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https://www.readbyqxmd.com/read/28431245/host-microbe-co-metabolism-dictates-cancer-drug-efficacy-in-c-%C3%A2-elegans
#1
Timothy A Scott, Leonor M Quintaneiro, Povilas Norvaisas, Prudence P Lui, Matthew P Wilson, Kit-Yi Leung, Lucia Herrera-Dominguez, Sonia Sudiwala, Alberto Pessia, Peter T Clayton, Kevin Bryson, Vidya Velagapudi, Philippa B Mills, Athanasios Typas, Nicholas D E Greene, Filipe Cabreiro
Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B6, B9, and ribonucleotide metabolism...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431244/bacterial-metabolism-affects-the-c-%C3%A2-elegans-response-to-cancer-chemotherapeutics
#2
Aurian P García-González, Ashlyn D Ritter, Shaleen Shrestha, Erik C Andersen, L Safak Yilmaz, Albertha J M Walhout
The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#3
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430867/emerging-evidence-for-the-role-of-differential-tumor-microenvironment-in-breast-cancer-racial-disparity-a-closer-look-at-the-surroundings
#4
Sachin Kumar Deshmukh, Sanjeev K Srivastava, Nikhil Tyagi, Aamir Ahmad, Ajay P Singh, Ahmed Al Ghadhban, Donna L Dyess, James E Carter, Kari Dugger, Seema Singh
Although increased awareness leading to early detection and prevention, as well as advancements in treatment strategies, have resulted in superior clinical outcomes, African American women with breast cancer continue to have greater mortality rates, compared to Caucasian American counterparts. Moreover, African American women are more likely to have breast cancer at a younger age and be diagnosed with aggressive tumor sub-types. Such racial disparities can be attributed to socioeconomic differences, but it is increasingly being recognized that these disparities may indeed be due to certain genetic and other non-genetic biological differences...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430823/modulation-the-alternative-splicing-of-gla-ivs4-919g-a-in-fabry-disease
#5
Wen-Hsin Chang, Dau-Ming Niu, Chi-Yu Lu, Shyr-Yi Lin, Ta-Chih Liu, Jan-Gowth Chang
While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA...
2017: PloS One
https://www.readbyqxmd.com/read/28430650/the-p-g534e-variant-of-habp2-is-not-associated-with-sporadic-papillary-thyroid-carcinoma-in-a-polish-population
#6
Artur Kowalik, Danuta Gąsior-Perczak, Martyna Gromek, Monika Siołek, Agnieszka Walczyk, Iwona Pałyga, Małgorzata Chłopek, Janusz Kopczyński, Ryszard Mężyk, Aldona Kowalska, Stanisław Góźdź
Thyroid cancer is one of the most frequently diagnosed cancers of the endocrine system. There are no known genetic risk factors for non-medullary thyroid cancer, other than a small number of hereditary syndromes; however, approximately 5% of non-medullary thyroid cancer, designated familial non-medullary thyroid cancer, exhibits heritability. The p.G534E (c.1601G>A) variant of HABP2 was recently reported as a risk factor for familial non-medullary thyroid cancer, including papillary thyroid carcinoma. We analyzed the incidence of the c...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430642/immunocompetent-mouse-allograft-models-for-development-of-therapies-to-target-breast-cancer-metastasis
#7
Yuan Yang, Howard H Yang, Ying Hu, Peter H Watson, Huaitian Liu, Thomas R Geiger, Miriam R Anver, Diana C Haines, Philip Martin, Jeffrey E Green, Maxwell P Lee, Kent W Hunter, Lalage M Wakefield
Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430593/genetic-variants-within-the-cancer-susceptibility-region-8q24-and-ovarian-cancer-risk-in-han-chinese-women
#8
Jing Han, Jing Zhou, Hua Yuan, Longbiao Zhu, Hongxia Ma, Dong Hang, Dake Li
Accumulating evidence suggests that genetic variants at chromosome 8q24 confer susceptibility to various types of cancer. This case-control study was designed to explore the relationship between genetic variants at 8q24 and ovarian cancer risk in Han Chinese women. Two variants (rs13281615 A > G and rs6983267 T > G) were genotyped in 377 ovarian cancer cases and 1034 cancer-free controls using TaqMan allelic discrimination assay. Logistic regression analysis revealed that the G allele of rs6983267 was significantly associated with increased risk of ovarian cancer (additive model: adjusted OR = 1...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430579/antiangiogenesis-and-gene-aberration-related-therapy-may-improve-overall-survival-in-patients-with-concurrent-kras-and-tp53-hotspot-mutant-cancer
#9
Zhijie Wang, Sarina Piha-Paul, Filip Janku, Vivek Subbiah, Naiyi Shi, Jing Gong, Chetna Wathoo, Kenna Shaw, Kenneth Hess, Russell Broaddus, Aung Naing, David Hong, Apostolia M Tsimberidou, Daniel Karp, James Yao, Funda Meric-Bernstam, Siqing Fu
PURPOSE: Genetic alterations such as activating KRAS and/or inactivating TP53 are thought to be the most common drivers to tumorigenesis. Therefore, we assessed phase I cancer patients with KRAS+/TP53+ mutations. RESULTS: Approximately 8% of patients referred to phase I clinical trials harbored concurrent KRAS and TP53 mutations. Patients who received a phase I trial therapy (n = 57) had a median OS of 12 months, compared with 4.6 months in those who were not treated (n = 106; p = 0...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430524/mirna-related-polymorphisms-in-mir-423-rs6505162-and-pex6-rs1129186-and-risk-of-esophageal-squamous-cell-carcinoma-in-an-iranian-cohort
#10
Ziba Nariman-Saleh-Fam, Milad Bastami, Mohammad Hossein Somi, Farkhondeh Behjati, Yaser Mansoori, Abdolreza Daraei, Zahra Saadatian, Lida Nariman-Saleh-Fam, Habibollah Mahmoodzadeh, Yashar Makhdoumi, Fatemeh Varshoee Tabrizi, Bahador Ebrahimi-Sharif, Azam Hezarian, Shahnaz Naghashi, Mohammad Reza Abbaszadegan, Javad Tavakkoly-Bazzaz
AIMS: Iran is located in the Asian esophageal cancer belt. It is a high-risk region for esophageal squamous cell carcinoma (ESCC). The extent to which genetic components, especially variants within miRNAs or their binding sites, contribute to risk of ESCC in the region is not yet fully understood. Herein, tests were done on an Iranian cohort to evaluate the association of miRNA-related polymorphisms in miR-423 (rs6505162) and peroxisomal biogenesis factor 6 (PEX6) (rs1129186 within a miR-149-5p-binding site) with risk of ESCC risk...
April 21, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28429737/the-glutamate-cystine-xct-antiporter-antagonizes-glutamine-metabolism-and-reduces-nutrient-flexibility
#11
Chun-Shik Shin, Prashant Mishra, Jeramie D Watrous, Valerio Carelli, Marilena D'Aurelio, Mohit Jain, David C Chan
As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system xc(-)), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429735/phylogenetic-analysis-of-metastatic-progression-in-breast-cancer-using-somatic-mutations-and-copy-number-aberrations
#12
David Brown, Dominiek Smeets, Borbála Székely, Denis Larsimont, A Marcell Szász, Pierre-Yves Adnet, Françoise Rothé, Ghizlane Rouas, Zsófia I Nagy, Zsófia Faragó, Anna-Mária Tőkés, Magdolna Dank, Gyöngyvér Szentmártoni, Nóra Udvarhelyi, Gabriele Zoppoli, Lajos Pusztai, Martine Piccart, Janina Kulka, Diether Lambrechts, Christos Sotiriou, Christine Desmedt
Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#13
Pedro da Silva-Coelho, Leonie I Kroeze, Kenichi Yoshida, Theresia N Koorenhof-Scheele, Ruth Knops, Louis T van de Locht, Aniek O de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M A Blijlevens, Petra Muus, Gerwin Huls, Bert A van der Reijden, Seishi Ogawa, Joop H Jansen
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429638/an-unusual-presentation-of-a-cervical-paraspinal-leiomyoma-in-an-adolescent-female
#14
Jeffrey A Swarz, Arayamparambil C Anilkumar, Douglas C Miller, N Scott Litofsky, Tomoko Tanaka
Objective We describe an apparently unique case of an extra-uterine leiomyoma in the cervical paraspinus including its evaluation and management. Methods A 14-year-old girl was referred to the neurology clinic for an abnormal head CT following a concussion. MRI revealed a homogenously enhancing left cervical paraspinal mass. The patient underwent complete resection and subsequent genetic testing and counseling were obtained to determine the presence of Li-Fraumeni Syndrome (LFS) or Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) mutations...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28429243/slco1b1-polymorphisms-and-plasma-estrone-conjugates-in-postmenopausal-women-with-er-%C3%A2-breast-cancer-genome-wide-association-studies-of-the-estrone-pathway
#15
Tanda M Dudenkov, James N Ingle, Aman U Buzdar, Mark E Robson, Michiaki Kubo, Irada Ibrahim-Zada, Anthony Batzler, Gregory D Jenkins, Tracy L Pietrzak, Erin E Carlson, Poulami Barman, Matthew P Goetz, Donald W Northfelt, Alvaro Moreno-Aspita, Clark V Williard, Krishna R Kalari, Yusuke Nakamura, Liewei Wang, Richard M Weinshilboum
BACKGROUND: Estrone (E1), the major circulating estrogen in postmenopausal women, promotes estrogen-receptor positive (ER+) breast tumor growth and proliferation. Two major reactions contribute to E1 plasma concentrations, aromatase (CYP19A1) catalyzed E1 synthesis from androstenedione and steroid sulfatase (STS) catalyzed hydrolysis of estrone conjugates (E1Cs). E1Cs have been associated with breast cancer risk and may contribute to tumor progression since STS is expressed in breast cancer where its activity exceeds that of aromatase...
April 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28429075/toward-personalized-management-in-bladder-cancer-the-promise-of-novel-molecular-taxonomy
#16
REVIEW
Marie-Lisa Eich, Lars Dyrskjøt, George J Netto
Empowered by the recent advances in next generation sequencing and bioinformatics technology, an unprecedented wave of integrated transcriptomic and genomic studies have impacted the field of bladder cancer. These studies not only have confirmed previously charted genetic pathways in bladder cancer development but also have led to the discovery of numerous additional crucial driver genetic alterations. As a result, a novel genomic-based taxonomy is emerging that promises to better define clinically relevant intrinsic subtypes of bladder cancer...
April 21, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28428902/nonfamilial-juvenile-polyposis-syndrome-with-exon-5-novel-mutation-in-smad-4-gene
#17
Amna Ahmed, Badr Alsaleem
Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder, characterized by multiple juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. JPS is most frequently caused by mutations in the SMAD4 or BMPR1A genes. Herein, we report a child with juvenile polyposis syndrome (JPS) with a novel mutation in the SMAD4 gene. An 8-year-old boy presented with recurrent rectal bleeding and was found to have multiple polyps in the entire colon. The histology of the resected polyps was consistent with juvenile polyps...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28428723/what-is-the-quantitative-risk-of-gastric-cancer-in-the-first-degree-relatives-of-patients-a-meta-analysis
#18
Mohammad Yaghoobi, Julia McNabb-Baltar, Raheleh Bijarchi, Richard H Hunt
AIM: To quantify the risk of gastric cancer in first-degree relatives of patients with the cancer. METHODS: A comprehensive literature search was performed. Case-control trials comparing the frequency of a positive family history of gastric cancer in patients with gastric cancer, vs non-gastric cancer controls were retrieved. Studies with missed or non-extractable data, studies in children, abstracts, and duplicate publications were excluded. A meta-analysis of pooled odd ratios was performed using Review Manager 5...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428503/-cancer-immunotherapy-utilizing-t-cell-receptor-gene-engineering
#19
Hiroaki Ikeda
Immune-checkpoint inhibitors have shown their efficacy in the treatment of patients with many kinds of progressive/relapsed cancers. However, the efficacy remains as 10-40%of the patients in most type of cancers, suggesting that the development of new therapy for patients resistant to the therapy is an urgent unmet need. Adoptive therapy with tumor-specific T cells is a promising therapy that can be effective in patients who are not benefited from the immune-checkpoint inhibitors. The T cell therapy with genetic engineering in T cell receptor(TCR)is expected to be a universal therapy because this therapy can be applicable for patients with many kinds of cancers...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28428355/plasma-urate-cancer-incidence-and-all-cause-mortality-a-mendelian-randomization-study
#20
Camilla J Kobylecki, Shoaib Afzal, Børge G Nordestgaard
BACKGROUND: Observationally, high plasma urate is associated with high risk of cancer. We using a Mendelian randomization design to test the hypothesis that high concentrations of plasma urate are associated with high cancer incidence and all-cause mortality observationally and genetically. METHODS: We performed observational and genetic analyses using plasma urate and the urate solute carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from the Copenhagen General Population Study...
April 20, 2017: Clinical Chemistry
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