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https://www.readbyqxmd.com/read/29776633/molecular-diagnostics-in-colorectal-carcinoma-advances-and-applications-for-2018
#1
REVIEW
Amarpreet Bhalla, Muhammad Zulfiqar, Martin H Bluth
The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29774219/effect-and-safety-of-sorafenib-in-patients-with-intermediate-hepatocellular-carcinoma-who-received-transarterial-chemoembolization-a-retrospective-comparative-study
#2
Xue-Fen Lei, Yang Ke, Tian-Hao Bao, Hao-Ran Tang, Xue-Song Wu, Zhi-Tian Shi, Jie Lin, Zhi-Xian Zhang, Hou Gu, Lin Wang
AIM: To evaluate the safety and efficacy of sorafenib plus transarterial chemoembolization (TACE) treatment for intermediate hepatocellular carcinoma (HCC). METHODS: Sixty-seven patients with intermediate-stage [Barcelona Clinic liver cancer stage B (BCLC-B)] HCC who were treated with sorafenib plus TACE or TACE alone between 2009 and 2011 were included in the study. Follow-up was until 2014 or patient death. Two groups were defined in the experiment: The experimental group, treated with sorafenib plus TACE, and the control group, treated with standard TACE alone...
May 16, 2018: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/29774103/bevacizumab-exacerbates-sinusoidal-obstruction-syndrome-sos-in-the-animal-model-and-increases-mmp-9-production
#3
Azin Jafari, Hanno Matthaei, Sven Wehner, Tolga Tonguc, Jörg C Kalff, Steffen Manekeller
Background: Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. Results: After MCT administration 67% of animals developed SOS...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774075/plectin-targeted-liposomes-enhance-the-therapeutic-efficacy-of-a-parp-inhibitor-in-the-treatment-of-ovarian-cancer
#4
Siva Sai Krishna Dasa, Galina Diakova, Ryo Suzuki, Anne M Mills, Michael F Gutknecht, Alexander L Klibanov, Jill K Slack-Davis, Kimberly A Kelly
Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise...
2018: Theranostics
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#5
Horrick Sharma
Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG)...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29772993/shoulder-lesion-in-a-69-year-old-woman
#6
Andrew J Hayden, Srinivas Kolla, Adele L Boskey, Steven Burekhovich, Chuanyong Lu, Michael Stracher, Aditya V Maheshwari
Milwaukee Shoulder Syndrome (MSS) is a painful progressive arthropathy in which hydroxyapatite crystal deposition in synovial tissue induces lysosomal release of collagenase and neutral proteases. These enzymes are destructive to periarticular tissue, including the synovium, articular cartilage, rotator cuff muscles, and the intrasynovial cortical bone. MSS predominantly occurring in women (90%) over the age of 70 years of age with a clinical history marked by recurrent joint effusions and pain, which classically worsens at night...
2018: Journal of Long-term Effects of Medical Implants
https://www.readbyqxmd.com/read/29772620/-development-of-ectopic-adrenocorticotropic-hormone-syndrome-in-a-patient-with-prostate-cancer-during-combined-androgen-blockade-therapy
#7
Yosuke Sekii, Mitsuhiro Yoshinaga, Masahiro Nakagawa, Hidefumi Kishikawa, Kazumasa Oka, Kenji Nishimura
A 74-year old man presented to us with difficulty urinating. The laboratory examinations revealed an elevated prostate-specific antigen (PSA) level. A prostate biopsy revealed prostate adenocarcinoma. The computed tomography scan showed metastasis to lymph nodes in the pelvic cavity and both adrenal glands. Combined androgen blockade therapy was started, and PSA levels began to decrease gradually. However, 2 months later, he was hospitalized for treatment of cellulitis and was found to have hypertension, hyperglycemia, and hypokalemia...
April 2018: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/29772554/antibodies-against-gpcr
#8
Carlotto Meyer, Harald Heidecke
G-protein-coupled receptors (GPCRs) are the largest family of receptors in humans. GPCRs are seven-transmembrane receptors that are activated by the binding of a ligand to the extracellular domain. In addition to the endogenous ligands, auto-antibodies (aab) can also bind to the GPCRs. They can activate different and specific cellular pathways which contribute to various diseases. In this review, the authors summarize the knowledge about antibodies targeting GPCRs and their effects and relevance in the pathogenesis of various diseases and their use in clinical diagnostics...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772527/a-novel-role-for-cd26-dipeptidyl-peptidase-iv-as-a-therapeutic-target
#9
Kei Ohnuma, Ryo Hatano, Eriko Komiya, Haruna Otsuka, Takumi Itoh, Noriaki Iwao, Yutaro Kaneko, Taketo Yamada, Nam H Dang, Chikao Morimoto
CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV activity that is expressed on numerous cell types and has a multitude of biological functions. The role of CD26 in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell-T-cell interaction. In this paper, we will review emerging data on CD26-mediated immune regulation suggesting that CD26 may be an appropriate therapeutic target for the treatment of selected immune disorders as well as Middle East respiratory syndrome coronavirus...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29771800/left-sided-dominance-of-early-onset-colorectal-cancers-a-rationale-for-screening-flexible-sigmoidoscopy-in-the-young
#10
Lior Segev, Matthew F Kalady, James M Church
BACKGROUND: National databases show a recent significant increase in the incidence of colorectal cancer in people younger than 50. With current recommendations to begin average-risk screening at age 50, these patients do not have the opportunity to be screened. We hypothesized that most of the cancers among the young would be left sided, which would create an opportunity for screening the young by flexible sigmoidoscopy. OBJECTIVE: This study aims to analyze the anatomic distribution of sporadic colorectal cancers in patients under the age of 50...
May 15, 2018: Diseases of the Colon and Rectum
https://www.readbyqxmd.com/read/29770436/all-i-s-on-the-radar-role-of-adar-in-gene-regulation
#11
REVIEW
Galina Shevchenko, Kevin V Morris
Adenosine to inosine (A-to-I) editing is the most abundant form of RNA modification in mammalian cells, which is catalyzed by adenosine deaminase acting on the double-stranded RNA (ADAR) protein family. A-to-I editing is currently known to be involved in the regulation of the immune system, RNA splicing, protein recoding, microRNA biogenesis, and formation of heterochromatin. Editing occurs within regions of double-stranded RNA, particularly within inverted Alu repeats, and is associated with many diseases including cancer, neurological disorders, and metabolic syndromes...
May 16, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29769720/rspo2-inhibition-of-rnf43-and-znrf3-governs-limb-development-independently-of-lgr4-5-6
#12
Emmanuelle Szenker-Ravi, Umut Altunoglu, Marc Leushacke, Célia Bosso-Lefèvre, Muznah Khatoo, Hong Thi Tran, Thomas Naert, Rivka Noelanders, Amin Hajamohideen, Claire Beneteau, Sergio B de Sousa, Birsen Karaman, Xenia Latypova, Seher Başaran, Esra Börklü Yücel, Thong Teck Tan, Lena Vlaeminck, Shalini S Nayak, Anju Shukla, Katta Mohan Girisha, Cédric Le Caignec, Natalia Soshnikova, Zehra Oya Uyguner, Kris Vleminckx, Nick Barker, Hülya Kayserili, Bruno Reversade
The four R-spondin secreted ligands (RSPO1-RSPO4) act via their cognate LGR4, LGR5 and LGR6 receptors to amplify WNT signalling1-3 . Here we report an allelic series of recessive RSPO2 mutations in humans that cause tetra-amelia syndrome, which is characterized by lung aplasia and a total absence of the four limbs. Functional studies revealed impaired binding to the LGR4/5/6 receptors and the RNF43 and ZNRF3 transmembrane ligases, and reduced WNT potentiation, which correlated with allele severity. Unexpectedly, however, the triple and ubiquitous knockout of Lgr4, Lgr5 and Lgr6 in mice did not recapitulate the known Rspo2 or Rspo3 loss-of-function phenotypes...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769598/germline-mutation-in-the-tp53-gene-in-uveal-melanoma
#13
Nikola Hajkova, Jan Hojny, Kristyna Nemejcova, Pavel Dundr, Jan Ulrych, Katerina Jirsova, Johana Glezgova, Ivana Ticha
We performed comprehensive molecular analysis of five cases of metastasizing uveal malignant melanoma (UM) (fresh-frozen samples) with an NGS panel of 73 genes. A likely pathogenic germline TP53 mutation c.760A > G (p.I254V) was found in two tumor samples and matched nontumor tissue. In three cases, pathogenic BAP1 mutation was detected together with germline missense variants of uncertain significance in ATM. All cases carried recurrent activating GNAQ or GNA11 mutation. Moreover, we analyzed samples from another 16 patients with primary UM by direct Sanger sequencing focusing only on TP53 coding region...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768958/bevacizumab-induced-atypical-hemolytic-uremic-syndrome-and-treatment-with-eculizumab
#14
Anusha Vakiti, Daulath Singh, Ravi Pilla, Muhamad A Moustafa, Kelly W Fitzpatrick
Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody used for the management of various solid malignancies including colorectal, lung, brain, renal, and ovarian cancers as well as age-related macular degeneration of the eye. It is a vascular endothelial growth factor inhibitor which exhibits its action by blocking the growth of blood vessels in cancerous tissue. Common side effects include hypertension, fatigue, headaches, and increased risk of infections. Atypical hemolytic uremic syndrome is a serious side effect associated with bevacizumab due to its anti-angiogenic effect...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29768710/improving-the-safety-of-high-dose-methotrexate-for-children-with-hematologic-cancers-in-settings-without-access-to-mtx-levels-using-extended-hydration-and-additional-leucovorin
#15
Kalthi Vaishnavi, Deepak Bansal, Amita Trehan, Richa Jain, Savita Verma Attri
BACKGROUND: A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. METHODS: The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively...
May 16, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29767721/bhd-associated-kidney-cancer-exhibits-unique-molecular-characteristics-and-a-wide-variety-of-variants-in-chromatin-remodeling-genes
#16
Hisashi Hasumi, Mitsuko Furuya, Kenji Tatsuno, Shogo Yamamoto, Masaya Baba, Yukiko Hasumi, Yasuhiro Isono, Kae Suzuki, Ryosuke Jikuya, Shinji Otake, Kentaro Muraoka, Kimito Osaka, Narihiko Hayashi, Kazuhide Makiyama, Yasuhide Miyoshi, Keiichi Kondo, Noboru Nakaigawa, Takashi Kawahara, Koji Izumi, Junichi Teranishi, Yasushi Yumura, Hiroji Uemura, Yoji Nagashima, Adam R Metwalli, Laura S Schmidt, Hiroyuki Aburatani, W Marston Linehan, Masahiro Yao
Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using LC/MS and GC/MS...
May 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29767474/mesenchymal-stromal-cells-from-shwachman-diamond-syndrome-patients-fail-to-recreate-a-bone-marrow-niche-in-vivo-and-exhibit-impaired-angiogenesis
#17
Donatella Bardelli, Erica Dander, Cristina Bugarin, Claudia Cappuzzello, Alice Pievani, Grazia Fazio, Paolo Pierani, Paola Corti, Piero Farruggia, Carlo Dufour, Simone Cesaro, Marco Cipolli, Andrea Biondi, Giovanna D'Amico
Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS-MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29766473/mr-imaging-findings-in-some-rare-neurological-complications-of-paediatric-cancer
#18
REVIEW
Tetsuhiko Okabe, Taiki Nozaki, Noriko Aida, Jay Starkey, Mikako Enokizono, Tetsu Niwa, Atsuhiko Handa, Yuji Numaguchi, Yasuyuki Kurihara
Neurological complications of paediatric cancers are a substantial problem. Complications can be primary from central nervous system (CNS) spread or secondary from indirect or remote effects of cancer, as well as cancer treatments such as chemotherapy and radiation therapy. In this review, we present the clinical and imaging findings of rare but important neurological complications in paediatric patients with cancer. Neurological complications are classified into three phases: pre-treatment, treatment and post-remission...
May 15, 2018: Insights Into Imaging
https://www.readbyqxmd.com/read/29766468/gemcitabine-induced-thrombotic-microangiopathy-with-nephrotic-syndrome
#19
Daisuke Katagiri, Fumihiko Hinoshita
We encountered a case of gemcitabine (GEM)-induced secondary thrombotic microangiopathy (TMA) with nephrotic syndrome. Advanced pancreatic cancer with liver metastasis had originally been diagnosed. Renal biopsy showed focal reduplication of the glomerular basement membrane, endothelial cell swelling, and narrowed capillary lumens with fragmented erythrocytes and fibrin deposition, compatible with TMA. Regular monitoring of renal function during GEM treatment and discontinuation of treatment if acute kidney injury (AKI) might occur is crucial, because AKI combined with TMA is life-threatening...
May 15, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29766397/novel-variant-of-unknown-significance-in-mutyh-in-a-patient-with-mutyh-associated-polyposis-a-case-to-reclassify
#20
Trilokesh D Kidambi, Dena Goldberg, Robert Nussbaum, Amie Blanco, Sarah E Umetsu, Jonathan P Terdiman, Jeffrey K Lee
MUTYH-associated polyposis (MAP) is a hereditary cancer syndrome that is caused by biallelic pathogenic variants in the MUTYH gene and should be evaluated for in patients with an attenuated colonic polyposis phenotype. Monoallelic pathogenic variants in MUTYH are associated with a moderate increased risk of colorectal cancer but not with the polyposis phenotype. We present a case of a patient presenting with multiple colonic adenomatous polyps, whose germline testing revealed a heterozygous pathogenic variant in MUTYH in exon 13, c...
May 15, 2018: Clinical Journal of Gastroenterology
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