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https://www.readbyqxmd.com/read/28732326/therapeutic-applications-of-histone-deacetylase-inhibitors-in-sarcoma
#1
REVIEW
Fan Tang, Edwin Choy, Chongqi Tu, Francis Hornicek, Zhenfeng Duan
Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis...
July 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28732118/pd-1-checkpoint-blockade-in-combination-with-an-mtor-inhibitor-restrains-hepatocellular-carcinoma-growth-induced-by-hepatoma-cell-intrinsic-pd-1
#2
Hui Li, Xiaoqiang Li, Shuang Liu, Lei Guo, Bo Zhang, Jubo Zhang, Qinghai Ye
Inhibitors of PD-1 administered as single agents have resulted in durable tumor regression in advanced cancer patients. However, only a minority of cancer patients respond to anti PD-1 immunotherapy. Here, we show that PD-1 expression in hepatocellular carcinoma (HCC) promotes tumor growth independently of adaptive immunity. Knockdown of PD-1 suppress tumor growth, whereas PD-1 overexpression enhances tumorigenesis in immunodeficient xenografted mice. Mechanistically, PD-1 binds the downstream mTOR effectors eukaryotic initiation factor 4E (eIF4E) and ribosomal protein S6 (S6), thus promoting their phosphorylation...
July 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28731945/the-changing-paradigm-of-radiotherapy-in-the-elderly-population
#3
Myer Raphael Pfeffer, Philip Blumenfeld
There is increasing awareness of the special needs for care of the elderly cancer patient. Newer precise conformal radiotherapy techniques allow the safe delivery of higher doses of radiotherapy to the target tumor while reducing the dose to surrounding critical organs. This has led to a shortening of radiotherapy protocols for both curative and palliative indications. We review these novel techniques and protocols and the published clinical studies that include elderly patients treated with these techniques...
July 2017: Cancer Journal
https://www.readbyqxmd.com/read/28731328/bisphosphonate-functionalized-hydroxyapatite-nanoparticles-for-the-delivery-of-the-bromodomain-inhibitor-jq1-in-the-treatment-of-osteosarcoma
#4
Victoria Wu, Jarrett Mickens, Vuk Uskokovic
Osteosarcoma (OS) is one of the most common neoplasia among children and its survival statistics have been stagnating since the combinatorial anticancer therapy triad was first introduced. Here we report on the assessment of the effect of hydroxyapatite (HAp) nanoparticles loaded with medronate, the simplest bisphosphonate, as a bone-targeting agent and JQ1, a small-molecule bromodomain inhibitor, as a chemotherapeutic in different 2D and 3D K7M2 OS in vitro models. Both additives decreased the crystallinity of HAp, but the effect was more intense for medronate because of its higher affinity for HAp...
July 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28731194/smurf1-promotes-the-proliferation-migration-and-invasion-of-gastric-cancer-cells
#5
Youmao Tao, Caixia Sun, Tao Zhang, Yan Song
Smad ubiquitin regulatory factor 1 (SMURF1), a well-known E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Accumulating studies have shown that SMURF1 acts as an oncogenic factor in human malignancies. However, the clinical significance of SMURF1 and its role in gastric cancer (GC) remain unclear. The expression of SMURF1 was detected in 68 cases of GC and corresponding tumor-adjacent specimens. Our results revealed that SMURF1 was prominently overexpressed in GC specimens compared to corresponding tumor-adjacent tissues...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731187/isolation-and-purification-of-novel-peptides-derived-from-sepia-ink-effects-on-apoptosis-of-prostate-cancer-cell-pc%C3%A2-3
#6
Fangfang Huang, Yinwen Jing, Guofang Ding, Zuisu Yang
Novel prostate cancer therapeutics are in high demand. In order to identify potential therapeutic targets, protein from sepia ink was hydrolyzed by utilizing pepsin in an orthogonal array design. Pepsin hydrolysate (SH) obtained at optimal conditions exhibited the highest antitumor activity. Subsequently, a novel antitumor peptide, which was termed SHP, was isolated through ultrafiltration, gel filtration chromatography and reversed phase high‑performance liquid chromatography. The amino acid sequence of SHP was identified as Leu‑Lys‑Glu‑Glu‑Asn‑Arg‑Arg‑Arg‑Arg‑Asp with a molecular mass of 1371...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28731178/microrna-379-acts-as-a-tumor-suppressor-in-non-small-cell-lung-cancer-by-targeting-the-igf%C3%A2-1r-mediated-akt-and-erk-pathways
#7
Fangzheng Zhou, Long Nie, Dali Feng, Siyan Guo, Ren'na Luo
Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR‑379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR‑379 was downregulated in both NSCLC tissue and cell lines...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#8
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#9
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730960/protein-kinases-as-tumor-biomarkers-and-therapeutic-targets
#10
Chuntao Quan, Juanjuan Xiao, Lin Liu, Qiuhong Duan, Ping Yuan, Feng Zhu
Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied in clinical settings and have achieved very good treatment efficacy, many cancer patients died of tumor metastasis, drug toxicity or drug resistance due to tumor heterogeneity. Targeted molecular treatments based on the genes, receptors, and kinases expressed by a tumor make individualized treatment possible...
July 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28730725/targeting-nano-drug-delivery-to-cancer-cells-using-tunable-multi-layer-silver-decorated-gold-nanorods
#11
Zeid A Nima, Ahmed M Alwbari, Vijayalakshmi Dantuluri, Rabab N Hamzah, Natasha Sra, Pooja Motwani, Konstantinos Arnaoutakis, Rebecca A Levy, Amani F Bohliqa, Dmitry Nedosekin, Vladimir P Zharov, Issam Makhoul, Alexandru S Biris
Multifunctional nanoparticles have high potential as targeting delivery vehicles for cancer chemotherapy. In this study, silver-decorated gold nanorods (AuNR\Ag) have been successfully used to deliver specific, targeted chemotherapy against breast cancer (MCF7) and prostate carcinoma (PC3) cell lines. Doxorubicin, a commonly used chemotherapy, and anti-Epithelial cell adhesion molecule (anti-EpCAM) antibodies were covalently bonded to thiolated polyethylene glycol-coated AuNR\Ag, and the resultant system was used to deliver the drugs to cancer cells in vitro...
July 21, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#12
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#13
REVIEW
J K Winkler, K Buder-Bakhaya, A Dimitrakopoulou-Strauss, A Enk, J C Hassel
CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used...
July 20, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28729775/role-of-tumor-microenvironment-in-triple-negative-breast-cancer-and-its-prognostic-significance
#14
Tianjian Yu, Genhong Di
Breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells. Diverse components of the breast cancer microenvironment, such as suppressive immune cells, re-programmed fibroblast cells, altered extracellular matrix (ECM) and certain soluble factors, synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis...
June 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28729678/tumor-ldh-a-expression-and-serum-ldh-status-are-two-metabolic-predictors-for-triple-negative-breast-cancer-brain-metastasis
#15
Tieying Dong, Zhaoliang Liu, Qijia Xuan, Zhuozhong Wang, Wenjie Ma, Qingyuan Zhang
There are limited therapeutic methods for triple negative breast cancer in the clinic, which is easy to progress into the brain to form metastatic lesions and evolve into the terminal stage. Because both the primary cancer and the brain metastasis have high glycolysis, we hypothesize that lactate dehydrogenase (LDH), which catalyzes the final step of glycolysis, may be a predictor, as well as a treatment target, for breast cancer brain metastasis. Therefore, the expression of LDH-A was detected on 119 triple negative breast cancer tissues with immunohistochemistry, and the serum LDH levels were also measured...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#16
Eliana Mc Tacconi, Xianning Lai, Cecilia Folio, Manuela Porru, Gijs Zonderland, Sophie Badie, Johanna Michl, Irene Sechi, Mélanie Rogier, Verónica Matía García, Ankita Sati Batra, Oscar M Rueda, Peter Bouwman, Jos Jonkers, Anderson Ryan, Bernardo Reina-San-Martin, Joannie Hui, Nelson Tang, Alejandra Bruna, Annamaria Biroccio, Madalena Tarsounas
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. We demonstrate that inactivation of HR factors BRCA1, BRCA2, or RAD51 hypersensitizes cells to acetaldehyde treatment, in spite of the FA pathway being functional...
July 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28729431/sandostatin-lar-therapy-differentially-alters-68-ga-dotatate-uptake-in-normal-tissues-compared-to-primary-tumors-and-metastatic-lesions
#17
Narjess Ayati, Sze Ting Lee, Seyed Rasoul Zakavi, Kunthi Pathmaraj, Loai Qatawneh, Aurora Poon, Andrew Scott
Synthetic somatostatin analogs have been posed as a potential source of error in somatostatin receptor imaging by interfering with tumor detection; however, experimental models and clinical studies have shown a complex mechanism of octreotide effect on tumors. This study aimed to assess whether (68)Ga-DOTATATE uptake differs before and after treatment with long-acting somatostatin analogs. Methods: Thirty patients with intermediate to well differentiated neuroendocrine tumors (NET) who underwent (68)Ga-DOTATATE Positron Emission Tomography/Computed Tomography (PET/CT) scanning before and after receiving long-acting repeatable (LAR) Sandostatin were included in the study...
July 20, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28729418/myc-regulated-mevalonate-metabolism-maintains-brain-tumor-initiating-cells
#18
Xiuxing Wang, Zhi Huang, Qiulian Wu, Briana C Prager, Stephen C Mack, Kailin Yang, Leo J Y Kim, Ryan C Gimple, Yu Shi, Sisi Lai, Qi Xie, Tyler E Miller, Christopher G Hubert, Anne Song, Zhen Dong, Wenchao Zhou, Xiaoguang Fang, Zhe Zhu, Vaidehi Mahadev, Shideng Bao, Jeremy N Rich
Metabolic dysregulation drives tumor initiation in a subset of glioblastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastomas with wildtype IDH are poorly understood. MYC promotes metabolic reprogramming in cancer, but targeting MYC has proven notoriously challenging. Here, we link metabolic dysregulation in patient-derived brain tumor initiating cells (BTICs) to a nexus between MYC and mevalonate signaling, which can be inhibited by statin or 6-fluoromevalonate treatment...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28729415/an-essential-role-for-the-tumor-suppressor-merlin-in-regulating-fatty-acid-synthesis
#19
Dina S Stepanova, Galina Semenova, Yin-Ming Kuo, Andrew J Andrews, Sylwia Ammoun, C Oliver Hanemann, Jonathan Chernoff
Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of the NF2 gene encoding the protein Merlin is found in most sporadic and inherited schwannomas, but the molecular mechanisms underlying neoplastic changes in schwannoma cells remain unclear. We report here that NF2-deficient cells display elevated expression levels of key enzymes involved in lipogenesis and that this upregulation is caused by increased activity of Torc1...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28729406/tumor-evolution-as-a-therapeutic-target
#20
REVIEW
Nabil Amirouchene-Angelozzi, Charles Swanton, Alberto Bardelli
Recent technological advances in the field of molecular diagnostics (including blood-based tumor genotyping) allow the measurement of clonal evolution in patients with cancer, thus adding a new dimension to precision medicine: time. The translation of this new knowledge into clinical benefit implies rethinking therapeutic strategies. In essence, it means considering as a target not only individual oncogenes but also the evolving nature of human tumors. Here, we analyze the limitations of targeted therapies and propose approaches for treatment within an evolutionary framework...
July 20, 2017: Cancer Discovery
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