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https://www.readbyqxmd.com/read/28341751/low-recombination-proficiency-score-rps-predicts-heightened-sensitivity-to-dna-damaging-chemotherapy-in-breast-cancer
#1
Sean Pitroda, Riyue Bao, Jorge Andrade, Ralph R Weichselbaum, Philip P Connell
PURPOSE: Molecular-based cancer tests have been developed to augment the standard clinical and pathologic features used to tailor treatments to individual breast cancer patients. Homologous recombination (HR) repairs double-stranded DNA breaks and promotes tolerance to lesions that disrupt DNA replication. Recombination Proficiency Score (RPS) quantifies HR efficiency based on the expression of four genes involved in DNA damage repair. We hypothesized low RPS values can identify HR-deficient breast cancers most sensitive to DNA-damaging chemotherapy...
March 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28338192/application-of-percutaneous-epididymal-sperm-aspiration-in-azoospermia
#2
L Hao, Z-G Li, H-G He, Z-G Zhang, J-J Zhang, Y Dong, Z-B Li, C-H Han
OBJECTIVE: The present study introduces the application of percutaneous epididymal sperm aspiration (PESA) for diagnosis of obstructive azoospermia and non-obstructive azoospermia. PATIENTS AND METHODS: 96 cases diagnosed with azoospermia were selected, standard methods were used to measure testicular volume, chemiluminescence was used to test serum sexual hormone levels, and No. 7 butterfly needles were applied to puncture the head of the epididymis and aspirate epididymal luminal fluid...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28337939/bidirectional-apical-basal-traffic-of-the-cation-independent-mannose-6-phosphate-receptor-in-brain-endothelial-cells
#3
Piotr Siupka, Maria Ns Hersom, Karin Lykke-Hartmann, Kasper B Johnsen, Louiza B Thomsen, Thomas L Andresen, Torben Moos, N Joan Abbott, Birger Brodin, Morten S Nielsen
Brain capillary endothelium mediates the exchange of nutrients between blood and brain parenchyma. This barrier function of the brain capillaries also limits passage of pharmaceuticals from blood to brain, which hinders treatment of several neurological disorders. Receptor-mediated transport has been suggested as a potential pharmaceutical delivery route across the brain endothelium, e.g. reports have shown that the transferrin receptor (TfR) facilitates transcytosis of TfR antibodies, but it is not known whether this recycling receptor itself traffics from apical to basal membrane in the process...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28331237/restricted-axillary-staging-in-clinically-and-sonographically-node-negative-early-invasive-breast-cancer-c-it1-2-in-the-context-of-breast-conserving-therapy-first-results-following-commencement-of-the-intergroup-sentinel-mamma-insema-trial
#4
T Reimer, A Stachs, V Nekljudova, S Loibl, S Hartmann, K Wolter, G Hildebrandt, B Gerber
Axillary lymph node status remains an important prognostic factor in early breast cancer. It is regarded as an indicator for (neo)adjuvant systemic treatment and postoperative radiotherapy of the regional lymphatics. Commenced in September 2015, the INSEMA trial is investigating whether operative determination of nodal status as part of breast conserving therapy (BCT) for early stage breast cancer (c/iT1-2 c/iN0) can be avoided without reducing oncological safety. After inclusion of 1001 patients there was general acceptance of the complex study design by patients and study doctors so that recruitment for the first randomisation (axillary sentinel lymph node biopsy [SLNB]: yes or no) achieved predicted case numbers...
February 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/28327201/detecting-gene-signature-activation-in-breast-cancer-in-an-absolute-single-patient-manner
#5
E R Paquet, R Lesurf, A Tofigh, V Dumeaux, M T Hallett
BACKGROUND: The ability to reliably identify the state (activated, repressed, or latent) of any molecular process in the tumor of a patient from an individual whole-genome gene expression profile obtained from microarray or RNA sequencing (RNA-seq) promises important clinical utility. Unfortunately, all previous bioinformatics tools are only applicable in large and diverse panels of patients, or are limited to a single specific pathway/process (e.g. proliferation). METHODS: Using a panel of 4510 whole-genome gene expression profiles from 10 different studies we built and selected models predicting the activation status of a compendium of 1733 different biological processes...
March 21, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28320888/mutual-reinforcement-of-pathophysiological-host-microbe-interactions-in-intestinal-stasis-models
#6
Ketrija Touw, Daina L Ringus, Nathaniel Hubert, Yunwei Wang, Vanessa A Leone, Anuradha Nadimpalli, Betty R Theriault, Yong E Huang, Johnathan D Tune, Paul B Herring, Gianrico Farrugia, Purna C Kashyap, Dionysios A Antonopoulos, Eugene B Chang
Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models - an opioid-induced constipation model in mice, and a humanized mouse model where germ-free mice were colonized with stool from a patient with constipation-predominant irritable bowel syndrome (IBS-C) in humans...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28319095/rcn1-suppresses-er-stress-induced-apoptosis-via-calcium-homeostasis-and-perk-chop-signaling
#7
S Xu, Y Xu, L Chen, Q Fang, S Song, J Chen, J Teng
Endoplasmic reticulum (ER) stress is caused by the disturbance of ER homeostasis and leads to the activation of the unfolded protein response (UPR), which alleviates stress at an early stage and triggers apoptosis if homeostasis fails over a prolonged timeframe. Here, we report that reticulocalbin 1 (RCN1), a member of the CREC family, is transactivated by nuclear factor kappa B (NF-κB) during ER stress and inhibits ER stress-induced apoptosis. The depletion of RCN1 increases the UPR during drug-induced ER stress by activating PRKR-like ER kinase-CCAAT/enhancer-binding protein-homologous protein (PERK-CHOP) signaling, thus inducing apoptosis...
March 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28316088/gata3-expression-in-benign-prostate-glands-with-radiation-atypia-a-diagnostic-pitfall
#8
Wei Tian, David Dorn, Shi Wei, Ronald D Sanders, Andres Matoso, Rajal B Shah, Jennifer Gordetsky
OBJECTIVE: Patients who have undergone prostate radiation are at an increased risk for developing urothelial carcinoma. Radiation changes can cause significant cytologic atypia in benign prostate glands that may mimic pagetoid spread of urothelial carcinoma. GATA3 is a common marker to differentiate prostatic adenocarcinoma from urothelial carcinoma. We investigated the expression of GATA3 in the epithelium of irradiated benign and malignant prostate tissue. METHODS: We performed a retrospective review of prostate cases with radiation atypia...
March 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28315938/the-relationship-between-breast-cancer-molecular-subtypes-and-mast-cell-populations-in-tumor-microenvironment
#9
Anna Glajcar, Joanna Szpor, Agnieszka Pacek, Katarzyna Ewa Tyrak, Florence Chan, Joanna Streb, Diana Hodorowicz-Zaniewska, Krzysztof Okoń
Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples...
March 18, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28315445/evaluation-of-pept1-transport-of-food-derived-antihypertensive-peptides-ile-pro-pro-and-leu-lys-pro-using-in-vitro-ex-vivo-and-in-vivo-transport-models
#10
John P Gleeson, David J Brayden, Sinéad M Ryan
Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP) are food-derived antihypertensive peptides which inhibit angiotensin-converting enzyme (ACE) and may have potential to attenuate hypertension. There is debate over their mechanism of uptake across small intestinal epithelia, but paracellular and PepT1 carrier-mediated uptake are thought to be important routes. The aim of this study was to determine their routes of intestinal permeability using in vitro, ex vivo and in vivo intestinal models. The presence of an apical side pH of 6...
March 14, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28315066/failure-patterns-according-to-molecular-subtype-in-patients-with-invasive-breast-cancer-following-postoperative-adjuvant-radiotherapy-long-term-outcomes-in-contemporary-clinical-practice
#11
Yu Jin Lim, Sea-Won Lee, Noorie Choi, Jeanny Kwon, Keun-Yong Eom, Eunyoung Kang, Eun-Kyu Kim, Sung-Won Kim, Jee Hyun Kim, Yu Jung Kim, Se Hyun Kim, So Yeon Park, Jae-Sung Kim, In Ah Kim
PURPOSE: Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer. METHODS: We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(-), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St...
March 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28295860/relationships-between-mri-breast-imaging-reporting-and-data-system-bi-rads-lexicon-descriptors-and-breast-cancer-molecular-subtypes-internal-enhancement-is-associated-with-luminal-b-subtype
#12
Lars J Grimm, Jing Zhang, Jay A Baker, Mary S Soo, Karen S Johnson, Maciej A Mazurowski
The aim of this study was to determine the associations between breast MRI findings using the Breast Imaging-Reporting and Data System (BI-RADS) lexicon descriptors and breast cancer molecular subtypes. In this retrospective, IRB-approved, single institution study MRIs from 278 women with breast cancer were reviewed by one of six fellowship-trained breast imagers. Readers reported BI-RADS descriptors for breast masses (shape, margin, internal enhancement) and non-mass enhancement (distribution, internal enhancement)...
March 13, 2017: Breast Journal
https://www.readbyqxmd.com/read/28295245/body-mass-index-pam50-subtype-recurrence-and-survival-among-patients-with-nonmetastatic-breast-cancer
#13
Elizabeth M Cespedes Feliciano, Marilyn L Kwan, Lawrence H Kushi, Wendy Y Chen, Erin K Weltzien, Adrienne L Castillo, Carol Sweeney, Philip S Bernard, Bette J Caan
BACKGROUND: Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. METHODS: This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013...
March 13, 2017: Cancer
https://www.readbyqxmd.com/read/28288348/a-microengineered-collagen-scaffold-for-generating-a-polarized-crypt-villus-architecture-of-human-small-intestinal-epithelium
#14
Yuli Wang, Dulan B Gunasekara, Mark I Reed, Matthew DiSalvo, Scott J Bultman, Christopher E Sims, Scott T Magness, Nancy L Allbritton
The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available...
March 6, 2017: Biomaterials
https://www.readbyqxmd.com/read/28275418/sex-differences-of-the-natriuretic-peptide-polymorphism-associated-with-angiographic-coronary-atherosclerosis
#15
Terry Y Li, M Yat Tse, Stephen C Pang, Catherine S McLellan, Will D King, Amer M Johri
BACKGROUND: Polymorphisms within natriuretic peptide (NP) genes have been associated with clinical outcomes for cardiovascular disease (CVD), but no previous study has compared the effect of these polymorphisms between men and women. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in key genes of the NP system and coronary angiographic outcomes, with the focus on the sexual dimorphism in the effects of these SNPs. METHODS: Patients undergoing clinically indicated coronary angiography (n = 513, 328 men and 185 women) were consented and genotyped for NPPA rs5065, NPPB rs198389 and NPR2 rs10758325...
February 2017: Cardiology Research
https://www.readbyqxmd.com/read/28273970/clinicopathological-features-of-triple-negative-breast-carcinoma
#16
Gowry Maram Reddy, Pooja K Suresh, Radha R Pai
INTRODUCTION: Breast carcinoma is one of the most common malignancies affecting women in developing countries. Molecular studies of breast carcinoma have classified the tumour based on the immunohistochemical staining into 4 subtypes, such as Luminal A, Luminal B, HER2/neu Positive and Triple Negative Breast Carcinoma (TNBC). TNBCs are reported to have an aggressive behaviour and wide metastasis, leading to selective treatment outcomes. AIM: The aim was to study the clinicopathological features such as age, site, tumour size, histopathological type, histologic grade, lymph node status, stage and treatment outcomes of triple negative breast carcinoma...
January 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28270497/neopalana-neoadjuvant-palbociclib-a-cyclin-dependent-kinase-4-6-inhibitor-and-anastrozole-for-clinical-stage-2-or-3-estrogen-receptor-positive-breast-cancer
#17
Cynthia X Ma, Feng Gao, Jingqin Luo, Donald W Northfelt, Matthew P Goetz, Andres Forero, Jeremy Hoog, Michael J Naughton, Foluso Ademuyiwa, Rama Suresh, Karen S Anderson, Julie Margenthaler, Rebecca Aft, Timothy J Hobday, Timothy Moynihan, William Gillanders, Amy Cyr, Timothy J Eberlein, Tina Hieken, Helen Krontiras, Zhanfang Guo, Michelle Lee, Nicholas C Spies, Zachary L Skidmore, Obi L Griffith, Malachi Griffith, Shana Thomas, Caroline Bumb, Kiran Vij, Cynthia Huang Bartlett, Maria Koehler, Hussam Al-Kateb, Souzan Sanati, Matthew J Ellis
PURPOSE: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. EXPERIMENTAL DESIGN: Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28262971/the-opportunity-of-precision-medicine-for-breast-cancer-with-context-sensitive-tumor-suppressor-maspin
#18
Margarida M Bernardo, Sijana H Dzinic, Maria J Matta, Ivory Dean, Lina Saker, Shijie Sheng
To improve the precision of molecular diagnosis and to develop and guide targeted therapies of breast cancer, it is essential to determine the mechanisms that underlie the specific tumor phenotypes. To this end, the application of a snapshot of gene expression profile for breast cancer diagnosis and prognosis is fundamentally challenged since the tissue-based data are derived from heterogonous cell types and are not likely to reflect the dynamics of context-dependent tumor progression and drug sensitivity. The intricate network of epithelial differentiation program can be concertedly controlled by tumor suppressor maspin, a homologue of clade B serine protease inhibitors (serpin), through its multifaceted molecular interactions in multiple subcellular localizations...
March 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28262504/mitochondrial-ca-2-uniporter-is-a-mitochondrial-luminal-redox-sensor-that-augments-mcu-channel-activity
#19
Zhiwei Dong, Santhanam Shanmughapriya, Dhanendra Tomar, Naveed Siddiqui, Solomon Lynch, Neeharika Nemani, Sarah L Breves, Xueqian Zhang, Aparna Tripathi, Palaniappan Palaniappan, Massimo F Riitano, Alison M Worth, Ajay Seelam, Edmund Carvalho, Ramasamy Subbiah, Fabián Jaña, Jonathan Soboloff, Yizhi Peng, Joseph Y Cheung, Suresh K Joseph, Jeffrey Caplan, Sudarsan Rajan, Peter B Stathopulos, Muniswamy Madesh
Ca(2+) dynamics and oxidative signaling are fundamental mechanisms for mitochondrial bioenergetics and cell function. The MCU complex is the major pathway by which these signals are integrated in mitochondria. Whether and how these coactive elements interact with MCU have not been established. As an approach toward understanding the regulation of MCU channel by oxidative milieu, we adapted inflammatory and hypoxia models. We identified the conserved cysteine 97 (Cys-97) to be the only reactive thiol in human MCU that undergoes S-glutathionylation...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28260828/differential-site-based-expression-of-pentose-phosphate-pathway-related-proteins-among-breast-cancer-metastases
#20
Yoon Jin Cha, Woo Hee Jung, Ja Seung Koo
Purpose. We aimed to investigate the expression of pentose phosphate pathway- (PPP-) related proteins in metastatic breast cancer and its relationship with clinicopathologic factors. Methods. Tissue samples from 126 metastatic breast cancers were included in a tissue microarray. Expression of PPP-related proteins [glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL), 6-phosphogluconate dehydrogenase (6PGDH), and nuclear factor erythroid 2-related factor (NRF2)] was determined by immunohistochemistry...
2017: Disease Markers
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