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Discovery Medicine

Amanda J Craig, Johann von Felden, Augusto Villanueva
Liver cancer has the highest increase in incidence and mortality of all cancers in the United States in recent decades. A major effort has been taken over the last 10 years to understand molecular heterogeneity between tumors of different patients through the development of mutation signatures and molecular classifications. More recently, attention has shifted to understanding intra-tumor heterogeneity (ITH). Several possibilities exist as to the underlying mechanisms that drive ITH in liver cancer, including cancer stem cells (CSCs) and neutral and clonal evolution...
September 2017: Discovery Medicine
Thein Hlaing Oo, Cristhiam Mauricio Rojas-Hernandez
Pernicious anemia (PA) is an autoimmune disease of multifactorial etiologies characterized by autoimmune chronic atrophic gastritis, cobalamin deficiency (CD) due to defective absorption of dietary cobalamin from the terminal ileum, and by the presence of intrinsic factor and parietal cell antibodies. PA is a very common cause of CD-related anemia worldwide. Despite advances in the understanding molecular biology and pathophysiology of PA, the diagnosis of PA remains challenging in many circumstances for many clinicians because of its diverse clinical manifestations and the limitations of currently available diagnostic tools...
September 2017: Discovery Medicine
Lingbo Kong, Yu Lu, Siyu Zhang, Yuemin Nan, Liang Qiao
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. The nutrients play important roles in the development and progression of NAFLD. High-calorie diet, especially the diet rich in saturated fatty acids and cholesterol, as well as sugary drinks with high fructose content, induces hepatic steatosis and triggers progression of steatohepatitis, fibrosis, and even hepatocellular carcinoma. Disordered micronutrient status and gut microbiota are also involved in the pathogenesis of NAFLD...
September 2017: Discovery Medicine
Zhaobin Cai, Keyang Xu, Yan Li, Yuanlin Lv, Jianfeng Bao, Liang Qiao
Hepatocellular carcinoma (HCC) is one of the most common malignancies and a major cause of cancer-related deaths. HCC often has an insidious onset, fast progression, and high tendency of metastasis and recurrence, hence it is a highly fatal malignant tumor. The origin of HCC is still a topic of debate but studies over the past decade have clearly identified liver cancer stem cells (LCSCs) being a cardinal source of liver cancer. LCSCs are a small subset of cells with the unlimited ability of self-renewal, differentiation, and uncontrollable growth...
September 2017: Discovery Medicine
Xing Yang, Qian Hu, Lan-Xin Hu, Xiao-Rong Lin, Jie-Qiong Liu, Xiao Lin, Xiao-Xiao Dinglin, Jia-Yi Zeng, Hai Hu, Man-Li Luo, He-Rui Yao
Chemotherapy is a cornerstone treatment for early and advanced stage breast cancer patients. However, resistance to chemotherapy remains a major obstacle, resulting in disease relapse and progression. Emerging studies demonstrated that miRNAs regulate chemotherapy-induced epithelial-mesenchymal transition (EMT) and drug resistance, but the underlying mechanisms remain unclear. Here we established a doxorubicin-resistant breast cancer cell line MCF-7/Adr, and found these cells exhibited an EMT phenotype featured by a fibroblast-like morphology, increased the capacity of migration and invasion, and underwent the changes of molecular markers of EMT including E-cadherin, N-cadherin, and vimentin...
September 2017: Discovery Medicine
Justina X Caushi, Kellie N Smith
The use of immunotherapy in the treatment of cancer has resulted in a paradigm shift in clinical outcomes and in the correlative biomarkers that are most useful to evaluate in cancer patients. While several immunotherapeutic approaches have shown great promise, and several checkpoint inhibitors have been approved in the first and second line setting for multiple cancer types, major challenges remain in identifying the population of patients most likely to respond and in accurately monitoring clinical response while patients are receiving treatment...
August 2017: Discovery Medicine
Edward A Copelan, Michael R Grunwald, Srinivasa R Sanikommu, Mohammad J Hussain, Belinda Avalos
Myelodysplastic syndrome (MDS) is a heterogeneous group of malignant disorders of blood cell production occurring predominantly in elderly patients. While low intensity treatments are appropriate initially in most patients with favorable prognoses, hematopoietic cell transplantation (HCT) is the only curative therapy and is the best therapy for many higher risk patients. In patients who present with lower-risk disease, HCT may be considered at the time of meaningful disease progression. In patients receiving hypomethylating treatment, outcome of HCT is best when performed during response, and HCT is less effective when performed after resistance occurs...
August 2017: Discovery Medicine
Shigeo Koido, Masato Okamoto, Masanori Kobayashi, Shigetaka Shimodaira, Haruo Sugiyama
Pancreatic ductal adenocarcinoma (PDA) is characterized by a very poor prognosis, despite novel chemotherapeutic treatments. Moreover, the majority of PDA patients with complete surgical resection show recurrence within 5 years of resection. Therefore, new targeted cancer vaccines are urgently needed to extend PDA patient survival. The Wilms' tumor 1 (WT1) antigen was identified as an excellent antigen in a list of 75 tumor-associated antigens by a National Cancer Institute prioritization project based on several factors, such as therapeutic function...
August 2017: Discovery Medicine
Marianne Strazza, Adam Mor
Subsets of T cells can be classified by the functions executed or by the anatomic location at which they operate. In vitro analysis of T cell subsets and even commercial kits for subset separation often incorporate chemokine receptors into the panel of markers to distinguish among them, but what is the functional significance of these receptors? In this review, we discuss chemokine receptors that are expressed exclusively on different T cell subsets as well as those that are commonly expressed across subsets with the goal of linking receptor expression to cellular localization and intended cellular function...
August 2017: Discovery Medicine
Ying Zhang, Zhaoyong Liu
The first STAT family member, STAT1, is an essential component of interferon (IFN)-signaling, which mediates several cellular functions in response to stimulation by cytokines, growth factors, and hormones, such as the IFNs and IL-6. The role and significance of STAT1 in cancer biology have been studied for a decade. The majority of evidence shows that activating STAT1 plays a tumor suppressor role in cancer cells. Nevertheless, results from some experiments and clinical studies suggest that STAT1 also exerts tumor promoter effects under specific conditions...
August 2017: Discovery Medicine
Yuquan Tao, Feng Cai, Liang Shan, Hongyuan Jiang, Lifang Ma, Yongchun Yu
The Hippo signaling is a highly conserved pathway that plays important roles in tumorigenesis, stem cell self-renewal and differentiation, organ size control, and many other biological processes. Functions of the Hippo signaling pathway are regulated by complicated intracellular and extracellular signaling networks. When activated, the Hippo pathway functions as a tumor suppressor. However, dysregulation of this pathway contributes to increased cell proliferation and decreased apoptosis and differentiation...
August 2017: Discovery Medicine
Mark W Ball
Despite advances in systemic therapy for metastatic renal cell carcinoma, durable responses remain rare and surgical management remains a mainstay of treatment for many patients with metastatic disease. Management of the primary tumor in metastatic patients can occur as 1) palliative nephrectomy for symptomatic patients in whom cure is not achievable, 2) cytoreductive nephrectomy before systemic therapy, or 3) consolidative nephrectomy after systemic therapy. Palliative nephrectomy is rarely performed in centers where angioembolization is available...
June 2017: Discovery Medicine
Olympia Bikou, Kiyotake Ishikawa
Gene therapy is recently attracting increased attention and cardiac gene therapy is not an exception. Advances in gene transfer vectors, development of new vector delivery methods, and discovery of new gene targets continue to fuel our motivation to use this approach in routine bedside care. In the past two years, we have witnessed important advances in the field, as the results of three recently completed cardiac gene therapy programs have been published. Unfortunately, none of the trials have met their primary efficacy endpoints, but sub-analysis demonstrated potential efficacy...
June 2017: Discovery Medicine
Hannah R Milbourn, Lillian M Toomey, Nikolas Gavriel, Chloe G G Gray, Alexander H Gough, Marcus K Giacci, Melinda Fitzgerald
Following injury to the central nervous system, secondary degeneration is mediated by Ca2+ imbalances and overproduction of reactive oxygen species from mitochondria, and is associated with myelin deficits and loss of function. Preventing intracellular Ca2+ influx at the acute phase of injury is a potential strategy for limiting these deficits and preserving function. The use of single ion channel inhibitors has had little success in attenuating morphological and functional deficits, potentially due to the many pathways by which calcium can traverse the cell membrane...
June 2017: Discovery Medicine
John Redmond, Debbie O'Rilley, Paul Buchanan
Progression of cancer to advanced states is associated with treatment resistance and metastatic spread -- features that are linked to poor prognosis and patient mortality. Investigations into potential new treatments to reduce cancer spread are ongoing, with immunotherapy generating much interest. Natural killer (NK) cells are part of the body's innate immune system and are known for their ability to target and lyse cancer cells. Ion channels have previously been linked to the growth and development of tumors, but recent research suggests that these channels may also serve to alter immune cell functioning...
June 2017: Discovery Medicine
Yi Lu, Weizhong Gu, Yanhong Ren, Jia Feng, Lili Yang, Ji Jin
Retinal fibrosis, including epiretinal membrane (ERM) and proliferative vitreoretinopathy (PVR), is an ocular disease that can lead to blindness. An efficacious therapy remains an unmet medical challenge. In this study, we intended to explore the inhibitory effects of the nanoparticle-mediated delivery of plasminogen kringle 5 (K5-NPs) on laser-induced ERM and to identify the potential anti-fibrosis targets of K5-NPs. A rat model of laser-induced ERM was used. Control-NPs or K5-NPs were intravitreally injected...
June 2017: Discovery Medicine
Hirva Mamdani, Howard Wu, Bert H O'Neil, Amikar Sehdev
Hepatocellular carcinoma (HCC) is an aggressive cancer associated with high mortality worldwide. HCC develops in the setting of underlying cirrhosis due to chronic liver disease. Surgery is usually considered the treatment of choice for early disease; however, most patients have locally advanced or metastatic HCC at diagnosis in which case treatments are limited. Immune checkpoint blockade of programmed death receptor-1 (PD-1) pathway offers a potential treatment strategy based on the encouraging results of the phase I/II trial of nivolumab (Checkmate 040 trial)...
May 2017: Discovery Medicine
Tadas Rimkus, Sherona Sirkisoon, Alexandra Harrison, Hui-Wen Lo
Tumor suppressor candidate 2 (TUSC2, also known as FUS1) was identified in 2000 as a candidate tumor suppressor gene located in a region on chromosome 3p21.3 that is homozygously deleted in some lung and breast cancers. The deletion is rare in lung and breast cancers, but is frequent in malignant pleural mesothelioma. Evidence to date indicates that TUSC2 behaves as a tumor suppressor in lung cancer; however, its role as a tumor suppressor for other tumor types has not been fully established. Loss of TUSC2 expression at the mRNA and protein levels has been reported in various cancers...
May 2017: Discovery Medicine
Wenyi Wu, Hetian Lei, Junhui Shen, Luosheng Tang
Netrin-1 is an axon guidance cue and is necessary for neural and vascular development. It is involved in regulating axon guidance for attraction or repulsion, and it has a dual function in endothelial tip cell migration during angiogenesis. Netrin-1 has been shown to play an important role in angiogenesis, cancer progression, and inflammatory disease. Here we review the role of netrin-1 in retinal and angiogenesis development and the associated signaling pathways in diabetic retinopathy. The currently available data suggest that netrin-1 is a promising target for the development of anti-angiogenesis drugs...
May 2017: Discovery Medicine
Nadya D Markova
From a historical perspective, intriguing assumptions about unknown "live units" in human blood have attracted the attention of researchers, reflecting their desire to define a new class of microorganisms. Thus, the concept of "blood microbiota" brings about many questions about the nature, origin, and biological significance of the "unusual microbial cohabitants" in human blood. In contrast to current views that bloodstream in healthy humans is sterile, the hypothesis about the existence of microbes as L-forms (cell wall deficient bacteria) in human blood has evolved on the basis of known facts about their unique biology, as observed in our studies and those of other authors...
May 2017: Discovery Medicine
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