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Molecular therapy

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https://www.readbyqxmd.com/read/28545181/hepatocellular-carcinoma-a-comprehensive-review-of-biomarkers-clinical-aspects-and-therapy
#1
Nathalia Martines Tunissiolli, Márcia Maria Urbanin Castanhole-Nunes, Patrícia Matos Biselli-Chicote, Érika Cristina Pavarino, Renato Ferreira da Silva, Rita de Cássia Martins Alves da Silva, Eny Maria Goloni-Bertollo
Hepatocellular carcinoma (HCC) is a cause of several deaths related to cancer worldwidely. In early stage, curative treatments such as surgical resection, liver transplant and local ablation can improve the patient ´s survival. However, the disease is detected in advanced stage; moreover some available therapies are restricted to palliative care and local treatment. Early detections of HCC and adequate therapy are crucial to increase survival as well as to improve the patient´s quality of life. Therefore, researchers have been investigating molecular biomarkers with high sensibility and reliability as Golgi 73 protein (GP73), Glypican-3 (GPC3), Osteopontin (OPN), microRNAs and others...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28545141/prion-pathogenesis-is-unaltered-in-the-absence-of-sirp%C3%AE-mediated-don-t-eat-me-signaling
#2
Mario Nuvolone, Marta Paolucci, Silvia Sorce, Veronika Kana, Rita Moos, Takashi Matozaki, Adriano Aguzzi
Prion diseases are neurodegenerative conditions caused by misfolding of the prion protein, leading to conspicuous neuronal loss and intense microgliosis. Recent experimental evidence point towards a protective role of microglia against prion-induced neurodegeneration, possibly through elimination of prion-containing apoptotic bodies. The molecular mechanisms by which microglia recognize and eliminate apoptotic cells in the context of prion diseases are poorly defined. Here we investigated the possible involvement of signal regulatory protein α (SIRPα), a key modulator of host cell phagocytosis; SIRPα is encoded by the Sirpa gene that is genetically linked to the prion gene Prnp...
2017: PloS One
https://www.readbyqxmd.com/read/28545088/transcriptional-activation-of-hif-1-by-a-ros-erk-axis-underlies-the-resistance-to-photodynamic-therapy
#3
María Julia Lamberti, María Florencia Pansa, Renzo Emanuel Vera, Martín Ernesto Fernández-Zapico, Natalia Belén Rumie Vittar, Viviana Alicia Rivarola
Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT...
2017: PloS One
https://www.readbyqxmd.com/read/28545033/microrna-expression-levels-as-diagnostic-biomarkers-for-intraductal-papillary-mucinous-neoplasm
#4
Lei Wang, Jianming Zheng, Chang Sun, Li Wang, Gang Jin, Lei Xin, Zhendong Jin, Dong Wang, Zhaoshen Li
Intraductal papillary mucinous neoplasms (IPMNs) are deadly exocrine mucinous tumors. Currently the molecular features and diagnostic markers of IPMNs are not well understood. In this study, we performed microRNA (miRNA) profiling assays to study the potential roles of miRNAs in IPMNs using 78 cases of IPMN patients and controls. When comparing the miRNA expression between IPMN patient samples and controls, we found that miR-210, miR-223, miR-221, miR-155 and miR-187 were differentially expressed in normal pancreas and IPMNs...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545020/microtubule-inhibitor-sp-6-27-inhibits-angiogenesis-and-induces-apoptosis-in-ovarian-cancer-cells
#5
Arpita Kulshrestha, Gajendra K Katara, Safaa A Ibrahim, Renukadevi Patil, Shivaputra A Patil, Kenneth D Beaman
In ovarian cancer (OVCA), treatment failure due to chemo-resistance is a serious challenge. It is therefore critical to identify new therapies that are effective against resistant tumors and have reduced side effects. We recently identified 4-H-chromenes as tubulin depolymerizing agents that bind to colchicine site of beta-tubulin. Here, we screened a chemical library of substituted 4-H-chromenes and identified SP-6-27 to exhibit most potent anti-proliferative activity towards a panel of human cisplatin sensitive and resistant OVCA cell lines with 50% inhibitory concentration (IC50; mean ± SD) ranging from 0...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544984/histo-blood-group-antigens-as-mediators-of-infections
#6
REVIEW
Julie E Heggelund, Annabelle Varrot, Anne Imberty, Ute Krengel
The critical first step of a microbial infection is usually the attachment of pathogens to host cell glycans. Targets on host tissues are in particular the histo-blood group antigens (HBGAs), which are present in rich diversity in the mucus layer and on the underlying mucosa. Recent structural and functional studies have revealed significant new insight into the molecular mechanisms, explaining why individuals with certain blood groups are at increased risk of some infections. The most prominent example of blood-group-associated diseases is cholera, caused by infection with Vibrio cholerae...
May 22, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28544969/prior-treatment-with-non-anti-tb-antibiotics-and-the-duration-of-symptoms-have-no-effect-on-diagnostics-of-tuberculous-meningitis
#7
Marcin Paciorek, Andrzej Pihowicz, Dominik Bursa, Joanna Schöntaler Humięcka, Justyna D Kowalska, Mateusz Antosiewicz, Magda E Thompson, Agata Skrzat-Wojdacz, Agnieszka Bednarska, Andrzej Horban
PURPOSE: Our objective was to investigate whether diagnosis of tuberculous meningitis (TBM) with microbiological and molecular analysis was affected by prior empirical non anti tuberculosis antibiotics or by duration of symptoms before lumbar puncture. MATERIALS AND METHODS: We retrospectively evaluated medical records of patients with TBM confirmed by positive culture, nucleic acid amplification techniques (NAATs) or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) or by characteristic results of biochemical analysis of CSF combined with a typical clinical manifestation...
May 22, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28544770/review-article-screening-genetics-risk-factors-and-treatment-of-neonatal-cataracts
#8
REVIEW
Jinyu Li, Chun-Hong Xia, Eddie Wang, Ke Yao, Xiaohua Gong
Neonatal cataracts remain the most common cause of visual loss in children worldwide and have diverse, often unknown, etiologies. This review summarizes current knowledge about the detection, treatment, genetics, risk factors, and molecular mechanisms of congenital cataracts. We emphasize significant progress and topics requiring further study in both clinical cataract therapy and basic lens research. Advances in genetic screening and surgical technologies have improved the diagnosis, management, and visual outcomes of affected children...
May 22, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28544569/maintenance-of-the-contractile-phenotype-in-corpus-cavernosum-smooth-muscle-cells-by-myocardin-gene-therapy-ameliorates-erectile-dysfunction-in-bilateral-cavernous-nerve-injury-rats
#9
H-B Zhang, Z-Q Wang, F-Z Chen, W Ding, W-B Liu, Z-R Chen, S-H He, A-Y Wei
The pathophysiology of erectile dysfunction post radical prostatectomy is not clearly clarified, and the low efficacy of traditional PDE5i treatment remains a major complaint in contemporary practice. This study aimed to demonstrate phenotypic modulation in bilateral cavernous nerve injury (BCNI) rats within 7 days, and subsequently validate gene therapy with Myocardin (Mycod) by maintaining a contractile phenotype in corpus cavernosum smooth muscle cells. Initially, 36 male rats were randomly divided into BCNI and negative control (NC) groups for histological and phenotypic molecular measurements at 3, 5, and 7 days...
May 23, 2017: Andrology
https://www.readbyqxmd.com/read/28544403/serine-protease-inhibitor-kazal-type-1-spink1-downregulates-e-cadherin-and-induces-emt-of-hepatoma-cells-to-promote-hepatocellular-carcinoma-metastasis-via-the-mek-erk-signaling-pathway
#10
Ying Hai-Yan, Gong Chao-Jie, Feng Yi, Jing Da-Dao, Lun-Gen Lu
OBJECTIVE: To investigate serine protease inhibitor Kazal type 1(SPINK1) expression and its influence on the prognosis of human hepatocellular carcinoma(HCC) and to explore the underlying molecular mechanisms involved. METHODS: Eighty patients with HCC who underwent curative resection were followed-up with a median observation time of 58.6 months.SPINK1expression was detected in the primary HCC samples by immunohistochemistry . Its role in tumor invasion and metastasis was evaluated in vitro by gene silence using siRNA-mediated approach, rSPINK1 and U0126(an inhibitor of MEK/ERK)...
May 23, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28544222/usefulness-of-detection-of-clarithromycin-resistant-helicobacter-pylori-from-fecal-specimens-for-young-adults-treated-with-eradication-therapy
#11
Takako Osaki, Katsuhiro Mabe, Cynthia Zaman, Hideo Yonezawa, Masumi Okuda, Kenji Amagai, Shinji Fujieda, Mitsuhide Goto, Wataru Shibata, Mototsugu Kato, Shigeru Kamiya
BACKGROUND: To prevent Helicobacter pylori infection in the younger generation, it is necessary to investigate the prevalence of antibiotic-resistant H. pylori. OBJECTIVE: The aim of this study was to evaluate the method of PCR-based sequencing to detect clarithromycin (CAM) resistance-associated mutations using fecal samples as a noninvasive method. METHODS: DNA extracted from fecal specimens and isolates from gastric biopsy specimens were collected from patients with H...
May 22, 2017: Helicobacter
https://www.readbyqxmd.com/read/28544002/biological-effects-and-osteoarthritic-disease-modifying-activity-of-small-molecule-cm-01
#12
Yubo Sun, Andrea Roberts, David R Mauerhan, Michael Cox, Edward N Hanley
Phosphocitrate inhibits cartilage degeneration, however, the prospect of phosphocitrate as an oral disease modifying drug might be limited. The purpose of this study was to investigate the biological effects and disease-modifying activity of a phosphocitrate "analogue", CM-01 (Carolinas Molecule-01), and test the hypothesis that CM-01 is a disease modifying drug for osteoarthritis therapy. The effects of CM-01 on calcium crystal-induced expression of matrix metalloproteinase-1 and interleukin-1 beta, cell-mediated calcification and production of proteoglycan by chondrocytes were examined in cell cultures...
May 25, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28543700/interaction-of-molecular-alterations-with-immune-response-in-melanoma
#13
REVIEW
Robert A Szczepaniak Sloane, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, Xue Zhang, Alexandre Reuben, Jennifer A Wargo
Major advances have been made in melanoma treatment with the use of molecularly targeted therapies and immunotherapies, and numerous regimens are now approved by the US Food and Drug Administration for patients with stage IV disease. However, therapeutic resistance remains an issue to both classes of agents, and reliable biomarkers of therapeutic response and resistance are lacking. Mechanistic insights are being gained through preclinical studies and translational research, offering potential strategies to enhance responses and survival in treated patients...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543699/immune-and-molecular-correlates-in-melanoma-treated-with-immune-checkpoint-blockade
#14
REVIEW
Elizabeth H Byrne, David E Fisher
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543697/molecular-insights-into-melanoma-brain-metastases
#15
REVIEW
Dana Westphal, Isabella C Glitza Oliva, Heike Niessner
Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543695/mechanisms-and-strategies-to-overcome-resistance-to-molecularly-targeted-therapy-for-melanoma
#16
REVIEW
Su Yin Lim, Alexander M Menzies, Helen Rizos
The identification of driver mutations in melanoma has changed the field of cancer treatment. BRAF and NRAS mutations are predominant in melanoma and lead to overactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Selective inhibitors targeting key effectors of the MAPK pathway have revolutionized the treatment of patients with advanced metastatic BRAF-mutant melanoma. However, resistance to therapy is almost universal and remains a major challenge in clinical care, with the majority of patients progressing within 1 year...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28542792/on-the-complexity-of-clinical-and-molecular-bases-of-neurodegeneration-with-brain-iron-accumulation
#17
REVIEW
Cristina Tello, Alejandra Darling, Vincenzo Lupo, Belén Pérez-Dueñas, Carmen Espinós
Neurodegeneration with brain iron accumulation (NBIA) are a group of inherited heterogeneous neurodegenerative rare disorders. These patients present with dystonia, spasticity, parkinsonism and neuropsychiatric disturbances, along with brain MRI evidence of iron accumulation. In sum, they are devastating disorders and to date, there is no specific treatment. Ten NBIA genes are accepted: PANK2, PLA2G6, C19orf12, COASY, FA2H, ATP13A2, WDR45, FTL, CP, and DCAF17, and. Nonetheless, a relevant percentage of patients remain without genetic diagnosis, suggesting that other novel NBIA genes remain to be discovered...
May 23, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28542706/modulatory-features-of-the-novel-spider-toxin-%C3%AE-trtx-df1a-isolated-from-the-venom-of-the-spider-davus-fasciatus
#18
Fernanda C Cardoso, Zoltan Dekan, Jennifer J Smith, Jennifer R Deuis, Irina Vetter, Volker Herzig, Paul F Alewood, Glenn F King, Richard J Lewis
BACKGROUND AND PURPOSE: Naturally occurring dysfunction in NaV channels results in complex disorders such as chronic pain, making these channels an attractive target for new therapies. In the pursuit of novel NaV modulators, we investigated spider venoms for new inhibitors of NaV channels. EXPERIMENTAL APPROACH: We used high-throughput screens to identify a NaV modulator in venom of the spider Davus fasciatus. Further characterization of this venom peptide was undertaken using fluorescent and electrophysiological assays, molecular modeling and a rodent pain model...
May 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28542590/the-mth1-inhibitor-th588-demonstrates-anti-tumoral-effects-alone-and-in-combination-with-everolimus-5-fu-and-gamma-irradiation-in-neuroendocrine-tumor-cells
#19
Elke Tatjana Aristizabal Prada, Michael Orth, Svenja Nölting, Gerald Spöttl, Julian Maurer, Christoph Auernhammer
Modulation of the redox system in cancer cells has been considered a promising target for anti-cancer therapy. The novel MTH1 inhibitor TH588 proved tremendous potential in terms of cancer cell eradication, yet its specificity has been questioned by recent reports, indicating that TH588 may also induce cancer cell death by alternative mechanisms than MTH1 inhibition. Here we used a panel of heterogeneous neuroendocrine tumor cells in order to assess cellular mechanisms and molecular signaling pathways implicated in the effects of TH588 alone as well as dual-targeting approaches combining TH588 with everolimus, cytotoxic 5-fluorouracil or γ-irradiation...
2017: PloS One
https://www.readbyqxmd.com/read/28542439/host-mediated-inflammatory-influence-on-glioblastoma-multiforme-recurrence-following-high-dose-ionizing-radiation
#20
J Tyson McDonald, Xuefeng Gao, Cole Steber, Jawon Lee Breed, Caitlin Pollock, Lili Ma, Lynn Hlatky
Despite optimal clinical treatment, glioblastoma multiforme (GBM) inevitably recurs. Standard treatment of GBM, exposes patients to radiation which kills tumor cells, but also modulates the molecular fingerprint of any surviving tumor cells and the cross-talk between those cells and the host. Considerable investigation of short-term (hours to days) post-irradiation tumor cell response has been undertaken, yet long-term responses (weeks to months) which are potentially even more informative of recurrence, have been largely overlooked...
2017: PloS One
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