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chemotherapy induced liver injury

Sachio Fushida, Jun Kinoshita, Masahide Kaji, Katsunobu Oyama, Yasuo Hirono, Tomoya Tsukada, Takashi Fujimura, Tetsuo Ohta
BACKGROUND: Weekly paclitaxel (wPTX) is the preferred second-line chemotherapy for gastric cancer in Japan. Histone deacetylase inhibitors have been shown to decrease proliferation through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One histone deacetylase inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis and enhances the efficacy of paclitaxel (PTX), shown in a murine gastric cancer model. This Phase II trial was designed to evaluate the benefits of adding VPA to wPTX in patients with gastric cancer refractory to first-line treatment with fluoropyrimidine...
2016: Drug Design, Development and Therapy
Xue-Lian Gong, Xiao-Lei Gu, Yong-Chun Chen, Hai Zhu, Zhen-Na Xia, Jian-Zhong Li, Guo-Cai Lu
EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0...
September 15, 2016: Toxicology and Applied Pharmacology
Yukihiko Hiroshima, Kiyohiko Shuto, Kazuto Yamazaki, Daisuke Kawaguchi, Masatoshi Yamada, Yutaro Kikuchi, Kohei Kasahara, Takashi Murakami, Atsushi Hirano, Mikito Mori, Chihiro Kosugi, Kenichi Matsuo, Yasuo Ishida, Keiji Koda, Kuniya Tanaka
BACKGROUND: Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. METHODS: We examined 34 patients (10 female and 24 male; mean age, 68...
July 20, 2016: Annals of Surgical Oncology
Saiho Ko, Yuuki Kirihataya, Masanori Matsusaka, Tomohide Mukogawa, Hirofumi Ishikawa, Akihiko Watanabe
BACKGROUND: Resectability of colorectal liver metastasis (CRLM) depends on major vascular involvement and is affected by chemotherapy-induced liver injury. Parenchyma-sparing with combined resection and reconstruction of involved vessels may expand the indications and safety of hepatectomy. METHODS: Of 92 patients who underwent hepatectomy for CRLM, 15 underwent major vascular resection and reconstruction. The reconstructed vessels were the portal vein (PV) in five cases, the major hepatic vein (HV) in nine cases, and the inferior vena cava in six cases...
August 2016: Annals of Surgical Oncology
Jung-Hye Choi, Young-Woong Won, Hyun Sung Kim, Young-Ha Oh, Sanghyeok Lim, Han-Joon Kim
Oxaliplatin is an effective chemotherapeutic agent for the treatment of colorectal cancer; however, it may cause liver injury, particularly sinusoidal obstruction syndrome (SOS). Although SOS does not usually present with focal lesions on radiological images, the present study describes the case of a 22-year-old woman with oxaliplatin-induced SOS mimicking metastatic colon cancer in the liver. An abdominal computed tomography revealed a novel 1 cm, low-density lesion in segment 1 of the liver following the administration of the fourth round of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer...
April 2016: Oncology Letters
Fernando Bessone, Marcelo Gabriel Roma
Ursodeoxycholic acid (UDCA) is the first choice medication for most cholestatic hepatopathies, due to its capability to counteract inflammation and bile-acid-induced liver damage, two common features in cholestasis. However, UDCA is usually contraindicated in obstructive cholestasis, due to the alleged risk of biliary integrity disruption due to its choleretic effect. We report on an 83-year-old man with an unsuspected malignant biliary obstruction who received moderate doses of UDCA (8-12 mg/kg/day) for 5 weeks, because the preliminary evidence suggested he had chemotherapy-induced cholestasis...
May 2016: Annals of Hepatology
J Martins, H Alexandrino, R Oliveira, M A Cipriano, D Falcão, L Ferreira, R Martins, M Serôdio, M Martins, J G Tralhão, L Prado e Castro, F Castro E Sousa
INTRODUCTION: Advances in neoadjuvant chemotherapy (NCT) have allowed surgical treatment in otherwise unresectable patients with colorectal liver metastases (CRLM). It is well known that NCT induces liver lesions such as sinusoidal obstruction syndrome (SOS) and steatohepatitis (SH). However, whether it affects postoperative morbidity remains controversial. The aim of this study was both to evaluate the impact of NCT on liver parenchyma and postoperative morbidity, and to identify preoperative predictive markers for liver injury...
May 2016: European Journal of Surgical Oncology
Qin Sun, Qing Zhang, Jin Gu, Wen-Wen Sun, Peng Wang, Chong Bai, He-Ping Xiao, Wei Sha
PURPOSE: Antituberculosis drug-induced liver injury (ATDILI) is one of the most deleterious side effects associated with chemotherapy against tuberculosis (TB). In this study, our objective was to determine the incidence, risk factors, and management of ATDILI and analyze its impact on the treatment outcome in patients receiving standard anti-TB chemotherapy. METHODS: A prospective cohort study of ATDILI prevalence was conducted in 938 enrolled patients of the 1426 TB cases in Shanghai from March 2011 to September 2012...
August 2016: Pharmacoepidemiology and Drug Safety
Andrea Janz Moreira, Raquel Ordoñez, Carlos Thadeu Cerski, Jaqueline Nascimento Picada, Andrés García-Palomo, Norma Possa Marroni, Jose L Mauriz, Javier González-Gallego
Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide because of its high incidence, its metastatic potential and the low efficacy of conventional treatment. Inactivation of apoptosis is implicated in tumour progression and chemotherapy resistance, and has been linked to the presence of endoplasmic reticulum stress. Melatonin, the main product of the pineal gland, exerts anti-proliferative, pro-apoptotic and anti-angiogenic effects in HCC cells, but these effects still need to be confirmed in animal models...
2015: PloS One
Hiren Mandaliya, Pinky Baghi, Amy Prawira, Mathew K George
Paclitaxel induced mild derangement of liver functions including bilirubin, alkaline phosphatase, and AST has been infrequently noticed in clinical trials. Contrary to Paclitaxel, hepatocellular injury, hepatitis, and liver tenderness are common laboratory and clinical findings with Trastuzumab. However, hepatic failure/necrosis secondary to Paclitaxel or Trastuzumab has never been reported in literature. A 62-year-old lady, previously healthy, was treated with adjuvant therapy for left breast stage II, high grade invasive ductal carcinoma which was node negative, oestrogen receptor negative, progesterone receptor positive, and HER2 receptor positive...
2015: Case Reports in Oncological Medicine
Bo Zhang, Cheng Lu, Ming Bai, Xiaojuan He, Yong Tan, Yanqin Bian, Cheng Xiao, Ge Zhang, Aiping Lu, Shao Li
ETHNOPHARMACOLOGICAL RELEVANCE: Tetramethylpyrazine (TMP) is one of the active constituents extracted from a frequently used herb, Ligusticum wallichii Franchat (Chuan-Xiong in Chinese), in traditional Chinese medicine. TMP can exert multiple pharmacological actions such as anti-inflammatory, anti-oxidative damage, anti-platelet and neuroprotective effects, and its applications deserve further explored. AIM OF THE STUDY: This study aimed to determine the new role of TMP identified by a network pharmacology approach to alleviate the methotrexate (MTX)-induced oxidative injury and characterize their mechanism of combinational actions...
December 4, 2015: Journal of Ethnopharmacology
Justin D Schumacher, Grace L Guo
Drug-induced steatohepatitis is a rare form of liver injury known to be caused by only a handful of compounds. These compounds stimulate the development of steatohepatitis through their toxicity to hepatocyte mitochondria; inhibition of beta-oxidation, mitochondrial respiration, and/or oxidative phosphorylation. Other mechanisms discussed include the disruption of phospholipid metabolism in lysosomes, prevention of lipid egress from hepatocytes, targeting mitochondrial DNA and topoisomerase, decreasing intestinal barrier function, activation of the adenosine pathway, increasing fatty acid synthesis, and sequestration of coenzyme A...
November 15, 2015: Toxicology and Applied Pharmacology
Wei Geng, Chung-Mau Lo, Kevin T P Ng, Chang-Chun Ling, Xiang Qi, Chang-Xian Li, Yuan Zhai, Xiao-Bing Liu, Yuen-Yuen Ma, Kwan Man
Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort...
September 29, 2015: Oncotarget
Eman Kandil, Nahed Abdel Aziz
Combining chemotherapy with radiotherapy represents a key oncology strategy for a more comprehensive attack toward cancers and improves treatment outcome for various solid tumor malignancies. The present study aims to evaluate the synergistic antitumor effect of γ-radiation together with gallium trichloride (GaCl3) and/or doxorubicin (DOX) against solid Ehrlich carcinoma (EC) in female mice. GaCl3 (300 mg/kg body weight (b.w.)) was administered by gavages daily on the seventh day after tumor inoculation, while the cytotoxic drug DOX (4 mg/kg b...
February 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Anne-Clémence Vion, Pierre-Emmanuel Rautou, François Durand, Chantal M Boulanger, Dominique C Valla
Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients...
September 2015: Seminars in Thrombosis and Hemostasis
Guichao Li, Jiazhou Wang, Weigang Hu, Zhen Zhang
PURPOSE: This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT. METHODS AND MATERIALS: Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed...
2015: PloS One
Hidehiro Tajima, Tetsuo Ohta, Tomoharu Miyashita, Shinichi Nakanuma, Miki Matoba, Takashi Miyata, Seisho Sakai, Koichi Okamoto, Isamu Makino, Jun Kinoshita, Hironori Hayashi, Keishi Nakamura, Katsunobu Oyama, Masafumi Inokuchi, Hisatoshi Nakagawara, Hiroyuki Takamura, Hirohisa Kitagawa, Sachio Fushida, Hiroko Ikeda
Oxaliplatin-based chemotherapy plays a central role in the treatment of patients with colorectal liver metastasis (CRLM). This treatment, however, has been associated with hepatic sinusoidal obstruction syndrome (SOS), a clinically important adverse effect characterized by a bluish hue of the liver, splenomegaly and thrombocytopenia, resulting in liver dysfunction. The significant association between the sinusoidal endothelium and platelets has suggested that oxaliplatin-based chemotherapy affects platelets in the liver...
May 2015: Molecular and Clinical Oncology
Bruno Vincenzi, Marco Imperatori, Antonio Picardi, Umberto Vespasiani Gentilucci, Paolo Gallo, Valentina Fausti, Mariella Spalato Ceruso, Daniele Santini, Giuseppe Tonini
BACKGROUND: Chemotherapy-induced toxic liver injury is a relevant issue in the clinical management of patients affected with metastatic colorectal cancer (mCRC). This retrospective study evaluated patterns of liver toxicity in patients treated with FOLinic acid, Fluorouracil, IRInotecan (FOLFIRI)-based regimens. METHODS: One hundred and fifty-six mCRC patients treated at the University Campus Bio-Medico between January 2003 and January 2013 were included in this retrospective analysis...
2015: Expert Review of Anticancer Therapy
Xiaojiang Li, Baole Li, Yingjie Jia
Haoqin Qingdan decoction (HQQD), a modern Chinese formula, has been widely used in Eastern Asia. Our study focuses on the hepatoprotective effect of HQQD against cyclophosphamide-induced hepatotoxicity. S180, a kind of ascites tumor cells, was used to establish S180-bearing mice, followed by the injection of cyclophosphamide (CP, 80 mg/kg) every other day for 5 times. HQQD was used intragastrically at the dose of 80 g/kg, 40 g/kg, and 20 g/kg twice a day for 12 days. HL-7702 hepatic cell line was incubated with HQQD-medicated serum...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
Songyu Cao, Cheng Wang, Hongxia Ma, Rong Yin, Meng Zhu, Wei Shen, Juncheng Dai, Yongqian Shu, Lin Xu, Zhibin Hu, Hongbing Shen
Platinum-based chemotherapy has been shown to improve the survival of advanced non-small cell lung cancer (NSCLC) patients; the platinum-induced toxicity severely impedes the success of chemotherapy. Genetic variations, such as single nucleotide polymorphisms (SNPs), may contribute to patients' responses to the platinum-based chemotherapy. To identify SNPs that modify the risk of hepatotoxicity in NSCLC patients receiving platinum-based chemotherapy, we performed a genome-wide association scan in 334 subjects followed by a replication study among 375 subjects...
June 23, 2015: Scientific Reports
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