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Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Hai-Jie Hu, Rong-Xing Zhou, Fei Liu, Jun-Ke Wang, Fu-Yu Li
RATIONALE: Pancreatic mucoepidermoid carcinoma (MEC) is a rare disease with no more than 10 cases reported in literature. The prognosis is poor and few patients can survival more than 1 year. PATIENT CONCERNS: We presented a case of patient manifested as left upper abdominal pain. Computed tomography demonstrated a low-density shadow measuring 2.1 × 2.4 cm situated at the transition area of neck and body of the pancreas with obscure boundary and irregular enhancement...
March 2018: Medicine (Baltimore)
Jiyan Mohammad, Harsharan Dhillon, Shireen Chikara, Sujan Mamidi, Avinash Sreedasyam, Kishore Chittem, Megan Orr, John C Wilkinson, Katie M Reindl
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to a late diagnosis and poor response to available treatments. There is a need to identify complementary treatment strategies that will enhance the efficacy and reduce the toxicity of currently used therapeutic approaches. We investigated the ability of a known ROS inducer, piperlongumine (PL), to complement the modest anti-cancer effects of the approved chemotherapeutic agent gemcitabine (GEM) in PDAC cells in vitro and in vivo . PDAC cells treated with PL + GEM showed reduced cell viability, clonogenic survival, and growth on Matrigel compared to control and individually-treated cells...
February 13, 2018: Oncotarget
Chrysovalantou Mihailidou, Pavlos Papakotoulas, Athanasios G Papavassiliou, Michalis V Karamouzis
Ciclopirox olamine (CPX) is an antifungal agent that has recently demonstrated promising anti-neoplastic activity against hematologic and solid tumors. Here, we evaluated CPX compared with gemcitabine alone as well as their combination in human pancreatic cancer cell lines; BxPC-3, Panc-1, and MIA PaCa-2 and in humanized xenograft mouse models. We also examined the preclinical pharmacodynamic activity of CPX. CPX caused a pronounced decrease in cell proliferation and clonogenic growth potential. These inhibitory effects were accompanied by induction of reactive oxygen species (ROS), which were strongly associated with reduced Bcl-xL and survivin levels and activation of a panel of caspases, especially caspase-3, and finally resulted in apoptotic death...
February 13, 2018: Oncotarget
Julia Tschirka, Madlen Kreisor, Janina Betz, Dirk Grundemann
The candidate vitamin ergothioneine (ET) is a unique antioxidant. Expression of the ergothioneine transporter (ETT) (gene symbol SLC22A4) in distinct cells is thought to signal intracellular ET activity, since we have previously shown that the ETT is highly selective for ET. Unfortunately, some continue to hold the ETT as a relevant drug transporter, using the misleading functional name OCTN1, novel organic cation transporter. The present study was provoked by 2 recent reports in which new ETT substrates were declared...
March 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Susana Cedrés, Enriqueta Felip, Cristina Cruz, Ana Martinez de Castro, Nuria Pardo, Alejandro Navarro, Alex Martinez-Marti, Jordin Remon, Jorge Zeron-Medina, Judith Balmaña, Alba Llop-Guevara, Josep M Miquel, Irene Sansano, Paolo Nuciforo, Francesco Mancuso, Violeta Serra, Ana Vivancos
Heat shock proteins (HSPs) are molecular chaperones that maintain proteins in their correct conformation to ensure stability and protect carcinoma cells from apoptosis. HSP90 inhibitors (HSP90i) block multiple targets simultaneously, and despite responses in a selected population, no HSP90i have yet been approved. We present a patient with a lung tumor with an exceptional response to cisplatin/gemcitabine in combination with HSP90i, which nowadays continues with HSP90i maintenance after three years. Whole-exome sequencing of the lung tumor unveiled a BRCA1/2 deficiency mutational signature, and mutation analysis confirmed a germline BRCA1 mutation...
February 26, 2018: Journal of the National Cancer Institute
Hiroshi Ishii, Natsumi Yamashita, Makoto Ueno, Shinichi Ohkawa, Akiko M Saito, Mitsugu Sekimoto
Introduction: In Japan, the age of patients with pancreatic cancer has increased. Combination chemotherapies such as 5-fluorouracil/leucovorin, oxaliplatin and irinotecan therapy and gemcitabine hydrochloride (GEM) +nab paclitaxel therapy have been developed as the standard treatments for young patients with advanced recurrent pancreatic cancer. However, both therapies produce toxicity and their administration is limited by the patients' age or performance status. The efficacy and safety data obtained in the GEST study-a large-scale randomised controlled study conducted in patients with pancreatic cancer in Japan-suggested that GEM +S-1 (GS) combination therapy is a promising candidate for those aged between 75 and 80 years...
2018: BMJ Open Gastroenterology
Libin Wang, Feng Wang, Li Na, Jingjing Yu, Liya Huang, Zhi-Qiang Meng, Zhen Chen, Hao Chen, Liu-Lu Ming, Yong-Qiang Hua
BACKGROUND: Recent study revealed that abnormal long noncoding RNAs (lncRNAs) expression are association with chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC). OBJECTIVE: The present study was aimed to investigate the effects of lncRNA AB209630 expression for gemcitabine resistance in PDAC cells. METHODS: In the study, increased expression of lncRNA AB209630 could suppress cell proliferation and cell colony formation ability in gemcitabine resistance cells of PDAC...
February 28, 2018: Cancer Biomarkers: Section A of Disease Markers
Brian J McArdle, Patricia Vidal, Sarah P Psutka, Courtney M P Hollowell
It is rare to see an adult presenting with exstrophy of the bladder. Malignant conversion in exstrophy occurs in 4%, with adenocarcinoma as the most common histopathology. We report the first case of metastatic high grade urothelial carcinoma with squamous and sarcomatoid differentiation arising from undiagnosed, closed bladder exstrophy in a female at advanced age with associated bilateral deep vein thrombosis and clot retention. The patient developed clinical progression of disease despite neoadjuvant gemcitabine-cisplatin and salvage (or palliative) radiotherapy...
February 2018: Canadian Journal of Urology
N O Elander, K Aughton, P Ghaneh, J P Neoptolemos, D H Palmer, T F Cox, F Campbell, E Costello, C M Halloran, J R Mackey, A G Scarfe, J W Valle, A C McDonald, R Carter, N C Tebbutt, D Goldstein, J Shannon, C Dervenis, B Glimelius, M Deakin, R M Charnley, A Anthoney, M M Lerch, J Mayerle, A Oláh, M W Büchler, W Greenhalf
BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups...
March 9, 2018: British Journal of Cancer
Xu Zhu, Xiaomeng Shen, Jun Qu, Robert M Straubinger, William J Jusko
Pancreatic cancer is characterized by mutated signaling pathways and a high incidence of drug resistance. Comprehensive, large-scale proteomic analysis can provide a system-wide view of signaling networks, assist in understanding drug mechanisms of action and interactions, and serve as a useful tool for pancreatic cancer research. In this study, liquid chromatography-mass spectrometry-based proteomic analysis was applied to characterize the combination of gemcitabine and birinapant in pancreatic cancer cells, which was shown previously to be synergistic...
2018: Frontiers in Pharmacology
Jean Davidson, Zhewei Shen, Xue Gong, Jonathan R Pollack
While gemcitabine has been the mainstay therapy for advanced pancreatic cancer, newer combination regimens (e.g. FOLFIRINOX) have extended patient survival, though carry greater toxicity. Biomarkers are needed to better stratify patients for appropriate therapy. Previously, we reported that one-third of pancreatic cancers harbor deletions or deleterious mutations in key subunits of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. The SWI/SNF complex mobilizes nucleosomes on DNA, and plays a key role in modulating DNA transcription and repair...
February 9, 2018: Oncotarget
Tarik Mahfoud, Rachid Tanz, Mohamed Réda Khmamouche, Mohamed Allaoui, Rhizlane Belbaraka, Mouna Khouchani, Mohamed Ichou
Synchronous primary cancers involving the pancreas and kidney are extremely rare and poorly documented. We report the first case of this association treated with chemotherapy and tyrosine kinase inhibitor. A 70-year-old woman presented with a 2-month history of epigastric pain with weight loss of 12 kg. Two weeks previously, she had presented with jaundice and pelvic pain. A computed tomography (CT) scan of the body revealed the presence of an irregular mass in the body of the pancreas, encasing the celiac trunk, with dilatation of the biliary tract...
September 2017: Case Reports in Oncology
N O Elander, K Aughton, P Ghaneh, J P Neoptolemos, D H Palmer, T F Cox, F Campbell, E Costello, C M Halloran, J R Mackey, A G Scarfe, J W Valle, A C McDonald, R Carter, N C Tebbutt, D Goldstein, J Shannon, C Dervenis, B Glimelius, M Deakin, R M Charnley, Alan Anthoney, M M Lerch, J Mayerle, A Oláh, M W Büchler, W Greenhalf
BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA)...
March 8, 2018: British Journal of Cancer
Kitti Intuyod, Aroonsri Priprem, Chawalit Pairojkul, Chariya Hahnvajanawong, Kulthida Vaeteewoottacharn, Porntip Pinlaor, Somchai Pinlaor
Cholangiocarcinoma (CCA) is a deleterious bile duct tumor with poor prognosis and is relatively resistant to chemotherapy. Therefore, alternative or supplementary agents with anticancer and chemosensitizing activities may be useful for the treatment of CCA. A novel anthocyanin complex (AC) nanoparticle, developed from extracts of cobs of purple waxy corn and petals of blue butterfly pea, has exhibited chemopreventive potential in vivo. In the present study, the anti-CCA activities of AC and their underlying molecular mechanisms were investigated further in vitro using a CCA cell line (KKU213)...
March 7, 2018: International Journal of Oncology
Faizule Hassan, Shuisong Ni, Tyler C Arnett, Melanie C McKell, Michael A Kennedy
High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition...
March 30, 2018: Molecular Therapy Oncolytics
Serkan Dogan, Martin Hennig, Tanja Frank, Julian P Struck, Angelika Cebulla, Johannes Salem, Hendrik Borgmann, Tobias Klatte, Axel S Merseburger, Mario Kramer, Sebastian L Hofbauer
BACKGROUND: Guidelines support the use of neoadjuvant (NAC) and adjuvant (AC) chemotherapy in muscle-invasive bladder cancer. However, data from North America reported the underutilization of NAC in favor of AC despite the lower level of scientific evidence supporting AC. We aimed to assess current practice patterns of NAC and AC in -Germany. METHODS: A 15-question online survey was developed and sent via email newsletters to members of the -German Association of Urology and of the German Society of Residents in Urology in October 2016 to analyze current practice patterns...
March 6, 2018: Urologia Internationalis
M Uccello, M Moschetta, G Mak, T Alam, C Murias Henriquez, H-T Arkenau
Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear...
February 2018: Current Oncology
Nikolaos Spetsieris, Nefeli Giannakopoulou, Eleni Variami, Konstantinos Zervakis, Niki Rougala, Georgios Garefalakis, Vasiliki Skarlatou, Nora-Athina Viniou, Panagiotis Diamantopoulos
RATIONALE: Diffuse large B cell lymphoma (DLBCL) is a malignancy of the B cells with extranodal primary involvement being estimated at 30% to 40% of cases. Primary skeletal muscle presentation of DLBCL is extremely rare, with an estimated incidence of about 0.5% of extranodal lymphomas, presenting mostly in the lower extremities. The possible mechanisms of muscle involvement of DLBCL include primary extranodal disease, extension from adjacent organs (such as lymph nodes) or disseminated disease...
January 2018: Medicine (Baltimore)
Yongchun Wang, Yongqiang Xu, Yinyuan Zheng, Ying Bao, Ping Wang
Objective: To determine the effect of postoperative hepatic arterial infusion chemotherapy (HAIC) on long-term survival of patients with pancreatic cancer (PC) after radical pancreatectomy. Methods: A total of 87 patients with PC underwent radical pancreatectomy in the First People's Hospital affiliated to Huzhou Normal College between June 2008 and May 2013. Among these patients, after surgery, 43 received two sessions of HAIC followed by four sessions of systemic chemotherapy (HAIC group), while 44 received six sessions of systemic chemotherapy alone (control group)...
2018: OncoTargets and Therapy
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