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https://www.readbyqxmd.com/read/29770561/investigating-the-interaction-of-anticancer-drug-temsirolimus-with-human-transferrin-molecular-docking-and-spectroscopic-approach
#1
Anas Shamsi, Azaj Ahmed, Mohd Shahnawaz Khan, Fohad Mabood Husain, Samreen Amani, Bilqees Bano
In our present study, binding between an important anti renal cancer drug temsirolimus and human transferrin (hTF) was investigated employing spectroscopic and molecular docking approach. In the presence of temsirolimus, hyper chromaticity is observed in hTF in UV spectroscopy suggestive of complex formation between hTF and temsirolimus. Fluorescence spectroscopy revealed the occurrence of quenching in hTF in the presence of temsirolimus implying complex formation taking place between hTF and temsirolimus. Further, the mode of interaction between hTF and temsirolimus was revealed to be static by fluorescence quenching analysis at 3 different temperatures...
May 16, 2018: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29730285/a-new-strategy-to-identify-hepatitis-b-virus-entry-inhibitors-by-alphascreen-technology-targeting-the-envelope-receptor-interaction
#2
Wakana Saso, Senko Tsukuda, Hirofumi Ohashi, Kento Fukano, Ryo Morishita, Satoko Matsunaga, Mio Ohki, Akihide Ryo, Sam-Yong Park, Ryosuke Suzuki, Hideki Aizaki, Masamichi Muramatsu, Camille Sureau, Takaji Wakita, Tetsuro Matano, Koichi Watashi
Current anti-hepatitis B virus (HBV) agents have limited effect in curing HBV infection, and thus novel anti-HBV agents with different modes of action are in demand. In this study, we applied AlphaScreen assay to high-throughput screening of small molecules inhibiting the interaction between HBV large surface antigen (LHBs) and the HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). From the chemical screening, we identified that rapamycin, an immunosuppressant, strongly inhibited the LHBs-NTCP interaction...
May 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29721158/acquired-resistance-to-temsirolimus-is-associated-with-integrin-%C3%AE-7-driven-chemotactic-activity-of-renal-cell-carcinoma-in-vitro
#3
Tobias Engl, Jochen Rutz, Sebastian Maxeiner, Sorel Fanguen, Eva Juengel, Sebastian Koschade, Frederik Roos, Wael Khoder, Igor Tsaur, Roman A Blaheta
The mechanistic target of the rapamycin (mTOR) inhibitor, temsirolimus, has significantly improved the outcome of patients with renal cell carcinoma (RCC). However, development of temsirolimus-resistance limits its effect and metastatic progression subsequently recurs. Since integrin α7 (ITGA7) is speculated to promote metastasis, this investigation was designed to investigate whether temsirolimus-resistance is associated with altered ITGA7 expression in RCC cell lines and modified tumor cell adhesion and invasion...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29692506/efficacy-and-safety-of-third-and-fourth-line-targeted-therapy-in-japanese-patients-with-metastatic-renal-cell-carcinoma-a-retrospective-analysis
#4
Negishi Takahito, Nagase Kei, Iwai Hidenori, Furubayashi Nobuki, Taguchi Kenichi, Nakamura Motonobu
Introduction: There is limited data on the efficacy of sequential targeted therapy for metastatic renal cell carcinoma (mRCC) beyond the second line, especially for Asian patients. We evaluated the efficacy and side effects of targeted therapy beyond the second line. Materials and Methods: We retrospectively reviewed 69 patients who were administered targeted therapy for mRCC at our institution between 2008 and 2016. Sunitinib, pazopanib, sorafenib, axitinib, everolimus, and temsirolimus were available in Japan in 2016, and treatment had been conducted with those six agents...
April 2018: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/29674440/lenalidomide-in-pretreated-mantle-cell-lymphoma-patients-an-italian-observational-multicenter-retrospective-study-in-daily-clinical-practice-the-lenamant-study
#5
Vittorio Stefoni, Cinzia Pellegrini, Alessandro Broccoli, Luca Baldini, Monica Tani, Emanuele Cencini, Amalia Figuera, Michela Ansuinelli, Elisa Bernocco, Maria Cantonetti, Maria Christina Cox, Filippo Ballerini, Chiara Rusconi, Carlo Visco, Luca Arcaini, Angelo Fama, Roberto Marasca, Stefano Volpetti, Alessia Castellino, Catello Califano, Marina Cavaliere, Guido Gini, Anna Marina Liberati, Gerardo Musuraca, Anna Lucania, Giuseppina Ricciuti, Lisa Argnani, Pier Luigi Zinzani
BACKGROUND: Mantle cell lymphoma (MCL) has the worst prognosis of B-cell subtypes owing to its aggressive clinical disease course and incurability with standard chemo-immunotherapy. Options for relapsed MCL are limited, although several single agents have been studied. Lenalidomide is available in Italy for patients with MCL based on a local disposition of the Italian Drug Agency. SUBJECTS, MATERIALS, AND METHODS: An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on effectiveness and safety of lenalidomide use in real practice...
April 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29669553/significant-response-to-nivolumab-for-metastatic-chromophobe-renal-cell-carcinoma-with-sarcomatoid-differentiation-a-case-report
#6
Go Noguchi, Sohgo Tsutsumi, Masato Yasui, Shinji Ohtake, Susumu Umemoto, Noboru Nakaigawa, Masahiro Yao, Takeshi Kishida
BACKGROUND: The treatment of advanced or metastatic renal cell carcinoma (RCC) has drastically changed since the approval of immune checkpoint therapy. Nivolumab is a treatment option for patients with metastatic RCC, previously treated with targeted antiangiogenic therapy. The efficacy of nivolumab for patients with RCC was established by the Checkmate 025 clinical trial. Chromophobe RCC (CRCC) represents around 5% of RCC cases, but non-clear cell RCC (non-ccRCC) subtypes were excluded from the Checkmate 025 clinical trial...
April 18, 2018: BMC Urology
https://www.readbyqxmd.com/read/29668485/prolonged-activity-and-toxicity-of-sirolimus-in-a-patient-with-metastatic-renal-perivascular-epithelioid-cell-tumor-a-case-report-and-literature-review
#7
Alessandra Raimondi, Francesca Colombo, Giulia Pintarelli, Carlo Morosi, Salvatore L Renne, Anna M Frezza, Maristella Saponara, Angelo P Dei Tos, Arabella Mazzocchi, Salvatore Provenzano, Paolo G Casali, Silvia Stacchiotti
Perivascular epithelioid cell tumor (PEComa) is a family of mesenchymal tumors. Conventional chemotherapy has little activity in this disease, but case reports are available on the activity of mammalian target of rapamycin inhibitors (e.g. sirolimus and temsirolimus). Pharmacokinetic assays of sirolimus are available as this drug has a precise therapeutic window and blood levels might be influenced by CYP3A4 polymorphisms and drug interactions. We report on a case of a patient with metastatic, progressive PEComa who started sirolimus at a dose of 5 mg/day with evidence of grade (G) 3 mucositis, G2 thrombocytopenia, and G1 leucopenia 10 days after the treatment started, in absence of concomitant medications or prohibited food assumption...
April 17, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29588458/personalised-drug-repositioning-for-clear-cell-renal-cell-carcinoma-using-gene-expression
#8
Karel K M Koudijs, Anton G T Terwisscha van Scheltinga, Stefan Böhringer, Kirsten J M Schimmel, Henk-Jan Guchelaar
Reversal of cancer gene expression is predictive of therapeutic potential and can be used to find new indications for existing drugs (drug repositioning). Gene expression reversal potential is currently calculated, in almost all studies, by pre-aggregating all tumour samples into a single group signature or a limited number of molecular subtype signatures. Here, we investigate whether drug repositioning based on individual tumour sample gene expression signatures outperforms the use of tumour group and subtype signatures...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29588307/comprehensive-genomic-profiling-aids-in-treatment-of-a-metastatic-endometrial-cancer
#9
Jatinder Dhami, Kim M Hirshfield, Shridar Ganesan, Mira Hellmann, Veronica Rojas, Judith K Amorosa, Gregory M Riedlinger, Hua Zhong, Siraj M Ali, Dean Pavlick, Julia A Elvin, Lorna Rodriguez-Rodriguez
PURPOSE: FGFR-TACC fusions, including FGFR3-TACC3, have been identified as potential oncogenic drivers and actionable alterations in a number of different cancer types. The clinical relevance of FGFR3-TACC3 fusions in endometrial cancer has not yet been described. METHODS: Formalin-fixed, paraffin-embedded metastatic endometrial carcinoma from the spleen and peritoneum were sent for comprehensive genomic profiling (CGP) using the FoundationOne platform as part of a prospective tumor genomic profiling protocol...
March 27, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29572505/ibrutinib-versus-temsirolimus-3-year-follow-up-of-patients-with-previously-treated-mantle-cell-lymphoma-from-the-phase-3-international-randomized-open-label-ray-study
#10
S Rule, W Jurczak, M Jerkeman, C Rusconi, M Trneny, F Offner, D Caballero, C Joao, M Witzens-Harig, G Hess, I Bence-Bruckler, S-G Cho, C Thieblemont, W Zhou, T Henninger, J Goldberg, J Vermeulen, M Dreyling
No abstract text is available yet for this article.
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29563341/active-epithelial-hippo-signaling-in-idiopathic-pulmonary-fibrosis
#11
Jason J Gokey, Anusha Sridharan, Yan Xu, Jenna Green, Gianni Carraro, Barry R Stripp, Anne-Karina T Perl, Jeffrey A Whitsett
Hippo/YAP signaling plays pleiotropic roles in the regulation of cell proliferation and differentiation during organogenesis and tissue repair. Herein we demonstrate increased YAP activity in respiratory epithelial cells in lungs of patients with idiopathic pulmonary fibrosis (IPF), a common, lethal form of interstitial lung disease (ILD). Immunofluorescence staining in IPF epithelial cells demonstrated increased nuclear YAP and loss of MST1/2. Bioinformatic analyses of epithelial cell RNA profiles predicted increased activity of YAP and increased canonical mTOR/PI3K/AKT signaling in IPF...
March 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29508857/targeting-the-pi3k-pathway-in-cancer-are-we-making-headway
#12
REVIEW
Filip Janku, Timothy A Yap, Funda Meric-Bernstam
The PI3K-AKT-mTOR pathway is one of the most frequently dysregulated pathways in cancer and, consequently, more than 40 compounds that target key components of this signalling network have been tested in clinical trials involving patients with a range of different cancers. The clinical development of many of these agents, however, has not advanced to late-phase randomized trials, and the antitumour activity of those that have been evaluated in comparative prospective studies has typically been limited, or toxicities were found to be prohibitive...
May 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29492762/cabozantinib-versus-standard-of-care-comparators-in-the-treatment-of-advanced-metastatic-renal-cell-carcinoma-in-treatment-na%C3%A3-ve-patients-a-systematic-review-and-network-meta-analysis
#13
Elvira Schmidt, Johanna Lister, Monika Neumann, Witold Wiecek, Shuai Fu, Anne-Lise Vataire, Jelena Sostar, Shengnan Huang, Florence Marteau
BACKGROUND: Cabozantinib has recently been evaluated as a first-line treatment in advanced renal cell carcinoma (aRCC). OBJECTIVE: To indirectly assess efficacy of cabozantinib versus standard-of-care (SoC) comparators in the first-line treatment of aRCC. METHODS: We conducted a systematic literature review (SLR) to identify randomized controlled studies in the first-line setting for aRCC. The outcomes analyzed were overall survival (OS) and progression-free survival (PFS)...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29484131/dual-targeting-of-mitochondrial-function-and-mtor-pathway-as-a-therapeutic-strategy-for-diffuse-intrinsic-pontine-glioma
#14
Maria Tsoli, Jie Liu, Laura Franshaw, Han Shen, Cecilia Cheng, MoonSun Jung, Swapna Joshi, Anahid Ehteda, Aaminah Khan, Angel Montero-Carcabosso, Pierre J Dilda, Philip Hogg, David S Ziegler
Diffuse Intrinsic Pontine Gliomas (DIPG) are the most devastating of all pediatric brain tumors. They mostly affect young children and, as there are no effective treatments, almost all patients with DIPG will die of their tumor within 12 months of diagnosis. A key feature of this devastating tumor is its intrinsic resistance to all clinically available therapies. It has been shown that glioma development is associated with metabolic reprogramming, redox state disruption and resistance to apoptotic pathways...
January 26, 2018: Oncotarget
https://www.readbyqxmd.com/read/29483097/patient-customized-drug-combination-prediction-and-testing-for-t-cell-prolymphocytic-leukemia-patients
#15
Liye He, Jing Tang, Emma I Andersson, Sanna Timonen, Steffen Koschmieder, Krister Wennerberg, Satu Mustjoki, Tero Aittokallio
The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway cross-talk, personalized combination treatments targeting multiple cancer growth and survival pathways are required. Here we implemented a computational-experimental drug combination prediction and testing (DCPT) platform for efficient in silico prioritization and ex vivo testing in patient-derived samples to identify customized synergistic combinations for individual cancer patients...
May 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29480626/oral-stomatitis-and-mtor-inhibitors-a-review-of-current-evidence-in-20-915-patients
#16
L Lo Muzio, C Arena, G Troiano, A Villa
BACKGROUND: Traditional treatment of malignancies with chemotherapeutic agents is often affected by the damage inflicted on non-cancerous cells. Toxicities of the oral cavity, such as mucositis and stomatitis, are some of the most significant and unavoidable toxicities associated with anti-cancer therapies. For such reason, in the last decades, newer targeted agents have been developed aiming to decrease the rates of side effects on healthy cells. Unfortunately, targeted anti-cancer therapies also showed significant rate of toxicity on healthy tissues...
March 2018: Oral Diseases
https://www.readbyqxmd.com/read/29464355/fdg-pet-ct-after-first-molecular-targeted-therapy-predicts-survival-of-patients-with-renal-cell-carcinoma
#17
Noboru Nakaigawa, Keiichi Kondo, Tomohiro Kaneta, Ukihide Tateishi, Ryogo Minamimoto, Kazuhiro Namura, Daiki Ueno, Kazuki Kobayashi, Takeshi Kishida, Ichiro Ikeda, Hisashi Hasumi, Kazuhide Makiyama, Narihiko Hayashi, Kimito Osaka, Kentaro Muraoka, Koji Izumi, Takashi Kawahara, Jun-Ichi Teranishi, Yasuhide Miyoshi, Yasushi Yumura, Hiroji Uemura, Tomio Inoue, Masahiro Yao
PURPOSE: We investigated prospectively whether 18 F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) can predict the overall survival (OS) of patients with advanced renal cell carcinoma (RCC) previously treated by molecular targeted therapies. METHODS: Between 2009 and 2016, 81 patients who had received single molecular targeted therapies (43 sorafenib, 27 sunitinib, 8 temsirolimus and others) and were scheduled for second line molecular targeted therapies for advanced RCC were enrolled in this prospective study...
April 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29455379/comparative-study-of-different-classification-models-in-renal-cell-carcinoma
#18
Alejandro José Sastre-Heres, Irene Iglesias, Miguel Alaguero-Calero, Daniel Ruiz-Sánchez, Benito García-Díaz, Jaime Peña-Díaz
The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of aRCC patients. In addition, the model developed from the pivotal trial of temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng et al., Choueiri et al. and Bamias et al. were examined. An observational, retrospective study of patients starting first-line systemic therapy was conducted between 2008 and 2011. The variables used to evaluate the classification models were median overall survival (mOS) and median progression-free survival (mPFS)...
February 17, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29454321/safety-and-efficacy-of-temsirolimus-as-second-line-treatment-for-patients-with-recurrent-bladder-cancer
#19
Marina Pulido, Guilhem Roubaud, Anne-Laure Cazeau, Hakim Mahammedi, Lionel Vedrine, Florence Joly, Loic Mourey, Christian Pfister, Alejandro Goberna, Barbara Lortal, Carine Bellera, Philippe Pourquier, Nadine Houédé
BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29435166/acquired-resistance-to-tyrosine-kinase-inhibitors-may-be-linked-with-the-decreased-sensitivity-to-x-ray-irradiation
#20
Maxim Sorokin, Roman Kholodenko, Anna Grekhova, Maria Suntsova, Margarita Pustovalova, Natalia Vorobyeva, Irina Kholodenko, Galina Malakhova, Andrew Garazha, Artem Nedoluzhko, Raif Vasilov, Elena Poddubskaya, Olga Kovalchuk, Leila Adamyan, Vladimir Prassolov, Daria Allina, Denis Kuzmin, Kirill Ignatev, Andreyan Osipov, Anton Buzdin
Acquired resistance to chemotherapy and radiation therapy is one of the major obstacles decreasing efficiency of treatment of the oncologic diseases. In this study, on the two cell lines (ovarian carcinoma SKOV-3 and neuroblastoma NGP-127), we modeled acquired resistance to five target anticancer drugs. The cells were grown on gradually increasing concentrations of the clinically relevant tyrosine kinase inhibitors (TKIs) Sorafenib, Pazopanib and Sunitinib, and rapalogs Everolimus and Temsirolimus, for 20 weeks...
January 12, 2018: Oncotarget
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