagnosed at advanced stages at presentation, and difficulty with treatment options and post-treatment surveillance can lead to poor outcomes. In this setting, tools for early and precise detection of disease will be highly valuable. Liquid biopsies, or use of analytes in blood, saliva, and other body fluid samples, provide new avenues for cancer screening with the potential for earl...
Source: Discovery Medicine - June 17, 2018 Category: Research Tags: Discov Med Source Type: research