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https://www.readbyqxmd.com/read/28062115/genotype-matched-treatment-for-patients-with-advanced-type-i-epithelial-ovarian-cancer-eoc
#1
A Spreafico, A M Oza, B A Clarke, H J Mackay, P Shaw, M Butler, N C Dhani, S Lheureux, M K Wilson, S Welch, T Zhang, C Yu, T Stockley, L L Siu, S Kamel-Reid, P L Bedard
BACKGROUND: Genomic alterations that activate the MAPK signaling pathway frequently occur in Type I Epithelial Ovarian Cancers (EOCs). We evaluated therapeutic response outcomes in patients with type I EOC treated with genotype-matched therapy on clinical trials enrolled in a prospective molecular profiling program. MATERIAL AND METHODS: Formalin fixed paraffin embedded tumor tissues were prospectively screened for genomic alterations using MALDI-ToF mass-spectrometry platform or targeted sequencing using the Illumina MiSeq TruSeq Amplicon Cancer Panel...
January 3, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28049216/cancer-implications-for-patients-with-endometriosis
#2
Mary Ann Wilbur, Ie-Ming Shih, James H Segars, Amanda N Fader
Endometriosis is defined as the presence of viable endometrial glands and stroma outside of the uterus. It is a common disease, occurring in 5 to 15% of all women. Endometriosis is associated with chronic pelvic pain and infertility and often requires surgical intervention for definitive treatment. Although it is a benign gynecologic condition, endometriosis shares pathophysiologic features with cancer. In recent years, both histologic and epidemiologic evidence has accumulated, suggesting that ovarian endometriosis may give rise to malignant ovarian tumors, primarily those that are epithelial in origin, known as endometriosis-associated ovarian carcinoma (EAOC) including ovarian clear cell carcinoma, endometrioid carcinoma, and the least common, seromucinous tumors...
January 3, 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#3
REVIEW
Reem Ali, Emad A Rakha, Srinivasan Madhusudan, Helen E Bryant
The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors...
December 26, 2016: Pathology
https://www.readbyqxmd.com/read/27999207/roles-of-gsk-3-and-micrornas-on-epithelial-mesenchymal-transition-and-cancer-stem-cells
#4
REVIEW
James A McCubrey, Timothy L Fitzgerald, Li V Yang, Kvin Lertpiriyapong, Linda S Steelman, Stephen L Abrams, Giuseppe Montalto, Melchiorre Cervello, Luca M Neri, Lucio Cocco, Alberto M Martelli, Piotr Laidler, Joanna DuliÅ Ska-Litewka, Dariusz Rakus, Agnieszka Gizak, Ferdinando Nicoletti, Luca Falzone, Saverio Candido, Massimo Libra
Various signaling pathways exert critical roles in the epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). The Wnt/beta-catenin, PI3K/PTEN/Akt/mTORC, Ras/Raf/MEK/ERK, hedgehog (Hh), Notch and TP53 pathways elicit essential regulatory influences on cancer initiation, EMT and progression. A common kinase involved in all these pathways is moon-lighting kinase glycogen synthase kinase-3 (GSK-3). These pathways are also regulated by micro-RNAs (miRs). TP53 and components of these pathways can regulate the expression of miRs...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27995550/somatic-mutations-in-prostate-cancer-closer-to-personalized-medicine
#5
REVIEW
M J Alvarez-Cubero, L J Martinez-Gonzalez, I Robles-Fernandez, J Martinez-Herrera, G Garcia-Rodriguez, M Pascual-Geler, J M Cozar, J A Lorente
The molecular cause of prostate cancer (PCa) is still unclear; however, its progression involves androgen, PI3K/Akt, and PTEN signaling, as cycle and apoptotic pathways. Alterations in oncogenes and tumor suppressor genes as PIK3CA, BRAF, KRAS and TP53 are not very common. Recently, somatic mutations have been discovered in relation to cancer progression mainly in genes such as PIK3CA; however, little data has been described in PCa. Nowadays genetic tools allow us to investigate multiple details about the biological heterogeneity of PCa, to better understand the mechanisms of disease progression and treatment resistance...
December 19, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27959386/pink1-signaling-in-mitochondrial-homeostasis-and-in-aging-review
#6
Yasuko Kitagishi, Noriko Nakano, Mako Ogino, Mayuko Ichimura, Akari Minami, Satoru Matsuda
Mitochondrial dysfunction is involved in the pathology of Parkinson's disease, an age-associated neurodegenerative disorder. Phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1) is responsible for the most common form of recessive Parkinson's disease. PINK1 is a mitochondrial kinase that is involved in mitrochondrial quality control and promotes cell survival. PINK1 has been shown to protect against neuronal cell death induced by oxidative stress. Accordingly, PINK1 deficiency is associated with mitochondrial dysfunction as well as increased oxidative cellular stress and subsequent neuronal cell death...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27941540/new-and-emerging-diagnostic-and-prognostic-immunohistochemical-biomarkers-in-prostate-pathology
#7
Giovanna A Giannico, Shanna A Arnold, Lan L Gellert, Omar Hameed
The diagnosis of minimal prostatic adenocarcinoma can be challenging on prostate needle biopsy, and immunohistochemistry may be used to support the diagnosis of cancer. The International Society of Urologic Pathology currently recommends the use of the basal cell markers high-molecular-weight cytokeraratin and p63, and α-methylacyl-coenzyme-A racemase. However, there are caveats associated with the interpretation of these markers, particularly with benign mimickers. Another issue is that of early detection of presence and progression of disease and prediction of recurrence after clinical intervention...
January 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/27913052/evaluation-of-erg-and-pten-protein-expression-in-cribriform-architecture-prostate-carcinomas
#8
Michelle R Downes, Swati Satturwar, Dominique Trudel, Theo H van der Kwast
ERG and PTEN have been suggested as potential prognostic markers in prostatic adenocarcinoma. We assessed the relationship between ERG and PTEN protein expression in cribriform architecture prostatic carcinomas and adjacent acinar non-cribriform carcinoma and determined the interobserver variability in assessment of these markers. A contemporary cohort of radical prostatectomy cases (n=246) were reviewed and cribriform architecture carcinomas (intraductal carcinoma and cribriform Gleason 4 carcinomas) were identified and confirmed with triple cocktail immunostaining...
January 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27911343/pink1-parkin-and-mitochondrial-quality-control-what-can-we-learn-about-parkinson-s-disease-pathobiology
#9
Dominika Truban, Xu Hou, Thomas R Caulfield, Fabienne C Fiesel, Wolfdieter Springer
The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy...
November 30, 2016: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/27903278/an-overview-on-the-role-of-dietary-phenolics-for-the-treatment-of-cancers
#10
REVIEW
Preethi G Anantharaju, Prathima C Gowda, Manjunatha G Vimalambike, SubbaRao V Madhunapantula
Plant derived phenolic compounds have been shown to inhibit the initiation and progression of cancers by modulating genes regulating key processes such as: (a) oncogenic transformation of normal cells; (b) growth and development of tumors; and (c) angiogenesis and metastasis. Recent studies focusing on identifying the molecular basis of plant phenolics-induced cancer cell death have demonstrated down-regulation of: (a) oncogenic survival kinases such as PI3K and Akt; (b) cell proliferation regulators that include Erk1/2, D-type Cyclins, and Cyclin Dependent Kinases (CDKs); (c) transcription factors such as NF-kβ, NRF2 and STATs; (d) histone deacetylases HDAC1 and HDAC2; and (e) angiogenic factors VEGF, FGFR1 and MIC-1...
December 1, 2016: Nutrition Journal
https://www.readbyqxmd.com/read/27889578/molecular-neurobiology-of-mtor
#11
REVIEW
Katarzyna Switon, Katarzyna Kotulska, Aleksandra Janusz-Kaminska, Justyna Zmorzynska, Jacek Jaworski
Mammalian/mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that controls several important aspects of mammalian cell function. mTOR activity is modulated by various intra- and extracellular factors; in turn, mTOR changes rates of translation, transcription, protein degradation, cell signaling, metabolism, and cytoskeleton dynamics. mTOR has been repeatedly shown to participate in neuronal development and the proper functioning of mature neurons. Changes in mTOR activity are often observed in nervous system diseases, including genetic diseases (e...
January 26, 2017: Neuroscience
https://www.readbyqxmd.com/read/27881603/a-protective-role-of-il-37-in-cancer-a-new-hope-for-cancer-patients
#12
REVIEW
Ayoub Abulkhir, Suzanne Samarani, Devendra Amre, Michel Duval, Elie Haddad, Daniel Sinnett, Jean-Marie Leclerc, Caroline Diorio, Ali Ahmad
IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties. It is produced as a precursor without a classic signal peptide. The precursor is cleaved into mature form in the cytoplasm by caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to the nucleus, and suppresses transcription of several proinflammatory genes...
November 23, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27866258/fat-containing-soft-tissue-masses-in-children
#13
REVIEW
Elizabeth F Sheybani, Eric P Eutsler, Oscar M Navarro
The diagnosis of soft-tissue masses in children can be difficult because of the frequently nonspecific clinical and imaging characteristics of these lesions. However key findings on imaging can aid in diagnosis. The identification of macroscopic fat within a soft-tissue mass narrows the differential diagnosis considerably and suggests a high likelihood of a benign etiology in children. Fat can be difficult to detect with sonography because of the variable appearance of fat using this modality. Fat is easier to recognize using MRI, particularly with the aid of fat-suppression techniques...
December 2016: Pediatric Radiology
https://www.readbyqxmd.com/read/27860216/somatic-overgrowth-disorders-of-the-pi3k-akt-mtor-pathway-therapeutic-strategies
#14
REVIEW
Kim M Keppler-Noreuil, Victoria E R Parker, Thomas N Darling, Julian A Martinez-Agosto
The phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway plays an essential role in regulation of normal cell growth, metabolism, and survival. Somatic activating mutations in the PI3K/AKT/mTOR pathway are among the most common mutations identified in cancer, and have been shown to cause a spectrum of overgrowth syndromes including PIK3CA-Related Overgrowth Spectrum, Proteus syndrome, and brain overgrowth conditions. Clinical findings in these disorders may be isolated or multiple, including sporadic or mosaic overgrowth (adipose, skeletal, muscle, brain, vascular, or lymphatic), and skin abnormalities (including epidermal nevi, hyper-, and hypopigmented lesions), and have the potential risk of tumorigenesis...
December 2016: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/27843613/mechanisms-of-resistance-to-egfr-targeted-drugs-lung-cancer
#15
REVIEW
Floriana Morgillo, Carminia Maria Della Corte, Morena Fasano, Fortunato Ciardiello
Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains unfavourable because of the occurrence of either intrinsic or acquired resistance. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing EGFR-TKIs resistance mechanisms discovered in preclinical models and in patients with NSCLC...
2016: ESMO Open
https://www.readbyqxmd.com/read/27826621/effective-pi3k-modulators-for-improved-therapy-against-malignant-tumors-and-for-neuroprotection-of-brain-damage-after-tumor-therapy-review
#16
Satoru Matsuda, Mayuko Ichimura, Mako Ogino, Noriko Nakano, Akari Minami, Toshiyuki Murai, Yasuko Kitagishi
Due to the key role in various cellular processes including cell proliferation and cell survival on many cell types, dysregulation of the PI3K/AKT pathway represents a crucial step of the pathogenesis in many diseases. Furthermore, the tumor suppressor PTEN negatively regulates the PI3K/AKT pathway through its lipid phosphatase activity, which is recognized as one of the most frequently deleted and/or mutated genes in human cancer. Given the pervasive involvement of this pathway, the development of the molecules that modulate this PI3K/AKT signaling has been initiated in studies which focus on the extensive effective drug discovery...
November 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27821131/frequency-of-egfr-t790m-mutation-and-multimutational-profiles-of-rebiopsy-samples-from-non-small-cell-lung-cancer-developing-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors-in-japanese-patients
#17
Ryo Ko, Hirotsugu Kenmotsu, Masakuni Serizawa, Yasuhiro Koh, Kazushige Wakuda, Akira Ono, Tetsuhiko Taira, Tateaki Naito, Haruyasu Murakami, Mitsuhiro Isaka, Masahiro Endo, Takashi Nakajima, Yasuhisa Ohde, Nobuyuki Yamamoto, Kazuhisa Takahashi, Toshiaki Takahashi
BACKGROUND: The majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs. METHODS: We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs...
November 8, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27807828/anxa7-gtpase-as-tumor-suppressor-mechanisms-and-therapeutic-opportunities
#18
Ximena Leighton, Ofer Eidelman, Catherine Jozwik, Harvey B Pollard, Meera Srivastava
Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity at 10q, are commonly observed in most human tumors, including prostate, breast, and kidney cancers. The ANXA7-GTPase is a tumor suppressor, which is frequently inactivated by genomic alterations at 10q21. In the last few years, considerable amounts of data have accumulated describing inactivation of ANXA7-GTPase in a variety of human malignancies and demonstrating the tumor suppressor potential of ANXA7-GTPase. ANXA7-GTPase contains a calcium binding domain that classifies it as a member of the annexin family...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27785100/current-advances-in-biomarkers-for-targeted-therapy-in-triple-negative-breast-cancer
#19
REVIEW
Brett Fleisher, Charlotte Clarke, Sihem Ait-Oudhia
Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27753448/the-molecular-underpinnings-of-prostate-cancer-impacts-on-management-and-pathology-practice
#20
REVIEW
Daniel Nava Rodrigues, Gunther Boysen, Semini Sumanasuriya, George Seed, Angelo M De Marzo, Johann de Bono
Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognised as biomarkers of resistance to AR-targeted therapies such as abiraterone or enzalutamide...
January 2017: Journal of Pathology
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