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Yaping Li, Dajun Sun, Weixuan Sun, Dexin Yin
BACKGROUND: Uveal melanoma (UM) is an intraocular malignant tumor characterized by rapid progression and recurrence. The current conventional treatments are unsatisfactory. Histone acetylation at H3 lysine 56 (H3K56ac) has been reported to be a tumor suppressor in breast cancer. However, whether H3K56ac prevents the occurrence and development of UM remains uninvestigated. The study aimed to explore the regulatory effect of H3K56ac on Ras-PI3K-AKT induced UM cells proliferation and migration...
February 15, 2019: Journal of Cellular Physiology
Sherene Loi, Sathana Dushyanthen, Paul A Beavis, Roberto Salgado, Carsten Denkert, Peter Savas, Susan Combs, David L Rimm, Jennifer M Giltnane, Monica V Estrada, Violeta Sánchez, Melinda E Sanders, Rebecca S Cook, Mark A Pilkinton, Simon A Mallal, Kai Wang, Vincent A Miller, Phil J Stephens, Roman Yelensky, Franco D Doimi, Henry Gómez, Sergey V Ryzhov, Phillip K Darcy, Carlos L Arteaga, Justin M Balko
No abstract text is available yet for this article.
February 15, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rachel Sexton, Gabriel Mpilla, Steve Kim, Philip A Philip, Asfar S Azmi
Ras gene (HRAS, NRAS, and KRAS) has been observed to be mutated and hyper-activated in a significant proportion of cancers. However, mutant Ras remains a challenging therapeutic target. Similarly, inhibition of targets upstream and downstream of Ras has shown limited clinical utility. There have been attempts to develop and deliver mutant K-Ras silencing RNAs either through their encapsulation in liposomes or nanoparticles. However, these approaches show very limited success due to the lack of stability of such carrier molecules alongside associated toxicity...
February 12, 2019: Seminars in Cancer Biology
S O Sukhikh, K B Kolontarev, A O Vasilyev, D Yu Pushkar
Pelvic organ prolapse (POP) is the most common urogynecological disease in women of middle and older age groups. This disease causes numerous urogenital symptoms and significantly reduces the quality of life of patients. Surgical correction of POP is the optimal method f treatment for this category of patients, however, the choice of surgery and access remains controversial. In recent decades, thanks to the development of robotic technologies, the use of robot-assisted sacrocolpopexy (RAS) has become increasingly popular...
December 2018: Urologii︠a︡
Pan Wang, Xinhua Song, Kirsten Utpatel, Runze Shang, Yoon Mee Yang, Meng Xu, Jie Zhang, Li Che, John Gordan, Antonio Cigliano, Ekihiro Seki, Matthias Evert, Diego F Calvisi, Xiaosong Hu, Xin Chen
PD901, a MEK inhibitor, has been demonstrated of therapeutic efficacy against cholangiocarcinoma (CCA) harboring K-Ras oncogenic mutations. However, most CCA exhibit no K-Ras mutations. In the current study, we investigated the therapeutic potential of PD901, either alone or in combination with the pan-mTOR inhibitor MLN0128, for the treatment of K-Ras wild-type CCA in vitro using human CCA cell lines, and in vivo using AKT/YapS127A CCA mouse model. We discovered that in vitro, PD901 treatment strongly inhibited CCA cell proliferation, and combined PD901 and MLN0128 therapy further increased growth inhibition...
February 11, 2019: Cell Death & Disease
Diva S Whalen, Sarrah E Widatalla, Olga Y Korolkova, Gladys S Nangami, Heather K Beasley, Stephen D Williams, Carlos Virgous, Brian D Lehmann, Josiah Ochieng, Amos M Sakwe
The role of AnxA6 in breast cancer and in particular, the mechanisms underlying its contribution to tumor cell growth and/or motility remain poorly understood. In this study, we established the tumor suppressor function of AnxA6 in triple negative breast cancer (TNBC) cells by showing that loss of AnxA6 is associated with early onset and rapid growth of xenograft TNBC tumors in mice. We also identified the Ca2+ activated RasGRF2 as an effector of AnxA6 mediated TNBC cell growth and motility. Activation of Ca2+ mobilizing oncogenic receptors such as epidermal growth factor receptor (EGFR) in TNBC cells or pharmacological stimulation of Ca2+ influx led to activation, subsequent degradation and altered effector functions of RasGRF2...
January 4, 2019: Oncotarget
Zeynep Kabakci, Simon Käppeli, Claudio Cantù, Lasse D Jensen, Christiane König, Janine Toggweiler, Christian Gentili, Giovanni Ribaudo, Giuseppe Zagotto, Konrad Basler, Lorenzo A Pinna, Giorgio Cozza, Stefano Ferrari
CDC25 phosphatases play a key role in cell cycle transitions and are important targets for cancer therapy. Here, we set out to discover novel CDC25 inhibitors. Using a combination of computational methods, we defined a minimal common pharmacophore in established CDC25 inhibitors and performed virtual screening of a proprietary library. Based on the availability of crystal structures for CDC25A and CDC25B, we implemented a molecular docking strategy and carried out hit expansion/optimization. Enzymatic assays revealed that naphthoquinone scaffolds were the most promising CDC25 inhibitors among selected hits...
February 4, 2019: Scientific Reports
Imran Khan, Russell Spencer-Smith, John P O'Bryan
Additionally, a further error has been corrected on page five in the sentence: Subsequent improvements to the chemistry of these lead compounds have resulted in the most recent interaction, with ARS-1620, which demonstrates selective inhibition of K-RAS(G12C) mutant tumor models in vivo [23]. The word 'with' has been removed from this sentence to ensure the correct meaning is communicated, such that the sentence now is: Subsequent improvements to the chemistry of these lead compounds have resulted in the most recent interaction, ARS-1620, which demonstrates selective inhibition of K-RAS(G12C) mutant tumor models in vivo [23]...
February 1, 2019: Oncogene
Hassan Awada, Yasunobu Nagata, Abhinav Goyal, Mohammad F Asad, Bhumika Patel, Cassandra M Hirsch, Teodora Kuzmanovic, Yihong Guan, Bartlomiej P Przychodzen, Mai Aly, Vera Adema, Wenyi Shen, Louis Williams, Aziz Nazha, Mohamed E Abazeed, Mikkael A Sekeres, Tomas Radivoyevitch, Torsten Haferlach, Babal K Jha, Valeria Visconte, Jaroslaw P Maciejewski
Somatic TET2 mutations ( TET2 MT ) are frequent in myeloid neoplasia (MN), particularly chronic myelomonocytic leukemia (CMML). TET2 MT includes mostly loss-of-function/hypomorphic hits. Impaired TET2 activity skews differentiation of hematopoietic stem cells toward proliferating myeloid precursors. This study was prompted by the observation of frequent biallelic TET2 gene inactivations ( biTET2 i ) in CMML. We speculated that biTET2 i might be associated with distinct clinicohematological features. We analyzed TET2 MT in 1045 patients with MN...
February 12, 2019: Blood Advances
Jianying Jin, Qunyi Guo, Jingjing Xie, Dan Jin, Yanan Zhu
The study aimed to investigate the reason of HCT116 cell resistance to MEK inhibitor, and the combination treatment effects of MEK inhibitor AZD6244 and JAK2/STAT3 inhibitor AG490 on colon cancer in vitro and in vivo, including cell viability, apoptosis, and explore the partial mechanisms focused on AZD6244 promoted the activation of JAK2-STAT3 pathways. In vitro, we examined the HCT116 cell viability by CCK8, cell apoptosis by flow cytometry; Western blot measured p-ERK, p-JAK2, p-STAT3 and STAT3 expression...
January 31, 2019: Pathology Oncology Research: POR
Jeffrey K Mito, Devarati Mitra, Constance M Barysauskas, Adrián Mariño-Enriquez, Elizabeth A Morgan, Christopher D M Fletcher, Chandrajit P Raut, Elizabeth H Baldini, Leona A Doyle
PURPOSE: Radiation-associated sarcomas (RAS) are considered to have a poor prognosis. While the incidence is anticipated to rise, contemporary data regarding predictors of outcomes are few. We performed a retrospective analysis to identify RAS prognostic factors, as well as subset analyses for radiation-associated angiosarcoma arising after treatment for breast cancer (RAAB) and other RAS subtypes (other-RAS). METHODS AND MATERIALS: Patients with localized RAS evaluated at an institutional multidisciplinary sarcoma clinic were identified...
January 28, 2019: International Journal of Radiation Oncology, Biology, Physics
Matthew A Loberg, Rebecca K Bell, Leslie O Goodwin, Elizabeth Eudy, Linde A Miles, Jennifer M SanMiguel, Kira Young, David E Bergstrom, Ross L Levine, Rebekka K Schneider, Jennifer J Trowbridge
Clonal hematopoiesis (CH) is a common aging-associated condition with increased risk of hematologic malignancy. Knowledge of the mechanisms driving evolution from CH to overt malignancy has been hampered by a lack of in vivo models that orthogonally activate mutant alleles. Here, we develop independently regulatable mutations in DNA methyltransferase 3A (Dnmt3a) and nucleophosmin 1 (Npm1), observed in human CH and AML, respectively. We find Dnmt3a mutation expands hematopoietic stem and multipotent progenitor cells (HSC/MPPs), modeling CH...
January 28, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Nancy M Joseph, Christos G Tsokos, Sarah E Umetsu, A Hunter Shain, Robin K Kelley, Courtney Onodera, Sarah Bowman, Eric Talevich, Linda D Ferrell, Sanjay Kakar, Gregor Krings
Combined hepatocellular-cholangiocarcinomas (CHC) are mixed tumours with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) components. CHC prognosis is similar to intrahepatic cholangiocarcinoma (ICC) and worse than HCC, and staging and treatment generally follow ICC algorithms. However, the molecular biology of CHC remains poorly characterized. We performed capture-based next generation sequencing of 20 CHC and for comparison, 10 ICC arising in cirrhosis. Intratumour heterogeneity was assessed by separately sequencing the HCC and CC components of nine CHC...
January 28, 2019: Journal of Pathology
Holger Hebart, Michael Kiehl, Jiri Tomasek, Tibor Csoszi, Reija Koukakis, George Kafatos, Anja Kuhn, Katja Bjorklof, Gaston Demonty, Tomas Buchler
INTRODUCTION: This study aimed to better understand panitumumab use in real-life clinical practice in first- and second-line treatment of metastatic colorectal cancer in five European countries. METHODS: This is a combined analysis of two observational, non-interventional prospective cohort studies, one of which was conducted in Germany and France, the other in Bulgaria, Czech Republic, and Hungary. The studies observed patients with wild-type [Kirsten] rat sarcoma viral oncogene homolog ([K]RAS/RAS) metastatic colorectal cancer (mCRC), who had been treated with panitumumab in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in the first line or with panitumumab combined with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the second line following fluoropyrimidine-based chemotherapy...
January 28, 2019: Advances in Therapy
Antonio Agraz-Doblas, Clara Bueno, Rachael Bashford-Rogers, Anindita Roy, Pauline Schneider, Michela Bardini, Paola Ballerini, Gianni Cazzaniga, Thaidy Moreno, Carlos Revilla, Marta Gut, Maria G Valsecchi, Irene Roberts, Rob Pieters, Paola De Lorenzo, Ignacio Varela, Pablo Menendez, Ronald W Stam
B-cell acute lymphoblastic leukemia is the commonest childhood cancer. In infants, B-cell acute lymphoblastic leukemia remains fatal, especially in patients with t(4;11), present in ~80% of cases. The pathogenesis of t(4;11)/KMT2A-AFF1+ (MLL-AF4+) infant B-cell acute lymphoblastic leukemia remains difficult to model, and the pathogenic contribution in cancer of the reciprocal fusions resulting from derivative translocated-chromosomes remains obscure. Here, a multi-layered genome-wide analyses and validation was performed on a total of 124 de novo infant B-cell acute lymphoblastic leukemias uniformly diagnosed/treated according to Interfant99/06 protocol...
January 24, 2019: Haematologica
Tatiana Vidaurre, Sandro Casavilca, Paola Montenegro, Henry Gomez, Mónica Calderón, Jeannie Navarro, Jessica Aramburu, Ebert Poquioma, Yasuo Tsuchiya, Takao Asai, Yoichi Ajioka, Ayako Sato, Toshikazu Ikoma, Kazutoshi Nakamura
Background: Recent studies have shown that genetic alterations are associated with the effect of patient geographic location on gallbladder cancer development. Peru has a high incidence of gallbladder cancer, but causative factors have not yet been identified. We examined the frequency of mutations in TP53 and K-ras genes in Peruvian patients with gallbladder cancer, and compared this with data from Bolivia, Hungary, Chile, and Japan, which have a high gallbladder cancer incidence. Methods: DNA was extracted from formalin-fixed paraffin-embedded gallbladder tissue sections of 30 gallbladder cancer patients (9 men and 21 women) obtained using microdissection...
January 25, 2019: Asian Pacific Journal of Cancer Prevention: APJCP
S Y Zhou, Q Xue, J M Ying, X S Hu, J L Yang, H Lin, Y K Shi
Objective: Adenosquamous carcinoma of lung is an uncommon subtype with more aggressive behavior and poor prognosis than adenocarcinoma and squamous cell carcinoma. This study was aimed to investigate the clinicopathological characteristics and prognostic factors of lung adenosquamous carcinoma. Methods: The pathological features and follow-up data of 133 patients were collected and the prognostic factors of these patients were retrospectively analyzed. Results: Among the 133 patients, 81 cases (60.9%) smoked...
January 23, 2019: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Nobuyuki Nishizawa, Yusuke Kumamoto, Hiroshi Katoh, Hideki Ushiku, Keigo Yokoi, Toshimichi Tanaka, Satoru Ishii, Kazuharu Igarashi, Hiroshi Tajima, Takashi Kaizu, Tsutomu Yoshida, Makoto Saegusa, Masahiko Watanabe, Keishi Yamashita
We previously reported that the dissected pancreatic tissue margin (DPM) and the preoperative serum level of carbohydrate antigen 19-9 (preCA19-9) were independent prognostic factors in pancreatic ductal adenocarcinoma (PDAC). In the current study, the prognostic relevance of these factors, including their molecular associations, were validated. A total of 161 patients with PDAC underwent a pancreatectomy between 1986 and 2013, and a multivariate Cox proportional hazards model and a propensity score-based model validated the prognostic importance of DPM...
February 2019: Oncology Letters
Li Wei, Haiyan Chang, Song Huo
Mutations of K-rat sarcoma (K-ras) in patients with cardia cancer and their effects on the expression of fascin were investigated. A total of 90 cardia cancer patients treated in Jining First People's Hospital from March 2014 to March 2017 were randomly selected. Genomic deoxyribonucleic acid (DNA) was extracted from paraffin-embedded cardia cancer specimens. Pyrosequencing was applied to detect sequences of K-ras gene in all patients and to analyze the mutations of K-ras gene. Then, genotyping of mutations at each mutation site was carried out using quantitative polymerase chain reaction (qPCR)...
February 2019: Oncology Letters
Maristella Bianconi, Alessia Cimadamore, Luca Faloppi, Mario Scartozzi, Matteo Santoni, Antonio Lopez-Beltran, Liang Cheng, Marina Scarpelli, Rodolfo Montironi
Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1-2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment...
January 2019: Therapeutic Advances in Urology
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