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https://www.readbyqxmd.com/read/28428516/-long-term-survival-of-a-gastric-neuroendocrine-carcinoma-patient-with-extra-regional-lymph-node-metastases
#1
Yosuke Ozawa, Naokazu Chiba, Kosuke Hikita, Masaaki Okihara, Toru Sano, Koichi Tomita, Kiminori Takano, Shigeyuki Kawachi
A 56-year-old man with advanced gastric tumor in the pyloric antrum had multiple lymph node metastases(lymph nodes #5, 6, 8, and 13), as revealed by abdominal computed tomography(CT).The patient was diagnosed with coexisting clinical Stage III A gastric cancer(cT2[SS], cN2, cM0)with concomitant malignant lymphoma.Distal gastrectomy, D2 lymph node dissection, and resection of lymph node #13 were performed.Histopathological findings indicated that both the primary tumor and lymph node metastases were neuroendocrine carcinomas...
April 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28424615/huangqin-decoction-attenuates-cpt-11-induced-gastrointestinal-toxicity-by-regulating-bile-acids-metabolism-homeostasis
#2
Xu Wang, Dong-Ni Cui, Xiao-Min Dai, Jing Wang, Wei Zhang, Zun-Jian Zhang, Feng-Guo Xu
Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28421347/tu-100-exerts-a-protective-effect-against-bacterial-translocation-by-maintaining-the-tight-junction
#3
Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara, Toru Kono, Mitsuo Shimada
PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i...
April 18, 2017: Surgery Today
https://www.readbyqxmd.com/read/28415835/the-role-of-chemotherapy-in-unresectable-or-metastatic-adenocarcinoma-of-the-stomach-and-gastroesophageal-junction
#4
Mustafa Bozkurt, Fatemeh G Amlashi, Mariela Blum Murphy
Gastric cancer including gastro-esophageal junction adenocarcinomas are most challenging and deadly cancers of the gastrointestinal tract. Gastric cancer has a fatality-to-case ratio of 0.66, translating that nearly two thirds of newly diagnosed patients will have disseminated disease and in need of systemic therapy (1). Advanced gastric adenocarcinoma (AGC) is a heterogenous disease with differences in geographical distribution, histopathology, and molecular subtypes. Fluoropyrimidines (5-FU, S-1, and capecitabine), platinum compounds (cisplatin, oxaliplatin), taxanes (paclitaxel, docetaxel), and the topoisomerase inhibitory irinotecan are active drugs against AGC...
April 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28414298/access-granted-irgd-helps-silicasome-encased-drugs-breach-the-tumor-barrier
#5
Erkki Ruoslahti
In this issue of the JCI, Liu et al. use irinotecan-loaded nanoparticles to treat pancreatic adenocarcinomas in mice. Encapsulating drugs into nanoparticles has distinct advantages: it can improve the pharmacokinetics of the drug, enhance efficacy, and reduce unwanted side effects. A drawback is that the large size of nanoparticles restricts their access to the tumor interior. Liu and colleagues show that the cyclic tumor-penetrating peptide iRGD, reported to be capable of enhancing tumor penetration by drugs, can overcome this limitation to a substantial degree when administered together with the nanoparticles...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#6
Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E Nel, Huan Meng
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28413661/non-alcoholic-fatty-liver-disease-fibrosis-score-predicts-hematological-toxicity-of-chemotherapy-including-irinotecan-for-colorectal-cancer
#7
Masashi Yahagi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Yuko Kitagawa
Liver dysfunction that may affect drug metabolism is a major concern in patients treated with chemotherapy. Thus, assessment of the degree of liver dysfunction is crucial for predicting the adverse events of chemotherapy. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive clinical scoring system constructed from routine clinical and laboratory variables. The aim of this study was to evaluate whether NFS was useful for predicting the adverse events of chemotherapy including irinotecan (CPT-11) for colorectal cancer...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28413395/a-case-of-advanced-gastric-cancer-with-para-aortic-lymph-node-metastasis-treated-with-preoperative-folfox-chemotherapy-followed-by-radical-subtotal-gastrectomy-and-d2-lymph-node-dissection
#8
Byoung Jo Suh
We report the case of a 73-year-old female who was diagnosed with advanced gastric cancer. Esophagogastroduodenoscopy was used to diagnose Borrmann type 3 advanced gastric cancer located at the gastric antrum. A biopsy revealed poorly differentiated adenocarcinoma. Abdominopelvic computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography-CT (FDG-PET-CT) scans demonstrated multiple lymph node metastases, including the para-aortic lymph nodes. Systemic chemotherapy with 5-fluoruracil (5-FU), oxaliplatin, and leucovorin (FOLFOX) was initiated...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28412590/baseline-carcinoembryonic-antigen-as-a-predictive-factor-of-ramucirumab-efficacy-in-raise-a-second-line-metastatic-colorectal-carcinoma-phase-iii-trial
#9
Takayuki Yoshino, Radka Obermannová, György Bodoky, Rocio Garcia-Carbonero, Tudor Ciuleanu, David C Portnoy, Tae Won Kim, Yanzhi Hsu, David Ferry, Federico Nasroulah, Josep Tabernero
BACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab + (folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved overall survival (OS) versus placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73-0.98, P = 0.022). Post hoc analyses of RAISE patient data examined the association of carcinoembryonic antigen (CEA) subgroups with efficacy parameters...
April 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28409562/chemotherapy-induced-intestinal-inflammatory-responses-are-mediated-by-exosome-secretion-of-double-strand-dna-via-aim2-inflammasome-activation
#10
Qiaoshi Lian, Jun Xu, Shanshan Yan, Min Huang, Honghua Ding, Xiaoyu Sun, Aiwei Bi, Jian Ding, Bing Sun, Meiyu Geng
Chemotherapies are known often to induce severe gastrointestinal tract toxicity but the underlying mechanism remains unclear. This study considers the widely applied cytotoxic agent irinotecan (CPT-11) as a representative agent and demonstrates that treatment induces massive release of double-strand DNA from the intestine that accounts for the dose-limiting intestinal toxicity of the compound. Specifically, "self-DNA" released through exosome secretion enters the cytosol of innate immune cells and activates the AIM2 (absent in melanoma 2) inflammasome...
April 14, 2017: Cell Research
https://www.readbyqxmd.com/read/28404981/characterization-of-the-transcriptional-and-metabolic-responses-of-pediatric-high-grade-gliomas-to-mtor-hif-1a-axis-inhibition
#11
Aurélia Nguyen, François Marie Moussallieh, Alan Mackay, A Ercument Cicek, Andres Coca, Marie Pierre Chenard, Noelle Weingertner, Benoit Lhermitte, Eric Letouzé, Eric Guérin, Erwan Pencreach, Sarah Jannier, Dominique Guenot, Izzie Jacques Namer, Chris Jones, Natacha Entz-Werlé
Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured in both normoxic and hypoxic conditions...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402965/curcumin-enhances-the-effects-of-irinotecan-on-colorectal-cancer-cells-through-the-generation-of-reactive-oxygen-species-and-activation-of-the-endoplasmic-reticulum-stress-pathway
#12
Yan-Feng Huang, Da-Jian Zhu, Xiao-Wu Chen, Qi-Kang Chen, Zhen-Tao Luo, Chang-Chun Liu, Guo-Xin Wang, Wei-Jie Zhang, Nv-Zhu Liao
Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan's effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401446/liposomal-irinotecan-a-review-in-metastatic-pancreatic-adenocarcinoma
#13
Yvette N Lamb, Lesley J Scott
Intravenous liposomal irinotecan injection (Onivyde(®)) is approved for use in combination with 5-fluorouracil and leucovorin (5-FU/LV) in patients with metastatic pancreatic adenocarcinoma that has progressed following gemcitabine-based therapy. Liposomal irinotecan is a liposome-encapsulated formulation of the topoisomerase-1 inhibitor irinotecan, developed to overcome the pharmacological and clinical limitations of non-liposomal irinotecan. In the pivotal multinational, phase III NAPOLI-1 trial in patients with metastatic pancreatic adenocarcinoma that had progressed following gemcitabine-based therapy, liposomal irinotecan in combination with 5-FU/LV significantly prolonged median overall survival (OS; primary endpoint) and median progression-free survival (PFS) at the time of the primary analysis (after 313 events) and final analysis (after 382 events) compared with 5-FU/LV control therapy...
April 11, 2017: Drugs
https://www.readbyqxmd.com/read/28397089/virtual-clinical-studies-to-examine-the-probability-distribution-of-the-auc-at-target-tissues-using-physiologically-based-pharmacokinetic-modeling-application-to-analyses-of-the-effect-of-genetic-polymorphism-of-enzymes-and-transporters-on-irinotecan-induced
#14
Kota Toshimoto, Atsuko Tomaru, Masakiyo Hosokawa, Yuichi Sugiyama
PURPOSE: To establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported. METHODS: To optimize biochemical parameters of irinotecan and its metabolites in the PBPK modeling, a Cluster Newton method was introduced...
April 10, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#15
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28395759/a-multicenter-phase-ii-study-of-personalized-folfiri-cetuximab-for-safe-dose-intensification
#16
Michèle Boisdron-Celle, Jean Philippe Metges, Olivier Capitain, Antoine Adenis, Jean Luc Raoul, Thierry Lecomte, You Heng Lam, Roger Faroux, Claude Masliah, Anne Lise Poirier, Virginie Berger, Alain Morel, Erick Gamelin
We conducted a multicenter proof of concept phase II trial in patients with advanced colorectal cancer receiving FOLFIRI-cetuximab regimens to explore individual drug tailoring using pharmacogenetics and pharmacokinetics (PK) monitoring. Patients were stratified by their pharmacogenetic/phenotypic status: the irinotecan dose was adjusted according to the number of TA tandem repeats in the UGT1A1 promoter, while the 5-fluorouracil (5-FU) dose was initially adjusted according to dihydropyrimidine dehydrogenase (DPD) activity at initial screening (5-FU(ODPM Tox)) followed by PK-guided dose optimization (5-FU(ODPM Protocol))...
February 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28393405/determination-of-irinotecan-sn-38-and-sn-38-glucuronide-using-hplc-ms-ms-application-in-a-clinical-pharmacokinetic-and-personalized-medicine-in-colorectal-cancer-patients
#17
Chalirmporn Atasilp, Pichai Chansriwong, Ekapob Sirachainan, Thanyanan Reungwetwattana, Apichaya Puangpetch, Santirhat Prommas, Suwannee Sirilerttrakul, Budsaba Rerkarmnuaychoke, Sansanee Wongwaisayawan, Chonlaphat Sukasem
BACKGROUND: Irinotecan (CPT-11) is chemotherapy used mainly in the metastatic colorectal cancer. The purpose of this study was to develop and validate the LC-MS/MS for the simultaneous determination of CPT-11, SN-38, and SN-38G. METHODS: A 100 μL of plasma was prepared after protein precipitation and analyzed on a C18 column using 0.1% acetic acid in water and 0.1% acetic acid in acetonitrile as mobile phases. The mass spectrometer worked with multiple reaction monitoring (MRM) in positive scan mode...
April 10, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28391777/remarkable-response-to-fluorouracil-leucovorin-oxaliplatin-and-irinotecan-therapy-in-urothelial-cancer-of-the-renal-pelvis-a-case-report
#18
Takuya Tsujino, Kiyoshi Takahara, Tomohisa Matsunaga, Yuki Yoshikawa, Tomoaki Takai, Taizo Uchimoto, Kenkichi Saito, Naoki Tanda, Hajime Hirano, Hayahito Nomi, Naokazu Ibuki, Teruo Inamoto, Haruhito Azuma
BACKGROUND: No standard chemotherapy regimen for advanced urothelial cancer has been established, except for cisplatin-based regimens. We report the case of a patient with double primary cancer, urothelial carcinoma of the upper urinary tract and colorectal cancer, who underwent oxaliplatin-based chemotherapies. CASE PRESENTATION: A 56-year-old Japanese man presented to our hospital with the diagnosis of a left renal pelvic tumor and rectal cancer. Several examinations including ureteroscopic biopsy and computed tomography-guided biopsy were performed; however, the diagnosis of renal pelvic cancer could not be made...
April 10, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28388962/the-involvement-of-mast-cells-in-the-irinotecan-induced-enteric-neurons-loss-and-reactive-gliosis
#19
Ludmila T Nogueira, Deiziane V S Costa, Antoniella S Gomes, Conceição S Martins, Angeline M H P Silva, Juliana M Coelho-Aguiar, Patrícia Castelucci, Roberto C P Lima-Júnior, Renata F C Leitão, Vivaldo Moura-Neto, Gerly A C Brito
BACKGROUND: The irinotecan (CPT-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ENS). In inflammatory condition, mast cells release a variety of pro-inflammatory mediators that can interact with the ENS cells. It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis...
April 7, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28388581/temozolomide-combined-with-irinotecan-caused-regression-in-an-adult-pleomorphic-rhabdomyosarcoma-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#20
Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Takashi Murakami, Shinji Miwa, Scott D Nelson, Sarah M Dry, Yunfeng Li, Arun S Singh, Hiroaki Kimura, Katsuhiro Hayashi, Norio Yamamoto, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and recalcitrant, highly-malignant mesenchymal tumor in need of improved therapeutic strategies. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). We previously described the development of a PDOX model of adult pleomorphic RMS where the tumor behaved similar to the patient donor. A high-grade pleomorphic rhabdomyosarcoma from a striated muscle was previously grown orthotopically in the right biceps-femoris muscle of nude mice to establish the PDOX model...
March 24, 2017: Oncotarget
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