Sample records for liver cancer treatment

  1. Childhood Liver Cancer Treatment (PDQ®)—Patient Version

    Cancer.gov

    Treatment for pediatric liver cancer depends on many factors, including the type of cancer and whether it has spread. When possible, liver cancer is removed by surgery. Learn about the types of treatment options for childhood liver cancers.

  2. Adult Primary Liver Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Adult primary liver cancer treatment options include surveillance, surgery, liver transplant, ablation, embolization, targeted therapy, and radiation. Get comprehensive information about liver cancer and treatment options in this clinician summary

  3. Childhood Liver Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Treatment options for children with liver cancer include surgery, chemotherapy, radiation, and transarterial chemoembolization or radioembolization. Get detailed information about newly diagnosed and recurrent childhood liver cancer treatment in this summary for clinicians.

  4. Adult Primary Liver Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Adult primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma. Treatments include surveillance, surgery, liver transplant, ablation therapy, embolization therapy, targeted therapy, and radiation therapy. Get comprehensive information about liver cancer and treatment in this clinician summary.

  5. Childhood Liver Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Childhood liver cancer has two major histologic subgroups: hepatoblastoma and hepatocellular carcinoma. Less common histologies are undifferentiated embryonal sarcoma of the liver, infantile choriocarcinoma, and vascular liver tumors. Get detailed information about newly diagnosed and recurrent childhood liver cancers including tumor biology, presentation, prognosis, staging, and treatment in this summary for clinicians.

  6. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... Hepatitis C Hepatitis D Hepatitis E Hepatitis G Liver cancer is a disease in which malignant (cancer) cells ... Primary Liver Cancer Treatment Childhood Liver Cancer Treatment Liver cancer is not common in the United States. Liver ...

  7. Dietary Natural Products for Prevention and Treatment of Liver Cancer

    PubMed Central

    Zhou, Yue; Li, Ya; Zhou, Tong; Zheng, Jie; Li, Sha; Li, Hua-Bin

    2016-01-01

    Liver cancer is the most common malignancy of the digestive system with high death rate. Accumulating evidences suggests that many dietary natural products are potential sources for prevention and treatment of liver cancer, such as grapes, black currant, plum, pomegranate, cruciferous vegetables, French beans, tomatoes, asparagus, garlic, turmeric, ginger, soy, rice bran, and some edible macro-fungi. These dietary natural products and their active components could affect the development and progression of liver cancer in various ways, such as inhibiting tumor cell growth and metastasis, protecting against liver carcinogens, immunomodulating and enhancing effects of chemotherapeutic drugs. This review summarizes the potential prevention and treatment activities of dietary natural products and their major bioactive constituents on liver cancer, and discusses possible mechanisms of action. PMID:26978396

  8. Stages of Childhood Liver Cancer

    MedlinePlus

    ... Liver Cancer Prevention Liver Cancer Screening Research Childhood Liver Cancer Treatment (PDQ®)–Patient Version Treatment Option Overview Go ... different types of treatment for patients with childhood liver cancer. Different types of treatments are available for children ...

  9. Treatment for liver metastases from breast cancer: Results and prognostic factors

    PubMed Central

    Li, Xiao-Ping; Meng, Zhi-Qiang; Guo, Wei-Jian; Li, Jie

    2005-01-01

    AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients may benefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE). We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACE or systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%, respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the

  10. Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.

    PubMed

    Zhou, Feilong; Teng, Fangfang; Deng, Peizong; Meng, Ning; Song, Zhimei; Feng, Runliang

    2018-02-07

    Liver cancer is one of serious diseases which threaten human life and health. Studies on the treatment of liver cancer have attracted widespread attention. Application of nano-drug delivery system (NDDS) can not only improve selective drug delivery to liver tissue and improve the bioavailability of drug, but also can reduce the side effects of drugs when it is specially modified in the respects of structure modification or specific target molecules decoration. This review will address the latest development of liver-targeted drug delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Treatment Option Overview (Adult Primary Liver Cancer)

    MedlinePlus

    ... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...

  12. Treatment Options for Adult Primary Liver Cancer

    MedlinePlus

    ... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...

  13. Induction of an altered lipid phenotype by two cancer promoting treatments in rat liver.

    PubMed

    Riedel, S; Abel, S; Swanevelder, S; Gelderblom, W C A

    2015-04-01

    Changes in lipid metabolism have been associated with tumor promotion in rat liver. Similarities and differences of lipid parameters were investigated using the mycotoxin fumonisin B1 (FB1) and the 2-acetylaminofluorene/partial hepatectomy (AAF/PH) treatments as cancer promoters in rat liver. A typical lipid phenotype was observed, including increased membranal phosphatidylethanolamine (PE) and cholesterol content, increased levels of C16:0 and monounsaturated fatty acids in PE and phosphatidylcholine (PC), as well as a decrease in C18:0 and long-chained polyunsaturated fatty acids in the PC fraction. The observed lipid changes, which likely resulted in changes in membrane structure and fluidity, may represent a growth stimulus exerted by the cancer promoters that could provide initiated cells with a selective growth advantage. This study provided insight into complex lipid profiles induced by two different cancer promoting treatments and their potential role in the development of hepatocyte nodules, which can be used to identify targets for the development of chemopreventive strategies against cancer promotion in the liver. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Outcome of 1000 liver cancer patients evaluated at the UPMC Liver Cancer Center.

    PubMed

    Geller, David A; Tsung, Allan; Marsh, J Wallis; Dvorchik, Igor; Gamblin, T Clark; Carr, Brian I

    2006-01-01

    We evaluated 1000 consecutive patients with liver tumors at the University of Pittsburgh Medical Center (UPMC) Liver Cancer Center over the 4-year period from August 2000 to August 2004. Of the 1000 patients seen, 573 had primary liver cancer and 427 had metastatic cancer to the liver. The mean age of the patients evaluated was 62.2 years, and 61% were male. Treatment consisted of a liver surgical procedure (resection or radiofrequency ablation) in 369 cases (36.9%), hepatic intra-arterial regional therapy (transarterial chemoembolization or (90)yttrium microspheres) in 524 cases (52.4%), systemic chemotherapy in 35 cases (3.5%), and palliative care in 72 patients (7.2%). For treated patients, median survival was 884 days for those undergoing resection/radiofrequency ablation, compared to 295 days with regional therapy. These data indicate that over 90% of patients with liver cancer evaluated at a tertiary referral center can be offered some form of therapy. Survival rates are superior with a liver resection or ablation procedure, which is likely consistent with selection bias. Hepatocellular carcinoma was the most common tumor seen due to referral pattern and screening of hepatitis patients at a major liver transplant center. The most common reason for offering palliative care was hepatic insufficiency usually associated with cirrhosis.

  15. [The surgical treatment of ovarian cancer metastasis between liver and diaphragm: a report of 83 cases].

    PubMed

    Xu, Y Y; Lu, X; Mao, Y L; Xiong, J P; Bian, J; Huang, H C; Yang, H Y; Sang, X T; Zhao, H T; Xu, H F; Chi, T Y; Du, S D; Zhong, S X; Huang, J F

    2017-11-01

    Objective: To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer. Methods: Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed. Results: Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination. Conclusion: Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.

  16. High intensity focused ultrasound ablation for patients with inoperable liver cancer.

    PubMed

    Chen, Lianyu; Wang, Kun; Chen, Zhen; Meng, Zhiqiang; Chen, Hao; Gao, Huifeng; Wang, Peng; Zhu, Huili; Lin, Junhua; Liu, Luming

    2015-01-01

    To analyses the feasibility and efficacy of high intensity focused ultrasound (HIFU) treatment in patients with inoperable liver cancer. 187 patients were treated with HIFU, of all these patients 116 cases were Primary Liver Cancer (PLC) and 71 cases were Metastatic Liver Cancer (MLC). According to some parameters, such as clinical symptoms, the basis of main organs functional tests, imaging examinations, and progression-free survival (PFS) time to assess the safety and efficacy of HIFU in the treatment of liver cancer. 55 patients (29.4%) achieved CR and 73 patients (39.0%) achieved PR, 32 patients (17.1%) had responses of SD, and 27 patients (14.4%) were PD, respectively. Response rates were 90.5% (32 CR + 6 PR/42) in left lobe cancer and 64.1% (22 CR + 62 PR/131) in right lobe cancer. The median PFS for those CR case was 7 months, of PLC was 8 months, of MLC was 5 months. HIFU is effective and feasible in the treatment of liver cancer. It offer a significant noninvasive therapy for local treatment of liver cancer. For those right lobe liver cancers or with poor ultrasonic window, increasing treatment time or repeated treatment may improve the efficiency of HIFU ablation.

  17. Novel Antibody Targets Glypican-3 in Liver Cancer | Center for Cancer Research

    Cancer.gov

    New treatments for patients with liver cancer, the third most common cause of cancer-related death, are desperately needed. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and HCC tumors are particularly insensitive to chemotherapy. Surgery is the standard treatment for HCCs caught early, but only about a third of cases are identified at this stage.

  18. MCNP simulation of the dose distribution in liver cancer treatment for BNC therapy

    NASA Astrophysics Data System (ADS)

    Krstic, Dragana; Jovanovic, Zoran; Markovic, Vladimir; Nikezic, Dragoslav; Urosevic, Vlade

    2014-10-01

    The Boron Neutron Capture Therapy ( BNCT) is based on selective uptake of boron in tumour tissue compared to the surrounding normal tissue. Infusion of compounds with boron is followed by irradiation with neutrons. Neutron capture on 10B, which gives rise to an alpha particle and recoiled 7Li ion, enables the therapeutic dose to be delivered to tumour tissue while healthy tissue can be spared. Here, therapeutic abilities of BNCT were studied for possible treatment of liver cancer using thermal and epithermal neutron beam. For neutron transport MCNP software was used and doses in organs of interest in ORNL phantom were evaluated. Phantom organs were filled with voxels in order to obtain depth-dose distributions in them. The result suggests that BNCT using an epithermal neutron beam could be applied for liver cancer treatment.

  19. Novel Antibody Targets Glypican-3 in Liver Cancer | Center for Cancer Research

    Cancer.gov

    New treatments for patients with liver cancer, the third most common cause of cancer-related death, are desperately needed. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and HCC tumors are particularly insensitive to chemotherapy. Surgery is the standard treatment for HCCs caught early, but only about a third of cases are identified at this stage. Antibody therapy offers a potential alternative for treating later-stage tumors.

  20. Cancer stem cells in the development of liver cancer

    PubMed Central

    Yamashita, Taro; Wang, Xin Wei

    2013-01-01

    Liver cancer is an aggressive disease with a poor outcome. Several hepatic stem/progenitor markers are useful for isolating a subset of liver cells with stem cell features, known as cancer stem cells (CSCs). These cells are responsible for tumor relapse, metastasis, and chemoresistance. Liver CSCs dictate a hierarchical organization that is shared in both organogenesis and tumorigenesis. An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies. This Review highlights recent advances in understanding the pathogenesis of liver CSCs and discusses unanswered questions about the concept of liver CSCs. PMID:23635789

  1. [Early diagnosis and early treatment for liver cancer in Qidong: survival of patients and effectiveness of screening].

    PubMed

    Chen, J G; Zhang, Y H; Zhu, J; Lu, J H; Wang, J B; Sun, Y; Xue, X F; Lu, L L; Chen, Y S; Wu, Y; Jiang, X P; Ding, L L; Zhang, Q N; Zhu, Y R

    2017-12-23

    Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B

  2. [Oligometastasized colorectal cancer-modern treatment strategies].

    PubMed

    Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

    2018-06-05

    The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.

  3. Immune checkpoint therapy in liver cancer.

    PubMed

    Xu, Feng; Jin, Tianqiang; Zhu, Yuwen; Dai, Chaoliu

    2018-05-29

    Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan. Preclinical and clinical studies show immune checkpoint therapy provides survival benefit for greater numbers of patients with liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, two main primary liver cancers. The combination of anti-PD-1/PD-L1 with anti-CTLA-4 antibodies is being evaluated in phase 1, 2 or 3 trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. In addition, studies on activating co-stimulatory receptors to enhance anti-tumor immune responses have increased our understanding regarding this immunotherapy in liver cancer. Epigenetic modulations of checkpoints for improving the tumor microenvironment also expand our knowledge of potential therapeutic targets in improving the tumor microenvironment and restoring immune recognition and immunogenicity. In this review, we summarize current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma and attempt to clarify the mechanisms underlying its effects.

  4. Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance.

    PubMed

    Li, Xiao-Feng; Chen, Cheng; Xiang, Dai-Min; Qu, Le; Sun, Wen; Lu, Xin-Yuan; Zhou, Teng-Fei; Chen, Shu-Zhen; Ning, Bei-Fang; Cheng, Zhuo; Xia, Ming-Yang; Shen, Wei-Feng; Yang, Wen; Wen, Wen; Lee, Terence Kin Wah; Cong, Wen-Ming; Wang, Hong-Yang; Ding, Jin

    2017-12-01

    The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6-positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage-secreted tumor necrosis factor-α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self-renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6-positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. Our results not only clarify the cellular and molecular mechanisms underlying the inflammation-mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934-1951). © 2017 by the American Association for the Study of Liver Diseases.

  5. CWP232228 targets liver cancer stem cells through Wnt/β-catenin signaling: a novel therapeutic approach for liver cancer treatment.

    PubMed

    Kim, Ji-Young; Lee, Hwa-Yong; Park, Kwan-Kyu; Choi, Yang-Kyu; Nam, Jeong-Seok; Hong, In-Sun

    2016-04-12

    Liver cancer stem cells (CSCs) are resistant to conventional chemotherapy and radiation, which may destroy tumor masses, but not all liver CSCs contribute to tumor initiation, metastasis, and relapse. In the present study, we showed that liver CSCs with elevated Wnt/β-catenin signaling possess much greater self-renewal and clonogenic potential. We further documented that the increased clonogenic potential of liver CSCs is highly associated with changes in Wnt/β-catenin signaling and that Wnt/β-catenin signaling activity is positively correlated with CD133 expression and aldehyde dehydrogenase (ALDH) enzymatic activity. Notably, the small molecule inhibitor CWP232228, which antagonizes the binding of β-catenin to TCF in the nucleus, inhibits Wnt/β-catenin signaling and depletes CD133+/ALDH+ liver CSCs, thus ultimately diminishing the self-renewal capacity of CSCs and decreasing tumorigenicity in vitro and in vivo. Taken together, our findings suggest that CWP232228 acts as a candidate therapeutic agent for liver cancer by preferentially targeting liver CSCs.

  6. Preference elicitation approach for measuring the willingness to pay for liver cancer treatment in Korea.

    PubMed

    Cho, Donghun; Jo, Changik

    2015-09-01

    The Korean government has expanded the coverage of the national insurance scheme for four major diseases: cancers, cardiovascular diseases, cerebrovascular diseases, and rare diseases. This policy may have a detrimental effect on the budget of the national health insurance agency. Like taxes, national insurance premiums are levied on the basis of the income or wealth of the insured. Using a preference elicitation method, we attempted to estimate how much people are willing to pay for insurance premiums that would expand their coverage for liver cancer treatment. We calculated the marginal willingness to pay (MWTP) through the marginal rate of substitution between the two attributes of the insurance premium and the total annual treatment cost by adopting conditional logit and mixed logit models. The effects of various other terms that could interact with socioeconomic status were also estimated, such as gender, income level, educational attainment, age, employment status, and marital status. The estimated MWTP values of the monthly insurance premium for liver cancer treatment range from 4,130 KRW to 9,090 KRW.

  7. Monte Carlo simulation of liver cancer treatment with 166Ho-loaded glass microspheres

    NASA Astrophysics Data System (ADS)

    da Costa Guimarães, Carla; Moralles, Maurício; Roberto Martinelli, José

    2014-02-01

    Microspheres loaded with pure beta-emitter radioisotopes are used in the treatment of some types of liver cancer. The Instituto de Pesquisas Energéticas e Nucleares (IPEN) is developing 166Ho-loaded glass microspheres as an alternative to the commercially available 90Y microspheres. This work describes the implementation of a Monte Carlo code to simulate both the irradiation effects and the imaging of 166Ho and 90Y sources localized in different parts of the liver. Results obtained with the code and perspectives for the future are discussed.

  8. A Novel Nitinol Spherical Occlusion Device for Liver Cancer

    PubMed Central

    Hsiao, Hao-Ming; Wang, Yi-Ping; Ko, Chun-Yi; Cheng, Yu-Han; Lee, Han-Yu

    2016-01-01

    Liver cancer or hepatic cancer is a cancer that originates in the liver. It is formed from either the liver itself or from structures within the liver, including blood vessels or the bile duct. Liver cancer can be a life-threatening condition, but it may be cured if found early. Hepatic artery embolization is one of the treatment options involving the injection of substances to reduce the blood flow to cancer cells in the livers of patients with tumors that cannot be removed by surgery; however, this treatment has some limitations. In this paper, we propose a novel nitinol “spherical occlusion device” concept, the first of its kind in the world. Our proposed spherical occlusion device is able to reduce the blood flow to cancer cells by deploying it in the upstream hepatic artery supplying blood to the liver. Moreover, it could carry multiple chemotherapy or radioactive drugs for delivery directly to the target site. Nitinol alloy was chosen as the device material due to its excellent super-elastic property. Computational models were developed to predict the mechanical response of the device during manufacturing and deployment procedures, as well as its hemodynamic behavior. Simulation results showed that the presence of the spherical occlusion device with 14%–27% metal density deployed at the upstream location of the right hepatic artery had significant occlusion effects, with the average blood flow rate cut down by 30%–50%. A pulsed fiber laser and a series of expansions and heat treatments were developed to make the first prototype of the spherical occlusion device for the demonstration of our novel concept. PMID:28787820

  9. Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

    PubMed

    Oki, Eiji; Tokunaga, Shoji; Emi, Yasunori; Kusumoto, Tetsuya; Yamamoto, Manabu; Fukuzawa, Kengo; Takahashi, Ikuo; Ishigami, Sumiya; Tsuji, Akihito; Higashi, Hidefumi; Nakamura, Toshihiko; Saeki, Hiroshi; Shirabe, Ken; Kakeji, Yoshihiro; Sakai, Kenji; Baba, Hideo; Nishimaki, Tadashi; Natsugoe, Shoji; Maehara, Yoshihiko

    2016-07-01

    The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

  10. Investigation of the roles of exosomes in colorectal cancer liver metastasis.

    PubMed

    Wang, Xia; Ding, Xiaoling; Nan, Lijuan; Wang, Yiting; Wang, Jing; Yan, Zhiqiang; Zhang, Wei; Sun, Jihong; Zhu, Wei; Ni, Bing; Dong, Suzhen; Yu, Lei

    2015-05-01

    The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.

  11. Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells.

    PubMed

    Chen, Kaiyun; Zhu, Shuguang; Xiang, Guoan; Duan, Xiaopeng; He, Jiwen; Chen, Guihua

    2016-05-01

    To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.

  12. Adjunctive traditional Chinese medicine therapy improves survival of liver cancer patients.

    PubMed

    Liao, Yueh-Hsiang; Lin, Cheng-Chieh; Lai, Hsueh-Chou; Chiang, Jen-Huai; Lin, Jaung-Geng; Li, Tsai-Chung

    2015-12-01

    Traditional Chinese medicine (TCM) is an alternative treatment for cancer with its effect by stimulating host immune response for cytotoxic activity against liver cancer. No studies evaluated TCM treatment on survival of liver cancer patients. This study determined whether the combination of TCM and conventional cancer treatment affects the survival of liver cancer patients. A retrospective cohort study was conducted in 127 237 newly diagnosed liver cancer patients from 2000 to 2009 in the National Health Insurance Program database. Among these patients, 30 992 (24.36%) used TCM for liver cancer care. All patients were followed up until 2011. The mean follow-up was 5.67 years (SD 1.47) for TCM users and 5.49 years (SD 3.64) for non-TCM users. Compared with patients without TCM use, patients with TCM use were significantly associated with a decreased risk of death [hazard ratio (HR) = 0.65, 95% confidence interval (CI) = 0.64-0.66] with multivariate adjustment. A similar significant protective effect of TCM use across various subgroups of chronic liver diseases was also observed. Jia Wei Xiao Yao San (HR = 0.89, 95% CI = 0.81-0.96) and Chai Hu Shu Gan Tang (HR = 0.86, 95% CI = 0.78-0.95) were the most effective TCM agents that improved survival. This cohort study provided information that adjunctive therapy with TCM may improve the survival in liver cancer patients. Further studies are needed to confirm the potential role of TCM in HCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Rectal cancer with synchronous liver metastases: Do we have a clear direction?

    PubMed

    Pathak, S; Nunes, Q M; Daniels, I R; Smart, N J; Poston, G J; Påhlman, L

    2015-12-01

    Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Janus "nano-bullets" for magnetic targeting liver cancer chemotherapy.

    PubMed

    Shao, Dan; Li, Jing; Zheng, Xiao; Pan, Yue; Wang, Zheng; Zhang, Ming; Chen, Qi-Xian; Dong, Wen-Fei; Chen, Li

    2016-09-01

    Tumor-targeted delivery of anti-cancer drugs with controlled drug release function has been recognized as a promising strategy for pursuit of increased chemotherapeutic efficacy and reduced adverse effects. Development of magnetic nanoparticulates as delivery carriers to accommodate cytotoxic drugs for liver cancer treatment has evoked immense interest with respect to their convenience in biomedical application. Herein, we engineered multifunctional Janus nanocomposites, characterized by a head of magnetic Fe3O4 and a body of mesoporous SiO2 containing doxorubicin (DOX) as "nano-bullets" (M-MSNs-DOX). This nanodrug formulation possessed nanosize with controlled aspect-ratio, defined abundance in pore structures, and superior magnetic properties. M-MSN-DOX was determined to induce selective growth inhibition to the cancer cell under magnetic field rather than human normal cells due to its preferable endocytosis by the tumor cells and pH-promoted DOX release in the interior of cancer cells. Ultimately, both subcutaneous and orthotropic liver tumor models in mice have demonstrated that the proposed Janus nano-bullets imposed remarkable suppression of the tumor growth and significantly reduced systematic toxicity. Taken together, this study demonstrates an intriguing targeting strategy for liver cancer treatment based on a novel Janus nano-bullet, aiming for utilization of nanotechnology to obtain safe and efficient treatment of liver cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Stopping Liver Cancer's Rogue COP | Center for Cancer Research

    Cancer.gov

    Liver cancer is the fourth most common cancer type and the third leading cause of cancer death worldwide. Many liver tumors are actually metastases, tumors seeded in the liver by cancer cells from another organ, but hepatocellular carcinomas (HCCs), the most common liver tumors, are a heterogeneous family of cancers that arise in hepatocytes, the functional cells of the liver.

  16. Fighting liver cancer with combination immunotherapies | Center for Cancer Research

    Cancer.gov

    A new clinical trial testing the effectiveness of immunotherapy treatment combinations against liver cancer is enrolling patients at the NIH Clinical Center in Bethesda, Maryland. Individually, immunotherapy drugs harness the power of the human immune system to better identify and kill cancer cells. Now, researchers at the NIH’s Center for Cancer Research have begun to find

  17. Cancer and liver cirrhosis: implications on prognosis and management

    PubMed Central

    Pinter, Matthias; Trauner, Michael; Peck-Radosavljevic, Markus; Sieghart, Wolfgang

    2016-01-01

    Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies. PMID:27843598

  18. Management of Liver Cancer Argon-helium Knife Therapy with Functional Computer Tomography Perfusion Imaging.

    PubMed

    Wang, Hongbo; Shu, Shengjie; Li, Jinping; Jiang, Huijie

    2016-02-01

    The objective of this study was to observe the change in blood perfusion of liver cancer following argon-helium knife treatment with functional computer tomography perfusion imaging. Twenty-seven patients with primary liver cancer treated with argon-helium knife and were included in this study. Plain computer tomography (CT) and computer tomography perfusion (CTP) imaging were conducted in all patients before and after treatment. Perfusion parameters including blood flows, blood volume, hepatic artery perfusion fraction, hepatic artery perfusion, and hepatic portal venous perfusion were used for evaluating therapeutic effect. All parameters in liver cancer were significantly decreased after argon-helium knife treatment (p < 0.05 to all). Significant decrease in hepatic artery perfusion was also observed in pericancerous liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy. © The Author(s) 2014.

  19. Stopping Liver Cancer's Rogue COP | Center for Cancer Research

    Cancer.gov

    Liver cancer is the fourth most common cancer type and the third leading cause of cancer death worldwide. Many liver tumors are actually metastases, tumors seeded in the liver by cancer cells from another organ, but hepatocellular carcinomas (HCCs), the most common liver tumors, are a heterogeneous family of cancers that arise in hepatocytes, the functional cells of the liver. HCCs are often associated with cirrhosis or liver scarring. Because of the variation in tumor phenotypes, the poor understanding of the molecular origins of these tumors, and the increasing number of diagnoses especially in the US, HCC is a major clinical challenge.

  20. Identification of liver cancer-specific aptamers using whole live cells.

    PubMed

    Shangguan, Dihua; Meng, Ling; Cao, Zehui Charles; Xiao, Zeyu; Fang, Xiaohong; Li, Ying; Cardona, Diana; Witek, Rafal P; Liu, Chen; Tan, Weihong

    2008-02-01

    Liver cancer is the third most deadly cancers in the world. Unfortunately, there is no effective treatment. One of the major problems is that most cancers are diagnosed in the later stage, when surgical resection is not feasible. Thus, accurate early diagnosis would significantly improve the clinical outcome of liver cancer. Currently, there are no effective molecular probes to recognize biomarkers that are specific for liver cancer. The objective of our current study is to identify liver cancer cell-specific molecular probes that could be used for liver cancer recognition and diagnosis. We applied a newly developed cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) method for the generation of molecular probes for specific recognition of liver cancer cells. The cell-SELEX uses whole live cells as targets to select aptamers (designed DNA/RNA) for cell recognition. In generating aptamers for liver cancer recognition, two liver cell lines were used: a liver cancer cell line BNL 1ME A.7R.1 (MEAR) and a noncancer cell line, BNL CL.2 (BNL). Both cell lines were originally derived from Balb/cJ mice. Through multiple rounds of selection using BNL as a control, we have identified a panel of aptamers that specifically recognize the cancer cell line MEAR with Kd in the nanomolar range. We have also demonstrated that some of the selective aptamers could specifically bind liver cancer cells in a mouse model. There are two major new results (compared with our reported cell-SELEX methodology) in addition to the generation of aptamers specifically for liver cancer. The first one is that our current study demonstrates that cell-based aptamer selection can select specific aptamers for multiple cell lines, even for two cell lines with minor differences (MEAR cell is derived from BNL by chemical inducement); and the second result is that cell-SELEX can be used for adhesive cells and thus open the door for solid tumor selection and investigation. The newly

  1. Endoscopic stenting in bile duct cancer increases liver volume.

    PubMed

    Lee, Chang Hun; Kim, Seong Hun; Kim, In Hee; Kim, Sang Wook; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul; Cho, Baik Hwan; Lee, Seung Ok

    2014-09-01

    Objective evaluation tools for assessing the effectiveness of stenting in palliative treatment of malignant biliary obstruction are not satisfactory. Effects of biliary stenting on liver volume change have never been studied. We aimed to use volumetry to analyze liver volume changes after endoscopic stenting in bile duct cancer according to the location and number of stents. Retrospective review. University hospital. Patients with a diagnosis of hilar or distal bile duct cancer and who underwent biliary metal stenting. ERCP with self-expandable metal stent placement. Liver volume change after biliary stenting and its comparison according to the location (hilar vs distal common bile duct) and number (hilar bilateral vs hilar unilateral). There were 60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean follow-up duration was 11.7 ± 4.9 weeks. Liver volume increased 17.4 ± 24.1%. The rate of liver growth was rapid during the early period from 4 to 8 weeks. Stenting in hilar bile duct cancer tended to increase liver volume more than distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer, unilateral and bilateral stents showed similar liver volume increases (20.1% and 25.8%, respectively; P = .512). Single center, retrospective. Biliary stenting markedly increased liver volume in both hilar and distal bile duct cancer. Our data suggest that liver volume assessment could be a useful tool for evaluating stent efficacy. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  2. Survival benefit of liver resection for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma.

    PubMed

    Kim, H; Ahn, S W; Hong, S K; Yoon, K C; Kim, H-S; Choi, Y R; Lee, H W; Yi, N-J; Lee, K-W; Suh, K-S

    2017-07-01

    Although transarterial chemoembolization is recommended as the standard treatment for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (BCLC-B HCC), other treatments including liver resection have been used. This study aimed to determine the survival benefit of treatment strategies including resection for BCLC-B HCC compared with non-surgical treatments. The nationwide multicentre database of the Korean Liver Cancer Association was reviewed. Patients with BCLC-B HCC who underwent liver resection as a first or second treatment within 2 years of diagnosis and patients who received non-surgical treatment were selected randomly. Survival outcomes of propensity score-matched groups were compared. Among 887 randomly selected patients with BCLC-B HCC, 83 underwent liver resection as first or second treatment and 597 had non-surgical treatment. After propensity score matching, the two groups were well balanced (80 patients in each group). Overall median survival in the resection group was better than that for patients receiving non-surgical treatment (50·9 versus 22·1 months respectively; P < 0·001). The 1-, 2-, 3- and 5-year overall survival rates in the resection group were 90, 88, 75 and 63 per cent, compared with 79, 48, 35 and 22 per cent in the no-surgery group (P < 0·001). In multivariable analysis, non-surgical treatment only (hazard ratio (HR) 3·35, 95 per cent c.i. 2·16 to 5·19; P < 0·001), albumin level below 3·5 g/dl (HR 1·96, 1·22 to 3·15; P = 0·005) and largest tumour size greater than 5·0 cm (HR 1·81, 1·20 to 2·75; P = 0·005) were independent predictors of worse overall survival. Treatment strategies that include liver resection offer a survival benefit compared with non-surgical treatments for potentially resectable BCLC-B HCC. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  3. Controlling liver cancer internationally: A qualitative study of clinicians' perceptions of current public policy needs.

    PubMed

    Bridges, John Fp; Gallego, Gisselle; Blauvelt, Barri M

    2011-07-28

    Liver cancer is the fifth most common cancer in men and the seventh for women. Usually because of late diagnosis, the prognosis for liver cancer remains poor, resulting in liver cancer being the third most common cause of death from cancer. While some countries have treatment guidelines, little is known or understood about the strategies needed for liver cancer control internationally. To explore leading liver cancer clinician's perceptions of the current public policy needs to control liver cancer internationally. Key informant interviews were conducted with a range of liver cancer clinicians involved in policy in eleven countries. Interviews were digitally recorded, transcribed verbatim, translated (where necessary), de-identified and analyzed by two researchers using a constant comparative method. Twenty in-depth semi-structured interviews were conducted in: Australia, China, France, Germany, Italy, Japan, Spain, South Korea, Taiwan, Turkey and the United States. Nine themes were identified and cluster into three groups: 1) Promoting prevention via early risk assessment, focusing on viral hepatitis and other lifestyle factors; 2) Increasing political, public and medical community awareness; and 3) Improving funding for screening, liver cancer surveillance and treatment. This study is an important step towards developing an evidence-based approach to assessing preparedness for implementing comprehensive liver cancer control strategies. Evaluation mechanisms to assess countries' performance on the needs described are needed. Future research will concentrate of understanding how these needs vary across countries and the optimal strategies to improve the diagnosis and prognosis of patients with liver cancer internationally.

  4. Quercetin Potentiates Doxorubicin Mediated Antitumor Effects against Liver Cancer through p53/Bcl-xl

    PubMed Central

    Wang, Guanyu; Sharma, Sherven; Dong, Qinghua

    2012-01-01

    Background The dose-dependent toxicities of doxorubicin (DOX) limit its clinical applications, particularly in drug-resistant cancers, such as liver cancer. In this study, we investigated the role of quercetin on the antitumor effects of DOX on liver cancer cells and its ability to provide protection against DOX-mediated liver damage in mice. Methodology and Results The MTT and Annexin V/PI staining assay demonstrated that quercetin selectively sensitized DOX-induced cytotoxicity against liver cancer cells while protecting normal liver cells. The increase in DOX-mediated apoptosis in hepatoma cells by quercetin was p53-dependent and occurred by downregulating Bcl-xl expression. Z-VAD-fmk (caspase inhibitor), pifithrin-α (p53 inhibitor), or overexpressed Bcl-xl decreased the effects of quercetin on DOX-mediated apoptosis. The combined treatment of quercetin and DOX significantly reduced the growth of liver cancer xenografts in mice. Moreover, quercetin decreased the serum levels of alanine aminotransferase and aspartate aminotransferase that were increased in DOX-treated mice. Quercetin also reversed the DOX-induced pathological changes in mice livers. Conclusion and Significance These results indicate that quercetin potentiated the antitumor effects of DOX on liver cancer cells while protecting normal liver cells. Therefore, the development of quercetin may be beneficial in a combined treatment with DOX for increased therapeutic efficacy against liver cancer. PMID:23240061

  5. Liver cancer mortality rate model in Thailand

    NASA Astrophysics Data System (ADS)

    Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

    2013-09-01

    Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

  6. [Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].

    PubMed

    Hagymási, Krisztina; Tulassay, Zsolt

    2008-03-23

    Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

  7. Molecular Signature Reveals Which Liver Cancer Patients May Benefit from a New Drug | Center for Cancer Research

    Cancer.gov

    Only one drug currently on the market has the potential to extend survival for patients with advanced-stage liver cancer and only 30 percent of patients are eligible to receive it. As the fastest-growing type of cancer by incidence in the United States, liver cancer represents a major public health problem and there is an urgent need to develop new treatment strategies.

  8. Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

    PubMed Central

    Sag, Alan Alper; Selcukbiricik, Fatih; Mandel, Nil Molinas

    2016-01-01

    Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population. PMID:27003990

  9. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

    PubMed Central

    Thoppil, Roslin J; Bishayee, Anupam

    2011-01-01

    Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called “isoprenoids”) are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed. PMID:21969877

  10. Long-term Survivors After Liver Resection for Breast Cancer Liver Metastases.

    PubMed

    BacalbaȘa, Nicolae; Balescu, Irina; Dima, Simona; Popescu, Irinel

    2015-12-01

    Although breast cancer liver metastases are considered a sign of systemic recurrence and are considered a poor prognostic factor that transforms the patient into a candidate for palliative chemotherapy, surgery might be performed with good results. Success reported after liver resection for colorectal hepatic metastases encouraged the oncological surgeon to apply similar protocols in breast cancer liver metastases. Data of patients submitted to hepatectomies for breast cancer liver metastases in the "Dan Setlacec" Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute, Bucharest were retrospectively reviewed. Among five cases survival after liver surgery surpassed 5 years and was considered long-term survival. One of the five cases was submitted to a second liver resection. Most often long-term survivors were reported among patients with single, metachronous and smaller than 5-cm lesions. In selected cases liver resection for breast cancer liver metastases can be associated with a significant increase in survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2018-02-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  12. Lessons Learned From a Case of Gastric Cancer After Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Yang, Kun; Zhu, Hong; Chen, Chong-Cheng; Wen, Tian-Fu; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Guo, Dong-Jiao; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Abstract Nowadays, de novo malignancies have become an important cause of death after transplantation. According to the accumulation of cases with liver transplantation, the incidence of de novo gastric cancer is anticipated to increase among liver transplant recipients in the near future, especially in some East Asian countries where both liver diseases requiring liver transplantation and gastric cancer are major burdens. Unfortunately, there is limited information regarding the relationship between de novo gastric cancer and liver transplantation. Herein, we report a case of stage IIIc gastric cancer after liver transplantation for hepatocellular carcinoma, who was successfully treated by radical distal gastrectomy with D2 lymphadenectomy but died 15 months later due to tumor progression. Furthermore, we extract some lessons to learn from the case and review the literatures. The incidence of de novo gastric cancer following liver transplantations is increasing and higher than the general population. Doctors should be vigilant in early detection and control the risk factors causing de novo gastric cancer after liver transplantation. Curative gastrectomy with D2 lymphadenectomy is still the mainstay of treatment for such patients. Preoperative assessments, strict postoperative monitoring, and managements are mandatory. Limited chemotherapy could be given to the patients with high risk of recurrence. Close surveillance, early detection, and treatment of posttransplant cancers are extremely important and essential to improve the survival. PMID:26886605

  13. Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression.

    PubMed

    Bao, Tianhao; Ke, Yang; Wang, Yifan; Wang, Weiwei; Li, Yuehua; Wang, Yan; Kui, Xiang; Zhou, Qixin; Zhou, Han; Zhang, Cheng; Zhou, Dongming; Wang, Lin; Xiao, Chunjie

    2018-07-01

    Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterol on the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumor suppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes. Furthermore, Taraxasterol upregulated Hint1 and Bax, but downregulated Bcl2 and cyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. The effects of Taraxasterol were abrogated by Hint1 silencing and partially mitigated by Bax silencing, Bcl2 or cyclin D1 over-expression in HepG2 cells. Moreover, oral administration with Taraxasterol did not affect body weight, urinary protein levels, and the heart, liver, and kidney morphology in BALB/c mice but effectively inhibited the growth of implanted SK-Hep1 tumor in vivo. Collectively, we demonstrate that Taraxasterol inhibits the growth of liver cancer at least partially by enhancing Hint1 expression to regulate Bax, Bcl2, and cyclin D1 expression. Taraxasterol may be a drug candidate for the treatment of human liver cancer. Taraxasterol inhibits growth and induces apoptosis in human liver cancer cells. Taraxasterol enhances Hint1 expression by promoting demethylation in Hint1 promoter. Taraxasterol increases Hint1 levels to regulate Bax, Bcl2, and cyclinD1 expression. The effects of Taraxasterol are abrogated by Hint1 silencing in liver cancer cells. Taraxasterol inhibits the growth of subcutaneously implanted liver cancers in mice.

  14. Fighting liver cancer with combination immunotherapies | Center for Cancer Research

    Cancer.gov

    A new clinical trial testing the effectiveness of immunotherapy treatment combinations against liver cancer is enrolling patients at the NIH Clinical Center in Bethesda, Maryland. Individually, immunotherapy drugs harness the power of the human immune system to better identify and kill cancer cells. Now, researchers at the NIH’s Center for Cancer Research have begun to find evidence that the drugs may work far more effectively when taken in combination with other therapies and with each other than when taken alone.

  15. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

    PubMed Central

    Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

  16. Application of Cox model in coagulation function in patients with primary liver cancer.

    PubMed

    Guo, Xuan; Chen, Mingwei; Ding, Li; Zhao, Shan; Wang, Yuefei; Kang, Qinjiong; Liu, Yi

    2011-01-01

    To analyze the distribution of coagulation parameters in patients with primary liver cancer; explore the relationship between clinical staging, survival, and coagulation parameters by using Coxproportional hazard model; and provide a parameter for clinical management and prognosis. Coagulation parameters were evaluated in 228 patients with primary liver cancer, 52 patients with common liver disease, and 52 normal healthy controls. The relationship between primary livercancer staging and coagulation parameters wasanalyzed. Follow-up examinations were performed. The Cox proportional hazard model was used to analyze the relationship between coagulationparameters and survival. The changes in the coagulation parameters in patients with primary liver cancer were significantly different from those in normal controls. The effect of the disease on coagulation function became more obvious as the severity of liver cancer increased (p<0.05). The levels of D-dimer, fibrinogen degradation products (FDP), fibrinogen (FIB), and platelets (PLT) were negatively correlated with the long-term survival of patients with advanced liver cancer. The stages of primary liver cancer are associated with coagulation parameters. Coagulation parameters are related to survival and risk factors. Monitoring of coagulation parameters may help ensure better surveillance and treatment for liver cancer patients.

  17. International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007.

    PubMed

    Petrick, Jessica L; Braunlin, Megan; Laversanne, Mathieu; Valery, Patricia C; Bray, Freddie; McGlynn, Katherine A

    2016-10-01

    Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence. © 2016 UICC.

  18. Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer.

    PubMed

    Samson, Adel; Bentham, Matthew J; Scott, Karen; Nuovo, Gerard; Bloy, Abigail; Appleton, Elizabeth; Adair, Robert A; Dave, Rajiv; Peckham-Cooper, Adam; Toogood, Giles; Nagamori, Seishi; Coffey, Matthew; Vile, Richard; Harrington, Kevin; Selby, Peter; Errington-Mais, Fiona; Melcher, Alan; Griffin, Stephen

    2018-03-01

    Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein-Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue. We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Shuangbai San for Treating Primary Liver Cancer Patients With Cancer Pain.

    PubMed

    Ye, Xiaowei; Lu, Dongyan; Chen, Xinlin; Li, Suihui; Chen, Yao; Deng, Li

    2016-06-01

    Shuangbai San is a Chinese herb preparation used externally to treat pain. There have been few randomized controlled trials addressing the safety and usefulness of Shuangbai San, such as its effect on pain relief and quality of life (QOL) improvement. This study was conducted to evaluate the effect of Shuangbai San on relieving pain and improving QOL in primary liver cancer patients with cancer pain. A total of 134 primary liver cancer patients with mild pain (numerical rating scale [NRS] ≤ 3), either locally in the liver or in the upper abdomen, were enrolled and randomly allocated to the group receiving Shuangbai San or the control group (receiving placebo). The primary outcome measures were the NRS score and QOL scales, including the QOL scale for patients with liver cancer, version 2.0 and the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30. The secondary outcome measures included the Karnofsky Performance Status score, blood indicators, and liver and kidney function before and after treatment. The NRS scores decreased more significantly in the Shuangbai San group than in the placebo group (P < 0.05) at the corresponding time points. The changes in the scores for the physical function, psychological function, and symptoms/adverse effects domains of the QOL scale for patients with liver cancer, version 2.0 and the physical, emotional, and cognitive domains of the European Organization for Research and Treatment of Cancer QOL Questionnaire-C30 were significantly greater in the Shuangbai San group than in the placebo group (P < 0.05). The changes in the scores for the other domains were not significantly different (P > 0.05). The use of Shuangbai San can relieve mild pain in liver cancer patients and improve their QOL. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  20. General Information about Liver (Hepatocellular) Cancer

    MedlinePlus

    ... condition or to keep cancer from starting. General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer ... PDQ Screening and Prevention Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  1. Herbal Medicine Practices of Patients With Liver Cancer in Peru: A Comprehensive Study Toward Integrative Cancer Management

    PubMed Central

    Rojas Rojas, Teresa; Bourdy, Geneviève; Ruiz, Eloy; Cerapio, Juan-Pablo; Pineau, Pascal; Gardon, Jacques; Doimi, Franco; Deparis, Xavier; Deharo, Eric; Bertani, Stéphane

    2016-01-01

    Rationale: The highest burden of liver cancer occurs in developing countries, where the use of herbal medicine (HM) is still widespread. Despite this trend, few studies have been conducted to report HM practices of patients with a hepatic tumor in the developing world. Hence, this study aimed to document the use of HM among patients with liver cancer in Peru. Study Design and Methods: A comparative behavioral epidemiological survey was conducted among liver cancer patients attending the National Cancer Institute of Peru. Information was obtained by direct interviews based on a semistructured questionnaire. The use of HM in Peruvian liver cancer patients was reported, first, regarding general consumption prior to the onset of disease, and second, after the appearance of symptoms that patients would relate to their tumor. In parallel, general consumption of HM in noncancerous people was assessed as a comparative figure. A correspondence analysis was performed to reveal potential associations between the symptoms of cancer and the specific use of HM. Results: Eighty-eight patients and 117 noncancerous individuals participated in the survey. Overall, 68.3% of the people interviewed claimed to use HM on a regular basis for general health preservation. Furthermore, 56.8% of the patients turned to plants first to treat the disorders for which they later came to the cancer care center. When compared with the number of plant species used routinely (n = 78), a selection of plants was made by patients in response to the symptoms of cancer (n = 46). At least 2 plant species, Aloe vera and Morinda citrifolia, were significantly associated with the treatment of liver cancer–related symptoms in the patient group. Conclusions: The present study is the first survey on the HM practices of patients with liver cancer in Latin America and, more broadly, in the developing world. Our findings confirm that HM remains one of the principal primary health care resources in Peru, even for a

  2. The prognostic value of functional and anatomical parameters for the selection of patients receiving yttrium-90 microspheres for the treatment of liver cancer

    NASA Astrophysics Data System (ADS)

    Mesoloras, Geraldine

    Yttrium-90 (90Y) microsphere therapy is being utilized as a treatment option for patients with primary and metastatic liver cancer due to its ability to target tumors within the liver. The success of this treatment is dependent on many factors, including the extent and type of disease and the nature of prior treatments received. Metabolic activity, as determined by PET imaging, may correlate with the number of viable cancer cells and reflect changes in viable cancer cell volume. However, contouring of PET images by hand is labor intensive and introduces an element of irreproducibility into the determination of functional target/tumor volume (FTV). A computer-assisted method to aid in the automatic contouring of FTV has the potential to substantially improve treatment individualization and outcome assessment. Commercial software to determine FTV in FDG-avid primary and metastatic liver tumors has been evaluated and optimized. Volumes determined using the automated technique were compared to those from manually drawn contours identified using the same cutoff in the standard uptake value (SUV). The reproducibility of FTV is improved through the introduction of an optimal threshold value determined from phantom experiments. Application of the optimal threshold value from the phantom experiments to patient scans was in good agreement with hand-drawn determinations of the FTV. It is concluded that computer-assisted contouring of the FTV for primary and metastatic liver tumors improves reproducibility and increases accuracy, especially when combined with the selection of an optimal SUV threshold determined from phantom experiments. A method to link the pre-treatment assessment of functional (PET based) and anatomical (CT based) parameters to post-treatment survival and time to progression was evaluated in 22 patients with colorectal cancer liver metastases treated using 90Y microspheres and chemotherapy. The values for pre-treatment parameters that were the best

  3. Liver metastases from colorectal cancer: regional intra-arterial treatment following failure of systemic chemotherapy

    PubMed Central

    Cyjon, A; Neuman-Levin, M; Rakowsky, E; Greif, F; Belinky, A; Atar, E; Hardoff, R; Brenner, B; Sulkes, A

    2001-01-01

    This study was designed to determine response rate, survival and toxicity associated with combination chemotherapy delivered intra-arterially to liver in patients with hepatic metastases of colorectal origin refractory to standard systemic treatment. A total of 28 patients who failed prior systemic treatment with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment consisting of 5-fluorouracil 700 mg/m2/d, leucovorin 120 mg/m2/d, and cisplatin 20 mg/m2/d for 5 consecutive days. Cycles were repeated at intervals of 5–6 weeks. A major response was achieved in 48% of patients: complete response in 8% and partial response in 40%. The median duration of response was 11.5 months. Median survival was 12 months at a median follow up of 12 months. On multivariate analysis, the only variables with a significant impact on survival were response to treatment and performance status. Toxicity was moderate: grades III–IV neutropenia occurred in 29% of patients. Most of the patients complained of fatigue lasting for a few days following each cycle. There were no cases of hepatobiliary toxicity. These findings indicate that regional intra-arterial treatment should be considered in selected patients with predominantly liver disease following failure of standard treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11506487

  4. Effects of tocotrienols on cell viability and apoptosis in normal murine liver cells (BNL CL.2) and liver cancer cells (BNL 1ME A.7R.1), in vitro.

    PubMed

    Har, Chan Hooi; Keong, Chan Kok

    2005-01-01

    The effects of tocotrienols on murine liver cell viability and their apoptotic events were studied over a dose range of 0-32 microg mL(-1). Normal murine liver cells (BNL CL.2) and murine liver cancer cells (BNL 1ME A.7R.1) were treated with tocotrienols (T(3)), alpha tocopherol (alpha-T) and the chemo drug, Doxorubicin (Doxo, as a positive control). Cell viability assay showed that T(3) significantly (P < or = 0.05) lowered the percentage of BNL 1ME A.7R.1 cell viability in a dose-responsive manner (8-16 microg mL(-1)), whereas T did not show any significant (P>0.05) inhibition in cell viability with increasing treatment doses of 0-16 microg mL(-1). The IC(50) for tocotrienols were 9.8, 8.9, 8.1, 9.7, 8.1 and 9.3 microg mL(-1) at 12, 24, 36, 48, 60 and 72 hours respectively. Early apoptosis was detected 6 hours following T(3) treatment of BNL 1ME A.7R.1 liver cancer cells, using Annexin V-FITC fluorescence microscopy assay for apoptosis, but none were observed for the non-treated liver cancer cells at the average IC(50) of 8.98 microg mL(-1) tocotrienols for liver cancer cells. Several apoptotic bodies were detected in BNL 1ME A.7R.1 liver cancer cells at 6 hours post-treatment with tocotrienols (8.98 microg mL(-1)) using Acridine Orange/Propidium Iodide fluorescence assay. However, only a couple of apoptotic bodies were seen in the non-treated liver cancer cells and the BNL CL.2 normal liver cells. Some mitotic bodies were also observed in the T(3)-treated BNL 1ME A.7R.1 liver cancer cells but were not seen in the untreated BNL 1ME A.7R.1 cells and the BNL CL.2 liver cells. Following T(3)-treatment (8.98 microg mL(-1)) of the BNL 1ME A.7R.1 liver cancer cells, 24.62%, 25.53% and 44.90% of the cells showed elevated active caspase 3 activity at 9, 12 and 24 hours treatment period, respectively. DNA laddering studies indicated DNA fragmentation occurred in the T(3)-treated liver cancer cells, BNL 1ME A.7R.1 but not in non-treated liver cancer cells and the T(3

  5. Know HBV: What Every Asian and Pacific Islander Should Know About Hepatitis B and Liver Cancer

    MedlinePlus

    ... liver cancer that it is called “the first anti-cancer vaccine” by the World Health Organization. Asian Liver ... be excluded from work, school, or other daily activities. If you are starting any cancer chemotherapy, you should be on HBV treatment to ...

  6. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  7. Liquid biopsy in liver cancer.

    PubMed

    Labgaa, Ismail; Villanueva, Augusto

    2015-04-01

    Liver cancer has become the second cause of cancer-related death worldwide. Most patients are still diagnosed at intermediate or advanced stage, where potentially curative treatment options are not recommended. Unlike other solid tumors, there are no validated oncogenic addiction loops and the only systemic agent to improve survival in advanced disease is sorafenib. All phase 3 clinical trials testing molecular therapies after sorafenib have been negative, none of which selected patients based on predictive biomarkers of response. Theoretically, analysis of circulating cancer byproducts (e.g., circulating tumor cells, cell-free nucleic acids), namely "liquid biopsy," could provide easy access to molecular tumor information, improve patients' stratification and allow to assess tumor dynamics over time. Recent technical developments and preliminary data from other malignancies indicate that liquid biopsy might have a role in the future management of cancer patients.

  8. Transient receptor potential vanilloid-type 2 targeting on stemness in liver cancer.

    PubMed

    Hu, Zecheng; Cao, Xiaocheng; Fang, Yu; Liu, Guoxing; Xie, Chengzhi; Qian, Ke; Lei, Xiaohua; Cao, Zhenyu; Du, Huihui; Cheng, Xiangding; Xu, Xundi

    2018-06-12

    The malignant phenotype of the cells resulting from human liver cancer is driven by liver cancer stem-like cells (LCSLCs). Transient Receptor Potential Vanilloid-type 2 channel (TRPV2) contributes to the progression of different tumor types, including liver cancer. In the current study, the TRPV2 expression levels give rise to the effect on stemness in liver cancer cell lines. TRPV2 knockdown in HepG2 cells enhanced spheroid and colony formation, and expression levels of CD133, CD44 and ALDH1 whereas the opposite effects were observed in TRPV2 enforced expression in SMMC-7721 cells. Furthermore, TRPV2 overexpression restored inhibition of spheroid and colony formation, and stem cell markers expression in HepG2 cells with TRPV2 silencing. The addition of the TRPV2 agonist probenecid and the TRPV2 antagonist tranilast suppressed and/or increased in vitro spheroid and colony formation, and stem cell marker expression of LCSLCs and/or liver cancer cell lines, respectively. Notably, probenecid and tranilast significantly inhibited or promoted tumor growth of HepG2 xenografts in the severe combined immunodeficiency (SCID) mouse model, respectively. TRPV2 expression at protein levels revealed converse correlation with those of CD133 and CD44 in human hepatocellular carcinoma (HCC) tissue. Collectively, the data demonstrate that TRPV2 exert effects on stemness of liver cancer and is a potential target in the treatment of human liver cancer patients. Copyright © 2018. Published by Elsevier Masson SAS.

  9. Association of nonalcoholic fatty liver disease and liver cancer

    PubMed Central

    Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

    2015-01-01

    AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

  10. Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival

    PubMed Central

    Sawai, Hirozumi; Yasuda, Akira; Ochi, Nobuo; Ma, Jiachi; Matsuo, Yoichi; Wakasugi, Takehiro; Takahashi, Hiroki; Funahashi, Hitoshi; Sato, Mikinori; Takeyama, Hiromitsu

    2008-01-01

    Background The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases. Methods Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls. Results PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012). Conclusion Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients. PMID:19036165

  11. iRGD-conjugated DSPE-PEG2000 nanomicelles for targeted delivery of salinomycin for treatment of both liver cancer cells and cancer stem cells.

    PubMed

    Mao, Xiaoli; Liu, Junjie; Gong, Zhirong; Zhang, He; Lu, Ying; Zou, Hao; Yu, Yuan; Chen, Yan; Sun, Zhiguo; Li, Wei; Li, Bohua; Gao, Jie; Zhong, Yanqiang

    2015-01-01

    To develop novel iRGD (internalizing Arg-Gly-Asp peptide)-conjugated DSPE-PEG2000 nanomicelles (M-SAL-iRGD) for delivery of salinomycin to both liver cancer cells and cancer stem cells (CSCs). The characterization, antitumor activity and mechanism of action of M-SAL-iRGD were evaluated. M-SAL-iRGD possessed a small size of around 10 nm, and drug encapsulation efficacy higher than 90%. M-SAL-iRGD showed significantly increased cytotoxic effect toward both nontargeted M-SAL (salinomycin-loaded DSPE-PEG2000 nanomicelles) and salinomycin in both liver cancer cells and CSCs. The tissue distribution and antitumor assays in mice bearing liver cancer xenograft confirmed the superior penetration tumor efficacy and antitumor activity of M-SAL-iRGD. M-SAL-iRGD represent a potential effective nanomedicine against liver cancer.

  12. Liver (Hepatocellular) Cancer Prevention (PDQ®)—Patient Version

    Cancer.gov

    Liver cancer risk factors include hepatitis B and C, cirrhosis, and aflatoxin (poison from certain foods). Learn about these and other risk factors for liver cancer and how to prevent liver cancer in this expert-reviewed and evidence-based summary.

  13. Prostate Cancer in Deceased Liver Donors.

    PubMed

    Skalski, M; Gierej, B; Ziarkiewicz-Wróblewska, B; Hołówko, W; Krawczyk, M

    2016-06-01

    Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P = .578) or age (P = .730) was not statistically significant. Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Behavior of HepG2 liver cancer cells using microfluidic-microscopy: a preliminary study

    NASA Astrophysics Data System (ADS)

    Karamahmutoglu, Hande; ćetin, Metin; Yaǧcı, Tamer; Elitaş, Meltem

    2018-02-01

    Hepatocellular carcinoma is one of the most common types of liver cancer causing death all over the world. Although early-stage liver cancer can sometimes be treated with partial hepatectomy, liver transplantation, ablation, and embolization, sorafenib treatment is the only approved systemic therapy for advanced HCC. The aim of this research is to develop tools and methods to understand the individuality of hepatocellular carcinoma. Microfluidic cell-culture platform has been developed to observe behavior of single-cells; fluorescence microscopy has been implemented to investigate phenotypic changes of cells. Our preliminary data proved high-level heterogeneity of hepatocellular carcinoma while verifying limited growth of liver cancer cell lines on the silicon wafer.

  15. Temporal trends in population-based death rates associated with chronic liver disease and liver cancer in the United States over the last 30 years.

    PubMed

    Kim, Yuhree; Ejaz, Aslam; Tayal, Amit; Spolverato, Gaya; Bridges, John F P; Anders, Robert A; Pawlik, Timothy M

    2014-10-01

    The health and economic burden from liver disease in the United States is substantial and rising. The objective of this study was to characterize temporal trends in mortality from chronic liver disease and liver cancer and the incidence of associated risk factors using population-based data over the past 30 years. Population-based mortality data were obtained from the National Vital Statistics System, and population estimates were derived from the national census for US adults (aged >45 years). Crude death rates (CDRs), age-adjusted death rates (ADRs), and average annual percentage change (AAPC) statistics were calculated. In total, 690,414 deaths (1.1%) were attributable to chronic liver disease, whereas 331,393 deaths (0.5%) were attributable to liver cancer between 1981 and 2010. The incidence of liver cancer was estimated at 7.1 cases per 100,000 population. Mortality rates from chronic liver disease and liver cancer increased substantially over the past 3 decades, with ADRs of 23.7 and 16.6 per 100,000 population in 2010, respectively. The AAPC from 2006 to 2010 demonstrated an increased ADR for chronic liver disease (AAPC, 1.5%; 95% confidence interval, 0.3%-2.8%) and liver cancer (AAPC, 2.6%; 95% confidence interval, 2.4%-2.7%). A comprehensive approach that involves primary and secondary prevention, increased access to treatment, and more funding for liver-related research is needed to address the high death rates associated with chronic liver disease and liver cancer in the United States. © 2014 American Cancer Society.

  16. Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease.

    PubMed

    Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

    Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. BMS-247550 in Treating Patients With Liver or Gallbladder Cancer

    ClinicalTrials.gov

    2014-05-13

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  18. Silibinin administration improves hepatic failure due to extensive liver infiltration in a breast cancer patient.

    PubMed

    Bosch-Barrera, Joaquim; Corominas-Faja, Bruna; Cuyàs, Elisabet; Martin-Castillo, Begoña; Brunet, Joan; Menendez, Javier A

    2014-08-01

    Silibinin exerts hepatoprotective, anti-inflammatory and anti-fibrotic effects. Several pre-clinical studies have shown anti-tumoral activity of silibinin in breast cancer cell lines. We present the case of a heavily pre-treated breast cancer patient with extensive liver infiltration. The patient presented with progressive liver failure despite several chemotherapy treatments, including paclitaxel, capecitabine and vinorelbine. After four cycles of a fourth-line chemotherapy treatment consisting of carboplatin and gemcitabine, the patient's liver blood test results deteriorated to life-threatening levels. The compassionate use of Legasil®, a new commercially available nutraceutical product containing a new silibinin formulation, was offered to the patient according to article 37 of the 2013 Declaration of Helsinki. After treatment initiation, the patient presented clinical and liver improvement, which permitted the patient to continue palliative chemotherapy. This is the first case report of a clinical benefit of silibinin administration in a breast cancer patient. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Ultrasound-guided interventional PDT of liver cancer

    NASA Astrophysics Data System (ADS)

    Zeng, Chaoying; Yang, Dong; Huang, Ping; Zhang, Huijuan; Huang, Muyin; Chen, Ji; Lu, Guorong

    1996-09-01

    Thirty patients with advanced liver cancer were treated by interstitial photodynamic therapy (PDT). These included 28 hepatocellular carcinoma and two adenocarcinoma, 19 primary tumors and 11 recurred follow other treatments. The diameter of tumors were 7-10cm in 13 cases and 10-16cm in 17 cases. In this study, an argon laser pumped dye laser system was used to give a CW laser beam at 630 nm which was split and coupled into there optical fibers. The patients were injected intravenously with photosensitizer hematoporphyrin derivative at a dose of 5mg/kg body weight 48 hours before PDT. Then the fibers were inserted into tumor by ultrasound- guided percutaneous puncture. The inserted irradiation points were spaced in entire tumor with the light release power 300mW and the irradiation time 12 minutes per point. Total 52 treatments were performed in 30 patients. Among them, 14 cases were treated only one time and 16 cases via 2-3 times. The follow-up was carried out in 25 cases for 12- 24 months. The results show that significant remission was 22 percent in those patients by only one treatment and 62 percent in those via 2 to 3 treatments. The shrink rate of tumor size was over 90 percent in five of six cases after treatment 3. The survival time has been over one year in 12 cases. No obvious change to be found for all patients in liver function test, renal function test and blood routine examination. The level of AFP indicated a descending trend after PDT. This work indicate that PDT is effective and safe for the treatment of large liver cancers including those recurred follow hepatic resection and those failed in hepatic artery infusion embolic chemotherapy.

  20. Bile Duct Cancer (Cholangiocarcinoma) Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Bile duct cancer (also called cholangiocarcinoma) can occur in the bile ducts in the liver (intrahepatic) or outside the liver (perihilar or distal extrahepatic). Learn about the types of bile duct cancer, risk factors, clinical features, staging, and treatment for bile duct cancer in this expert-reviewed summary.

  1. Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer.

    PubMed

    Jeon, Min Jeong; Gordon, Andrew C; Larson, Andrew C; Chung, Jin Wook; Kim, Young Il; Kim, Dong-Hyun

    2016-05-01

    A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Cetuximab as treatment for head and neck cancer patients with a previous liver transplant: report of two cases.

    PubMed

    Holguin, Francia; Rubió-Casadevall, Jordi; Saigi, Maria; Marruecos, Jordi; Taberna, Miren; Tobed, Marc; Maños, Manuel; Mesía, Ricard

    2017-10-01

    Cetuximab is a monoclonal antibody against epidermal growth factor receptor useful in the treatment of patients with Head and Neck Squamous Cell Carcinoma combined with radiotherapy or chemotherapy. Its pharmacokinetics are not influenced by hepatic status and there are no specific warnings concerning its indication in patients with impaired hepatic function. Patients with a previous liver transplant are at risk for hepatic toxicity and use immunosupressants to avoid rejection that can interact with other drugs. We present two cases of patients with a previous liver transplant in which cetuximab was administered to treat head and neck cancer.

  3. Histone Deacetylase Inhibitors Facilitate Dihydroartemisinin-Induced Apoptosis in Liver Cancer In Vitro and In Vivo

    PubMed Central

    Zhang, Chris Zhiyi; Pan, Yinghua; Cao, Yun; Lai, Paul B. S.; Liu, Lili; Chen, George Gong; Yun, Jingping

    2012-01-01

    Liver cancer ranks in prevalence and mortality among top five cancers worldwide. Accumulating interests have been focused in developing new strategies for liver cancer treatment. We have previously showed that dihydroartemisinin (DHA) exhibited antitumor activity towards liver cancer. In this study, we demonstrated that histone deacetylase inhibitors (HDACi) significantly augmented the antineoplastic effect of DHA via increasing apoptosis in vitro and in vivo. Inhibition of ERK phosphorylation contributed to DHA-induced apoptosis, due to the fact that inhibitor of ERK phosphorylation (PD98059) increased DHA-induced apoptosis. Compared with DHA alone, the combined treatment with DHA and HDACi reduced mitochondria membrane potential, released cytochrome c into cytoplasm, increased p53 and Bak, decreased Mcl-1 and p-ERK, activated caspase 3 and PARP, and induced apoptotic cells. Furthermore, we showed that HDACi pretreatment facilitated DHA-induced apoptosis. In Hep G2-xenograft carrying nude mice, the intraperitoneal injection of DHA and SAHA resulted in significant inhibition of xenograft tumors. Results of TUNEL and H&E staining showed more apoptosis induced by combined treatment. Immunohistochemistry data revealed the activation of PARP, and the decrease of Ki-67, p-ERK and Mcl-1. Taken together, our data suggest that the combination of HDACi and DHA offers an antitumor effect on liver cancer, and this combination treatment should be considered as a promising strategy for chemotherapy. PMID:22761917

  4. Changes in the renin angiotensin system during the development of colorectal cancer liver metastases.

    PubMed

    Neo, Jaclyn H; Ager, Eleanor I; Angus, Peter W; Zhu, Jin; Herath, Chandana B; Christophi, Christopher

    2010-04-10

    Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade.

  5. The Impact of Liver Graft Injury on Cancer Recurrence Posttransplantation.

    PubMed

    Li, Chang-Xian; Man, Kwan; Lo, Chung-Mau

    2017-11-01

    Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma. However, cancer recurrence, posttransplantation, remains to be the critical issue that affects the long-term outcome of hepatocellular carcinoma recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute-phase liver graft injury is a result of hepatic ischemia reperfusion injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death, and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute-phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating the tumor cell invasion and migration but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic ischemia reperfusion injury on tumor recurrence posttransplantation, both in clinical and animal cohorts.

  6. Hepatic stellate cells in liver development, regeneration, and cancer

    PubMed Central

    Yin, Chunyue; Evason, Kimberley J.; Asahina, Kinji; Stainier, Didier Y.R.

    2013-01-01

    Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases. PMID:23635788

  7. Donor transmitted and de novo cancer after liver transplantation

    PubMed Central

    Desai, Rajeev; Neuberger, James

    2014-01-01

    Cancers in solid organ recipients may be classified as donor transmitted, donor derived, de novo or recurrent. The risk of donor-transmitted cancer is very low and can be reduced by careful screening of the donor but cannot be abolished and, in the United Kingdom series is less than 0.03%. For donors with a known history of cancer, the risks will depend on the nature of the cancer, the interventions given and the interval between diagnosis and organ donation. The risks of cancer transmission must be balanced against the risks of death awaiting a new graft and strict adherence to current guidelines may result increased patient death. Organs from selected patients, even with high-grade central nervous system (CNS) malignancy and after a shunt, can, in some circumstances, be considered. Of potential donors with non-CNS cancers, whether organs may be safely used again depends on the nature of the cancer, the treatment and interval. Data are scarce about the most appropriate treatment when donor transmitted cancer is diagnosed: sometimes substitution of agents and reduction of the immunosuppressive load may be adequate and the impact of graft removal should be considered but not always indicated. Liver allograft recipients are at increased risk of some de novo cancers, especially those grafted for alcohol-related liver disease and hepatitis C virus infection. The risk of lymphoproliferative disease and cancers of the skin, upper airway and bowel are increased but not breast. Recipients should be advised to avoid risk behavior and monitored appropriately. PMID:24876738

  8. Drugs Approved for Liver Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  9. High cytidine deaminase expression in the liver provides sanctuary for cancer cells from decitabine treatment effects.

    PubMed

    Ebrahem, Quteba; Mahfouz, Reda Z; Ng, Kwok Peng; Saunthararajah, Yogen

    2012-10-01

    We document for the first time that sanctuary in an organ which expresses high levels of the enzyme cytidine deaminase (CDA) is a mechanism of cancer cell resistance to cytidine analogues. This mechanism could explain why historically, cytidine analogues have not been successful chemotherapeutics against hepatotropic cancers, despite efficacy in vitro. Importantly, this mechanism of resistance can be readily reversed, without increasing toxicity to sensitive organs, by combining a cytidine analogue with an inhibitor of cytidine deaminase (tetrahydrouridine). Specifically, CDA rapidly metabolizes cytidine analogues into inactive uridine counterparts. Hence, to determine if sheltering/protection of cancer cells in organs which express high levels of CDA (e.g., liver) is a mechanism of resistance, we utilized a murine xenotransplant model of myeloid cancer that is sensitive to epigenetic therapeutic effects of the cytidine analogue decitabine in vitro and hepato-tropic in vivo. Treatment of tumor-bearing mice with decitabine (subcutaneous 0.2mg/kg 2X/week) doubled median survival and significantly decreased extra-hepatic tumor burden, but hepatic tumor burden remained substantial, to which the animals eventually succumbed. Combining a clinically-relevant inhibitor of CDA (tetrahydrouridine) with a lower dose of decitabine (subcutaneous 0.1mg/kg 2X/week) markedly decreased liver tumor burden without blood count or bone marrow evidence of myelotoxicity, and with further improvement in survival. In conclusion, sanctuary in a CDA-rich organ is a mechanism by which otherwise susceptible cancer cells can resist the effects of decitabine epigenetic therapy. This protection can be reversed without increasing myelotoxicity by combining tetrahydrouridine with a lower dose of decitabine.

  10. [Analysis of liver cancer incidence and trend in China].

    PubMed

    Zuo, Tingting; Zheng, Rongshou; Zeng, Hongmei; Zhang, Siwei; Chen, Wanqing

    2015-09-01

    The national population-based cancer registration data were used to analyze the liver cancer incidence and trend in China, in order to provide advise for making further strategy on liver cancer prevention and control. Liver cancer data of 2011 were retrieved from the database of the National Cancer Registry. The incident cases of liver cancer were estimated using age-specific rate by urban or rural areas and gender according to the national population in 2011. Liver cancer incidence data from 22 cancer registries were used to analyze the incidence trend during 2000-2011. The estimates of new cases of liver cancer were about 356 thousand in China in 2011. The incidence rate was 26.39/10(5,) and the age-standardized incidence rates by Chinese standard population and by world population were 19.48/10(5) and 19.10/10(5,) respectively.There was an increasing trend of incidence rate of liver cancer in China during 2000-2011 with an average annual percentage change(AAPC) of 1.0% (95%CI: 0.5%-1.4%), 1.2% (95%CI: 0.7%-1.8%)in urban areas and 1.1% (95%CI: 0.5%-1.8%) in rural areas. After age standardization, the incidence rate was significantly decreased, with an AAPC of -1.8% (95%CI: -2.4% to -1.2%), -1.6% (95%CI: -2.2% to -0.9%) in urban and -1.4% (95%CI: -2.5% to -0.3%) in rural areas. Liver cancer is a common cancer in China. As changing in people's dietary habits and implementing neonatal HBV vaccination for years, the exposure to risk factors is reducing, and age-standardized incidence rate is decreasing. While cardinal number of population is big and aging population is growing rapidly in the country, trend of incidence rate is increasing, and the burden of liver cancer is still high in China.

  11. APSA Awardee Submission: Tumor/cancer stem cell marker doublecortin-like kinase 1 in liver diseases.

    PubMed

    Nguyen, Charles B; Houchen, Courtney W; Ali, Naushad

    2017-02-01

    Liver diseases are the fourth leading cause of mortality among adults in the United States. Patients with chronic liver diseases such as viral hepatitis, fibrosis, and cirrhosis have significantly higher risks of developing hepatocellular carcinoma (HCC). With a dismal five-year survival rate of 11%, HCC is the third most common cause of cancer-related deaths worldwide. Regardless of the underlying cause, late presentation and a lack of effective therapy are the major impediments for successful treatment of HCC. Therefore, there is a considerable interest in developing new strategies for the prevention and treatment of chronic liver diseases at the early stages. Cancer stem cells (CSCs), a small cell subpopulation in a tumor, exhibit unlimited self-renewal and differentiation capacity. These cells are believed to play pivotal roles in the initiation, growth, metastasis, and drug-resistance of tumors. In this review, we will briefly discuss pivotal roles of the CSC marker doublecortin-like kinase 1 (DCLK1) in hepatic tumorigenesis. Recent evidence suggests that anti-DCLK1 strategies hold promising clinical potential for the treatment of cancers of the liver, pancreas, and colon.

  12. [Two Cases of Laparoscopic Resection of Colon Cancer Manifested by Liver Abscess].

    PubMed

    Ohashi, Motonari; Iwama, Masahiro; Ikenaga, Shojirokazunori; Yokoyama, Makoto

    2017-11-01

    We report 2 cases of laparoscopic surgery for patients who had liver abscess as the initial manifestation of underlying colon cancer. The first case was in an 80-year-old woman who presented to our hospital with a diagnosis ofliver abscess. Percutaneous transhepatic abscess drainage(PTAD)was performed as initial treatment. Subsequent colonoscopy revealed a type 1 tumor in the cecum, and biopsy results ofthe mass indicated adenocarcinoma. The patient underwent laparoscopic right hemicolectomy as curative treatment. The pathological findings were as follows: tub1, T2, N0, M0 and Stage I . Two years later, she remains disease free. The second case was in a 59-year-old man with liver abscess. Colonoscopy also revealed a type 2 tumor in the sigmoid colon. After treatment of the liver abscess with PTAD, laparoscopic sigmoidectomy was performed with a preoperative diagnosis of sigmoid colon cancer. The pathological findings were as follows: tub2, T3, N0, M0 and Stage II . Lung metastases appeared 10 months after surgery, and systemic chemotherapy was administered. In conclusion, liver abscess is occasionally caused by malignancy, and complete gastrointestinal evaluation should be conducted. Laparoscopic radical surgery can be safely performed in cases in which the liver abscesses are controlled.

  13. Increasing burden of liver cancer despite extensive use of antiviral agents in a hepatitis B virus-endemic population.

    PubMed

    Choi, Jonggi; Han, Seungbong; Kim, Namkug; Lim, Young-Suk

    2017-11-01

    Most mortalities from liver disease and liver cancer worldwide are attributable to hepatitis B virus (HBV) and hepatitis C virus. Despite remarkable advances in the treatment of HBV over past decades, limited population-level data are available regarding its impact on burden of liver disease and liver cancer. Mortality data from liver disease and liver cancer were obtained from the national death certificate database of Korea, an HBV-endemic country, between 1999 and 2013, and were analyzed by Joinpoint analysis. For liver disease, number of annual deaths decreased by 62.3% (95% confidence interval [CI], 62.0-62.6), crude death rate (CDR) decreased by 64.6% (95% CI, 64.3-64.9) from 21.2 to 7.5 per 100,000 population, and age-standardized death rate (ADR) declined by 75.0% (95% CI, 74.7-75.3), between 1999 and 2013. In contrast, for liver cancer, number of annual deaths increased by 17.8% (95% CI, 17.6-18.0) and CDR increased by 10.2% (95% CI, 10.0-10.4) from 20.5 to 22.6, although ADR decreased by 26.9% (95% CI, 26.6-27.2). The annual number of patients receiving oral antiviral agents against HBV increased from 1,716 to 187,226 during the study period. The increase in mean age at death from liver disease was significantly greater than that from liver cancer (8.8 vs. 6.1 years: P = 0.02). Marked reduction in liver disease mortality by widespread use of antiviral treatments against HBV may increase the life expectancy and number of patients at risk of developing liver cancer, inadvertently leading to increased burden of liver cancer in an HBV-endemic population. The competing nature between death from liver disease and that from liver cancer should be carefully considered in establishing a health care policy. (Hepatology 2017;66:1454-1463). © 2017 by the American Association for the Study of Liver Diseases.

  14. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

    PubMed

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

    2016-07-01

    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  15. Automatic liver contouring for radiotherapy treatment planning

    NASA Astrophysics Data System (ADS)

    Li, Dengwang; Liu, Li; Kapp, Daniel S.; Xing, Lei

    2015-09-01

    To develop automatic and efficient liver contouring software for planning 3D-CT and four-dimensional computed tomography (4D-CT) for application in clinical radiation therapy treatment planning systems. The algorithm comprises three steps for overcoming the challenge of similar intensities between the liver region and its surrounding tissues. First, the total variation model with the L1 norm (TV-L1), which has the characteristic of multi-scale decomposition and an edge-preserving property, is used for removing the surrounding muscles and tissues. Second, an improved level set model that contains both global and local energy functions is utilized to extract liver contour information sequentially. In the global energy function, the local correlation coefficient (LCC) is constructed based on the gray level co-occurrence matrix both of the initial liver region and the background region. The LCC can calculate the correlation of a pixel with the foreground and background regions, respectively. The LCC is combined with intensity distribution models to classify pixels during the evolutionary process of the level set based method. The obtained liver contour is used as the candidate liver region for the following step. In the third step, voxel-based texture characterization is employed for refining the liver region and obtaining the final liver contours. The proposed method was validated based on the planning CT images of a group of 25 patients undergoing radiation therapy treatment planning. These included ten lung cancer patients with normal appearing livers and ten patients with hepatocellular carcinoma or liver metastases. The method was also tested on abdominal 4D-CT images of a group of five patients with hepatocellular carcinoma or liver metastases. The false positive volume percentage, the false negative volume percentage, and the dice similarity coefficient between liver contours obtained by a developed algorithm and a current standard delineated by the expert group

  16. [Mortality and survival analysis of liver cancer in China].

    PubMed

    Zheng, Rongshou; Zuo, Tingting; Zeng, Hongmei; Zhang, Siwei; Chen, Wanqing

    2015-09-01

    Based on the cancer registry data to analyze the mortality and survival of liver cancer in China. Liver cancer data of 2011 were retrieved from the National Cancer Registry Database.Liver cancer deaths were estimated using age-specific rate by areas and gender according to the national population in 2011. Mortality data from 22 cancer registries during 2000-2011 were used to analyze the mortality trend, and data from 17 cancer registries during 2003-2005 were used for survival analysis. The estimates of liver cancer deaths were about 322 thousand in 2011 with a crude mortality rate of 23.93/10(5).There was an increasing trend of crude mortality rate of liver cancer during 2000-2011 in 22 Chinese cancer registries with an average annual percentage change of 0.7% (95%CI: 0.2%-1.2%), 1.1% in urban and 0.4% in rural areas. After age standardization with Segi's population, the mortality rate was significantly decreased, with an APC of -2.3%, -1.9% in urban and -2.2% in rural populations. The 5-year age standardized relative survival was 10.1% (95%CI: 9.5% to 10.7%), and the 1-, 3- and the 5-year observed survival rates were 27.2%, 12.7%, and 8.9%, respectively. Liver cancer is a major cancer threatening people's lives and health in China, and the liver cancer burden is still high.

  17. Medical expenditure for liver cancer in urban China: A 10-year multicenter retrospective survey (2002-2011).

    PubMed

    Qiu, Wu-Qi; Shi, Ju-Fang; Guo, Lan-Wei; Mao, A-Yan; Huang, Hui-Yao; Hu, Guang-Yu; Dong, Pei; Bai, Fang-Zhou; Yan, Xiao-Ling; Liao, Xian-Zhen; Liu, Guo-Xiang; Bai, Ya-Na; Ren, Jian-Song; Sun, Xiao-Jie; Zhu, Xin-Yu; Zhou, Jin-Yi; Gong, Ji-Yong; Zhu, Lin; Mai, Ling; Du, Ling-Bing; Zhou, Qi; Xing, Xiao-Jing; Song, Bing-Bing; Liu, Yu-Qin; Lou, Pei-An; Sun, Xiao-Hua; Wu, Shou-Ling; Cao, Rong; Qi, Xiao; Lan, Li; Ren, Ying; Zhang, Kai; He, Jie; Qu, Chunfeng; Dai, Min

    2018-01-01

    This study aims to understand the medical expenditure for liver cancer during 2002-2011 in urban areas of China. This is a retrospective study. Based on a stratified cluster sampling method, a medical expenditure survey collected basic personal information from related medical records. Two-tailed independent sample t-test, variance analysis, and Student-Newman-Keuls Tests were used in cost analysis for the corresponding data types. A total of 12,342 liver cancer patients were included in the analysis. Overall average medical expenditure per case for liver cancer diagnosis and treatment in China has increased from ¥21, 950 to ¥40, 386 over the study period. For each liver cancer patient diagnosed between 2009 and 2011, the average expenditures were 29,332 CNY for stage I, 35,754 CNY for stage II, 34,288 CNY for stage III, and 30,275 CNY for stage IV diseases (P < 0.001). Pharmaceuticals accounted for the biggest part of the medical expenditure and it rose from 48.01% to 52.96% during these ten years, and the share of nursing fee expenses was the lowest (around 1%). Over the entire 10-year data period, the per capita expenditure of the east region (32,983 CNY) was higher than that of the west region (26,219 CNY) and slightly higher than the central region (31,018 CNY, P < 0.001). As a major cancer in China, liver cancer accounts for a large portion of health economic burden and its medical expenditure is heavy for families. Early diagnosis and treatment for liver cancer will save medical expenditure. The economic burden of liver cancer is high in China and related medical expenditure has increased.

  18. [Endoscopic radiofrequency ablation for liver metastasis of colorectal cancer].

    PubMed

    Takahashi, Masahiro; Nitta, Hiroyuki; Sasaki, Akira; Fujita, Tomohiro; Obuchi, Toru; Hoshikawa, Koichi; Otsuka, Koki; Kawamura, Hidenobu; Higuchi, Taro; Asahi, Hiroshi; Saito, Kazuyoshi

    2005-10-01

    The application of radiofrequency ablation (RFA) for liver metastasis of colorectal cancer has not yet acquired an established status in clinical cancer therapy research. Removing as much tumor tissue as possible is desirable, but some cases do not allow optimal surgical ablation due to general condition of the patient and tumor status. We introduced endoscopic RFA for liver cancer in 2003, and have applied the procedure to 6 cases with H1 or H2 liver metastases of colorectal cancer to which surgical ablation could not be applied due to the poor general health of patients. Mean tumor diameter was 22.9 mm, and mean number of tumors per patient was 1.2. Tumor location was: S4, n = 2; S5, n = 1; S4, n = 1; S7, n = 2; and S8, n = 1. Mean frequency of session was 3.0. No complications occurred in any cases, and no reoperations were required. Although no recurrence of tumors in the vicinity of ablation was observed, 2 cases of each lung metastasis and intrahepatic recurrence were identified. Intrahepatic recurrence underwent hepatic arterial infusion (HAI) chemotherapy for simultaneous metastatic hepatic tumors (H2) prior to RFA, and relapses occurred in the metastatic focus where the efficacy of HAI was observed. At this point, 2 deaths were reported, 1 each from cancer and other diseases, and mean duration of survival after the procedure was 451.2 days. These results indicate that endoscopic RFA with good local control should be an available treatment for cases involving colorectal cancer with metastasis to the liver in which surgical ablation is difficult to apply.

  19. Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

    PubMed Central

    Barbier-Torres, Lucía; Delgado, Teresa C.; García-Rodríguez, Juan L.; Zubiete-Franco, Imanol; Fernández-Ramos, David; Buqué, Xabier; Cano, Ainara; Juan, Virginia Gutiérrez-de; Fernández-Domínguez, Itziar; Lopitz-Otsoa, Fernando; Fernández-Tussy, Pablo; Boix, Loreto; Bruix, Jordi; Villa, Erica; Castro, Azucena; Lu, Shelly C.; Aspichueta, Patricia; Xirodimas, Dimitris; Varela-Rey, Marta; Mato, José M.; Beraza, Naiara; Martínez-Chantar, María L.

    2015-01-01

    The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma. PMID:25650664

  20. Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

    PubMed Central

    2010-01-01

    Background Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Methods Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Results Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. Conclusions These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade. PMID:20380732

  1. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

    PubMed Central

    Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki; Hosaka, Kayoko; Seki, Takahiro; Andersson, Patrik; Lim, Sharon; Fischer, Carina; Nakamura, Masaki; Abe, Mitsuhiko; Cao, Renhai; Skov, Peter Vilhelm; Chen, Fang; Chen, Xiaoyun; Lu, Yongtian; Nie, Guohui; Cao, Yihai

    2016-01-01

    The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the ‘off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers. PMID:27580750

  2. Postoperative liver volume was accurately predicted by a medical image three dimensional visualization system in hepatectomy for liver cancer.

    PubMed

    Cai, Wei; Fan, Yingfang; Hu, Haoyu; Xiang, Nan; Fang, Chihua; Jia, Fucang

    2017-06-01

    Liver cancer is the second most common cause of cancer death worldwide. The hepatectomy is the most effective and the only potentially curative treatment for patients with resectable neoplasm. Precisely preoperative assessment of remnant liver volume is essential in preventing postoperative liver failure. The aim of our study is to report our experience of using a medical image three dimensional (3D) visualization system (MI-3DVS), which was developed by our team, in assisting hepatectomy for patients with liver cancer. Between January 2010 and June 2016, 69 patients with liver cancer underwent hepatic resection based on the MI-3DVS were enrolled in this study. All patients underwent CT scan 5 days before the surgery and within 5 days after resection. CT images were reconstructed with the MI-3DVS to assist to perform hepatectomy. Simple linear regression, intra-class correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate the relationship and agreement between actual excisional liver volume (AELV) and predicted excisional liver volume (PELV). Among 69 patients in this study, 62(89.85%) of them were diagnosed with hepatocellular carcinoma by histopathologic examination, and 41(59.42%) underwent major hepatectomy. The average AELV was 330.13 cm 3 and the average PELV was 287.67 cm 3 . The simple regression equation is AELV = 1.016 × PELV+30.39(r = 0.966; p < 0.0003). PELV (ICC = 0.964) achieved an excellent agreement with AELV with statistical significance (p < 0.001). 65 of 69 dots are in the range of 95% confidence interval in Bland-Altman analyses. The MI-3DVS has advantages of simple usage and convenient hold. It is accurate in assessment of postoperative liver volume and improve safety in liver resection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Ulinastatin Reduces the Resistance of Liver Cancer Cells to Epirubicin by Inhibiting Autophagy

    PubMed Central

    Shao, Cheng Hao; Li, Gang; Liu, An An; Jing, Wei; Liu, Rui; Zhang, Yi-Jie; Zhou, Ying-Qi; Hu, Xian-Gui; Jin, Gang

    2015-01-01

    During chemotherapy, drug resistance caused by autophagy remains a major challenge to successful treatment of cancer patients. The purpose of this study is to show that ulinastatin (UTI), a trypsin inhibitor, could reduce the resistance of liver cancer cells to chemotherapeutic agent epirubicin (EPI). We achieved this conclusion by analyzing the effect of EPI alone or UTI plus EPI on SMMC-7721 and MHCC-LM3 liver cancer cells. We also generated an EPI-resistant liver cancer cell line (MHCC-LM3er cells), and found that UTI could sensitize the LM3er cells to EPI. Autophagy usually functions to protect cancer cells during chemotherapy. Our study showed that UTI inhibited the autophagy induced by EPI in liver cancer cells, which promoted apoptosis, and therefore, reduced the resistance of the cancer cells to EPI. Further studies showed that the UTI-mediated inhibition on autophagy was achieved by inhibiting transcriptional factor nuclear factor-κB (NF-κB) signaling pathway. To verify our results in vivo, we injected MHCC-LM3 liver cancer cells or EPI-resistant LM3er cells into mice, and found that EPI could only effectively inhibit the growth of tumor in MHCC-LM3 cell-injected mice, but not in LM3er cell-injected mice. However, when UTI was also administered, the growth of tumor was inhibited in the MHCC-LM3er cell-injected mice as well. Our results suggest that UTI may be used in combination with anti-cancer drugs, such as EPI, to improve the outcome of cancer therapy. PMID:25815885

  4. Liver (Hepatocellular) Cancer Screening (PDQ®)—Patient Version

    Cancer.gov

    Liver (hepatocellular) cancer screening is not currently recommended as a routine part of cancer screening. Not all screening tests are helpful, and many have risks. Learn more about liver cancer and the tests used to detect it in this expert-reviewed summary.

  5. Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

    PubMed

    Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

    2008-09-01

    Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

  6. Donor-transmitted, donor-derived, and de novo cancer after liver transplant.

    PubMed

    Chapman, Jeremy R; Lynch, Stephen V

    2014-03-01

    Cancer is the third most common cause of death (after cardiovascular disease and infection) for patients who have a functioning kidney allograft. Kidney and liver transplant recipients have similar cancer risks because of immunosuppression but different risks because of differences in primary diseases that cause renal and hepatic failure and the inherent behavior of cancers in the liver. There are 4 types of cancer that may develop in liver allograft recipients: (1) recurrent cancer, (2) donor-transmitted cancer, (3) donor-derived cancer, and (4) de novo cancer. Identification of potential donor cancer transmission may occur at postmortem examination of a deceased donor or when a probable donor-transmitted cancer is identified in another recipient. Donor-transmitted cancer after liver transplant is rare in Australia, the United Kingdom, and the United States. Aging of the donor pool may increase the risk of subclinical cancer in donors. Liver transplant recipients have a greater risk of de novo cancer than the general population, and risk factors for de novo cancer in liver transplant recipients include primary sclerosing cholangitis, alcoholic liver disease, smoking, and increased age. Liver transplant recipients may benefit from cancer screening because they have a high risk, are clearly identifiable, and are under continuous medical supervision.

  7. Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice.

    PubMed

    Huang, Chun; Li, Runqin; Zhang, Yinglin; Gong, Jianping

    2017-10-01

    Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer. The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin. The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53. The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.

  8. Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

    PubMed Central

    Li, Runqin; Zhang, Yinglin

    2016-01-01

    Background and Objective: Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer. Materials and Methods: The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin. Results: The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53. Conclusion: The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells. PMID:27402632

  9. Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy

    NASA Astrophysics Data System (ADS)

    Velec, Michael

    The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely

  10. Application of traditional Chinese medicine injection in treatment of primary liver cancer: a review.

    PubMed

    Li, Mouduo; Qiao, Cuixia; Qin, Liping; Zhang, Junyong; Ling, Changquan

    2012-09-01

    To investigate the application of Traditional Chinese Medicine Injections (TCMIs) for treatment of primary liver cancer (PLC). A literature review was conducted using PubMed/Medline, Cochrane Library Controlled Clinical Trials Database, China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJD) and China Biology Medicine (CBM). Online websites including journal websites and databases of ongoing trials, as well as some Traditional Chinese Medicine journals that are not indexed in the electronic databases were also searched. as adjunctive medication for the treatment of PLC could regulate patient immunity, reduce bone marrow suppression, relieve clinical symptoms, and improve quality of life, as well as control disease progression and prolong survival time. Within the limitations of this review, we conclude that application of TCMIs as adjunctive medication may provide benefits for patients with PLC. Further large, high-quality trials are warranted.

  11. Sorafenib tosylate, Ribavirn and Sofosbuvir combination therapy for HCV virus infected patients with decompensated liver cancer.

    PubMed

    Munir, Bushra; Ahmed, Bilal; Kiran, Shumaila; Jalal, Fatima; Zahoor, Muhammad Kashif; Shehzadi, Saba; Oranab, Sadaf; Kamran, Sayed Kashif; Ghaffar, Abdul

    2017-11-01

    Hepatitis C is the most common health problem worldwide and is major cause of death due to proliferation of hepatocellular carcinoma. The medicines available for HCV treatment overcome up-to 95% complications of HCV. However, liver cancer needs some additional care. Normally Sorafenib tosylate 200 mg is recommended for liver cancer. There is no such trial in which this drug could effectively be used in combination of direct acting antivirals for HCV. The study was conducted for HCV patients (n=30) with liver cancer having decompensated stage. Combination of Sorafenib tosylate, Ribavirn and Sofosbuvir were used for the pharmacokinetics of these medicines. Child pugh score less then 7 (CP A) in adults during treatment phase (received 12 weeks of Sorafenib tosylate 200 mg, Ribavirn and Sofosbuvir 400 mg once daily) have no side effect while child pugh score 7-9 (CP B) have evidence of hypertension. The main efficiency end point sustained virology response with overcoming liver cancer as well in 12 weeks after end treatment (SVR-LLC 12). Mean pharmacokinetic exposure to Sorafenib tosylate 200 mg, Ribavirn and Sofosbuvir at week 8th was 2.1, 1.5,1.2 times greater in CP B than in CP A. Adverse effects (AEs) were observed in 12 out of 30 patients but not severe as lethal for life. Treatment with Sorafenib tosylate, Ribavirn and Sofosbuvir for twelve weeks was harmless and well accepted, 100 % patients achieve (SVR LLC 12) with 10-fold cure rate more than previous ones. The combination therapy of Sorafenib tosylate, Ribavirn and Sofosbuvir was found helpful for the management of decompensated liver cancer.

  12. Age-associated change of C/EBP family proteins causes severe liver injury and acceleration of liver proliferation after CCl4 treatments.

    PubMed

    Hong, Il-Hwa; Lewis, Kyle; Iakova, Polina; Jin, Jingling; Sullivan, Emily; Jawanmardi, Nicole; Timchenko, Lubov; Timchenko, Nikolai

    2014-01-10

    The aged liver is more sensitive to the drug treatments and has a high probability of developing liver disorders such as fibrosis, cirrhosis, and cancer. Here we present mechanisms underlying age-associated severe liver injury and acceleration of liver proliferation after CCl4 treatments. We have examined liver response to CCl4 treatments using old WT mice and young C/EBPα-S193D knockin mice, which express an aged-like isoform of C/EBPα. Both animal models have altered chromatin structure as well as increased liver injury and proliferation after acute CCl4 treatments. We found that these age-related changes are associated with the repression of key regulators of liver biology: C/EBPα, Farnesoid X Receptor (FXR) and telomere reverse transcriptase (TERT). In quiescent livers of old WT and young S193D mice, the inhibition of TERT is mediated by HDAC1-C/EBPα complexes. After CCl4 treatments, TERT, C/EBPα and FXR are repressed by different mechanisms. These mechanisms include the increase of a dominant negative isoform, C/EBPβ-LIP, and subsequent repression of C/EBPα, FXR, and TERT promoters. C/EBPβ-LIP also disrupts Rb-E2F1 complexes in C/EBPα-S193D mice after CCl4 treatments. To examine if these alterations are involved in drug-mediated liver diseases, we performed chronic treatments of mice with CCl4. We found that C/EBPα-S193D mice developed fibrosis much more rapidly than WT mice. Thus, our data show that the age-associated alterations of C/EBP proteins create favorable conditions for the increased liver proliferation after CCl4 treatments and for development of drug-mediated liver diseases.

  13. Bio-responsive chitin-poly(L-lactic acid) composite nanogels for liver cancer.

    PubMed

    Arunraj, T R; Sanoj Rejinold, N; Ashwin Kumar, N; Jayakumar, R

    2014-01-01

    Hepatic carcinoma (HCC) is one of the most common cancer and its treatment has been considered a therapeutic challenge. Doxorubicin (Dox) is one of the most important chemotherapeutic agents used in the treatment for liver cancer. However, the efficacy of Dox therapy is restricted by the dose-dependent toxic side effects. To overcome the cardiotoxicity of Dox as well as the current problems of conventional modality treatment of HCC, we developed a locally injectable, biodegradable, and pH sensitive composite nanogels for site specific delivery. Both control and Dox loaded composite nanogel systems were analyzed by DLS, SEM, FTIR and TG/DTA. The size ranges of the control composite nanogels and their drug loaded counterparts were found to be 90±20 and 270±20 nm, respectively. The control chitin-PLA CNGs and Dox-chitin-PLA CNGs showed higher swelling and degradation in acidic pH. Drug entrapment efficiency and in vitro drug release studies were carried out and showed a higher drug release at acidic pH compared to neutral pH. Cellular internalization of the nanogel systems was confirmed by fluorescent microscopy. The cytotoxicity of the composite nanogels was analyzed toward HepG2 (human liver cancer) cell lines. Furthermore, the results of in vitro hemolytic assay and coagulation assay substantiate the blood compatibility of the system. Overall Dox-chitin-PLA CNGs system could be a promising anticancer drug delivery system for liver cancer therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Is MRI of the Liver Needed During Routine Preoperative Workup for Colorectal Cancer?

    PubMed

    Kang, Sung Il; Kim, Duck-Woo; Cho, Jai Young; Park, Jihoon; Lee, Kyung Ho; Son, Il Tae; Oh, Heung-Kwon; Kang, Sung-Bum

    2017-09-01

    The clinical efficacy of gadoxetic acid-enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer remains unclear. The purpose of this study was to evaluate the efficacy of preoperative gadoxetic acid-enhanced liver MRI for the diagnosis of liver metastasis in patients with colorectal cancer. This was a retrospective analysis from a prospective cohort database. All of the patients were from a subspecialty practice at a tertiary referral hospital. Patients who received preoperative gadoxetic acid-enhanced liver MRI after CT and attempted curative surgery for colorectal cancer were included. The number of equivocal hepatic lesions based on CT and gadoxetic acid-enhanced liver MRI and diagnostic use of the gadoxetic acid-enhanced liver MRI were measured. We reviewed the records of 690 patients with colorectal cancer. Equivocal hepatic lesions were present in 17.2% of patients based on CT and in 4.5% based on gadoxetic acid-enhanced liver MRI. Among 496 patients with no liver metastasis based on CT, gadoxetic acid-enhanced liver MRI detected equivocal lesions in 15 patients and metastasis in 3 patients. Among 119 patients who had equivocal liver lesions on CT, gadoxetic acid-enhanced liver MRI indicated hepatic lesions in 103 patients (86.6%), including 90 with no metastasis and 13 with metastasis. Among 75 patients who had liver metastasis on CT, gadoxetic acid-enhanced liver MRI indicated that the hepatic lesions in 2 patients were benign, in contrast to CT findings. The initial surgical plans for hepatic lesions according to CT were changed in 17 patients (3%) after gadoxetic acid-enhanced liver MRI. This study was limited by its retrospective design. The clinical efficacy of gadoxetic acid-enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer is low, in spite of its high diagnostic value for detecting liver metastasis. However, this study showed gadoxetic acid-enhanced liver MRI was

  15. Liver transplantation in the treatment of severe iatrogenic liver injuries

    PubMed Central

    Lauterio, Andrea; De Carlis, Riccardo; Di Sandro, Stefano; Ferla, Fabio; Buscemi, Vincenzo; De Carlis, Luciano

    2017-01-01

    The place of liver transplantation in the treatment of severe iatrogenic liver injuries has not yet been widely discussed in the literature. Bile duct injuries during cholecystectomy represent the leading cause of liver transplantation in this setting, while other indications after abdominal surgery are less common. Urgent liver transplantation for the treatment of severe iatrogenic liver injury may-represent a surgical challenge requiring technically difficult and time consuming procedures. A debate is ongoing on the need for centralization of complex surgery in tertiary referral centers. The early referral of patients with severe iatrogenic liver injuries to a tertiary center with experienced hepato-pancreato-biliary and transplant surgery has emerged as the best treatment of care. Despite widespread interest in the use of liver transplantation as a treatment option for severe iatrogenic injuries, reported experiences indicate few liver transplants are performed. This review analyzes the literature on liver transplantation after hepatic injury and discusses our own experience along with surgical advances and future prospects in this uncommon transplant setting. PMID:28932348

  16. Platelets in liver disease, cancer and regeneration.

    PubMed

    Kurokawa, Tomohiro; Ohkohchi, Nobuhiro

    2017-05-14

    Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

  17. Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX.

    PubMed

    Xu, Jiehua; Teng, I-Ting; Zhang, Liqin; Delgado, Stefanie; Champanhac, Carole; Cansiz, Sena; Wu, Cuichen; Shan, Hong; Tan, Weihong

    2015-01-01

    Most clinical cases of liver cancer cannot be diagnosed until they have evolved to an advanced stage, thus resulting in high mortality. It is well recognized that the implementation of early detection methods and the development of targeted therapies for liver cancer are essential to reducing the high mortality rates associated with this disease. To achieve these goals, molecular probes capable of recognizing liver cancer cell-specific targets are needed. Here we describe a panel of aptamers able to distinguish hepatocarcinoma from normal liver cells. The aptamers, which were selected by cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment), have Kd values in the range of 64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian cancer cells and lung adenocarcinoma. The proteinase treatment experiment indicated that all aptamers could recognize target HepG2 cells through surface proteins. This outcome suggested that these aptamers could be used as potential probes for further research in cancer studies, such as developing early detection assays, targeted therapies, and imaging agents, as well as for the investigation of common membrane proteins in these distinguishable cancers.

  18. Liver resection for colorectal cancer metastases

    PubMed Central

    Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

    2013-01-01

    Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

  19. Complete Resolution of an Alveolar Echinococcosis Liver Lesion Following Percutaneous Treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koroglu, Mert; Akhan, Okan; Gelen, Mustafa Tekinalp

    Herein we present a 63-year-old male patient with a solid hepatic alveolar echinococcosis diagnosed by surgical biopsy. His liver lesion, which was infected, was drained by percutaneous catheterization. The lesion surprisingly disappeared completely after the treatment. The patient was followed-up without any symptoms for 20 months after the drainage. As alveolar echinococcosis of the liver behaves like a slow-growing liver cancer, the disappearance of our patient's lesion was a very unusual and rare outcome, which, to the best of our knowledge, has never been published in the literature.

  20. Age-associated Change of C/EBP Family Proteins Causes Severe Liver Injury and Acceleration of Liver Proliferation after CCl4 Treatments*

    PubMed Central

    Hong, Il-Hwa; Lewis, Kyle; Iakova, Polina; Jin, Jingling; Sullivan, Emily; Jawanmardi, Nicole; Timchenko, Lubov; Timchenko, Nikolai

    2014-01-01

    The aged liver is more sensitive to the drug treatments and has a high probability of developing liver disorders such as fibrosis, cirrhosis, and cancer. Here we present mechanisms underlying age-associated severe liver injury and acceleration of liver proliferation after CCl4 treatments. We have examined liver response to CCl4 treatments using old WT mice and young C/EBPα-S193D knockin mice, which express an aged-like isoform of C/EBPα. Both animal models have altered chromatin structure as well as increased liver injury and proliferation after acute CCl4 treatments. We found that these age-related changes are associated with the repression of key regulators of liver biology: C/EBPα, Farnesoid X Receptor (FXR) and telomere reverse transcriptase (TERT). In quiescent livers of old WT and young S193D mice, the inhibition of TERT is mediated by HDAC1-C/EBPα complexes. After CCl4 treatments, TERT, C/EBPα and FXR are repressed by different mechanisms. These mechanisms include the increase of a dominant negative isoform, C/EBPβ-LIP, and subsequent repression of C/EBPα, FXR, and TERT promoters. C/EBPβ-LIP also disrupts Rb-E2F1 complexes in C/EBPα-S193D mice after CCl4 treatments. To examine if these alterations are involved in drug-mediated liver diseases, we performed chronic treatments of mice with CCl4. We found that C/EBPα-S193D mice developed fibrosis much more rapidly than WT mice. Thus, our data show that the age-associated alterations of C/EBP proteins create favorable conditions for the increased liver proliferation after CCl4 treatments and for development of drug-mediated liver diseases. PMID:24273171

  1. Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model.

    PubMed

    Wang, Huan; Wu, Xia; Lezmi, Stephane; Li, Qian; Helferich, William G; Xu, Yueqing; Chen, Hong

    2017-12-02

    Metastasis refers to the spread of a primary tumor cell from the primary site to other locations in the body and it is generally associated with the severity of a tumor. Extract of Ginkgo biloba (EGb) contains various bioactive compounds and it exerts beneficial effects including improvements in brain function and reduced risk of cardiovascular diseases. On the other hand, increased risk of thyroid and liver cancers by EGb have been reported in animals. A colon cancer metastasis model was established using intrasplenic injection of a human colon cancer cell line, SW620-luc in athymic mice to investigate the potential impact of EGb on colon cancer progression. After tumor establishment, EGb was intraperitonically injected daily for 5 wks. EGb significantly increased the rate of metastasis in mouse liver and decreased the number of necrotic and apoptotic cells in the metastatic liver when compared to the control. Meanwhile, EGb significantly induced proliferation of tumor cells in the metastatic liver, indicated by increased staining of Ki67 and H3S10p. mRNA expression of genes involved in cell cycle, metastasis, apoptosis, and oxidative stress were altered by EGb treatment in livers with tumors. Moreover, EGb activated the stress-responsive MAPK pathways in the liver with metastatic tumors. EGb exacerbated liver metastasis in a mouse colon cancer metastasis model. This is potentially due to the increased tumor cell proliferation involving stimulated MAPK pathways.

  2. Evaluation of the anti-neoplastic effect of sorafenib on liver cancer through bioluminescence tomography

    NASA Astrophysics Data System (ADS)

    Liang, Qian; Ye, Jinzuo; Du, Yang; Chi, Chongwei; Tian, Jie

    2017-03-01

    Hepatocellular carcinoma (HCC) is one of the most important leading causes of cancer-related deaths worldwide. In this study, we evaluated the efficacy of sorafenib on hepatocellular carcinoma through bioluminescence tomography (BLT) based on Micro-CT/BLT multi-modal system. Initially, the human hepatocellular carcinoma cell line HepG2-Red-FLuc, which was transfected with luciferase gene, was cultured. And then, the orthotopic liver tumor mouse model was established on 4 5 weeks old athymic male Balb/c nude mice by inoculating the HepG2-Red-FLuc cell suspension into the liver lobe under isoflurane anesthesia. 15 20 days after tumor cells implantation, the mice were divided into two groups including the sorafenib treatment group and the control group. The mice in the treatment group were treated with sorafenib with dosage of 62 mg/kg/day by oral gavage for continuous 14 days, and the mice in the control group were treated with sterile water at equal volume. The tumor growth and drug treatment efficacy were dynamically monitored through BLT. The results in this study showed that the growth of liver cancer can be dynamically monitored from very early stage, and also the sorafenib treatment efficacy can be reliably and objectively assessed using BLT imaging method. Our experimental result demonstrated sorafenib can inhibit the tumor growth effectively. BLT enabled the non-invasive and reliable assessment of anti-neoplastic drug efficacy on liver cancer.

  3. Role of surgical treatment in breast cancer liver metastases: a single center experience.

    PubMed

    Bacalbasa, Nicolae; Dima, Simona Olimpia; Purtan-Purnichescu, Raluca; Herlea, Vlad; Popescu, Irinel

    2014-10-01

    The aim of the present study was to review a single hepatobiliary center experience, the benefit of hepatic metastasectomy in breast cancer liver metastases (BCLM) patients and to identify predictors of survival. Fifty-two female patients underwent surgery for BCLM between 2002 and 2013. Only patients with liver resections (n=43) were included in the analysis. The median survival of the 43 patients with liver resection was 32.2 months. The factors significantly associated with overall post-hepatectomy survival were estrogen/progesteron receptor (ER/PR) status (p=0.002), node involvement of the primary tumor (p=0.049), size (p=0.005) and number (p=0.006) of the metastatic lesions. The 1-, 3- and 5-year survival rates after curative liver resection were 93.02%, 74.42%, 58.14%, respectively. BCLM resection is a safe procedure and offers survival benefit, especially in patients with reduced liver metastatic burden (solitary metastases, diameter of the metastases <5 cm) and positive ER/PR status. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Hepatitis-Associated Liver Cancer: Gaps and Opportunities to Improve Care

    PubMed Central

    McMahon, Brian; Block, Timothy; Cohen, Chari; Evans, Alison A.; Hosangadi, Anu; London, W. Thomas; Sherman, Morris

    2016-01-01

    The global burden of hepatocellular carcinoma (HCC; primary liver cancer) is increasing. HCC is often unaccompanied by clear symptomatology, causing patients to be unaware of their disease. Moreover, effective treatment for those with advanced disease is lacking. As such, effective surveillance and early detection of HCC are essential. However, current screening and surveillance guidelines are not being fully implemented. Some at-risk populations fall outside of the guidelines, and patients who are screened are often not diagnosed at an early enough stage for treatment to be effective. From March 17 to 19, 2015, the Hepatitis B Foundation sponsored a workshop to identify gaps and limitations in current approaches to the detection and treatment of HCC and to define research priorities and opportunities for advocacy. In this Commentary, we summarize areas for further research and action that were discussed throughout the workshop to improve the recognition of liver disease generally, improve the recognition of liver cancer risk, and improve the recognition that screening for HCC makes a life-saving difference. Participants agreed that primary prevention of HCC relies on prevention and treatment of viral hepatitis and other underlying etiologies. Earlier diagnosis (secondary prevention) needs to be substantially improved. Areas for attention include increasing practitioner awareness, better definition of at-risk populations, and improved performance of screening approaches (ultrasound, biomarkers for detection, risk stratification, targeted therapies). The heterogeneous nature of HCC makes it unlikely that a single therapeutic agent will be universally effective. Medical management will benefit from the development of new, targeted treatment approaches. PMID:26626106

  5. Adult Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

    Cancer.gov

    Hepatocellular carcinoma is the most common type of adult primary liver cancer. The Barcelona Clinical Liver Cancer (BCLC) Staging System is used to stage liver cancer. Learn more about risk factors, signs and symptoms, tests to diagnose, prognosis, and stages of adult primary liver cancer.

  6. Liver Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. [Disease burden of liver cancer in the Chinese population, in 1990 and 2013].

    PubMed

    Wang, L J; Yin, P; Liu, Y N; Liu, J M; Qi, J L; Zhou, M G

    2016-06-01

    To analyze the disease burden of liver cancer in the Chinese population in 1990 and 2013. Data from Global Burden of Diseases 2013 (GBD2013) was used to analyze the disease burden of liver cancer in China. The main outcome measurements would include mortality and disability-adjusted life years (DALY). Again, GBD global standard population in 2013 was used as the reference population to calculate the age-standardized rate. Related changes on percentage from 1990 to 2013 were calculated to analyze the changing patterns of disease burden for liver cancer in China. In 2013, a total of 358 100 people died of liver cancer, with the crude death rate as 25.85/100 000, in China. Number of deaths due to liver cancer secondary to hepatitis B was 163 600 (accounting for 45.69%). Number of deaths due to liver cancer secondary to hepatitis C was 134 200 (accounting for 37.48%) with DALY due to liver cancer appeared as 40.80 million person years. In 2013, the leading causes of DALY related to liver cancer was liver cancer secondary to hepatitis B, followed by liver cancer secondary to hepatitis C, liver cancer secondary to alcohol use, other liver cancers, with related DALYs as 4 652.0, 3 394.3, 964.3 and 592.1 thousands person years, respectively. The disease burdens of liver cancer secondary to various kinds of liver cancer were significantly higher in males than in females. Compared with 1990, the standardized mortality of liver cancer reduced by 25.00%, the DALY attributable to liver cancer increased by 16.95% and the standardized DALY rate attributable to liver cancer reduced by 33.47%. The burden of liver cancer secondary to hepatitis C became more serious and the standardized death rate increased by 106.18%, together with the standardized DALY rate increased by 91.68% in the past 23 years. Disease burden of liver cancer among young adults and the elderly were most serious. When comparing with the data in 1990, the standardized DALY rate showed declining trend in all the

  8. Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study.

    PubMed

    Chiou, Wen-Yen; Chang, Chun-Ming; Tseng, Kuo-Chih; Hung, Shih-Kai; Lin, Hon-Yi; Chen, Yi-Chun; Su, Yu-Chieh; Tseng, Chih-Wei; Tsai, Shiang-Jiun; Lee, Moon-Sing; Li, Chung-Yi

    2015-02-01

    The aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis. This was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated. The median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03). Our study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer

    ClinicalTrials.gov

    2013-06-03

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  10. The SHH/Gli axis regulates CD90-mediated liver cancer stem cell function by activating the IL6/JAK2 pathway.

    PubMed

    Zhang, Ketao; Che, Siyao; Pan, Chuzhi; Su, Zheng; Zheng, Shangyou; Yang, Shanglin; Zhang, Huayao; Li, Wenda; Wang, Weidong; Liu, Jianping

    2018-05-02

    The cell surface antigen CD90 has recently been established as a promising marker for liver cancer stem cells. This study aimed to investigate potential implications of SHH/Gli signalling in CD90+ liver cancer stem cells. Correlation of the expression of SHH signalling components and CD90 in liver cancer cells and clinical tissues, as well as in enriched CD90+ liver cancer stem cells and the TCGA database, were analysed by quantitative RT-PCR, Western blotting and flow cytometry. Functional analysis was conducted by siRNA-mediated CD90, Gli1 and Gli3 gene knockdown, SHH treatment and application of the JAK2 inhibitor AZD1480 and IL6 neutralizing antibody in CD90+ liver cancer stem cells, followed by cell proliferation, migration, sphere formation and tumorigenicity assays. CD90 expression exhibited a high positive correlation with Gli1 and Gli3 in multiple liver cancer cell lines and human cancerous liver tissues, both of which showed a significant increase in liver cancer. Analysis of TCGA data revealed an association of CD90, Gli1 and Gli3 with a short overall survival and positive correlation between CD90 expression and Gli3 expression level. The stem cell potentials of CD90+ 97L liver cancer cells were greatly impaired by Gli1/3 knockdown with siRNA but enhanced by SHH treatment. Application of the JAK2 inhibitor AZD1480 and IL6 neutralizing antibody showed the CD90 and SHH/Gli-regulated liver cancer stem cell functions were mediated by the IL6/JAK2/STAT3 pathway. The stem cell properties of CD90+ liver cancer cells are regulated by the downstream SHH/Gli and IL6/JAK2/STAT3 signalling pathways. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. Hepatectomy As A First Choice Treatment For Liver Metastasis From Gastric Cancer: A Single Center Experience.

    PubMed

    Sakamoto, Hirohiko; Amikura, Katsumi; Tanaka, Yoichi; Kawashima, Yoshiyuki

    2014-05-01

    Indication of hepatectomy for liver metastases from gastric cancer (LMGC) is still controversial despite many papers favoring surgery. The aim of this study is to claim that we should accept hepatectomy as first choice treatment for LMGC. It is important to have a consensus on this matter for surgeons to treat LMGC properly. Fifty three patients undergoing hepatectomy for LMGC from 1990 through 2010 were retrospectively analysed for survival and prognostic factors. Analyses were made on size, multiplicity, synchronicity and positive surgical margin as liver metastasis factors. Serosal invasion, node metastasis, histological differentiation and UICC stage were analysed as primary site factors. Multivariate analysis was performed for those positive for univariate analysis. Cumulative 5 year survival rate was 27%. Multiplicity, positive margin and node metastasis (N > 2) yielded significant difference on univariate analysis. On multivariate analysis multiplicity and node metastasis (N > 2) were significant. Hepatectomy for LMGC is potentially curative and should be regarded as first choice. Solitary and N < 3 are good prognostic factors.

  12. Real-time confocal laser endomicroscopic evaluation of primary liver cancer based on human liver autofluorescence.

    PubMed

    Maki, Harufumi; Kawaguchi, Yoshikuni; Arita, Junichi; Akamatsu, Nobuhisa; Kaneko, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Harihara, Yasushi; Kokudo, Norihiro

    2017-02-01

    Confocal laser endomicroscopy (CLE) is available for real-time microscopic examination. This study aims to evaluate the usefulness of intraoperative CLE examination as a modality to evaluate surgical margins in surgery for primary liver cancer. A probe-based CLE system (Cellvizio 100, Mauna Kea Technologies, Paris, France) was used. The subjects comprised seven specimens obtained from six patients with primary liver cancer in November 2015. The probe was manually attached to the surfaces of specimens, and images were collected without external fluorophores. CLE images were compared with hematoxylin and eosin-stained slides. Fluorescence intensity (FI) values of the CLE images were assessed using luminance-analyzing software. CLE examination visualized non-cancerous regions in the background liver as regular structures with high fluorescence because of human liver autofluorescence. Conversely, hepatocellular carcinoma and intrahepatic cholangiocarcinoma were depicted as irregular structures with low fluorescence. The median FI values of the non-cancerous regions and the cancerous regions were 104 (79.8-156) and 74.9 (60.6-106), respectively, and were significantly different (P = 0.031). The probe-based CLE enables real-time differentiation of cancerous regions from non-cancerous tissues in surgical specimens because of human liver autofluorescence. CLE can be used to confirm negative surgical margins in the operating room. J. Surg. Oncol. 2017;115:151-157. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Stages of Adult Primary Liver Cancer

    MedlinePlus

    ... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...

  14. Listening to the consumer voice: developing multilingual cancer information resources for people affected by liver cancer.

    PubMed

    Robotin, Monica C; Porwal, Mamta; Hopwood, Max; Nguyen, Debbie; Sze, Minglo; Treloar, Carla; George, Jacob

    2017-02-01

    In Australia, liver cancer incidence is rising, particularly among people born in hepatitis B-endemic countries. We sought to build an understanding of the information needs of people affected by liver cancer, to inform the design of in-language consumer information resources. We searched the World Wide Web for available in-language consumer information and conducted a literature search on consumers' information needs and their preferred means of accessing it. Qualitative data collection involved bilingual researchers conducting focus group discussions (26 participants) and in-depth interviews (22 participants) with people affected by liver cancer in English, Vietnamese, Cantonese and Mandarin. Sessions were audio-recorded, transcribed, translated and thematically analysed. The key themes and salient findings informed the development of in-language multimedia information resources. Many consumer resources did not cater for people with low literacy levels. The participants wanted more information on cancer diagnostic and treatment options, nutrition and Chinese Medicine and experienced communication challenges speaking to health professionals. While Vietnamese speakers relied entirely on information provided by their doctors, other participants actively searched for additional treatment information and commonly used the Internet to source it. We developed multilingual, multimedia consumer information resources addressing identified consumer information needs through an iterative process, in collaboration with our multilingual consumer panel. These resources are available in four languages, as separate modules accessible online and in DVD format. This process enabled the development of user-friendly patient resources, which complement health-care provider information and supports informed patient decision making. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

  15. DAPK1 as an independent prognostic marker in liver cancer.

    PubMed

    Li, Ling; Guo, Libin; Wang, Qingshui; Liu, Xiaolong; Zeng, Yongyi; Wen, Qing; Zhang, Shudong; Kwok, Hang Fai; Lin, Yao; Liu, Jingfeng

    2017-01-01

    The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort ( n  = 115;  p  = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression ( p  = 0.002) and overall survival ( p  = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

  16. Evaluation of tumour markers as differential diagnostic tool in patients with suspicion of liver metastases from breast cancer.

    PubMed

    Liska, Vaclav; Holubec, Lubos; Treska, Vladislav; Vrzalova, Jindra; Skalicky, Tomas; Sutnar, Alan; Kormunda, Stanislav; Bruha, Jan; Vycital, Ondrej; Finek, Jindrich; Pesta, Martin; Pecen, Ladislav; Topolcan, Ondrej

    2011-04-01

    The liver is the site of breast cancer metastasis in 50% of patients with advanced disease. Tumour markers have been demonstrated as being useful in follow-up of patients with breast cancer, in early detection of recurrence of breast cancer after radical surgical treatments, and in assessing oncologic therapy effect, but no study has been carried out on their usefullness in distinguishing benign liver lesions from breast cancer metastases. The aim of this study was therefore to evaluate the importance of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen CA19-9 (CA19-9), thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin 19 fragment (CYFRA 21-1) in differential diagnosis between benign liver lesions and liver metastases of breast cancer. The study includes 3 groups: 22 patients with liver metastases of breast cancer; 39 patients with benign liver lesions (hemangioma, focal nodular hyperplasia, liver cyst, hepatocellular adenoma); and 21 patients without any liver disease or lesion that were operated on for benign extrahepatic diseases (groin hernia, varices of lower limbs) as a control group. The serum levels of tumour markers were assessed by means of immunoanalytical methods. Preoperative serum levels of CYFRA 21-1, TPA, TPS and CEA were significantly higher in patients with liver metastases of breast cancer in contrast to healthy controls and patients with benign liver lesions (p-value<0.05). Serum levels of CA19-9 and TK were higher in patients with malignancy in comparison with benign liver disease and healthy controls but these differences were not statistically significant. Tumour markers CEA, CYFRA 21-1, TPA and TPS can be recommended as a good tool for differential diagnosis between liver metastases of breast cancer and benign liver lesions.

  17. Detection of liver cancer and abnormal liver tissue by Raman spectroscopy and fluorescence

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Ding, Jianhua; Zhang, Xiujun; Lin, Junxiu; Wang, Deli

    2005-01-01

    In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver disease patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5nm is higher than that excited by 488.0nm. For the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. Except for human serum, we use rats serum for researching either. Compared with results of path al examination, we analyze the spectra of normal cases, hepatic fibrosis and hepatocirrhosis respectively in an attempt to find some difference between them. Red shift of fluorescence peak is observed with disease evolution using 514.5nm excitation of an Ar-ion laser. However, no distinct changes happen with 488.0nm excitation. These results have important reference values to explore the method of laser spectrum diagnosis.

  18. FXR-Gankyrin axis is involved in development of pediatric liver cancer.

    PubMed

    Valanejad, Leila; Lewis, Kyle; Wright, Mary; Jiang, Yanjun; D'Souza, Amber; Karns, Rebekah; Sheridan, Rachel; Gupta, Anita; Bove, Kevin; Witte, David; Geller, James; Tiao, Gregory; Nelson, David L; Timchenko, Lubov; Timchenko, Nikolai

    2017-07-01

    The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins. We next analyzed FXR-Gank-Tumor suppressor pathways in a large cohort of HBL patients which include 6 controls and 53 HBL samples. Systemic analysis of these samples and RNA-Seq approach revealed that the FXR-Gank axis is activated; markers of hepatic stem cells are dramatically elevated and hepatocyte markers are reduced in HBL samples. In the course of these studies, we found that RNA binding protein CUGBP1 is a new tumor suppressor protein which is reduced in all HBL samples. Therefore, we generated CUGBP1 KO mice and examined HBL signatures in the liver of these mice. Micro-array studies revealed that the HBL-specific molecular signature is developed in livers of CUGBP1 KO mice at very early ages. Thus, we conclude that FXR-Gank-TSPs-Stem cells pathway is a key determinant of liver cancer in animal models and in pediatric liver cancer. Our data provide a strong basis for development of FXR-Gank-based therapy for treatment of patients with hepatoblastoma. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Treatment and care of patients with metastatic breast cancer.

    PubMed

    Beaumont, T; Leadbeater, M

    This article provides an overview of the treatment options available for patients diagnosed with metastatic breast cancer. The article focuses on the four common organ sites affected by metastatic breast cancer, including the bone, lungs, liver and brain. The implications for nursing care are addressed, highlighting common side effects of treatment and frequent areas of concern for patients.

  20. Liver (Hepatocellular) Cancer Screening (PDQ®)—Health Professional Version

    Cancer.gov

    Liver (hepatocellular) cancer screening, even in high risk individuals, has not been shown to be beneficial. Get detailed information about liver cancer screening, potential screening modalities, and research directions in this summary for clinicians.

  1. Clinical characteristics and prognostic factors of prostate cancer with liver metastases.

    PubMed

    Wang, HaiTao; Li, BaoGuo; Zhang, PengYu; Yao, YanHong; Chang, JiWu

    2014-01-01

    Liver metastasis from prostate cancer is uncommon and remains poorly understood. We computer searched the clinical records of all our patients registered into a database to identify patients that presented or developed liver metastases. A total of 27 prostate cancer patients with ultrasound or CT/MR imaging evidence of liver metastases were included in our analysis. The liver metastasis rate from metastatic prostate cancer was 4.29%. Eight (29.63%) patients had previously untreated, hormone-naive prostate cancer (synchronous liver metastases at diagnosis of prostate cancer), whereas 19 (70.37%) patients had already been diagnosed as having hormone-refractory prostate cancer. In the hormone-naive group, the median overall survival after liver metastases diagnosis was 38 months and half of the patients were still alive at the latest follow-up, whereas only 6 months in the hormone-refractory group (p = 0.003). High concentration of serum neuron-specific enolase and previous chemotherapy were associated with a significantly poor overall survival after liver metastases in the hormone-refractory group using Kaplan–Meier curves and logrank tests for univariate analysis.

  2. Potent 19-norvitamin D analogs for prostate and liver cancer therapy

    PubMed Central

    Kittaka, Atsushi; Yoshida, Akihiro; Chiang, Kun-Chun; Takano, Masashi; Sawada, Daisuke; Sakaki, Toshiyuki; Chen, Tai C

    2013-01-01

    The active form of vitamin D3, 1α,25(OH)2D3 or calcitriol, is known to inhibit the proliferation and invasiveness of many types of cancer cells, including prostate and liver cancer cells. These findings support the use of 1α,25(OH)2D3 for prostate and liver cancer therapy. However, 1α,25(OH)2D3 can cause hypercalcemia, thus, analogs of 1α,25(OH)2D3 that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. We have developed 2α-functional group substituted 19-norvitamin D3 analogs with and without 14-epimerization. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (MART-10 and -11, respectively) and 14-epi-2α- and 14-epi-2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (14-epi-MART-10 and 14-epi-MART-11, respectively) were found to be the most promising. In this review, we discuss the synthesis of this unique class of vitamin D analogs, the molecular mechanism of anticancer actions of vitamin D, and the biological evaluation of these analogs for potential application to the prevention and treatment of prostate and liver cancer. PMID:23157238

  3. Wnt Inactivation for Liver Cancer Therapy | Center for Cancer Research

    Cancer.gov

    Hepatocellular carcinoma (HCC) is the fifth most common and third most deadly type of cancer in the world. The majority of cases occur in Asia and Africa, resulting in most cases being diagnosed only at advanced stages of the disease when drug resistance is high. HCC typically follows damage to the liver such as cirrhosis, making radiation and chemotherapy a more challenging prospect. Surgery is also not a very viable option because less than one in four carcinomas can be completely removed. The limitations in these treatment modalities create the need for alternative therapeutic approaches.

  4. Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan.

    PubMed

    Lee, Kwai-Fong; Tsai, Yi-Ting; Lin, Chih-Yuan; Hsieh, Chung-Bao; Wu, Sheng-Tang; Ke, Hung-Yen; Lin, Yi-Chang; Lin, Feng-Yen; Lee, Wei-Hwa; Tsai, Chien-Sung

    2016-01-01

    Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex.

  5. The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

    PubMed

    Lai, G Y; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; Sinha, R; Freedman, N D

    2013-09-03

    Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

  6. Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer

    PubMed Central

    Dai, Dejian; Hou, Yiming

    2017-01-01

    The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82.9 nm, +21.8 mV, 85.7% and 35.4%, respectively. Bio-CS exhibited an apparent liver cancer targeting effect in vitro and in vivo, as demonstrated by confocal laser scanning, green fluorescent protein transfection, and in vivo imaging assays. In addition, the Bio-CS/plasmid DNA nanoparticles significantly increased the survival period of the orthotropic liver cancer mouse model compared with the plasmid DNA, with no apparent side effects on the cells. Bio-CS nanomaterials stimulated an immune response in hepatoma cells via increased expression of GM-CSF, IL-21 and Rae-1 markers. The data suggest that Bio-CS increased the inhibition of liver cancer cell proliferation in vitro and the activation of the cellular immunity in vivo. PMID:28938619

  7. [The value of serum alpha-L-fucosidase activity in the diagnosis of primary liver cancer].

    PubMed

    Wei, X; Wang, S; Rui, J

    2000-03-01

    To analyse the value of serum alpha-L-fucosidase (AFU) in the diagnosis of primary liver cancer (PLC). Serum AFU was studied in 141 patients with PLC, 17 patients with secondary liver cancer, 16 patients with cirrhosis, and 30 controls. Rank correlation analysis was used to assess the relation between value of AFU activity and TNM staging. The results were compared to those of serum AFP determination. AFU was increased in 108 of 141 (76.6%) patients. The positive rate was statistically different from that in patients with secondary liver cancer, cirrhosis, and that in normal individual. The AFU level was correlated with TNM stage. In 25 PLC patients with AFU > 500 nmol.L-1.S-1, the average survival time was only 71 days. In 36 PLC patients who had received effective treatment, the serum AFU decreased to a significantly lower level than that examined before treatment. The positive rate of AFP in PLC patients was 64.5%. It rose to 86.2% if both parameters were used. AFU is a useful marker of PLC for diagnosis and posttreatment monitoring.

  8. Liver (Hepatocellular) Cancer Prevention (PDQ®)—Health Professional Version

    Cancer.gov

    Liver (hepatocellular) cancer prevention strategies include avoiding risk factors and vaccinating against hepatitis B. Risk factors include hepatitis B and C infection, cirrhosis, and aflatoxin. Get detailed information about risk factors and preventing liver cancer in this clinician summary.

  9. Sonodynamic action of pyropheophorbide-a methyl ester in liver cancer cells.

    PubMed

    Xu, Jing; Xia, Xinshu; Wang, Xinna; Xu, Chuanshan; Wang, Ping; Xiang, Junyan; Jiang, Yuan; Leung, Albert Wingnang

    2010-07-01

    This study aimed to investigate the sonodynamic action of pyropheophorbide-a methyl ester (MPPa) in liver cancer cells to explore a novel therapeutic modality. H22 cells were chosen as model cells to investigate the sonodynamic action of MPPa on liver cancer. The MPPa concentration was kept constant at 2 micromol/L, and the cells were subjected to ultrasound exposure at an intensity of 0.97 W/cm(2). Cytotoxicity was investigated 24 hours after ultrasound exposure. Apoptosis was evaluated using flow cytometry with annexin V-fluorescein isothiocyanate and propidium iodine staining and nuclear staining with Hoechst 33258. Reactive oxygen species (ROS) were analyzed using flow cytometry with 2,7-dichlorodihydrofluorescein diacetate staining. No significant dark cytotoxicity of MPPa was shown in the H22 cells at the concentration of 2 micromol/L. The cell death rate induced by ultrasound treatment was significantly higher in the presence of MPPa than in the absence of it (P < .05). Flow cytometry showed that the sonodynamic action of MPPa significantly increased the early and late apoptotic rates of the H22 cells. Nuclear condensation and an ROS increase were found after sonodynamic treatment. Our findings showed that MPPa-mediated sonodynamic action significantly enhanced death of H22 cells and the ROS level, suggesting that MPPa is a novel sonosensitizer and the sonodynamic action of MPPa might be a potential therapeutic modality in the management of liver cancer.

  10. Oncologic and surgical outcomes in colorectal cancer patients with liver cirrhosis: A propensity-matched study.

    PubMed

    Han, Eon Chul; Ryoo, Seung-Bum; Park, Ji Won; Yi, Jin Wook; Oh, Heung-Kwon; Choe, Eun Kyung; Ha, Heon-Kyun; Park, Byung Kwan; Moon, Sang Hui; Jeong, Seung-Yong; Park, Kyu Joo

    2017-01-01

    The management of colorectal cancer in patients with liver cirrhosis requires a thorough understanding of both diseases. This study evaluated the effect of liver cirrhosis on oncologic and surgical outcomes and prognostic factors in colorectal cancer patients. Fifty-five consecutive colorectal cancer patients with liver cirrhosis underwent colorectal resection (LC group). Using a prospectively maintained database, these patients were matched 1:4 using propensity scoring with R programming language, package "MatchIt" and "optmatch" by sex, age, cancer location, and tumor stage with 220 patients without liver cirrhosis (non-LC group), resulting in 275 patients. The 5-year overall survival (OS) was significantly worse in the LC group than in the non-LC group (46.7% vs. 76.2% respectively, P < 0.001); however, the 5-year proportion of recurrence free (PRF) rates were similar (73.1% vs. 84.5% respectively, P = 0.094). On multivariate analysis of the LC group, tumor-node-metastasis (TNM) stage ≥III disease, venous invasion, and a model for end-stage liver disease plus serum sodium (MELD-Na) score >10 were prognostic factors for OS. However, the OS was not different between the LC group with MELD-Na score ≤10 and the non-LC group (5-year OS rate, TNM stage ≤II, 85.7 vs 89.5%, p = 0.356; TNM stage ≥III, 41.1 vs 66.2%, p = 0.061). Colorectal cancer patients with liver cirrhosis have poorer OS compared to those without liver cirrhosis; however, the PRF rates are similar. It might be due to the mortality from the liver, and surgical treatment should be actively considered for patients with MELD-Na score <10.

  11. Liver and Bile Duct Cancer—Patient Version

    Cancer.gov

    Liver cancer includes hepatocellular carcinoma and bile duct cancer (cholangiocarcinoma). Risk factors for HCC include chronic infection with hepatitis B or C and cirrhosis of the liver. Start here to find information on liver and bile duct cancer treatment, causes and prevention, screening, research, and statistics.

  12. FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, Xiongfei, E-mail: xiongfeihuang@hotmail.com; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian; Zeng, Yeting

    The nuclear receptor Farnesoid X Receptor (FXR) is likely a tumor suppressor in liver tissue but its molecular mechanism of suppression is not well understood. In this study, the gene expression profile of human liver cancer cells was investigated by microarray. Bioinformatics analysis of these data revealed that FXR might regulate the mTOR/S6K signaling pathway. This was confirmed by altering the expression level of FXR in liver cancer cells. Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. FXR upregulation also intensified the inhibition of cell growth bymore » rapamycin. Downregulation of FXR produced the opposite effect. Finally, we found that ectopic expression of FXR in SK-Hep-1 xenografts inhibits tumor growth and reduces expression of the phosphorylated protein S6K. Taken together, our data provide the first evidence that FXR suppresses proliferation of human liver cancer cells via the inhibition of the mTOR/S6K signaling pathway. FXR expression can be used as a biomarker of personalized mTOR inhibitor treatment assessment for liver cancer patients. -- Highlights: •FXR inhibits the proliferation of liver cancer cells by prolonging G0/G1 phase. •Microarray results indicate that mTOR-S6k signaling is involved in cellular processes in which FXR plays an important role. •FXR blocks the growth of liver cancer cells via the inhibition of the mTOR/S6K signaling pathway in vitro and in vivo.« less

  13. Estimating liver cancer deaths in Thailand based on verbal autopsy study.

    PubMed

    Waeto, Salwa; Pipatjaturon, Nattakit; Tongkumchum, Phattrawan; Choonpradub, Chamnein; Saelim, Rattikan; Makaje, Nifatamah

    2014-01-01

    Liver cancer mortality is high in Thailand but utility of related vital statistics is limited due to national vital registration (VR) data being under reported for specific causes of deaths. Accurate methodologies and reliable supplementary data are needed to provide worthy national vital statistics. This study aimed to model liver cancer deaths based on verbal autopsy (VA) study in 2005 to provide more accurate estimates of liver cancer deaths than those reported. The results were used to estimate number of liver cancer deaths during 2000-2009. A verbal autopsy (VA) was carried out in 2005 based on a sample of 9,644 deaths from nine provinces and it provided reliable information on causes of deaths by gender, age group, location of deaths in or outside hospital, and causes of deaths of the VR database. Logistic regression was used to model liver cancer deaths and other variables. The estimated probabilities from the model were applied to liver cancer deaths in the VR database, 2000-2009. Thus, the more accurately VA-estimated numbers of liver cancer deaths were obtained. The model fits the data quite well with sensitivity 0.64. The confidence intervals from statistical model provide the estimates and their precisions. The VA-estimated numbers of liver cancer deaths were higher than the corresponding VR database with inflation factors 1.56 for males and 1.64 for females. The statistical methods used in this study can be applied to available mortality data in developing countries where their national vital registration data are of low quality and supplementary reliable data are available.

  14. Evaluation of Bufadienolides as the Main Antitumor Components in Cinobufacin Injection for Liver and Gastric Cancer Therapy.

    PubMed

    Wei, Xiaolu; Si, Nan; Zhang, Yuefei; Zhao, Haiyu; Yang, Jian; Wang, Hongjie; Wang, Lianmei; Han, Linyu; Bian, Baolin

    2017-01-01

    Cinobufacin injection, also known as huachansu, is a preparation form of Cinobufacini made from Cinobufacin extract liquid. Despite that Cinobufacin injection is shown to shrink liver and gastric tumors, improving patient survival and life quality, the effective components in Cinobufacin remain elusive. In this study, we aim to screen antitumor components from Cinobufacin injection to elucidate the most effective antitumor components for treatment of liver and gastric cancers. High performance liquid chromatography (HPLC) and LC-MS/MS analysis were used to separate and determine the components in Cinobufacin injection. Inhibition rates of various components in Cinobufacin injection on liver and gastric cancer cells were determined with MTT assay; Hepatocellular carcinoma and gastric cancer models were used to assess the antitumor effect of the compounds in vivo. The major constituents in Cinobufacin injection include peptides, nucleic acids, tryptamines and bufotalins. MTT assay revealed that bufadienolides had the best antitumor activity, with peptides being the second most effective components. Bufadienolides showed significant inhibition rates on gastric and hepatocellular tumour growth in vivo. Bufadienolides are the most effective components in Cinobufacini injection for the treatment of liver and gastric cancers. This discovery can greatly facilitate further research in improving the therapeutic effects of Cinobufacin injection, meanwhile reducing its adverse reaction.

  15. Particulate matter air pollution and liver cancer survival.

    PubMed

    Deng, Huiyu; Eckel, Sandrah P; Liu, Lihua; Lurmann, Frederick W; Cockburn, Myles G; Gilliland, Frank D

    2017-08-15

    Particulate matter (PM) air pollution exposure has been associated with cancer incidence and mortality especially with lung cancer. The liver is another organ possibly affected by PM due to its role in detoxifying xenobiotics absorbed from PM. Various studies have investigated the mechanistic pathways between inhaled pollutants and liver damage, cancer incidence, and tumor progression. However, little is known about the effects of PM on liver cancer survival. Twenty thousand, two hundred and twenty-one California Cancer Registry patients with hepatocellular carcinoma (HCC) diagnosed between 2000 and 2009 were used to examine the effect of exposure to ambient PM with diameter <2.5 μm (PM 2.5 ) on HCC survival. Cox proportional hazards models were used to estimate hazard ratios (HRs) relating PM 2.5 to all-cause and liver cancer-specific mortality linearly and nonlinearly-overall and stratified by stage at diagnosis (local, regional and distant)-adjusting for potential individual and geospatial confounders.PM 2.5 exposure after diagnosis was statistically significantly associated with HCC survival. After adjustment for potential confounders, the all-cause mortality HR associated with a 1 standard deviation (5.0 µg/m 3 ) increase in PM 2.5 was 1.18 (95% CI: 1.16-1.20); 1.31 (95% CI:1.26-1.35) for local stage, 1.19 (95% CI:1.14-1.23) for regional stage, and 1.05 (95% CI:1.01-1.10) for distant stage. These associations were nonlinear, with substantially larger HRs at higher exposures. The associations between liver cancer-specific mortality and PM 2.5 were slightly attenuated compared to all-cause mortality, but with the same patterns.Exposure to elevated PM 2.5 after the diagnosis of HCC may shorten survival, with larger effects at higher concentrations. © 2017 UICC.

  16. GPU-based RFA simulation for minimally invasive cancer treatment of liver tumours.

    PubMed

    Mariappan, Panchatcharam; Weir, Phil; Flanagan, Ronan; Voglreiter, Philip; Alhonnoro, Tuomas; Pollari, Mika; Moche, Michael; Busse, Harald; Futterer, Jurgen; Portugaller, Horst Rupert; Sequeiros, Roberto Blanco; Kolesnik, Marina

    2017-01-01

    Radiofrequency ablation (RFA) is one of the most popular and well-standardized minimally invasive cancer treatments (MICT) for liver tumours, employed where surgical resection has been contraindicated. Less-experienced interventional radiologists (IRs) require an appropriate planning tool for the treatment to help avoid incomplete treatment and so reduce the tumour recurrence risk. Although a few tools are available to predict the ablation lesion geometry, the process is computationally expensive. Also, in our implementation, a few patient-specific parameters are used to improve the accuracy of the lesion prediction. Advanced heterogeneous computing using personal computers, incorporating the graphics processing unit (GPU) and the central processing unit (CPU), is proposed to predict the ablation lesion geometry. The most recent GPU technology is used to accelerate the finite element approximation of Penne's bioheat equation and a three state cell model. Patient-specific input parameters are used in the bioheat model to improve accuracy of the predicted lesion. A fast GPU-based RFA solver is developed to predict the lesion by doing most of the computational tasks in the GPU, while reserving the CPU for concurrent tasks such as lesion extraction based on the heat deposition at each finite element node. The solver takes less than 3 min for a treatment duration of 26 min. When the model receives patient-specific input parameters, the deviation between real and predicted lesion is below 3 mm. A multi-centre retrospective study indicates that the fast RFA solver is capable of providing the IR with the predicted lesion in the short time period before the intervention begins when the patient has been clinically prepared for the treatment.

  17. Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population-based cohort study of 32,839 one-year survivors.

    PubMed

    Bonnesen, Trine Gade; Winther, Jeanette F; Andersen, Klaus K; Asdahl, Peter H; de Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Sällfors Holmqvist, Anna; Madanat-Harjuoja, Laura-Maria; Tryggvadottir, Laufey; Wesenberg, Finn; Heilmann, Carsten; Olsen, Jørgen H; Hasle, Henrik

    2018-02-15

    Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications. © 2017 UICC.

  18. Diabetes, plasma glucose and incidence of fatty liver, cirrhosis and liver cancer: A prospective study of 0.5 million people.

    PubMed

    Pang, Yuanjie; Kartsonaki, Christiana; Turnbull, Iain; Guo, Yu; Clarke, Robert; Chen, Yiping; Bragg, Fiona; Yang, Ling; Bian, Zheng; Millwood, Iona Y; Hao, Juanzhi; Han, Xianyong; Zang, Yajing; Chen, Junshi; Li, Liming; Holmes, Michael V; Chen, Zhengming

    2018-05-07

    The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We aimed to examine the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults, and to assess the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalised non-alcoholic fatty liver disease (NAFLD), and 244 hospitalised alcoholic liver disease (ALD) were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared with those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% CI 1.30-1.70) for liver cancer, 1.81 (1.57-2.09) for cirrhosis, 1.76 (1.47-2.16) for NAFLD, and 2.24 (1.42-3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03-1.06) for liver cancer, 1.07 (1.05-1.09) for cirrhosis, 1.07 (1.05-1.10) for NAFLD, and 1.10 (1.05-1.15) for ALD. These associations did not differ by HBV infection. In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with increased risks of liver cancer and major chronic liver diseases. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  19. The Results of the Combine Treatment of Patients with Liver Bilobar Metastases from Colorectal Cancer Using Radiofrequency Ablation.

    PubMed

    Kaganov, Oleg Igorevich; Kozlov, Sergei Vasilevich; Orlov, Andrei Evgenyevich; Blinov, Nikita Vyacheslavovich

    2018-06-01

    Colorectal cancer (CRC) is the third most common cancer worldwide. The mortality from CRC remains very high. The main cause of such a high mortality is a disseminate process with the appearance of distant metastases. In this regard, the treatment of metastatic lesions is recognized as an important trend in modern oncology. The program of study included 176 patients with colorectal cancer after primary tumor removal with the malignant progression-multiple (more than 4) bilobar liver metastases. The research was organized in Samara Regional Oncology Centre from 2001 to 2014. By the treatment method, patients were divided into two groups. Main group got the combined (chemotherapy + radiofrequency ablation (RFA)) treatment ( n  = 98). In control group, only chemotherapy was applied ( n  = 78). One-, two-, and three-year OS were 73.5, 25.1, and 7.2% in the main group and 39.6, 6.3, and 2.1% in the control group. The RFA application allowed us to reach the index of 4-year survival 1.8% in the main group, while we received only 2.1 of 3-year survival in the control group. The OS median reached 18 months in the main group and 11 months in the control group. So, the OS curves in two comparing groups were significantly different according to statistics (log-rank test 3.77, р  = 0.000). The application of RFA in combination with chemotherapy in the treatment of bilobar metastasis colorectal cancer allows to improve the performance of disease-free survival and overall survival significantly, compared with the group of patients who received only chemotherapy.

  20. Childhood Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

    Cancer.gov

    Liver cancer is rare in children and adolescents. There are two main types of childhood liver cancer. Hepatoblastoma usually affects children 3 years and younger, and hepatocellular carcinoma occurs in older children and teenagers. Learn about risk factors, tests to diagnose, and stages of childhood liver cancer.

  1. POP exposure from fish liver consumption and risk of cancer--the Norwegian Women and Cancer Study.

    PubMed

    Brustad, Magritt; Sandanger, Torkjel Manning; Andersen, Vegard; Lund, Eiliv

    2007-07-01

    The aim of the study was to investigate the hypothesis that consumption of fish liver increases cancer risk in humans due to increased intake of persistent organic pollutants (POPs). This study is based on data from the Norwegian Women and Cancer Study (NOWAC). The study has a prospective cohort design with questionnaire data from 64 285 randomly selected Norwegian women (aged 40-70 at baseline) and linkage to the Norwegian Cancer Registry. Cox proportional hazards regression was used to calculate risk ratios associated with consumption of fish liver and total cancer and cancer in breast, uterus, and colon. Fish liver consumption was, after adjusting for known risk factors, associated with a significant reduced risk for total cancer (RR = 0.92, 95% CI: 0.85, 0.99), and non-significant reduced risk for breast cancer (RR = 0.90, 95% CI: 0.78, 1.04), and colon cancer (RR = 0.82, 95% CI: 0.63, 1.07). Relative risk for uterus cancer was 0.82 (95% CI: 0.61-1.12). No significant dose-response effect was found for frequency of fish liver consumption (when divided into three intake groups) and total cancer, nor for any of the other cancer sites.We have concluded that in Norwegian women, fish liver consumption was not associated with an increased cancer risk in breast, uterus, or colon. In contrast, a decreased risk for total cancer was found.

  2. Liver Cancer and Hepatitis B

    MedlinePlus

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  3. Hepatic Stellate Cells Alter Liver Immune Environment to Promote Cancer | Center for Cancer Research

    Cancer.gov

    Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for up to 90 percent of cases, and is the second most common cause of cancer-related deaths worldwide according to the World Health Organization’s 2014 World Cancer Report. Even when caught early, HCC often recurs, either from intra-liver metastases or new primary tumors, and recurrence is the

  4. Non-viral causes of liver cancer: does obesity led inflammation play a role?

    PubMed

    Alzahrani, Badr; Iseli, Tristan J; Hebbard, Lionel W

    2014-04-10

    Liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Hepatocellular carcinoma (HCC) accounts for around 90% of primary liver cancers. Chronic infection with hepatitis B and hepatitis C viruses are two of most common causes of liver cancer. However, there are non-viral factors that are associated with liver cancer development. Numerous population studies have revealed strong links between obesity and the development of liver cancer. Obesity can alter hepatic pathology, metabolism and promote inflammation, leading to nonalcoholic fatty liver disease (NAFLD) and the progression to the more severe form, non-alcoholic steatohepatitis (NASH). NASH is characterised by prominent steatosis and inflammation, and can lead to HCC. Here, we discuss the role of obesity in inflammation and the principal signalling mechanisms involved in HCC formation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer.

    PubMed

    Ryerson, A Blythe; Eheman, Christie R; Altekruse, Sean F; Ward, John W; Jemal, Ahmedin; Sherman, Recinda L; Henley, S Jane; Holtzman, Deborah; Lake, Andrew; Noone, Anne-Michelle; Anderson, Robert N; Ma, Jiemin; Ly, Kathleen N; Cronin, Kathleen A; Penberthy, Lynne; Kohler, Betsy A

    2016-05-01

    Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born

  6. Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.

    PubMed

    Cheng, Chiung-Chi; Chao, Wei-Ting; Liao, Chen-Chun; Tseng, Yu-Hui; Lai, Yen-Chang Clark; Lai, Yih-Shyong; Hsu, Yung-Hsiang; Liu, Yi-Hsiang

    2018-01-02

    Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib. Hepatoma cell lines PLC/PRF/5 and HepG2 were used to examine the level of plectin expression and cell migration in comparison with Chang liver cell line. In addition, sensitivity of the 3 cell lines to sorafenib treatment was also measured. Expression of plectin was lower in PLC/PRF/5 and HepG2 hepatoma cells than that of Chang liver cells whereas HepG2 and PLC/PRF/5 cells exhibit higher rate of cell migration in trans-well migration assay. Immunohistofluorecent staining on E-cadherin revealed the highest rate of collective cell migration in HepG2 cells and the lowest was found in Chang liver cells. Likewise, HepG2 cell line was most sensitive to sorafenib treatment and Chang liver cells exhibited the least sensitivity. The drug sensitivity to sorafenib treatment showed inverse correlation with the expression of plectin. We suggest that plectin deficiency and increased E-cadherin in hepatoma cells were associated with higher rates of cell motility, collective cell migration as well as higher drug sensitivity to sorafenib treatment.

  7. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  8. Liver immunology and herbal treatment

    PubMed Central

    Balaban, Yasemin H; Aka, Ceylan; Koca-Caliskan, Ufuk

    2017-01-01

    Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review. PMID:28660010

  9. The role of external beam radiotherapy in the treatment of hepatocellular cancer.

    PubMed

    Chino, Fumiko; Stephens, Sarah Jo; Choi, Steve S; Marin, Daniele; Kim, Charles Y; Morse, Michael A; Godfrey, Devon J; Czito, Brian G; Willett, Christopher G; Palta, Manisha

    2018-04-12

    Hepatocellular carcinoma (HCC) is increasing in incidence and mortality. Although the prognosis remains poor, long-term survival has improved from 3% in 1970 to an 18% 5-year survival rate today. This is likely because of the introduction of well tolerated, oral antiviral therapies for hepatitis C. Curative options for patients with HCC are often limited by underlying liver dysfunction/cirrhosis and medical comorbidities. Less than one-third of patients are candidates for surgery, which is the current gold standard for cure. Nonsurgical treatments include embolotherapies, percutaneous ablation, and ablative radiation. Technological advances in radiation delivery in the past several decades now allow for safe and effective ablative doses to the liver. Conformal techniques allow for both dose escalation to target volumes and normal tissue sparing. Multiple retrospective and prospective studies have demonstrated that hypofractionated image-guided radiation therapy, used as monotherapy or in combination with other liver-directed therapies, can provide excellent local control that is cost effective. Therefore, as the HCC treatment paradigm continues to evolve, ablative radiation treatment has moved from a palliative treatment to both a "bridge to transplant" and a definitive treatment. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  10. PDXliver: a database of liver cancer patient derived xenograft mouse models.

    PubMed

    He, Sheng; Hu, Bo; Li, Chao; Lin, Ping; Tang, Wei-Guo; Sun, Yun-Fan; Feng, Fang-You-Min; Guo, Wei; Li, Jia; Xu, Yang; Yao, Qian-Lan; Zhang, Xin; Qiu, Shuang-Jian; Zhou, Jian; Fan, Jia; Li, Yi-Xue; Li, Hong; Yang, Xin-Rong

    2018-05-09

    Liver cancer is the second leading cause of cancer-related deaths and characterized by heterogeneity and drug resistance. Patient-derived xenograft (PDX) models have been widely used in cancer research because they reproduce the characteristics of original tumors. However, the current studies of liver cancer PDX mice are scattered and the number of available PDX models are too small to represent the heterogeneity of liver cancer patients. To improve this situation and to complement available PDX models related resources, here we constructed a comprehensive database, PDXliver, to integrate and analyze liver cancer PDX models. Currently, PDXliver contains 116 PDX models from Chinese liver cancer patients, 51 of them were established by the in-house PDX platform and others were curated from the public literatures. These models are annotated with complete information, including clinical characteristics of patients, genome-wide expression profiles, germline variations, somatic mutations and copy number alterations. Analysis of expression subtypes and mutated genes show that PDXliver represents the diversity of human patients. Another feature of PDXliver is storing drug response data of PDX mice, which makes it possible to explore the association between molecular profiles and drug sensitivity. All data can be accessed via the Browse and Search pages. Additionally, two tools are provided to interactively visualize the omics data of selected PDXs or to compare two groups of PDXs. As far as we known, PDXliver is the first public database of liver cancer PDX models. We hope that this comprehensive resource will accelerate the utility of PDX models and facilitate liver cancer research. The PDXliver database is freely available online at: http://www.picb.ac.cn/PDXliver/.

  11. CD133+CD54+CD44+ circulating tumor cells as a biomarker of treatment selection and liver metastasis in patients with colorectal cancer

    PubMed Central

    Wang, Cun; Huang, Qiaorong; Meng, Wentong; Yu, Yongyang; Yang, Lie; Peng, Zhihai; Hu, Jiankun; Li, Yuan; Mo, Xianming; Zhou, Zongguang

    2016-01-01

    Introduction Liver is the most common site of distant metastasis in colorectal cancer (CRC). Early diagnosis and appropriate treatment selection decides overall prognosis of patients. However, current diagnostic measures were basically imaging but not functional. Circulating tumor cells (CTCs) known as hold the key to understand the biology of metastatic mechanism provide a novel and auxiliary diagnostic strategy for CRC with liver metastasis (CRC-LM). Results The expression of CD133+ and CD133+CD54+CD44+ cellular subpopulations were higher in the peripheral blood of CRC-LM patients when compared with those without metastasis (P<0.001). Multivariate analysis proved the association between the expression of CD133+CD44+CD54+ cellular subpopulation and the existence of CRC-LM (P<0.001). The combination of abdominal CT/MRI, CEA and the CD133+CD44+CD54+ cellular subpopulation showed increased detection and discrimination rate for liver metastasis, with a sensitivity of 88.2% and a specificity of 92.4%. Meanwhile, it also show accurate predictive value for liver metastasis (OR=2.898, 95% C.I.1.374–6.110). Materials and Method Flow cytometry and multivariate analysis was performed to detect the expression of cancer initiating cells the correlation between cellular subpopulations and liver metastasis in patients with CRC. The receiver operating characteristic curves combined with the area under the curve were generated to compare the predictive ability of the cellular subpopulation for liver metastasis with current CT and MRI images. Conclusions The identification, expression and application of CTC subpopulations will provide an ideal cellular predictive marker for CRC liver metastasis and a potential marker for further investigation. PMID:27764803

  12. Treatments for colorectal liver metastases: A new focus on a familiar concept.

    PubMed

    Zampino, M G; Magni, E; Ravenda, P S; Cella, C A; Bonomo, G; Della Vigna, P; Galdy, S; Spada, F; Varano, G M; Mauri, G; Fazio, N; Orsi, F

    2016-12-01

    A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is <30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Studying liver cancer metastasis by in vivo imaging and flow cytometer

    NASA Astrophysics Data System (ADS)

    Wang, Chen; Gu, Zhengqin; Guo, Jin; Li, Yan; Liu, Guangda; Wei, Xunbin

    2009-11-01

    Primary liver cancer (hepatocellular carcinoma, or HCC) is associated with liver cirrhosis 60-80% of the time. Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. About 80% of people with primary liver cancer are male. Although two-thirds of people have advanced liver disease when they seek medical help, one third of the patients have cancer that has not progressed beyond the liver. HCC may metastasize to the lung, bones, kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes are poor: the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of HCC cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern liver tumor cell spread through the microenvironment in vivo with real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess liver tumor cell spreading and the circulation kinetics of liver tumor cells. A real- time quantitative monitoring of circulating liver tumor cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  14. Hazardous air pollutants and primary liver cancer in Texas.

    PubMed

    Cicalese, Luca; Curcuru, Giuseppe; Montalbano, Mauro; Shirafkan, Ali; Georgiadis, Jeremias; Rastellini, Cristiana

    2017-01-01

    The incidence of hepatocellular carcinoma (HCC), the most common primary liver cancer, is increasing in the US and tripled during the past two decades. The reasons for such phenomenon remain poorly understood. Texas is among continental states with the highest incidence of liver cancer with an annual increment of 5.7%. Established risk factors for HCC include Hepatitis B and C (HBV, HCV) viral infection, alcohol, tobacco and suspected risk factors include obesity and diabetes. While distribution of these risk factors in the state of Texas is similar to the national data and homogeneous, the incidence of HCC in this state is exceptionally higher than the national average and appears to be dishomogeneous in various areas of the state suggesting that other non-recognized risk factors might play a role. No population-based studies are currently available investigating the effect of exposure to Hazardous Air Pollutants (HAPs) as a contributing risk factor for liver cancer. Incidence rate of liver cancer in Texas by counties for the time period between 2002 and 2012 was obtained from the Texas Cancer Registry (TCR). Through Principal Component Analysis (PCA) a subgroup of pollutants, explaining almost all the dataset variability, were identified and used to cluster Texas counties. The analysis generated 4 clusters showing liver cancer rate either higher or lower than national average in association with either high or low levels of HAPs emission in the environment. The study shows that the selected relevant HAPs, 10 among 253 analyzed, produce a significant correlation (P = 0.01-0.05) and some of these have been previously identified as carcinogens. An association between the increased production and consequent exposure to these HAPs and a higher presence of liver cancer in certain counties is suggested. This study provides a new insight on this complex multifactorial disease suggesting that environmental substances might play a role in the etiology of this cancer.

  15. Hepatic Resection for Liver Metastases from Cervical Cancer Is Safe and May Have Survival Benefit.

    PubMed

    Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona; Popescu, Irinel

    2016-06-01

    The goal of this study was to evaluate the single-centre experience with hepatectomy for liver metastases from cervical cancer (CCLM). Fifteen patients who underwent such surgery at the Fundeni Clinical Hospital between January 2002 and April 2014 were retrospectively reviewed. Liver lesions diagnosed at more than 6 months from cervical cancer diagnosis were classified as metachronous lesions, while lesions occurring within the first 6 months were considered synchronous lesions. Two patients were diagnosed with synchronous CCLM, while the other 13 patients had metachronous. Early postoperative death occurred in a single patient with metachronous liver metastases and pelvic recurrence, but this was not related to liver surgery. The median overall survival for the entire cohort was 18 months from the time of liver resection; patients with metachronous lesions had an improved outcome when compared to those with synchronous lesions. In patients with metachronous liver metastases, prognostic factors associated with an improved outcome were the general biological status of the patient, grade of tumoural differentiation and absence of other abdomino-pelvic recurrences. In multivariate analysis, only the grade of differentiation was statistically significant. In conclusion, hepatic resection for liver metastases from cervical cancer can be performed safely, may prove effective, and should be part of the multimodal treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. A review of epidemiological data on epilepsy, phenobarbital, and risk of liver cancer.

    PubMed

    La Vecchia, Carlo; Negri, Eva

    2014-01-01

    Phenobarbital is not genotoxic, but has been related to promotion of liver cancer (as well as inhibition) in rodents. In October 2012, we carried out a systematic literature search in the Medline database and searched reference lists of retrieved publications. We identified 15 relevant papers. Epidemiological data on epileptics/anticonvulsant use and liver cancer were retrieved from eight reports from seven cohort (record linkage) studies of epileptics, and data on phenobarbital use from a pharmacy-based record linkage investigation of patients treated with phenobarbital (three reports), plus a case-control study nested in one of the cohort studies and including information on phenobarbital use. Of the studies of cancer in epileptics, two showed no excess risk of liver cancer. A long-term (1933-1984) Danish cohort study of epileptics found relative risks (RRs) of 4.7 [95% confidence interval (CI) 3.2-6.8] of liver cancer and of 2.2 (95% CI 1.2-3.5) of biliary tract cancers. Such apparent excess risks could, however, be largely or completely attributed to thorotrast, a contrast medium used in the past in epileptic patients for cerebral angiography. A Finnish cohort study of epileptics obtained an RR of 1.7 (95% CI 1.2-2.4). Such an apparent excess risk, however, was not related to phenobarbital or to any specific anticonvulsant drug. The long-term follow-up of two UK cohorts found some excess risk of liver cancer among severe, but not among mild, epileptics. Some excess risk of liver cancer was also found in cohort studies of patients hospitalized for epilepsy in Sweden and Taiwan, in the absence, however, of association with any specific drugs. A UK General Practice database, comparing epileptics treated with valproate with unexposed ones, found a very low incidence of liver cancer. Of the studies of cancer in patients treated with phenobarbital, a large US pharmacy-based cohort investigation showed no excess risk of liver cancer. In a case-control study, nested in

  17. Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase.

    PubMed

    Song, Xinhua; Yin, Shutao; Zhang, Enxiang; Fan, Lihong; Ye, Min; Zhang, Yong; Hu, Hongbo

    2016-10-04

    Glycycoumarin (GCM) is a major bioactive coumarin compound isolated from licorice and the anti-cancer activity of GCM has not been scientifically addressed. In the present study, we have tested the anti-liver cancer activity of GCM using both in vitro and in vivo models and found for the first time that GCM possesses a potent activity against liver cancer evidenced by cell growth inhibition and apoptosis induction in vitro and tumor reduction in vivo. Mechanistically, GCM was able to bind to and inactivate oncogenic kinase T-LAK cell-originated protein kinase (TOPK), which in turn led to activation of p53 pathway. Our findings supported GCM as a novel active compound that contributed to the anti-cancer activity of licorice and TOPK could be an effective target for hepatocellular carcinoma (HCC) treatment.

  18. One shot of carbon-ion radiotherapy cured a 6-cm chemo-resistant metastatic liver tumor: a case of breast cancer.

    PubMed

    Harada, Mayumi; Karasawa, Kumiko; Yasuda, Shigeo; Kamada, Tadashi; Nemoto, Kenji

    2015-09-01

    The standard treatment for metastatic liver tumor from breast cancer is systemic medical treatment, and there is controversy regarding the value of local treatment. However, there are some exceptional cases that do benefit from local therapy. We describe the case of a 54-year-old woman with systemic therapy-resistant liver metastasis from breast cancer successfully treated with a single shot of 36-GyE carbon-ion radiotherapy and surviving more than 8 years without local recurrence. This case represents a good example of the usefulness and safety of carbon-ion radiotherapy, and who might benefit from local therapy.

  19. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model.

    PubMed

    Li, Qi; Ma, Zhuang; Liu, Yinhua; Kan, Xiaoxi; Wang, Changjun; Su, Bingnan; Li, Yuchen; Zhang, Yingmei; Wang, Pingzhang; Luo, Yang; Na, Daxiang; Wang, Lanlan; Zhang, Guoying; Zhu, Xiaoxin; Wang, Lu

    2016-08-01

    Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. In addition to its well-known cytotoxic effects, recent studies have shown that paclitaxel has tumor-supportive activities. Importantly, paclitaxel levels are not maintained at the effective concentration through one treatment cycle; rather, the concentration decreases during the cycle as a result of drug metabolism. Therefore, a comprehensive understanding of paclitaxel's effects requires insight into the dose-specific activities of paclitaxel and their influence on cancer cells and the host microenvironment. Here we report that a low dose of paclitaxel enhances metastasis of breast cancer cells to the liver in mouse models. We used microarray analysis to investigate gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel. We also investigated the effects of low doses of paclitaxel on cell migration, invasion and metastasis in vitro and in vivo. The results showed that low doses of paclitaxel promoted inflammation and initiated the epithelial-mesenchymal transition, which enhanced tumor cell migration and invasion in vitro. These effects could be reversed by inhibiting NF-κB. Furthermore, low doses of paclitaxel promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver. Collectively, these findings reveal the paradoxical and dose-dependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment. Gene expression microarray data are available in the GEO database under accession number GSE82048. © 2016 Federation of European Biochemical Societies.

  20. Liver Cancer Mortality and Food Consumption in Serbia, 1991-2010: An Ecological Study.

    PubMed

    Ilić, Milena; Radoman, Kristina; Konević, Slavica; Ilić, Irena

    2016-06-01

    This paper investigates the correlation between liver cancer mortality and consumption of food-groups in Serbia. We conducted an ecological study. The study comprised the population of the Republic of Serbia (about 7.5 million inhabitants) during the period 1991-2010. This ecological study included the data on food consumption per capita which were obtained by the Household Budget Survey and mortality data for liver cancer made available by the National Statistical Office. Linear trend model was used to assess a trend of age-adjusted liver cancer mortality rates (per 100,000 persons) that were calculated by the method of direct standardization using the World Standard Population. Pearson correlation was performed to examine the association between liver cancer mortality and per capita food consumption quantified with a correlation coefficient (r value). In Serbia, over the past two decades a significantly decreasing trend of liver cancer mortality rates has been observed (p<0.001). Liver cancer mortality was significantly (p<0.01) positively correlated with animal fat, beef, wine and spirits intake (r=0.713, 0.631, 0.632 and 0.745, respectively). A weakly positive correlation between milk consumption and mortality from liver cancer (r=0.559, p<0.05) was found only among women. The strongest correlation was found between spirits consumption and liver cancer mortality rates in women (r=0.851, p<0.01). A negative correlation between coffee consumption and age-adjusted liver cancer mortality rates was found (r=0.516, p<0.05) only for the eldest men (aged 65 years or older). Correlations between liver cancer and dietary habits were observed and further effort is needed in order to investigate a possible causative association, using epidemiological analytical studies. Copyright© by the National Institute of Public Health, Prague 2015.

  1. Parasite-Associated Cancers (Blood Flukes/Liver Flukes).

    PubMed

    Feng, Meng; Cheng, Xunjia

    2017-01-01

    Parasitic infection remains as a persistent public health problem and can be carcinogenic. Three helminth parasites, namely, Clonorchis sinensis (liver fluke) and Opisthorchis viverrini as well as Schistosoma haematobium (blood fluke), are classified as Group 1 carcinogens by the World Health Organization's International Agency for Research on Cancer (IARC Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis), World Health Organization, International Agency for Research on Cancer, 2011). Infection by these parasites is frequently asymptomatic and is thus rarely diagnosed at early exposure. Persistent infection can cause severe cancer complications. Until now, the cellular and molecular mechanisms linking fluke infections to cancer formation have yet to be defined, although many studies have focused on these mechanisms in recent years, and numerous findings were made in various aspects of parasite-associated cancers. Herein, we only introduce the fluke-induced cholangiocarcinoma (CCA) and bladder carcinoma and mainly focus on key findings in the last 5 years.

  2. Prevalence and risk factors of nonalcoholic fatty liver disease in breast cancer patients.

    PubMed

    Lee, Seokwon; Jung, Younglae; Bae, Youngtae; Yun, Sung Pil; Kim, Suk; Jo, Hongjae; Seo, Hyung-Il

    2017-03-24

    We aimed to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) in breast cancer patients using liver magnetic resonance imaging (MRI), and to investigate factors associated with NAFLD. We evaluated 104 patients surgically treated for breast cancer at our hospital between September and November 2013. None of the patients had any other causes of secondary hepatic fat accumulation (such as significant alcohol consumption, use of steatogenic medication or inborn disorders). Hepatic fat accumulation was measured using liver MRI perfomed in all patients before surgical treatment. Based on the fat signal percentage from liver MRIs, 19 of 104 breast cancer patients were diagnosed with NAFLD, so the prevalence of NAFLD was 18.3%. In univariate analysis, factors associated with NAFLD were older age, high body mass index, type 2 diabetes mellitus (DM), hypertension, elevated aspartate aminotransferase, elevated alanine aminotransferase and elevated triglycerides (TG). In multivariate analysis, factors associated with NAFLD were high body mass index (BMI) (odds ratio [OR] 1.403; 95% confidence interval [CI] 1.111-1.771; p = 0.005), type 2 DM (OR 11.872; 95% CI 1.065-132.373; p = 0.044), and an elevated TG level (OR 50.267; 95% CI 4.409-573.030; p = 0.002). The prevalence of NAFLD in breast cancer patients was not different from that of the general population. High BMI, type 2 DM and an elevated serum TG level were factors associated with NAFLD.

  3. Hepatic Stellate Cells Alter Liver Immune Environment to Promote Cancer | Center for Cancer Research

    Cancer.gov

    Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for up to 90 percent of cases, and is the second most common cause of cancer-related deaths worldwide according to the World Health Organization’s 2014 World Cancer Report. Even when caught early, HCC often recurs, either from intra-liver metastases or new primary tumors, and recurrence is the leading cause of death for patients with HCC. The liver microenvironment is an important contributor to HCC initiation and progression and also likely plays a role in tumor recurrence. Xin Wei Wang, Ph.D., of CCR’s Laboratory of Human Carcinogenesis, and his colleagues wondered whether activated hepatic stellate cells (A-HSCs), stromal cells in the liver known to participate in repair following injury and in the development of fibrosis, contribute directly to HCC recurrence.

  4. Spices for Prevention and Treatment of Cancers

    PubMed Central

    Zheng, Jie; Zhou, Yue; Li, Ya; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

    2016-01-01

    Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action. PMID:27529277

  5. Spices for Prevention and Treatment of Cancers.

    PubMed

    Zheng, Jie; Zhou, Yue; Li, Ya; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

    2016-08-12

    Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action.

  6. Annual Report to the Nation on the Status of Cancer, 1975–2012, Featuring the Increasing Incidence of Liver Cancer

    PubMed Central

    Ryerson, A. Blythe; Eheman, Christie R.; Altekruse, Sean F.; Ward, John W.; Jemal, Ahmedin; Sherman, Recinda L.; Henley, S. Jane; Holtzman, Deborah; Lake, Andrew; Noone, Anne-Michelle; Anderson, Robert N.; Ma, Jiemin; Ly, Kathleen N.; Cronin, Kathleen A.; Penberthy, Lynne; Kohler, Betsy A.

    2016-01-01

    BACKGROUND Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. METHODS Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC’s National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992–2012 and mortality for 1975–2012) and short-term trends (2008–2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. RESULTS Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence

  7. Liver and Bile Duct Cancer—Health Professional Version

    Cancer.gov

    Liver cancer includes two major types: hepatocellular carcinoma (HCC) and intrahepatic bile duct cancer, also known as cholangiocarcinoma. Find evidence-based information on liver and bile duct cancer treatment, causes and prevention, screening, research, genomics and statistics.

  8. Predictive Models of Liver Cancer

    EPA Science Inventory

    Predictive models of chemical-induced liver cancer face the challenge of bridging causative molecular mechanisms to adverse clinical outcomes. The latent sequence of intervening events from chemical insult to toxicity are poorly understood because they span multiple levels of bio...

  9. STAT3 activation in monocytes accelerates liver cancer progression.

    PubMed

    Wu, Wen-Yong; Li, Jun; Wu, Zheng-Sheng; Zhang, Chang-Le; Meng, Xiang-Ling

    2011-12-05

    Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor ubiquitously expressed in different cell types. STAT3 plays an essential role in cell survival, proliferation, and differentiation. Aberrantly hyper-activated STAT3 signaling in cancer cells and in the tumor microenvironment has been detected in a wide variety of human cancers and is considered an important factor for cancer initiation, development, and progression. However, the role of STAT3 activation in monocytes in the development of HCC has not been well understood. Immunohistochemical analysis of phosphorylated STAT3 was performed on tissue microarray from HCC patients. Using a co-culture system in vivo, HCC cell growth was determined by the MTT assay. In vivo experiments were conducted with mice given diethylinitrosamine (DEN), which induces HCC was used to investigate the role of STAT3 expression in monocytes on tumor growth. Real-time PCR was used to determine the expression of cell proliferation and cell arrest associated genes in the tumor and nontumor tissue from liver. Phosphorylated STAT3 was found in human hepatocellular carcinoma tissue samples and was expressed in tumor cells and also in monocytes. Phosphorylated STAT3 expression in monocyte was significantly correlated to advanced clinical stage of HCC and a poor prognosis. Using a co-culture system in vivo, monocytes promoted HCC cell growth via the IL-6/STAT3 signaling pathway. The STAT3 inhibitor, NSC 74859, significantly suppressed tumor growth in vivo in mice with diethylinitrosamine (DEN)-induced HCC. In this animal model, blockade of STAT3 with NSC 74859 induced tumor cell apoptosis, while inhibiting both tumor cells and monocytes proliferation. Furthermore, NSC 74859 treatment suppressed cancer associated inflammation in DEN-induce HCC. Our data suggest constitutively activated STAT3 monocytes promote liver tumorigenesis in clinical patients and animal experiments. Thus, STAT3 in tumor

  10. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors.

    PubMed

    De Martin, Eleonora; Michot, Jean-Marie; Papouin, Barbara; Champiat, Stéphane; Mateus, Christine; Lambotte, Olivier; Roche, Bruno; Antonini, Teresa Maria; Coilly, Audrey; Laghouati, Salim; Robert, Caroline; Marabelle, Aurélien; Guettier, Catherine; Samuel, Didier

    2018-06-01

    severity of liver injury is helpful for tailoring patient management, which does not require systematic corticosteroid administration. Immunotherapy for metastatic cancer can be complicated by immune-related adverse events in the liver. In patients receiving immunotherapy for metastatic cancer who develop immune-mediated hepatitis, liver biopsy is helpful for the diagnosis and evaluation of the severity of liver injury. This study demonstrates the need for patient-oriented management, which could eventually avoid unnecessary systemic corticosteroid treatment. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  11. Shizukaol D, a Dimeric Sesquiterpene Isolated from Chloranthus serratus, Represses the Growth of Human Liver Cancer Cells by Modulating Wnt Signalling Pathway.

    PubMed

    Tang, Lisha; Zhu, Hengrui; Yang, Xianmei; Xie, Fang; Peng, Jingtao; Jiang, Deke; Xie, Jun; Qi, Meiyan; Yu, Long

    2016-01-01

    Natural products have become sources of developing new drugs for the treatment of cancer. To seek candidate compounds that inhibit the growth of liver cancer, components of Chloranthus serratus were tested. Here, we report that shizukaol D, a dimeric sesquiterpene from Chloranthus serratus, exerted a growth inhibition effect on liver cancer cells in a dose- and time-dependent manner. We demonstrated that shizukaol D induced cells to undergo apoptosis. More importantly, shizukaol D attenuated Wnt signalling and reduced the expression of endogenous Wnt target genes, which resulted in decreased expression of β-catenin. Collectively, this study demonstrated that shizukaol D inhibited the growth of liver cancer cells by modulating Wnt pathway.

  12. The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis

    PubMed Central

    Goddard, Erica T.; Hill, Ryan C.; Nemkov, Travis; D’Alessandro, Angelo; Hansen, Kirk C.; Maller, Ori; Mongoue-Tchokote, Solange; Mori, Motomi; Partridge, Ann H.; Borges, Virginia F.; Schedin, Pepper

    2017-01-01

    Postpartum breast cancer patients are at increased risk for metastasis compared to age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the post-lactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, ECM remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent with weaning-induced liver involution and establishment of a pro-metastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning Balb/c mice compared to nulliparous controls. Human relevance is suggested by a ~3-fold increase in liver metastasis in postpartum breast cancer patients (n=564) and by liver-specific tropism (n=117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer. PMID:27974414

  13. Using Nanoparticles in Medicine for Liver Cancer Imaging.

    PubMed

    Moghadam, Farideh Farokhi

    2017-07-01

    One of the most important types of liver cancer is hepatocellular carcinoma (HCC). HCC is the fifth most common cancer, and its correct diagnosis is very important. For the quick diagnosis of HCC, the use of nanoparticles is helpful. The major applications of nanoparticles are in medicine for organ imaging. Two methods of liver imaging are X-ray computed tomography (CT) and magnetic resonance imaging (MRI). In this review, we attempt to summarize some of the contrast agents used in imaging such as superparamagnetic iron oxide nanoparticles (SPIONs) and iron oxide nanoparticles (IONPs), various types of enhanced MRI for the liver, and nanoparticles like gold (AuNPs), which is used to develop novel CT imaging agents.

  14. Profiling for primary-care presentation, investigation and referral for liver cancers: evidence from a national audit.

    PubMed

    Hughes, Daniel L; Neal, Richard D; Lyratzopoulos, Georgios; Rubin, Greg

    2016-04-01

    The incidence of liver cancer across Europe is increasing. There is a lack of evidence within the current literature on the identification and investigation of liver cancer within primary care. We aimed to profile liver cancer recognition and assessment as well as the timeliness of liver cancer diagnosis from within the primary-care setting in the UK. Data were obtained from the National Audit of Cancer Diagnosis in Primary Care 2009-2010 and analysed. We calculated the patient interval, the primary-care interval and the number of prereferral consultations for liver cancer. We then compared these data with prior data on the respective indicators for other common cancers. The median patient interval was 9 days (interquartile range 0-31 days), and the median primary-care interval for liver cancer was 11 days (interquartile range 0-40 days). Of the 90 patients, 21 (23.3%) had three or more consultations with their general practitioner before specialist referral. For the three metrics (patient interval, primary-care interval and number of prereferral consultations), liver cancer has average or longer intervals when compared with other cancers. The most common symptomatic presentation of liver cancer within the primary-care setting was right upper quadrant pain (11%), followed by decompensated liver failure (9%). Of the patients, 12% were diagnosed with liver cancer on the basis of an incidental finding of an abnormal liver function test. This study provides a detailed and thorough overview of the recognition of liver cancer and the promptness of liver cancer identification in an English context, and should inform strategies for improving the timeliness of diagnosis.

  15. Claudin-2 Promotes Breast Cancer Liver Metastasis by Facilitating Tumor Cell Interactions with Hepatocytes

    PubMed Central

    Tabariès, Sébastien; Dupuy, Fanny; Dong, Zhifeng; Monast, Anie; Annis, Matthew G.; Spicer, Jonathan; Ferri, Lorenzo E.; Omeroglu, Atilla; Basik, Mark; Amir, Eitan; Clemons, Mark

    2012-01-01

    We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to levels in their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, the reduction of the claudin-2 expression level, either in cancer cells or in primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell-hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes. PMID:22645303

  16. Cytoreduction of diaphragmatic metastasis from ovarian cancer with involvement of the liver using a ventral liver mobilization technique.

    PubMed

    Kato, Kazuyoshi; Katsuda, Takahiro; Takeshima, Nobuhiro

    2016-03-01

    Upper abdominal spreading of advanced-stage ovarian cancer often involves the diaphragm. In addition, bulky diaphragmatic tumors occasionally infiltrate the liver. Here, we describe our early experiences with a ventral liver mobilization technique to remove diaphragmatic tumors with liver involvement. Two patients with primary ovarian cancer and 1 patient with recurrent ovarian cancer underwent en bloc resections of a diaphragmatic tumor together with the full-thickness diaphragm and the liver tissue using a ventral liver mobilization technique. The surgical technique involved a full-thickness division of the diaphragm at the central tendon and a ventral mobilization of the right lobe of the liver, with entry into the pleural cavity. During the parenchymal transection of the liver, the posterior area of the right lobe of the liver was pressed using the surgeon's hand to reduce bleeding from the resection surface. After the completion of the en bloc resection, the diaphragmatic opening was closed using running sutures. All the diaphragmatic tumors were completely removed without severe bleeding in the current series. No intraoperative or postoperative complications occurred. Diaphragmatic tumors with involvement of the liver can be safely and effectively removed using a ventral liver mobilization technique. This surgical procedure may be suitable for the management of bulky diaphragmatic tumors in select patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Liver and gallbladder cancer in immigrants to Sweden.

    PubMed

    Hemminki, Kari; Mousavi, Seyed Mohsen; Brandt, Andreas; Ji, Jianguang; Sundquist, Jan

    2010-03-01

    The changes of cancer incidence upon immigration can be used as an estimator of environmental influence on cancer risk. We studied site-specific liver and biliary cancers in first-generation immigrants to Sweden with an aim to search for aetiological clues and to find evidence for indigenous incidence rates. We used the nation-wide Swedish Family-Cancer Database to calculate standardised incidence ratios (SIRs) in immigrants compared to native Swedes. A total of 1428 cancers were identified in immigrants whose median ages (years) at immigration were 27 for men and 26 for women and whose median diagnostic ages were 64 and 66, respectively. The highest SIRs of 6.7 for primary liver cancer were observed for men from East Asia and sub-Saharan Africa. Increased SIRs were recorded for male immigrants from previous Yugoslavia (1.78), Southern Europe (2.91), Turkey (2.15) and Asian Arab countries (2.89). For gallbladder cancer, only women from the Indian subcontinent (3.84) and Chile (2.34) had increased risk while some Northern European immigrants showed decreased risks. Primary liver cancer was increased in immigrants from endemic regions of hepatitis B virus infection but also from large regions lacking cancer incidence data, North Africa, Asian Arab countries, Turkey and previous Yugoslavia; these are probably intermediary risk regions for this infection. The consideration of these regions as risk areas would justify active diagnostic and vaccination programs. The increase in gallbladder cancer in Chileans and Indians suggests that some persistent damage was inflicted before emigration, characterisation of which will be a challenge for aetiological studies. Copyright 2009 Elsevier Ltd. All rights reserved.

  18. A primary tumor of mixed histological type is a novel poor prognostic factor for patients undergoing resection of liver metastasis from gastric cancer.

    PubMed

    Ikari, Naoki; Taniguchi, Kiyoaki; Serizawa, Akiko; Yamada, Takuji; Yamamoto, Masakazu; Furukawa, Toru

    2017-05-01

    Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer. We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014. The median overall survival of the patients was 28 months. The 5-year survival rate was 33.9%. Primary tumors of a mixed histological type, and residual tumors during the course of treatment were identified as significant independent poor prognostic factors. Histological evaluation of primary tumors may aid to identify patients suitable for undergoing surgical resection of liver metastasis from gastric cancer. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  19. Neoadjuvant chemotherapy does not impair liver regeneration following hepatectomy or portal vein embolization for colorectal cancer liver metastases.

    PubMed

    Simoneau, Eve; Alanazi, Reema; Alshenaifi, Jumanah; Molla, Nouran; Aljiffry, Murad; Medkhali, Ahmad; Boucher, Louis-Martin; Asselah, Jamil; Metrakos, Peter; Hassanain, Mazen

    2016-03-01

    Treatment strategies for colorectal cancer liver metastasis (CRCLM) such as major hepatectomy and portal vein embolization (PVE) rely on liver regeneration. We aim to investigate the effect of neoadjuvant chemotherapy on liver regeneration occurring after PVE and after major hepatectomy. CRCLM patients undergoing PVE or major resection were identified retrospectively from our database. Liver regeneration data (expressed as future liver remnant [FLR] and percentage of liver regeneration [%LR]), total liver volume (TLV) and clinical characteristics were collected. Between 2003 and 2013, 226 patients were included (85 major resection, 141 PVE). The median chemotherapy cycles was six in both groups. The median time interval between the last chemotherapy and the intervention was 51 days in the PVE group and 79 days in the hepatectomy group. In the PVE group, chemotherapy was not associated with altered liver regeneration (number of cycles [P = 0.435], timing [P = 0.563], or chemotherapy agent [P = 0.116]). Similarly in the major hepatectomy group, preoperative chemotherapy (number of cycles [P = 0.114]; agent [P = 0.061], timing [P = 0.126]) were not significantly associated with differences in liver regeneration (P = 0.592). In both groups, the predicted FLR% was inversely correlated with the %LR (P < 0.001). Chemotherapy does not affect liver regeneration following PVE or major resection. J. Surg. Oncol. 2016;113:449-455. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines.

    PubMed

    Berardocco, Martina; Radeghieri, Annalisa; Busatto, Sara; Gallorini, Marialucia; Raggi, Chiara; Gissi, Clarissa; D'Agnano, Igea; Bergese, Paolo; Felsani, Armando; Berardi, Anna C

    2017-10-10

    Liver cancer (LC) is one of the most common cancers and represents the third highest cause of cancer-related deaths worldwide. Extracellular vesicle (EVs) cargoes, which are selectively enriched in RNA, offer great promise for the diagnosis, prognosis and treatment of LC. Our study analyzed the RNA cargoes of EVs derived from 4 liver-cancer cell lines: HuH7, Hep3B, HepG2 (hepato-cellular carcinoma) and HuH6 (hepatoblastoma), generating two different sets of sequencing libraries for each. One library was size-selected for small RNAs and the other targeted the whole transcriptome. Here are reported genome wide data of the expression level of coding and non-coding transcripts, microRNAs, isomiRs and snoRNAs providing the first comprehensive overview of the extracellular-vesicle RNA cargo released from LC cell lines. The EV-RNA expression profiles of the four liver cancer cell lines share a similar background, but cell-specific features clearly emerge showing the marked heterogeneity of the EV-cargo among the individual cell lines, evident both for the coding and non-coding RNA species.

  1. Immunotoxin Targeting Glypican-3 Effective against Liver Tumors | Center for Cancer Research

    Cancer.gov

    Worldwide, liver cancer is the fifth most common malignancy, and hepatocellular carcinoma (HCC) makes up about two-thirds of those cases. Unfortunately, surgery is still the most effective treatment for HCC but is only available to patients diagnosed at early stages. HCC is known for being particularly drug resistant, sorafenib being the only FDA-approved chemotherapy

  2. Arsenic levels in drinking water and mortality of liver cancer in Taiwan.

    PubMed

    Lin, Hung-Jung; Sung, Tzu-I; Chen, Chi-Yi; Guo, How-Ran

    2013-11-15

    The carcinogenic effect of arsenic is well documented, but epidemiologic data on liver cancer were limited. To evaluate the dose-response relationship between arsenic in drinking water and mortality of liver cancer, we conducted a study in 138 villages in the southwest coast area of Taiwan. We assessed arsenic levels in drinking water using data from a survey conducted by the government and reviewed death certificates from 1971 to 1990 to identify liver cancer cases. Using village as the unit, we conducted multi-variate regression analyses and then performed post hoc analyses to validate the findings. During the 20-year period, 802 male and 301 female mortality cases of liver cancer were identified. After adjusting for age, arsenic levels above 0.64 mg/L were associated with an increase in the liver cancer mortality in both genders, but no significant effect was observed for lower exposure categories. Post hoc analyses and a review of literature supported these findings. We concluded that exposures to high arsenic levels in drinking water are associated with the occurrence of liver cancer, but such an effect is not prominent at exposure levels lower than 0.64 mg/L. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Liver Contrast-Enhanced Ultrasound Improves Detection of Liver Metastases in Patients with Pancreatic or Periampullary Cancer.

    PubMed

    Taimr, Pavel; Jongerius, Vivian L; Pek, Chulja J; Krak, Nanda C; Hansen, Bettina E; Janssen, Harry L A; Metselaar, Herold J; van Eijck, Casper H J

    2015-12-01

    The aim of this study is to provide a diagnostic performance evaluation of contrast-enhanced ultrasonography (CEUS) in detecting liver metastases in patients with suspected of pancreatic or periampullary cancer. Computed tomography (CT) is often insufficient for detection of liver metastases, but their presence plays a crucial role in the choice of therapy. Eighty-nine patients with suspected pancreatic or periampullary cancer were included in this prospective study with retrospective analysis. Patients underwent an abdominal CT and CEUS. Fifteen patients had liver metastases. The CT sensitivity was 73.3% (11/15), the specificity 93.2% (69/74), the positive predictive value (PPV) 68.8% (11/16) and the negative predictive value (NPV) 94.6% (69/73). Based on CEUS, the sensitivity was 80% (12/15), specificity 98.6% (73/74), PPV 92.3% (12/13) and NPV 96.1% (73/76). CEUS improved characterization of liver lesions in patients with suspected pancreatic or periampullary cancer compared with CT. CEUS can better detect benign liver lesions and distinguish false-positive or indeterminate CT results. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  4. Identification of copy number variation-driven genes for liver cancer via bioinformatics analysis.

    PubMed

    Lu, Xiaojie; Ye, Kun; Zou, Kailin; Chen, Jinlian

    2014-11-01

    To screen out copy number variation (CNV)-driven differentially expressed genes (DEGs) in liver cancer and advance our understanding of the pathogenesis, an integrated analysis of liver cancer-related CNV data from The Cancer Genome Atlas (TCGA) and gene expression data from EBI Array Express database were performed. The DEGs were identified by package limma based on the cut-off of |log2 (fold-change)|>0.585 and adjusted p-value<0.05. Using hg19 annotation information provided by UCSC, liver cancer-related CNVs were then screened out. TF-target gene interactions were also predicted with information from UCSC using DAVID online tools. As a result, 25 CNV-driven genes were obtained, including tripartite motif containing 28 (TRIM28) and RanBP-type and C3HC4-type zinc finger containing 1 (RBCK1). In the transcriptional regulatory network, 8 known cancer-related transcription factors (TFs) interacted with 21 CNV-driven genes, suggesting that the other 8 TFs may be involved in liver cancer. These genes may be potential biomarkers for early detection and prevention of liver cancer. These findings may improve our knowledge of the pathogenesis of liver cancer. Nevertheless, further experiments are still needed to confirm our findings.

  5. Alcohol, nutrition and liver cancer: Role of Toll-like receptor signaling

    PubMed Central

    French, Samuel W; Oliva, Joan; French, Barbara A; Li, Jun; Bardag-Gorce, Fawzia

    2010-01-01

    This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (TLR) signaling as the mechanism of liver stem cell/progenitor transformation to HCC. Two exemplary models of this phenomenon are reviewed in detail. One model applies chronic ethanol/lipopolysaccharide feeding to the activated TLR4 signaling pathway. The other applies chronic feeding of a carcinogenic drug, in which TLR2 and 4 signaling pathways are activated. In the drug-induced model, two major methyl donors, S-adenosylmethionine and betaine, prevent the upregulation of the TLR signaling pathways and abrogate the stem cell/progenitor proliferation response when fed with the carcinogenic drug. This observation supports a nutritional approach to liver cancer prevention and treatment. The observation that upregulation of the TLR signaling pathways leads to liver tumor formation gives evidence to the popular concept that the chronic pro-inflammatory response is an important mechanism of liver oncogenesis. It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases. PMID:20238401

  6. MicroRNAs and liver cancer associated with iron overload: Therapeutic targets unravelled

    PubMed Central

    Greene, Catherine M; Varley, Robert B; Lawless, Matthew W

    2013-01-01

    Primary liver cancer is a global disease that is on the increase. Hepatocellular carcinoma (HCC) accounts for most primary liver cancers and has a notably low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs/miRs) are regulatory RNAs that modulate protein synthesis. miRNAs are involved in several biological and pathological processes including the development and progression of HCC. Given the poor outcomes with current HCC treatments, miRNAs represent an important new target for therapeutic intervention. Several studies have demonstrated their role in HCC development and progression. While many risk factors underlie the development of HCC, one process commonly altered is iron homeostasis. Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised. Aberrant miRNA expression in hepatic fibrosis and injury response have been reported, as have dysregulated miRNA expression patterns affecting cell cycle progression, evasion of apoptosis, invasion and metastasis. In 2009, miR-26a delivery was shown to prevent HCC progression, highlighting its therapeutic potential. Several studies have since investigated the clinical potential of other miRNAs with one drug, Miravirsen, currently in phase II clinical trials. miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes. PMID:23983424

  7. The Impact of a Hepatobiliary Multidisciplinary Team Assessment in Patients with Colorectal Cancer Liver Metastases: A Population-Based Study.

    PubMed

    Engstrand, Jennie; Kartalis, Nikolaos; Strömberg, Cecilia; Broberg, Mats; Stillström, Anna; Lekberg, Tobias; Jonas, Eduard; Freedman, Jacob; Nilsson, Henrik

    2017-09-01

    Assessing patients with colorectal cancer liver metastases (CRCLM) by a liver multidisciplinary team (MDT) results in higher resection rates and improved survival. The aim of this study was to evaluate the potentially improved resection rate in a defined cohort if all patients with CRCLM were evaluated by a liver MDT. A retrospective analysis of patients diagnosed with colorectal cancer during 2008 in the greater Stockholm region was conducted. All patients with liver metastases (LM), detected during 5-year follow-up, were re-evaluated at a fictive liver MDT in which previous imaging studies, tumor characteristics, medical history, and patients' own treatment preferences were presented. Treatment decisions for each patient were compared to the original management. Odds ratios (ORs) and 95% confidence intervals were estimated for factors associated with referral to the liver MDT. Of 272 patients diagnosed with LM, 102 patients were discussed at an original liver MDT and 69 patients were eventually resected. At the fictive liver MDT, a further 22 patients were considered as resectable/potentially resectable, none previously assessed by a hepatobiliary surgeon. Factors influencing referral to liver MDT were age (OR 3.12, 1.72-5.65), American Society of Anaesthesiologists (ASA) score (OR 0.34, 0.18-0.63; ASA 2 vs. ASA 3), and number of LM (OR 0.10, 0.04-0.22; 1-5 LM vs. >10 LM), while gender ( p  = .194) and treatment at a teaching hospital ( p  = .838) were not. A meaningful number of patients with liver metastases are not managed according to best available evidence and the potential for higher resection rates is substantial. Patients with liver metastatic colorectal cancer who are assessed at a hepatobiliary multidisciplinary meeting achieve higher resection rates and improved survival. Unfortunately, patients who may benefit from resection are not always properly referred. In this study, the potential improved resection rate was assessed by re

  8. [A Long-Term Disease-Free Survival Case of Synchronous Pulmonary and Liver Metastasis of Rectal Cancer with Systemic Chemotherapy and Radiofrequency Ablation Therapy for Liver Metastasis].

    PubMed

    Enomoto, Masaya; Katsumata, Kenji; Kasahara, Kenta; Kuwabara, Hiroshi; Matsudo, Takaaki; Shigoka, Masatoshi; Enomoto, Masanobu; Ishizaki, Tetsuo; Tsuchida, Akihiko

    2017-11-01

    A 55-year-old woman underwent laparoscopic anterior resection and D2 lymph node dissection for recto-sigmoid colon cancer in November 2014, which was diagnosed as T3N1M1(H3, PUL2), stage IV , for the purpose of preserving the ileus. FOLFOX therapy with panitumumab(Pmab)was started in January 2015.A t the end of 11 courses, pulmonary metastasis changed to CR, and liver metastasis was down-graded to H2 on the CT.Because of the risk of hepatic dysfunction with advanced fatty liver due to chemotherapy and extrahepatic lesions, we chose radiofrequency ablation(RFA)therapy for liver metastasis.Pmab combined FOLFIRI therapy was administered, and maintenance therapy was initiated.This patient is alive 2 years and 7 months after surgery and 10 months after RFA without relapse.It is suggested that RFA therapy for liver metastasis of colon cancer with pulmonary metastasis combined with chemotherapy could be an effective treatment strategy.

  9. Retrospective review of efficacy of radiofrequency ablation for treatment of colorectal cancer liver metastases from a Canadian perspective.

    PubMed

    Kwan, Benjamin Y M; Kielar, Ania Z; El-Maraghi, Robert H; Garcia, Lourdes M

    2014-02-01

    A retrospective single-center review of ultrasound-guided radiofrequency ablation (RFA) treatment of colorectal cancer liver metastases was performed. This study reviews the primary and secondary technical effectiveness, overall survival of patients, recurrence-free survival, tumour-free survival, rates of local recurrence, and postprocedural RFA complications. Technical effectiveness and rates of complication with respect to tumour location and size were evaluated. Our results were compared with similar studies from Europe and North America. A total of 63 patients (109 tumours) treated with RFA between February 2004 and December 2009 were reviewed. Average and median follow-up time was 19.4 and 16.5 months, respectively (range, 1-54 months). Data from patient charts, pathology, and Picture Archiving and Communication System was integrated into an Excel database. Statistical Analysis Software was used for statistical analysis. Primary and secondary technical effectiveness of percutaneous and intraoperative RFA were 90.8% and 92.7%, respectively. Average (SE) tumour-free survival was 14.4 ± 1.4 months (range, 1-43 months), and average (SE) recurrence-free survival was 33.5 ± 2.3 months (range, 2-50 months). Local recurrence was seen in 31.2% of treated tumours (range, 2-50 months) (34/109). Overall survival was 89.4% at 1 year, 70.0% at 2 years, and 38.1% at 3 years, with an average (SE) overall survival of 37.0 ± 2.8 months. There were 14 postprocedural complications. There was no statistically significant difference in technical effectiveness for small tumours (1-2 cm) vs intermediate ones (3-5 cm). There was no difference in technical effectiveness for peripheral vs parenchymal tumours. This study demonstrated good-quality outcomes for RFA treatment of colorectal cancer liver metastases from a Canadian perspective and compared favorably with published studies. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights

  10. Prioritizing Popular Proteins in Liver Cancer: Remodelling One-Carbon Metabolism.

    PubMed

    Mora, María Isabel; Molina, Manuela; Odriozola, Leticia; Elortza, Félix; Mato, José María; Sitek, Barbara; Zhang, Pumin; He, Fuchu; Latasa, María Uxue; Ávila, Matías Antonio; Corrales, Fernando José

    2017-12-01

    Primary liver cancer (HCC) is recognized as the fifth most common neoplasm and the second leading cause of cancer death worldwide. Most risk factors are known, and the molecular pathogenesis has been widely studied in the past decade; however, the underlying molecular mechanisms remain to be unveiled, as they will facilitate the definition of novel biomarkers and clinical targets for more effective patient management. We utilize the B/D-HPP popular protein strategy. We report a list of popular proteins that have been highly cocited with the expression "liver cancer". Several enzymes highlight the known metabolic remodeling of liver cancer cells, four of which participate in one-carbon metabolism. This pathway is central to the maintenance of differentiated hepatocytes, as it is considered the connection between intermediate metabolism and epigenetic regulation. We designed a targeted selective reaction monitoring (SRM) method to follow up one-carbon metabolism adaptation in mouse HCC and in regenerating liver following exposure to CCl 4 . This method allows systematic monitoring of one-carbon metabolism and could prove useful in the follow-up of HCC and of chronically liver-diseased patients (cirrhosis) at risk of HCC. The SRM data are available via ProteomeXchange in PASSEL (PASS01060).

  11. A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

    PubMed Central

    Goddard, Erica T.; Fischer, Jacob; Schedin, Pepper

    2016-01-01

    Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas. PMID:28060292

  12. A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer.

    PubMed

    Goddard, Erica T; Fischer, Jacob; Schedin, Pepper

    2016-12-26

    Breast cancer is the leading cause of cancer-related mortality in women worldwide. Liver metastasis is involved in upwards of 30% of cases with breast cancer metastasis, and results in poor outcomes with median survival rates of only 4.8 - 15 months. Current rodent models of breast cancer metastasis, including primary tumor cell xenograft and spontaneous tumor models, rarely metastasize to the liver. Intracardiac and intrasplenic injection models do result in liver metastases, however these models can be confounded by concomitant secondary-site metastasis, or by compromised immunity due to removal of the spleen to avoid tumor growth at the injection site. To address the need for improved liver metastasis models, a murine portal vein injection method that delivers tumor cells firstly and directly to the liver was developed. This model delivers tumor cells to the liver without complications of concurrent metastases in other organs or removal of the spleen. The optimized portal vein protocol employs small injection volumes of 5 - 10 μl, ≥ 32 gauge needles, and hemostatic gauze at the injection site to control for blood loss. The portal vein injection approach in Balb/c female mice using three syngeneic mammary tumor lines of varying metastatic potential was tested; high-metastatic 4T1 cells, moderate-metastatic D2A1 cells, and low-metastatic D2.OR cells. Concentrations of ≤ 10,000 cells/injection results in a latency of ~ 20 - 40 days for development of liver metastases with the higher metastatic 4T1 and D2A1 lines, and > 55 days for the less aggressive D2.OR line. This model represents an important tool to study breast cancer metastasis to the liver, and may be applicable to other cancers that frequently metastasize to the liver including colorectal and pancreatic adenocarcinomas.

  13. Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma.

    PubMed

    Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek; Murawa, Dawid

    2016-01-01

    Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved - without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM.

  14. Incidence and Risk Factors for Liver Abscess After Thermal Ablation of Liver Neoplasm

    PubMed Central

    Su, Xiu-Feng; Li, Na; Chen, Xu-Fang; Zhang, Lei; Yan, Ming

    2016-01-01

    Background Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most frequently used thermal ablation methods for the treatment of liver cancer. Liver abscess is a common and severe complication of thermal ablation treatment. Objectives The objective of this study was to determine the incidence and risk factors of liver abscess formation after thermal ablation of liver cancer. Materials and Methods The clinical data of 423 patients who underwent 691 thermal ablation procedures for liver cancer were collected in order to retrospectively analyze the basic characteristics, incidence, and risk factors associated with liver abscess formation. Patients with multiple risk factors for liver abscess formation were enrolled in a risk factor group, and patients with no risk factors were enrolled in a control group. The chi-square test and multiple logistic regression analysis were used to analyze the relationship between the occurrence of liver abscesses and potential risk factors. Results Two hundred and eight patients underwent 385 RFA procedures, and 185 patients underwent 306 MWA procedures. The total incidence of liver abscesses was 1.7%, while the rates in the RFA group (1.8%) and MWA groups (1.6%) were similar (P > 0.05). The rates of liver abscesses in patients who had child-pugh class B and class C cirrhosis (P = 0.0486), biliary tract disease (P = 0.0305), diabetes mellitus (P = 0.0344), and porta hepatis tumors (P = 0.0123) were 4.0%, 6.7%, 6.5%, and 13.0%, respectively. There was a statistically significant difference between these four groups and the control group (all P < 0.05). The incidence of liver abscesses in the combined ablation and percutaneous ethanol injection (PEI) group (P = 0.0026) was significantly lower than that of the ablation group (P < 0.05). Conclusions The incidence of liver abscesses after liver cancer thermal ablation is low. Child-Pugh Class B and Class C cirrhosis, biliary tract disease, diabetes mellitus, and porta hepatis

  15. Hepatic artery infusion therapy is effective for chemotherapy-resistant liver metastatic colorectal cancer.

    PubMed

    Goi, Takanori; Naruse, Takayuki; Kimura, Youhei; Fujimoto, Daisuke; Morikawa, Mitsuhiro; Koneri, Kenji; Yamaguchi, Akio

    2015-10-09

    Systemic FOLFOX (folinic acid (leucovorin (LV)), 5-fluorouracil (5-FU), and oxaliplatin), FOLFIRI (LV, 5-FU, and irinotecan), or FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) chemotherapy regimens and additional molecular-target treatments, including anti-vascular endothelial growth factor, anti-epidermal growth factor receptor, and anti-multi-kinase antibodies, have been recommended for unresectable recurrent colorectal cancers. However, no effective treatments are currently available for cases refractory to these therapies. Therefore, the development of alternative therapies is desired. In the present study, we administered and observed the effectiveness of hepatic artery infusion therapy (HAIC) in patients with unresectable liver metastatic colorectal cancers refractory to systemic chemotherapy. In addition, we observed that in an experimental system with anticancer drug-resistant colorectal cancer lines, apoptosis and cell death could be induced by increasing anticancer drug concentrations. The subjects had liver metastatic colorectal cancers that were unresponsive to systemic chemotherapy (FOLFOX/FOLFIRI) or to additional molecular-target therapies for progressive disease. Hepatic infusion tube placement was conducted according to the Seldinger method to insert a catheter with a side hole via the right femoral artery. A coiling procedure was performed to prevent drug influx into the gastroduodenal artery. Ten subjects were selected, and the results were evaluated after HAIC (5-FU and LV administered once weekly). Moreover, anticancer drug-resistant colorectal cancer lines were subsequently prepared to investigate whether increased anticancer drug concentrations could induce apoptosis or cell death. Of the 10 subjects, 3 (30 %) showed partial response and 4 (40 %) showed no change according to computed tomography imaging findings obtained after hepatic artery infusion. The disease control rate was 70 %. Eight subjects had improved quality of life

  16. Effect of ultrasonography surveillance in patients with liver cancer: a population-based longitudinal study

    PubMed Central

    Chiang, Jui-Kun; Chih-Wen, Lin; Kao, Yee-Hsin

    2017-01-01

    Objective Liver cancer is a growing global public health problem. Ultrasonography is an imaging tool widely used for the early diagnosis of liver cancer. However, the effect of ultrasonography surveillance (US) on the survival of patients with liver cancer is unknown. Therefore, this study examined the association between survival and US frequency during the 2 years preceding patients’ liver cancer diagnosis. Methods This population-based longitudinal study was conducted in Taiwan, a region with high liver cancer incidence, by using the National Health Insurance Research Database. We compared survival between patients who received US three times or more (≥3 group) and less than three times (<3 group) during the 2 years preceding their liver cancer diagnosis, and identified the predictors for the ≥3 group. Results This study enrolled 4621 patients with liver cancer who had died between 1997 and 2010. The median survival rate was higher in the ≥3 group (1.42 years) than in the <3 group (0.51 years). Five-year survival probability was also significantly higher in the ≥3 group (14.4%) than in the <3 group (7.7%). The multivariate logistic regression results showed that the three most common positive predictors for receiving three or more US sessions were indications of viral hepatitis, gallbladder diseases and kidney–urinary–bladder diseases; the most common negative predictors for receiving three or more US sessions were male sex and indications of abdominal pain. Conclusion Patients with liver cancer who received US three times or more during the 2 years preceding their liver cancer diagnosis exhibited a higher 5-year survival probability. PMID:28645973

  17. Increased morbidity odds ratio of primary liver cancer and cirrhosis of the liver among vinyl chloride monomer workers

    PubMed Central

    Du C., L.; Wang, J. D.

    1998-01-01

    OBJECTIVES: To determine if there is an increased risk of admission to hospital for various diseases among vinyl chloride monomer (VCM) workers. METHODS: 2224 workers with occupational exposure to VCM were identified for occurrence of disease based on a search of hospital computer files on labour insurance. These data were compared with those of workers manufacturing optical equipment and motorcycles from 1 January 1985 to 31 March 1994. Cardiovascular and cerebrovascular diseases were used as reference diseases, and the age adjusted morbidity odds ratio (MOR) was calculated. RESULTS: A significantly increased risk of admission to hospital among VCM workers due to primary liver cancer (MOR 4.5-6.5), cirrhosis of the liver (MOR 1.7- 2.1), and other chronic diseases (MOR 1.5-2.0) was found. There were eight cases of primary liver cancer, all with heavy previous exposure to VCM. Another four cases of hepatoma in polyvinyl chloride (PVC) workers were found in the death registry. Ten out of 11 cases of hepatoma, with detailed medical information, were carriers of hepatitis B virus. The average latent period (20 years) was not different from other studies. Alternative agents of primary liver cancer were largely ruled out, suggesting that the combination of hepatitis B and VCM may lead to primary liver cancer. CONCLUSION: There is an increased risk of primary liver cancer in workers exposed to VCM, although the incomplete coverage of the Labor Insurance Bureau data warrants cautious interpretation of the results. Further study exploring the synergistic effects of VCM and hepatitis B is also indicated.   PMID:9849539

  18. Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer.

    PubMed

    Marquardt, Jens U; Gomez-Quiroz, Luis; Arreguin Camacho, Lucrecia O; Pinna, Federico; Lee, Yun-Han; Kitade, Mitsuteru; Domínguez, Mayrel Palestino; Castven, Darko; Breuhahn, Kai; Conner, Elizabeth A; Galle, Peter R; Andersen, Jesper B; Factor, Valentina M; Thorgeirsson, Snorri S

    2015-09-01

    The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-κB signaling. We evaluated the CSCs-depleting potential of NF-κB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of side population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. HCC cell lines exposed to curcumin exhibited differential responses to curcumin and were classified as sensitive and resistant. In sensitive lines, curcumin-mediated induction of cell death was directly related to the extent of NF-κB inhibition. The treatment also led to a selective CSC-depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-κB inhibition by SN50 and siRNA against p65 suppressed tumor cell growth. In contrast, curcumin-resistant cells displayed a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, an important component of the CSC-depleting activity of curcumin could be attributed to a NF-κB-mediated HDAC inhibition. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitivity with human HCC database indicated that HCCs with poor prognosis and progenitor features are most likely to benefit from NF-κB inhibition. These results demonstrate that blocking NF-κB can specifically target CSC populations and suggest a potential for combined inhibition of NF-κB and HDAC signaling for treatment of liver cancer patients with poor prognosis. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

  19. Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both liver cancer cells and cancer stem cells.

    PubMed

    Wang, Meiping; Xie, Fangyuan; Wen, Xikai; Chen, Han; Zhang, Hai; Liu, Junjie; Zhang, He; Zou, Hao; Yu, Yuan; Chen, Yan; Sun, Zhiguo; Wang, Xinxia; Zhang, Guoqing; Yin, Chuan; Sun, Duxin; Gao, Jie; Jiang, Beige; Zhong, Yanqiang; Lu, Ying

    2017-05-01

    Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells. The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo. SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells. In vivo, SCM showed the best tumor inhibitory effect with a safety profile. Thus, PEG-ceramide nanomicelles could serve as an effective and safe therapeutic drug carrier to deliver SAL into liver cancer, opening up the avenue of using PEG-ceramide as therapeutic drug carriers.

  20. Unresectable liver metastases in colorectal cancer: review of current strategies.

    PubMed

    Sueur, Benjamin; Pellerin, Olivier; Voron, Thibault; Pointet, Anne L; Taieb, Julien; Pernot, Simon

    2016-12-01

    The objective of the treatment of colorectal cancer patients with unresectable liver metastases should be clearly defined at the outset. Potentially resectable patients should be distinguished from clearly unresectable patients. In defining resectability, it is important to take into account both anatomic characteristics and patient characteristic (comorbidities, symptoms, age). According to this evaluation, treatment should be tailored to each patient. The most widely accepted standard is doublet cytotoxic regimen plus biotherapy (anti-EGFR or anti-VEGF antibodies according to RAS status, but some patients could benefit from an intensified regimen, as triplet chemotherapy ± bevacizumab, or intraarterial treatments (hepatic arterial infusion, radioembolization or chemoembolization), in order to allow resectability. It is therefore very important to discuss the treatments with a multidisciplinary team, including an experienced surgeon, an interventional radiologist and an oncologist. On the other hand, some patients could benefit in terms of quality of life and decreased toxicity from less intense treatment when resection is not an objective. First-line monotherapy or a maintenance strategy with biotherapy and/or cytotoxics could be discussed with these patients, and treatment holidays should be considered in selected patients. Finally, in patients with secondary resection of liver metastases, specificity should be considered in choosing the best adjuvant treatment, such as response to preoperative treatment and individual risk of relapse, which many in some cases justify intensification with hepatic arterial infusion in an adjuvant setting.

  1. Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

    PubMed

    Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

    2018-02-09

    Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

  2. 2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma.

    PubMed

    2015-01-01

    The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.

  3. Laboratory-Based Biomarkers and Liver Metastases in Metastatic Castration-Resistant Prostate Cancer.

    PubMed

    Cotogno, Patrick M; Ranasinghe, Lahiru K; Ledet, Elisa M; Lewis, Brian E; Sartor, Oliver

    2018-04-26

    Metastatic castrate-resistant prostate cancer (mCRPC) patients with liver metastases have a poor prognosis. No large studies have investigated the clinical and biochemical parameters associated with liver metastases in this population. Patient data made available via Project Data Sphere were collected from 1,281 men with mCRPC who were enrolled on to three phase III clinical trials for the treatment of their disease. Multiple logistic regression was performed on eight clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline radiographic imaging. Variables of interest included prior docetaxel exposure, Eastern Cooperative Oncology Group performance status, albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase (AST), hemoglobin (HGB), lactate dehydrogenase (LDH), prostate-specific antigen, and total bilirubin. Final models were compared when treating the variables as either continuous or categorized. Multiple variable analysis demonstrated that an increasing serum AST or LDH or a decreasing HGB was associated with an increased probability of having documented radiographic liver metastases ( p  < .0001). The area under the curve for the continuous model was 0.6842 and 0.6890 for the categorical one, with the latter model containing a dichotomized AST and LDH based on the upper limit of normal and tertile ranges of HGB based on the distribution of the outcome. Our analysis demonstrated a significant association between the presence of liver metastases and laboratory levels of AST, LDH, and HGB. These have implications for patient management. More research is needed to validate these biomarkers and prospectively determine their application in the clinical setting. The purpose of this study was to evaluate biochemical and clinical biomarkers associated with the presence of liver metastases in men diagnosed with metastatic castrate-resistant prostate cancer. The results indicate that

  4. Atypical onset of bicalutamide-induced liver injury.

    PubMed

    Yun, Gee Young; Kim, Seok Hyun; Kim, Seok Won; Joo, Jong Seok; Kim, Ju Seok; Lee, Eaum Seok; Lee, Byung Seok; Kang, Sun Hyoung; Moon, Hee Seok; Sung, Jae Kyu; Lee, Heon Young; Kim, Kyung Hee

    2016-04-21

    Anti-androgen therapy is the leading treatment for advanced prostate cancer and is commonly used for neoadjuvant or adjuvant treatment. Bicalutamide is a non-steroidal anti-androgen, used during the initiation of androgen deprivation therapy along with a luteinizing hormone-releasing hormone agonist to reduce the symptoms of tumor-related flares in patients with advanced prostate cancer. As side effects, bicalutamide can cause fatigue, gynecomastia, and decreased libido through competitive androgen receptor blockade. Additionally, although not as common, drug-induced liver injury has also been reported. Herein, we report a case of hepatotoxicity secondary to bicalutamide use. Typically, bicalutamide-induced hepatotoxicity develops after a few days; however, in this case, hepatic injury occurred 5 mo after treatment initiation. Based on this rare case of delayed liver injury, we recommend careful monitoring of liver function throughout bicalutamide treatment for prostate cancer.

  5. Effect of ultrasonography surveillance in patients with liver cancer: a population-based longitudinal study.

    PubMed

    Chiang, Jui-Kun; Chih-Wen, Lin; Kao, Yee-Hsin

    2017-06-23

    Liver cancer is a growing global public health problem. Ultrasonography is an imaging tool widely used for the early diagnosis of liver cancer. However, the effect of ultrasonography surveillance (US) on the survival of patients with liver cancer is unknown. Therefore, this study examined the association between survival and US frequency during the 2 years preceding patients' liver cancer diagnosis. This population-based longitudinal study was conducted in Taiwan, a region with high liver cancer incidence, by using the National Health Insurance Research Database. We compared survival between patients who received US three times or more (≥3 group) and less than three times (<3 group) during the 2 years preceding their liver cancer diagnosis, and identified the predictors for the ≥3 group. This study enrolled 4621 patients with liver cancer who had died between 1997 and 2010. The median survival rate was higher in the ≥3 group (1.42 years) than in the <3 group (0.51 years). Five-year survival probability was also significantly higher in the ≥3 group (14.4%) than in the <3 group (7.7%). The multivariate logistic regression results showed that the three most common positive predictors for receiving three or more US sessions were indications of viral hepatitis, gallbladder diseases and kidney-urinary-bladder diseases; the most common negative predictors for receiving three or more US sessions were male sex and indications of abdominal pain. Patients with liver cancer who received US three times or more during the 2 years preceding their liver cancer diagnosis exhibited a higher 5-year survival probability. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Discrimination of liver cancer in cellular level based on backscatter micro-spectrum with PCA algorithm and BP neural network

    NASA Astrophysics Data System (ADS)

    Yang, Jing; Wang, Cheng; Cai, Gan; Dong, Xiaona

    2016-10-01

    The incidence and mortality rate of the primary liver cancer are very high and its postoperative metastasis and recurrence have become important factors to the prognosis of patients. Circulating tumor cells (CTC), as a new tumor marker, play important roles in the early diagnosis and individualized treatment. This paper presents an effective method to distinguish liver cancer based on the cellular scattering spectrum, which is a non-fluorescence technique based on the fiber confocal microscopic spectrometer. Combining the principal component analysis (PCA) with back propagation (BP) neural network were utilized to establish an automatic recognition model for backscatter spectrum of the liver cancer cells from blood cell. PCA was applied to reduce the dimension of the scattering spectral data which obtained by the fiber confocal microscopic spectrometer. After dimensionality reduction by PCA, a neural network pattern recognition model with 2 input layer nodes, 11 hidden layer nodes, 3 output nodes was established. We trained the network with 66 samples and also tested it. Results showed that the recognition rate of the three types of cells is more than 90%, the relative standard deviation is only 2.36%. The experimental results showed that the fiber confocal microscopic spectrometer combining with the algorithm of PCA and BP neural network can automatically identify the liver cancer cell from the blood cells. This will provide a better tool for investigating the metastasis of liver cancers in vivo, the biology metabolic characteristics of liver cancers and drug transportation. Additionally, it is obviously referential in practical application.

  7. Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

    PubMed Central

    Lam, Chi Tat; Ng, Michael N. P.; Yu, Wan Ching; Lau, Joyce; Wan, Timothy; Wang, Xiaoqi; Yan, Zhixiang; Liu, Hang; Fan, Sheung Tat

    2012-01-01

    Background Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90+ liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90+ cells sorted from tumor (CD90+CSCs) with parallel non-tumorous liver tissues (CD90+NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings CD90+ cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90+ cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90+CSCs and CD90+NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90+CSCs and CD90+NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90+CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90+CSCs compared to CD90+NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90+CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90+CSCs in liver tumor tissues. Conclusions/Significance The identified genes

  8. Interaction of vinyl chloride monomer exposure and hepatitis B viral infection on liver cancer.

    PubMed

    Wong, Ruey-Hong; Chen, Pau-Chung; Wang, Jung-Der; Du, Chung-Li; Cheng, Tsun-Jen

    2003-04-01

    Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2-69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9-229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6 -infinity) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.

  9. Dietary factors and special epidemiological situations of liver cancer in Thailand and Africa.

    PubMed

    Wogan, G N

    1975-11-01

    Incidence patterns of primary liver cancer in Swaziland and Uganda have been compared with frequency of contamination of dietary staples by aflatoxins. Geographical regions or tribal groups with elevated cancer incidence were associated with increased frequency of contamination. In further studies, aflatoxin ingestion has been quantitatively measured in populations in Thailand, Kenya, and Mozambique, in subgroups of which the incidence of primary liver cancer varied over a wide range. In each instance, elevated cancer incidence was associated with highest levels of aflatoxin intake. In view of the potency of these compounds as liver carcinogens in many animal species, these data collectively suggest that the aflatoxins are also carcinogenic for man and that regular ingestion of foods heavily contaminated with aflatoxins increases the risk of liver cancer in human populations.

  10. Dietary broccoli protects against fatty liver development but not against progression of liver cancer in mice pretreated with diethylnitrosamine

    PubMed Central

    Chen, Yung-Ju; Myracle, Angela D.; Wallig, Matthew A.; Jeffery, Elizabeth H.

    2016-01-01

    Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months. Dietary broccoli decreased hepatic triacylglycerols, NAFLD, liver damage and tumour necrosis factor by month 5 without changing body weight or relative liver weight, but did not slow carcinogenesis, seen in 100% of mice. We conclude that broccoli, a good source of sulforaphane, slows progression of hepatic lipidosis, but not tumourigenesis in this robust model. PMID:27672403

  11. Label-free detection of liver cancer cells by aptamer-based microcantilever biosensor.

    PubMed

    Chen, Xuejuan; Pan, Yangang; Liu, Huiqing; Bai, Xiaojing; Wang, Nan; Zhang, Bailin

    2016-05-15

    Liver cancer is one of the most common and highly malignant cancers in the world. There are no effective therapeutic options if an early liver cancer diagnosis is not achieved. In this work, detection of HepG2 cells by label-free microcantilever array aptasensor was developed. The sensing microcantilevers were functionalized by HepG2 cells-specific aptamers. Meanwhile, to eliminate the interferences induced by the environment, the reference microcantilevers were modified with 6-mercapto-1-hexanol self-assembled monolayers. The aptasensor exhibits high specificity over not only human liver normal cells, but also other cancer cells of breast, bladder, and cervix tumors. The linear relation ranges from 1×10(3) to 1×10(5)cells/mL, with a detection limit of 300 cells/mL (S/N=3). Our work provides a simple method for detection of liver cancer cells with advantages in terms of simplicity and stability. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Selective CD4+ T Cell Loss Promotes Liver Cancer Development | Center for Cancer Research

    Cancer.gov

    Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, commonly develops in patients with underlying chronic liver disease, such as hepatitis B or C virus infection or non-alcoholic fatty liver disease (NAFLD).

  13. RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines

    PubMed Central

    Berardocco, Martina; Radeghieri, Annalisa; Busatto, Sara; Gallorini, Marialucia; Raggi, Chiara; Gissi, Clarissa; D’Agnano, Igea; Bergese, Paolo; Felsani, Armando; Berardi, Anna C.

    2017-01-01

    Liver cancer (LC) is one of the most common cancers and represents the third highest cause of cancer-related deaths worldwide. Extracellular vesicle (EVs) cargoes, which are selectively enriched in RNA, offer great promise for the diagnosis, prognosis and treatment of LC. Our study analyzed the RNA cargoes of EVs derived from 4 liver-cancer cell lines: HuH7, Hep3B, HepG2 (hepato-cellular carcinoma) and HuH6 (hepatoblastoma), generating two different sets of sequencing libraries for each. One library was size-selected for small RNAs and the other targeted the whole transcriptome. Here are reported genome wide data of the expression level of coding and non-coding transcripts, microRNAs, isomiRs and snoRNAs providing the first comprehensive overview of the extracellular-vesicle RNA cargo released from LC cell lines. The EV-RNA expression profiles of the four liver cancer cell lines share a similar background, but cell-specific features clearly emerge showing the marked heterogeneity of the EV-cargo among the individual cell lines, evident both for the coding and non-coding RNA species. PMID:29137313

  14. MiR-525-3p Enhances the Migration and Invasion of Liver Cancer Cells by Downregulating ZNF395

    PubMed Central

    Pang, Fei; Zha, Ruopeng; Zhao, Yingjun; Wang, Qifeng; Chen, Di; Zhang, Zhenfeng; Chen, Taoyang; Yao, Ming; Gu, Jianren; He, Xianghuo

    2014-01-01

    Liver cancer is one of leading causes of cancer-related deaths. A deeper mechanistic understanding of liver cancer could lead to the development of more effective therapeutic strategies. In our previous work, we screened 646 miRNAs and identified 11 that regulate liver cancer cell migration. The current study shows that miR-525-3p is frequently up-regulated in liver cancer tissues, and enhanced expression of miR-525-3p can promote liver cancer cell migration and invasion. Zinc finger protein 395 (ZNF395) is the direct functional target gene for miR-525-3p, and it is frequently down-regulated in liver cancer tissues. High expression of ZNF395 can significantly inhibit while knockdown of ZNF395 expression can markedly enhance the migration and invasion of liver cancer cells, suggesting that ZNF395 suppresses metastasis in liver cancer. Down-regulation of ZNF395 can mediate miR-525-3p induced liver cancer cell migration and invasion. In conclusion, miR-525-3p promotes liver cancer cell migration and invasion by directly targeting ZNF395, and the fact that miR-525-3p and ZNF395 both play important roles in liver cancer progression makes them potential therapeutic targets. PMID:24599008

  15. Transcatheter embolization therapy in liver cancer: an update of clinical evidences

    PubMed Central

    De Baere, Thierry; Idée, Jean-Marc; Ballet, Sébastien

    2015-01-01

    Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients’ life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Although being used for decades, Lipiodol® (Lipiodol® Ultra Fluid®, Guerbet, France) remains important as a tumor-seeking and radio-opaque drug delivery vector in interventional oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem® (CeloNova Biosciences Inc., USA), DC-Beads® (BTG, UK) and HepaSphere® (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres® (Sirtex Medical Limited, Australia) and TheraSphere® (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key

  16. Relationship between Non-Alcoholic Fatty Liver Disease and Breast Cancer.

    PubMed

    Nseir, William; Abu-Rahmeh, Zuhair; Tsipis, Alex; Mograbi, Julnar; Mahamid, Mahmud

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis. Breast cancer is now the most common cancer in women and is the leading cause of death from cancer among women. To assess the relationship between NAFLD and newly diagnosed cases of breast cancer. The results of mammography screening examinations in women referred to the Breast Center, Holy Family Hospital, Nazareth during a 4 year period were collected. We identified cases of women who were newly diagnosed with breast cancer and who underwent abdominal computed tomography (CT) within 1 month of the diagnosis. The control group comprised 73 women with normal mammography and breast ultrasonography who underwent abdominal CT within 3 months from the date of the breast cancer screening during the same study period. The control cases were matched by age and body mass index (BMI). We compared the cases with the controls in terms of the presence of diffuse hepatic fatty liver and other known risk factors for breast cancer. Of the 133 women who were screened, 73 with new diagnosis of breast cancer were eligible for the study. NAFLD was found in 33 of the women with breast cancer and in 12 in the control group (45.2% vs.16.4%, respectively, P = 0.002). Multivariate analysis showed NAFLD (odds ratio 2.82, 95% confidence interval 1.2-5.5, P = 0.016) to be associated with breast cancer. NAFLD is associated with breast cancer.

  17. RNA Binding Protein CUGBP1 Inhibits Liver Cancer in a Phosphorylation-Dependent Manner.

    PubMed

    Lewis, Kyle; Valanejad, Leila; Cast, Ashley; Wright, Mary; Wei, Christina; Iakova, Polina; Stock, Lauren; Karns, Rebekah; Timchenko, Lubov; Timchenko, Nikolai

    2017-08-15

    Despite intensive investigations, mechanisms of liver cancer are not known. Here, we identified an important step of liver cancer, which is the neutralization of tumor suppressor activities of an RNA binding protein, CUGBP1. The translational activity of CUGBP1 is activated by dephosphorylation at Ser302. We generated CUGBP1-S302A knock-in mice and found that the reduction of translational activity of CUGBP1 causes development of a fatty liver phenotype in young S302A mice. Examination of liver cancer in diethylnitrosamine (DEN)-treated CUGBP1-S302A mice showed these mice develop much more severe liver cancer that is associated with elimination of the mutant CUGBP1. Searching for mechanisms of this elimination, we found that the oncoprotein gankyrin (Gank) preferentially binds to and triggers degradation of dephosphorylated CUGBP1 (de-ph-S302-CUGBP1) or S302A mutant CUGBP1. To test the role of Gank in degradation of CUGBP1, we generated mice with liver-specific deletion of Gank. In these mice, the tumor suppressor isoform of CUGBP1 is protected from Gank-mediated degradation. Consistent with reduction of CUGBP1 in animal models, CUGBP1 is reduced in patients with pediatric liver cancer. Thus, this work presents evidence that de-ph-S302-CUGBP1 is a tumor suppressor protein and that the Gank-UPS-mediated reduction of CUGBP1 is a key event in the development of liver cancer. Copyright © 2017 American Society for Microbiology.

  18. Using anti-VEGF McAb and magnetic nanoparticles as double-targeting vector for the radioimmunotherapy of liver cancer.

    PubMed

    Chen, Jing; Wu, Hua; Han, Deyan; Xie, Changsheng

    2006-01-18

    To study the biodistribution of a new radioimmunoconjugate-131I-anti-VEGF monoclonal antibody (Sc-7269)-Dextran Magnetic Nanoparticles (DMN) in nude mice bearing human liver cancer where an external magnetic field was focused on, and to evaluate its therapeutic effects and safety. Tumor Growth Delay (TGD) and tumor inhibition rate were observed as antitumor effect. Peripheral white blood cells counts and the loss of body weight were tested as an indicator of systemic toxicity. The results suggests that the radioimmunotherapy of intratumoral injection of 131I-Sc-7269-DMN may be safe and efficient for the treatment of liver cancer. Furthermore, the radioimmunotherapy using DMN as a 'carrier system' may be a highly potential approach in the treatment of other kind of tumors.

  19. A CD13-targeting peptide integrated protein inhibits human liver cancer growth by killing cancer stem cells and suppressing angiogenesis.

    PubMed

    Zheng, Yan-Bo; Gong, Jian-Hua; Liu, Xiu-Jun; Li, Yi; Zhen, Yong-Su

    2017-05-01

    CD13 is a marker of angiogenic endothelial cells, and recently it is proved to be a biomarker of human liver cancer stem cells (CSCs). Herein, the therapeutic effects of NGR-LDP-AE, a fusion protein composed of CD13-targeting peptide NGR and antitumor antibiotic lidamycin, on human liver cancer and its mechanism were studied. Western blot and immunofluorescence assay demonstrated that CD13 (WM15 epitope) was expressed in both human liver cancer cell lines and vascular endothelial cells, while absent in normal liver cells. MTT assay showed that NGR-LDP-AE displayed potent cytotoxicity to cultured tumor cell lines with IC 50 values at low nanomolar level. NGR-LDP-AE inhibited tumorsphere formation of liver cancer cells, and the IC 50 values were much lower than that in MTT assay, indicating selectively killing of CSCs. In endothelial tube formation assay, NGR-LDP-AE at low cytotoxic dose significantly inhibited the formation of intact tube networks. Animal experiment demonstrated that NGR-LDP-AE inhibited the growth of human liver cancer xenograft. Immunohistochemical analysis showed that NGR-LDP-AE induced the down-regulation of CD13. In vitro experiment using cultured tumor cells also confirmed this result. NGR-LDP-AE activated both apoptotic and autophagic pathways in cultured tumor cells, while the induced autophagy protected cells from death. Conclusively, NGR-LDP-AE exerts its antitumor activity via killing liver CSCs and inhibiting angiogenesis. With one targeting motif, NGR-LDP-AE acts on both liver CSCs and angiogenic endothelial cells. It is a promising dual targeting fusion protein for liver cancer therapy, especially for advanced or relapsed cancers. © 2017 Wiley Periodicals, Inc.

  20. Herbal Compound Songyou Yin and Moderate Swimming Suppress Growth and Metastasis of Liver Cancer by Enhancing Immune Function.

    PubMed

    Zhang, Quan-Bao; Meng, Xiang-Ting; Jia, Qing-An; Bu, Yang; Ren, Zheng-Gang; Zhang, Bo-Heng; Tang, Zhao-You

    2016-09-01

    Objective Both the Chinese herbal compound Songyou Yin (SYY) and swimming exercise have been shown to have protective effects against liver cancer in animal models. In this study, we investigated whether SYY and moderate swimming (MS) have enhanced effect on suppressing progression of liver cancer by immunomodulation. Methods C57BL/6 mice were transplanted with Hepa1-6 murine liver cancer cell lines and received treatment with SYY alone or SYY combined with MS. The green fluorescent protein (GFP)-positive metastatic foci in lungs were imaged with a stereoscopic fluorescence microscope. Flow cytometry was used to test the proportion of CD4 +, CD8 + T cells in peripheral blood and the proportions of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood, spleen, and tumor tissues. Cytokine transforming growth factor (TGF)-β1 level in serum was detected by ELISA. Results SYY plus MS significantly suppressed the growth and lung metastasis of liver cancer and prolonged survival in tumor-burdened mice. SYY plus MS markedly raised the CD4 to CD8 ratio in peripheral blood and lowered the serum TGF-β1 level and the proportions of Treg cells in peripheral blood, spleen, and tumor tissue. The effects of the combined intervention were significantly superior to SYY or MS alone. Conclusion The combined application of SYY and MS exerted an enhanced effect on suppressing growth and metastasis of liver cancer by strengthening immunity. © The Author(s) 2015.

  1. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosomemore » protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.« less

  2. Natural Medicines Used in the Traditional Tibetan Medical System for the Treatment of Liver Diseases

    PubMed Central

    Li, Qi; Li, Hai-Jiao; Xu, Tong; Du, Huan; Huan Gang, Chen-Lei; Fan, Gang; Zhang, Yi

    2018-01-01

    Liver disease is one of the most risk factors threatening human health. It is of great significance to find drugs that can treat liver diseases, especially for acute and chronic hepatitis, non-alcoholic fatty liver disease, and liver cancer. The search for drugs with good efficacy from traditional natural medicines has attracted more and more attention. Tibetan medicine, one of the China's traditional medical systems, has been widely used by the Tibetan people for the prevention and treatment of liver diseases for hundreds of years. The present paper summarized the natural Tibetan medicines that have been used in Tibetan traditional system of medicine to treat liver diseases by bibliographic investigation of 22 Tibetan medicine monographs and drug standards. One hundred and ninety three species including 181 plants, 7 animals, and 5 minerals were found to treat liver diseases in traditional Tibetan medicine system. The most frequently used species are Carthamus tinctorius, Brag-zhun, Swertia chirayita, Swertia mussotii, Halenia elliptica, Herpetospermum pedunculosum, and Phyllanthus emblica. Their names, families, medicinal parts, traditional uses, phytochemicals information, and pharmacological activities were described in detail. These natural medicines might be a valuable gift from the old Tibetan medicine to the world, and would be potential drug candidates for the treatment of liver diseases. Further studies are needed to prove their medicinal values in liver diseases treatment, identify bioactive compounds, elucidate the underlying mechanism of action, and clarify their side effects or toxicity with the help of modern phytochemical, pharmacological, metabonomics, and/or clinical trial methods. PMID:29441019

  3. Systems approach to characterize the metabolism of liver cancer stem cells expressing CD133

    NASA Astrophysics Data System (ADS)

    Hur, Wonhee; Ryu, Jae Yong; Kim, Hyun Uk; Hong, Sung Woo; Lee, Eun Byul; Lee, Sang Yup; Yoon, Seung Kew

    2017-04-01

    Liver cancer stem cells (LCSCs) have attracted attention because they cause therapeutic resistance in hepatocellular carcinoma (HCC). Understanding the metabolism of LCSCs can be a key to developing therapeutic strategy, but metabolic characteristics have not yet been studied. Here, we systematically analyzed and compared the global metabolic phenotype between LCSCs and non-LCSCs using transcriptome and metabolome data. We also reconstructed genome-scale metabolic models (GEMs) for LCSC and non-LCSC to comparatively examine differences in their metabolism at genome-scale. We demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. We also confirmed that MYC, a central point of regulation in cancer metabolism, was significantly up-regulated in LCSCs compared with non-LCSCs. Moreover, LCSCs tend to have less active fatty acid oxidation. In this study, the metabolic characteristics of LCSCs were identified using integrative systems analysis, and these characteristics could be potential cures for the resistance of liver cancer cells to anticancer treatments.

  4. Psorinum Therapy in Treating Stomach, Gall Bladder, Pancreatic, and Liver Cancers: A Prospective Clinical Study

    PubMed Central

    Chatterjee, Aradeep; Biswas, Jaydip; Chatterjee, Ashim; Bhattacharya, Sudin; Mukhopadhyay, Bishnu; Mandal, Syamsundar

    2011-01-01

    We prospectively studied the clinical efficacy of an alternative cancer treatment “Psorinum Therapy” in treating stomach, gall bladder, pancreatic and liver cancers. Our study was observational, open level and single arm. The participants' eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum-6x was administered orally to all the participants up to 0.02 ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. 158 participants (42 of stomach, 40 of gall bladder, 44 of pancreatic, 32 of liver) were included in the final analysis of the study. Complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) cases. Double-blind randomized controlled clinical trial should be conducted for further scientific exploration of this alternative cancer treatment. PMID:21197093

  5. A prospective development study of software-guided radio-frequency ablation of primary and secondary liver tumors: Clinical intervention modelling, planning and proof for ablation cancer treatment (ClinicIMPPACT).

    PubMed

    Reinhardt, Martin; Brandmaier, Philipp; Seider, Daniel; Kolesnik, Marina; Jenniskens, Sjoerd; Sequeiros, Roberto Blanco; Eibisberger, Martin; Voglreiter, Philip; Flanagan, Ronan; Mariappan, Panchatcharam; Busse, Harald; Moche, Michael

    2017-12-01

    Radio-frequency ablation (RFA) is a promising minimal-invasive treatment option for early liver cancer, however monitoring or predicting the size of the resulting tissue necrosis during the RFA-procedure is a challenging task, potentially resulting in a significant rate of under- or over treatments. Currently there is no reliable lesion size prediction method commercially available. ClinicIMPPACT is designed as multicenter-, prospective-, non-randomized clinical trial to evaluate the accuracy and efficiency of innovative planning and simulation software. 60 patients with early liver cancer will be included at four European clinical institutions and treated with the same RFA system. The preinterventional imaging datasets will be used for computational planning of the RFA treatment. All ablations will be simulated simultaneously to the actual RFA procedure, using the software environment developed in this project. The primary outcome measure is the comparison of the simulated ablation zones with the true lesions shown in follow-up imaging after one month, to assess accuracy of the lesion prediction. This unique multicenter clinical trial aims at the clinical integration of a dedicated software solution to accurately predict lesion size and shape after radiofrequency ablation of liver tumors. Accelerated and optimized workflow integration, and real-time intraoperative image processing, as well as inclusion of patient specific information, e.g. organ perfusion and registration of the real RFA needle position might make the introduced software a powerful tool for interventional radiologists to optimize patient outcomes.

  6. Effects of pirfenidone in acute and sub-chronic liver fibrosis, and an initiation-promotion cancer model in the mouse.

    PubMed

    Seniutkin, Oleksii; Furuya, Shinji; Luo, Yu-Syuan; Cichocki, Joseph A; Fukushima, Hisataka; Kato, Yuki; Sugimoto, Hiromi; Matsumoto, Tomoko; Uehara, Takeki; Rusyn, Ivan

    2018-01-15

    Liver fibrosis results from chronic tissue damage and excessive regeneration with accumulation of extracellular matrix proteins; it is a precursor of liver cirrhosis and hepatocellular carcinoma. Liver fibrosis treatments are primarily directed at inflammation, with few options to combat fibrogenesis. Pirfenidone is a drug approved for idiopathic pulmonary fibrosis and this study was focused on anti-fibrotic and anti-cancer potential of pirfenidone in the liver of male B6C3F1/J mice. In a dose-finding study, mice were treated with CCl 4 (0.2ml/kg ip, 2×wk for 4weeks) while on a pirfenidone-containing (0-600mg/kg) diet. Pirfenidone at doses of 300 and 600mg/kg had significant anti-fibrotic (collagen) and anti-inflammatory (serum transaminases and "ballooning" hepatocyte) effects. In a sub-chronic study (14weeks), mice received CCl 4 while on pirfenidone (300mg/kg) diet. Pirfenidone significantly reduced collagen deposition, but had little effect of inflammation and injury. In an initiation-promotion cancer study with N-nitrosodiethylamine and CCl 4 , pirfenidone (300mg/kg) did not affect incidence, size, or multiplicity of liver tumors. Overall, we conclude that while pirfenidone exhibits strong anti-fibrotic effects in early stage liver fibrosis, it is less effective in advanced liver fibrosis and was not protective in an initiation-promotion liver cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

    PubMed Central

    Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek

    2016-01-01

    Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved – without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM. PMID:27095938

  8. Current treatment for non-alcoholic fatty liver disease.

    PubMed

    Moctezuma-Velázquez, C

    Non-alcoholic fatty liver disease is the most prevalent hepatopathy, estimated at 30% in the general population. In the coming years, it will likely be the most common indication for liver transplantation and the most frequent cause of hepatocellular carcinoma. Current treatment for non-alcoholic fatty liver disease is based on dietary and exercise interventions that have been shown to be efficacious, even for reverting fibrosis. Unfortunately, compliance with general measures involving lifestyle modifications is very poor, making pharmacologic strategies a necessary option. At present, there are no treatments for non-alcoholic fatty liver disease approved by regulatory agencies, and the only ones with sufficient evidence and recommended by international societies are treatments with pioglitazone and vitamin E, which are not exempt from adverse effects. We review herein the current management of non-alcoholic fatty liver disease, including dietary and physical activity interventions, available treatments, equivocal therapies, emerging treatments, and treatments presently in clinical trials. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  9. 2014 Korean Liver Cancer Study Group-National Cancer Center Korea Practice Guideline for the Management of Hepatocellular Carcinoma

    PubMed Central

    2015-01-01

    The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC. PMID:25995680

  10. Development of a web-based liver cancer prediction model for type II diabetes patients by using an artificial neural network.

    PubMed

    Rau, Hsiao-Hsien; Hsu, Chien-Yeh; Lin, Yu-An; Atique, Suleman; Fuad, Anis; Wei, Li-Ming; Hsu, Ming-Huei

    2016-03-01

    hyperlipidemia. The performance of the ANN was superior to that of LR, according to the sensitivity (0.757), specificity (0.755), and the area under the receiver operating characteristic curve (0.873). After developing the optimal prediction model, we base on this model to construct a web-based application system for liver cancer prediction, which can provide support to physicians during consults with diabetes patients. In the original dataset (n=2060), 33% of diabetes patients were diagnosed with liver cancer (n=515). After using 70% of the original data to training the model and other 30% for testing, the sensitivity and specificity of our model were 0.757 and 0.755, respectively; this means that 75.7% of diabetes patients can be predicted correctly to receive a future liver cancer diagnosis, and 75.5% can be predicted correctly to not be diagnosed with liver cancer. These results reveal that this model can be used as effective predictors of liver cancer for diabetes patients, after discussion with physicians; they also agreed that model can assist physicians to advise potential liver cancer patients and also helpful to decrease the future cost incurred upon cancer treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis.

    PubMed

    Togo, Shinji; Tanaka, Kuniya; Morioka, Daisuke; Sugita, Mitsutaka; Ueda, Michio; Miura, Yasuhiko; Kubota, Toru; Nagano, Yasuhiko; Matsuo, Kenichi; Endo, Itaru; Sekido, Hitoshi; Shimada, Hiroshi

    2005-04-01

    Nutritional disturbances such as ascites and hypoalbuminemia frequently arise after hepatectomy for liver cancer with liver cirrhosis. We examined the possibility of maintaining a favorable state of nutrition by outpatient administration of branched-chain amino acid (BCAA) granules. Forty-three patients who had gross liver cirrhosis complicated by liver cancer and underwent surgery up to May 2002 were given BCAA granules (n = 21, BCAA group) or no granules (n = 22, control group). 1) Background details such as age, sex, surgical technique, blood loss, and duration of surgery showed no significant differences. 2) Among objective findings, improvement of ascites and edema tended to occur sooner in the BCAA group, but without a significant difference. 3) Although serum albumin recovered its preoperative value 9 mo after surgery in the control group, only 6 mo was required for recovery in the BCAA group. Total protein showed similar changes, but neither group showed any difference in changes of aspartate aminotransferase, alanine transferase, or platelets. 4) One year postoperatively, the change from the preoperative indocyanine green retention rate at 15 min after intravenous administration tended to be worse in the control group, but not significantly so. 5) In the BCAA group, hyaluronic acid and type IV collagen 7S improved significantly sooner than in the control group. BCAA supplementation after hepatectomy promotes rapid improvement in protein metabolism and inhibits progression to liver cirrhosis. Administration of BCAA after hepatectomy is considered beneficial to a patient's nutritional state.

  12. The nanomechanical signature of liver cancer tissues and its molecular origin

    NASA Astrophysics Data System (ADS)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

    2015-07-01

    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus

  13. The application of antitumor drug-targeting models on liver cancer.

    PubMed

    Yan, Yan; Chen, Ningbo; Wang, Yunbing; Wang, Ke

    2016-06-01

    Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.

  14. Immunotoxin Targeting Glypican-3 Effective against Liver Tumors | Center for Cancer Research

    Cancer.gov

    Worldwide, liver cancer is the fifth most common malignancy, and hepatocellular carcinoma (HCC) makes up about two-thirds of those cases. Unfortunately, surgery is still the most effective treatment for HCC but is only available to patients diagnosed at early stages. HCC is known for being particularly drug resistant, sorafenib being the only FDA-approved chemotherapy currently available. Thus, new strategies for treating the disease are urgently needed.

  15. Sonodynamic action of pyropheophorbide-a methyl ester induces mitochondrial damage in liver cancer cells.

    PubMed

    Xu, Jing; Xia, Xinshu; Leung, Albert Wingnang; Xiang, Junyan; Jiang, Yuan; Yu, Heping; Bai, Dingqun; Li, Xiaohong; Xu, Chuanshan

    2011-05-01

    Sonodynamic therapy with pyropheophorbide-a methyl ester (MPPa) presents a promising aspect in treating liver cancer. The present study aims to investigate the mitochondrial damage of liver cancer cells induced by MPPa-mediated sonodynamic action. Mouse hepatoma cell line H(22) cells were incubated with MPPa (2 μM) for 20 h and then exposed to ultrasound with an intensity of 0.97 W/cm(2) for 8 s. Cytotoxicity was investigated 24h after sonodynamic action using MTT assay and light microscopy. Mitochondrial membrane potential (ΔΨm) was analyzed using flow cytometry with rhodamine 123 staining and ultrastructural changes were observed using transmission electron microscopy (TEM). The cytotoxicity of MPPa-mediated SDT on H(22) cell line was 73.00±3.42%, greater than ultrasound treatment alone (28.12±5.19%) significantly while MPPa treatment alone had no significant effect on H(22) cells. Moreover, after MPPa-mediated SDT cancer cells showed swollen mitochondria under TEM and a significant collapse of mitochondrial membrane potential. Our findings demonstrated that MPPa-mediated SDT could remarkably induce cell death of H(22) cells, and highlighted that mitochondrial damage might be an important cause of cell death induced by MPPa-mediated SDT. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Combining Angiogenesis-Targeted Treatments for Liver Cancer

    Cancer.gov

    In this trial, patients with unresectable hepatocellular carcinoma who are ineligible for a liver transplant or other local therapies will be given oral sorafenib at the standard approved dose and intravenous TRC105.

  17. Characterization of HBV integration patterns and timing in liver cancer and HBV-infected livers.

    PubMed

    Furuta, Mayuko; Tanaka, Hiroko; Shiraishi, Yuichi; Unida, Takuro; Imamura, Michio; Fujimoto, Akihiro; Fujita, Masahi; Sasaki-Oku, Aya; Maejima, Kazuhiro; Nakano, Kaoru; Kawakami, Yoshiiku; Arihiro, Koji; Aikata, Hiroshi; Ueno, Masaki; Hayami, Shinya; Ariizumi, Shun-Ichi; Yamamoto, Masakazu; Gotoh, Kunihito; Ohdan, Hideki; Yamaue, Hiroki; Miyano, Satoru; Chayama, Kazuaki; Nakagawa, Hidewaki

    2018-05-18

    Integration of Hepatitis B virus (HBV) into the human genome can cause genetic instability, leading to selective advantages for HBV-induced liver cancer. Despite the large number of studies for HBV integration into liver cancer, little is known about the mechanism of initial HBV integration events owing to the limitations of materials and detection methods. We conducted an HBV sequence capture, followed by ultra-deep sequencing, to screen for HBV integrations in 111 liver samples from human-hepatocyte chimeric mice with HBV infection and human clinical samples containing 42 paired samples from non-tumorous and tumorous liver tissues. The HBV infection model using chimeric mice verified the efficiency of our HBV-capture analysis and demonstrated that HBV integration could occur 23 to 49 days after HBV infection via microhomology-mediated end joining and predominantly in mitochondrial DNA. Overall HBV integration sites in clinical samples were significantly enriched in regions annotated as exhibiting open chromatin, a high level of gene expression, and early replication timing in liver cells. These data indicate that HBV integration in liver tissue was biased according to chromatin accessibility, with additional selection pressures in the gene promoters of tumor samples. Moreover, an integrative analysis using paired non-tumorous and tumorous samples and HBV-related transcriptional change revealed the involvement of TERT and MLL4 in clonal selection. We also found frequent and non-tumorous liver-specific HBV integrations in FN1 and HBV-FN1 fusion transcript. Extensive survey of HBV integrations facilitates and improves the understanding of the timing and biology of HBV integration during infection and HBV-related hepatocarcinogenesis.

  18. Clinical outcomes for patients with liver-limited metastatic colorectal cancer: Arguing the case for specialist hepatobiliary multidisciplinary assessment.

    PubMed

    Thillai, K; Repana, D; Korantzis, I; Kane, P; Prachalias, A; Ross, P

    2016-09-01

    In patients with liver-limited metastatic colorectal cancer, hepatic resection can offer a significant survival benefit over systemic therapy alone. Specialist hepatobiliary multidisciplinary meetings are currently believed to provide the best forum to discuss the management for these patients. A retrospective analysis was undertaken of patients diagnosed with liver-limited metastatic colorectal cancer over 6 months within a cancer network in the United Kingdom. In addition, patients who were diagnosed but not referred to the hepatobiliary meeting were discussed within a virtual multi-disciplinary setting. Contributors were blinded and proposed management recorded. 159 newly diagnosed patients with liver-limited metastatic colorectal cancer were identified. 68 (43%) were referred at initial diagnosis and 38 (24%) referred following systemic treatment. 35 (51%) who were discussed at baseline underwent a subsequent hepatectomy or radiofrequency ablation, as did 18 (47%) patients referred after chemotherapy. Of the remaining 53 (33%) patients not referred, imaging was available for 31 (58%). Decisions regarding potential liver-directed therapy were discussed within a multi-disciplinary setting. 13 (42%) were identified as resectable or potentially resectable and 11 (36%) may have been suitable for a clinical trial. In reality, none of these 31 patients (100%) underwent surgery or ablation. Whilst the majority of patients with liver-limited metastatic colorectal cancer were referred appropriately, this study demonstrates that a significant number with potentially resectable disease are not being discussed at specialist meetings. A review of all diagnosed cases would ensure that an increased number of patients are offered hepatic resection or ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

    PubMed

    Bu, Pengcheng; Chen, Kai-Yuan; Xiang, Kun; Johnson, Christelle; Crown, Scott B; Rakhilin, Nikolai; Ai, Yiwei; Wang, Lihua; Xi, Rui; Astapova, Inna; Han, Yan; Li, Jiahe; Barth, Bradley B; Lu, Min; Gao, Ziyang; Mines, Robert; Zhang, Liwen; Herman, Mark; Hsu, David; Zhang, Guo-Fang; Shen, Xiling

    2018-06-05

    Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. 20-Years of Population-Based Cancer Registration in Hepatitis B and Liver Cancer Prevention in The Gambia, West Africa

    PubMed Central

    Bah, Ebrima; Carrieri, Maria Patrizia; Hainaut, Pierre; Bah, Yusupha; Nyan, Ousman; Taal, Makie

    2013-01-01

    Background The Gambia Hepatitis Intervention Study (GHIS) was designed as a randomised control trial of infant hepatitis B vaccination applied to public health policy, with the main goal of preventing primary liver cancer later in adult life in The Gambia. To that effect, the National Cancer Registry of The Gambia (NCR), a population-based cancer registry (PBCR), was established in 1986 to actively collect data on all cancer diagnosis nation-wide. We extracted 20-years (1990-2009) of data to assess for the first time, the evolution of the most common cancers, also describe and demonstrate the role of the PBCR in a hepatitis B and liver cancer prevention programme in this population. Methods and Findings We estimated Age-Standardised Incidence Rates (ASR (W)) of the most common cancers registered during the period by gender. The registration period was divided into four 5-year intervals and incidence rates were estimated for each interval. The most common cancers in males were liver, prostate, lung plus bronchus, non-Hodgkin lymphoma (NHL) and stomach, accounting for 60%, 5%, 4%, 5% and 3%, respectively. Similarly, cancers of the cervix uteri, liver, breast and NHL, were the most common in females, accounting for 33%, 24%, 11% and 4% of the female cancers, respectively. Conclusions Cancer incidence has remained relatively stable over time, but as shown elsewhere in sub-Saharan Africa the disease is a threat in The Gambia. The infection related cancers which are mostly preventable (HBV in men and HPV/HIV in women) were the most common. At the moment the data is not enough to detect an effect of hepatitis B vaccination on liver cancer incidence in The Gambia. However, we observed that monitoring case occurrence through PBCR is a key public health pre-requisite for rational planning and implementation of targeted interventions for improving the health of the population. PMID:24098724

  1. Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor.

    PubMed

    Liu, Xiang-Feng; Long, Hai-Jiao; Miao, Xiong-Ying; Liu, Guo-Li; Yao, Hong-Liang

    2017-07-01

    Fisetin (3,3',4',7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein‑coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF‑β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression.

  2. Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor

    PubMed Central

    Liu, Xiang-Feng; Long, Hai-Jiao; Miao, Xiong-Ying; Liu, Guo-Li; Yao, Hong-Liang

    2017-01-01

    Fisetin (3,3′,4′,7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein-coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF-β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression. PMID:28560391

  3. Microwave Ablation (MWA) for the Treatment of a Solitary, Chemorefractory Testicular Cancer Liver Metastasis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Violari, Elena G., E-mail: eviolari@live.com; Petre, Elena N., E-mail: petree@mskcc.org; Feldman, Darren R., E-mail: feldmand@mskcc.org

    2015-04-15

    We present a case of a patient with stage IIIC metastatic seminoma with a persistent chemorefractory liver lesion. The patient was deemed a poor surgical candidate due to the tumor’s aggressive biology with numerous other liver lesions treated with chemotherapy and a relatively high probability for additional recurrences. Further chemotherapy with curative intent was not a feasible option due to the fact that the patient had already received second-line high-dose chemotherapy and four cycles of third-line treatment complicated by renal failure, refractory thrombocytopenia, and debilitating neuropathy. After initial failure of laser, microwave ablation of the chemorefractory liver metastasis resulted inmore » prolonged local tumor control and rendered the patient disease-free for more than 35 months, allowing him to regain an improved quality of life.« less

  4. Rapid diagnosis of liver cancer by ultrasound-guided fine-needle aspiration biopsy.

    PubMed

    Huber, K; Heuhold, N

    1987-01-01

    Because of the relatively favorable prognosis to the patient with early detected hepatocarcinoma followed by surgical treatment if resection is possible, it is important to differentiate quickly between primary and secondary liver cancer. Ultrasound-guided percutaneous fine needle aspiration biopsy (US-FNAB) was used as a first diagnostic measure in patients with sonographic evidence of liver tumors. Biopsies were done under sonographic control and antiseptic conditions from the center and the border zone of solid tumors of the liver, and the aspirated cell material was air dried on glass slides and Giemsa stained. The cytologic diagnosis was proved by clinical course and in most cases by surgical or autoptic histology. Cytologic evaluation lead in 15 cases to the diagnosis of definitive or suspicious malignant liver disease; the sensitivity was 93% and the specificity was 87%. One case classified as suspicious for malignancy by cytologic examination could be identified as cirrhotic nodule by further investigations. In none of the patients did we find complications from the biopsy procedure. From these data it is concluded that US-FNAB can serve as a rapid, inexpensive, safe, and highly accurate first diagnostic step in patients with solid lesions of the liver.

  5. Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

    PubMed

    Godos, Justyna; Micek, Agnieszka; Marranzano, Marina; Salomone, Federico; Rio, Daniele Del; Ray, Sumantra

    2017-08-28

    A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.

  6. Molecular profiles suggest two types of liver cancer should be treated as one | Center for Cancer Research

    Cancer.gov

    A comprehensive molecular analysis of two types of liver cancer, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), has identified common molecular subtypes that can be found among patients with either disease. Although HCC and ICC are considered separate diseases, the finding suggests that a unified clinical approach could benefit patients with both types of liver cancer.  Read more...

  7. [Study on the application of value of digital medical technology in the operation on primary liver cancer].

    PubMed

    Fang, Chi-hua; Lu, Chao-min; Huang, Yan-peng; Li, Xiao-feng; Fan, Ying-fang; Yang, Jian; Xiang, Nan; Pan, Jia-hui

    2009-04-01

    To study the clinical application of digital medical in the operation on primary liver cancer. The patients (n=11) with primary hepatic carcinoma treated between February and July 2008, including 9 cases of hepatocellular carcinoma, 2 cases of cholangiocellular carcinoma, were scanned using 64 slices helicon computerized tomography (CT) and the datasets was collected. Segment and three-dimensional (3D) reconstruction of the CT image was carried out by the medical image processing system which was developed. And the 3D moulds were imported to the FreeForm Modeling System for smoothing. Then the hepatectomy in treatment of hepatoma and implanting of catheter were simulated with the force-feedback equipment (PHANToM). Finally, 3D models and results of simulation surgery were used for choosing mode of operation and comparing with the findings during the operation. The reconstructed models were true to life, and their spatial disposition and correlation were shown clearly; Blood supply of primary liver cancer could be seen easily. In the simulation surgery system, the process of virtual partial hepatectomy and implanting of catheter using simulation scalpel and catheter on 3D moulds with PHANToM was consistent with the clinical course of surgery. Life-like could be felt and power feeling can be touched during simulation operation. Digital medical benefited knowing the relationship between primary liver cancer and the intrahepatic pipe. It gave an advantage to complete primary liver cancer resection with more liver volume remained. It can improve the surgical effect and decrease the surgical risk and reduce the complication through demonstrating visualized operation before surgery.

  8. Identification Of Inequalities In The Selection Of Liver Surgery For Colorectal Liver Metastases In Sweden.

    PubMed

    Norén, A; Sandström, P; Gunnarsdottir, K; Ardnor, B; Isaksson, B; Lindell, G; Rizell, M

    2018-04-01

    Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%-58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. Data were retrieved from the Swedish Colorectal Cancer Registry (2007-2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If "not bowel resected" were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p < 0.0001). Patients with liver metastases from rectal cancer (p < 0.0001) and men more often underwent liver resection (p = 0.006). A difference was found between health-care regions for the frequency of liver surgery (p < 0.0001). Patients >70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the

  9. Intraarterial Liver-Directed Therapies: The Role of Interventional Oncology

    PubMed Central

    Ma, Jenson; Sandow, Tyler; Devun, Daniel; Kirsch, David; Gulotta, Paul; Gilbert, Patrick; Kay, Dennis

    2017-01-01

    Background: Since the early 1990s, the minimally invasive image-guided therapies used in interventional oncology to treat hepatocellular carcinoma have continued to evolve. Additionally, the range of applications has been expanded to the treatment of hepatic metastases from colorectal cancer, neuroendocrine tumors, cholangiocarcinoma, breast cancer, melanoma, and sarcoma. Methods: We searched the literature to identify publications from 1990 to the present on various image-guided intraarterial therapies and their efficacy, as well as their role in the management of primary and secondary liver malignancies. Results: Chemoembolization and radioembolization are considered a standard of care in treating, delaying progression of disease, and downstaging to bridge to liver transplantation. Progression-free survival and overall survival outcomes are promising in patients with colorectal cancer and neuroendocrine tumors with liver metastases. Applications in the treatment of hepatic metastases from cholangiocarcinoma, breast cancer, melanoma, and sarcoma also show potential. Conclusion: Interventional oncology and its image-guided intraarterial therapies continue to gain recognition as treatment options for primary and secondary liver cancers. Growing evidence supports their role as a standard of care alongside medical oncology, surgery, and radiation oncology. PMID:29230127

  10. Novel therapeutic Strategies for Targeting Liver Cancer Stem Cells

    PubMed Central

    Oishi, Naoki; Wang, Xin Wei

    2011-01-01

    The cancer stem cell (CSC) hypothesis was first proposed over 40 years ago. Advances in CSC isolation were first achieved in hematological malignancies, with the first CSC demonstrated in acute myeloid leukemia. However, using similar strategies and technologies, and taking advantage of available surface markers, CSCs have been more recently demonstrated in a growing range of epithelial and other solid organ malignancies, suggesting that the majority of malignancies are dependent on such a compartment. Primary liver cancer consists predominantly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It is believed that hepatic progenitor cells (HPCs) could be the origin of some HCCs and ICCs. Furthermore, stem cell activators such as Wnt/β-catenin, TGF-β, Notch and Hedgehog signaling pathways also expedite tumorigenesis, and these pathways could serve as molecular targets to assist in designing cancer prevention strategies. Recent studies indicate that additional factors such as EpCAM, Lin28 or miR-181 may also contribute to HCC progression by targeting HCC CSCs. Various therapeutic drugs that directly modulate CSCs have been examined in vivo and in vitro. However, CSCs clearly have a complex pathogenesis, with a considerable crosstalk and redundancy in signaling pathways, and hence targeting single molecules or pathways may have a limited benefit for treatment. Many of the key signaling molecules are shared by both CSCs and normal stem cells, which add further challenges for designing molecularly targeted strategies specific to CSCs but sparing normal stem cells to avoid side effects. In addition to the direct control of CSCs, many other factors that are needed for the maintenance of CSCs, such as angiogenesis, vasculogenesis, invasion and migration, hypoxia, immune evasion, multiple drug resistance, and radioresistance, should be taken into consideration when designing therapeutic strategies for HCC. Here we provide a brief review of

  11. Using cancer registries to assess the accuracy of primary liver or intrahepatic bile duct cancer as the underlying cause of death, 1999-2010.

    PubMed

    Polednak, Anthony P

    2013-01-01

    Inaccuracies in primary liver cancer (ie, excluding intrahepatic bile duct [IHBD]) or IHBD cancer as the underlying cause of death on the death certificate vs the cancer site in a cancer registry should be considered in surveillance of mortality rates in the population. Concordance between cancer site on the death record (1999-2010) and diagnosis (1973-2010) in the database for 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program was examined for decedents with only 1 cancer recorded. Overreporting of deaths coded to liver cancer (ie, lack of confirmation in SEER) was largely balanced by underreporting (ie, a cancer site other than liver cancer in SEER). For IHBD cancer, overreporting was much more frequent than underreporting. Using modified rates, based on the most accurate numerators available, had little impact on trends for liver cancer in the SEER population, which were similar to trends for the entire US population based on routine statistics. An increase in the death rate for IHBD cancer, however, was no longer evident after modification. The findings support the use of routine data on underlying cause of death for surveillance of trends in death rates for liver cancer but not for IHBD cancer. Additional population-based cancer registries could potentially be used for surveillance of recent and future trends in mortality rates from these cancers.

  12. Investigation of phosphorylated adjuvants co-encapsulated with a model cancer peptide antigen for the treatment of colorectal cancer and liver metastasis.

    PubMed

    Goodwin, Tyler J; Huang, Leaf

    2017-05-02

    The lipid calcium phosphate nanoparticle is a versatile platform capable of encapsulating a wide range of phosphorylated molecules from single nucleotides to pDNA. The use of this platform has shown great success as an immunotherapeutic vaccine carrier, capable of delivering co-encapsulated phosphorylated adjuvants and peptides. Three potent vaccine formulations were investigated for anti-cancer efficacy. The phosphorylated adjuvants, CpG, 2'3'cGAMP, and 5'pppdsRNA were co-encapsulated with a model phosphorylated tumor specific peptide antigen (p-AH1-A5). The anti-cancer efficacy of these adjuvants was assessed using an orthotopic colorectal liver metastasis model based on highly aggressive and metastatic CT-26 FL3 cells implanted into the cecum wall. The results clearly indicate that the RIG-1 ligand, 5'pppdsRNA, co-encapsulated with the p-AH1-A5 peptide antigen greatly reduced the growth rate of the primary colon cancer as well as arrested the establishment of liver metastasis in comparison to the other adjuvant formulations and unvaccinated controls. Further evaluation of the immune cell populations within the primary tumor confirms the ability of the 5'pppdsRNA adjuvant to boost the adaptive CD8+ T-cell population, while not inciting increased populations of immune suppressive cell types such as T-regulatory cells or myeloid derived suppressor cells. Furthermore, to our knowledge this is the first study to investigate the anti-cancer efficacy of a specific RIG-1 receptor ligand, 5'pppdsRNA, alongside more established TLR 9 (CpG) and STING (2'3'cGAMP) adjuvants in a cancer vaccine. The 5'pppdsRNA vaccine formulation can be a potent immunotherapy, especially when combined with agents that remodel the immune suppressive microenvironment of the tumor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. [Primary cancer of the liver].

    PubMed

    Orozco, H; Mercado, M A

    1997-01-01

    The epidemiologic and pathogenic aspects of primary hepatic malignancies are discussed. The role of viruses in the etiology of the disease is stressed. Imageology methods have a preponderant role for diagnosis and treatment options. Liver resection has a one years survival between 60 and 80% and a five years survival of 20 to 40%. A good surgical results is expected for tumors with no more than 5 cm in diameter, encapsulated and without vascular invasion non-cirrhotic livers, large tumors can also be removed. Surgical resection margin should be of 1 cm. For cirrhotic livers, a good liver function is needed (Child A-B) and no safe major resection can be done. History of bleeding portal hypertension has a negative role in the outcome. Liver transplantation should be limited to selected case, in which the tumors are small and asymptomatic (incidental). For larger tumors, long term results are not good with invariable recurrency of the tumor.

  14. Optimizing global liver function in radiation therapy treatment planning

    NASA Astrophysics Data System (ADS)

    Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

    2016-09-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and

  15. Predicting liver metastasis of gastrointestinal tract cancer by diffusion-weighted imaging of apparent diffusion coefficient values

    PubMed Central

    Zheng, De-Xian; Meng, Shu-Chun; Liu, Qing-Jun; Li, Chuan-Ting; Shang, Xi-Dan; Zhu, Yu-Seng; Bai, Tian-Jun; Xu, Shi-Ming

    2016-01-01

    AIM: To determine if efficacy of chemotherapy on liver metastasis of gastrointestinal tract cancer can be predicted by apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). METHODS: In total, 86 patients with liver metastasis of gastrointestinal tract cancer (156 metastatic lesions) diagnosed in our hospital were included in this study. The maximum diameters of these tumors were compared with each other before treatment, 2 wk after treatment, and 12 wk after treatment. Selected patients were classified as the effective group and the ineffective group, depending on the maximum diameter of the tumor after 12 wk of treatment; and the ADC values at different treatment times between the two groups were compared. Spearman rank correlation was used to analyze the relationship between ADC value and tumor diameter. Receiver operating characteristic curve (ROC curve) was used to analyze the ADC values before treatment to predict the patient’s sensitivity and specificity degree of efficacy to the chemotherapy. RESULTS: There was no difference in age between the two groups and in maximum tumor diameter before treatment and 2 wk after treatment. However, after 12 wk of treatment, maximum tumor diameter in the effective group was significantly lower than that in the ineffective group (P < 0.05). Before treatment, ADC values in the ineffective group were significantly higher than those in the effective group (P < 0.05). There was no difference in ADC values between the effective and ineffective groups after 2 and 12 wk of treatment. However, ADC values were significantly higher after 2 and 12 wk of treatment compared to before treatment in the effective group (P < 0.05). Spearman rank correlation analysis showed that ADC value before treatment and the reduced percentage of the maximum tumor diameter after 12 wk of treatment were negatively correlated, while the increase in the percentage of the ADC value 12 wk after treatment and the decrease in the

  16. Meta-analysis reveals gender difference in the association of liver cancer incidence and excess BMI.

    PubMed

    Yao, Kun-Fang; Ma, Ming; Ding, Guo-Yong; Li, Zhan-Ming; Chen, Hui-Ling; Han, Bing; Chen, Qiang; Jiang, Xin-Quan; Wang, Li-Shun

    2017-09-22

    Excess body weight has a positive association with risk of liver cancer, but the gender difference in the relationship between body mass index and liver cancer risk remains uncertainty. In this work, we performed meta-analysis for excess body weight and risk of liver cancer incidence to identify the gender difference. We searched the English-languages database and the Chinese literature databases to May 12, 2017. Overall, a total of 17 studies were included. Relative risks (RRs) with 95% confidence intervals was used to evaluate the strength of these associations. The RRs of liver cancer incidence for obese men and women were 2.04 (1.70-2.44) and 1.56 (1.37-1.78). The former one was significantly higher than the later one (P for interaction = 0.02). Notably, the RR of liver cancer incidence in non-Asian obese men was even higher than their counter part (2.31(1.85-2.91) vs. 1.56 (1.31-1.86), P for interaction = 0.01). Similar gender difference was observed in the dose-response curve. As example, at the point of BMI = 32 kg/m 2 , the RRs for men and women were 1.61 (1.45-1.79) and 1.41 (1.02-1.94) respectively. Findings from this meta-analysis indicate that obesity is associated with a higher risk of liver cancer incidence in men, especially in non-Asian men, which might partially contribute to the male dominance of liver cancer incidence.

  17. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2018-03-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  18. How Effective Are Percutaneous Liver-Directed Therapies in Patients with Non-Colorectal Liver Metastases?

    PubMed Central

    Vogl, Thomas J.; Emam, Ahmed; Naguib, Nagy N.; Eichler, Katrin; Zangos, Stefan

    2015-01-01

    Summary Background The purpose of this review is to demonstrate the clinical indications, technical developments, and outcome of liver-directed therapies in interventional oncology of non-colorectal liver metastases. Methods Liver-directed therapies are classified into vascular transarterial techniques such as chemoperfusion (TACP), chemoembolization (TACE), radioembolization (selective internal radiation therapy (SIRT)), and chemosaturation, as well as thermal ablation techniques like microwave ablation (MWA), radiofrequency ablation (RFA), laser-induced thermotherapy (LITT), cryotherapy, and irreversible electroporation (IRE). The authors searched the database PubMed using the following terms: ‘image-guided tumor ablation’, ‘thermal ablation therapies’, ‘liver metastases of uveal melanoma’, ‘neuroendocrine carcinoma’, ‘breast cancer’, and ‘non-colorectal liver metastases’. Results Various combinations of the above-mentioned therapy protocols are possible. In neuroendocrine carcinomas, oligonodular liver metastases are treated successfully via thermal ablation like RFA, LITT, or MWA, and diffuse involvement via TACE or SIRT. Although liver involvement in breast cancer is a systemic disease, non-responding nodular metastases can be controlled via RFA or LITT. In ocular or cutaneous melanoma, thermal ablation is rarely considered as an interventional treatment option, as opposed to TACE, SIRT, or chemosaturation. Rarely liver-directed therapies are used in pancreatic cancer, most likely due to problems such as biliary digestive communications after surgery and the risk of infections. Rare indications for thermal ablation are liver metastases of other primary cancers like non-small cell lung, gastric, and ovarian cancer. Conclusion Interventional oncological techniques play a role in patients with liver-dominant metastases. PMID:26889144

  19. Curcumin effectively inhibits oncogenic NF-kB signaling and restrains stemness features in liver cancer

    PubMed Central

    Marquardt, Jens U.; Gomez-Quiroz, Luis; Camacho, Lucrecia O. Arreguin; Pinna, Federico; Lee, Yun-Han; Kitade, Mitsuteru; Domínguez, Mayrel Palestino; Castven, Darko; Breuhahn, Kai; Conner, Elizabeth A.; Galle, Peter R.; Andersen, Jesper B.; Factor, Valentina M.; Thorgeirsson, Snorri S.

    2015-01-01

    Background & Aims The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-kB signaling. Methods We evaluated the CSCs-depleting potential of NF-kB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of Side Population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. Results HCC cell lines exposed to curcumin exhibited differential responses to curcumin and were classified as sensitive and resistant. In sensitive lines, curcumin-mediated induction of cell death was directly related to the extent of NF-kB inhibition. The treatment also led to a selective CSC-depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-kB inhibition by SN50 and siRNA against p65 suppressed tumor cell growth. In contrast, curcumin-resistant cells displayed a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, an important component of the CSC-depleting activity of curcumin could be attributed to a NF-kB-mediated HDAC inhibition. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitivity with human HCC database indicated that HCCs with poor prognosis and progenitor features are most likely to benefit from NF-kB inhibition. Conclusions These results demonstrate that blocking NF-kB can specifically target CSC populations and suggest a potential for combined inhibition of NF-kB and HDAC signaling for treatment of liver cancer patients with poor prognosis. PMID:25937435

  20. Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose–Response Meta-Analysis of Prospective Cohort Studies

    PubMed Central

    Micek, Agnieszka; Marranzano, Marina; Ray, Sumantra

    2017-01-01

    Background: A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Methods: Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose–response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. Results: We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose–response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). Conclusions: The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC. PMID:28846640

  1. [Treatment of liver cirrhosis - actually possibility of ambulant internist].

    PubMed

    Ehrmann, Jiří; Aiglová, Květa; Konečný, Michal; Procházka, Vlastimil; Vrzalová, Drahomíra

    There are 40 000-60 000 patients with cirrhosis in the Czech Republic. 2 000 die of this disease yearly. This group of patients needs a complex treatment and it is mostly an internist cooperating with other specialists. The most important for an ambulant internist is to diagnose the disease as soon as possible and start with treatment of chronic liver disease that could lead to a cirrhosis. It means especially chronic viral hepatitis, alcoholic or non-alcoholic steatosis/steatohepatitis, auto-immune liver damage and metabolic disease. The next step is to diagnose the cirrhosis in time when it is in no manifest stage. The third step is to diagnose and treat the liver decompensation. It means consequences of the portal hypertension, it is ascit, esophageal or gastric varices, hepatorenal syndrome. Next there are consequences of the metabolic insufficiency, it is icterus, coagulopathy and hepatic encephalopathy. It is necessary to diagnose and cure cholestasis from the very first extrahepatic causes. For a successful treatment of the hepatocellular carcinoma originated almost exclusively in the grounds of the cirrhosis must be early diagnosed. The ambulant internist respective hepatologist must diagnose the stage of the cirrhosis and decide when a hospitalization is necessary. Also a close cooperation with other specialists is urgent if it is about a liver transplantation. The treatment of successive stages of the cirrhosis is a topic of the showed educational article. compensated/decompensated liver cirrhosis - diet/nutrition in liver cirrhosis - etiology and diagnose of liver cirrhosis - treatment of liver insufficiency/failure - treatment of portal hypertension and its complications.

  2. Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

    PubMed Central

    French, Samuel W.

    2013-01-01

    Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

  3. Associations of NSAID and paracetamol use with risk of primary liver cancer in the Clinical Practice Research Datalink.

    PubMed

    Yang, Baiyu; Petrick, Jessica L; Chen, Jie; Hagberg, Katrina Wilcox; Sahasrabuddhe, Vikrant V; Graubard, Barry I; Jick, Susan; McGlynn, Katherine A

    2016-08-01

    Liver cancer incidence has been rising rapidly in Western countries. Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are widely-used analgesics that may modulate the risk of liver cancer, but population-based evidence is limited. We conducted a case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink to examine the association between the use of prescription NSAIDs and paracetamol and development of liver cancer. Multivariable-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Overall, ever-use of NSAIDs was not associated with risk of liver cancer (aOR=1.05, 95% CI=0.88-1.24), regardless of recency and intensity of use. Use of paracetamol was associated with a slightly increased risk of liver cancer (aOR=1.18, 95% CI=1.00-1.39), particularly among individuals with body mass index<25kg/m(2) (aOR=1.56, 95% CI=1.17-2.09). Our results suggest that NSAID use was not associated with liver cancer risk in this population. Ever-use of paracetamol may be associated with slightly higher liver cancer risk, but results should be interpreted cautiously due to methodological limitations. Given that paracetamol is a widely-used analgesic, further examination of its relationship with liver cancer is warranted. Published by Elsevier Ltd.

  4. Pharmacokinetic variations in cancer patients with liver dysfunction: applications and challenges of pharmacometabolomics.

    PubMed

    Aboel Dahab, Ali; El-Hag, Dhia; Moutamed, Gamal M; Aboel Dahab, Sarah; Abuknesha, Ramadan; Smith, Norman W

    2016-09-01

    In cancer patients, pharmacokinetic variations between individuals and within individuals due to impairments in organs' function and other reasons such as genetic polymorphisms represent a major problem in disease management, which can result in unpredictable toxicity and variable antineoplastic effects. Addressing pharmacokinetic variations in cancer patients with liver dysfunction and their implications on anticancer and analgesic drugs, in addition to the use of advanced analytical techniques such as metabolomics and pharmacometabolomics, to monitor altered kinetic and discover metabolic biomarkers during therapeutic intervention will help in understanding and reducing pharmacokinetic variations of drugs in cancer patients as a step forward towards personalised medicine. Reviewing published literature addressing and/or related to complications resulting from altered pharmacokinetics (PKs) in cancer patients with liver dysfunction, anticancer and analgesic drugs, evaluating recent advances of pharmacokinetic detection using metabolomics/pharmacometabolomics and the challenges that are currently facing these techniques. The current situation presents a pressing need to reduce pharmacokinetic variations of drugs in cancer patients. Although most of the omics technologies are not entirely focussed on the study of pharmacokinetic variations and some studies are met with uncertainty, the use of pharmacometabolomics combined with other omics technology such as pharmacogenomics can provide clues to personalised cancer treatments by providing useful information about the cancer patient's response to medical interventions via identification of patients' dependent variables, understanding of correlations between individuals and population PKs, and therapy outcomes to achieve optimum therapeutic effects with minimum toxicity. We also propose an approach for PKs' evaluation using pharmacometabolomics.

  5. Prospective Longitudinal Assessment of Quality of Life for Liver Cancer Patients Treated With Stereotactic Body Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Klein, Jonathan, E-mail: jonathan.klein@rmp.uhn.on.ca; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario; Dawson, Laura A.

    Purpose: To evaluate quality of life (QoL), an important outcome owing to poor long-term survival, after stereotactic body radiation therapy (SBRT) to the liver. Methods and Materials: Patients (n=222) with hepatocellular carcinoma (HCC), liver metastases, or intrahepatic cholangiocarcinoma and Child-Pugh A liver function received 24-60 Gy of 6-fraction image-guided SBRT. Prospective QoL assessment was completed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and/or Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep, version 4) questionnaires at baseline and 1, 3, 6, and 12 months after treatment. Ten HCC patients with Child-Pugh B liver function were alsomore » treated. Results: The QLQ-C30 was available for 205 patients, and 196 completed the FACT-Hep. No difference in baseline QoL (P=.17) or overall survival (P=.088) was seen between the HCC, liver metastases, and intrahepatic cholangiocarcinoma patients. Appetite loss and fatigue measured by the QLQ-C30 clinically and statistically worsened by 1 month after treatment but recovered by 3 months. At 3 and 12 months after treatment, respectively, the FACT-Hep score had improved relative to baseline in 13%/19%, worsened in 36%/27%, and remained stable in 51%/54%. Using the QLQ-C30 Global Health score, QoL improved in 16%/23%, worsened in 34%/39%, and remained stable in 50%/38% at 3 and 12 months, respectively. Median survival was 17.0 months (95% confidence interval [CI] 12.3-19.8 months). Higher baseline scores on both FACT-Hep and QLQ-C30 Global Health were associated with improved survival. Hazard ratios for death, per 10-unit decrease in QoL, were 0.90 (95% CI 0.83-0.98; P=.001) and 0.88 (95% CI 0.82-0.95; P=.001), respectively. Tumor size was inversely correlated with survival. Conclusions: Liver SBRT temporarily worsens appetite and fatigue, but not overall QoL. Stereotactic body radiation therapy is well tolerated and

  6. Hyperspectral Stimulated Raman Scattering Microscopy Unravels Aberrant Accumulation of Saturated Fat in Human Liver Cancer.

    PubMed

    Yan, Shuai; Cui, Sishan; Ke, Kun; Zhao, Bixing; Liu, Xiaolong; Yue, Shuhua; Wang, Ping

    2018-06-05

    Lipid metabolism is dysregulated in human cancers. The analytical tools that could identify and quantitatively map metabolites in unprocessed human tissues with submicrometer resolution are highly desired. Here, we implemented analytical hyperspectral stimulated Raman scattering microscopy to map the lipid metabolites in situ in normal and cancerous liver tissues from 24 patients. In contrast to the conventional wisdom that unsaturated lipid accumulation enhances tumor cell survival and proliferation, we unexpectedly visualized substantial amount of saturated fat accumulated in cancerous liver tissues, which was not seen in majority of their adjacent normal tissues. Further analysis by mass spectrometry confirmed significant high levels of glyceryl tripalmitate specifically in cancerous liver. These findings suggest that the aberrantly accumulated saturated fat may have great potential to be a metabolic biomarker for liver cancer.

  7. Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases.

    PubMed

    Qian, Yun; Sang, Yiwen; Wang, Frederick X C; Hong, Bo; Wang, Qi; Zhou, Xinhui; Weng, Tianhao; Wu, Zhigang; Zheng, Min; Zhang, Hong; Yao, Hangping

    2016-11-01

    Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.

  8. [Preliminary use of HoloLens glasses in surgery of liver cancer].

    PubMed

    Shi, Lei; Luo, Tao; Zhang, Li; Kang, Zhongcheng; Chen, Jie; Wu, Feiyue; Luo, Jia

    2018-05-28

    To establish the preoperative three dimensional (3D) model of liver cancer, and to precisely match the preoperative planning with the target organs during the operation.
 Methods: The 3D model reconstruction based on magnetic resonance data, which was combined with virtual reality technology via HoloLens glasses, was applied in the operation of liver cancer to achieve preoperative 3D modeling and surgical planning, and to directly match it with the operative target organs during operation.
 Results: The 3D model reconstruction of liver cancer based on magnetic resonance data was completed. The exact match with the target organ was performed during the operation via HoloLens glasses leaded by the 3D model.
 Conclusion: Magnetic resonance data can be used for the 3D model reconstruction to improve preoperative assessment and accurate match during the operation.

  9. Electrochemical lesions in the rat liver support its potential for treatment of liver tumors.

    PubMed

    Wemyss-Holden, S A; Robertson, G S; Dennison, A R; de la M Hall, P; Fothergill, J C; Jones, B; Maddern, G J

    2000-09-01

    An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors. Copyright 2000 Academic Press.

  10. Automated geometric optimization for robotic HIFU treatment of liver tumors.

    PubMed

    Williamson, Tom; Everitt, Scott; Chauhan, Sunita

    2018-05-01

    High intensity focused ultrasound (HIFU) represents a non-invasive method for the destruction of cancerous tissue within the body. Heating of targeted tissue by focused ultrasound transducers results in the creation of ellipsoidal lesions at the target site, the locations of which can have a significant impact on treatment outcomes. Towards this end, this work describes a method for the optimization of lesion positions within arbitrary tumors, with specific anatomical constraints. A force-based optimization framework was extended to the case of arbitrary tumor position and constrained orientation. Analysis of the approximate reachable treatment volume for the specific case of treatment of liver tumors was performed based on four transducer configurations and constraint conditions derived. Evaluation was completed utilizing simplified spherical and ellipsoidal tumor models and randomly generated tumor volumes. The total volume treated, lesion overlap and healthy tissue ablated was evaluated. Two evaluation scenarios were defined and optimized treatment plans assessed. The optimization framework resulted in improvements of up to 10% in tumor volume treated, and reductions of up to 20% in healthy tissue ablated as compared to the standard lesion rastering approach. Generation of optimized plans proved feasible for both sub- and intercostally located tumors. This work describes an optimized method for the planning of lesion positions during HIFU treatment of liver tumors. The approach allows the determination of optimal lesion locations and orientations, and can be applied to arbitrary tumor shapes and sizes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer.

    PubMed

    Zhu, Dunwan; Tao, Wei; Zhang, Hongling; Liu, Gan; Wang, Teng; Zhang, Linhua; Zeng, Xiaowei; Mei, Lin

    2016-01-01

    Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle (NP) surfaces with ligands and/or additional polymeric layers. In this work, we developed DTX-loaded formulations using polydopamine-modified NPs synthesized using D-α-tocopherol polyethylene glycol 1000 succinate-poly(lactide) (pD-TPGS-PLA/NPs). To target liver cancer cells, galactosamine was conjugated on the prepared NPs (Gal-pD-TPGS-PLA/NPs) to enhance the delivery of DTX via ligand-mediated endocytosis. The size and morphology of pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs changed obviously compared with TPGS-PLA/NPs. In vitro studies showed that TPGS-PLA/NPs, pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs had similar release profiles of DTX. Both confocal laser scanning microscopy and flow cytometric results showed that coumarin 6-loaded Gal-pD-TPGS-PLA/NPs had the highest cellular uptake efficiency in liver cancer cell line HepG2. Moreover, DTX-loaded Gal-pD-TPGS-PLA/NPs inhibited the growth of HepG2 cells more potently than TPGS-PLA/NPs, pD-TPGS-PLA/NPs, and a clinically available DTX formulation (Taxotere®). The in vivo biodistribution experiments show that the Gal-pD-TPGS-PLA/NPs are specifically targeted to the tumor. Furthermore, the in vivo anti-tumor effects study showed that injecting DTX-loaded Gal-pD-TPGS-PLA/NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. These results suggest that Gal-pD-TPGS-PLA/NPs prepared in the study specifically interacted with the hepatocellular carcinoma cells through ligand-receptor recognition and they may be used as a potentially eligible drug delivery system targeting liver cancers. Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle surfaces with ligands and/or additional polymeric layers. In this work, we developed docetaxel (DTX)-loaded formulations using polydopamine-modified NPs synthesized from D-α-tocopherol polyethylene glycol 1000 succinate

  12. Increased incidence of head and neck cancer in liver transplant recipients: a meta-analysis.

    PubMed

    Liu, Qian; Yan, Lifeng; Xu, Cheng; Gu, Aihua; Zhao, Peng; Jiang, Zhao-Yan

    2014-10-22

    It is unclear whether liver transplantation is associated with an increased incidence of post-transplant head and neck cancer. This comprehensive meta-analysis evaluated the association between liver transplantation and the risk of head and neck cancer using data from all available studies. PubMed and Web of Science were systematically searched to identify all relevant publications up to March 2014. Standardized incidence ratio (SIR) and 95% confidence intervals (CIs) for risk of head and neck cancer in liver transplant recipients were calculated. Tests for heterogeneity, sensitivity, and publishing bias were also performed. Of the 964 identified articles, 10 were deemed eligible. These studies included data on 56,507 patients with a total follow-up of 129,448.9 patient-years. SIR for head and neck cancer was 3.836-fold higher (95% CI 2.754-4.918, P = 0.000) in liver transplant recipients than in the general population. No heterogeneity or publication bias was observed. Sensitivity analysis indicated that omission of any of the studies resulted in an SIR for head and neck cancer between 3.488 (95% CI: 2.379-4.598) and 4.306 (95% CI: 3.020-5.592). Liver transplant recipients are at higher risk of developing head and neck cancer than the general population.

  13. Histologic analysis of rabbit liver cancer treated by bulk ultrasound ablation

    NASA Astrophysics Data System (ADS)

    Karunakaran, Chandra Priya; Rudich, Steven M.; Alqadah, Amel; Burgess, Mark T.; Narmoneva, Daria A.; Mast, T. Douglas

    2012-10-01

    VX2 rabbit liver cancer, treated in vivo using bulk ultrasound ablation by miniaturized image-ablate arrays, was histologically analyzed using TTC vital stain and DAPI nucleic acid stain. VX2 cells were implanted into rabbit liver lobes and allowed to grow for 11-21 days. Liver lobes containing solid VX2 tumors were then treated with 4.8 MHz, 22.5-38.5 W/cm2 in situ intensity, unfocused ultrasound for exposure times of 20-120 s. After animal sacrifice, thermal lesions were bisected along the imaging/treatment plane, one face stained with TTC, and the other with DAPI. Levels of TTC uptake (no uptake, partial uptake, and complete uptake) in liver parenchyma corresponded to three discrete regions of tan, pink and red color. By processing images of DAPI-stained parenchymal tissue from these three regions, cellular damage was quantified. A viability index parameter incorporating the size and shape of DAPI-stained nuclei correlated significantly with levels of TTC uptake, and thus with local tissue viability. For ablation of normal liver, viability indices for parenchymal regions of no TTC uptake and partial TTC uptake were significantly different from those for viable tissue. For ablation of VX2 tumor, differences in viability index between regions of no TTC uptake and complete TTC uptake were smaller, but significant overall.

  14. Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study.

    PubMed

    Wu, Wenrui; He, Xingkang; Andayani, Dewi; Yang, Liya; Ye, Jianzhong; Li, Yating; Chen, Yanfei; Li, Lanjuan

    2017-01-01

    Background and Aims : Primary liver cancer remains still the common cause of cancer-related deaths globally and the prognosis for patients with extrahepatic metastasis is poor. The aim of our study was to assess extrahepatic metastatic pattern of different histological subtypes and evaluate prognostic effects of extrahepatic metastasis in patients with advanced disease. Methods: Based on the Surveillance, Epidemiology and End Results (SEER) database, eligible patients diagnosed with primary liver cancer was identified between 2010 to 2012. We adopted Chi-square test to compared metastasis distribution among different histological types. We compared survival difference of patients with different extrahepatic metastasises by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify other prognostic factors of overall survival. Results: We finally identified 8677 patients who were diagnosed with primary liver cancer from 2010 to 2012 and 1775 patients were in distant metastasis stages. Intrahepatic cholangiocarcinoma was more invasive and had a higher percentage of metastasis compared with hepatocellular carcinoma. Lung was the most common metastasis and brain was the least common site for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Extrahepatic metastasis could consider as an independent prognostic factor for patients with liver cancer. Patients with brain metastasis had the worst prognosis, compared with other metastasis in overall survival (OS) and cancer-specific survival (CSS) analysis. Conclusions: Different histological subtypes of liver cancer had different metastasis patterns. There were profound differences in risk of mortality among distant extrahepatic metastatic sites. Results from our studies would provide some information for follow-up strategies and future studies.

  15. Role of bicyclol in preventing chemotherapeutic agent-induced liver injury in patients over 60 years of age with cancer.

    PubMed

    Li, Xiaoyuan; Zhou, Jianfeng; Chen, Shuchang; Guan, Mei; Wang, Yingyi; Zhao, Lin; Ying, Hongyan; Zhou, Yanping

    2014-08-01

    To evaluate the efficacy of bicyclol in preventing chemotherapy-induced liver damage. Patients ≥60 years of age with cancer were equally randomized into control (chemotherapy alone) or prophylactic (chemotherapy supplemented with 75 mg bicyclol, oral, daily) groups. Liver function indices were assessed immediately before treatment, during each therapy cycle and following treatment. Of 306 patients enrolled, 300 patiets completed the study (n = 147 and n = 153; prophylactic and control groups, respectively). Incidence of grade I-IV elevation of serum transaminase and/or bilirubin was significantly lower in the prophylactic group (17.1%) compared with the control group (47.1%). Incidence of grade II-IV hepatic injury was also significantly lower in the prophylactic group (0.7%) than in the control group (12.4%). Prophylactic bicyclol (75 mg daily) could significantly reduce the incidence and degree of chemotherapeutic agent-induced liver damage in elderly patients with cancer. Further studies are recommended with larger sample sizes and long-term follow up. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. Blood glucose concentration and risk of liver cancer: systematic review and meta-analysis of prospective studies.

    PubMed

    Han, Hedong; Zhang, Tianyi; Jin, Zhichao; Guo, Honglei; Wei, Xin; Liu, Yuzhou; Chen, Qi; He, Jia

    2017-07-25

    The question of whether elevated blood glucose is a risk factor for liver cancer has been intensively studied, yet with inconsistent results. To explore the relationship between blood glucose concentration and risk of liver cancer, we conduct a meta-analysis of prospective studies. Literature search was comprehensively performed using database of PubMed, EMBASE and the Cochrane Library through October 2016. Random-effect models were used to combine the effect estimations. Eight articles containing ten studies with a total of 1975 liver cancer cases were included. The pooled RRs demonstrated that elevated fasting blood glucose was associated with increased risk of liver cancer (combined RRs: 1.77; 95% CI: 1.46, 2.13) with mild heterogeneity (I2 = 30.40%, P = 0.17). In sensitivity analysis, the pooled result remained significant (combined RRs: 1.33; 95% CI: 1.12, 1.59; I2 = 33.90%, P = 0.16) when we restricted blood glucose categories in the range of nondiabetic subjects. We also detected a J-shaped non-linear dose-response relationship between blood glucose concentration and risk of liver cancer. There is evidence that elevated blood glucose increases risk of liver cancer across the range of prediabetes and diabetes. Considering the rapidly increasing prevalence of prediabetes and diabetes, controlling blood glucose may lower the risk of liver cancer.

  17. The Role of Re-resection for Breast Cancer Liver Metastases-a Single Center Experience.

    PubMed

    BacalbaȘa, Nicolae; Balescu, Irina; Dima, Simona; Popescu, Irinel

    2015-12-01

    The aim of the present study was to evaluate the effectiveness and safety of hepatic re-resection for breast cancer liver metastases. Between January 2004 and December 2014 seven patients were submitted to liver re-resection for breast cancer liver metastases at our Center. The main inclusion criteria were presence of isolated liver metastases and absence of systemic recurrent disease Results: The median age at the time of breast surgery was 51 years (range=39-69 years). The first liver resection was performed after a median period of 34.7 months and consisted of minor hepatectomies in six and major hepatectomy in one patient. The second liver resection was performed after a median interval of 22 months from the first liver resection and consisted of major resection in one case and minor resection in the other six cases. Postoperative complications occurred in a single case after the first liver surgery and in two cases after the second hepatic resection, all cases being successfully managed conservatively. Overall postoperative mortality was 0. The median overall survival after the second liver resection was 28 months. Re-resection for breast cancer liver metastases can be safely performed and may bring survival benefit. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Role of functional imaging in treatment plan optimization of stereotactic body radiation therapy for liver cancer.

    PubMed

    De Bari, Berardino; Jumeau, Raphael; Deantonio, Letizia; Adib, Salim; Godin, Sarah; Zeverino, Michele; Moeckli, Raphael; Bourhis, Jean; Prior, John O; Ozsahin, Mahmut

    2016-10-13

    We report the first known instance of the clinical use of 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) for the optimization of radiotherapy treatment planning and for the follow-up of acute toxicity in a patient undergoing stereotactic body radiation therapy for hepatocellular carcinoma. In our experience, HBS allowed the identification and the sparing of more functioning liver areas, thus potentially reducing the risk of radiation-induced liver toxicity.

  19. Construction and analysis of circular RNA molecular regulatory networks in liver cancer.

    PubMed

    Ren, Shuangchun; Xin, Zhuoyuan; Xu, Yinyan; Xu, Jianting; Wang, Guoqing

    2017-01-01

    Liver cancer is the sixth most prevalent cancer, and the third most frequent cause of cancer-related deaths. Circular RNAs (circRNAs), a kind of special endogenous ncRNAs, have been coming back to the forefront of cancer genomics research. In this study, we used a systems biology approach to construct and analyze the circRNA molecular regulatory networks in the context of liver cancer. We detected a total of 127 differentially expressed circRNAs and 3,235 differentially expressed mRNAs. We selected the top-5 upregulated circRNAs to construct a circRNA-miRNA-mRNA network. We enriched the pathways and gene ontology items and determined their participation in cancer-related pathways such as p53 signaling pathway and pathways involved in angiogenesis and cell cycle. Quantitative real-time PCR was performed to verify the top-five circRNAs. ROC analysis showed circZFR, circFUT8, circIPO11 could significantly distinguish the cancer samples, with an AUC of 0.7069, 0.7575, and 0.7103, respectively. Our results suggest the circRNA-miRNA-mRNA network may help us further understand the molecular mechanisms of tumor progression in liver cancer, and reveal novel biomarkers and therapeutic targets.

  20. Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer.

    PubMed

    Miao, Ruoyu; Wu, Yan; Zhang, Haohai; Zhou, Huandi; Sun, Xiaofeng; Csizmadia, Eva; He, Lian; Zhao, Yi; Jiang, Chengyu; Miksad, Rebecca A; Ghaziani, Tahereh; Robson, Simon C; Zhao, Haitao

    2016-09-13

    Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer.

  1. Hematoporphyrin-Augmented Phototherapy: Dosimetric Studies In Experimental Liver Cancer In The Rat

    NASA Astrophysics Data System (ADS)

    Pimstone, N. R.; Horner, I. J.; Shaylor-Billings, J.; Gandhi, S. N.

    1982-12-01

    log of incident light energy (joules/sq cm). 3) The photodynamic effect of red coherent light (545-625 nm) from a tunable dye pulse laser system was no different from that of red light from a continuous noncoherent (Tungsten) source. 4) There was a logarithmic relationship between the dose of HP administered and the depth of liver necrosis. 5) If one interposed a photoopaque shield between the incident laser light and the liver, a considerable back scattering of light caused tissue necrosis behind the shield. However, when the diameter of the shield was greater than 1.3 mm, there always was a surviving island of tissue which escaped destruction. 6) The depth of necrosis in liver (mms) was significantly less than adjacent non-pigment tumor (cms) which suggests that the optical density of the tissue is a major factor in determining effective light penetration. We conclude that measurement of tissue porphyrin, and optical density with reference to the liver, will allow precise calculation potentially of major clinical importance in the treatment of skin and mucosal cancers.

  2. Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

    ClinicalTrials.gov

    2015-05-14

    Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  3. High-Content Functional Screening of AEG-1 and AKR1C2 for the Promotion of Metastasis in Liver Cancer.

    PubMed

    Li, Cong; Wu, Xia; Zhang, Wei; Li, Jia; Liu, Huawei; Hao, Ming; Wang, Junsong; Zhang, Honghai; Yang, Gengxia; Hao, Meijun; Sheng, Shoupeng; Sun, Yu; Long, Jiang; Li, Juan; Zhuang, Fengfeng; Hu, Caixia; Li, Li; Zheng, Jiasheng

    2016-01-01

    Liver cancer is one of the most lethal cancer types in humans, but our understanding of the molecular mechanisms underlying this process remains insufficient. Here, we conducted high-content screening of the potential genes involved in liver cancer metastasis, which we selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, based on the SAMcell method and RNA interference technology. We identified two powerful genes in the liver cancer metastasis process, AEG-1 and AKR1C2, both of which proved to be positive regulators in promoting metastasis in liver cancer. Further clinical results verified their roles in liver cancer. In summary, these findings could provide new insight into the liver cancer mechanism and potentially therapeutic novel targets for liver cancer therapies in the future. © 2015 Society for Laboratory Automation and Screening.

  4. Basic and clinical research on the therapeutic effect of intervention in primary liver cancer by targeted intra-arterial verapamil infusion.

    PubMed

    Pingsheng, Fan; Tengyue, Zhang; Qiang, Huang; Qiang, Wei; Xin, Sun; Liting, Qian

    2012-01-01

    The aim of this study was assess the therapeutic effect of targeted intra-arterial verapamil infusion in liver cancer patients and its side-effects in a dog model. The blood verapamil levels in dogs were determined after one-off intra-arterial infusion (0.7 mg/kg). Blood pressure, breathing state, and II-lead electrocardiogram were measured. Primary liver cancer patients (100) were randomly assigned into two groups. Controls (50) were treated with targeted intra-arterial infusion, and every patient received once-a-month interventional therapy, twice. Treatment group (50) received chemotherapeutics plus verapamil. Therapeutic and toxic side effects were evaluated. Control (41) and treatment group (45) patients were further treated with a second round of targeted intra-arterial infusion of chemotherapeutics plus verapamil, in 30 days after the 2-time interventional therapy. Every patient accepted interventional therapy 4-5 times during the 6 months after the first confirmed diagnosis. Following verapamil infusion, verapamil in dog liver was tenfold higher than in blood and was 4- to 20-fold higher than that needed for reversing carcinoma drug resistance. After interventional therapy, there were no significant changes in iconographic evaluation indices between the groups. Average activities of aminotransferases were 332 and 178 U/l in the treatment and control groups (P < 0.05). The imaging parameters of the treatment group were significantly better than those of control group. No side effects were found among the 91 patients who accepted verapamil infusion. After verapamil infusion, verapamil levels in dog hepatic tissue exceeded the effective concentration that reverses carcinoma multidrug resistance without any visible changes in the vital signs. Targeted intra-arterial verapamil infusion could improve the chemotherapy for the primary liver cancer patients without any side effects.

  5. Anti-LRP/LR Specific Antibody IgG1-iS18 Impedes Adhesion and Invasion of Liver Cancer Cells

    PubMed Central

    Chetty, Carryn; Khumalo, Thandokuhle; Da Costa Dias, Bianca; Reusch, Uwe; Knackmuss, Stefan; Little, Melvyn; Weiss, Stefan F. T.

    2014-01-01

    Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson's correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction. PMID:24798101

  6. Weighted gene co-expression network analysis of colorectal cancer liver metastasis genome sequencing data and screening of anti-metastasis drugs.

    PubMed

    Gao, Bo; Shao, Qin; Choudhry, Hani; Marcus, Victoria; Dong, Kung; Ragoussis, Jiannis; Gao, Zu-Hua

    2016-09-01

    Approximately 9% of cancer-related deaths are caused by colorectal cancer (CRC). CRC patients are prone to liver metastasis, which is the most important cause for the high CRC mortality rate. Understanding the molecular mechanism of CRC liver metastasis could help us to find novel targets for the effective treatment of this deadly disease. Using weighted gene co-expression network analysis on the sequencing data of CRC with and with metastasis, we identified 5 colorectal cancer liver metastasis related modules which were labeled as brown, blue, grey, yellow and turquoise. In the brown module, which represents the metastatic tumor in the liver, gene ontology (GO) analysis revealed functions including the G-protein coupled receptor protein signaling pathway, epithelial cell differentiation and cell surface receptor linked signal transduction. In the blue module, which represents the primary CRC that has metastasized, GO analysis showed that the genes were mainly enriched in GO terms including G-protein coupled receptor protein signaling pathway, cell surface receptor linked signal transduction, and negative regulation of cell differentiation. In the yellow and turquoise modules, which represent the primary non-metastatic CRC, 13 downregulated CRC liver metastasis-related candidate miRNAs were identified (e.g. hsa-miR-204, hsa-miR-455, etc.). Furthermore, analyzing the DrugBank database and mining the literature identified 25 and 12 candidate drugs that could potentially block the metastatic processes of the primary tumor and inhibit the progression of metastatic tumors in the liver, respectively. Data generated from this study not only furthers our understanding of the genetic alterations that drive the metastatic process, but also guides the development of molecular-targeted therapy of colorectal cancer liver metastasis.

  7. Utilization pattern of traditional Chinese medicine for liver cancer patients in Taiwan.

    PubMed

    Liao, Yueh-Hsiang; Lin, Cheng-Chieh; Li, Tsai-Chung; Lin, Jaung-Geng

    2012-09-05

    Traditional Chinese Medicine (TCM) is one of the most popular complementary and alternative medicine modalities worldwide. In Chinese and East Asian societies, TCM plays an active role in the modern health care system and is even covered by the National Health Insurance Program of Taiwan. Liver cancer is the second most common cancer in Taiwan. This study aimed to analyze the TCM utilization patterns of patients with liver cancer from 1996-2007 using a population-based random sample of one million insured patients. A cross-sectional study was conducted using registration and claim data sets from 1996 to 2007 obtained from the Longitudinal Health Insurance Database 2005 (LHID2005). The outpatient datasets contained the encounter form-based dates of visit, three items from the International Classification of Diseases (Ninth Revision, Clinical Modification codes), the primary procedure (e.g., drug or diagnostic procedure), type of copayment, billed amount, and paid amount. Only ambulatory care was analyzed. A total of 6358 liver cancer patients utilized ambulatory care during the study period. Among them, 1240 (19.50%) availed of TCM outpatient services. The prevalence of TCM use fluctuated during the study period, with a peak of 25.11% in 2001. After multivariable adjustment, the likelihood of TCM users was lower in participants aged 70 years and older (odds ratio, OR = 0.79, 95% confidence interval, CI: 0.64-0.97), males (OR = 0.60, 95% CI: 0.52-0.68), residents of Taipei (OR = 0.75, 95% CI: 0.58-0.96) as well as farmers and fishermen (OR = 0.71, 95% CI: 0.54-0.94), but was higher in residents of central Taiwan (OR = 1.99, 95% CI: 1.56-2.54. Most biomedicine and TCM outpatient services were provided by private clinics, followed by private hospitals. The two most frequently recorded coexisting diseases for both biomedicine and TCM outpatient visits specifically for liver cancer were (1) chronic liver disease and cirrhosis, and (2) malignant

  8. Radiation-induced liver injury mimicking liver metastases on FDG-PET-CT after chemoradiotherapy for esophageal cancer : A retrospective study and literature review.

    PubMed

    Voncken, Francine E M; Aleman, Berthe M P; van Dieren, Jolanda M; Grootscholten, Cecile; Lalezari, Ferry; van Sandick, Johanna W; Steinberg, Jeffrey D; Vegt, Erik

    2018-02-01

    For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F‑18-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. A systematic search for potential cases of RILI after (chemo)radiotherapy for esophageal cancer was performed in the electronic reports from all PET-CT scans made between 2006 and 2015 in our hospital. Additional data about potential cases were obtained from the electronic medical records. A literature review of RILI was also performed. Of 205 patients undergoing nCRT, 6 cases with localized increased FDG uptake in the caudate or left liver lobe following nCRT for esophageal cancer were identified. None of these patients had signs of liver metastases with additional imaging, during surgery, on biopsy, or during follow-up (range 11-46 months). At our institute, the incidence of RILI after neoadjuvant chemoradiotherapy for esophageal cancer was 3%. In the literature, RILI is described in about 8% of patients at the time of restaging. FDG-avid lesions occur in the high radiation dose area, usually corresponding to the caudate or left liver lobe. FDG accumulation in the caudate or left liver lobe after CRT in the area that received a high radiation dose may be caused by metastases or RILI. Awareness of the pitfall of high FDG uptake in RILI is crucial to avoid misinterpretation and overstaging.

  9. Body mass index, waist circumference, type 2 diabetes mellitus and risk of liver cancer for U.S. adults

    PubMed Central

    Campbell, Peter T.; Newton, Christina C.; Freedman, Neal D.; Koshiol, Jill; Alavanja, Michael C.; Beane Freeman, Laura E.; Buring, Julie E.; Chan, Andrew T.; Chong, Dawn Q.; Datta, Mridul; Gaudet, Mia M.; Gaziano, J. Michael; Giovannucci, Edward; Graubard, Barry; Hollenbeck, Albert R.; King, Lindsey; Lee, I-Min; Linet, Martha; Palmer, Julie; Petrick, Jessica L.; Poynter, Jenny N.; Purdue, Mark; Robien, Kim; Rosenberg, Lynn; Sahasrabuddhe, Vikrant; Schairer, Catherine; Sesso, Howard D.; Sigurdson, Alice; Stevens, Victoria L.; Wactowski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Renehan, Andrew G.; McGlynn, Katherine A.

    2016-01-01

    Incidence rates for liver cancer have increased threefold since the mid-1970s in the United States in parallel with increasing trends for obesity and type 2 diabetes mellitus (T2DM). We conducted an analysis of baseline body mass index (BMI), waist circumference (WC), and T2DM with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and T2DM). Stratified analyses assessed whether the BMI-liver cancer associations differed by hepatitis sera-positivity in nested analyses for a subset of cases (n=220) and controls (n=547). After enrollment, 2,162 incident liver cancer diagnoses were identified. BMI, per 5 kg/m2, was associated with higher risks of liver cancer, more so for men (HR: 1.38; 95% CI: 1.30 to 1.46) than women (HR: 1.25; 95% CI: 1.17 to 1.35; p-interaction: 0.02). WC, per 5 cm, was associated with higher risks of liver cancer, approximately equally by sex (overall, HR: 1.08; 95% CI: 1.04 to 1.13). T2DM was associated with higher risk of liver cancer (HR: 2.61; 95% CI: 2.34 to 2.91). In stratified analyses, there was a null association between BMI and liver cancer risk for participants who were sera-positive for hepatitis. This study suggests that high BMI, high WC, and T2DM are associated with higher risks of liver cancer and that the association may differ by status of viral hepatitis infection. PMID:27742674

  10. What You Need to Know about Liver Cancer

    MedlinePlus

    ... Cancers Late Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer ... PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics ...

  11. n-3 fatty acid-based parenteral nutrition improves postoperative recovery for cirrhotic patients with liver cancer: A randomized controlled clinical trial.

    PubMed

    Zhang, Binhao; Wei, Gang; Li, Rui; Wang, Yanjun; Yu, Jie; Wang, Rui; Xiao, Hua; Wu, Chao; Leng, Chao; Zhang, Bixiang; Chen, Xiao-Ping

    2017-10-01

    A new lipid emulsion enriched in n-3 fatty acid has been reported to prevent hepatic inflammation in patients following major surgery. However, the role of n-3 fatty acid-based parenteral nutrition for postoperative patients with cirrhosis-related liver cancer is unclear. We investigated the safety and efficacy of n-3 fatty acid-based parenteral nutrition for cirrhotic patients with liver cancer followed hepatectomy. A prospective randomized controlled clinical trial (Registered under ClinicalTrials.gov Identifier no. NCT02321202) was conducted for cirrhotic patients with liver cancer that underwent hepatectomy between March 2010 and September 2013 in our institution. We compared isonitrogenous total parenteral nutrition with 20% Structolipid and 10% n-3 fatty acid (Omegaven, Fresenius-Kabi, Germany) (treatment group) to Structolipid alone (control group) for five days postoperatively, in the absence of enteral nutrition. We enrolled 320 patients, and 312 (97.5%) were included in analysis (155 in the control group and 157 in the treatment group). There was a significant reduction of morbidity and mortality in the treatment group, when compared with the control group (total complications 78 [50.32%] vs. 46 [29.30%]; P < 0.001, total infective complications, 30 [19.35%] vs. 15 [9.55%]; P = 0.014), overall mortality (5 [3.23%] vs. 1 [0.64%]; P = 0.210), and hospital stay (12.56 ± 3.21 d vs. 10.17 ± 3.15 d; P = 0.018). We found that addition of n-3 fatty acid-based parenteral nutrition significantly improved postoperative recovery for cirrhotic patients with liver cancer following hepatectomy, with a significant reduction in overall mortality and length of hospital stay. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  12. Prioritizing strategies for comprehensive liver cancer control in Asia: a conjoint analysis.

    PubMed

    Bridges, John F P; Dong, Liming; Gallego, Gisselle; Blauvelt, Barri M; Joy, Susan M; Pawlik, Timothy M

    2012-10-30

    Liver cancer is a complex and burdensome disease, with Asia accounting for 75% of known cases. Comprehensive cancer control requires the use of multiple strategies, but various stakeholders may have different views as to which strategies should have the highest priority. This study identified priorities across multiple strategies for comprehensive liver cancer control (CLCC) from the perspective of liver cancer clinical, policy, and advocacy stakeholders in China, Japan, South Korea and Taiwan. Concordance of priorities was assessed across the region and across respondent roles. Priorities for CLCC were examined as part of a cross-sectional survey of liver cancer experts. Respondents completed several conjoint-analysis choice tasks to prioritize 11 strategies. In each task, respondents judged which of two competing CLCC plans, consisting of mutually exclusive and exhaustive subsets of the strategies, would have the greatest impact. The dependent variable was the chosen plan, which was then regressed on the strategies of different plans. The restricted least squares (RLS) method was utilized to compare aggregate and stratified models, and t-tests and Wald tests were used to test for significance and concordance, respectively. Eighty respondents (69.6%) were eligible and completed the survey. Their primary interests were hepatitis (26%), hepatocellular carcinoma (HCC) (58%), metastatic liver cancer (10%) and transplantation (6%). The most preferred strategies were monitoring at-risk populations (p<0.001), clinician education (p<0.001), and national guidelines (p<0.001). Most priorities were concordant across sites except for three strategies: transplantation infrastructure (p=0.009) was valued lower in China, measuring social burden (p=0.037) was valued higher in Taiwan, and national guidelines (p=0.025) was valued higher in China. Priorities did not differ across stakeholder groups (p=0.438). Priorities for CLCC in Asia include monitoring at-risk populations

  13. Vegetable-based dietary pattern and liver cancer risk: results from the Shanghai women's and men's health studies.

    PubMed

    Zhang, Wei; Xiang, Yong-Bing; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ji, Bu-Tian; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao-Ou

    2013-10-01

    Although dietary patterns, specific foods, and their constituents have been linked to cancer risk, the role of dietary patterns and specific food groups in liver cancer risk has not been investigated. In the Shanghai Women's Health Study (SWHS) and Shanghai Men's Health Study (SMHS), two cohort studies of 132 837 Chinese women and men, we evaluated the relationship between dietary patterns, food groups, and liver cancer risk. Through in-person interviews, dietary information intake over the preceding year was collected by using a validated food-frequency questionnaire. Cox regression model was used to estimate hazard ratios and 95% confidence intervals with adjustment for potential confounders. During an average follow-up of 10.9 (SWHS) or 5.5 (SMHS) years, 267 incident liver cancer cases were identified after the first 2 years of study enrolment. Three dietary patterns were derived by factor analysis. A vegetable-based dietary pattern was inversely associated with liver cancer; hazard ratios (95% confidence intervals) for the lowest to highest quartiles were: 1.00; 0.98 (0.71-1.35); 0.93 (0.67-1.29); and 0.58 (0.40-0.84); P(trend) = 0.01. The association was stronger among participants with a history of chronic liver disease. Further analyses showed high intakes of celery, mushrooms, allium vegetables, composite vegetables (including asparagus lettuce and garland chrysanthemum), legumes and legume products were associated with reduced liver cancer risk (all P(trend) < 0.05). Fruit- and meat-based dietary patterns were not associated with liver cancer risk. Our study suggests that a vegetable-based dietary pattern is associated with reduced liver cancer risk. © 2013 Japanese Cancer Association.

  14. Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases.

    PubMed

    Rahbari, Nuh N; Kedrin, Dmitriy; Incio, Joao; Liu, Hao; Ho, William W; Nia, Hadi T; Edrich, Christina M; Jung, Keehoon; Daubriac, Julien; Chen, Ivy; Heishi, Takahiro; Martin, John D; Huang, Yuhui; Maimon, Nir; Reissfelder, Christoph; Weitz, Jurgen; Boucher, Yves; Clark, Jeffrey W; Grodzinsky, Alan J; Duda, Dan G; Jain, Rakesh K; Fukumura, Dai

    2016-10-12

    The survival benefit of anti-vascular endothelial growth factor (VEGF) therapy in metastatic colorectal cancer (mCRC) patients is limited to a few months because of acquired resistance. We show that anti-VEGF therapy induced remodeling of the extracellular matrix with subsequent alteration of the physical properties of colorectal liver metastases. Preoperative treatment with bevacizumab in patients with colorectal liver metastases increased hyaluronic acid (HA) deposition within the tumors. Moreover, in two syngeneic mouse models of CRC metastasis in the liver, we show that anti-VEGF therapy markedly increased the expression of HA and sulfated glycosaminoglycans (sGAGs), without significantly changing collagen deposition. The density of these matrix components correlated with increased tumor stiffness after anti-VEGF therapy. Treatment-induced tumor hypoxia appeared to be the driving force for the remodeling of the extracellular matrix. In preclinical models, we show that enzymatic depletion of HA partially rescued the compromised perfusion in liver mCRCs after anti-VEGF therapy and prolonged survival in combination with anti-VEGF therapy and chemotherapy. These findings suggest that extracellular matrix components such as HA could be a potential therapeutic target for reducing physical barriers to systemic treatments in patients with mCRC who receive anti-VEGF therapy. Copyright © 2016, American Association for the Advancement of Science.

  15. Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine.

    PubMed

    Ling, Chang-Quan; Fan, Jia; Lin, Hong-Sheng; Shen, Feng; Xu, Zhen-Ye; Lin, Li-Zhu; Qin, Shu-Kui; Zhou, Wei-Ping; Zhai, Xiao-Feng; Li, Bai; Zhou, Qing-Hui

    2018-05-17

    Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

  16. Environmental contributions to gastrointestinal and liver cancer in the Asia-Pacific region.

    PubMed

    Ko, Kwang-Pil; Shin, Aesun; Cho, Sooyoung; Park, Sue K; Yoo, Keun-Young

    2018-01-01

    In the Asia-Pacific region, gastric, colorectal, and hepatocellular (liver) cancer show substantial regional variation in incidence consistent with the presence of important environmental factors. For gastric cancer, global incidence is concentrated in Asia with substantially higher rates in East Asia than in South-East Asia and Australia. The differences in incidence rates for gastric cancer in the Asia-Pacific region may be due, in part, to differences in the prevalence of Helicobacter pylori infection and the prevalence of H. pylori virulence factors. Smoking is also correlated with gastric cancer risk and is responsible for the highest population attributable fraction among men in East Asia. Colorectal cancer has increased rapidly in incidence to become the third most common digestive cancer in Asia. According to cohort studies in Asia, smoking, alcohol use, obesity, and physical inactivity increase the risk of colorectal cancer. Unlike West Asia, East Asia and Australia have high incidence rates for colorectal cancer that correlates to a high Human Development Index and a high prevalence of alcohol consumption and obesity. Liver cancer is the second most common digestive cancer in Asia. The high incidence of liver cancer in East Asia and South-East Asia is concordant with the high prevalence of hepatitis B virus and hepatitis C virus infection. Other important risk factors include alcohol use, smoking, and diabetes. The identification of the earlier and other environmental factors (currently under investigation) is central to the development and implementation of effective cancer control programs for the region. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  17. Lung, liver and bone cancer mortality after plutonium exposure in beagle dogs and nuclear workers.

    PubMed

    Wilson, Dulaney A; Mohr, Lawrence C; Frey, G Donald; Lackland, Daniel; Hoel, David G

    2010-01-01

    The Mayak Production Association (MPA) worker registry has shown evidence of plutonium-induced health effects. Workers were potentially exposed to plutonium nitrate [(239)Pu(NO(3))(4)] and plutonium dioxide ((239)PuO(2)). Studies of plutonium-induced health effects in animal models can complement human studies by providing more specific data than is possible in human observational studies. Lung, liver, and bone cancer mortality rate ratios in the MPA worker cohort were compared to those seen in beagle dogs, and models of the excess relative risk of lung, liver, and bone cancer mortality from the MPA worker cohort were applied to data from life-span studies of beagle dogs. The lung cancer mortality rate ratios in beagle dogs are similar to those seen in the MPA worker cohort. At cumulative doses less than 3 Gy, the liver cancer mortality rate ratios in the MPA worker cohort are statistically similar to those in beagle dogs. Bone cancer mortality only occurred in MPA workers with doses over 10 Gy. In dogs given (239)Pu, the adjusted excess relative risk of lung cancer mortality per Gy was 1.32 (95% CI 0.56-3.22). The liver cancer mortality adjusted excess relative risk per Gy was 55.3 (95% CI 23.0-133.1). The adjusted excess relative risk of bone cancer mortality per Gy(2) was 1,482 (95% CI 566.0-5686). Models of lung cancer mortality based on MPA worker data with additional covariates adequately described the beagle dog data, while the liver and bone cancer models were less successful.

  18. Water extract from Pleurotus pulmonarius with antioxidant activity exerts in vivo chemoprophylaxis and chemosensitization for liver cancer.

    PubMed

    Xu, Wen Wen; Li, Bin; Lai, Emily Tsz Ching; Chen, Lei; Huang, Jim Jun Hui; Cheung, Annie Lai Man; Cheung, Peter Chi Keung

    2014-01-01

    Chemoprophylaxis and chemosensitization are promising strategies to combat human cancers. Natural antioxidant agents show great promise in cancer therapy, and the use of edible mushrooms against cancer is receiving more interest globally. In this study, the radical scavenging activities including diphenyl-1-picrylhydrazyl, superoxide anion radical, hydroxyl radical, and hydrogen peroxide were compared among hot water extracts from 3 edible mushrooms, among which Pleurotus pulmonarius (Pp) possessed the highest antioxidant potential. Oral administration of Pp 2 wk in advance could markedly inhibit the incidence and size of tumor (Huh7 liver cancer cells) with an inhibition rate of 93.1% in nude mice. No obvious side effect was observed in the Pp-treated mice as indicated by their body weight and histological analysis of major organs. The cancer prevention by Pp treatment might be explained by the inhibition of cancer cell proliferation indicated by reduction of ki-67 staining and the inactivation of phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in the Pp-treated mice. Furthermore, a significant synergistic effect was observed when the mice were treated with a combination of low dose of cisplatin and Pp. Taken together, these results suggest the potential application of Pp as an adjuvant in the chemotherapy of liver cancer.

  19. Pesticide exposure and liver cancer: a review

    PubMed Central

    VoPham, Trang; Bertrand, Kimberly A.; Hart, Jaime E.; Laden, Francine; Brooks, Maria M.; Yuan, Jian-Min; Talbott, Evelyn O.; Ruddell, Darren; Chang, Chung-Chou H.; Weissfeld, Joel L.

    2017-01-01

    Purpose To review the epidemiologic literature examining pesticide exposure and liver cancer incidence. Methods A search of the MEDLINE and Embase databases was conducted in October 2015. Eligibility criteria included examining hepatocellular carcinoma (HCC) or primary liver cancer, pesticides as an exposure of interest, and individual-level incidence. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Forty-eight papers were assessed for eligibility and 15 studies were included in the review. The majority of studies were conducted in China and Egypt (n=8), used a case-control design (n=14), and examined HCC (n=14). Most studies showed no association between self-reported and/or occupational exposure to pesticides and liver cancer risk. Six studies demonstrated statistically significant positive associations, including three biomarker-based studies (two using pre-diagnostic sera) that reported higher serum levels of dichlorodiphenyltrichloroethane (DDT) were associated with increased HCC risk. Studies indirectly measuring pesticide exposure using self-reported exposure, occupation, job-exposure matrices, or geographic residence demonstrated inconsistent results. These studies were limited by exposure assessment methods, lack of confounder information, minimal case confirmation, selection bias, and/or over-adjustment. Conclusions There is mixed evidence suggesting a possible association between specific pesticides and HCC risk, with the strongest evidence observed in biomarker-based studies. In particular, organochlorine pesticides, including DDT, may increase HCC risk. Future research should focus on improved pesticide exposure assessment methods, potentially incorporating multiple approaches including biomonitoring while considering the chemicals of interest, historical exposure to address latency periods, and examining specific chemicals and exposure pathways. PMID:28194594

  20. Liver cancer diagnosis by fluorescence spectra of blood and urine

    NASA Astrophysics Data System (ADS)

    AlSalhi, Mohamad Saleh; Al Mehmadi, Abdulaziz Mayuof; Abdoo, Aiman; Masilamani, Vadivel

    2012-03-01

    Liver cancer or hepatocellular carcinoma (HCC) is a serious malady with only 10% survival rate. HCC incidence and mortality both are highest in China. This disease is detected and diagnosed by ultra sound, CT or MRI scans which are quite expensive. Also the discrimination between cirrhosis and HCC are poor by this imaging technique. The conventional tissue biopsy is quite invasive and painful. In this context, in the new diagnostic procedure presented in this paper, all the three liver malfunctions, particularly liver cancer, could be detected and discriminated by the spectral feature of blood and urine with accuracy about 80%. All that we need are 5 ml of blood and 5 ml of urine. Hence this inexpensive non invasive, optical technique will have significant impact in screening, diagnosis and also prognosis of HCC in large segment of people in the populous Asian countries.

  1. Lipid Biomarkers Identified for Liver Cancer | Center for Cancer Research

    Cancer.gov

    Hepatocellular carcinoma (HCC) is an aggressive cancer of the liver with poor prognosis and growing incidence in developed countries. Pathology and genetic profiles of HCC are heterogeneous, suggesting that it can begin growing in different cell types. Although human tumors such as HCC have been profiled in-depth by genomics-based studies, not much is known about their overall

  2. Case of cytomegalovirus retinitis aggravated by sub-Tenon injection of triamcinolone acetonide with subsequent metastatic liver cancer

    PubMed Central

    Yamamoto, Yumiko; Kato, Yoshitake; Tabuchi, Hitoshi; Fukushima, Atsuki

    2013-01-01

    We report a case of cytomegalovirus (CMV) retinitis in an immunocompetent patient who was resistant to antiviral treatment, and in whom fatal metastatic liver cancer was later detected. A 74-year-old Japanese man visited our ophthalmology clinic in May 2011. He had a history of well controlled type 2 diabetes and colon cancer, and underwent successful surgical treatment in 2008. In April 2011, he was diagnosed with uveitis affecting his left eye and received posterior sub-Tenon injection of triamcinolone acetonide. He was referred to us because of aggravation of the retinal lesion. Funduscopic examination of the left eye revealed arcuate, whitish, necrotizing retinitis with hemorrhage along the temporal arcade of the retina. Polymerase chain reaction of the aqueous fluid was positive for CMV DNA. Because of diagnosis of CMV retinitis in his left eye, he was referred to an internist and investigated for systemic CMV infection or any serious disease which could cause immunocompromise, but neither was detected. Despite an intensive course of intravitreous ganciclovir and oral valganciclovir, the retinitis did not resolve. In June 2012, 14 months after the initial ocular symptoms, metastatic liver cancer was found and the patient passed away. When CMV retinitis is resistant to antiviral treatment or recurs in an immunocompetent patient, it is important that ophthalmologists undertake systemic investigation for occult malignancy. PMID:23467884

  3. Overexpression of Klotho suppresses liver cancer progression and induces cell apoptosis by negatively regulating wnt/β-catenin signaling pathway.

    PubMed

    Sun, Huidong; Gao, Yanchao; Lu, Kemei; Zhao, Guimei; Li, Xuehua; Li, Zhu; Chang, Hong

    2015-10-24

    proliferation of liver cancer cells partly due to negative regulation of Wnt/β-catenin signaling pathway. So, Klotho might be used as a potential target, and the study will contribute to treatment for therapy of liver cancer patients.

  4. Cancer

    MedlinePlus

    ... most common types of cancer treatment are surgery, radiotherapy, and chemotherapy. Treatment is aimed at removing the ... vital organs, such as the liver or brain. Radiotherapy Radiotherapy uses radiation to damage cancer cells so ...

  5. Prognostic effect of liver metastasis in lung cancer patients with distant metastasis.

    PubMed

    Ren, Yijiu; Dai, Chenyang; Zheng, Hui; Zhou, Fangyu; She, Yunlang; Jiang, Gening; Fei, Ke; Yang, Ping; Xie, Dong; Chen, Chang

    2016-08-16

    Because the need of clinical prognostic evaluation by specific metastatic organ, we aim to analyze the prognostic factors in lung cancer patients with M1b disease with Surveillance Epidemiology and End-Results database (SEER). This retrospective study evaluated lung cancer patients of adenocarcinoma (AD), squamous cell carcinoma (SQCC), and small cell lung cancer (SCLC) selected from SEER. We provided the prognostic correlates of overall survival (OS) and lung cancer-specific survival (LCSS) in this population. 23,679 eligible patients were included. Bone was the most common metastatic site in AD (63.1%) and SQCC (61.1%), while liver was the most prevalent site (61.9%) in SCLC. Single site metastasis was significantly associated with better outcome compared to multiple sites metastases in all patients. Among patients with single site metastasis, OS and LCSS were longer for AD and SCLC if involving brain or bone, with median survival time of 5 to 7 months, comparing to 3 months if invloving liver (all p-values < 0.001). Similarly, among patients with multiple metastases, better outcomes were observed in AD patients (4 vs 3 months; OS and LCSS, p < 0.001) and SCLC patients (6 vs 4 months; OS, p = 0.017; LCSS, p = 0.023) without liver metastasis compared to those with liver metastasis. In conclusion, we estimated multiple survival outcomes by histology of primary tumor and sites of metastasis. Liver metastasis is found to be the worst prognostic factor for AD and SCLC patients with distant metastasis. More in-depth research is warranted to identify patients who are prone to develop distance metastasis, especially to liver.

  6. Increased E-selectin in hepatic ischemia-reperfusion injury mediates liver metastasis of pancreatic cancer

    PubMed Central

    YOSHIMOTO, KATSUHIRO; TAJIMA, HIDEHIRO; OHTA, TETSUO; OKAMOTO, KOICHI; SAKAI, SEISHO; KINOSHITA, JUN; FURUKAWA, HIROYUKI; MAKINO, ISAMU; HAYASHI, HIRONORI; NAKAMURA, KEISHI; OYAMA, KATSUNOBU; INOKUCHI, MASAFUMI; NAKAGAWARA, HISATOSHI; ITOH, HIROSHI; FUJITA, HIDETO; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; KITAGAWA, HIROHISA; FUSHIDA, SACHIO; FUJIMURA, TAKASHI; WAKAYAMA, TOMOHIKO; ISEKI, SHOICHI; SHIMIZU, KOICHI

    2012-01-01

    Several recent studies have reported that selectins are produced during ischemia-reperfusion injury, and that selectin ligands play an important role in cell binding to the endothelium and in liver metastasis. Portal clamping during pancreaticoduodenectomy with vessel resection for pancreatic head cancer causes hepatic ischemia-reperfusion injury, which might promote liver metastasis. We investigated the liver colonization of pancreatic cancer cells under hepatic ischemia-reperfusion and examined the involvement of E-selectin and its ligands. A human pancreatic cancer cell line (Capan-1) was injected into the spleen of mice after hepatic ischemia-reperfusion (I/R group). In addition, to investigate the effect of an anti-E-selectin antibody on liver colonization in the IR group, mice received an intraperitoneal injection of the anti-E-selectin antibody following hepatic ischemia-reperfusion and tumor inoculation (IR+Ab group). Four weeks later, mice were sacrificed and the number of tumor nodules on the liver was compared to mice without hepatic ischemia-reperfusion (control group). The incidence of liver metastasis in the I/R group was significantly higher (16 of 20, 80%) than that in the control group (6 of 20, 30%) (P<0.01). Moreover, mice in the I/R group had significantly more tumor nodules compared to those in the control group (median, 9.9 vs. 2.7 nodules) (P<0.01). In the I/R+Ab group, only 2 of 5 (40%) mice developed liver metastases. RT-PCR and southern blotting of the liver extracts showed that the expression of IL-1 and E-selectin mRNA after hepatic ischemia-reperfusion was significantly higher than the basal levels. Hepatic ischemia-reperfusion increases liver metastases and E-selectin expression in pancreatic cancer. These results suggest that E-selectin produced due to hepatic ischemia-reperfusion is involved in liver metastasis. PMID:22766603

  7. Intra-arterial radioembolization of breast cancer liver metastases: a structured review.

    PubMed

    Smits, Maarten L J; Prince, Jip F; Rosenbaum, Charlotte E N M; van den Hoven, Andor F; Nijsen, J Frank W; Zonnenberg, Bernard A; Seinstra, Beatrijs A; Lam, Marnix G E H; van den Bosch, Maurice A A J

    2013-06-05

    Radioembolization using yttrium-90 microspheres (⁹⁰Y-RE) is an emerging treatment option for breast cancer liver metastases (BCLM) patients if other locoregional and systemic treatment options fail. The purpose of this study was to provide a systematic overview of the current literature concerning ⁹⁰Y-RE for BCLM patients. A systematic search for relevant articles was performed in MEDLINE, EMBASE, and The Cochrane Library (January 2012) by combining an extensive list of synonyms for the determinants 'radioembolization', 'yttrium-90' and 'microsphere' with synonyms for the domain 'liver'. Data on tumor response, survival and toxicity were extracted and collected from all relevant articles. The search yielded 4078 studies, of which six were finally included for analysis, concerning a total of 198 patients. Tumor response was scored in five studies using either RECIST (n=3) or WHO criteria (n=2). Overall disease control rates (complete response, partial response and stable disease) at 2-4 months post treatment ranged from 78% to 96%. Median survival, available in four studies, ranged from 10.8 to 20.9 months. In total, gastric ulceration was reported in ten patients (5%) and treatment related mortality in three patients (2%). The results from the analyzed studies consistently show that ⁹⁰Y-RE is a safe and effective treatment option for BCLM patients. Comparative studies, especially combining ⁹⁰Y-RE with systemic therapy are strongly encouraged. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues.

    PubMed

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health.Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper,we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameter scan provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  9. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues

    NASA Astrophysics Data System (ADS)

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health. Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper, we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameters can provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  10. Magnetic Resonance Imaging of Liver Metastasis.

    PubMed

    Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa Nasuh; Akata, Deniz; Karcaaltincaba, Musturay

    2016-12-01

    Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Results of percutaneous sclerotherapy and surgical treatment in patients with symptomatic simple liver cysts and polycystic liver disease

    PubMed Central

    Erdogan, Deha; van Delden, Otto M; Rauws, Erik AJ; Busch, Olivier RC; Lameris, Johan S; Gouma, Dirk J; van Gulik, Thomas M

    2007-01-01

    AIM: To evaluate the results of the treatment of simple liver cysts (solitary and multiple) and polycystic liver disease (PLD) using percutaneous sclerotherapy and/or surgical procedures in a single tertiary referral centre. METHODS: Retrospective analysis of 54 patients referred for evaluation and possible treatment of simple liver cysts (solitary and multiple) and PLD, from January 1997 to July 2006. RESULTS: Simple liver cysts were treated in 41 pts (76%) with a mean size of 12.6 cm. The most common reason for referral was abdominal pain or discomfort (85%). Percutaneous sclerotherapy was performed as initial treatment in 30 pts, showing cyst recurrence in 6 pts (20%). Surgical treatment was initially performed in 11 pts with cyst recurrence in 3 pts (27%). PLD was treated in 13 pts (24%) with a mean size of the dominant cyst of 13 cm. Percutaneous sclerotherapy for PLD was performed in 9 pts with recurrence in 7 pts (77.8%). Surgical treatment for PLD was undertaken in 4 pts (30.8%) with recurrence in all. Eventually, 2 pts with PLD in the presence of polycystic kidney disease underwent liver- and kidney transplantation because of deterioration of liver and kidney function. CONCLUSION: The majority of patients with simple liver cysts and PLD are referred for progressive abdominal pain. As initial treatment, percutaneous sclerotherapy is appropriate. Surgical deroofing is indicated in case of cyst recurrence after percutaneous sclerotherapy. However, the results of percutaneous sclerotherapy and surgical treatment for PLD are disappointing. Partial liver resection is indicated when there is suspicion of a pre-malignant lesion. PMID:17589926

  12. Predictors of high healthcare costs in elderly patients with liver cancer in end-of-life: a longitudinal population-based study.

    PubMed

    Chiang, Jui-Kun; Kao, Yee-Hsin

    2017-08-24

    Studies have indicated a pervasive pattern of decreasing healthcare costs during elderly patients' last year of life. The aim of this study was to explore the predictors of high healthcare costs (HC) in elderly liver cancer patients in Taiwan during their last month of life (LML). Costs of hospitalization, outpatient visits, aggressiveness of care, and associated costs for elderly (age ≥ 65 y) patients with liver cancer in the LML were analyzed using a national insurance database. An HC was defined as being greater than the 90th percentile (US $5093) in the LML, amounting to 38.95% of total healthcare costs. We enrolled 2121 subjects who died during 1997-2011. Mean healthcare costs per person in their LML were US $8042 ± 3477 in the HC group and US $1407 ± 1464 in the non-HC group (p < 0.001). For patients receiving aggressive end-of-life (EOL) cancer care (e.g. intensive care, cardiopulmonary resuscitation, anticancer treatment, and a high number of admission days), comorbidities of chronic kidney disease, esophageal bleeding, and receiving opioids in the LML, were significantly independent positive predictors of HCs; but admission times, comorbidities of ascites, and hypertension were negative predictors. These findings could inform healthcare providers by avoiding aggressive treatments during EOL for elderly patients with liver cancer and to save on healthcare costs. Shorter admission days and more admission times in the last month of life could decrease healthcare costs.

  13. Nuclear Receptor Activity and Liver Cancer Lesion Progression

    EPA Science Inventory

    Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs is a non-genotoxic mechanism of rodent liver cancer with unclear relevance to humans. We explored this question using human CAR, PXR, PPARα,...

  14. American Liver Foundation

    MedlinePlus

    ... Media Helpful Links Liver Cancer Information Available in Chinese Learn more about liver cancer HERE . Thanks to ... in Northern California, you can speak to a Chinese speaking agent with your liver cancer questions. Call ...

  15. Dual-specificity tyrosine-regulated kinase 2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer.

    PubMed

    Ito, Daisuke; Yogosawa, Satomi; Mimoto, Rei; Hirooka, Shinichi; Horiuchi, Takashi; Eto, Ken; Yanaga, Katsuhiko; Yoshida, Kiyotsugu

    2017-08-01

    Colorectal cancer is a common cancer and a leading cause of cancer-related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial-mesenchymal transition is the key step for metastasis of cancer cells. We recently reported that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls epithelial-mesenchymal transition in breast cancer and ovarian serous adenocarcinoma. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We show that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  16. Wnt Inactivation for Liver Cancer Therapy | Center for Cancer Research

    Cancer.gov

    Hepatocellular carcinoma (HCC) is the fifth most common and third most deadly type of cancer in the world. The majority of cases occur in Asia and Africa, resulting in most cases being diagnosed only at advanced stages of the disease when drug resistance is high. HCC typically follows damage to the liver such as cirrhosis, making radiation and chemotherapy a more challenging

  17. Benefit of FOLFOX to unresectable liver metastases secondary from colorectal carcinoma in an oncologic emergency.

    PubMed

    Sugimoto, Maki; Yasuda, Hideki; Koda, Keiji; Yamazaki, Masato; Tezuka, Tohru; Takenoue, Tomohiro; Kosugi, Chihiro; Higuchi, Ryota; Yamamoto, Shiho; Watayo, Yoshihisa; Yagawa, Yohsuke; Suzuki, Masato

    2007-09-01

    Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.

  18. Transforming growth factor‐β in liver cancer stem cells and regeneration

    PubMed Central

    Rao, Shuyun; Zaidi, Sobia; Banerjee, Jaideep; Jogunoori, Wilma; Sebastian, Raul; Mishra, Bibhuti; Nguyen, Bao‐Ngoc; Wu, Ray‐Chang; White, Jon; Deng, Chuxia; Amdur, Richard; Li, Shulin

    2017-01-01

    Cancer stem cells have established mechanisms that contribute to tumor heterogeneity as well as resistance to therapy. Over 40% of hepatocellular carcinomas (HCCs) are considered to be clonal and arise from a stem‐like/cancer stem cell. Moreover, HCC is the second leading cause of cancer death worldwide, and an improved understanding of cancer stem cells and targeting these in this cancer are urgently needed. Multiple studies have revealed etiological patterns and multiple genes/pathways signifying initiation and progression of HCC; however, unlike the transforming growth factor β (TGF‐β) pathway, loss of p53 and/or activation of β‐catenin do not spontaneously drive HCC in animal models. Despite many advances in cancer genetics that include identifying the dominant role of TGF‐β signaling in gastrointestinal cancers, we have not reached an integrated view of genetic mutations, copy number changes, driver pathways, and animal models that support effective targeted therapies for these common and lethal cancers. Moreover, pathways involved in stem cell transformation into gastrointestinal cancers remain largely undefined. Identifying the key mechanisms and developing models that reflect the human disease can lead to effective new treatment strategies. In this review, we dissect the evidence obtained from mouse and human liver regeneration, and mouse genetics, to provide insight into the role of TGF‐β in regulating the cancer stem cell niche. (Hepatology Communications 2017;1:477–493) PMID:29404474

  19. [Complete responses in patients with unresectable liver metastases from colorectal cancer with weekly high-dose 5-FU plus one-shot CDDP HAI].

    PubMed

    Udagawa, M; Okabe, S; Kuwabara, H; Ootsukasa, S; Arai, T; Maruyama, S; Murase, N; Yamashita, H; Iwai, T

    1999-10-01

    Thirty-two patients with unresectable liver metastases from colorectal cancer, treated by intermittent hepatic arterial infusion of high-dose 5-FU combined with CDDP, were assessed. As a result of this treatment, the overall response rate was 65.6%, and eight patients (25%) which contained three autopsy cases revealed a complete response. The mean doses of 5-FU and CDDP which was administered in the eight patients were 24.3 g and 65 mg, respectively. One of the eight patients showed complete disappearance of liver metastasis on the CT scan after arterial infusion of 4.5 g of 5-FU, and necrosis or disappearance of the tumor was present in more than 2/3 of the whole lesion. Autopsy showed focal or zonal necrosis, distorted reconstruction of architecture, and cholangiolitis of the liver which were administered more than 15 g of 5-FU. Intermittent hepatic arterial infusion of high-dose 5-FU combined with CDDP is proved to be a useful locoregional chemotherapy for liver metastasis from colorectal cancer. We should evolve new treatment modalities for extrahepatic metastases, as HAI combined with the systemic chemotherapeutic regimen.

  20. Mutational landscape of a chemically-induced mouse model of liver cancer.

    PubMed

    Connor, Frances; Rayner, Tim F; Aitken, Sarah J; Feig, Christine; Lukk, Margus; Santoyo-Lopez, Javier; Odom, Duncan T

    2018-06-26

    Carcinogen-induced mouse models of liver cancer are used extensively to study pathogenesis of the disease and have a critical role in validating candidate therapeutics. These models can recapitulate molecular and histological features of human disease. However, it is not known if the genomic alterations driving these mouse tumour genomes are comparable to those found in human tumours. Here, we provide a detailed genomic characterisation of tumours from a commonly used mouse model of hepatocellular carcinoma (HCC). We analysed whole exome sequences of liver tumours arising in mice exposed to diethylnitrosamine (DEN). DEN-initiated tumours had a high, uniform number of somatic single nucleotide variants (SNVs), with few insertions, deletions or copy number alterations, consistent with the known genotoxic action of DEN. Exposure of hepatocytes to DEN left a reproducible mutational imprint in resulting tumour exomes which we could computationally reconstruct using six known COSMIC mutational signatures. The tumours carried a high diversity of low-incidence, non-synonymous point mutations in many oncogenes and tumour suppressors, reflecting the stochastic introduction of SNVs into the hepatocyte genome by the carcinogen. We identified four recurrently mutated genes that were putative oncogenic drivers of HCC in this model. Every neoplasm carried activating hotspot mutations either in codon 61 of Hras, in codon 584 of Braf or in codon 254 of Egfr. Truncating mutations of Apc occurred in 21% of neoplasms, which were exclusively carcinomas supporting a role for deregulation of Wnt/β-catenin signalling in cancer progression. Our study provides detailed insight into the mutational landscape of tumours arising in a commonly-used carcinogen model of HCC, facilitating the future use of this model to understand the human disease. Mouse models are widely used to study the biology of cancer and to test potential therapies. Here, we have described the mutational landscape of

  1. Association of inorganic arsenic exposure with liver cancer mortality: A meta-analysis.

    PubMed

    Wang, Weijing; Cheng, Shuo; Zhang, Dongfeng

    2014-11-01

    The association of long-term inorganic arsenic (iAs) exposure through drinking water with risk of liver cancer mortality remains controversial. Therefore, we reviewed and quantitatively summarized the evidence from observational studies with a meta-analysis. Pertinent studies were identified by searching PubMed and China National Knowledge Infrastructure through May 2014 and by reviewing the reference lists of retrieved articles. Studies that reported standardized mortality ratios (SMRs) with 95% confidence interval (95% CIs) for the association of iAs in drinking water with liver cancer were eligible. The random effect model was adopted as the pooling method to generate summary effect estimates (meta-SMRs). Of the 4851 articles identified through searching databases, 7 articles including 12 studies were included in the meta-analysis. The meta-SMR with 95% CI of liver cancer for the highest versus lowest category of iAs exposure level in drinking water was 1.80 (1.61 to 2.02). Furthermore, an increased risk of liver cancer mortality was found in both females [1.80 (1.45 to 2.24)] and males [1.84 (1.56 to 2.16)]. In subgroup analysis, the meta-SMRs were 1.93 (1.72 to 2.15) for cohort studies, 1.60 (1.22 to 2.10) for ecological studies, 1.93 (1.72 to 2.15) for studies conducted in Asia, and 1.60 (1.22 to 2.10) for studies conducted in South America, respectively. After removing the 3 studies conducted by Smith et al. (having two studies separately for males and females) and Chen et al. that had a strong effect on heterogeneity, a significant association was also found [1.85 (1.72 to 1.99)]. This meta-analysis indicates that long-term iAs exposure through drinking water increases the risk of liver cancer mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer

    PubMed Central

    Zhou, Xiaorong; Comerford, Sarah A.; York, Brian; O’Donnell, Kathryn A.

    2017-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis. To determine if genetic loss of SRC-2 is sufficient to accelerate MYC-mediated liver tumorigenesis, we bred Src-2-/- mice with a MYC-induced liver tumor model and observed a significant increase in liver tumor burden. RNA sequencing of liver tumors and in vivo chromatin immunoprecipitation assays revealed a set of direct target genes that are bound by SRC-2 and exhibit downregulated expression in Src-2-/- liver tumors. We demonstrate that activation of SHP (Small Heterodimer Partner), DKK4 (Dickkopf-4), and CADM4 (Cell Adhesion Molecule 4) by SRC-2 suppresses tumorigenesis in vitro and in vivo. These studies suggest that SRC-2 may exhibit oncogenic or tumor suppressor activity depending on the target genes and nuclear receptors that are expressed in distinct tissues and illuminate the mechanisms of tumor suppression by SRC-2 in liver. PMID:28273073

  3. [The incidence differences among sex, geographical areas and mean age of diagnosis for liver cancer in China, 1989-2008].

    PubMed

    Zhang, Siwei; Zheng, Rongshou; Zeng, Hongmei; Chen, Wanqing

    2014-05-01

    Using the incidence data from 1989 to 2008 of liver cancer from population in cancer registration areas in China, the differences and changes of gender, urban and rural areas for liver cancer incidence in different years were studied, and the mean age of incidence was analyzed. The incidence data of liver cancer from National Cancer Registration database were sorted and checked. A total of 181 097 new liver cancer cases were collected, covering 711 843 051 person years from 1989 to 2008.Using Poisson regression model, Stratified by gender and areas, changes of incidence gender ratio, ratio of urban and rural, and mean age were analyzed. After adjusting the age, the liver cancer incidence in male was about 3 times higher than that in females (ranging from 2.64-3.54), and the ratio change between male and female for the 20 years did not have statistically significant (P = 0.150). The incidence ratio between urban and rural areas has increased from 0.51 in 1989 to 0.61 in 2008 (P < 0.01). The mean ages of diagnosis for male and female increased from 57.14 years to 60.34 years, 61.69 years to 66.47 years, respectively from 1989 to 2008. The mean age of liver cancer diagnosis has increased in the 20 years (P < 0.01). The liver cancer incidence between male and female did not change significantly among 20 years. The difference of liver cancer incidence between urban and rural areas has reduced, and the mean age of diagnosis was deferred.

  4. Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer.

    PubMed

    Kimbung, Siker; Johansson, Ida; Danielsson, Anna; Veerla, Srinivas; Egyhazi Brage, Suzanne; Frostvik Stolt, Marianne; Skoog, Lambert; Carlsson, Lena; Einbeigi, Zakaria; Lidbrink, Elisabet; Linderholm, Barbro; Loman, Niklas; Malmström, Per-Olof; Söderberg, Martin; Walz, Thomas M; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2016-01-01

    The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. ©2015 American Association for Cancer Research.

  5. Radiation-induced liver disease as a mimic of liver metastases at serial PET/CT during neoadjuvant chemoradiation of distal esophageal cancer.

    PubMed

    Grant, Michael J; Didier, Ryne A; Stevens, Jeffrey S; Beyder, Dmitry D; Hunter, John G; Thomas, Charles R; Coakley, Fergus V

    2014-10-01

    To determine the frequency and appearance of radiation-induced liver disease on PET/CT in patients undergoing serial imaging during neoadjuvant chemoradiation of distal esophageal cancer. In this IRB-approved, HIPAA-compliant retrospective analysis, we identified 112 patients with distal esophageal cancer treated by neoadjuvant chemoradiation who had serial PET/CT imaging available for review. Two readers reviewed all studies in consensus and recorded those cases where new foci of visually detectable increased FDG avidity appeared in the liver during therapy. The etiology of such foci was determined from corresponding findings at CT or MRI, by hepatic biopsy during surgery, by characteristic evolution on post-operative imaging, or by a combination of these methods. New foci of FDG avidity developed in the liver during neoadjuvant therapy in 10 of 112 (9%) patients, of whom nine (8%) were determined to have radiation-induced liver disease based on further imaging and/or biopsy and one of whom had developed interval metastatic disease based on biopsy. In the cases of radiation-induced liver disease, the abnormal foci were found only in the caudate and left hepatic lobes, near the primary tumor, while the patient who developed interval metastatic disease had involvement of the inferior right hepatic lobe, remote from the radiation therapy field. New foci of increased FDG avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation of distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease.

  6. [Management of synchronous colorectal liver metastases].

    PubMed

    Dupré, Aurélien; Gagnière, Johan; Chen, Yao; Rivoire, Michel

    2013-04-01

    At time of diagnosis, 10 to 25% of patients with colorectal cancer present synchronous liver metastases. The treatment of such patients remains controversial without any evidence based organization. Therapeutic sequences are discussed including chemotherapy, colorectal surgery, liver resection and even radio-chemotherapy for some rectal cancers. In case of resectable liver metastases, preoperative chemotherapy offers the advantage of earlier treatment of micro-metastases as well as evaluation of tumor responsiveness, which can help shape future therapy. In this setting, different surgical strategies can be chosen (classical staged procedures with colorectal surgery followed by liver surgery, simultaneous resections or liver first approach) depending on the importance of the primary and metastatic tumors. The literature remains limited, but the results of these strategies seem identical in term of postoperative morbidity and long-term survival. Staged procedures are preferred in case of major liver resection. Location of the primary tumor on the low or mid rectum will necessitate preoperative long course chemoradiotherapy and a more complex multidisciplinary organization. For patients with extensive liver metastases, non-resectability must be assessed by experienced surgeon and radiologist before treatment and during chemotherapy. In this group of patients, improved chemotherapy regimen associated with targeted therapies and new surgical strategies (portal vein embolization, ablation, staged hepatectomies…) have improved resection rate (15 to 30-40%) and long-term survival. Treatment organization for the primary tumor remains controversial. Resection of the primary to manage symptoms such as obstruction, perforation or bleeding is advocated. For patients with asymptomatic primary a non-surgical approach permits to begin rapidly chemotherapy and obtain a better control of the disease. On the other hand, initial resection of the primary may avoid complications and

  7. Bioinformatics approaches for cross-species liver cancer analysis based on microarray gene expression profiling

    PubMed Central

    Fang, H; Tong, W; Perkins, R; Shi, L; Hong, H; Cao, X; Xie, Q; Yim, SH; Ward, JM; Pitot, HC; Dragan, YP

    2005-01-01

    Background The completion of the sequencing of human, mouse and rat genomes and knowledge of cross-species gene homologies enables studies of differential gene expression in animal models. These types of studies have the potential to greatly enhance our understanding of diseases such as liver cancer in humans. Genes co-expressed across multiple species are most likely to have conserved functions. We have used various bioinformatics approaches to examine microarray expression profiles from liver neoplasms that arise in albumin-SV40 transgenic rats to elucidate genes, chromosome aberrations and pathways that might be associated with human liver cancer. Results In this study, we first identified 2223 differentially expressed genes by comparing gene expression profiles for two control, two adenoma and two carcinoma samples using an F-test. These genes were subsequently mapped to the rat chromosomes using a novel visualization tool, the Chromosome Plot. Using the same plot, we further mapped the significant genes to orthologous chromosomal locations in human and mouse. Many genes expressed in rat 1q that are amplified in rat liver cancer map to the human chromosomes 10, 11 and 19 and to the mouse chromosomes 7, 17 and 19, which have been implicated in studies of human and mouse liver cancer. Using Comparative Genomics Microarray Analysis (CGMA), we identified regions of potential aberrations in human. Lastly, a pathway analysis was conducted to predict altered human pathways based on statistical analysis and extrapolation from the rat data. All of the identified pathways have been known to be important in the etiology of human liver cancer, including cell cycle control, cell growth and differentiation, apoptosis, transcriptional regulation, and protein metabolism. Conclusion The study demonstrates that the hepatic gene expression profiles from the albumin-SV40 transgenic rat model revealed genes, pathways and chromosome alterations consistent with experimental and

  8. Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver.

    PubMed

    Kaifi, Jussuf T; Kunkel, Miriam; Dicker, David T; Joude, Jamal; Allen, Joshua E; Das, Avisnata; Zhu, Junjia; Yang, Zhaohai; Sarwani, Nabeel E; Li, Guangfu; Staveley-O'Carroll, Kevin F; El-Deiry, Wafik S

    2015-01-01

    Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

  9. Unique activation of matrix metalloproteinase-9 within human liver metastasis from colorectal cancer.

    PubMed Central

    Zeng, Z. S.; Guillem, J. G.

    1998-01-01

    Experimental in vitro and animal data support an important role for matrix metalloproteinases (MMPs) in cancer invasion and metastasis via proteolytic degradation of the extracellular matrix (ECM). Our previous data have shown that MMP-9 mRNA is localized to the interface between liver metastasis and normal liver tissue, indicating that MMP-9 may play an important role in liver metastasis formation. In the present study, we analysed the cellular enzymatic expression of MMP-9 in 18 human colorectal cancer (CRC) liver metastasis specimens by enzyme-linked immunosorbent assay (ELISA) and zymography. ELISA analysis reveals that the latent form of MMP-9 is present in both liver metastasis and paired adjacent normal liver tissue. The mean level of the latent form of MMP-9 is 580+/-270 ng per mg total tissue protein (mean+/-s.e.) in liver metastasis vs 220+/-90 in normal liver tissue. However, this difference is not significantly different (P = 0.26). Using gelatin zymography, the 92-kDa band representative of the latent form is present in both liver metastasis and normal liver tissue. However, the 82 kDa band, representative of the active form of MMP-9, was seen only in liver metastasis. This was confirmed by Western blot analysis. Our observation of the unique presence of the active form of MMP-9 within liver metastasis suggests that proMMP-9 activation may be a pivotal event during CRC liver metastasis formation. Images Figure 3 Figure 4 PMID:9703281

  10. [Liver and lung metastases of colorectal cancer. Long-term survival and prognostic factors].

    PubMed

    Sponholz, S; Bölükbas, S; Schirren, M; Oguzhan, S; Kudelin, N; Schirren, J

    2016-02-01

    The resection of liver and lung metastases from colorectal cancer has not yet been completely investigated. The aim of this study was to investigate the overall survival and prognostic factors for patients with liver and lung metastases from colorectal cancer. A retrospective review of a prospective database of 52 patients with liver and lung metastases from colorectal cancer, undergoing metastasectomy with curative intent from 1999-2009 at a single institution was carried out. The mean overall survival (OS) was 64 months. For synchronous liver and lung metastases the mean overall survival was 63 months (5-year survival 54 %) and for metachronous liver and lung metastases 74 months (5-year survival 58 %, p = 0.451). A poor prognostic outcome was observed in cases of localization of the primary tumor in the rectum (OS 81 vs. 38 months, p = 0.004), with multiple lung metastases (≥ 2 metastases, OS 74 vs. 59 months, p = 0.032) and with disease progression after premetastasectomy chemotherapy (OS 74 vs. 63 vs. 15 months, p < 0.001). No influence on overall survival was detected for bilateral lung metastases, thoracic lymph node metastases, disease recurrence and disease-free interval < 36 months. Metastasectomy for liver and lung metastases of colorectal cancer is associated with a good overall survival in selected cases. Patients with liver and lung metastases should not be routinely excluded from metastasectomy and patients with thoracic lymph node metastases should also not be routinely excluded. Negative prognostic factors for survival are localization of the tumor in the rectum, multiple metastases and disease progression after premetastasectomy chemotherapy. Patients with disease progression after premetastasectomy chemotherapy should be excluded from metastasectomy.

  11. [Cancer treatment situation in Japan with regard to the type of medical facility using medical claim data of Health Insurance Societies].

    PubMed

    Tanaka, Hirokazu; Nakamura, Fumiaki; Higashi, Takahiro; Kobayashi, Yasuki

    2015-01-01

    Analyzing the cancer treatment situation in Japan is an important public health issue, especially because of increasing crude cancer morbidity in a rapidly aging society. This study aimed to examine where cancer patients received treatment, with special attention to designated regional cancer hospitals, and the treatment modality they received. Using health insurance claim data (1,064,875 subjects on December 2011) managed by the Japan Medical Data Center, we included patients that received treatments for stomach, colon, liver, lung, or breast cancer, the most common cancers in Japan, between 2005 and 2011. We divided the medical facilities where they were treated into five groups: prefectural designated regional cancer hospitals, local designated regional cancer hospitals, large/medium hospitals (≥100 beds), small hospitals (20-99 beds), and clinics (0-19 beds). We calculated the percentage of patients treated at each type of medical facility with different treatment modalities. The study included 2,901 patients. In total, 43.9% patients were treated at designated regional cancer hospitals (prefectural or local). This percentage was the highest for lung cancer (60.0%) and the lowest for colon cancer (31.3%). Surgeries for liver cancer (67.6%) and lung cancer (61.9%) were performed more at designated regional cancer hospitals (prefectural or local) than surgeries for stomach cancer (45.5%), colon cancer (40.1%), and breast cancer (49.8%). Some procedures were performed at small hospitals or clinics (surgery for stomach cancer [9.4%], surgery for breast cancer [9.3%], endoscopic procedures for stomach cancer [14.1%] and colon cancer [40.6%], and chemotherapy for breast cancer [11.4%]). Colon and breast cancer patients treated at prefectural designated regional cancer hospitals or clinics were younger than those treated at other types of facilities. The distribution of facilities at which cancer patients received treatment differed significantly according to cancer

  12. Changes in survival patterns in urban Chinese patients with liver cancer

    PubMed Central

    Hao, Xi-Shan; Chen, Ke-Xin; Wang, Peizhong Peter; Rohan, Tom

    2003-01-01

    AIM: To examine the survival patterns and determinants of primary liver cancer in a geographically defined Chinese population. METHODS: Primary liver cancer cases (n = 13685) diagnosed between 1981 and 2000 were identified by the Tianjin Cancer Registry. Age-adjusted and age-specific incidence rates were examined in both males and females. Proportional hazards (Cox) regression was utilized to explore the effects of time of diagnosis, sex, age, occupation, residence, and hospital of diagnosis on survival. RESULTS: Crude and age-adjusted incidence rates in the study period were: 27.4/100000 and 26.3/100000 in males; and 11.5/100000 and 10.4/100000 in females, respectively. Cox regression analyses indicated that there was a significant improvement in survival rates over time. Industrial workers and older people had relatively poor survival rates. The hospital in which the liver cancer was diagnosed was a statistically significant predictor of survival; patients diagnosed in city hospitals were more likely to have better survival than those diagnosed in community/district hospitals. CONCLUSION: Patients diagnosed in recent years appeared to have a better outcome than those diagnosed in early times. There were also significant survival disparities with respect to occupation and hospital of diagnosis, which suggest that socioeconomic status may play an important role in determining prognosis. PMID:12800226

  13. Liver disease stage determines whether the immune response stifles or stimulates tumor growth | Center for Cancer Research

    Cancer.gov

    Researchers at the Center for Cancer Research and colleagues from three cancer research centers in Germany have discovered a mechanism whereby precancerous liver cells, found in individuals with chronic liver disease, can prevent neighboring cells from becoming cancerous but can also speed the growth of cells that have already become cancerous.  Learn more...

  14. Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes.

    PubMed

    Spraggs, C F; Parham, L R; Briley, L P; Warren, L; Williams, L S; Fraser, D J; Jiang, Z; Aziz, Z; Ahmed, S; Demetriou, G; Mehta, A; Jackson, N; Byrne, J; Andersson, M; Toi, M; Harris, L; Gralow, J; Zujewski, J A; Crescenzo, R; Armour, A; Perez, E; Piccart, M

    2018-05-22

    HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatment optimisation). HLA-DRB1*07:01 carriage was associated with serum alanine aminotransferase (ALT) elevations in lapatinib-treated patients (odds ratio 6.5, P=3 × 10 -26 , n=4482) and the risk and severity of ALT elevation for lapatinib-treated patients was higher in homozygous than heterozygous HLA-DRB1*07:01 genotype carriers. A higher ALT case incidence plus weaker HLA association observed during concurrent administration of lapatinib and taxane suggested a subset of liver injury in this combination group that was HLA-DRB1*07:01 independent. Furthermore, the incidence of ALT elevation demonstrated an expected correlation with geographic HLA-DRB1*07:01 carriage frequency. Robust ALT elevation risk estimates for HLA-DRB1*07:01 may support causality discrimination and safety risk management during the use of lapatinib combination therapy for the treatment of metastatic breast cancer.

  15. S-ADENOSYLMETHIONINE IN LIVER HEALTH, INJURY, AND CANCER

    PubMed Central

    Lu, Shelly C.; Mato, José M.

    2013-01-01

    S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well. PMID:23073625

  16. Researchers discover promising new targets for treatment of fatty liver disease | Center for Cancer Research

    Cancer.gov

    Researchers have identified potential new drug targets for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). The new study, which was a collaborative effort between scientists in the Laboratory of Metabolism at CCR and Peking University, was published October 9, 2017, in Nature Medicine. Read more…

  17. Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China.

    PubMed

    Zhao, Jin-Kou; Wu, Ming; Kim, Claire H; Jin, Zi-Yi; Zhou, Jin-Yi; Han, Ren-Qiang; Yang, Jie; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Gu, Xiaoping; Su, Ming; Hu, Xu; Sun, Zheng; Li, Gang; Li, Liming; Mu, Lina; Zhang, Zuo-Feng

    2017-07-01

    Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.

  18. Gastroesphageal Variceal Hemorrhage Induced by Metastatic Liver Tumor of Lung Cancer

    PubMed Central

    Honda, Takayuki; Kobayashi, Hiroaki; Saiki, Masafumi; Sogami, Yusuke; Miyashita, Yoshihiro; Inase, Naohiko

    2012-01-01

    Gastroesophageal variceal hemorrhage is a lethal complication of portal hypertension. Liver cirrhosis is often the principal cause of the portal hypertensive state. Malignant tumors coexist with portal hypertension in some cases. Non-small-cell lung cancer (NSCLC) is likely to become metastatic. Liver is a frequent site of cancer metastasis, but diffuse hepatic sinusoidal metastasis is uncommon as a metastatic form of NSCLC. This report describes a patient with gastroesophageal variceal hemorrhage owing to a metastatic liver tumor of NSCLC. The patient, a male smoker with stage IV NSCLC, was free of any hepatitis viral infection and had no alcohol addiction. Liver dysfunction and liver disease had never been pointed out in his medical history. His tumor harbored an L858R epidermal growth factor receptor mutation. Gefitinib was initiated but had to be ceased because of interstitial lung disease. Sequential steroid therapy was effective and bevacizumab-containing chemotherapy was commenced. Both chemotherapy regimens produced favorable effects against the metastatic liver tumor, eliciting atrophic change regardless of the chemotherapy-free interval. One day the patient was admitted to our hospital because of black stool and hypotension. Upper gastrointestinal endoscopy revealed a beaded appearance of the gastroesophageal varix with bloody gastric contents. The portal hypertension might have been caused by changes in portal vein hemodynamics induced by the conformational changes underlying the favorable response of the liver tumor to molecular targeted chemotherapy and notable regression. PMID:23275780

  19. CRISPR-mediated direct mutation of cancer genes in the mouse liver

    PubMed Central

    Xue, Wen; Chen, Sidi; Yin, Hao; Tammela, Tuomas; Papagiannakopoulos, Thales; Joshi, Nikhil S.; Cai, Wenxin; Yang, Gillian; Bronson, Roderick; Crowley, Denise G.; Zhang, Feng; Anderson, Daniel G.; Sharp, Phillip A.; Jacks, Tyler

    2014-01-01

    The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem (ES) cells1. Here we describe a new method of cancer model generation using the CRISPR/Cas system in vivo in wild-type mice. We have used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs)2–4 to the liver and directly target the tumor suppressor genes Pten5 and p536, alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology7, 8. Simultaneous targeting of Pten and p53 induced liver tumors that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumor tissue revealed insertion or deletion (indel) mutations of the tumor suppressor genes, including bi-allelic mutations of both Pten and p53 in tumors. Furthermore, co-injection of Cas9 plasmids harboring sgRNAs targeting the β-Catenin gene (Ctnnb1) and a single-stranded DNA (ssDNA) oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of β-Catenin. This study demonstrates the feasibility of direct mutation of tumor suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics. PMID:25119044

  20. CRISPR-mediated direct mutation of cancer genes in the mouse liver.

    PubMed

    Xue, Wen; Chen, Sidi; Yin, Hao; Tammela, Tuomas; Papagiannakopoulos, Thales; Joshi, Nikhil S; Cai, Wenxin; Yang, Gillian; Bronson, Roderick; Crowley, Denise G; Zhang, Feng; Anderson, Daniel G; Sharp, Phillip A; Jacks, Tyler

    2014-10-16

    The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem cells. Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs) to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology. Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the β-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of β-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics.

  1. First clinical implementation of audiovisual biofeedback in liver cancer stereotactic body radiation therapy.

    PubMed

    Pollock, Sean; Tse, Regina; Martin, Darren; McLean, Lisa; Cho, Gwi; Hill, Robin; Pickard, Sheila; Aston, Paul; Huang, Chen-Yu; Makhija, Kuldeep; O'Brien, Ricky; Keall, Paul

    2015-10-01

    This case report details a clinical trial's first recruited liver cancer patient who underwent a course of stereotactic body radiation therapy treatment utilising audiovisual biofeedback breathing guidance. Breathing motion results for both abdominal wall motion and tumour motion are included. Patient 1 demonstrated improved breathing motion regularity with audiovisual biofeedback. A training effect was also observed. © 2015 The Authors. Journal of Medical Imaging and Radiation Oncology published by Wiley Publishing Asia Pty Ltd on behalf of The Royal Australian and New Zealand College of Radiologists.

  2. Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors and Dose Limitations.

    PubMed

    Li, Guichao; Wang, Jiazhou; Hu, Weigang; Zhang, Zhen

    2015-01-01

    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. 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. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann-Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum albumin (ALB)] after RT. The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury. In 3D-CRT for gastric cancer patients

  3. Chemokine Receptor CXCR4 Expression in Patients With Melanoma and Colorectal Cancer Liver Metastases and the Association With Disease Outcome

    PubMed Central

    Kim, Joseph; Mori, Takuji; Chen, Steven L.; Amersi, Farin F.; Martinez, Steve R.; Kuo, Christine; Turner, Roderick R.; Ye, Xing; Bilchik, Anton J.; Morton, Donald L.; Hoon, Dave S. B.

    2006-01-01

    Objective: To determine the role of chemokine receptor (CR) expression in patients with melanoma and colorectal cancer (CRC) liver metastases. Summary Background Data: Murine and in vitro models have identified CR as potential factors in organ-specific metastasis of multiple cancers. Chemokines via their respective receptors have been shown to promote cell migration to distant organs. Methods: Patients who underwent hepatic surgery for melanoma or CRC liver metastases were assessed. Screening cDNA microarrays of melanoma/CRC cell lines and tumor specimens were analyzed to identify CR. Microarray data were validated by quantitative real-time RT-PCR (qRT) in paraffin-embedded liver metastases. Migration assays and immunohistochemistry were performed to verify CR function and confirm CR expression, respectively. Results: Microarray analysis identified CXCR4 as the most common CR expressed by both cancers. qRT demonstrated CXCR4 expression in 24 of 27 (89%) melanoma and 28 of 29 (97%) CRC liver metastases. In vitro treatment of melanoma or CRC cells with CXCL12, the ligand for CXCR4, significantly increased cell migration (P < 0.001). Low versus high CXCR4 expression in CRC liver metastases correlated with a significant difference in overall survival (median 27 months vs. 10 months, respectively; P = 0.036). In melanoma, low versus high CXCR4 expression in liver metastases demonstrated no difference in overall survival (median 11 months vs. 8 months, respectively; P = not significant). Conclusions: CXCR4 is expressed and functional on melanoma and CRC cells. The ligand for CXCR4 is highly expressed in liver and may specifically attract melanoma and CRC CXCR4 (+) cells. Quantitative analysis of CXCR4 gene expression in patients with liver metastases has prognostic significance for disease outcome. PMID:16794396

  4. Assessment of the Hong Kong Liver Cancer Staging System in Europe.

    PubMed

    Kolly, Philippe; Reeves, Helen; Sangro, Bruno; Knöpfli, Marina; Candinas, Daniel; Dufour, Jean-François

    2016-06-01

    European and American guidelines have endorsed the Barcelona Clinic Liver Cancer (BCLC) staging system. The aim of this study was to assess the performance of the recently developed Hong Kong Liver Cancer (HKLC) classification as a staging system for hepatocellular carcinoma (HCC) in Europe. We used a pooled set of 1693 HCC patients combining three prospective European cohorts. Discrimination ability between the nine substages and five stages of the HKLC classification system was assessed. To evaluate the predictive power of the HKLC and BCLC staging systems on overall survival, Nagelkerke pseudo R2, Bayesian Information Criterion and Harrell's concordance index were calculated. The number of patients who would benefit from a curative therapy was assessed for both staging systems. The HKLC classification in nine substages shows suboptimal discrimination between the staging groups. The classification in five stages shows better discrimination between groups. However, the BCLC classification performs better than the HKLC classification in the ability to predict overall survival (OS). The HKLC treatment algorithm tags significantly more patients to curative therapy than the BCLC. The BCLC staging system performs better for European patients than the HKLC staging system in predicting OS. Twice more patients are eligible for a curative therapy with the HKLC algorithm; whether this translates in survival benefit remains to be investigated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. The complete mitochondrial genome of a chronic hepatitis associated liver cancer LEC rat strain.

    PubMed

    Zhang, Sihao; Jiang, Zhaoming; Zhang, Shuai; Xia, Mingfeng; Tian, Fang; Tian, Hu

    2016-05-01

    We sequenced a complete mitochondrial genome sequencing of a chronic hepatitis-associated liver cancer disease LEC rat strain for the first time. The total length of the mitogenome was 16,316 bp with 13 protein-coding genes, two ribosomal RNA genes and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into liver cancer disease.

  6. HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer.

    PubMed

    Styczen, Hanna; Nagelmeier, Iris; Beissbarth, Tim; Nietert, Manuel; Homayounfar, Kia; Sprenger, Thilo; Boczek, Ute; Stanek, Kathrin; Kitz, Julia; Wolff, Hendrik A; Ghadimi, B Michael; Middel, Peter; Liersch, Torsten; Rüschoff, Josef; Conradi, Lena-Christin

    2015-06-20

    In this study, we evaluate the frequency of HER-2 and HER-3 expression in liver metastases from patients with colorectal cancer (CRLM). We analyzed the potential of HER-2 and HER-3 as therapeutic targets and evaluated their prognostic value. Overall 208 patients with CRLM were enrolled. HER-2 and HER-3 expression were determined in metastatic tissue of diagnostic punch biopsies (n = 29) or resection specimens (n = 179). The results of immunohistochemistry (IHC) scoring and In-situ-hybridization (ISH)-amplification were correlated with clinical parameters and for the 179 resected patients with cancer-specific (CSS) and overall survival (OS). The mean follow-up time was 56.7 months. Positivity of HER-2 status (IHC score 2+/ISH+ and IHC 3+) was found in 8.2% of CRLM. High expression of HER-3 (IHC score 2+ and IHC 3+) was detected in 75.0% of liver metastases. CSS after liver surgery was determined and was independent from the HER-2 status (p = 0.963); however HER-3 was prognostic with a favorable course for patients showing an overexpression of HER-3 (p = 0.037). HER-2 overexpression occurs in only 8% of patients with CRLM but with 75% of cases HER-3 is frequently overexpressed in CRLM. Therefore, HER-2 and particularly HER-3 could serve as novel targets to be addressed within multimodal treatment approaches.

  7. Anisotropic patterns of liver cancer prevalence in Guangxi in Southwest China: is local climate a contributing factor?

    PubMed

    Deng, Wei; Long, Long; Tang, Xian-Yan; Huang, Tian-Ren; Li, Ji-Lin; Rong, Min-Hua; Li, Ke-Zhi; Liu, Hai-Zhou

    2015-01-01

    Geographic information system (GIS) technology has useful applications for epidemiology, enabling the detection of spatial patterns of disease dispersion and locating geographic areas at increased risk. In this study, we applied GIS technology to characterize the spatial pattern of mortality due to liver cancer in the autonomous region of Guangxi Zhuang in southwest China. A database with liver cancer mortality data for 1971-1973, 1990-1992, and 2004-2005, including geographic locations and climate conditions, was constructed, and the appropriate associations were investigated. It was found that the regions with the highest mortality rates were central Guangxi with Guigang City at the center, and southwest Guangxi centered in Fusui County. Regions with the lowest mortality rates were eastern Guangxi with Pingnan County at the center, and northern Guangxi centered in Sanjiang and Rongshui counties. Regarding climate conditions, in the 1990s the mortality rate of liver cancer positively correlated with average temperature and average minimum temperature, and negatively correlated with average precipitation. In 2004 through 2005, mortality due to liver cancer positively correlated with the average minimum temperature. Regions of high mortality had lower average humidity and higher average barometric pressure than did regions of low mortality. Our results provide information to benefit development of a regional liver cancer prevention program in Guangxi, and provide important information and a reference for exploring causes of liver cancer.

  8. The chemokines CCR1 and CCRL2 have a role in colorectal cancer liver metastasis.

    PubMed

    Akram, Israa G; Georges, Rania; Hielscher, Thomas; Adwan, Hassan; Berger, Martin R

    2016-02-01

    C-C chemokine receptor type 1 (CCR1) and chemokine C-C motif receptor-like 2 (CCRL2) have not yet been sufficiently investigated for their role in colorectal cancer (CRC). Here, we investigated their expression in rat and human CRC samples, their modulation of expression in a rat liver metastasis model, as well as the effects on cellular properties resulting from their knockdown. One rat and five human colorectal cancer cell lines were used. CC531 rat colorectal cells were injected via the portal vein into rats and re-isolated from rat livers after defined periods. Following mRNA isolation, the gene expression was investigated by microarray. In addition, all cell lines were screened for mRNA expression of CCR1 and CCRL2 by reverse transcription polymerase chain reaction (RT-PCR). Cell lines with detectable expression were used for knockdown experiments; and the respective influence was determined on the cells' proliferation, scratch closure, and colony formation. Finally, specimens from the primaries of 50 patients with CRC were monitored by quantitative RT-PCR for CCR1 and CCRL2 expression levels. The microarray studies showed peak increases of CCR1 and CCRL2 in the early phase of liver colonization. Knockdown was sufficient at mRNA but only moderate at protein levels and resulted in modest but significant inhibition of proliferation (p < 0.05), scratch closure, and colony formation (p < 0.05). All human CRC samples were positive for CCR1 and CCRL2 and showed a significant pairwise correlation (p < 0.0004), but there was no correlation with tumor stage or age of patients. In summary, the data point to an important role of CCR1 and CCRL2 under conditions of organ colonization and both chemokine receptors qualify as targets of treatment during early colorectal cancer liver metastasis.

  9. Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

    PubMed

    Tran, K T; McMenamin, Ú C; Hicks, B; Murchie, P; Thrift, A P; Coleman, H G; Iversen, L; Johnston, B T; Lee, A J; Cardwell, C R

    2018-05-09

    Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research. © 2018 John Wiley & Sons Ltd.

  10. [Long-Term Multidisciplinary Therapy for Multiple Liver Metastases from Colorectal Cancer with Biliary Drainage for Occlusive Jaundice--A Case Report].

    PubMed

    Okamura, Shu; Mikami, Koji; Murata, Kohei; Nushijima, Yoichirou; Okada, Kazuyuki; Yanagisawa, Tetsu; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

    2015-11-01

    Here, we report the case of a 43-year-old man who was diagnosed with sigmoid colon cancer with synchronous multiple liver metastases following resection of a primary lesion. Subsequent mFOLFOX+BV therapy elicited a marked response in the liver metastases, which led to the patient undergoing hepatic (S7) radiofrequency ablation (RFA), hepatic resection (lateral segmentectomy and partial [S5] resection), and cholecystectomy. Six months later, transluminal RFA was repeated because liver (S7) metastasis recurred, and 8 courses of XELOX plus BV therapy were administered. As obstructive jaundice due to recurrence of the liver metastases developed after a 6 months hiatus in chemotherapy, we endoscopically inserted a biliary stent. Despite reducing IRIS plus BV therapy, obstructive jaundice developed again, and 3 intrahepatic biliary stents were inserted with percutaneous transhepatic biliary drainage. To date, the patient has been alive for 4 years since the initial resection of the primary lesion after undergoing consecutive systemic chemotherapy with different regimens. Some studies have shown that in cases of obstructive jaundice caused by advanced gastrointestinal cancer, longer survival could be expected by reducing the severity of jaundice, suggesting that resuming chemotherapy as well as improving the severity of jaundice could contribute to better outcomes. The patient in the present case was successfully treated twice with biliary drainage for occlusive jaundice and chemotherapy, suggesting that a combination of multidisciplinary therapy and adequate local therapy such as biliary drainage could be important for the treatment of metastatic liver cancer.

  11. Knowledge-based IMRT planning for individual liver cancer patients using a novel specific model.

    PubMed

    Yu, Gang; Li, Yang; Feng, Ziwei; Tao, Cheng; Yu, Zuyi; Li, Baosheng; Li, Dengwang

    2018-03-27

    The purpose of this work is to benchmark RapidPlan against clinical plans for liver Intensity-modulated radiotherapy (IMRT) treatment of patients with special anatomical characteristics, and to investigate the prediction capability of the general model (Model-G) versus our specific model (Model-S). A library consisting of 60 liver cancer patients with IMRT planning was used to set up two models (Model-S, Model-G), using the RapidPlan knowledge-based planning system. Model-S consisted of 30 patients with special anatomical characteristics where the distance from planning target volume (PTV) to the right kidney was less than three centimeters and Model-G was configurated using all 60 patients in this library. Knowledge-based IMRT plans were created for the evaluation group formed of 13 patients similar to those included in Model-S by Model-G, Model-S and manually (M), named RPG-plans, RPS-plans and M-plans, respectively. The differences in the dose-volume histograms (DVHs) were compared, not only between RP-plans and their respective M-plans, but also between RPG-plans and RPS-plans. For all 13 patients, RapidPlan could automatically produce clinically acceptable plans. Comparing RP-plans to M-plans, RP-plans improved V 95% of PTV and had greater dose sparing in the right kidney. For the normal liver, RPG-plans delivered similar doses, while RPS-plans delivered a higher dose than M-plans. With respect to RapidPlan models, RPS-plans had better conformity index (CI) values and delivered lower doses to the right kidney V 20Gy and maximizing point doses to spinal cord, while delivering higher doses to the normal liver. The study shows that RapidPlan can create high-quality plans, and our specific model can improve the CI of PTV, resulting in more sparing of OAR in IMRT for individual liver cancer patients.

  12. Gut microbiome can control antitumor immune function in liver

    Cancer.gov

    An NCI study in mice that found a connection between gut bacteria and antitumor immune responses in the liver has implications for understanding mechanisms that lead to liver cancer and for potential treatments. The study was published in Science.

  13. Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH.

    PubMed

    Urosevic, Jelena; Garcia-Albéniz, Xabier; Planet, Evarist; Real, Sebastián; Céspedes, María Virtudes; Guiu, Marc; Fernandez, Esther; Bellmunt, Anna; Gawrzak, Sylwia; Pavlovic, Milica; Mangues, Ramon; Dolado, Ignacio; Barriga, Francisco M; Nadal, Cristina; Kemeny, Nancy; Batlle, Eduard; Nebreda, Angel R; Gomis, Roger R

    2014-07-01

    The mechanisms that allow colon cancer cells to form liver and lung metastases, and whether KRAS mutation influences where and when metastasis occurs, are unknown. We provide clinical and molecular evidence showing that different MAPK signalling pathways are implicated in this process. Whereas ERK2 activation provides colon cancer cells with the ability to seed and colonize the liver, reduced p38 MAPK signalling endows cancer cells with the ability to form lung metastasis from previously established liver lesions. Downregulation of p38 MAPK signalling results in increased expression of the cytokine PTHLH, which contributes to colon cancer cell extravasation to the lung by inducing caspase-independent death in endothelial cells of the lung microvasculature. The concerted acquisition of metastatic traits in the colon cancer cells together with the sequential colonization of liver and lung highlights the importance of metastatic lesions as a platform for further dissemination.

  14. C/EBPα-dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer.

    PubMed

    Cast, Ashley; Valanejad, Leila; Wright, Mary; Nguyen, Phuong; Gupta, Anita; Zhu, Liqin; Shin, Soona; Timchenko, Nikolai

    2018-05-01

    Recent publications show that classic hepatoblastoma (HBL) is the result of failure of hepatic stem cells to differentiate into hepatocytes, while hepatocellular carcinoma (HCC) is caused by the dedifferentiation of hepatocytes into cancer stem cells. However, the mechanisms of aggressive HBL and the mechanisms that cause dedifferentiation of hepatocytes into cancer stem cells are unknown. We found that, similar to HCC but opposite to classic HBL, aggressive HBL is the result of dedifferentiation of hepatocytes into cancer stem cells. In both cases of liver cancer, the dephosphorylation of tumor suppressor protein CCAAT/enhancer binding protein α (C/EBPα) at Ser193 (Ser190 in human protein) or mutation of Ser193 to Ala results in a modified protein with oncogenic activities. We have investigated liver cancer in a mouse model C/EBPα-S193A, in a large cohort of human HBL samples, and in Pten/p53 double knockout mice and found that these cancers are characterized by elevation of C/EBPα that is dephosphorylated at Ser190/193. We found that dephosphorylated C/EBPα creates preneoplastic foci with cancer stem cells that give rise to HCC and aggressive HBL. C/EBPα-dependent dedifferentiation of hepatocytes into cancer stem cells includes increased proliferation of hepatocytes, followed by generation of multinucleated hepatocytes and subsequent appearance of hepatocytes with delta-like 1 homolog-positive intranuclear inclusions. We further isolated C/EBPα-dependent multinucleated hepatocytes and found that they possess characteristics of tumor-initiating cells, including elevation of stem cell markers. C/EBPα-dependent cancer stem cells are observed in patients with aggressive HBL and in patients with a predisposition for liver cancer. The earliest steps of adult HCC and aggressive pediatric liver cancer have identical features that include conversion of the tumor suppressor C/EBPα into an oncogenic isoform, which further creates preneoplastic foci where

  15. Induction of Chromosome Instability by Activation of Yes-Associated Protein and Forkhead Box M1 in Liver Cancer.

    PubMed

    Weiler, Sofia M E; Pinna, Federico; Wolf, Thomas; Lutz, Teresa; Geldiyev, Aman; Sticht, Carsten; Knaub, Maria; Thomann, Stefan; Bissinger, Michaela; Wan, Shan; Rössler, Stephanie; Becker, Diana; Gretz, Norbert; Lang, Hauke; Bergmann, Frank; Ustiyan, Vladimir; Kalin, Tatiana V; Singer, Stephan; Lee, Ju-Seog; Marquardt, Jens U; Schirmacher, Peter; Kalinichenko, Vladimir V; Breuhahn, Kai

    2017-06-01

    with thiostrepton, reduced the chromosome instability gene expression patterns. Hyperplastic livers and tumors from YAP S127A mice had increased CIN25 and CIN70 gene expression patterns, aneuploidy, and defects in mitosis. Injection of YAP S127A mice with thiostrepton reduced liver overgrowth and signs of chromosomal instability. In human HCC tissues, high levels of nuclear YAP correlated with increased chromosome instability gene expression patterns and aneuploidy. By analyzing cell lines, genetically modified mice, and HCC tissues, we found that YAP cooperates with FOXM1 to contribute to chromosome instability. Agents that disrupt this pathway might be developed as treatments for liver cancer. Transcriptome data are available in the Gene Expression Omnibus public database (accession numbers: GSE32597 and GSE73396). Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Defeating EpCAM(+) liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma.

    PubMed

    Nio, Kouki; Yamashita, Taro; Okada, Hikari; Kondo, Mitsumasa; Hayashi, Takehiro; Hara, Yasumasa; Nomura, Yoshimoto; Zeng, Sha Sha; Yoshida, Mariko; Hayashi, Tomoyuki; Sunagozaka, Hajime; Oishi, Naoki; Honda, Masao; Kaneko, Shuichi

    2015-11-01

    Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM(+) liver cancer stem cells. Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of CHD4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. CHD4 was abundantly expressed in EpCAM(+) hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of CHD4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM(+) liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model. CHD4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. Pyogenic liver abscesses associated with nonmetastatic colorectal cancers: An increasing problem in Eastern Asia

    PubMed Central

    Qu, Kai; Liu, Chang; Wang, Zhi-Xin; Tian, Feng; Wei, Ji-Chao; Tai, Ming-Hui; Zhou, Lei; Meng, Fan-Di; Wang, Rui-Tao; Xu, Xin-Sen

    2012-01-01

    AIM: To elaborate the clinicopathologic features of colorectal cancer-related pyogenic liver abscess (PLA). METHODS: Reported cases of colorectal cancer-related PLAs were collected from the literature published up to October 2011 and evaluated for their clinicopathologic features. Data of collected cases included demographics, clinical presentation, microbial findings and treatment. Categorical variables were compared by χ2 analysis and continuous variables were evaluated using Student’s t test. RESULTS: A total 96 cases of colorectal cancer-related PLA were collected from the previous literature. Most patients (60%) were male and 40% cases occurred in the age group of 61-70 years. Apart from some special types of PLA, there were significant differences in the microbiological spectrum between Eastern Asia and non-Eastern Asian countries, which implied different risk factors and courses of the disease. Gram negative bacteria especially Klebsiella pneumoniae (K. pneumoniae) PLA was predominant in Eastern Asia (80.0%) in contrast to non-Eastern Asian countries (P < 0.01). Meanwhile, most of the Eastern Asian patients exhibited smaller size of liver abscess and atypical presentation. Sigmoid colon and rectum (72.73%) were the main sites of tumor in Eastern Asian patients, whereas tumor sites were uneven among most of the non-Easter Asian PLA patients. CONCLUSION: K. pneumoniae PLA was strongly associated with colorectal cancer, especially those occurring in sigmoid colon and rectum, in elderly Eastern Asian male patients. PMID:22736918

  18. Spectrum of De Novo Cancers and Predictors in Liver Transplantation: Analysis of the Scientific Registry of Transplant Recipients Database.

    PubMed

    Zhou, Jie; Hu, Zhenhua; Zhang, Qijun; Li, Zhiwei; Xiang, Jie; Yan, Sheng; Wu, Jian; Zhang, Min; Zheng, Shusen

    2016-01-01

    De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. To describe the overall pattern of de novo cancers in liver transplant recipients. Data from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies. Among 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation. De novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention.

  19. Composite fatty acid ether amides suppress growth of liver cancer cells in vitro and in an in vivo allograft mouse model.

    PubMed

    Cao, Mengde; Prima, Victor; Nelson, David; Svetlov, Stanislav

    2013-06-01

    The heterogeneity of liver cancer, in particular hepatocellular carcinoma (HCC), portrays the requirement of multiple targets for both its treatment and prevention. Multifaceted agents, minimally or non-toxic for normal hepatocytes, are required to address the molecular diversity of HCC, including the resistance of putative liver cancer stem cells to chemotherapy. We designed and synthesized two fatty acid ethers of isopropylamino propanol, C16:0-AIP-1 and C18:1-AIP-2 (jointly named AIPs), and evaluated their anti-proliferative effects on the human HCC cell line Huh7 and the murine hepatoma cell line BNL 1MEA.7R.1, both in vitro and in an in vivo allograft mouse model. We found that AIP-1 and AIP-2 inhibited proliferation and caused cell death in both Huh7 and BNL 1MEA.7R.1 cells. Importantly, AIP-1 and AIP-2 were found to block the activation of putative liver cancer stem cells as manifested by suppression of clonal 'carcinosphere' development in growth factor-free and anchorage-free medium. The AIPs exhibited a relatively low toxicity against normal human or rat hepatocytes in primary cultures. In addition, we found that the AIPs utilized multifaceted pathways that mediate both autophagy and apoptosis in HCC, including the inhibition of AKTs and CAMK-1. In immune-competent mice, the AIPs significantly reduced BNL 1MEA.7R.1 cell-driven tumor allograft development, with a higher efficiency than sorafenib. A combination of AIP-1 + AIP-2 was most effective in reducing the tumor allograft incidence. AIPs represent a novel class of simple fatty acid derivatives that are effective against liver tumors via diverse pathways. They show a low toxicity towards normal hepatocytes. The addition of AIPs may represent a new avenue towards the management of chronic liver injury and, ultimately, the prevention and treatment of HCC.

  20. Resection of synchronous liver metastases between radiotherapy and definitive surgery for locally advanced rectal cancer: short-term surgical outcomes, overall survival and recurrence-free survival.

    PubMed

    Labori, K J; Guren, M G; Brudvik, K W; Røsok, B I; Waage, A; Nesbakken, A; Larsen, S; Dueland, S; Edwin, B; Bjørnbeth, B A

    2017-08-01

    There is debate as to the correct treatment algorithm sequence for patients with locally advanced rectal cancer with liver metastases. The aim of the study was to assess safety, resectability and survival after a modified 'liver-first' approach. This was a retrospective study of patients undergoing preoperative radiotherapy for the primary rectal tumour, followed by liver resection and, finally, resection of the primary tumour. Short-term surgical outcome, overall survival and recurrence-free survival are reported. Between 2009 and 2013, 45 patients underwent liver resection after preoperative radiotherapy. Thirty-four patients (76%) received neoadjuvant chemotherapy, 24 (53%) concomitant chemotherapy during radiotherapy and 17 (43%) adjuvant chemotherapy. The median time interval from the last fraction of radiotherapy to liver resection and rectal surgery was 21 (range 7-116) and 60 (range 31-156) days, respectively. Rectal resection was performed in 42 patients but was not performed in one patient with complete response and two with progressive metastatic disease. After rectal surgery three patients did not proceed to a planned second stage liver (n = 2) or lung (n = 1) resection due to progressive disease. Clavien-Dindo ≥Grade III complications developed in 6.7% after liver resection and 19% after rectal resection. The median overall survival and recurrence-free survival in the patients who completed the treatment sequence (n = 40) were 49.7 and 13.0 months, respectively. Twenty of the 30 patients who developed recurrence underwent further treatment with curative intent. The modified liver-first approach is safe and efficient in patients with locally advanced rectal cancer and allows initial control of both the primary tumour and the liver metastases. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  1. S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells.

    PubMed

    Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

    2017-12-19

    S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent.

  2. [Trends in the mortality of liver cancer in Qidong, China: an analysis of fifty years].

    PubMed

    Chen, Jian-guo; Zhu, Jian; Zhang, Yong-hui; Chen, Yong-sheng; Ding, Lu-lu; Lu, Jian-hua; Zhu, Yuan-rong

    2012-07-01

    To describe and analyze the charecteristics and trends of liver cancer mortality during the past fifty years in Qidong, China. Retrospective mortality survey was conducted to get the data on liver cancer death in the period of 1958-1971, and the data from 1972 to 2007 were obtained from the records of cancer registration in Qidong. The crude mortality rate (CR) of liver cancer, and age-standardized rate by Chinese population (CASR) and by world population (WASR) were calculated and analyzed. The total percent changes (PC) and annual percent changes (APC) were used for evaluating the increasing trends of the mortality. The sex-specific rate, age-specific rate, truncated rate of the age group 35 - 64, cumulative rate of the age group 0-74, cumulative risk, period-rate, and the rate for age-birth cohort were compared. The natural death rate in Qidong residents for the past five-decade period experienced a wave interval of 8.62‰ in 1958 down to 5.37‰ in 1979, and up to 7.75‰ in 2007. The mortality rate for all-site cancers was increased from 56.69 per 100, 000 to 234.97 per 100, 000. The mortality rate of liver cancer, being 20.45 per 100, 100 in 1958 was increased to 49.04 per 100, 000 in 1972, and up to 69.29 per 100, 000 in 2007. According to the registration data of 1972 - 2007, the death from liver cancer was accounted for 34.88% of all deaths due to cancers, with a CR of 58.86 per 100, 000, CASR of 38.36 per 100, 000, and WASR, 49.37 Per 100, 000 in Qidong. The truncated rate for the age group 35 - 64 was 117.08 per 100, 000, and the cumulative rate for the age group 0-74 and the cumulative risk were 5.15% and 5.02%, respectively. The CRs for males was 90.52 per 100, 000 and for females was 27.93 per 100, 000, with a sex ratio of 3.24:1. For the period of 1972 - 2007, the PC for CR was 49.71%, and APC was +1.41%, showing an increasing variation tendency. The APCs for CASR and WASR, however, were decreasing, with a percentage of -1.11%, and -0

  3. Levetiracetam in the Treatment of Epileptic Seizures After Liver Transplantation

    PubMed Central

    Lin, Chih-Hsiang; Chen, Chao-Long; Lin, Tsu-Kung; Chen, Nai-Ching; Tsai, Meng-Han; Chuang, Yao-Chung

    2015-01-01

    Abstract After liver transplantation, patients may develop seizures or epilepsy due to a variety of etiologies. The ideal antiepileptic drugs for these patients are those with fewer drug interactions and less hepatic toxicity. In this study, we present patients using levetiracetam to control seizures after liver transplantation. We retrospectively enrolled patients who received levetiracetam for seizure control after liver transplantation. We analyzed the etiology of liver failure that required liver transplantation, etiology of the seizures, outcomes of seizure control, and the condition of the patient after follow-up at the outpatient department. Hematological and biochemical data before and after the use of levetiracetam were also collected. Fifteen patients who received intravenous or oral levetiracetam monotherapy for seizure control after liver transplantation were enrolled into this study. All of the patients remained seizure-free during levetiracetam treatment. Two patients died during the follow-up, and the other 13 patients were alive at the end of the study period and all were seizure-free without neurological sequelae that interfered with their daily activities. No patients experienced liver failure or rejection of the donor liver due to ineffective immunosuppressant medications. The dosage of immunosuppressants did not change before and after levetiracetam treatment, and there were no changes in hematological and biochemical data before and after treatment. Levetiracetam may be a suitable antiepileptic drug for patients who undergo liver transplantation due to fewer drug interactions and a favorable safety profile. PMID:26402799

  4. Levetiracetam in the Treatment of Epileptic Seizures After Liver Transplantation.

    PubMed

    Lin, Chih-Hsiang; Chen, Chao-Long; Lin, Tsu-Kung; Chen, Nai-Ching; Tsai, Meng-Han; Chuang, Yao-Chung

    2015-09-01

    After liver transplantation, patients may develop seizures or epilepsy due to a variety of etiologies. The ideal antiepileptic drugs for these patients are those with fewer drug interactions and less hepatic toxicity. In this study, we present patients using levetiracetam to control seizures after liver transplantation. We retrospectively enrolled patients who received levetiracetam for seizure control after liver transplantation. We analyzed the etiology of liver failure that required liver transplantation, etiology of the seizures, outcomes of seizure control, and the condition of the patient after follow-up at the outpatient department. Hematological and biochemical data before and after the use of levetiracetam were also collected. Fifteen patients who received intravenous or oral levetiracetam monotherapy for seizure control after liver transplantation were enrolled into this study. All of the patients remained seizure-free during levetiracetam treatment. Two patients died during the follow-up, and the other 13 patients were alive at the end of the study period and all were seizure-free without neurological sequelae that interfered with their daily activities. No patients experienced liver failure or rejection of the donor liver due to ineffective immunosuppressant medications. The dosage of immunosuppressants did not change before and after levetiracetam treatment, and there were no changes in hematological and biochemical data before and after treatment. Levetiracetam may be a suitable antiepileptic drug for patients who undergo liver transplantation due to fewer drug interactions and a favorable safety profile.

  5. [Perioperative changes of coagulation functions in the local advanced liver cancer patients receiving liver transplantation].

    PubMed

    Wang, Hao-Yuan; Zhao, Qing-Yu; Yuan, Yun-Fei

    2008-07-01

    Liver transplantation is widely accepted as an effective therapy of hepatoma. Perioperative dynamic observation of coagulation function is important for graft-receivers. This study was to explore perioperative changes of coagulation functions in the local advanced liver cancer patients who received liver transplantation. Clinical data of 31 local advanced liver cancer patients, underwent liver transplantation from Sep. 2003 to Jan. 2007, were analyzed. Platelet (PLT) counting, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) and international normalized ratio (INR) before operation, at anhepatic phase and the first week after operation were analyzed to evaluate congulation function. The coagulation functions of most patients were normal before operation. The six parameters varied significantly at anhepatic phase and on most days of the first week after operation when compared with the preoperative levels (P<0.05). The elevation of PT, APTT, TT and INR and the decrease of Fib and PLT were more apparent at anhepatic phase when compared with the preoperative levels [PT: (19.51+/-3.78) s vs. (14.16+/-1.46) sû APTT: (77.01+/-30.51) s vs. (40.19+/-4.11) sû TT: (27.50+/-15.10) s vs. (19.46+/-3.05) sû INR: 1.61+/-0.37 vs. 1.11+/-0.16û Fib: (1.73+/-0.70) g/L vs. (3.38+/-1.00) g/Lû PLT: (108+/-60)x10(9)/L vs. (184+/-108)x10(9)/L, all P<0.01]. In the first week after operation, the elevated PT, APTT, TT and INR levels decreased gradually, APTT was even lower than the preoperative level [(32.05+/-6.50) s vs. (40.19+/-4.11) s, P<0.01]. These changes appeared usually on 1-2 days after operation. Decreased PLT and Fib regained slowly at the first week after operation when compared with the preoperative levels [Fib: (2.13+/-0.53) g/L vs. (3.38+/-1.00) g/L, P<0.01û PLT: (145+/-90)x10(9)/L vs. 184+/-108]x10(9)/L, P<0.05], but the values were normal. According to stratification analysis, the hypocoagulability was more

  6. Stem Cells Transplantation in the Treatment of Patients with Liver Failure.

    PubMed

    Tao, Ya-Chao; Wang, Meng-Lan; Chen, En-Qiang; Tang, Hong

    2018-02-23

    Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Toxocariasis masquerading as liver and lung metastatic nodules in patents with gastrointestinal cancer: clinicopathologic study of five cases.

    PubMed

    Park, Sanghui; Kim, Yun Soo; Kim, Yu Jin; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Lee, Sang Pyo

    2012-01-01

    There are sporadic reports in the literature in which radiologic liver and lung lesions found incidentally during follow-up metastatic surveillance were shown to be caused by toxocariasis. The objective of the work discussed in this report was to identify common clinical and histopathological features of toxocariasis resembling metastatic nodules in five patients with gastrointestinal cancer. We retrospectively analyzed clinical features of five gastrointestinal cancer patients with liver or lung nodules mimicking metastasis. Serologic tests for parasitic infestations and pathologic examinations were performed. All five patients were males and three patients had gastric cancer and two had colorectal cancer. All the cases of toxocariasis were confirmed serologically. On follow-up imaging, the lesions improved or resolved, suggestive of the phenomenon of visceral larva migrans. In two patients, liver biopsy was performed and showed eosinophilic abscess. Serologic tests and liver or lung biopsy should be performed aggressively to exclude toxocariasis when patients with underlying gastrointestinal cancer present with hepatic or pulmonary nodules associated with eosinophilia, particularly if the patients have a clinical history of raw animal liver ingestion. Curative surgical intervention should not be excluded just because of multiple nodules in the liver or the lungs.

  8. Periportal low attenuation associated with liver metastasis from colorectal cancer: evaluation using multi-detector-row CT with pathological correlation.

    PubMed

    Takaji, Ryo; Matsumoto, Shunro; Kiyonaga, Maki; Yamada, Yasunari; Mori, Hiromu; Iwashita, Yukio; Ohta, Masayuki; Inomata, Masafumi; Hijiya, Naoki; Moriyama, Masatsugu; Takaki, Hajime; Fukuzawa, Kengo; Yonemasu, Hirotoshi

    2017-01-01

    Periportal low attenuation (PPLA) associated with metastatic liver cancer is occasionally seen on multi-detector-row CT (MDCT). The purpose of this study was to investigate the MDCT patterns of the PPLA and to correlate it with pathological findings. We retrospectively reviewed the MDCT images of 63 patients with metastatic liver cancers from colorectal adenocarcinoma. On MDCT scans, PPLA associated with liver metastasis was visualized in six patients with colorectal cancer. In these six patients who had undergone surgical resection, the radiologic-pathologic correlation was analyzed. All patients underwent a single contrast-enhanced MDCT within 1 month before surgical resection. The six liver cancers were pathologically proven to be moderately differentiated adenocarcinoma. We assessed the PPLA on MDCT concerning the distribution patterns and contrast enhancement with pathological correlation. In five of the patients, the PPLA extended to the hilar side from metastatic liver cancer. Pathologically, there was no cancer invasion into the intra-hepatic periportal area; however, massive lymphedema and fibrosis occurred in all six cases. PPLA on the hilar and peripheral sides of hepatic metastasis from colorectal cancer may be present suggesting lymphedema and fibrosis of portal tracts not always indicating cancer infiltration.

  9. Our Vision | Center for Cancer Research

    Cancer.gov

    Our Vision The mission of the NCI-CCR-LCP is to develop a multi-disciplinary program focused on the prevention, early detection, improved diagnosis and treatment of liver cancer. Liver cancer is the 2nd most common cause of cancer-related death worldwide.

  10. CUDR promotes liver cancer stem cell growth through upregulating TERT and C-Myc

    PubMed Central

    Pu, Hu; Zheng, Qidi; Li, Haiyan; Wu, Mengying; An, Jiahui; Gui, Xin; Li, Tianming; Lu, Dongdong

    2015-01-01

    Cancer up-regulated drug resistant (CUDR) is a novel non-coding RNA gene. Herein, we demonstrate excessive CUDR cooperates with excessive CyclinD1 or PTEN depletion to accelerate liver cancer stem cells growth and liver stem cell malignant transformation in vitro and in vivo. Mechanistically, we reveal the decrease of PTEN in cells may lead to increase binding capacity of CUDR to CyclinD1. Therefore, CUDR-CyclinD1 complex loads onto the long noncoding RNA H19 promoter region that may lead to reduce the DNA methylation on H19 promoter region and then to enhance the H19 expression. Strikingly, the overexpression of H19 increases the binding of TERT to TERC and reduces the interplay between TERT with TERRA, thus enhancing the cell telomerase activity and extending the telomere length. On the other hand, insulator CTCF recruits the CUDR-CyclinD1 complx to form the composite CUDR-CyclinD1-insulator CTCF complex which occupancied on the C-myc gene promoter region, increasing the outcome of oncogene C-myc. Ultimately, excessive TERT and C-myc lead to liver cancer stem cell and hepatocyte-like stem cell malignant proliferation. To understand the novel functions of long noncoding RNA CUDR will help in the development of new liver cancer therapeutic and diagnostic approaches. PMID:26513297

  11. Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species.

    PubMed

    Chen, Hanbei; Li, Yakui; Zhu, Yemin; Wu, Lifang; Meng, Jian; Lin, Ning; Yang, Dianqiang; Li, Minle; Ding, WenJin; Tong, Xuemei; Su, Qing

    2017-08-01

    The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.

  12. Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tomasi, Maria Lauda; USC Research Center for Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033; The Southern California Research Center for Alcoholic and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033

    Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70–75%, increased apoptosismore » and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100 pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell. -- Highlights: • MAT2A knockdown depletes putrescine and leads to apoptosis. • Putrescine attenuates MAT2A knockdown-induced apoptosis and

  13. [One staged laparoscopic surgery of colon cancer with liver metastasis in the Guillermo Almenara Hospital, Lima, Peru].

    PubMed

    Núñez Ju, Juan José; Coronado3, Cesar Carlos; Anchante Castillo, Eduardo; Sandoval Jauregui, Javier; Arenas Gamio, José

    2016-01-01

    We report a patient who was diagnosed sigmoid colon cancer associated with liver metastases in segment III. The patient underwent laparoscopic surgery where the sigmoid colon resection and hepatic metastasectomy were performed in a “one staged” surgical procedure. The pathological results showed moderately differentiated tubular adenocarcinoma in sigmoid colon, tubular adenocarcinoma metastases also in liver. Oncological surgical results were obtained with free edges of neoplasia, R0 Surgery, T3N0M1. After the optimal surgical results, the patient is handled by oncology for adjuvant treatment. We report here the sequence of events and a review of the literature.

  14. Chemoprevention of rat liver toxicity and carcinogenesis by Spirulina.

    PubMed

    Ismail, Mohamed F; Ali, Doaa A; Fernando, Augusta; Abdraboh, Mohamed E; Gaur, Rajiv L; Ibrahim, Wael M; Raj, Madhwa H G; Ouhtit, Allal

    2009-06-02

    Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phyto-antioxidant, anti-inflammatory and anti-cancerous properties. The present study aimed to investigate the chemopreventive effect of SP against rat liver toxicity and carcinogenesis induced by dibutyl nitrosamine (DBN) precursors, and further characterized its underlying mechanisms of action in HepG2 cell line. Investigation by light and electron microscopy showed that DBN treatment induced severe liver injury and histopathological abnormalities, which were prevented by SP supplementation. The incidence of liver tumors was significantly reduced from 80 to 20% by SP. Immunohistochemical results indicated that both PCNA and p53 were highly expressed in the liver of DBN-treated rats, but were significantly reduced by SP supplementation. Molecular analysis indicated that SP treatment inhibited cell proliferation, which was accompanied by increased p21 and decreased Rb expression levels at 48hrs post-treatment. In addition, SP increased Bax and decreased Bcl-2 expression, indicating induction of apoptosis by 48hrs. This is the first report of the in vivo chemopreventive effect of SP against DBN-induced rat liver cytotoxicity and carcinogenesis, suggesting its potential use in chemoprevention of cancer.

  15. Chemoprevention of rat liver toxicity and carcinogenesis by Spirulina

    PubMed Central

    Ismail, Mohamed F; Ali, Doaa A; Fernando, Augusta; Abdraboh, Mohamed E; Gaur, Rajiv L; Ibrahim, Wael M; Raj, Madhwa HG; Ouhtit, Allal

    2009-01-01

    Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phyto-antioxidant, anti-inflammatory and anti-cancerous properties. The present study aimed to investigate the chemopreventive effect of SP against rat liver toxicity and carcinogenesis induced by dibutyl nitrosamine (DBN) precursors, and further characterized its underlying mechanisms of action in HepG2 cell line. Investigation by light and electron microscopy showed that DBN treatment induced severe liver injury and histopathological abnormalities, which were prevented by SP supplementation. The incidence of liver tumors was significantly reduced from 80 to 20% by SP. Immunohistochemical results indicated that both PCNA and p53 were highly expressed in the liver of DBN-treated rats, but were significantly reduced by SP supplementation. Molecular analysis indicated that SP treatment inhibited cell proliferation, which was accompanied by increased p21 and decreased Rb expression levels at 48hrs post-treatment. In addition, SP increased Bax and decreased Bcl-2 expression, indicating induction of apoptosis by 48hrs. This is the first report of the in vivo chemopreventive effect of SP against DBN-induced rat liver cytotoxicity and carcinogenesis, suggesting its potential use in chemoprevention of cancer. PMID:19521547

  16. Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes.

    PubMed

    Hagberg, K W; McGlynn, K A; Sahasrabuddhe, V V; Jick, S

    2014-10-28

    Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication. To address this association, we conducted a nested case-control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45-1.20) for metformin-only, 1.10 (95% CI=0.66-1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58-1.37) for metformin+other OH, 1.11 (95% CI=0.60-2.05) for metformin+insulin, 0.81 (95% CI=0.23-2.85) for other OH+insulin, and 0.72 (95% CI=0.18-2.84) for insulin-only). Stratification by duration of diabetes did not alter the results. Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.

  17. Combined microwave ablation and systemic chemotherapy for liver metastases from oesophageal cancer: Preliminary results and literature review.

    PubMed

    Zhou, Fubo; Yu, Xiaoling; Liang, Ping; Cheng, Zhigang; Han, Zhiyu; Yu, Jie; Liu, Fangyi; Tan, Shuilian; Dai, Guanghai; Bai, Li

    2016-08-01

    Oesophageal cancer is a highly aggressive disease with about 50% of patients presenting with advanced or metastatic disease at initial diagnosis. In this study we assessed combined microwave ablation (MWA) and systemic chemotherapy in the treatment of liver metastases arising from oesophageal squamous cell carcinoma (OSCC). Between February 2009 and June 2014, OSCC patients who underwent percutaneous MWA + concurrent systemic chemotherapy and systemic chemotherapy alone for liver metastases were enrolled in this study. Overall survival (OS) and progression-free survival (PFS) were recorded and compared between groups. In total 15 patients with 25 liver metastases who underwent ultrasound-guided percutaneous MWA and chemotherapy were enrolled in this study. Technical success was achieved in 96% (24/25) of metastatic liver tumours. No major or minor complications associated with MWA procedures were observed. The median OS and PFS from initial MWA were 13 months and 4 months. The 1-, 2-, 3-, 4-year OS rates after MWA were 53.3%, 26.7%, 13.3%, and 13.3%, respectively. The 1- and 2-year PFS rates after MWA were 26.7% and 13.3%. The OS and PFS of the MWA + systemic chemotherapy group were superior than those of patients who received systemic chemotherapy alone (P = 0.011 and 0.030, respectively). Combined MWA with systemic chemotherapy is a feasible, safe and effective treatment for liver metastases from OSCC.

  18. Accuracy of Robotic Radiosurgical Liver Treatment Throughout the Respiratory Cycle

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Winter, Jeff D.; Wong, Raimond; Swaminath, Anand

    Purpose: To quantify random uncertainties in robotic radiosurgical treatment of liver lesions with real-time respiratory motion management. Methods and Materials: We conducted a retrospective analysis of 27 liver cancer patients treated with robotic radiosurgery over 118 fractions. The robotic radiosurgical system uses orthogonal x-ray images to determine internal target position and correlates this position with an external surrogate to provide robotic corrections of linear accelerator positioning. Verification and update of this internal–external correlation model was achieved using periodic x-ray images collected throughout treatment. To quantify random uncertainties in targeting, we analyzed logged tracking information and isolated x-ray images collected immediately beforemore » beam delivery. For translational correlation errors, we quantified the difference between correlation model–estimated target position and actual position determined by periodic x-ray imaging. To quantify prediction errors, we computed the mean absolute difference between the predicted coordinates and actual modeled position calculated 115 milliseconds later. We estimated overall random uncertainty by quadratically summing correlation, prediction, and end-to-end targeting errors. We also investigated relationships between tracking errors and motion amplitude using linear regression. Results: The 95th percentile absolute correlation errors in each direction were 2.1 mm left–right, 1.8 mm anterior–posterior, 3.3 mm cranio–caudal, and 3.9 mm 3-dimensional radial, whereas 95th percentile absolute radial prediction errors were 0.5 mm. Overall 95th percentile random uncertainty was 4 mm in the radial direction. Prediction errors were strongly correlated with modeled target amplitude (r=0.53-0.66, P<.001), whereas only weak correlations existed for correlation errors. Conclusions: Study results demonstrate that model correlation errors are the primary random source of

  19. Metabolic profiles are principally different between cancers of the liver, pancreas and breast.

    PubMed

    Budhu, Anuradha; Terunuma, Atsushi; Zhang, Geng; Hussain, S Perwez; Ambs, Stefan; Wang, Xin Wei

    2014-01-01

    Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens. Unsupervised principal component analysis showed that metabolites are principally unique to each tissue and cancer type. Such a difference can also be observed even among early stage cancers, suggesting a significant and unique alteration of global metabolic pathways associated with each cancer type. Our global high-throughput metabolomic profiling study shows that specific biochemical alterations distinguish liver, pancreatic and breast cancer and could be applied as cancer classification tools to differentiate tumors based on tissue of origin.

  20. Dietary trace element intake and liver cancer risk: Results from two population-based cohorts in China.

    PubMed

    Ma, Xiao; Yang, Yang; Li, Hong-Lan; Zheng, Wei; Gao, Jing; Zhang, Wei; Yang, Gong; Shu, Xiao-Ou; Xiang, Yong-Bing

    2017-03-01

    Dietary factors have been hypothesized to affect the risk of liver cancer via various mechanisms, but the influence has been not well studied and the evidence is conflicting. We investigated associations of dietary trace element intake, assessed through a validated food frequency questionnaire, with risk of liver cancer in two prospective cohort studies of 132,765 women (1997-2013) and men (2002-2013) in Shanghai, China. The associations were first evaluated in cohort studies and further assessed in a case-control study nested within these cohorts adjusting for hepatitis B virus infection. For cohort analyses, Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After a median follow-up time of 15.2 years for the Shanghai Women's Health Study and 9.3 years for the Shanghai Men's Health Study, 192 women and 344 men developed liver cancer. Dietary intake of manganese was inversely associated with liver cancer risk (highest vs. lowest quintile, HR = 0.51, 95% CI: 0.35-0.73; p trend  = 0.001). Further adjustment for hepatitis B virus infection in the nested case-control study yielded a similar result (highest vs. lowest quintile, OR = 0.38, 95% CI: 0.21-0.69; p trend  < 0.001). No significant association was found between dietary intake of selenium, iron, zinc, copper and liver cancer risk. The results suggest that higher intake of manganese may be associated with a lower risk of liver cancer in China. © 2016 UICC.

  1. [Effects of Feiji decoction for soothing the liver combined with psychotherapy on quality of life in primary lung cancer patients].

    PubMed

    Yao, Yilin

    2012-01-01

    Primary lung cancer is one of the most common malignant tumors. It causes great pain and mood disorders to patients, and significantly reduces their quality of life. The aim of the current study is to evaluate the effect of Feiji Decoction for soothing the liver combined with psychotherapy on quality of life (QoL) and physical status of patients with primary lung cancer. A total of 118 patients with primary non-small cell lung cancer were randomly divided into two groups. The 57 patients in the combined therapy group were treated with Feiji Decoction for soothing the liver and psychotherapy combined with chemotherapy, whereas the 61 patients in the control group were treated with chemotherapy only. Both groups were observed for the two treatment courses. The European Organization for Research and Treatment of Cancer QoL Questionnaire LC-43 (EORTC QLQ-LC43) was used to assess the QoL of every patient in both groups before and after treatment scales. At the same time, physical status was assessed using the Karnofsky performance status (KPS) and East Cooperative Oncology Group performance status (ECOG). The scores of physiology function, role function, emotion function, cognize function, society function, and general health in the therapy group were higher than that of the control group. The therapy group also showed better QoL results than the contol group. Significant differences were observed between the two groups (P<0.01). Meanwhile, the scores of fatigue, vomit, pain, polypnea, insomnia, anorexia, constipation, and specific manifestation of lung cancer in the therapy group were obviously lower than that of the control group; more patients were observed to be relieved. Significant differences between the two groups were observed (P<0.01). The KPS and ECOG scores of the patients were observed to have improved and stabilized in the therapy group than that of the control group; the differences were statistically significant (P<0.01). Feiji Decoction for soothing the

  2. Bile duct hamartomas (von Mayenburg complexes) mimicking liver metastases from bile duct cancer: MRC findings

    PubMed Central

    Nagano, Yasuhiko; Matsuo, Kenichi; Gorai, Katsuya; Sugimori, Kazuya; Kunisaki, Chikara; Ike, Hideyuki; Tanaka, Katsuaki; Imada, Toshio; Shimada, Hiroshi

    2006-01-01

    We present a case of a 72-year-old man with a common bile duct cancer, who was initially believed to have multiple liver metastases based on computed tomography findings, and in whom magnetic resonance cholangiography (MRC) revealed a diagnosis of bile duct hamartomas. At exploration for pancreaticoduodenectomy, liver palpation revealed disseminated nodules at the surface of the liver. These nodules showed gray-white nodular lesions of about 0.5 cm in diameter scattered on the surface of both liver lobes, which were looked like multiple liver metastases from bile duct cancer. Frozen section of the liver biopsy disclosed multiple bile ducts with slightly dilated lumens embedded in the collagenous stroma characteristics of multiple bile duct hamartomas (BDHs). Only two reports have described the MRC features of bile duct hamartomas. Of all imaging procedures, MRC provides the most relevant features for the imaging diagnosis of bile duct hamartomas. PMID:16534895

  3. Trends in net survival from liver cancer in six European Latin countries: results from the SUDCAN population-based study.

    PubMed

    Ferretti, Stefano; Bossard, Nadine; Binder-Fouchard, Florence; Faivre, Jean; Bordoni, Andrea; Biavati, Patrizia; Frassoldati, Antonio

    2017-01-01

    Liver cancer represents a major clinical challenge. The aim of the SUDCAN collaborative study was to compare the net survival from liver cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland) and provide trends in net survival and dynamics of excess mortality rates (EMRs) up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the period 2000-2004 using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. Results are reported from 1992 to 2004 in France, Italy, Spain and Switzerland and from 2000 to 2004 in Belgium and Portugal. These trend analyses were carried out using a flexible excess-rate modeling strategy. There were little differences between the six countries in the 5-year age-standardized net survival (2000-2004): it ranged from 13% (France and Portugal) to 16% (Belgium). An increase in the net age-standardized survival was observed in all countries between 1992 and 2004, both at 1 year and at 5 years (the highest in Spain, the lowest in France). Generally, patients aged 60 years showed the highest increase. There was a progressive decrease in EMR over the 5-year- period following diagnosis. The study confirmed the poor prognosis of liver cancer. Innovative treatments might improve the prognosis as well as preventive screening of cirrhotic patients with good liver function. Efforts are also needed to improve registration practices.

  4. Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer.

    PubMed

    Butte, Jean M; Gonen, Mithat; Ding, Peirong; Goodman, Karyn A; Allen, Peter J; Nash, Garrett M; Guillem, Jose; Paty, Philip B; Saltz, Leonard B; Kemeny, Nancy E; Dematteo, Ronald P; Fong, Yuman; Jarnagin, William R; Weiser, Martin R; D'Angelica, Michael I

    2012-11-01

    The optimal combination of available therapies for patients with resectable synchronous liver metastases from rectal cancer (SLMRC) is unknown, and the pattern of recurrence after resection has been poorly investigated. In this study, the authors examined recurrence patterns and survival after resection of SLMRC. Consecutive patients with SLMRC (disease-free interval, ≤12 months) who underwent complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor-related variables, and treatment-related variables were correlated with recurrence patterns. Competing risk analysis was used to determine the risk of pelvic and extrapelvic recurrence. In total, 185 patients underwent complete resection of rectal primary and liver metastases. One hundred eighty patients (97%) received chemotherapy during their treatment course, and 91 patients (49%) received pelvic radiation therapy either before (N = 65; 71.4%), or after (N = 26; 28.6%) rectal resection. The 5-year disease-specific survival rate was 51% for the entire cohort with a median follow-up of 44 months for survivors. One hundred thirty patients (70%) developed a recurrence: Eighteen patients (10%) had recurrences in the pelvis in combination with other sites, and 7 of these (4%) had an isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risk analysis demonstrated that the likelihood of a pelvic recurrence was significantly lower than that of an extrapelvic recurrence (P < .001). Of the patients with SLMRC who developed recurrent disease, systemic sites were overwhelmingly more common than pelvic recurrences. The current results indicated that the selective exclusion of radiotherapy may be considered in patients who are diagnosed with simultaneous disease. Copyright © 2012 American Cancer Society.

  5. Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

    PubMed

    Spelt, Lidewij; Sasor, Agata; Ansari, Daniel; Andersson, Roland

    2016-10-01

    To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

  6. The burden of liver cancer in Asians and Pacific Islanders in the Greater San Francisco Bay Area, 1990 through 2004

    PubMed Central

    Chang, Ellen T.; Keegan, Theresa H. M.; Gomez, Scarlett L.; Le, Gem M.; Clarke, Christina A.; So, Samuel K. S.; Glaser, Sally L.

    2009-01-01

    Background No previous U.S. study has examined time trends in the incidence rate of liver cancer in the high-risk Asian/Pacific Islander population. We evaluated liver cancer incidence trends in Chinese, Filipino, Japanese, Korean, and Vietnamese males and females in the Greater San Francisco Bay Area of California between 1990 and 2004. Methods Populations at risk were estimated using the cohort component demographic method. Annual percentage changes (APCs) in age-adjusted incidence rates of primary liver cancer among Asians/Pacific Islanders in the Greater Bay Area Cancer Registry were calculated using joinpoint regression analysis. Results The incidence rate of liver cancer between 1990 and 2004 did not change significantly in Asian/Pacific Islander males or females overall. However, the incidence rate declined, albeit statistically non-significantly, in Chinese males (APC =−1.6% [95% confidence interval (CI) =−3.4%, 0.3%], Japanese males (APC = −4.9%, 95% CI =−10.7%, 1.2%), and Japanese females (APC =−3.6%, 95% CI =−8.9%, 2.0%). Incidence rates remained consistently high for Vietnamese, Korean, and Filipino males and females. Trends in the incidence rate of hepatocellular carcinoma were comparable to those for liver cancer. While disparities in liver cancer incidence between Asians/Pacific Islanders and other racial/ethnic groups diminished between 1990–1994 and 2000–2004, those among Asian subgroups increased. Conclusions Liver cancer continues to affect Asian/Pacific Islander Americans disproportionately, with consistently high incidence rates in most subgroups. Culturally targeted prevention methods are needed to reduce the high rates of liver cancer in this growing population in the U.S. PMID:17385214

  7. CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity-associated cancer.

    PubMed

    Conroy, Melissa J; Galvin, Karen C; Kavanagh, Maria E; Mongan, Ann Marie; Doyle, Suzanne L; Gilmartin, Niamh; O'Farrelly, Cliona; Reynolds, John V; Lysaght, Joanne

    2016-07-01

    Obesity is a global health problem presenting serious risk of disease fuelled by chronic inflammation, including type 2 diabetes mellitus, cardiovascular disease, liver disease and cancer. Visceral fat, in particular the omentum and liver of obese individuals are sites of excessive inflammation. We propose that chemokine-mediated trafficking of pro-inflammatory cells to the omentum and liver contributes to local and subsequent systemic inflammation. Oesophagogastric adenocarcinoma (OAC) is an exemplar model of obesity and inflammation driven cancer. We have demonstrated that T cells actively migrate to the secreted factors from the omentum and liver of OAC patients and that both CD4(+) and CD8(+) T cells bearing the chemokine receptor CCR5 are significantly more prevalent in these tissues compared to matched blood. The CCR5 ligand and inflammatory chemokine MIP-1α is also secreted at significantly higher concentrations in the omentum and liver of our OAC patient cohort compared to matched serum. Furthermore, we report that MIP-1α receptor antagonism can significantly reduce T cell migration to the secreted factors from OAC omentum and liver. These novel data suggest that chemokine receptor antagonism may have therapeutic potential to reduce inflammatory T cell infiltration to the omentum and liver and in doing so, may ameliorate pathological inflammation in obesity and obesity-associated cancer.

  8. S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells

    PubMed Central

    Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

    2017-01-01

    S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent. PMID:29340097

  9. Detection of tumor DNA at the margins of colorectal cancer liver metastasis

    PubMed Central

    Holdhoff, Matthias; Schmidt, Kerstin; Diehl, Frank; Aggrawal, Nishant; Angenendt, Philipp; Romans, Katharine; Edelstein, Daniel L.; Torbenson, Michael; Kinzler, Kenneth W.; Vogelstein, Bert; Choti, Michael A.; Diaz, Luis A.

    2012-01-01

    Purpose Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. Experimental Design We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12 and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Results Mutations were identified in each patient’s resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in five of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA as well as of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Conclusions Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases. PMID:21531819

  10. Lipid Biomarkers Identified for Liver Cancer | Center for Cancer Research

    Cancer.gov

    Hepatocellular carcinoma (HCC) is an aggressive cancer of the liver with poor prognosis and growing incidence in developed countries. Pathology and genetic profiles of HCC are heterogeneous, suggesting that it can begin growing in different cell types. Although human tumors such as HCC have been profiled in-depth by genomics-based studies, not much is known about their overall metabolite modifications and how these changes can form a network that leads to aggressive disease and poor outcome.

  11. Microbiota-based treatments in alcoholic liver disease.

    PubMed

    Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae

    2016-08-07

    Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD.

  12. Laparoscopic versus open 1-stage resection of synchronous liver metastases and primary colorectal cancer

    PubMed Central

    Yazici, Pinar; Onder, Akin; Benlice, Cigdem; Yigitbas, Hakan; Kahramangil, Bora; Tasci, Yunus; Aksoy, Erol; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Berber, Eren

    2017-01-01

    Background The aim of this study is to compare the perioperative and oncologic outcomes of open and laparoscopic approaches for concomitant resection of synchronous colorectal cancer and liver metastases. Methods Between 2006 and 2015, all patients undergoing combined resection of primary colorectal cancer and liver metastases were included in the study (n=43). Laparoscopic and open groups were compared regarding clinical, perioperative and oncologic outcomes. Results There were 29 patients in the open group and 14 patients in the laparoscopic group. The groups were similar regarding demographics, comorbidities, histopathological characteristics of the primary tumor and liver metastases. Postoperative complication rate (44.8% vs. 7.1%, P=0.016) was higher, and hospital stay (10 vs. 6.4 days, P=0.001) longer in the open compared to the laparoscopic group. Overall survival (OS) was comparable between the groups (P=0.10); whereas, disease-free survival (DFS) was longer in laparoscopic group (P=0.02). Conclusions According to the results, in patients, whose primary colorectal cancer and metastatic liver disease was amenable to a minimally invasive resection, a concomitant laparoscopic approach resulted in less morbidity without compromising oncologic outcomes. This suggests that a laparoscopic approach may be considered in appropriate patients by surgeons with experience in both advanced laparoscopic liver and colorectal techniques. PMID:28861371

  13. Laparoscopic versus open 1-stage resection of synchronous liver metastases and primary colorectal cancer.

    PubMed

    Gorgun, Emre; Yazici, Pinar; Onder, Akin; Benlice, Cigdem; Yigitbas, Hakan; Kahramangil, Bora; Tasci, Yunus; Aksoy, Erol; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Berber, Eren

    2017-08-01

    The aim of this study is to compare the perioperative and oncologic outcomes of open and laparoscopic approaches for concomitant resection of synchronous colorectal cancer and liver metastases. Between 2006 and 2015, all patients undergoing combined resection of primary colorectal cancer and liver metastases were included in the study (n=43). Laparoscopic and open groups were compared regarding clinical, perioperative and oncologic outcomes. There were 29 patients in the open group and 14 patients in the laparoscopic group. The groups were similar regarding demographics, comorbidities, histopathological characteristics of the primary tumor and liver metastases. Postoperative complication rate (44.8% vs . 7.1%, P=0.016) was higher, and hospital stay (10 vs . 6.4 days, P=0.001) longer in the open compared to the laparoscopic group. Overall survival (OS) was comparable between the groups (P=0.10); whereas, disease-free survival (DFS) was longer in laparoscopic group (P=0.02). According to the results, in patients, whose primary colorectal cancer and metastatic liver disease was amenable to a minimally invasive resection, a concomitant laparoscopic approach resulted in less morbidity without compromising oncologic outcomes. This suggests that a laparoscopic approach may be considered in appropriate patients by surgeons with experience in both advanced laparoscopic liver and colorectal techniques.

  14. Short-Term Outcomes of Simultaneous Laparoscopic Colectomy and Hepatectomy for Primary Colorectal Cancer With Synchronous Liver Metastases

    PubMed Central

    Inoue, Akira; Uemura, Mamoru; Yamamoto, Hirofumi; Hiraki, Masayuki; Naito, Atsushi; Ogino, Takayuki; Nonaka, Ryoji; Nishimura, Junichi; Wada, Hiroshi; Hata, Taishi; Takemasa, Ichiro; Eguchi, Hidetoshi; Mizushima, Tsunekazu; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki

    2014-01-01

    Although simultaneous resection of primary colorectal cancer and synchronous liver metastases is reported to be safe and effective, the feasibility of a laparoscopic approach remains controversial. This study evaluated the safety, feasibility, and short-term outcomes of simultaneous laparoscopic surgery for primary colorectal cancer with synchronous liver metastases. From September 2008 to December 2013, 10 patients underwent simultaneous laparoscopic resection of primary colorectal cancer and synchronous liver metastases with curative intent at our institute. The median operative time was 452 minutes, and the median estimated blood loss was 245 mL. Median times to discharge from the hospital and adjuvant chemotherapy were 13.5 and 44 postoperative days, respectively. Negative resection margins were achieved in all cases, with no postoperative mortality or major morbidity. Simultaneous laparoscopic colectomy and hepatectomy for primary colorectal cancer with synchronous liver metastases appears feasible with low morbidity and favorable outcomes. PMID:25058762

  15. Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications.

    PubMed

    Liao, Yi-Jen; Fang, Cheng-Chieh; Yen, Chia-Hung; Hsu, Shih-Ming; Wang, Chung-Kwe; Huang, Shiu-Feng; Liang, Yu-Chih; Lin, Ying-Yu; Chu, Yu-Tseng; Arthur Chen, Yi-Ming

    2015-09-15

    Primary hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related death. It is important to identify new targets for early diagnosis and treatment of HCC. Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular cholesterol homeostasis via direct binding with free cholesterol. However, little is known about the significance of NPC2 in HCC tumorigenesis. In this study, we showed that NPC2 is abundantly expressed in normal liver, but is downregulated in human HCC tissues. The patients with NPC2 downregulation expressed much higher α-fetoprotein, multiple tumor type, vascular invasion, later pathological stage and shorter survival rate. Knockdown NPC2 in liver cancer cell lines promote cell proliferation, migration and xenograft tumorigenesis. In contrast, NPC2 overexpression inhibits HuH7 promoted tumor growth. Furthermore, administration of hepatotropic adeno-associated virus 8 (AAV8) delivered NPC2 decreased the inflammatory infiltration, the expression of two early HCC markers-glypican 3 and survivin and suppressed the spontaneous HCC development in mice. To identify the NPC2-dependent mechanism, we emphasized on the status of MAPK/ERK signaling. MEK1/2 inhibitor treatment demonstrated that the expression of NPC2 affected the activation of ERK1/2 but not MEK1/2. In addition, cholesterol trafficking inhibitor treatment did not alter the cell proliferation and the activation of MEK/ERK. In conclusion, our study demonstrates that NPC2 may play an important role in negatively regulate cell proliferation and ERK1/2 activation that were independent of cholesterol accumulation. AAV-NPC2 may thus represent a new treatment strategy for liver cancer. © 2015 UICC.

  16. Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

    ClinicalTrials.gov

    2015-09-10

    Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer

  17. A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

    PubMed

    Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

    2016-04-01

    Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Expression of multi-drug resistance-related genes MDR3 and MRP as prognostic factors in clinical liver cancer patients.

    PubMed

    Yu, Zheng; Peng, Sun; Hong-Ming, Pan; Kai-Feng, Wang

    2012-01-01

    To investigate the expression of multi-drug resistance-related genes, MDR3 and MRP, in clinical specimens of primary liver cancer and their potential as prognostic factors in liver cancer patients. A total of 26 patients with primary liver cancer were enrolled. The expression of MDR3 and MRP genes was measured by real-time PCR and the association between gene expression and the prognosis of patients was analyzed by the Kaplan-Meier method and COX regression model. This study showed that increases in MDR3 gene expression were identified in cholangiocellular carcinoma, cirrhosis and HBsAg-positive patients, while MRP expression increased in hepatocellular carcinoma, non-cirrhosis and HBsAg-negative patients. Moreover, conjugated bilirubin and total bile acid in the serum were significantly reduced in patients with high MRP expression compared to patients with low expression. The overall survival tended to be longer in patients with high MDR3 and MRP expression compared to the control group. MRP might be an independent prognostic factor in patients with liver cancer by COX regression analysis. MDR3 and MRP may play important roles in liver cancer patients as prognostic factors and their underlying mechanisms in liver cancer are worthy of further investigation.

  19. [Clinical effect of ultrasound-guided injection of biodegradable poly(lactic-co-glycolic acid)-Fe3O4 in situ implant for magnetic thermal ablation in treatment of nude mice with human liver cancer SMMC-7721 cells].

    PubMed

    Liang, B; Zuo, G Q; Zheng, Y Y; He, S; Zuo, D Y

    2016-12-20

    Objective: To prepare the Fe 3 O 4 -loaded biodegradable liquid-solid phase inversion poly(lactic-co-glycolic acid) (PLGA) in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an alternating magnetic field. Methods: An in situ implant containing 10% Fe 3 O 4 was prepared, and 50 μl Fe 3 O 4 -PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded. HE staining and Prussian blue staining were performed for the heart, liver, spleen, lung, and kidney of Kunming mice. Fresh ex vivo bovine liver was taken and cut into cubes with a dimension of 2 cm×2 cm×2 cm and then 50 μl Fe 3 O 4 -PLGA-NMP gel was injected; after phase inversion, the cubes of ex vivo bovine liver were heated for 1, 2, 3, 4, and 5 minutes, respectively, and then cut open for observing the range of ablation; HE staining was also performed. Micro-CT scan was performed after ultrasound-guided injection of 50 μl Fe 3 O 4 -PLGA gel into the tumors of the nude mice, and then the nude mice were divided into treatment group and control group. The mice in the treatment group were given thermomagnetic treatment for 3 minutes, and tumor growth was observed daily. Results: The biodegradation of Fe 3 O 4 -PLGA-NMP implant showed that the subcutaneously injected material was gradually metabolized at 2 weeks after injection and that the nude mice were in good condition. The bovine liver ablation experiment showed that the range of ablation of 50 μl Fe 3 O 4 -PLGA implant reached 1.46 ± 0.11 cm. HE staining showed that part of bovine liver had coagulative necrosis. The phase inversion experiment of Fe 3 O 4 -PLGA gel showed quick liquid-solid phase inversion of the material after injection into the tumor, and the process of liquid

  20. Oncosurgical Management of Liver Limited Stage IV Colorectal Cancer: Preliminary Data and Protocol for a Randomized Controlled Trial.

    PubMed

    Sutton, Paul; Vimalachandran, Dale; Poston, Graeme; Fenwick, Stephen; Malik, Hassan

    2018-05-09

    Colorectal cancer is the fourth commonest cancer and second commonest cause of cancer-related death in the United Kingdom. Almost 15% of patients have metastases on presentation. An increasing number of surgical strategies and better neoadjuvant treatment options are responsible for more patients undergoing resection of liver metastases, with prolonged survival in a select group of patients who present with synchronous disease. It is clear that the optimal strategy for the management of these patients remains unclear, and there is certainly a complete absence of Level 1 evidence in the literature. The objective of this study is to undertake preliminary work and devise an outline trial protocol to inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We have undertaken some preliminary work and begun the process of designing a randomized controlled trial and present a draft trial protocol here. This study is at the protocol development stage only, and as such no results are available. There is no funding in place for this study, and no anticipated start date. We have presented preliminary work and an outline trial protocol which we anticipate will inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We do not believe that the trial we have designed will answer the most significant clinical questions, nor that it is feasible to be delivered within the United Kingdom's National Health Service at this current time. ©Paul Sutton, Dale Vimalachandran, Graeme Poston, Stephen Fenwick, Hassan Malik. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.05.2018.

  1. SU-E-T-402: Y-90 Microspheres (SIR Spheres) for Treatment of Liver Metastasis : Technique

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nair, M

    2014-06-01

    Purpose: The purpose of this presentation is to discuss the radiation safety and dosimetric technique used for the therapeutic procedure using Y-90 microspheres through intra -arterial administration on patients with liver metastasis Methods: The radiation dosimetry, technique and safety aspects of 14 patients with primary and metastatic liver cancer, treated with Y-90 microsphere (SIR spheres) are discussed. The liver and tumor volumes were determined using the CT and MR scans . The images were imported into the treatment planning system and the liver and tumor volumes and the volume of the liver affected were outlined and the volume calculation wasmore » performed using the software. The lung shunt fraction (LSF) and tumor to liver uptake ratio (TLR) were determined using the nuclear medicine SPECT imaging with Tc-99m MAA. The absorbed dose to the target volume in liver was calculated using the following equation:Dose ? (Gy) = C x E? x 5.92 x 10-6 (Gy/s) x T(1/2)(days) x 1.44 x 8.64 x 104 (s) The distribution of activity in the tumor bed was confirmed by post Y-90 administration imaging using the Bremsstrahlung peak at 30% window. The patient and the procedure room were surveyed and radiation safety instructions were given to the patient Results: The tumor volume ranged from 77 cc to 700 cc, tumor to liver uptake ranged from 3 to 12. The lung shunt fraction varied from 1.08% to 9.0%. The activity administered ranged from 1.0GBq to 2.5 GBq, . The radiation survey in contact with the patient ranged from 1.8 mR/hr to 2.5 mR/hr and reading at 1 meter was less than 0.2 mR/hr Conclusion: The technique for radiation dosimetry and radiation safety for Y-90 microsphere therapy is established. The post treatment imaging helped to confirm the distribution of Y-90 microspheres inside the tumor bed.« less

  2. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity

    PubMed Central

    Shalapour, Shabnam; Lin, Xue-Jia; Bastian, Ingmar N.; Brain, John; Burt, Alastair D.; Aksenov, Alexander A.; Vrbanac, Alison F.; Li, Weihua; Perkins, Andres; Matsutani, Takaji; Zhong, Zhenyu; Dhar, Debanjan; Navas-Molina, Jose A.; Xu, Jun; Loomba, Rohit; Downes, Michael; Yu, Ruth T.; Evans, Ronald M.; Dorrestein, Pieter C.; Knight, Rob; Benner, Christopher; Anstee, Quentin M.; Karin, Michael

    2018-01-01

    The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8+ T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8+ T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA+ cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8+ T-lymphocyte activation as a tumour-promoting mechanism. PMID:29144460

  3. Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG).

    PubMed

    Huiskens, Joost; van Gulik, Thomas M; van Lienden, Krijn P; Engelbrecht, Marc R W; Meijer, Gerrit A; van Grieken, Nicole C T; Schriek, Jonne; Keijser, Astrid; Mol, Linda; Molenaar, I Quintus; Verhoef, Cornelis; de Jong, Koert P; Dejong, Kees H C; Kazemier, Geert; Ruers, Theo M; de Wilt, Johanus H W; van Tinteren, Harm; Punt, Cornelis J A

    2015-05-06

    Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and the lack of consensus on criteria for (un)resectability complicates the interpretation of published results. CAIRO5 is a multicentre, randomised, phase 3 clinical study. Colorectal cancer patients with initially unresectable liver-only metastases are eligible, and will not be selected for potential resectability. The (un)resectability status is prospectively assessed by a central panel consisting of at least one radiologist and three liver surgeons, according to predefined criteria. Tumours of included patients will be tested for RAS mutation status. Patients with RAS wild type tumours will be treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the addition of either bevacizumab or panitumumab, and patients with RAS mutant tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central panel, at an interval of two months. The primary study endpoint is median progression-free survival. Secondary endpoints are the R0/1 resection rate, median overall survival, response rate, toxicity, pathological response of resected lesions, postoperative morbidity, and correlation of baseline and follow-up evaluation with respect to outcomes by the central panel. CAIRO5 is a prospective multicentre trial that investigates the optimal systemic induction therapy for patients with initially unresectable, liver-only colorectal cancer metastases. CAIRO 5 is registered at European Clinical Trials Database (EudraCT) (2013-005435-24). CAIRO 5 is registered at ClinicalTrials.gov: NCT02162563 , June 10, 2014.

  4. The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer.

    PubMed

    Gu, Junsheng; Sun, Ranran; Shen, Shen; Yu, Zujiang

    2015-01-01

    This study was designed to explore the influence of Toll-like receptor 4 (TLR4) agonist lipopolysaccharides (LPS) on liver cancer cell and the feasibility to perform liver cancer adjuvant therapy. Human liver cancer cell lines HepG2, H7402, and PLC/PRF/5 were taken as models, and the expression of TLRs mRNA was detected by real time-polymerase chain reaction method semiquantitatively. WST-1 method was used to detect the influence of LPS on the proliferation ability of liver cancer cells; propidium iodide (PI) single staining and Annexin V/PI double staining were used to test the influence of LPS on the cell cycle and apoptosis, respectively, on human liver cancer cell line H7402. Fluorescent quantitative polymerase chain reaction and Western blot method were used to determine the change of expression of Cyclin D1. The results demonstrated that most TLRs were expressed in liver cancer cells; stimulating TLR4 by LPS could upregulate TLR4 mRNA and the protein level, activate NF-κB signaling pathway downstream of TLR4, and mediate the generation of inflammatory factors IL-6, IL-8, and TNF-α; LPS was found to be able to strengthen the proliferation ability of liver cancer cells, especially H7402 cells; the expression of Cyclin D1 rose and H7402 cells were promoted to transit from G1 stage to S stage under the stimulation of LPS, but cell apoptosis was not affected. It was also found that LPS was able to activate signal transducer and activator of transcription -3 (STAT3) signaling pathway in H7402 cells and meanwhile significantly increase the initiation activity of STAT3; proliferation promoting effect of LPS to liver cancer cells remarkably lowered once STAT3 was blocked or inhibited. Thus, TLR4 agonist LPS is proved to be able to induce liver cancer cells to express inflammation factors and mediate liver cancer cell proliferation and generation of multidrug resistance by activating the cyclooxygenase-2/prostaglandin signal axis as well as the STAT3 pathway.

  5. Attenuation of liver cancer development by oral glycerol supplementation in the rat.

    PubMed

    Capiglioni, Alejo M; Lorenzetti, Florencia; Quiroga, Ariel D; Parody, Juan P; Ronco, María T; Pisani, Gerardo B; Carrillo, María C; Ceballos, María P; Alvarez, María de Luján

    2018-04-01

    Glycerol usage is increasing in food industry for human and animal nutrition. This study analyzed the impact of glycerol metabolism when orally supplemented during the early stage of rat liver carcinogenesis. Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group). IP animals also received glycerol by gavage (200 mg/kg body weight, IPGly group). Glycerol treatment reduced the volume of preneoplastic lesions by decreasing the proliferative status of liver foci, increasing the expression of p53 and p21 proteins and reducing the expression of cyclin D1 and cyclin-dependent kinase 1. Besides, apoptosis was enhanced in IPGly animals, given by an increment of Bax/Bcl-2 ratio, Bad and PUMA mitochondrial expression, a concomitant increase in cytochrome c release and caspase-3 activation. Furthermore, hepatic levels of glycerol phosphate and markers of oxidative stress were increased in IPGly rats. Oxidative stress intermediates act as intracellular messengers, inducing p53 activation and changes in JNK and Erk signaling pathways, with JNK activation and Erk inhibition. The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.

  6. [Diagnostic and treatment experience with amebic lesions of the liver].

    PubMed

    Ivanov, K S; Basos, S F; Volzhanin, V M; Gorelov, A I

    1992-01-01

    The article studies the traits of diagnosis and treatment of 134 patients with amebic affections of liver. It is indicated that on the basis of clinical data it is possible to detect the development of amebic hepatitis or amebic abscess of liver. The most effective methods for treatment are: in case of amebic hepatitis--trans-umbilical injection of amebocytes; in case of amebic abscess of liver--percutaneous puncture of abscess under the ultrasonic sensor control, active aspiration of the content, cavity washing with antiamebic solutions and its trans-umbilical injections.

  7. PET/CT with 18F Fluorocholine as an Imaging Biomarker for Chronic Liver Disease: A Preliminary Radiopathologic Correspondence Study in Patients with Liver Cancer.

    PubMed

    Kwee, Sandi A; Wong, Linda; Chan, Owen T M; Kalathil, Sumodh; Tsai, Naoky

    2018-04-01

    Purpose To determine the relationship between hepatic uptake at preoperative fluorine 18 ( 18 F) fluorocholine combined positron emission tomography (PET) and computed tomography (CT) and the histopathologic features of chronic liver disease in patients with Child-Pugh class A or B disease who are undergoing hepatic resection for liver cancer. Materials and Methods Forty-eight patients with resectable liver tumors underwent preoperative 18 F fluorocholine PET/CT. Mean liver standardized uptake value (SUV mean ) measurements were obtained from PET images, while histologic indexes of inflammation and fibrosis were applied to nontumor liver tissue from resection specimens. Effects of histopathologic features on liver SUV mean were examined with analysis of variance. Results Liver SUV mean ranged from 4.3 to 11.6, correlating significantly with Knodell histologic activity index (ρ = -0.81, P < .001) and several clinical indexes of liver disease severity. Liver SUV mean also differed significantly across groups stratified by necroinflammatory severity and Metavir fibrosis stage (P < . 001). The area under the receiver operating characteristic curve for 18 F fluorocholine PET/CT detecting Metavir fibrosis stage F1 or higher was 0.89 ± 0.05, with an odds-ratio of 3.03 (95% confidence interval: 1.59, 5.88) and sensitivity and specificity of 82% and 93%, respectively. Conclusion Correlations found in patients undergoing hepatic resection for liver cancer between liver 18 F fluorocholine uptake and histopathologic indexes of liver fibrosis and inflammation support the use of 18 F fluorocholine PET/CT as a potential imaging biomarker for chronic liver disease. © RSNA, 2018.

  8. An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease.

    PubMed

    De Las Heras, Javier; Aldámiz-Echevarría, Luis; Martínez-Chantar, María-Luz; Delgado, Teresa C

    2017-04-01

    Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis.

  9. An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease

    PubMed Central

    de las Heras, Javier; Aldámiz-Echevarría, Luis; Martínez-Chantar, María-Luz; Delgado, Teresa C.

    2017-01-01

    Introduction Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas Covered We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert Opinion For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis. PMID:27860485

  10. Treatment of peritoneal carcinomatosis with hyperthermic intraperitoneal chemotherapy in colorectal cancer.

    PubMed

    Behrenbruch, Corina; Hollande, Frédéric; Thomson, Benjamin; Michael, Michael; Warrier, Satish K; Lynch, Craig; Heriot, Alexander

    2017-09-01

    The peritoneum is the second most common site of metastasis after the liver and the only site of metastatic disease in approximately 25% of patients with colorectal cancer (CRC). In the past, peritoneal carcinomatosis in CRC was thought to be equivalent to distant metastasis; however, the transcoelomic spread of malignant cells is an acknowledged alternative pathway. Metastasectomy with curative intent is well accepted in patients with liver metastasis in CRC despite the paucity of randomized trials. Therefore, there is rationale for local treatment with peritonectomy to eliminate macroscopic disease, followed by hyperthermic intraperitoneal chemotherapy to destroy any residual free tumour cells within the peritoneal cavity. The aim of this paper is to summarize the current evidence for cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis in CRC. © 2017 Royal Australasian College of Surgeons.

  11. Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis.

    PubMed

    Sia, Daniela; Villanueva, Augusto; Friedman, Scott L; Llovet, Josep M

    2017-03-01

    Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis and clarify the classes of liver cancer based on molecular features and how they affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis. A better understanding of the cell types originating liver cancer can aid in exploring molecular mechanisms of carcinogenesis and therapeutic options. Molecular studies have identified adult hepatocytes as the cell of origin. These cells have been proposed to transform directly into HCC cells (via a sequence of genetic alterations), to dedifferentiate into hepatocyte precursor cells (which then become HCC cells that express progenitor cell markers), or to transdifferentiate into biliary-like cells (which give rise to iCCA). Alternatively, progenitor cells also give rise to HCCs and iCCAs with markers of progenitor cells. Advances in genome profiling and next-generation sequencing have led to the classification of HCCs based on molecular features and assigned them to categories such as proliferation-progenitor, proliferation-transforming growth factor β, and Wnt-catenin β1. iCCAs have been assigned to categories of proliferation and inflammation. Overall, proliferation subclasses are associated with a more aggressive phenotype and poor outcome of patients, although more specific signatures have refined our prognostic abilities. Analyses of genetic alterations have identified those that might be targeted therapeutically, such as fusions in the FGFR2 gene and mutations in genes encoding isocitrate dehydrogenases (in approximately 60% of iCCAs) or

  12. Liver cancer: increased microwave delivery to ablation zone with cooled-shaft antenna--experimental and clinical studies.

    PubMed

    Kuang, Ming; Lu, Ming D; Xie, Xiao Y; Xu, Hui X; Mo, Li Q; Liu, Guang J; Xu, Zuo F; Zheng, Yan L; Liang, Jin Y

    2007-03-01

    To prospectively investigate whether the ablation zone induced with microwaves could be increased by delivering greater energy with a cooled-shaft antenna. All studies were animal care and ethics committee approved. Written informed consent was obtained from all patients. Microwave ablation was performed by using a cooled-shaft antenna in 48 ex vivo and 12 in vivo experiments with porcine livers. The coagulation diameters achieved in different microwave ablation parameter groups (60-90 W for 5-25 minutes) were compared. Ninety patients (78 men, 12 women; mean age, 53 years; age range, 20-82 years) with 133 0.8-8.0-cm (mean, 2.7 cm +/- 1.5 [standard deviation]) primary or metastatic liver cancers were treated with the same microwave ablation technique. Complete ablation (CA) and local tumor progression (LTP) rates were determined. Generalized estimating equations were used to compare differences in tumor size, ablation zone diameter, and CA and LTP rates between different patient subgroups. In the ex vivo livers, in vivo livers, and liver cancers, one application of microwave energy with 80 W for 25 minutes produced mean coagulation diameters of 5.6 x 7.4 cm, 3.5 x 5.9 cm, and 3.6 x 5.0 cm, respectively. Skin burn was not observed. CA rates in small (liver cancers were 94% (81 of 86), 91% (31 of 34), and 92% (12 of 13), respectively. During a mean follow-up period of 17.4 months, LTP occurred in seven (5%) treated cancers. There was a significant difference in LTP rate between the cirrhosis and no-cirrhosis groups (P = .03). Four patients had major complications. Delivery of greater microwave energy with cooled-shaft antennas yielded large ablation zones in ex vivo and in vivo livers and in liver cancers. Effective local tumor control was achieved during one microwave ablation session. (c) RSNA, 2007.

  13. [Surgical treatment of pulmonary metastases from colon and rectal cancer].

    PubMed

    Togashi, Ken-ichi; Aoki, K; Hirahara, H; Sugawara, M; Oguma, F

    2004-09-01

    We retrospectively studied the surgical treatment for pulmonary metastases from colon and rectal cancer. A total of 24 patients (9 males and 15 females; mean age 61 years) underwent 29 thoracotomies for metastatic colon carcinoma, while 22 patients (16 males and 6 females; mean age 63 years) underwent 29 thoracotomies for metastatic rectal cancer. The median interval between the primary procedure and lung resection for metastases was 26 months in the patients with colon carcinoma and 32 months in the patients with rectal cancer. In the patients with colon carcinoma, 16 underwent wedge resection or segmentectomy (including 4 video-assisted procedures) and 13 (54%) underwent lobectomy or pneumonectomy. In the patients with rectal cancer, 15 underwent wedge or segmentectomy (including 1 video-assisted procedure), 13 (59%) underwent lobectomy or pneumonectomy, and 1 underwent exploratory thoracotomy. All procedures except exploratory thoracotomy were curative operations. There was no mortality. Overall 5-year survival was 56% (n=46). Five-year survival was 65% for patients with colon metastases (n=24) and 45% for patients with rectal metastases (n=22), and there was no significant difference. Recurrent sites were 4 lungs (36%), 4 livers (36%), 1 bone, 1 uterus, and 1 peritoneum in patients with colon carcimoma, and 10 lungs (43%), 5 brains (22%), 3 livers (13%), 1 bone, and 1 vagina in patients with rectal cancer. Pulmonary resection for metastases from colon carcinoma may have better prognosis than that from rectal cancer. However, further investigation may be required to obtain convincing conclusions.

  14. Patterns and Trends of Liver Cancer Incidence Rates in Eastern and Southeastern Asian Countries (1983-2007) and Predictions to 2030.

    PubMed

    Wu, Jie; Yang, Shigui; Xu, Kaijin; Ding, Cheng; Zhou, Yuqing; Fu, Xiaofang; Li, Yiping; Deng, Min; Wang, Chencheng; Liu, Xiaoxiao; Li, Lanjuan

    2018-05-01

    We examined temporal trends in liver cancer incidence rates overall and by histological type from 1983 through 2007. We predict trends in liver cancer incidence rates through 2030 for selected Eastern and Southeastern Asian countries. Data on yearly liver cancer incident cases by age group and sex were drawn from 6 major selected Eastern and Southeastern Asian countries or regions with cancer registries available in the CI5plus database, including China, Japan, Hong Kong Special Administrative Region (SAR), the Philippines, Singapore, and Thailand. We also analyzed data for the United States and Australia for comparative purposes. Age-standardized incidence rates were calculated and plotted from 1983 through 2007. Numbers of new cases and incidence rates were predicted through 2030 by fitting and extrapolating age-period-cohort models. The incidence rates of liver cancer have been decreasing, and decreases will continue in all selected Eastern and Southeastern Asian countries, except for Thailand, whose liver cancer incidence rate will increase due to the increasing incidence rate of intrahepatic cholangiocarcinomas. Even though the incidence rates of liver cancer are predicted to decrease in most Eastern and Southeastern Asian countries, the burden, in terms of new cases, will continue to increase because of population growth and aging. Based on an analysis of data from cancer registries from Asian countries, incidence rates of liver cancer are expected to decrease through 2030 in most Eastern and Southeastern Asian countries. However, in Thailand, the incidence rate of intrahepatic cholangiocarcinomas is predicted to increase, so health education programs are necessary. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Wnt/β-catenin activation and macrophage induction during liver cancer development following steatosis.

    PubMed

    Debebe, A; Medina, V; Chen, C-Y; Mahajan, I M; Jia, C; Fu, D; He, L; Zeng, N; Stiles, B W; Chen, C-L; Wang, M; Aggarwal, K-R; Peng, Z; Huang, J; Chen, J; Li, M; Dong, T; Atkins, S; Borok, Z; Yuan, W; Machida, K; Ju, C; Kahn, M; Johnson, D; Stiles, B L

    2017-10-26

    Obesity confers an independent risk for carcinogenesis. In the liver, steatosis often proceeds cancer formation; however, the mechanisms by which steatosis promotes carcinogenesis is unknown. We hypothesize that steatosis alters the microenvironment to promote proliferation of tumor initiating cells (TICs) and carcinogenesis. We used several liver cancer models to address the mechanisms underlying the role of obesity in cancer and verified these findings in patient populations. Using bioinformatics analysis and verified by biochemical assays, we identified that hepatosteatosis resulting from either Pten deletion or transgenic expression of HCV core/NS5A proteins, promotes the activation of Wnt/β-catenin. We verified that high fat diet lipid accumulation is also capable of inducing Wnt/β-catenin. Caloric restriction inhibits hepatosteatosis, reduces Wnt/β-catenin activation and blocks the expansion of TICs leading to complete inhibition of tumorigenesis without affecting the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) loss regulated protein kinase B (AKT) activation. Pharmacological inhibition or loss of the Wnt/β-catenin signal represses TIC growth in vitro, and decreases the accumulation of TICs in vivo. In human liver cancers, ontology analysis of gene set enrichment analysis (GSEA)-defined Wnt signature genes indicates that Wnt signaling is significantly induced in tumor samples compared with healthy livers. Indeed, Wnt signature genes predict 90% of tumors in a cohort of 558 patient samples. Selective depletion of macrophages leads to reduction of Wnt and suppresses tumor development, suggesting infiltrating macrophages as a key source for steatosis-induced Wnt expression. These data established Wnt/β-catenin as a novel signal produced by infiltrating macrophages induced by steatosis that promotes growth of tumor progenitor cells, underlying the increased risk of liver tumor development in obese individuals.

  16. Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies.

    PubMed

    Turtoi, Andrei; Blomme, Arnaud; Debois, Delphine; Somja, Joan; Delvaux, David; Patsos, Georgios; Di Valentin, Emmanuel; Peulen, Olivier; Mutijima, Eugène Nzaramba; De Pauw, Edwin; Delvenne, Philippe; Detry, Olivier; Castronovo, Vincent

    2014-03-01

    Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens. © 2014 by the American Association for the Study of Liver Diseases.

  17. Microbiota-based treatments in alcoholic liver disease

    PubMed Central

    Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae

    2016-01-01

    Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD. PMID:27547010

  18. Comparative study of the calculated risk of radiation-induced cancer after photon- and proton-beam based radiosurgery of liver metastases.

    PubMed

    Mondlane, Gracinda; Gubanski, Michael; Lind, Pehr A; Ureba, Ana; Siegbahn, Albert

    2017-10-01

    The potential of proton therapy to improve the sparing of the healthy tissue has been demonstrated in several studies. However, even small doses delivered to the organs at risk (OAR) may induce long-term detriments after radiotherapy. In this study, we investigated the possibility to reduce the risk of radiation-induced secondary cancers with intensity modulated proton therapy (IMPT), when used for radiosurgery of liver metastases. Ten patients, previously treated for liver metastases with photon-beam based stereotactic body radiation therapy (SBRT) were retrospectively planned for radiosurgery with IMPT. A treatment plan comparison was then performed in terms of calculated risk of radiation-induced secondary cancer. The risks were estimated using two distinct models (Dasu et al., 2005; Schneider et al., 2005, 2009). The plans were compared pairwise with a two-sided Wilcoxon signed-rank test with a significance level of 0.05. Reduced risks for induction of fatal and other types of cancers were estimated for the IMPT plans (p<0.05) with the Dasu et al. Using the Schneider et al. model, lower risks for carcinoma-induction with IMPT were estimated for the skin, lungs, healthy part of the liver, esophagus and the remaining part of the body (p<0.05). The risk of observing sarcomas in the bone was also reduced with IMPT (p<0.05). The findings of this study indicate that the risks of radiation-induced secondary cancers after radiosurgery of liver metastases may be reduced, if IMPT is used instead of photon-beam based SBRT. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  19. Dynamic morphological examination and evaluation of biological characteristics of a multinodular liver cancer model in mice.

    PubMed

    Li, Yan-Ru; Wang, Jin-Rui; Zhang, Hai-Ying; Wu, Xiao-Fei; Li, Sheng-Nan; Wang, Lin; Wang, Xue-Yao

    2014-04-01

    Compared with single nodular liver cancer, the prominent biological characteristics of multinodular liver cancer include rapid progression and short survival. Here, we developed a multinodular liver cancer model in mice and assessed the biological characteristics of the resulting neoplasms. H22 hepatoma cells at a dose of 2 × 10(5)/mouse, suspended in 1.6 mL, 0.8 mL, or 200 µL saline were injected via the tail vein of BALB/c mice at a velocity of 200 µL per second. The mice were sacrificed at different time points after injection. And at the time of death the liver, lungs, spleen, kidneys and heart were removed for morphological study. The biological characteristics of the tumor nodules were evaluated by immunohistochemistry. In the mice treated with a large volume injection of H22 cells, by day 7, there was a 100% occurrence of multinodular tumors in the livers, determined by histology. At the time of death, there were 100%, 100%, 37.5% and 37.5% occurrences of tumors in the lungs, kidneys, spleen and heart, respectively. The neoplastic cells in the liver nodules showed pleomorphism, and exhibited high expression of proliferating cell nuclear antigen (PCNA), c-myc, vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2). In mice treated with a small or medium volume injection, no tumor cells were identified in the livers, spleen, kidneys or heart at any of the examined time points. By day 7 and at the time of death, there was a 100% occurrence of tumor in the lungs. A multinodular liver cancer model in mice was achieved using a large volume injection of H22 cells.

  20. Treatment of hepatic metastases of colorectal cancer by robotic stereotactic radiation (Cyberknife ®).

    PubMed

    Peiffert, D; Baumann, A-S; Marchesi, V

    2014-04-01

    Cyberknife(®) is a dedicated stereotactic radiotherapy device. This new technology permits precise delivery of high dose gradient radiation therapy while sparing the surrounding organs at risk. Hepatic metastases of colorectal cancer (HMCRC) are an example of a lesion where treatment with Cyberknife(®) is indicated because they are located in a radio-sensitive organ and curative treatment is based on focal eradication (resection, radiofrequency ablation,...). The local control rate at one year is reported to be 70 to 100% depending on the study. Tolerance is excellent with less than a 5% rate of acute grade 3 or 4 side effects (nausea, vomiting, gastro-duodenal ulcer). The specific hepatotoxicity of radiotherapy, so-called radiation-induced liver disease (RILD), was found in only one study. Candidates for stereotactic radiotherapy are patients in whom disease is controlled except for intrahepatic disease with 1-3 hepatic metastases ≤ 6 cm in size who have contraindications for surgery, a WHO stage ≤ 2, a volume of healthy liver ≥ 700 cm(3) and normal liver function. It is actually a very simple treatment that results in very good local control with few contraindications. Its place in the management strategy of liver metastases needs further clarification. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Numerical design of RF ablation applicator for hepatic cancer treatment

    NASA Astrophysics Data System (ADS)

    Rakhmadi, Aditya; Basari

    2017-02-01

    Currently, cancer has become one of health problems that is difficult to be overcomed. This disease is not only difficult to be cured, but also to be detected and may cause death. For this reason, RF ablation treatment method is proposed to cure cancer. RF ablation therapy is a method in which an applicator is inserted into the body to kill cancer cells by heating the cells. The cancer cells are exposed to the temperature more than 60°C in short duration (few second to few minutes) so thus cell destruction occurs locally. For the sake of the successful treatment, a minimally invasive method is selected in order for perfect local temperature distribution in cancer cells can be achieved. In this paper, a coax-fed dipole-type applicator with interstitial irradiation technique is proposed aimed at RF ablation into hepatic cells. Numerical simulation is performed to obtain a suitable geometric dimension at operating frequency around 2.45 GHz, in order to localize the ablation area. The proposed applicator is inserted into a simple phantom representing an adult human body model in which normal and cancerous liver cells. The simulated results show that the proposed applicator is able to operate at center frequency of 2.355 GHz with blood droplet-type ablation zone and the temperature around the cancer cell by 60°C can be achieved.

  2. SSAT/AHPBA Joint Symposium on Evaluation and Treatment of Benign Liver Lesions

    PubMed Central

    Chun, Yun Shin; House, Michael G.; Kaur, Harmeet; Loyer, Evelyne M.; Paradis, Valérie; Vauthey, Jean-Nicolas

    2013-01-01

    Background Benign liver lesions are common incidental radiologic findings. Methods Experts convened in 2011 at a Society for Surgery of the Alimentary Tract/ Americas Hepato-Pancreato-Biliary Association joint symposium to discuss the evaluation and treatment of benign liver lesions. Results Most benign liver lesions can be accurately diagnosed with high-quality imaging, including ultrasonography, multiphase computed tomography, and magnetic resonance imaging, particularly with hepatocyte-specific contrast agents. Percutaneous biopsy is reserved for lesions that cannot be characterized radiographically, and its accuracy is improved with immunophenotypic markers. Hepatic cysts are the most commonly diagnosed benign liver lesions; these must be distinguished from malignant cystic lesions, which are rare. Among the solid benign liver lesions, hemangiomas and focal nodular hyperplasia seldom require treatment. In contrast, hepatocellular adenomas are associated with a risk for complications. A new classification system for hepatocellular adenomas based on genetic and phenotypic features can help guide patient care. In patients who are symptomatic or at risk for complications, multidisciplinary evaluation and treatment based on clinicopathologic, radiographic, and molecular analysis is needed. Conclusions Most benign liver lesions can be accurately diagnosed radiographically and do not require treatment. Treatment is necessary for patients with symptoms or at risk for complications. PMID:23377783

  3. Cancer treatments

    MedlinePlus

    ... 2017. Doroshow JH. Approach to the patient with cancer. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 179. National Cancer Institute website. Types of cancer treatment. www.cancer. ...

  4. Liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus infection.

    PubMed

    Liu, Yu; Li, Zhan-Yi; Li, Xi; Wang, Jia-Ni; Huang, Qun-Ai; Huang, Yong

    2017-10-01

    Chemotherapy has greatly improved the prognosis of breast cancer patients. However, it may also result in undesirable side effects such as hepatitis virus reactivation. Little information is available on the liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus (HBV/HCV) infection. We performed a retrospective survey of 835 patients diagnosed with breast cancer between January 2010 and December 2015 at our institution. All patients had been screened for HBV/HCV infection at the time of breast cancer diagnosis. We retrospectively investigated the toxicity of chemotherapy and the changes in HBV/HCV load based on a medical record review. 52 patients with positive anti-HBV antibody test and 21 patients with positive anti-HCV antibody tests received chemotherapy. 762 patients without HBV and HCV infection served as the control group. The morbidity of liver toxicity and disruptions in chemotherapy attributable to liver toxicity were not significantly different among control group, HBV group and HCV groups (27.7% vs 34.6% vs 42.9%, P = 0.189 and 5.0% vs 9.6% vs 9.5%, P = 0.173, respectively). No patients presented with HBV/HCV reactivation. Breast cancer patients with HCV can be treated with chemotherapy and targeted therapy with trastuzumab. Breast cancer patients with HBV who accept antiviral therapy can be treated with chemotherapy and targeted therapy with trastuzumab and patients can benefit from prophylactic antiviral therapy before chemotherapy. However, a multidisciplinary cooperation and closely monitoring liver function during the course of chemotherapy may benefit patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Yanli

    Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg{sup −1}·d{sup −1} for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats atmore » high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg{sup −1}·d{sup −1} for females and 16 mg·kg{sup −}1·d{sup −1} for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.« less

  6. Liver failure posthepatectomy and biliary fistula: multidisciplinar treatment.

    PubMed

    Calleja Kempin, Javier; Colón Rodríguez, Arturo; Machado Liendo, Pedro; Acevedo, Agustín; Martín Gil, Jorge; Sánchez Rodríguez, Teresa; Zorrilla Matilla, Laura

    2016-05-01

    The main cause of morbimor-mortality after major liver surgery is the development of liver failure posthepatectomy(LFPH). Treatment must involve multiple options and will be aggressive from the beginning. We report a case of a patient with cholangiocarcinoma perihilar treated with surgery: right hepatectomy extended to sI + IVb with develop of LFPH and biliary fistula and being management successfully in a multidisciplinary way.

  7. Autophagy-dependent generation of Axin2+ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis

    PubMed Central

    Li, J; Hu, S B; Wang, L Y; Zhang, X; Zhou, X; Yang, B; Li, J H; Xiong, J; Liu, N; Li, Y; Wu, Y Z; Zheng, Q C

    2017-01-01

    Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis. Aberrant autophagy in liver cirrhosis resulted in hepatocyte growth factor (HGF) expression, leading to activation of Met/JNK and Met/STAT3 signaling in sorted hepatic Axin2/EGFP+ cells and their transition into Axin2/EGFP+CD90+ cells that possess CSC properties. In a transgenic rat liver cirrhosis model, induction or inhibition of autophagy in cirrhotic livers by systemic administration of rapamycin or chloroquine or transfection with Atg3- and Atg7-shRNAs significantly induced or suppressed HGF expression, which in turn increased or reduced generation of EGFP+CD90+ hepatic cells by activating or inactivating Met/JNK and Met/STAT3 signaling, thereby promoting or preventing hepatocarcinogenesis. Systemic treatment with HGF-shRNA, SP600125 or stattic also reduced generation of EGFP(Axin2)+ hepatic cell-originated CD90+ CSCs in aberrant autophagic cirrhotic livers by inactivating HGF/Met/JNK or HGF/Met/STAT3 signaling, further preventing hepatocarcinogenesis. These data suggest that activation of Met/JNK and Met/STAT3 signaling in Axin2+ hepatic cells via autophagy-dependent HGF expression and the resultant generation of Axin2+CD90+ CSCs is a major mechanism of hepatocarcinogenesis

  8. Autophagy-dependent generation of Axin2+ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis.

    PubMed

    Li, J; Hu, S B; Wang, L Y; Zhang, X; Zhou, X; Yang, B; Li, J H; Xiong, J; Liu, N; Li, Y; Wu, Y Z; Zheng, Q C

    2017-11-30

    Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis. Aberrant autophagy in liver cirrhosis resulted in hepatocyte growth factor (HGF) expression, leading to activation of Met/JNK and Met/STAT3 signaling in sorted hepatic Axin2/EGFP+ cells and their transition into Axin2/EGFP+CD90+ cells that possess CSC properties. In a transgenic rat liver cirrhosis model, induction or inhibition of autophagy in cirrhotic livers by systemic administration of rapamycin or chloroquine or transfection with Atg3- and Atg7-shRNAs significantly induced or suppressed HGF expression, which in turn increased or reduced generation of EGFP+CD90+ hepatic cells by activating or inactivating Met/JNK and Met/STAT3 signaling, thereby promoting or preventing hepatocarcinogenesis. Systemic treatment with HGF-shRNA, SP600125 or stattic also reduced generation of EGFP(Axin2)+ hepatic cell-originated CD90+ CSCs in aberrant autophagic cirrhotic livers by inactivating HGF/Met/JNK or HGF/Met/STAT3 signaling, further preventing hepatocarcinogenesis. These data suggest that activation of Met/JNK and Met/STAT3 signaling in Axin2+ hepatic cells via autophagy-dependent HGF expression and the resultant generation of Axin2+CD90+ CSCs is a major mechanism of hepatocarcinogenesis

  9. Targeting Alpha-Fetoprotein (AFP)-MHC Complex with CAR T-Cell Therapy for Liver Cancer.

    PubMed

    Liu, Hong; Xu, Yiyang; Xiang, Jingyi; Long, Li; Green, Shon; Yang, Zhiyuan; Zimdahl, Bryan; Lu, Jingwei; Cheng, Neal; Horan, Lucas H; Liu, Bin; Yan, Su; Wang, Pei; Diaz, Juan; Jin, Lu; Nakano, Yoko; Morales, Javier F; Zhang, Pengbo; Liu, Lian-Xing; Staley, Binnaz K; Priceman, Saul J; Brown, Christine E; Forman, Stephen J; Chan, Vivien W; Liu, Cheng

    2017-01-15

    The majority of tumor-specific antigens are intracellular and/or secreted and therefore inaccessible by conventional chimeric antigen receptor (CAR) T-cell therapy. Given that all intracellular/secreted proteins are processed into peptides and presented by class I MHC on the surface of tumor cells, we used alpha-fetoprotein (AFP), a specific liver cancer marker, as an example to determine whether peptide-MHC complexes can be targets for CAR T-cell therapy against solid tumors. We generated a fully human chimeric antigen receptor, ET1402L1-CAR (AFP-CAR), with exquisite selectivity and specificity for the AFP 158-166 peptide complexed with human leukocyte antigen (HLA)-A*02:01. We report that T cells expressing AFP-CAR selectively degranulated, released cytokines, and lysed liver cancer cells that were HLA-A*02:01 + /AFP + while sparing cells from multiple tissue types that were negative for either expressed proteins. In vivo, intratumoral injection of AFP-CAR T cells significantly regressed both Hep G2 and AFP 158 -expressing SK-HEP-1 tumors in SCID-Beige mice (n = 8 for each). Moreover, intravenous administration of AFP-CAR T cells in Hep G2 tumor-bearing NSG mice lead to rapid and profound tumor growth inhibition (n = 6). Finally, in an established intraperitoneal liver cancer xenograft model, AFP-CAR T cells showed robust antitumor activity (n = 6). This study demonstrates that CAR T-cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent antitumor response. Our approach expands the spectrum of antigens available for redirected T-cell therapy against solid malignancies and offers a promising new avenue for liver cancer immunotherapy. Clin Cancer Res; 23(2); 478-88. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

    PubMed

    Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

    2016-10-01

    Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects. © 2016 UICC.

  11. [A case of liver metastasis of gastric cancer which was made resectable by hypertheromo-chemo-radiotherapy].

    PubMed

    Urade, M; Yonemura, Y; Fujimura, T; Takegawa, S; Kamata, T; Fushida, Y; Miyazaki, I

    1989-03-01

    A 60-year-old woman was diagnosed as having liver metastasis from gastric cancer 14 months after total gastrectomy and total pancreatectomy. The liver tumor was so huge and the complication, diabetes mellitus, was so severe that she was palliatively treated by hyperthermo-chemo-radiotherapy (HCR therapy) with 8-MHz capacitive heating system. Because hyperthermia for deep seated tumor is very difficult, irradiation (10 MV X-ray, 36 Gy) and systemic chemotherapy (CDDP, MMC) were combinedly used. After 10 session of hyperthermia, the tumor showed a remarkable regression in size, followed by S8 subsegmentectomy of the liver. Histologically, cancer cells were still viable in the midst of fibrosis around coagulation necrosis, while normal liver cells remained intact. Multidisciplinary HCR therapy is quite a useful modality for liver tumors and may serve to expand the indication for surgical operation.

  12. Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

    PubMed

    Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2014-02-01

    Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P = 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. An international comparison of stakeholder motivation to implement liver cancer control.

    PubMed

    Bridges, John F P; Joy, Susan M; Blauvelt, Barri M; Yan, Weili; Marsteller, Jill A

    2015-06-01

    The World Health Organization offers clear guidance on the development of national cancer control programmes based on a country's level of resources, yet the motivation to implement such programmes may be driven by factors other than resources. To compare stakeholder motivation to implement a national liver cancer control programme and assess if variation in motivation was associated with stakeholder characteristics or with national indicators of need and resources. Relevant stakeholders were purposively selected from 13 countries (Australia, China, France, Germany, Italy, Japan, Nigeria, South Korea, Spain, Taiwan, Thailand, Turkey and USA) to participate in a structured survey on liver cancer control. Respondents included 12 individuals working in clinical, 5 in policy and 3 in advocacy roles from each country. Stakeholders' motivation was measured using a scale grounded in expectancy theory and knowledge gained during previous qualitative interviews. Comparisons across countries and respondent characteristics were conducted using hierarchical regression. Country level motivation scores, holding constant individual level covariates, were correlated with indicators of need and resources and tested using Pearson's correlation coefficients. In total, 260 stakeholders, equally drawn from the study countries, completed the survey (45% response rate). At the national level, motivation was highest in Nigeria, Thailand and China (P < 0.001), and lowest in Italy (P < 0.001) and Germany (P = 0.003). Higher motivation was observed among stakeholders working at the international level relative to the local level (P = 0.017). Motivation was positively associated with a country's relative burden of liver cancer (P = 0.015) and negatively associated with their level of resources (P = 0.018). This study provides the first empirical evidence on the motivation of stakeholders to implement national cancer control programmes. Furthermore, we demonstrate that motivation is more

  14. Modulatory effects of silibinin in various cell signaling pathways against liver disorders and cancer - A comprehensive review.

    PubMed

    Polachi, Navaneethakrishnan; Bai, Guirong; Li, Tingyang; Chu, Yang; Wang, Xiangyang; Li, Shuming; Gu, Ning; Wu, Jiang; Li, Wei; Zhang, Yanjun; Zhou, Shuiping; Sun, He; Liu, Changxiao

    2016-11-10

    Silibinin, a natural flavanone, derived from the milk thistle plant (Silybum marianum), was illustrated for several medicinal uses such as liver-protective, anti-oxidant, anti-cancer, anti-inflammation and many other. However, silibinin has poor absorbance and bioavailability due to low water solubility, thereby limiting its clinical applications and therapeutic efficiency. To overcome this problem, the combination of silibinin with phosphatidylcholine (PC) as a formulation was used to enhance the solubility and bioavailability. The results indicated that silibinin-PC taken orally markedly enhanced bioavailability and therapeutic efficiency. In addition, a deeper understanding of the signaling pathways modulated by silibinin is important to realize its potential in developing targeted therapies against liver disorders and cancer. Silibinin has been shown to inhibit many cell signaling pathways in preclinical models, demonstrating promising effects against liver disorders and cancer through in vitro and in vivo studies. This review summarizes the pharmacokinetic properties, bioavailability, safety data, clinical activities and modulatory effects of silibinin in different cell signaling pathways against liver disorders and cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Tolvaptan for the treatment of liver cirrhosis oedema.

    PubMed

    Sakaida, Isao

    2014-07-01

    No alternative therapeutic option exists if liver cirrhosis patients have insufficient response to conventional diuretics and/or experience conventional diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V2 receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in body weight, reduction in ascites volume and increases in urine volume when compared to placebo, despite the use of conventional diuretics. Additionally, approximately 60% of patients with oedema-related symptoms improved. Low-dose tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with placebo. For future research, the efficacy and safety of lower tolvaptan doses for the treatment of liver cirrhosis patients with oedema should be confirmed in Japan. The results of this research could be used as an indicator or a guideline for physicians around the world.

  16. Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.

    PubMed

    Saleem, Zikria; Ahmad, Mobasher; Hashmi, Furqan Khurshid; Saeed, Hamid; Aziz, Muhammad Tahir

    2016-09-01

    Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p<0.05) in patients of all age groups. However, the albumin levels were not significantly changed (p>0.05). The A/G ratio level increased (p<0.05) as a result of reduction in globulin levels. Significant changes in plasma protein levels were observed in the elderly patients (50 to 65 years) than patients between 20 to 50 years of age. AC protocol impairs liver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

  17. Indocyanine green fluorescence imaging in the surgical management of liver cancers: current facts and future implications.

    PubMed

    Lim, C; Vibert, E; Azoulay, D; Salloum, C; Ishizawa, T; Yoshioka, R; Mise, Y; Sakamoto, Y; Aoki, T; Sugawara, Y; Hasegawa, K; Kokudo, N

    2014-04-01

    Imaging detection of liver cancers and identification of the bile ducts during surgery, based on the fluorescence properties of indocyanine green, has recently been developed in liver surgery. The principle of this imaging technique relies on the intravenous administration of indocyanine green before surgery and the illumination of the surface of the liver by an infrared camera that simultaneously induces and collects the fluorescence. Detection by fluorescence is based on the contrast between the (fluorescent) tumoral or peri-tumoral tissues and the healthy (non-fluorescent) liver. Results suggest that indocyanine green fluorescence imaging is capable of identification of new liver cancers and enables the characterization of known hepatic lesions in real time during liver resection. The purpose of this paper is to present the fundamental principles of fluorescence imaging detection, to describe successively the practical and technical aspects of its use and the appearance of hepatic lesions in fluorescence, and to expose the diagnostic and therapeutic perspectives of this innovative imaging technique in liver surgery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women.

    PubMed

    Yang, Yang; Gao, Jing; Li, Hong-Lan; Zheng, Wei; Yang, Gong; Zhang, Wei; Ma, Xiao; Tan, Yu-Ting; Rothman, Nathaniel; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-Ou; Xiang, Yong-Bing

    2016-07-15

    We aimed at evaluating the risk of liver cancer in different levels of HBsAg among Chinese men and women. We carried out a nested case-control study including 363 cases and 3,511 controls in two population-based cohorts in Shanghai. Plasma samples collected at enrollment were quantified for HBsAg levels using the Architect QT assay. Conditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for liver cancer, with adjustment for potential confounders. HBsAg was detected in 6.29% of control subjects overall (7.02% in men and 4.98% in women). HBsAg levels were positively associated with liver cancer risk in a dose-response manner (ptrend  < 0.001). Such association showed a significant gender disparity. With increasing levels of HBsAg, liver cancer risks rose more steeply in men than in women. In men, the adjusted ORs increased from 7.27 (95% CI: 3.49-15.15) at the lowest detectable level of HBsAg (5-9 IU/ml) to 7.16 (95% CI: 3.21-15.96), 34.30 (95% CI: 16.94-69.44), and 47.33 (95% CI: 23.50-95.34) at the highest level of HBsAg (≥1,000 IU/ml) compared to those negative for HBsAg. The corresponding ORs were much lower for women, from 1.37 (95% CI: 0.25-7.47), 3.81 (95% CI: 1.09-13.28), 7.36 (95% CI: 2.41-22.46) and 16.86 (95% CI: 7.24-39.27), respectively. HBsAg quantification has potential to distinguish individuals at different risks of liver cancer. Men with the lowest detectable level of HBsAg should still pay attention to their liver cancer risks, but those with a higher level may be given a higher priority in future liver cancer surveillance program. © 2016 UICC.

  19. Incidence and mortality of primary liver cancer in England and Wales: changing patterns and ethnic variations.

    PubMed

    Ladep, Nimzing G; Khan, Shahid A; Crossey, Mary Me; Thillainayagam, Andrew V; Taylor-Robinson, Simon D; Toledano, Mireille B

    2014-02-14

    To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR). Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on

  20. Incidence and mortality of primary liver cancer in England and Wales: Changing patterns and ethnic variations

    PubMed Central

    Ladep, Nimzing G; Khan, Shahid A; Crossey, Mary ME; Thillainayagam, Andrew V; Taylor-Robinson, Simon D; Toledano, Mireille B

    2014-01-01

    AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR). RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had

  1. Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with Icotinib.

    PubMed

    Zhu, Zhouyu; Chai, Ying

    2016-11-01

    A 65-year-old Chinese male was referred to our hospital for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Aggressive combined therapy with surgical resection of the right upper lung lesion and chemotherapy was performed. One month later, continued Icotinib treatment was used as magnetic resonance imaging revealed liver metastasis (LM). Interestingly, complete remission of the patient's LM lesions was achieved in six months. To our knowledge, this is the first report documenting a successful case of an NSCLC patient with LM treated with Icotinib after receiving a radical resection for pulmonary carcinoma. Our experience could provide a treatment strategy for patients with similar disease. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  2. IL-4 mRNA Is Downregulated in the Liver of Pancreatic Cancer Patients Suffering from Cachexia.

    PubMed

    Prokopchuk, Olga; Steinacker, Jürgen M; Nitsche, Ulrich; Otto, Stephanie; Bachmann, Jeannine; Schubert, Elaine C; Friess, Helmut; Martignoni, Marc E

    2017-01-01

    Interleukin-4 (IL-4) together with interleukin-13 (IL-13) play an important role in inflammation and wound repair, and are known to be upregulated in human skeletal muscle after strenuous physical exercise. Additionally, these cytokines may act as autocrine growth factors in pancreatic cancer cells. We hypothesize that IL-4, IL-13, and their corresponding receptors are involved in mechanism of cancer cachexia. Tissue samples from human skeletal muscle, white fat, liver, healthy pancreas, and pancreatic ductal adenocarcinoma were analyzed by quantitative real-time polymerase chain reaction for mRNA expression levels of IL-4, IL-13, IL-4 receptor α, and IL-13 receptor α1. We demonstrate for the first time that liver IL-4 mRNA is downregulated in vivo in patients with pancreatic cancer and cachexia. Additionally, IL-4 mRNA in the liver inversely correlated with musculus psoas thickness. We speculate that suppression of IL-4 is involved in cancer cachexia, although the exact mechanisms have to be further elucidated.

  3. [A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].

    PubMed

    Hayashi, Keiko; Enomoto, Takumo; Oshida, Sayuri; Habiro, Takeyoshi; Hatate, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

    2013-11-01

    We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

  4. Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids.

    PubMed

    Yoshikawa, Kenichi; Kawashima, Reimi; Hirose, Yuki; Shibata, Keiko; Akasu, Takafumi; Hagiwara, Noriko; Yokota, Takeharu; Imai, Nami; Iwaku, Akira; Kobayashi, Go; Kobayashi, Hirohiko; Kinoshita, Akiyoshi; Fushiya, Nao; Kijima, Hiroyuki; Koike, Kazuhiko; Saruta, Masayuki

    2017-07-21

    We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid (ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury, and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa, from the rectum to the anus, and this is the first description of a case that developed a severe liver disorder after this treatment; hence, an analysis of future cases as they accumulate is desirable.

  5. Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin.

    PubMed

    Iancu, Cornel; Mocan, Lucian; Bele, Constantin; Orza, Anamaria Ioana; Tabaran, Flaviu A; Catoi, Cornel; Stiufiuc, Rares; Stir, Ariana; Matea, Cristian; Iancu, Dana; Agoston-Coldea, Lucia; Zaharie, Florin; Mocan, Teodora

    2011-01-17

    The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA-MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA-MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA-MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA-MWCNTs in a similar manner. Our results clearly show that HSA-MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

  6. Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin

    PubMed Central

    Iancu, Cornel; Mocan, Lucian; Bele, Constantin; Orza, Anamaria Ioana; Tabaran, Flaviu A; Catoi, Cornel; Stiufiuc, Rares; Stir, Ariana; Matea, Cristian; Iancu, Dana; Agoston-Coldea, Lucia; Zaharie, Florin; Mocan, Teodora

    2011-01-01

    The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA–MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA–MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA–MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA–MWCNTs in a similar manner. Our results clearly show that HSA–MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating. PMID:21289990

  7. How I Do It: Cone-Beam CT during Transarterial Chemoembolization for Liver Cancer

    PubMed Central

    Tacher, Vania; Radaelli, Alessandro; Lin, MingDe

    2015-01-01

    Cone-beam computed tomography (CBCT) is an imaging technique that provides computed tomographic (CT) images from a rotational scan acquired with a C-arm equipped with a flat panel detector. Utilizing CBCT images during interventional procedures bridges the gap between the world of diagnostic imaging (typically three-dimensional imaging but performed separately from the procedure) and that of interventional radiology (typically two-dimensional imaging). CBCT is capable of providing more information than standard two-dimensional angiography in localizing and/or visualizing liver tumors (“seeing” the tumor) and targeting tumors though precise microcatheter placement in close proximity to the tumors (“reaching” the tumor). It can also be useful in evaluating treatment success at the time of procedure (“assessing” treatment success). CBCT technology is rapidly evolving along with the development of various contrast material injection protocols and multiphasic CBCT techniques. The purpose of this article is to provide a review of the principles of CBCT imaging, including purpose and clinical evidence of the different techniques, and to introduce a decision-making algorithm as a guide for the routine utilization of CBCT during transarterial chemoembolization of liver cancer. © RSNA, 2015 Online supplemental material is available for this article. PMID:25625741

  8. The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography.

    PubMed

    Chew, Cindy; O'Dwyer, Patrick J

    2016-06-01

    Accurate staging of patients with pancreatic cancer is important to avoid unnecessary operations. The aim of this study was to prospectively assess the impact of magnetic resonance (MR) imaging on preoperative staging of liver in patients with findings of resectable pancreatic cancer on computed tomography (CT). All patients who presented to a tertiary referral centre with pancreatic cancer between April 2012 and December 2013 were included in the study. Patients with findings of resectable disease on CT underwent further liver diffusion-weighted MR imaging, using a hepatocyte-specific contrast agent. A total of 583 patients with pancreatic cancer were referred. 69 (11.8%) had resectable disease on CT. Of these 69 patients, 16 (23.2%) had liver metastases on MR imaging, while 6 (8.7%) had indeterminate lesions. Of the 16 patients with positive MR imaging findings of liver metastases, 11 died of pancreatic cancer, with a mean survival time of nine months (95% confidence interval [CI] 5.22-14.05). The mean survival time of the 47 patients with negative MR imaging findings was 16 months (95% CI 14.33-18.10; p = 0.001). Subsequently, 22 of these patients underwent surgery, and only 1 (4.5%) patient was found to have liver metastasis at surgery. The results of the present study indicate that MR imaging improves the staging of disease in patients with resectable pancreatic cancer. Copyright: © Singapore Medical Association.

  9. Surgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+- liver cells deficient for p53 and Rb.

    PubMed

    Matondo, Ramadhan B; Toussaint, Mathilda Jm; Govaert, Klaas M; van Vuuren, Luciel D; Nantasanti, Sathidpak; Nijkamp, Maarten W; Pandit, Shusil K; Tooten, Peter Cj; Koster, Mirjam H; Holleman, Kaylee; Schot, Arend; Gu, Guoqiang; Spee, Bart; Roskams, Tania; Rinkes, Inne Borel; Schotanus, Baukje; Kranenburg, Onno; de Bruin, Alain

    2016-08-23

    The long term prognosis of liver cancer patients remains unsatisfactory because of cancer recurrence after surgical interventions, particularly in patients with viral infections. Since hepatitis B and C viral proteins lead to inactivation of the tumor suppressors p53 and Retinoblastoma (Rb), we hypothesize that surgery in the context of p53/Rb inactivation initiate de novo tumorigenesis.We, therefore, generated transgenic mice with hepatocyte and cholangiocyte/liver progenitor cell (LPC)-specific deletion of p53 and Rb, by interbreeding conditional p53/Rb knockout mice with either Albumin-cre or Cytokeratin-19-cre transgenic mice.We show that liver cancer develops at the necrotic injury site after surgical resection or radiofrequency ablation in p53/Rb deficient livers. Cancer initiation occurs as a result of specific migration, expansion and transformation of cytokeratin-19+-liver (CK-19+) cells. At the injury site migrating CK-19+ cells formed small bile ducts and adjacent cells strongly expressed the transforming growth factor β (TGFβ). Isolated cytokeratin-19+ cells deficient for p53/Rb were resistant against hypoxia and TGFβ-mediated growth inhibition. CK-19+ specific deletion of p53/Rb verified that carcinomas at the injury site originates from cholangiocytes or liver progenitor cells.These findings suggest that human liver patients with hepatitis B and C viral infection or with mutations for p53 and Rb are at high risk to develop tumors at the surgical intervention site.

  10. Surgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+- liver cells deficient for p53 and Rb

    PubMed Central

    Govaert, Klaas M; van Vuuren, Luciel D; Nantasanti, Sathidpak; Nijkamp, Maarten W; Pandit, Shusil K; Tooten, Peter CJ; Koster, Mirjam H; Holleman, Kaylee; Schot, Arend; Gu, Guoqiang; Spee, Bart; Roskams, Tania; Rinkes, Inne Borel; Schotanus, Baukje; Kranenburg, Onno; de Bruin, Alain

    2016-01-01

    The long term prognosis of liver cancer patients remains unsatisfactory because of cancer recurrence after surgical interventions, particularly in patients with viral infections. Since hepatitis B and C viral proteins lead to inactivation of the tumor suppressors p53 and Retinoblastoma (Rb), we hypothesize that surgery in the context of p53/Rb inactivation initiate de novo tumorigenesis. We, therefore, generated transgenic mice with hepatocyte and cholangiocyte/liver progenitor cell (LPC)-specific deletion of p53 and Rb, by interbreeding conditional p53/Rb knockout mice with either Albumin-cre or Cytokeratin-19-cre transgenic mice. We show that liver cancer develops at the necrotic injury site after surgical resection or radiofrequency ablation in p53/Rb deficient livers. Cancer initiation occurs as a result of specific migration, expansion and transformation of cytokeratin-19+-liver (CK-19+) cells. At the injury site migrating CK-19+ cells formed small bile ducts and adjacent cells strongly expressed the transforming growth factor β (TGFβ). Isolated cytokeratin-19+ cells deficient for p53/Rb were resistant against hypoxia and TGFβ-mediated growth inhibition. CK-19+ specific deletion of p53/Rb verified that carcinomas at the injury site originates from cholangiocytes or liver progenitor cells. These findings suggest that human liver patients with hepatitis B and C viral infection or with mutations for p53 and Rb are at high risk to develop tumors at the surgical intervention site. PMID:27323406

  11. Prospective association of liver function biomarkers with development of hepatobiliary cancers.

    PubMed

    Stepien, Magdalena; Fedirko, Veronika; Duarte-Salles, Talita; Ferrari, Pietro; Freisling, Heinz; Trepo, Elisabeth; Trichopoulou, Antonia; Bamia, Christina; Weiderpass, Elisabete; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Racine, Antoine; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Lagiou, Pagona; Benetou, Vassiliki; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Naccarati, Alessio; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Peeters, Petra H; Lund, Eiliv; Quirós, J Ramón; Nápoles, Osmel Companioni; Sánchez, María-José; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Nystrom, Hanna; Khaw, Kay-Tee; Key, Timothy J; Gunter, Marc; Cross, Amanda; Riboli, Elio; Romieu, Isabelle; Jenab, Mazda

    2016-02-01

    Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI). In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09). This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Liver transplantation for hepatocellular cancer: UCL experience in 137 adult cirrhotic patients. Alpha-foetoprotein level and locoregional treatment as refined selection criteria.

    PubMed

    Ciccarelli, Olga; Lai, Quirino; Goffette, Pierre; Finet, Patrice; De Reyck, Chantal; Roggen, Francine; Sempoux, Christine; Doffagne, Erik; Reding, Raymond; Lerut, Jan

    2012-08-01

    Liver transplantation (LT) is a validated treatment for selected cirrhotics with hepatocellular cancer (HCC). A retrospective single center study including 137 recipients having proven HCC was done to refine inclusion criteria for LT as well as to look at impact of locoregional treatment (LRT) on outcome. At pre-LT imaging, 42 (30.6%) patients were Milan criteria (MC)-OUT; 28 (20.4%) were University of California San Francisco criteria (UCSFC)-OUT. Pre-LT LRT was performed in 109 (79.6%) patients. Multivariate analysis identified four factors to be independently predictive of recurrence: tumour number >3, AFP level ≥400 ng/ml, microvascular invasion and rejection needing anti-lymphocytic antibodies. When considering pre-transplant variables only, AFP level ≥400 ng/ml (HR = 5.13; P < 0.0001) was the unique risk factor for recurrence; conversely, application of LRT was protective (HR = 0.42; P = 0.04). MC-IN patients having LRT (n = 79) had the best 5-year tumour-free survival (TFS) (91.6%). MC-IN patients without LRT (n = 16) and MC-OUT patients with LRT (n = 30) had similar good TFS (72.7% vs.77.5%); finally MC-OUT patients without LRT (n = 12) had the worst results (45.0%; vs. 1st group: P < 0.0001). Immediate pre-LT AFP and aggressive pre-transplant LRT strategy, especially in MC-OUT patients, are both important elements to further expand inclusion criteria without compromising long-term results of HCC liver recipients. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

  13. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    ClinicalTrials.gov

    2017-07-10

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  14. CT-guided percutaneous ethanol injection with disposable curved needle for treatment of malignant liver neoplasms and their metastases in retroperitoneal lymph nodes

    PubMed Central

    Zuo, Chang-Jing; Wang, Pei-Jun; Shao, Cheng-Wei; Wang, Min-Jie; Tian, Jian-Ming; Xiao, Yi; Ren, Fang-Yuan; Hao, Xi-Yan; Yuan, Min

    2004-01-01

    AIM: To explore the feasibility of computed tomography (CT)-guided percutaneous ethanol injection (PEI) using a disposable curved needle for treatment of malignant liver neoplasms and their metastases in retroperitoneal lymph nodes. METHODS: CT-guided PEI was conducted using a disposable curved needle in 26 malignant liver tumors smaller than 5 cm in diameter and 5 lymph node metastases of liver cancer in the retroperitoneal space. The disposable curved needle was composed of a straight trocar (21G) and stylet, a disposable curved tip (25 G) and a fine stylet. For the tumors found in deep sites and difficult to reach, or for hepatic masses inaccessible to the injection using a straight needle because of portal vein and bile ducts, the straight trocar was used at first to reach the side of the tumor. Then, the disposable curved needle was used via the trocar. When the needle reached the tumor center, appropriate amount of ethanol was injected. For relatively large malignant liver tumors, multi-point injection was carried out for a better distribution of the ethanol injected throughout the masses. The curved needle was also used for treatment of the metastasis in retroperitoneal lymph nodes blocked by blood vessels and inaccessible by the straight needle. RESULTS: All of the 26 liver tumors received 2 or more times of successful PEI, through which ethanol was distributed throughout the whole tumor mass. Effect of the treatment was monitored by contrast-enhanced multi-phase CT and magnetic resonance imaging (MRI) examinations three months later. Of the 18 lesions whose diameters were smaller than 3 cm, the necrotic change across the whole mass and that in most areas were observed in 15 and 3 tumors, respectively. Among the 8 tumors sizing up to 5 cm, 5 were completely necrotic and 3 largely necrotic. Levels of tumor seromarkers were significantly reduced in some of the cases. In 5 patients with metastases of liver cancer in retroperitoneal lymph nodes who received 1

  15. Green tea and liver cancer risk: A meta-analysis of prospective cohort studies in Asian populations.

    PubMed

    Huang, Ya-Qing; Lu, Xin; Min, Han; Wu, Qian-Qian; Shi, Xiao-Ting; Bian, Kang-Qi; Zou, Xiao-Ping

    2016-01-01

    The aim of this meta-analysis was to investigate whether an association existed between green tea consumption and the risk for liver cancer in prospective cohort studies in Asian populations. Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science, and the Chinese Bio-medicine Database published before April 2015. Study-specific risk estimates for the highest versus non- or lowest and increment of daily cup of green tea consumption levels were combined based on fixed- or random-effects models. STATA 11.0 (Stata Corporation, College Station, TX, USA) software was used for statistical analysis. Nine prospective cohort articles involving 465,274 participants and 3694 cases of liver cancer from China, Japan, and Singapore were included. The summary relative risk (RR) indicated a significant association between the highest green tea consumption and reduced risk for liver cancer (summary RR, 0.88; 95% confidence interval [CI], 0.81-0.97). However, no statistically significant association was observed when analyzing daily consumption of one cup (summary RR, 0.97; 95% CI, 0.95-1.00). When stratified by sex, the protective effect of green tea consumption on risk for liver cancer was observed only in the group of women (summary RR, 0.78; 95% CI, 0.64-0.96), but not in men (summary RR, 0.89; 95% CI, 0.79-1.00). The present analysis indicated the preventive effects of green tea intake on the risk for liver cancer in female Asian populations. However, additional studies are needed to make a convincing case for this association. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Reactive Lymphoid Hyperplasia of the liver in a patient with colon cancer: report of two cases

    PubMed Central

    Takahashi, Hiroki; Sawai, Hirozumi; Matsuo, Yoichi; Funahashi, Hitoshi; Satoh, Mikinori; Okada, Yuji; Inagaki, Hiroshi; Takeyama, Hiromitsu; Manabe, Tadao

    2006-01-01

    Background Reactive lymphoid hyperplasia (RLH) of the liver is very rarely reported, and we encountered two cases of RLH of the liver in a patient with colon cancer. Case presentation In the first case, a 77-year-old woman was admitted for the surgical removal of a ascending colon cancer. A hepatic tumor in the left lobe was concurrently revealed by computed tomography (CT), and magnetic resonance imaging (MRI). The appearance suggested liver metastasis. Right hemicolectomy and partial hepatectomy were performed. On histopathological examination, lymphoid follicles with germinal centers were seen in the tumor-like lesion, and remarkable lymphoid infiltration with germinal centers was seen in the portal area around the nodule. Immunohistochemical studies revealed polyclonality of infiltrating lymphocyte. Consequently, this nodular lesion was diagnosed as RLH of the liver. In the second case, a 64-year-old woman who had a radical right hemicolectomy for stage II ascending colon cancer 10 years ago was admitted with dysuria. A hepatic tumor in the left lobe was concurrently revealed by CT and MRI, suggesting hepatocellular carcinoma. A left lateral segmentectomy was performed. Microscopically, this lesion revealed the almost same findings as the first case, so this nodular lesion was diagnosed as RLH of the liver. Conclusion Our two cases were the first report of RLH of the liver accompanying colon cancer. Because there are a very few cases, so it is not clear whether the malignancies were involved in the onset of RLH. But we believe that new factors involved in the onset mechanism of RLH may be identified by carefully monitoring the clinical course of our two patients. PMID:16965640

  17. Comparison of laser- and RF-based interstitial coagulation systems for the treatment of liver tumors (Invited Paper)

    NASA Astrophysics Data System (ADS)

    de Jager, Arjan A.; van Trier, Bart N.; Veenendaal, Liesbeth M.; van Hillegersberg, Richard; Verdaasdonk, Rudolf M.

    2005-04-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Surgical treatments, including hepatic resection and liver transplantation are considered as the most effective treatment of HCC. However, less than 20% of HCC patients can be treated surgically because of: multi-focal diseases, proximity of tumor to key vascular or biliary structures and inadequate functional hepatic reserve related coexistent cirrhosis. In this unfortunate groups of patients various palliative treatments modalities are being performed to extend the time of survival and quality of life. These techniques include trans-catheter arterial chemoembolization (TACE), percutaneous ethanol injection (PEI) and Interstitial Thermal Therapy: laser-induced interstitial thermotherapy (LITT) and radio-frequency ablation (RFA).

  18. Strategies to tackle the challenges of external beam radiotherapy for liver tumors.

    PubMed

    Lock, Michael I; Klein, Jonathan; Chung, Hans T; Herman, Joseph M; Kim, Edward Y; Small, William; Mayr, Nina A; Lo, Simon S

    2017-05-18

    Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity. Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis. However, the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment, management of motion and appropriate selection of dose regimen. This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines. Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation. Indeed, certain sub-populations, such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization, have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration. Implementing a liver radiation program requires three primary challenges to be addressed: (1) immobilization and motion management; (2) localization; and (3) dose regimen and constraint selection. Strategies to deal with motion include simple internal target volume (ITV) expansions, non-gated ITV reduction strategies, breath hold methods, and surrogate marker methods to enable gating or tracking. Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy, imaging modalities, and margin management. Finally, a dose response has been demonstrated and dose regimens appear to be converging. A more uniform approach to treatment in terms of technique, dose selection and patient selection will allow us to study liver radiation in larger and, hopefully, multicenter randomized

  19. Strategies to tackle the challenges of external beam radiotherapy for liver tumors

    PubMed Central

    Lock, Michael I; Klein, Jonathan; Chung, Hans T; Herman, Joseph M; Kim, Edward Y; Small, William; Mayr, Nina A; Lo, Simon S

    2017-01-01

    Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity. Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis. However, the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment, management of motion and appropriate selection of dose regimen. This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines. Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation. Indeed, certain sub-populations, such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization, have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration. Implementing a liver radiation program requires three primary challenges to be addressed: (1) immobilization and motion management; (2) localization; and (3) dose regimen and constraint selection. Strategies to deal with motion include simple internal target volume (ITV) expansions, non-gated ITV reduction strategies, breath hold methods, and surrogate marker methods to enable gating or tracking. Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy, imaging modalities, and margin management. Finally, a dose response has been demonstrated and dose regimens appear to be converging. A more uniform approach to treatment in terms of technique, dose selection and patient selection will allow us to study liver radiation in larger and, hopefully, multicenter randomized

  20. Does hypervascularity of liver metastases as detected on MRI predict disease progression in breast cancer patients?

    PubMed

    Braga, Larissa; Semelka, Richard C; Pietrobon, Ricardo; Martin, Diego; de Barros, Nestor; Guller, Ulrich

    2004-05-01

    The aim of our study was to evaluate the association of the vascularity of liver metastases, as characterized by MRI, and disease progression in breast cancer patients. Sixteen breast cancer patients with liver metastases who underwent MRI before and after systemic therapy were retrospectively identified. On the basis of comparison of each MRI examination with the previous examination, disease status of the patients was classified as complete response, partial response, stable disease, or progressive disease. Liver metastases were characterized as hyper- or hypovascular on the basis of the degree of enhancement in the arterial, portal, and interstitial phases of imaging after administration of a contrast agent. Fisher's exact test and ordinal logistic regression models, including the type of systemic therapy, presence of multiple metastases, and hormone receptor status, were used to estimate the unadjusted and risk-adjusted association between the presence of hypervascular liver metastases and disease progression. All patients in our sample (n = 16) were women and most (12/16, 75%) were white. Their median age was 51.5 years. In unadjusted analyses, the association between the presence of hypervascular liver metastases and disease progression was statistically significant (p < 0.0001). In multiple logistic regression analyses, hypervascular liver metastases were found to be an independent predictor of disease progression. Patients with hypervascular liver lesions were 20.5 times more likely to experience disease progression than patients without hypervascular metastases (odds ratio, 20.5; 95% confidence interval, 5.1-83.5; p < 0.0001). Our analysis provides suggestive evidence that disease progression can be predicted through MRI assessment of the vascularity of liver metastases in patients with breast cancer.

  1. Does pyogenic liver abscess increase the risk of delayed-onset primary liver cancer?

    PubMed Central

    Chu, Chia-Sheng; Lin, Che-Chen; Peng, Cheng-Yuan; Chuang, Po-Heng; Su, Wen-Pang; Lai, Shih-Wei; Chen, Hsuan-Ju; Chung, Chi-Jung; Lai, Hsueh-Chou

    2017-01-01

    Abstract Delayed-onset primary liver cancer (PLC) including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in patients with pyogenic liver abscess (PLA) is not common. The relationship between PLA and delayed-onset PLC is unclear. We investigated the association in a nationwide cohort study. From Taiwan National Health Insurance claims data, a cohort of 17,531 patients with PLA was generated after excluding patients with a history of cancer (n = 2034) and those diagnosed with PLC (n = 572) and other cancers (n = 627) within 1 year of a diagnosis of PLA. An age-, sex-, index year-, and diabetes mellitus (DM)-matched control cohort of 70,124 persons without PLA was selected from the same dataset. Both cohorts were followed up until the end of 2011. The risk of PLC was estimated for both cohorts. The incidence of PLC was nearly 2-fold greater in the PLA group than in the control cohort (29.3 per 10,000 person-years vs. 16.2 per 10,000 person-years). The incidences of HCC and ICC were 1.5- (22.1 per 10,000 person-years vs. 15.0 per 10,000 person-years) and 11-fold greater (6.73 per 10,000 person-years vs. 0.62 per 10,000 person-years), respectively, in the PLA group than in the control cohort. The PLA cohort also had high risks of PLC (adjusted hazard ratio [aHR] = 1.56; 95% confidence interval [CI] = 1.35–1.81), HCC (aHR = 1.34; 95% CI = 1.15–1.57), and ICC (aHR = 6.94; 95% CI = 4.23–11.57). In conclusion, in this nationwide cohort study, PLA increased the risk of delayed-onset PLC. PMID:28834881

  2. Is the skin a sanctuary for breast cancer cells during treatment with anti-HER2 antibodies?

    PubMed

    Graziano, Vincenzo; Scognamiglio, Maria Teresa; Zilli, Marinella; Giampietro, Jamara; Vici, Patrizia; Natoli, Clara; Grassadonia, Antonino

    2015-01-01

    The occurrence of skin metastases is a common event in patients affected by advanced breast cancer, usually associated with systemic disease progression. Here we describe 2 cases of diffuse cutaneous metastases from HER2-overexpressing breast cancer occurring despite a dramatic response in liver and bone, respectively, during treatment with anti-HER2 antibodies Trastuzumab and Pertuzumab. We discuss the reasons for this discrepancy and suggest a possible implication of impaired immune response in the skin. Future research should provide strategies to overcome the induction of immune privilege in the skin in order to avoid discontinuation of effective treatments.

  3. [Herbs for calming liver and suppressing yang in treatment of hyperthyroidism with hyperactive liver yang: herbal effects on lymphocyte protein expression].

    PubMed

    Li, Xiangping; Yin, Tao; Zhong, Guangwei; Li, Wei; Luo, Yanhong; Xiang, Lingli; Liu, Zhehao

    2011-07-01

    To observe the herbal effects on hyperthyroidism patients with syndrome of hyperactivity of liver-Yang by method for calming the liver and suppressing Yang and investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of the curative mechanisms of calming the liver and suppressing Yang treatment. A total of 48 hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were randomly divided into treatment group and control group. The treatment group was treated by method for calming the liver and suppressing Yang in accordance with traditional Chinese medicine (TCM) and the control group with thiamazole tablets for three periods of treatment The therapeutic effects, the score of TCM symptom, electrocardiogram (P wave), thyroid hormones and ultrasound were observed in both groups before and after the treatment. The side effects in the treatment course were observed in both groups. The level of differential protein expression was analyzed by two-dimensional electrphoresis and matrix assisted laser desorption/ionizaton time-of-flight mass spectrometry. The treatment group has the effect on stepping down the heart rate, cutting down the P wave amplitude changes, regulating the level of thyroid hormones and decreasing the volume of thyromegaly. There are not statistically significant between the treatment group and control group. However, the treatment group has obviously better effect on regulating TCM symptom and decreasing the side reaction than the control group (P<0.05). There are not statistically significant on the total effective between the treatment group and control group. The average spots in lymphocyte for normal people, before and after treating hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were (429 +/- 31), (452 +/- 28) and (437 +/- 36) spots respectively. Eight down-regulated protein expressions and 11 up-regulated protein expressions were obtained in

  4. If a picture is worth a thousand words, take a good look at the picture: Survival after liver metastasectomy for colorectal cancer.

    PubMed

    Morris, Eva; Treasure, Tom

    2017-08-01

    An analysis of NHS data published in by Morris et al. in 2010 is widely used as evidence in support of liver metastasectomy for colorectal cancer and its wider application. Recent evidence concerning better overall survival for patients with metastatic colorectal cancer challenges the notional assumptions about what survival would be without metastasectomy. Earlier detection of metastases for local treatments has not resulted in a survival benefit. The interpretation of its central graphical display is critically reviewed and the common the limitations of the analysis of registry data and resulting immortal time bias are explored. Recent evidence, including the 2017 CLOCC trial report make the original interpretation of the analysis suspect. Randomised trials are essential to detect a treatment effect of specific interventions among variable disease progression, selection bias, and multiple and repeated treatments that are inherent in the management of advanced cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. [AFP-producing gastric cancer and hepatoid gastric cancer].

    PubMed

    Wang, Y K; Zhang, X T

    2017-11-23

    AFP-producing gastric cancer(AFPGC) and hepatoid adenocarcinoma of the stomach (HAS) are two special subtypes of gastric cancer. There are both correlation and difference between them. AFPGC is usually identified as primary gastric cancer with serum AFP level more than 20 ng/ml or showed AFP positive staining by immunohistochemistry. The diagnosis of HAS is mainly dependent on the pathological character of hepatocellular carcinoma-like differentiation of gastric cancer. The morbidity of AFPGC and HAS are rather low, especially the incidence of HAS is about 1%. The prognoses of these two subtypes are poorer than that of common gastric adenocarcinoma, due to a high incidence rate of liver metastasis and lymph node metastasis. With the development of next-generation sequencing and other genomic technologies, gastric cancers, including these two rare subtypes, are now being investigated in more detail at the molecular level. Treatment remains the biggest challenge, early diagnosis and radical resection can dramatically improve patients'prognosis. Monitoring serum AFP and abdominal imaging examination during follow-up is important for early detection of liver metastasis. In combination with local treatment methods such as transarterial chemoembolization and radiofrequency ablation of liver may further extend patients'survival time. Targeted therapy owes a great potential value in the future.

  6. Sedanolide induces autophagy through the PI3K, p53 and NF-κB signaling pathways in human liver cancer cells.

    PubMed

    Hsieh, Shu-Ling; Chen, Chi-Tsai; Wang, Jyh-Jye; Kuo, Yu-Hao; Li, Chien-Chun; Hsieh, Lan-Chi; Wu, Chih-Chung

    2015-12-01

    Sedanolide (SN), a phthalide-like compound from celery seed oil, possesses antioxidant effects. However, the effect of SN on cell death in human liver cancer cells has yet to be determined. In this study, cell viability determination, monodansylcadaverine (MDC) fluorescent staining and immunoblot analysis were performed to determine autophagy induction and autophagy-induced protein expression changes via molecular examination after human liver cancer (J5) cells were treated with SN. Our studies demonstrate that SN suppressed J5 cell viability by inducing autophagy. Phosphoinositide 3-kinase (PI3K)-I, mammalian target of rapamycin (mTOR) and Akt protein levels decreased, whereas PI3K-III, LC3-II and Beclin-1 protein levels increased following SN treatment in J5 cells. In addition, SN treatment upregulated nuclear p53 and damage-regulated autophagy modulator (DRAM) and downregulated cytosolic p53 and Tp53-induced glycolysis and apoptosis regulator (TIGAR) expression in J5 cells. Furthermore, the cytosolic phosphorylation of inhibitor of kappa B (IκB) and nuclear p65 and the DNA-binding activity of NF-κB increased after SN treatment. These results suggest that SN induces J5 cell autophagy by regulating PI3K, p53 and NF-κB autophagy-associated signaling pathways in J5 cells.

  7. Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver.

    PubMed

    Francis, Sheena; Laurieri, Nicola; Nwokocha, Chukwuemeka; Delgoda, Rupika

    2016-05-31

    The effect of apocynin on the activity of arylamine N-acetyltransferases (NATs) in excised liver samples was examined using eighteen Sprague-Dawley rats. Three groups of six animals each were fed a normal diet alone or a treatment of 50 or 100 mg/kg/day of apocynin via gavages for eight (8) weeks. Chronic in vivo administration of apocynin led to significant (p < 0.001) reduction of in vitro liver NAT activity up to 93% as compared with untreated rats (18.80 ± 2.10 μmols p-anisidine/min/μg liver protein). In vitro exposure of untreated liver homogenates to apocynin led to a dose-dependent inhibition of NAT activity with IC50 = 0.69 ± 0.02 mM. In silico modelling of apocynin tautomers and radical species into human NAT crystal structures supported the hypothesis that thiol functionalities in NAT enzymes may be crucial in apocynin binding. The involvement of human NAT enzymes in different pathological conditions, such as cancer, has encouraged the research for selective NAT inhibitors in both humans and animal models with possible chemopreventive properties.

  8. Pyogenic liver abscess as a warning sign for primary liver cancer: a nationwide population-based study.

    PubMed

    Huang, Wen-Kuan; Lin, Yung-Chang; Chiou, Meng-Jiun; Yang, Tsai-Sheng; Chang, John Wen-Cheng; Yu, Kuang-Hui; Kuo, Chang-Fu; See, Lai-Chu

    2013-01-01

    There have been no large-scale population-based studies to estimate the subsequent risk of primary liver cancer (PLC) among patients with pyogenic liver abscess (PLA). This study aimed to provide relevant data. The Taiwan Longitudinal Health Insurance Database for the years 2000 and 2005 was used. The PLA group were adult inpatients who were newly diagnosed with PLA from 2000 to 2008. The control group was randomly selected and matched with the PLA group in terms of age, sex, and date in which medical treatment was sought other than for PLA. There were 1,987 patients each in the PLA and control groups. In total, 56 had PLC, 48 (2.4%, 601.5 per 100,000 person-years) from the PLA group, and 8 from the control group. After adjusting for potential covariates, the hazard ratio of PLC for the PLA group was 3.4 times that of the control group (95% confidence interval = 1.6-7.3, p <0.001). The PLC risk for the PLA group was significantly higher within the first year after PLA diagnosis (hazard ratio: 35.4) as compared with the control group and became insignificant (hazard ratio: 2.0, 95% confidence interval = 0.8-4.9) more than one year after PLA diagnosis. Patients with PLA have a higher rate of PLC than matched controls, especially within the first year after the diagnosis of PLA, suggesting PLA is a warning sign for PLC.

  9. Liver schwannoma incidentally discovered in a patient with breast cancer.

    PubMed

    Akin, Murat; Bozkirli, Bahadir; Leventoglu, Sezai; Unal, Kemal; Kapucu, L Ozlem; Akyurek, Nalan; Sare, Mustafa

    2009-01-01

    Benign schwannomas, also referred to as neurilemomas, neurinomas, and perineural fibroblastomas, are encapsulated nerve sheath tumors. Primary schwannomas of the liver are extremely rare. We present a case of liver schwannoma, incidentally found in a patient with breast cancer. A 66-year-old female consulted her physician for a mass she palpated on her left breast. The abdominal ultrasonography (USG) revealed a 44 x 28 mm mass in the medial segment of the left lobe of her liver suspicious of a metastasis. An USG-guided biopsy was performed and the histo-pathological examination revealed a "peripheral nerve sheath tumor". Positron emission tomography (PET-CT) revealed a pathologic FDG uptake in the lesion that was previously defined in the liver. The tumor resected from the liver was 5 x 4 x 3 cm, yellowish, soft, and capsulated tumor. Microscopic examination revealed that the mass consisted of bundles of spindle cells with hypercellular and hypocellular areas. In immunohistochemistry, there was a strong positive staining for S-100. The tumor was diagnosed as benign liver schwannoma. Schwannomas are benign, encapsulated neoplasms. Symptoms and signs vary depending on the anatomical site and the size of the neoplasm; however, most schwannomas present as an asymptomatic or painless mass. Recurrence is unusual, despite of an incomplete removal, and malignant transformation is exceedingly rare (Fig. 4, Ref. 8). Full Text (Free, PDF) www.bmj.sk.

  10. A comparison of laparoscopic radiofrequency ablation versus systemic therapy alone in the treatment of breast cancer metastasis to the liver

    PubMed Central

    Taşçi, Yunus; Aksoy, Erol; Taşkın, Halit Eren; Aliyev, Shamil; Moore, Halle; Ağcaoğlu, Orhan; Birsen, Onur; Siperstein, Allan; Berber, Eren

    2013-01-01

    Objectives There is controversy about the roles of locoregional therapies in patients with liver metastases from breast cancer (LMBC). The aim of this study was to analyse survival after laparoscopic radiofrequency ablation (RFA) of LMBC and to compare this with survival in patients receiving systemic therapy (ST) alone. Methods During 1996–2011, 24 patients who had failed to respond or had shown an incomplete response to ST underwent laparoscopic RFA for LMBC. Outcomes in these patients were compared with those in 32 patients with LMBC matched by tumour size and number, but treated with ST alone. Clinical parameters and overall survival were compared using t-tests, chi-squared tests and Kaplan–Meier analysis. Results The groups were similar in hormone receptor status and chemotherapy exposure. In the laparoscopic RFA and ST groups, respectively, the mean ± standard deviation size of the dominant liver tumour and the number of tumours per patient were 3.7 ± 0.4 cm and 2.4 ± 0.4 cm, and 2.6 ± 0.4 tumours and 3.3 ± 0.4 tumours, respectively. These differences were not significant. At a median follow-up of 20 months in the laparoscopic RFA group, 42% of patients were found to have developed local liver recurrence, 63% had developed new liver disease and 38% had developed extrahepatic disease. Overall survival after the diagnosis of liver metastasis was 47 months in the laparoscopic RFA group and 9 months in the ST-only group (P = 0.0001). Five-year survival after the diagnosis of liver metastasis was 29% in the RFA group and 0% in the ST-only group. Conclusions This is the first study to compare outcomes in RFA and ST, respectively, in LMBC. The results show that survival after laparoscopic RFA plus ST is better than that after ST alone. PMID:24028270

  11. Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer.

    PubMed

    Khanal, Tilak; Choi, Kwangmin; Leung, Yuet-Kin; Wang, Jiang; Kim, Dasom; Janakiram, Vinothini; Cho, Sung-Gook; Puga, Alvaro; Ho, Shuk-Mei; Kim, Kyounghyun

    2017-09-06

    The aryl hydrocarbon receptor (AHR) plays crucial roles in inflammation, metabolic disorder, and cancer. However, the molecular mechanisms regulating AHR expression remain unknown. Here, we found that an orphan nuclear NR2E3 maintains AHR expression, and forms an active transcriptional complex with transcription factor Sp1 and coactivator GRIP1 in MCF-7 human breast and HepG2 liver cancer cell lines. NR2E3 loss promotes the recruitment of LSD1, a histone demethylase of histone 3 lysine 4 di-methylation (H3K4me2), to the AHR gene promoter region, resulting in repression of AHR expression. AHR expression and responsiveness along with H3K4me2 were significantly reduced in the livers of Nr2e3 rd7 (Rd7) mice that express low NR2E3 relative to the livers of wild-type mice. SP2509, an LSD1 inhibitor, fully restored AHR expression and H3K4me2 levels in Rd7 mice. Lastly, we demonstrated that both AHR and NR2E3 are significantly associated with good clinical outcomes in liver cancer. Together, our results reveal a novel link between NR2E3, AHR, and liver cancer via LSD1-mediated H3K4me2 histone modification in liver cancer development.

  12. The interaction of bacterial magnetosomes and human liver cancer cells in vitro

    NASA Astrophysics Data System (ADS)

    Wang, Pingping; Chen, Chuanfang; Chen, Changyou; Li, Yue; Pan, Weidong; Song, Tao

    2017-04-01

    As the biogenic magnetic nanomaterial, bacterial magnetic nanoparticles, namely magnetosomes, provide many advantages for potential biomedical applications. As such, interactions among magnetosomes and target cells should be elucidated to develop their bioapplications and evaluate their biocompatibilities. In this study, the interaction of magnetosomes and human liver cancer HepG2 cells was examined. Prussian blue staining revealed numerous stained particles in or on the cells. Intracellular iron concentrations, measured through inductively coupled plasma optical emission spectroscopy, increased with the increasing concentration of the magnetosomes. Transmission electron microscopy images showed that magnetosomes could be internalized in cells, mainly encapsulated in membrane vesicles, such as endosomes and lysosomes, and partly found as free particles in the cytosol. Some of the magnetosomes on cellular surfaces were encapsulated through cell membrane ruffling, which is the initiating process of endocytosis. Applying low temperature treatment and using specific endocytic inhibitors, we validated that macropinocytosis and clathrin-mediated endocytosis were involved in magnetosome uptake by HepG2 cells. Consequently, we revealed the interaction and intrinsic endocytic mechanisms of magnetosomes and HepG2 cells. This study provides a basis for the further research on bacterial magnetosome applications in liver diseases.

  13. Characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver: A report from the National Cancer Database.

    PubMed

    Shi, Yan; Rojas, Yesenia; Zhang, Wei; Beierle, Elizabeth A; Doski, John J; Goldfarb, Melanie; Goldin, Adam B; Gow, Kenneth W; Langer, Monica; Meyers, Rebecka L; Nuchtern, Jed G; Vasudevan, Sanjeev A

    2017-04-01

    To examine patient characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver (UESL) using a multi-institutional database. UESL is a rare disease (incidence is one per million). Therefore, the current literature is mostly limited to small case series. The National Cancer Database was queried for primary UESL diagnosed between 1998 and 2012. A total of 103 patients (<18 years) were identified. The 5-year overall survival of the entire group was 86%. The best outcomes were seen in children who had tumors smaller than 15 cm and were able to undergo surgical resection with or without chemotherapy. Margin status did not appear to significantly affect survival. The most common type of resection was hemihepatectomy (37%), followed by sectionectomy (10%) and trisectionectomy (10%). Orthotopic liver transplant was performed in 10 children, all of whom survived to 5 years. Surgical resection with or without chemotherapy should be the mainstay of treatment in children with UESL, and is associated with very favorable outcomes. Negative surgical margins were not associated with improved survival. Orthotopic liver transplantation may be a viable method of attaining local control in tumors, which would otherwise be unresectable. © 2016 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

  14. [Change in Perioperative Hemostatic Function in Patients Undergoing Hepatic Resection for Primary and Metastatic Liver Cancer].

    PubMed

    Komasawa, Nobuyasu; Ueki, Ryusuke; Atagi, Kazuaki; Nishi, Shinichi

    2015-08-01

    Patients undergoing primary hepatic resection often develop hemostatic dysfunction associated with cirrhosis. We retrospectively surveyed pre- and postoperative prothrombin time (PT) and the PT expressed as international normalized ratio (PT-INR) in 39 patients undergoing primary liver resection. We also compared PT changes between primary and metastatic cancer cases (8 cases). Postoperative PT-INR was 1.40 ± 0.38, which was significantly prolonged compared to preoperative PT-INR of 1.08 ± 0.07. Preoperative PT was over 70% in all 39 patients undergoing primary liver resection, whereas postoperative PT was less than 60% in 13 of 39 patients. No significant difference was found in preoperative PT-INR between primary and metastatic cancer cases, but postoperative PT-INR was significantly prolonged in primary cancer cases. Patients undergoing primary liver resection are susceptible to hemostatic dysfunction, even with preoperative PT levels within normal limits.

  15. Simultaneous resection for colorectal cancer with synchronous liver metastases is a safe procedure: Outcomes at a single center in Turkey.

    PubMed

    Dulundu, Ender; Attaallah, Wafi; Tilki, Metin; Yegen, Cumhur; Coskun, Safak; Coskun, Mumin; Erdim, Aylin; Tanrikulu, Eda; Yardimci, Samet; Gunal, Omer

    2017-05-23

    The optimal surgical strategy for treating colorectal cancer with synchronous liver metastases is subject to debate. The current study sought to evaluate the outcomes of simultaneous colorectal cancer and liver metastases resection in a single center. Prospectively collected data on all patients with synchronous colorectal liver metastases who underwent simultaneous resection with curative intent were analyzed retrospectively. Patient outcomes were compared depending on the primary tumor location and type of liver resection (major or minor). Between January 2005 and August 2016, 108 patients underwent simultaneous resection of primary colorectal cancer and liver metastases. The tumor was localized to the right side of the colon in 24 patients (22%), to the left side in 40 (37%), and to the rectum in 44 (41%). Perioperative mortality occurred in 3 patients (3%). Postoperative complications were noted in 32 patients (30%), and most of these complications (75%) were grade 1 to 3 according to the Clavien-Dindo classification. Neither perioperative mortality nor the rate of postoperative complications after simultaneous resection differed among patients with cancer of the right side of the colon, those with cancer of the left side of the colon, and those with rectal cancer (4%, 2.5%, and 2%, respectively, p = 0.89) and (17%, 33%, and 34%, respectively; p = 0.29)]. The 5-year overall survival of the entire sample was 54% and the 3-year overall survival was 67 %. In conclusion, simultaneous resection for primary colorectal cancer and liver metastases is a safe procedure and can be performed without excess morbidity in carefully selected patients regardless of the location of the primary tumor and type of hepatectomy.

  16. Risk of liver cancer and exposure to organic solvents and gasoline vapors among Finnish workers.

    PubMed

    Lindbohm, Marja-Liisa; Sallmén, Markku; Kyyrönen, Pentti; Kauppinen, Timo; Pukkala, Eero

    2009-06-15

    We investigated the association between exposure to various groups of solvents and gasoline vapors and liver cancer. A cohort of economically active Finns born between 1906 and 1945 was followed up during the period 1971-1995. The incident cases of primary liver cancer (n = 2474) were identified in a record linkage with the Finnish Cancer Registry. Occupations from the 1970 census were converted to exposures using a job-exposure matrix. Cumulative exposure was calculated as the product of estimated prevalence, level and duration of exposure, and we used Poisson regression to calculate the relative risks (RR). Among the occupations entailing exposure to organic solvents, an elevated liver cancer incidence was observed in male printers, and varnishers and lacquerers. Among men, the risk was increased in the highest exposure category of aromatic hydrocarbons [RR 1.77, 95% confidence interval (CI) 1.30-2.40], aliphatic/alicyclic hydrocarbons (RR 1.47, 95% CI 0.99-2.18), chlorinated hydrocarbons (RR 2.65, 95% CI 1.38-5.11) and "other solvents" (RR 2.14, 95% CI 1.23-3.71). Among women, the risk was increased for the group "other solvents" that includes mainly alcohols, ketones, esters and glycol ethers (RR 2.73, 95% CI 1.21-6.16). Our finding of an increased risk among workers exposed to chlorinated hydrocarbons is in line with several earlier studies on trichloroethylene. The results also suggest a link between exposure to other types of solvents and the risk of liver cancer. The possibility that alcohol consumption contributes to the observed risks cannot be totally excluded. Copyright 2008 UICC.

  17. Cancer Treatment-Related Cardiotoxicity

    Cancer.gov

    Cancer Treatment-Related Cardiotoxicity includes efforts to identify individual toxicity risks and prevention strategies support the National Cancer Insitute's goal of reducing the burden of cancer diagnoses and treatment outcomes.

  18. Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer.

    PubMed

    Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

    2009-07-08

    Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC). The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC. A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials. Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival. Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases. Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24). Currently

  19. Co-existence of Echinococcus granulosus infection and cancer metastasis in the liver correlates with reduced Th1 immune responses.

    PubMed

    Turhan, N; Esendagli, G; Ozkayar, O; Tunali, G; Sokmensuer, C; Abbasoglu, O

    2015-01-01

    A possible relationship between cancer and Echinococcus granulosus infection has been postulated. As T cells are critical players in immune responses against both infections and malignancies, in an experimental model of secondary echinococcosis and breast cancer, this study aims to observe the progression of cancer and to determine the characters of T-cell responses. 4T1 breast tumour cells were subcutaneously injected into mammary region, whereas protoscoleces were intraperitoneally inoculated into the mice. Hydatid cysts, tumours and metastases were determined with macroscopic and histopathological evaluation. T cells found in spleen, liver and tumour were characterised by flow cytometric analysis of CD3, CD4, CD8, CD25, CCR5, CCR3, IL-4 and IFN-γ. In the mice inoculated both with protoscoleces and with breast tumour cells, increased frequency of cancer metastasis was observed in the liver. The amount of CD4(+) T cells was increased in the liver and in the spleen of mice infected with E. granulosus. However, co-existence of echinococcosis and metastatic lesions in the liver was associated with significant reduction in the IFN-γ(+) and CCR5(+) Th1 cells and increase in the CD25(+) T cells. Our results may indicate an immunological link between cystic echinococcosis and cancer that allows tumour metastasis to flourish in the liver. © 2014 John Wiley & Sons Ltd.

  20. Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles: in vitro liver cancer model

    NASA Astrophysics Data System (ADS)

    Loutfy, Samah A.; Alam El-Din, Hanaa M.; Elberry, Mostafa H.; Allam, Nanis G.; Hasanin, M. T. M.; Abdellah, Ahmed M.

    2016-09-01

    To evaluate the cytotoxic effect of chitosan nanoparticles (CS-NPs) on an in vitro human liver cancer cell model (HepG2) and their possible application as a drug delivery system, we synthesized water-soluble CS-NPs, investigated their properties and extensively evaluated their cytotoxic activity on the cellular and molecular levels. A human liver cancer cell line was used as a model of human liver cancer. The CS-NPs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta analysis. The cytotoxic effects of the CS-NPs on HepG2 cells were monitored by sulforhodamine B colorimetric assays for cytotoxicity screening and flow cytometric analysis. Molecular investigations including DNA fragmentation and the expression of some apoptotic genes on the transcriptional RNA level were conducted. Treatment of HepG2 with different concentrations of 150 nm diameter CS-NPs did not show alteration of cell morphology after 24 h of cell exposure. Also, when cells were treated with 100 μg ml-1 of CS-NPs, 12% of them were killed and IC50 reached 239 μg ml-1 after 48 h of cell exposure. Flow cytometry evaluation of the CS-NPs revealed mild accumulation in the G2/M phase followed by cellular DNA fragmentation after 48 h of cell exposure. Extensive evaluation of the cytotoxic effect of the CS-NPs showed messenger RNA (mRNA) apoptotic gene expression (p53, Bak, Caspase3) after 24 h of cell exposure with no expression of the mRNA of the caspase 3 gene after 48 h of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway by increasing the exposure time of 100 μg ml-1 of the CS-NPs. The engineered CS-NPs were controlled to a 150 nm size and charges of 40 mV and a concentration of 100 μg ml-1 revealed a genotoxic effect on HepG2 after 48 h of cell exposure through intrinsic apoptotic caspase-independent mechanisms. Further quantitative analysis on the molecular and protein levels is still required