Science.gov

Sample records for liver cancer importance

  1. Liver Cancer

    MedlinePlus

    ... body digest food, store energy, and remove poisons. Primary liver cancer starts in the liver. Metastatic liver ... and spreads to your liver. Risk factors for primary liver cancer include Having hepatitis B or C ...

  2. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

  3. What Is Liver Cancer?

    MedlinePlus

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  4. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  5. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  6. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... Liver cancer is not common in the United States. Liver cancer is the fourth most common cancer and the third leading cause of cancer death in the world. In the United States, men, especially Chinese American men, have an increased ...

  7. Lipids changes in liver cancer*

    PubMed Central

    Jiang, Jing-ting; Xu, Ning; Zhang, Xiao-ying; Wu, Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism. Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver. It depends on the integrity of liver cellular function, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs, these processes are impaired and the plasma lipid and lipoprotein patterns may be changed. Liver cancer is the fifth common malignant tumor worldwide, and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV). HBV and HCV infections are quite common in China and other Southeast Asian countries. In addition, liver cancer is often followed by a procession of chronic hepatitis or cirrhosis, so that hepatic function is damaged obviously on these bases, which may significantly influence lipid and lipoprotein metabolism in vivo. In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer. PMID:17565510

  8. Liver (Hepatocellular) Cancer Screening

    MedlinePlus

    ... United States than in other parts of the world. Liver cancer is uncommon in the United States, ... is the fourth most common cancer in the world. In the United States, men, especially Chinese American ...

  9. Oral contraceptives and liver cancer.

    PubMed

    1997-11-01

    To date, nine case-control studies conducted in developed countries have identified an association between oral contraceptives (OCs) and liver cancer. The most recent population-based data from both developed and developing countries failed to confirm such an association, however. A study conducted by the World Health Organization in eight developing countries (Chile, China, Colombia, Israel, Kenya, Nigeria, Philippines, and Thailand), in which 122 women with liver cancer were matched with 802 controls, found no elevated risk for OC users compared with never-users (relative risk, 0.7; 95% confidence interval, 0.4-1.2). This study is particularly significant since it was conducted in countries where hepatitis B virus infection, an important risk factor for primary liver cancer, is widespread. In addition, population mortality data from the US, UK, Japan, and Sweden have failed to document increases in liver cancer cases coincident with increases in OC use. Given that population statistics can detect changes on the magnitude of a 40-50% decrease in the risk of ovarian and endometrial cancer related to OC use, they should be able to detect increases of two to 20 times the risk of liver cancer. The increased risk of liver cancer found in the case-control studies may reflect bias resulting from the small size of these studies. PMID:12348250

  10. Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells.

    PubMed

    Wang, Ronghua; Sun, Qian; Wang, Peng; Liu, Man; Xiong, Si; Luo, Jing; Huang, Hai; Du, Qiang; Geller, David A; Cheng, Bin

    2016-02-01

    Human hepatocellular carcinoma (HCC) is driven and maintained by liver cancer stem cells (LCSCs) that display stem cell properties. These LCSCs are promoted by the intersecting of Notch and Wnt/β-Catenin signaling pathways. In this study, we demonstrate that LCSCs with markers CD90, CD24, CD13, and CD133 possess stem properties of self-renewal and tumorigenicity in NOD/SCID mice. The increased expression of these markers was correlated with advanced disease stage, larger tumors, and worse overall survival in 61 HCC cases. We also found that both Notch and Wnt/β-catenin signaling pathways played important roles in increasing the stem-ness characteristics of LCSCs. Our data suggested that Notch1 was downstream of Wnt/β-catenin. The active form of Notch1 intracellular domain (NICD) expression depended on Wnt/β-catenin pathway activation. Moreover, Notch1 negatively contributed to Wnt/β-catenin signaling modulation. Knock down of Notch1 with lentivirus N1ShRNA up-regulated the active form of β-catenin. Ectopic expression of NICD with LV-Notch1 in LCSCs attenuated β-catenin/TCF dependent luciferase activity significantly. In addition, there was a non-proteasome mediated feedback loop between Notch1 and Wnt/β-catenin signaling in LCSCs. The central role of Notch and the Wnt/β-catenin signaling pathway in LCSCs may provide an attractive therapeutic strategy against HCC. PMID:26735577

  11. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  12. Proteoglycans in liver cancer.

    PubMed

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  13. Proteoglycans in liver cancer

    PubMed Central

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  14. Glycosylation and Liver Cancer

    PubMed Central

    Mehta, Anand; Herrera, Harmin; Block, Timothy

    2015-01-01

    Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development. PMID:25727150

  15. 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.

  16. 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)

  17. Microcirculation of liver cancer, microenvironment of liver regeneration, and the strategy of Chinese medicine.

    PubMed

    Li, Han-min

    2016-03-01

    Microcirculation of liver cancer is the micro-vascular system which comes from the tissue of liver cancer. It can offer the nutritional requirement for accelerating the cancer cell proliferation and metastasis. The intrinsic mechanism of angiogenesis is the key link in the formation of liver cancer microcirculation system. Liver regeneration microenvironment also plays an important role in the construction of liver cancer microcirculation, through the improvement of liver regeneration microenvironment affecting tumor microcirculation is the new strategy of prevention and treatment of liver cancer. In recent years, it is found that many kinds of Chinese medicine can inhibit angiogenesis, decrease the microvessel density, and delay or prevent the development of liver cancer. PMID:26919996

  18. Ganetespib radiosensitization for liver cancer therapy

    PubMed Central

    Chettiar, Sivarajan T.; Malek, Reem; Annadanam, Anvesh; Nugent, Katriana M.; Kato, Yoshinori; Wang, Hailun; Cades, Jessica A.; Taparra, Kekoa; Belcaid, Zineb; Ballew, Matthew; Manmiller, Sarah; Proia, David; Lim, Michael; Anders, Robert A.; Herman, Joseph M.; Tran, Phuoc T.

    2016-01-01

    ABSTRACT Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33–1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies. PMID:26980196

  19. Percutaneous Cryoablation for Liver Cancer

    PubMed Central

    Niu, Li-Zhi; Li, Jia-Liang; Xu, Ke-Cheng

    2014-01-01

    Based on the primary tumor site, liver cancer can be divided into two categories: (1) primary liver cancer and (2) metastatic cancer to the liver from a distant primary site. Guided cryoablation via many imaging methods induces iceball formation and tumor necrosisand is an attractive option for treating unresectable hepatocellular carcinoma (HCC) and metastatic liver cancer. There are several advantages to using cryoablation for the treatment of liver cancer: it can be performed percutaneously, intraoperatively, and laparoscopically; iceball formation can be monitored; it has little impact on nearby large blood vessels; and it induces a cryo-immunological response in situ. Clinically, primary research has shown that percutaneous cryoablation of liver cancer is relatively safe and efficient, and it can be combined with other methods, such as radiation therapy, chemotherapy, and immunology, to control disease. Although research is preliminary, cryosurgery is fast becoming an alternative treatment method for HCC or liver tumors. Here, we review the mechanisms of liver tumor cryoablation, cryoablation program selection, clinical efficiency, and complications following treatment. PMID:26355719

  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. 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.

  2. Imaging of liver cancer

    PubMed Central

    Ariff, Ben; Lloyd, Claire R; Khan, Sameer; Shariff, Mohamed; Thillainayagam, Andrew V; Bansi, Devinder S; Khan, Shahid A; Taylor-Robinson, Simon D; Lim, Adrian KP

    2009-01-01

    Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identification and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality. PMID:19294758

  3. Liver Metastases in Colorectal Cancer.

    PubMed

    Folprecht, Gunnar

    2016-01-01

    Resection of colorectal liver metastases is a treatment standard because patients experience long-term disease-free survival or are even cured after undergoing this procedure. Improved surgical techniques for liver resection in combination with downsizing liver metastases by chemotherapy, interventions to induce liver hypertrophy before resection, and the use of ablative techniques have allowed us to expand the indications for liver surgery and local treatment in situations with limited metastatic colorectal cancer. Resectability and identification of patients who might benefit from liver surgery and local ablative techniques are key factors for the treatment of patients with colorectal cancer. Despite the wide acceptance of liver surgery and ablative techniques, there are many open questions on the management of limited metastatic disease, such as which patients benefit from an aggressive surgical approach, what the indications for ablative and other local techniques are, and what the role of chemotherapy is for patients with resectable or resected disease. Unfortunately, results of randomized trials are only available for a limited number of these questions. PMID:27249722

  4. General Information about Adult Primary Liver Cancer

    MedlinePlus

    ... Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. General Information about Childhood Liver Cancer

    MedlinePlus

    ... Childhood Liver Cancer Treatment (PDQ®)–Patient Version General Information About Childhood Liver Cancer Go to Health Professional ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  6. Liver cancer oncogenomics: opportunities and dilemmas for clinical applications

    PubMed Central

    Marquardt, Jens U; Andersen, Jesper B

    2015-01-01

    SUMMARY Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches. Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could contribute to new therapeutic approaches. Importantly, these investigations indicate that a classical oncogene addiction cannot be assumed for primary liver cancer. Therefore, hepatocarcinogenesis can be considered a paradigm suitable for individualized medicine. PMID:26257864

  7. 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...

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

    ClinicalTrials.gov

    2016-03-01

    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

  9. Liver cancer stem cell markers: Progression and therapeutic implications.

    PubMed

    Sun, Jing-Hui; Luo, Qing; Liu, Ling-Ling; Song, Guan-Bin

    2016-04-01

    Cancer stem cells (CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets. PMID:27053846

  10. Liver cancer stem cell markers: Progression and therapeutic implications

    PubMed Central

    Sun, Jing-Hui; Luo, Qing; Liu, Ling-Ling; Song, Guan-Bin

    2016-01-01

    Cancer stem cells (CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets. PMID:27053846

  11. Zebrafish: An Important Tool for Liver Disease Research

    PubMed Central

    Goessling, Wolfram; Sadler, Kirsten C.

    2016-01-01

    As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

  12. 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. PMID:25977189

  13. 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.

  14. Risks of Liver (Hepatocellular) Cancer Screening

    MedlinePlus

    ... United States than in other parts of the world. Liver cancer is uncommon in the United States, ... is the fourth most common cancer in the world. In the United States, men, especially Chinese American ...

  15. De Novo Gastric Cancer After Liver Transplantation.

    PubMed

    Gong, Chung-Sik; Yoo, Moon-Won; Kim, Beom-Su; Hwang, Shin; Kim, Ki-Hun; Yook, Jeong-Hwan; Kim, Byung-Sik; Lee, Sung-Gyu

    2016-01-01

    BACKGROUND In South Korea, which has a high incidence of gastric cancer, the most common de novo malignancy associated with liver transplantation is gastric cancer. This study sought to identify clinicopathologic characteristics in gastric cancer patients after liver transplantation, and to help manage these cases. MATERIAL AND METHODS We investigated gastric cancer patients after liver transplantation at Asan Medical Center. We analyzed sex, age, cause of liver transplantation, initiating immunosuppressant, pre-transplantation gastric fibroscopy findings, time interval between transplantation and gastric cancer occurrence, follow-up period, existence of gastric cancer screening, Helicobacter pylori infection, family cancer history, gastric cancer treatment, cancer location, size of tumor, macroscopic gross type, WHO histologic type, Lauren's classification, TNM stage, and survival. RESULTS Of 2968 adult liver transplantation patients at our hospital, 19 were diagnosed with gastric cancer. The mean age at the time of gastric cancer diagnosis was 60.2±6.8 (46-71) years and mean time interval between liver transplantation and diagnosis of gastric cancer was 56.0±30.7 (3.20-113) months. Endoscopic submucosal dissection was done for 10 patients, 4 of whom underwent surgical resection. Surgical resection as an initial treatment was done in 8 patients. One patient received chemotherapy first. The standard incidence ratio of gastric cancer in these patients was 1036 per 100 000 persons (95% CI, 623.7-1,619) in men and 318.9 per 100 000 (95% CI, 4.170-1,774) in women. CONCLUSIONS For long-term survival of liver transplant patients, early detection of de novo cancer is necessary. Therefore, annual screening for gastric cancer after liver transplantation is needed, especially in areas where the incidence of gastric cancer is high, such as South Korea. PMID:27334929

  16. Mouse models for liver cancer.

    PubMed

    Bakiri, Latifa; Wagner, Erwin F

    2013-04-01

    Hepatocellular carcinoma (HCC), the most common form of primary liver cancer is the third leading cause of cancer-related cell death in human and the fifth in women worldwide. The incidence of HCC is increasing despite progress in identifying risk factors, understanding disease etiology and developing anti-viral strategies. Therapeutic options are limited and survival after diagnosis is poor. Therefore, better preventive, diagnostic and therapeutic tools are urgently needed, in particular given the increased contribution from systemic metabolic disease to HCC incidence worldwide. In the last three decades, technological advances have facilitated the generation of genetically engineered mouse models (GEMMs) to mimic the alterations frequently observed in human cancers or to conduct intervention studies and assess the relevance of candidate gene networks in tumor establishment, progression and maintenance. Because these studies allow molecular and cellular manipulations impossible to perform in patients, GEMMs have improved our understanding of this complex disease and represent a source of great potential for mechanism-based therapy development. In this review, we provide an overview of the current state of HCC modeling in the mouse, highlighting successes, current challenges and future opportunities. PMID:23428636

  17. 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

  18. 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.

  19. Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer

    ClinicalTrials.gov

    2015-04-08

    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

  20. Heterogeneity of liver cancer and personalized therapy.

    PubMed

    Li, Liang; Wang, Hongyang

    2016-09-01

    Liver cancer is an extraordinarily heterogeneous malignant disease among the tumors that have so far been identified. Hepatocellular carcinoma (HCC) arises most frequently in the setting of chronic liver inflammation and fibrosis, and takes a variety of course in individual patients to process to tumor. The risk factors such as HBV and/or HCV infections, aflatoxin infection, abuse alcohol intake, metabolic syndrome, obesity and diabetes are closely related to the environmental and genetic susceptibilities to HCC. The consequent resulting genomic instability, molecular and signal transduction network disorders and microenvironmental discrepancies are characterized by the extraordinary heterogeneity of liver cancer. The histology-based definition of the morphological heterogeneity of liver cancer has been modified and refined to treat patients with targeted therapies, but this still cannot solve all the problems. Lack of consistent outcome for anticancer agents and conventional therapies in liver cancer treatment calls for assessing the benefits of new molecularly targeted drugs and combined therapy, under the heterogeneity condition of tumor. The present review article will provide the complex mechanism and phenotype of liver cancer heterogeneity, and help us to execute precision medicine in a really personalized manner. PMID:26213370

  1. Lung, liver and bone cancer mortality in Mayak workers

    PubMed Central

    Sokolnikov, Mikhail E.; Gilbert, Ethel S.; Preston, Dale L.; Ron, Elaine; Shilnikova, Natalia S.; Khokhryakov, Victor V.; Vasilenko, Evgeny K.; Koshurnikova, Nina A.

    2014-01-01

    Workers at the Mayak nuclear facility in the Russian Federation offer the only adequate human data for evaluating cancer risks from exposure to plutonium. Risks of mortality from cancers of the lung, liver and bone, the organs receiving the largest doses from plutonium, were evaluated in a cohort of 17,740 workers initially hired 1948–1972 using, for the first time, recently improved individual organ dose estimates. Excess relative risk (ERR) models were used to evaluate risks as functions of internal (plutonium) dose, external (primarily gamma) dose, gender, attained age and smoking. By December 31, 2003, 681 lung cancer deaths, 75 liver cancer deaths and 30 bone cancer deaths had occurred. Of these 786 deaths, 239 (30%) were attributed to plutonium exposure. Significant plutonium dose-response relationships (p < 0.001) were observed for all 3 endpoints, with lung and liver cancer risks reasonably described by linear functions. At attained age 60, the ERRs per Gy for lung cancer were 7.1 for males and 15 for females; the averaged-attained age ERRs for liver cancer were 2.6 and 29 for males and females, respectively; those for bone cancer were 0.76 and 3.4. This study is the first to present and compare dose-response analyses for cancers of all 3 organs. The unique Mayak cohort with its high exposures and well characterized doses has allowed quantification of the plutonium dose-response for lung, liver and bone cancer risks based on direct human data. These results will play an important role in plutonium risk assessment. PMID:18528867

  2. Characteristics of liver cancer stem cells and clinical correlations.

    PubMed

    Cheng, Zhuo; Li, Xiaofeng; Ding, Jin

    2016-09-01

    Liver cancer is an aggressive malignant disease with a poor prognosis. Patients with liver cancer are usually diagnosed at an advanced stage and thus miss the opportunity for surgical resection. Chemotherapy and radiofrequency ablation, which target tumor bulk, have exhibited limited therapeutic efficacy to date. Liver cancer stem cells (CSCs) are a small subset of undifferentiated cells existed in liver cancer, which are considered to be responsible for liver cancer initiation, metastasis, relapse and chemoresistance. Elucidating liver CSC characteristics and disclosing their regulatory mechanism might not only deepen our understanding of the pathogenesis of liver cancer but also facilitate the development of diagnostic, prognostic and therapeutic approaches to improve the clinical management of liver cancer. In this review, we will summarize the recent advances in liver CSC research in terms of the origin, identification, regulation and clinical correlation. PMID:26272183

  3. Targeted treatment of liver metastasis from gastric cancer using specific binding peptide

    PubMed Central

    Gong, Jianfeng; Tan, Gewen; Sheng, Nengquan; You, Weiqiang; Wang, Zhigang

    2016-01-01

    Gastric cancer ranks the first in China among all gastrointestinal cancers in terms of incidence, and liver metastasis is the leading cause of death for patients with advanced gastric cancer. Tumor necrosis factor (TNF) is a cytokine commonly chosen as the target for gene therapy against cancers. The specific binding peptide pd20 of gastric cancer cells with a high potential for liver metastasis was fused with human TNF to obtain the pd20-TNF gene using DNA recombinant technique. The expression of the fusion protein was induced and the protein was purified. In vitro activity test showed that the fusion protein greatly improved the membrane permeability of liver cells in nude mice with liver metastasis from gastric cancer. The tumor implantation experiment in nude mice showed that the fusion protein effectively mitigated the cancer lesions. The results provide important clues for developing the drugs for targeted treatment of liver metastasis from gastric cancer. PMID:27347305

  4. What Should You Ask Your Doctor about Liver Cancer?

    MedlinePlus

    ... survivor What should you ask your health care team about liver cancer? As you cope with liver ... have honest, open discussions with your cancer care team . Ask any question, no matter how small it ...

  5. What's New in Liver Cancer Research and Treatment?

    MedlinePlus

    ... Next Topic Additional resources for liver cancer What`s new in liver cancer research and treatment? Because there ... being made in treating chronic hepatitis. Screening Several new blood tests are being studied to see if ...

  6. How important is donor age in liver transplantation?

    PubMed

    Lué, Alberto; Solanas, Estela; Baptista, Pedro; Lorente, Sara; Araiz, Juan J; Garcia-Gil, Agustin; Serrano, M Trinidad

    2016-06-01

    The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation (LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed. PMID:27275089

  7. How important is donor age in liver transplantation?

    PubMed Central

    Lué, Alberto; Solanas, Estela; Baptista, Pedro; Lorente, Sara; Araiz, Juan J; Garcia-Gil, Agustin; Serrano, M Trinidad

    2016-01-01

    The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation (LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed. PMID:27275089

  8. The Geographic Distribution of Liver Cancer in Canada Does Not Associate with Cyanobacterial Toxin Exposure

    PubMed Central

    Labine, Meaghan A.; Green, Chris; Mak, Giselle; Xue, Lin; Nowatzki, Janet; Griffith, Jane; Minuk, Gerald Y.

    2015-01-01

    Background: The incidence of liver cancer has been increasing in Canada over the past decade, as has cyanobacterial contamination of Canadian freshwater lakes and drinking water sources. Cyanotoxins released by cyanobacteria have been implicated in the pathogenesis of liver cancer. Objective: To determine whether a geographic association exists between liver cancer and surrogate markers of cyanobacterial contamination of freshwater lakes in Canada. Methods: A negative binomial regression model was employed based on previously identified risk factors for liver cancer. Results: No association existed between the geographic distribution of liver cancer and surrogate markers of cyanobacterial contamination. As predicted, significant associations existed in areas with a high prevalence of hepatitis B virus infection, large immigrant populations and urban residences. Discussion and Conclusions: The results of this study suggest that cyanobacterial contamination of freshwater lakes does not play an important role in the increasing incidence of liver cancer in Canada. PMID:26633441

  9. Multisciplinary management of patients with liver metastasis from colorectal cancer

    PubMed Central

    De Greef, Kathleen; Rolfo, Christian; Russo, Antonio; Chapelle, Thiery; Bronte, Giuseppe; Passiglia, Francesco; Coelho, Andreia; Papadimitriou, Konstantinos; Peeters, Marc

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent (25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twenty-thirty per cent (20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to resectable to achieve cure. Since those results were published, a lot of regimens have been studied for resectability potential. Better results could be obtained by the combination of chemotherapy with targeted drugs, such as anti-VEGF and anti-EGFR monoclonal antibodies. However an accurate selection for patients to treat with these regimens and to operate for liver metastases is mandatory to reduce the risk of complications. A multidisciplinary team approach represents the best way for a proper patient management. The team needs to include surgeons, oncologists, diagnostic and interventional radiologists with expertise in hepatobiliary disease, molecular pathologists, and clinical nurse specialists. This review summarizes the most important findings on surgery and systemic treatment of CRC-related liver metastases. PMID:27621569

  10. Multisciplinary management of patients with liver metastasis from colorectal cancer.

    PubMed

    De Greef, Kathleen; Rolfo, Christian; Russo, Antonio; Chapelle, Thiery; Bronte, Giuseppe; Passiglia, Francesco; Coelho, Andreia; Papadimitriou, Konstantinos; Peeters, Marc

    2016-08-28

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent (25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twenty-thirty per cent (20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to resectable to achieve cure. Since those results were published, a lot of regimens have been studied for resectability potential. Better results could be obtained by the combination of chemotherapy with targeted drugs, such as anti-VEGF and anti-EGFR monoclonal antibodies. However an accurate selection for patients to treat with these regimens and to operate for liver metastases is mandatory to reduce the risk of complications. A multidisciplinary team approach represents the best way for a proper patient management. The team needs to include surgeons, oncologists, diagnostic and interventional radiologists with expertise in hepatobiliary disease, molecular pathologists, and clinical nurse specialists. This review summarizes the most important findings on surgery and systemic treatment of CRC-related liver metastases. PMID:27621569

  11. 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

  12. Liver Colonization Competence Governs Colon Cancer Metastasis

    NASA Astrophysics Data System (ADS)

    Kuo, Tsong-Hong; Kubota, Tetsuro; Watanabe, Masahiko; Furukawa, Toshiharu; Teramoto, Tatuso; Ishibiki, Kyuya; Kitajima, Masaki; Rahim Moosa, A.; Penman, Sheldon; Hoffman, Robert M.

    1995-12-01

    Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, >100 years ago, formulated his seed and soil hypothesis; i.e., the cells from a given tumor would "seed" only favorable "soil" offered by certain organs. The hypothesis implies that cancer cells must find a suitable "soil" in a target organ-i.e., one that supports colonization-for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behavior of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver. Both classes of tumors were equally invasive locally into tissues and blood vessels. However, the cells from each class of tumor behave very differently when directly injected into nude mouse livers. Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection. Also, tissue blocks from metastatic tumors affixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself. Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis. The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.

  13. 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

  14. Radio Frequency Ablation for Primary Liver Cancer

    PubMed Central

    2004-01-01

    Executive Summary Objective The Medical Advisory Secretariat undertook a review of the evidence on the safety, clinical effectiveness, and cost-effectiveness of radio frequency ablation (RFA) compared with other treatments for unresectable hepatocellular carcinoma (HCC) in Ontario. Background Liver cancer is the fifth most common type of cancer globally, although it is most prevalent in Asia and Africa. The incidence of liver cancer has been increasing in the Western world, primarily because of an increased prevalence of hepatitis B and C. Data from Cancer Care Ontario from 1998 to 2002 suggest that the age-adjusted incidence of liver cancer in men rose slightly from 4.5 cases to 5.4 cases per 100,000 men. For women, the rates declined slightly, from 1.8 cases to 1.4 cases per 100,000 women during the same period. Most people who present with symptoms of liver cancer have a progressive form of the disease. The rates of survival in untreated patients in the early stage of the disease range from 50% to 82% at 1 year and 26% to 32% at 2 years. Patients with more advanced stages have survival rates ranging from 0% to 36% at 3 years. Surgical resection and transplantation are the procedures that have the best prognoses; however, only 15% to 20% of patients presenting with liver cancer are eligible for surgery. Resection is associated with a 50% survival rate at 5 years. The Technology: Radio Frequency Ablation RFA is a relatively new technique for the treatment of small liver cancers that cannot be treated with surgery. This technique applies alternating high-frequency electrical currents to the cancerous tissue. The intense heat leads to thermal coagulation that can kill the tumour. RFA is done under general or local anesthesia and can be done percutaneously (through the skin with a small needle), laparoscopically (microinvasively, using a small video camera), or intraoperatively. Percutaneous RFA is usually a day procedure. Methods The leading international

  15. Imaging and IGRT in Liver Cancer

    PubMed Central

    Brock, Kristy K.

    2012-01-01

    Imaging for radiation therapy treatment planning and delivery is a critical component of the radiation planning process for liver cancer. Due to the lack of inherent contrast between liver tumors and the surrounding liver, intravenous contrast is required for accurate target delineation on the planning CT. The appropriate phase of contrast is tumor specific, with arterial phase imaging usually used to define hepatocellular carcinoma, and venous phase imaging for vascular thrombosis related to hepatocellular carcinoma and most types of liver metastases. Breathing motion and changes in the liver position day-to-day may be substantial and need to be considered at the time of radiation planning and treatment. Many types of integrated imaging-radiation treatment systems and image guidance strategies are available to produce volumetric and/or planar imaging at the time of treatment delivery to reduce the negative impact of geometric changes that may occur. Image guided radiation therapy (IGRT) can improve the precision of radiation therapy, so that the prescribed doses are more likely to represent those actually delivered. PMID:21939853

  16. 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

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

    ClinicalTrials.gov

    2014-12-18

    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. Activins and follistatins: Emerging roles in liver physiology and cancer

    PubMed Central

    Kreidl, Emanuel; Öztürk, Deniz; Metzner, Thomas; Berger, Walter; Grusch, Michael

    2009-01-01

    Activins are secreted proteins belonging to the TGF-β family of signaling molecules. Activin signals are crucial for differentiation and regulation of cell proliferation and apoptosis in multiple tissues. Signal transduction by activins relies mainly on the Smad pathway, although the importance of crosstalk with additional pathways is increasingly being recognized. Activin signals are kept in balance by antagonists at multiple levels of the signaling cascade. Among these, follistatin and FLRG, two members of the emerging family of follistatin-like proteins, can bind secreted activins with high affinity, thereby blocking their access to cell surface-anchored activin receptors. In the liver, activin A is a major negative regulator of hepatocyte proliferation and can induce apoptosis. The functions of other activins expressed by hepatocytes have yet to be more clearly defined. Deregulated expression of activins and follistatin has been implicated in hepatic diseases including inflammation, fibrosis, liver failure and primary cancer. In particular, increased follistatin levels have been found in the circulation and in the tumor tissue of patients suffering from hepatocellular carcinoma as well as in animal models of liver cancer. It has been argued that up-regulation of follistatin protects neoplastic hepatocytes from activin-mediated growth inhibition and apoptosis. The use of follistatin as biomarker for liver tumor development is impeded, however, due to the presence of elevated follistatin levels already during preceding stages of liver disease. The current article summarizes our evolving understanding of the multi-faceted activities of activins and follistatins in liver physiology and cancer. PMID:21160961

  19. Surgical treatment of double primary liver cancer

    PubMed Central

    Li, Aijun; Ma, Senlin; Pawlik, Timothy; Wu, Bin; Yang, Xiaoyu; Cui, Longjiu; Wu, Mengchao

    2016-01-01

    Abstract Double primary liver cancer (DPLC) is a special type of clinical situation. As such, a detailed analysis of the surgical management and prognosis of patients with DPLC is lacking. The objective of the current study was to define the management and outcome of patients undergoing surgery for DPLC at a major hepatobiliary center. A total of 87 patients treated by surgical resection at the Eastern Hepatobiliary Surgery Hospital from January 1st, 2007 to October 31st, 2013 who had DPLC demonstrated by final pathological diagnosis were identified. Among these, 50 patients had complete clinical and prognostic data. Demographic and tumor characteristics as well as the prognosis were analyzed. The proportion of hepatitis B surface antigen (HBsAg) (+) and hepatitis B virus e antigen (HBeAg) (+), HBsAg (+), and HBeAg (−) hepatocirrhosis in all patients was 21.84%, 67.82%, and 63.22%, respectively. Incidental findings accounted for 58.62% of patients; among those who had symptoms, the main symptom was abdominal pain (31.03%). Nonanatomic wedge resection was the main operative approach (62.07%). Postoperatively, the main complications included seroperitoneum (11.49%), hypoproteinemia (10.34%), and pleural effusion (8.05%). Factors associated with disease-free survival (DFS) included intrahepatic cholangiocarcinoma (ICC) tumor size (P = 0.002) and use of postoperative prophylactic transcatheter arterial chemoembolization (TACE) treatment (P = 0.015). Meanwhile, hepatocellular carcinoma (HCC) size (P = 0.045), ICC size (P < 0.001), and liver function (including aspartate aminotransferase [P = 0.001] and r-glutamyl transferase [P < 0.001]) were associated with overall survival (OS). Hepatitis B virus (HBV)-related hepatitis or cirrhosis is also an important factor in the pathogenesis of DPLC and surgical treatment is safe for it with low complication rates. In addition, it is effective to prolong DFS that DPLC patients undergo postoperative

  20. Surgery for Liver Metastases From Gastric Cancer

    PubMed Central

    Martella, Luca; Bertozzi, Serena; Londero, Ambrogio P.; Steffan, Agostino; De Paoli, Paolo; Bertola, Giulio

    2015-01-01

    Abstract The role of surgical therapy in patients with liver metastases from gastric cancer is still controversial. In this study, we investigated the results obtained with local treatment of hepatic metastases in patients with gastric cancer, by performing a systematic literature review and meta-analysis. We performed a systematic review and meta-analysis of observational studies published between 1990 and 2014. These works included multiple studies that evaluated the different survival rate among patients who underwent local treatment, such as hepatectomy or radiofrequency ablation, for hepatic metastases derived from primary gastric cancer. The collected studies were evaluated for heterogeneity, publication bias, and quality, and a pooled hazard ratio (HR) was calculated with a confidence interval estimated at 95% (95% CI). After conducting a thorough research among all published works, 2337 studies were found and after the review process 11 observational studies were included in the analysis. The total amount of patients considered in the survival analysis was 1010. An accurate analysis of all included studies reported a significantly higher survival rate in the group of patients who underwent the most aggressive local treatment for hepatic metastases (HR 0.54, 95% CI 0.46–0.95) as opposed to patients who underwent only palliation or systemic treatment. Furthermore, palliative local treatment of hepatic metastases had a higher survival rate if compared to surgical (without liver surgery) and systemic palliation (HR 0.50, 95% CI 0.26–0.96). Considering the only 3 studies where data from multivariate analyses was available, we found a higher survival rate in the local treatment groups, but the difference was not significant (HR 0.50, 95% CI 0.22–1.15). Curative and also palliative surgery of liver metastases from gastric cancer may improve patients’ survival. However, further trials are needed in order to better understand the role of surgery in this

  1. Liver cancer: Approaching a personalized care

    PubMed Central

    Bruix, Jordi; Han, Kwang-Hyub; Gores, Gregory; Llovet, Josep Maria; Mazzaferro, Vincenzo

    2015-01-01

    Summary The knowledge and understanding of all aspects of liver cancer [this including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA)] have experienced a major improvement in the last decades. New laboratory technologies have identified several molecular abnormalities that, at the very end, should provide an accurate stratification and optimal treatment of patients diagnosed with liver cancer. The seminal discovery of the TP53 hotspot mutation [1,2] was an initial landmark step for the future classification and treatment decision using conventional clinical criteria blended with molecular data. At the same time, the development of ultrasound, computed tomography (CT) and magnetic resonance (MR) has been instrumental for earlier diagnosis, accurate staging and treatment advances. Several treatment options with proven survival benefit if properly applied are now available. Major highlights include: i) acceptance of liver transplantation for HCC if within the Milan criteria [3], ii) recognition of ablation as a potentially curative option [4,5], iii) proof of benefit of chemoembolization (TACE), [6] and iv) incorporation of sorafenib as an effective systemic therapy [7]. These options are part of the widely endorsed BCLC staging and treatment model (Fig. 1) [8,9]. This is clinically useful and it will certainly keep evolving to accommodate new scientific evidence. This review summarises the data which are the basis for the current recommendations for clinical practice, while simultaneously exposes the areas where more research is needed to fulfil the still unmet needs (Table 1). PMID:25920083

  2. Minimally invasive local therapies for liver cancer

    PubMed Central

    Li, David; Kang, Josephine; Golas, Benjamin J.; Yeung, Vincent W.; Madoff, David C.

    2014-01-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed. PMID:25610708

  3. Minimally invasive local therapies for liver cancer.

    PubMed

    Li, David; Kang, Josephine; Golas, Benjamin J; Yeung, Vincent W; Madoff, David C

    2014-12-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed. PMID:25610708

  4. Liver cancer in Wisconsin: The potential for prevention

    SciTech Connect

    Mirkin, I.R.; Remington, P.L.; Moss, M.; Anderson, H. )

    1990-02-01

    In this study liver cancer deaths that could be attributed to certain risk factors were calculated. Applying population attributable risk methodology, the attributable risk of liver cancer was estimated for alcohol use, hepatitis B viral exposure, and occupational and industrial exposures. We found that these three risk factors accounted for 38% of liver cancer mortality in Wisconsin; 29% was attributable to alcohol consumption, 7% to occupational exposures, and 2% to hepatitis B viral infection. More than half of liver cancer mortality, however, was not accounted for by the three risk factors studied.

  5. [Importance for Cancer Education for Schoolchildren].

    PubMed

    Tanaka, Hideo

    2015-08-01

    Since the cancer incidence rate is generally very low in individuals aged 10 to 40 years, social concern for cancer prevention education for schoolchildren is likely to be insufficient in Japan.This paper presents epidemiological evidence to stress the importance of preferable health perceptions and behaviors in schoolchildren for the prevention of tobacco-related cancer, abnormal body mass index-related cancer, and cervical cancer.To improve the effectiveness of cancer education for schoolchildren, it is important to monitor their health perceptions and behaviors at least until junior high school.When a goal is set for the reduction of cancer incidence, it takes a very long time (at least 50 years).Therefore, the vision regarding cancer education for schoolchildren should not be changed for at least 50 years, whereas the methods and contents should be revised appropriately. PMID:26321703

  6. Zinc metallothionein imported into liver mitochondria modulates respiration

    PubMed Central

    Ye, Bin; Maret, Wolfgang; Vallee, Bert L.

    2001-01-01

    Metallothionein (MT) localizes in the intermembrane space of liver mitochondria as well as in the cytosol and nucleus. Incubation of intact liver mitochondria with physiological, micromolar concentrations of MT leads to the import of MT into the mitochondria where it inhibits respiration. This activity is caused by the N-terminal β-domain of MT; in this system, the isolated C-terminal α-domain is inactive. Free zinc inhibits respiration at concentrations commensurate with the zinc content of either MT or the isolated β-domain, indicating that MT inhibition involves zinc delivery to mitochondria. Respiratory inhibition of uncoupled mitochondria identifies the electron transfer chain as the primary site of inhibition. The apoform of MT, thionein, is an endogenous chelating agent and activates zinc-inhibited respiration with a 1:1 stoichiometry ([zinc binding sites]/[zinc]). Carbamoylation of the lysines of MT significantly attenuates the inhibitory effect, suggesting that these residues are critical for the passage of MT through the outer mitochondrial membrane. Such an import pathway has been proposed for other proteins that also lack a mitochondrial targeting sequence, e.g., apocytochrome c, and possibly Cox17, a mitochondrial copper chaperone that is the only protein known so far to exhibit significant primary sequence homology to MT. The presence and respiratory inhibition of MT in liver, but not heart, mitochondria suggest a hitherto unknown biological modulating activity of MT in cellular respiration and energy metabolism in a tissue-specific manner. PMID:11226237

  7. Extra vascular interventional treatment of liver cancer, present and future.

    PubMed

    Hou, Wenjing; Zhu, Xiaolin

    2015-10-01

    Interventional therapy for liver cancer is a new type of treatment, and its progress has been influenced by the development of the large scale imaging instrument and various therapeutic apparatus. This article, from these two aspects, discusses the status and progress of interventional treatment of liver cancer. PMID:26632542

  8. Radioembolization for primary and metastatic liver cancer

    PubMed Central

    Memon, Khairuddin; Lewandowski, Robert J; Kulik, Laura; Riaz, Ahsun; Mulcahy, Mary F; Salem, Riad

    2011-01-01

    The incidence of hepatocellular carcinoma is increasing. Most patients present beyond potentially curative options and are usually affected by underlying cirrhosis. In this scenario, trans-arterial therapies, such as radioembolization, are rapidly gaining acceptance as a potential therapy for hepatocellular carcinoma and liver metastases. Radioembolization is a catheter-based liver-directed therapy that involves injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous transarterial techniques. Cancer cells are preferentially supplied by arterial blood and normal hepatocytes by portal venous blood; radioembolization therefore specifically targets tumor cells with a high dose of lethal radiation and spares healthy hepatocytes. The antitumor effect mostly comes from radiation rather than embolization. The most commonly used radioisotope is Yttrium-90. The commercially available devices are TheraSphere® (glass-based) and SIR-Sphere® (resin-based). The procedure is performed on outpatient basis. The incidence of complications is generally less than other locoregional therapies and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, gastrointestinal ulcers and vascular injury. However, these can be avoided by meticulous pretreatment assessment, careful patient selection and adequate dosimetry. This article focuses on both the technical and clinical aspects of radioembolization with emphasis on patient selection, uses and complications. PMID:21939859

  9. 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

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

    PubMed

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

    2016-03-01

    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

  11. 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

  12. Pitavastatin suppressed liver cancer cells in vitro and in vivo.

    PubMed

    You, He-Yi; Zhang, Wei-Jian; Xie, Xue-Meng; Zheng, Zhi-Hai; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-01-01

    Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy. PMID:27621652

  13. Pitavastatin suppressed liver cancer cells in vitro and in vivo

    PubMed Central

    You, He-Yi; Zhang, Wei-Jian; Xie, Xue-Meng; Zheng, Zhi-Hai; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-01-01

    Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy. PMID:27621652

  14. Water soluble fluorescence quantum dot probe labeling liver cancer cells.

    PubMed

    Chang, Baoxing; Yang, Xianjun; Wang, Fang; Wang, Yinsong; Yang, Rui; Zhang, Ning; Wang, Baiqi

    2013-11-01

    Water soluble quantum dots (QDs) have been prepared by hydrothermal method and characterized by ultraviolet irradiation, XRD, TEM, UV-Vis absorption spectrometer and fluorescence spectrometer. Then the QD-antibody-AFP probes (QD-Ab-AFP) were synthesized by chemical process and specifically labeled AFP antigen in PLC/PRF/5 liver cancer cells. The results showed that the QDs were cubic structure and had excellent optical properties. Moreover, the QD-Ab-AFP with good stability could specifically label liver cancer cells. This work provides strong foundation for further studying and developing new approach to detect liver cancer at early stage. PMID:23888351

  15. Cancer of the Liver and Intrahepatic Bile Duct

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 39,230 % of All New Cancer Cases 2.3% Estimated Deaths in 2016 27,170 % of All Cancer ... of This Cancer : In 2013, there were an estimated 54,954 people living with liver and intrahepatic ...

  16. Differential effects of targeting Notch receptors in a mouse model of liver cancer

    PubMed Central

    Huntzicker, Erik G.; Hötzel, Kathy; Choy, Lisa; Che, Li; Ross, Jed; Pau, Gregoire; Sharma, Neeraj; Siebel, Christian W.; Chen, Xin; French, Dorothy M.

    2015-01-01

    Primary liver cancer encompasses both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). The Notch signaling pathway, known to be important for the proper development of liver architecture, is also a potential driver of primary liver cancer. However, with four known Notch receptors and several Notch ligands, it is not clear which Notch pathway members play the predominant role in liver cancer. To address this question we utilized antibodies to specifically target Notch1, Notch2, Notch3 or Jag1 in a mouse model of primary liver cancer driven by AKT and NRas. We show that inhibition of Notch2 reduces tumor burden by eliminating highly malignant hepatocellular carcinoma- and cholangiocarcinoma-like tumors. Inhibition of the Notch ligand Jag 1 had a similar effect, consistent with Jag1 acting in cooperation with Notch2. This effect was specific to Notch2, as Notch3 inhibition did not decrease tumor burden. Unexpectedly, Notch1 inhibition altered the relative proportion of tumor types, reducing HCC-like tumors but dramatically increasing CC-like tumors. Finally, we show that Notch2 and Jag1 are expressed in, and Notch2 signaling is activated in, a subset of human HCC samples. Conclusions: These findings underscore the distinct roles of different Notch receptors in the liver and suggest that inhibition of Notch2 signaling represents a novel therapeutic option in the treatment of liver cancer. PMID:25311838

  17. [Liver abscess formation after treatment of liver cancer by arterial injection using adriamycin/mitomycin C oil suspension (ADMOS)].

    PubMed

    Inoue, H; Hori, A; Satake, M; Kanetsuki, I; Ueno, K; Nishida, H; Ikeda, K; Kobayashi, H; Nakajo, M

    1992-02-25

    Of 210 patients with hepatocellular carcinoma (n = 135), metastatic liver cancer (n = 71) and cholangiocarcinoma (n = 4) who underwent intra-arterial infusion of adriamycin and/or mitomycin C oil suspension (ADMOS) and cisplatin, and both regimens, pyogenic liver abscess occurred in seven (3.3%). The percentages of abscess formation in the respective types of liver cancer were 0.8, 7.0 and 25%. These differences among the three types of liver cancer were attributed to the volume of the tumor vascular beds to be embolized, which might determine the relative amount or regional Lipiodol retention in the tumor and normal liver tissue. Four of seven patients with hepatic abscess had received the intra-arterial infusion of ADMOS, and their angiographic findings showed sequential decreases in the vascular beds of the tumor in comparison with those of previous infusion procedures; all had hypovascular liver tumors angiographically. We have never experienced this complication in other treatments such as embolization of the hepatic arteries and intra-arterial infusion of water-soluble anticancer drugs alone. These results suggest that the most important factor leading to abscess formation is the ischemic destruction of the intrahepatic ducts secondary to occlusion of the peribiliary arterial plexus by Lipiodol and/or the direct effects of anticancer drugs on these vessels. To avoid this complication, the volume of Lipiodol used for intraarterial infusion therapy should be carefully determined, especially when the patient has hypovascular tumors of the liver and a history of multiple previous intraarterial infusion procedures of anticancer drug. The use of ADMOS should be avoided in patients with hypovascular tumors of the liver such as secondary deposits and cholangiocarcinoma. PMID:1313961

  18. 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

  19. Oncogenic role of the Notch pathway in primary liver cancer

    PubMed Central

    LU, JIE; XIA, YUJING; CHEN, KAN; ZHENG, YUANYUAN; WANG, JIANRONG; LU, WENXIA; YIN, QIN; WANG, FAN; ZHOU, YINGQUN; GUO, CHUANYONG

    2016-01-01

    Primary liver cancer, which includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, is one of the most common malignancies and the third leading cause of cancer-associated mortality, worldwide. Despite the development of novel therapies, the prognosis of liver cancer patients remains extremely poor. Thus, investigation of the genetic background and molecular mechanisms underlying the development and progression of this disease has gained significant attention. The Notch signaling pathway is a crucial determinant of cell fate during development and disease in several organs. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis, and is also significant in the development of HCC and ICC. These findings suggest that the modulation of Notch pathway activity may have therapeutic relevance. The present review summarizes Notch signaling during HCC and ICC development and discusses the findings of recent studies regarding Notch expression, which reveal novel insights into its function in liver cancer progression. PMID:27347091

  20. Possible Role of Cancer Stem Cells in Colorectal Cancer Metastasizing to the Liver.

    PubMed

    Jiao, Zuo-Yi; Cao, Hong-Tai; Li, Yu-Min

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers in the world. In recent decades, drug therapy and surgery have not achieved satisfactory results in curing CRC. The identification of cancer stem cells (CSCs) has provided a possible mechanistic explanation of CRC growth and metastasis. Traditional chemotherapy targets rapidly dividing cells, and since the CSCs can escape these therapies and become circulating cells, CSCs may be responsible for cancer relapse and metastasis. A better understanding of the roles of CSCs in the pathogenesis of primary CRC and its metastasis, as well as how these CSCs are regulated at the molecular level, is of paramount importance. In this review, we summarize the current understanding of the role of colorectal CSCs in CRC liver metastasis, and provide some insights on the potential implication of colorectal CSCs to better design therapeutic regimens and prevent CRC metastasis. PMID:26832139

  1. Surgical management of breast cancer liver metastases

    PubMed Central

    Cassera, Maria A; Hammill, Chet W; Ujiki, Michael B; Wolf, Ronald F; Swanström, Lee L; Hansen, Paul D

    2011-01-01

    Introduction Selected patients with isolated breast cancer liver metastases (BCLM) may benefit from surgical management; however, indications remain unclear and the risks may outweigh the benefits in patients with a generally poor prognosis. Methods Between 1998 and 2006, 17 patients diagnosed with BCLM were considered for surgical management (<4 tumours, tumour <4 cm in diameter and no/stable extrahepatic metastases). Peri-operative and outcomes data were analysed and compared. Results Eight patients were found to have extensive or untreatable disease on staging laparoscopy and intra-operative ultrasound (SL/IOUS). The remaining nine patients underwent surgical management [seven laparoscopic radiofrequency ablations (RFA) and two hepatic resections]. Median length of follow-up for patients treated surgically was 40.0 months, median disease-free survival (DFS) was 32.2 months and median time to disease progression was 17.7 months. Of the eight patients not amenable to surgery, median length of follow-up was 21.8 months. Conclusion SL/IOUS prevented unnecessary laparotomy in half of the patients taken to the operating room for surgical treatment of BCLM. In patients with BCLM, SL/IOUS should be considered standard of care before surgical intervention. The small number of patients and short follow-up may be inadequate to determine the true value of surgical management in this group of patients with BCLM. PMID:21418133

  2. What Asian Americans Should Know about Liver Cancer and Hepatitis B

    MedlinePlus

    ... Asian Americans Should Know About Liver Cancer and Hepatitis B By the National Cancer Institute Liver cancer ... Asian Americans and Pacific Islanders. Certain types of hepatitis virus, including hepatitis B virus (also known as ...

  3. Web site construction for information and treatment on liver cancer.

    PubMed

    Roussakis, Sotiris; Ponirou, Paraskevi; Bizopoulou, Zoi; Diomidous, Marianna

    2013-01-01

    Liver cancer requires a considerable attention of health care scientists worldwide. A holistic treatment includes patient information about risk factors, education on pragmatic evaluation of the symptoms, as well as presentation of best and individualized treatment methods. In this direction, Internet seems to be a powerful tool that has an essential role. The aim of this study is the development of a web site in order to inform and present treatment options on liver cancer, it consists of four parts. In the first part, the presentation of the disease's knowledge base is attempted, whereas in the second part this knowledge base is organized in two conceptual entities: (a) information and (b) treatment. In the third part the importance of internet in the health care sector is highlighted. In the fourth and last part the web site is presented and a brief illustration of several relevant theories and specific implementation tools. The critical success factor of the implementation phase is considered to be the selection of the appropriate methods and development tools. Finally, the constant need for ongoing site maintenance is discussed and thus, is proposed to formulate one of the main aspects for further research, along with several issues concerning site usability. PMID:23823432

  4. Minnelide, a novel drug for pancreatic and liver cancer

    PubMed Central

    Banerjee, Sulagna; Saluja, Ashok

    2015-01-01

    Pancreatic cancer is the 10th leading cause of all new cancer cases for men and the fourth leading cause of death across genders, having very poor prognosis and survival rates. The current standard of care Gemcitabine fails to add any survival benefit for this disease (www.cancer.gov). Though the incidence of pancreatic cancer is found to be higher in developed countries, the aggressive biology of the cancer, its high rate of recurrence and chemo-resistance make it a formidable disease in all parts of the globe. Hepatocellular carcinoma (HCC) or liver cancer, on the other hand affects almost 750,000 people world wide with 84% of the cases coming from underdeveloped or developing countries. Our studies show that Minnelide, a water soluble pro-drug of triptolide (active compound from a chinese herb) is very effective against a number of malignant diseases. The current study discusses the efficacy of this compound in pancreatic and liver cancer. PMID:26122306

  5. Focused ultrasound as a local therapy for liver cancer.

    PubMed

    Fischer, Krisztina; Gedroyc, Wladyslaw; Jolesz, Ferenc A

    2010-01-01

    Conventional surgical treatments of liver cancer are invasive (including minimally invasive) with a high incidence of new metastasis and poor success, even after multiple resections or ablations. These limitations motivated research into new, less invasive solutions for liver cancer treatment.Focused ultrasound surgery (FUS), or high-intensity focused ultrasound, has been recognized as a noninvasive technology for benign and malignant tumor treatment. Previously, FUS was guided with ultrasound that has limited target definition and monitoring capability of the ablation process. Combining magnetic resonance imaging (MRI) with multiple-element phased-array transducers to create MRI-guided focused ultrasound thermal therapy provides more accurate targeting and real-time temperature monitoring. This treatment is hindered by the ribcage that limits the acoustic windows to the liver and the respiratory motion of the liver. New advances in MRI and transducer design will likely resolve these limitations and make MRI-guided FUS a powerful tool in local liver cancer therapy. This article reviews this technology and advances that can expand its use for cancer treatment in general and liver cancer in particular. PMID:20404608

  6. A Comprehensive Method for Predicting Fatal Liver Failure of Patients With Liver Cancer Resection

    PubMed Central

    Li, Jiangfa; Lei, Biao; Nie, Xingju; Lin, Linku; Tahir, Syed Abdul; Shi, Wuxiang; Jin, Junfei; He, Songqing

    2015-01-01

    Abstract There are many methods to assess liver function, but none of them has been verified as fully effective. The purpose of this study is to establish a comprehensive method evaluating perioperative liver reserve function (LRF) in patients with primary liver cancer (PLC). In this study, 310 PLC patients who underwent liver resection were included. The cohort was divided into a training set (n = 235) and a validation set (n = 75). The factors affecting postoperative liver dysfunction (POLD) during preoperative, intraoperative, and postoperative periods were confirmed by logistic regression analysis. The equation for calculating the preoperative liver functional evaluation index (PLFEI) was established; the cutoff value of PLFEI determined through analysis by receiver-operating characteristic curve was used to predict postoperative liver function. The data showed that body mass index, international normalized ratio, indocyanine green (ICG) retention rate at 15 minutes (ICGR15), ICG elimination rate, standard remnant liver volume (SRLV), operative bleeding volume (OBV), blood transfusion volume, and operative time were statistically different (all P < 0.05) between 2 groups of patients with and without POLD. The relationship among PLFEI, ICGR15, OBV, and SRLV is expressed as an equation of “PLFEI = 0.181 × ICGR15 + 0.001 × OBV − 0.008 × SRLV.” The cutoff value of PLFEI to predict POLD was −2.16 whose sensitivity and specificity were 90.3% and 73.5%, respectively. However, when predicting fatal liver failure (FLF), the cutoff value of PLFEI was switched to −1.97 whose sensitivity and specificity were 100% and 68.8%, respectively. PLFEI will be a more comprehensive, sensitive, and accurate index assessing perioperative LRF in liver cancer patients who receive liver resection. And keeping PLFEI <−1.97 is a safety margin for preventing FLF in PLC patients who underwent liver resection. PMID:25929924

  7. Why is Physics Important to Cancer Research?

    NASA Astrophysics Data System (ADS)

    Barker, Anna D.

    Cancer is increasingly described as a ''disease of the genes'', and while the genome (in fact all of the ``omes'') are important information molecules that drive aspects of the initiation and progression of cancer, they are far from the whole story. Cancer is an extraordinarily complex system (in fact a complex of systems) that occurs in three-dimensional space, across multiple scales - and often over extended periods of time. The most challenging issues that plague the cancer field such as metastasis, cellular heterogeneity and resistance to therapy are in large part more rationally explained in the context of the physics of these systems vs. genomics. For example, the biology of metastasis has been studied extensively for decades with little progress. Metastatic disease depends on cells acquiring (or expressing innate information) new properties that enable and sustain their ability to migrate to distant sites. Developing a fundamental understanding of key cancer processes ranging from metastasis to immunotherapeutic responses requires that physicists (and mathematicians and engineers) be integrated into a new generation of cancer research - period! The presentation will focus on those areas where physics is essential - and the how's and whose of achieving the integration required.

  8. Risk factors for cancer recurrence or death within 6 months after liver resection in patients with colorectal cancer liver metastasis

    PubMed Central

    Jung, Sung Won; Yu, Young Dong; Han, Jae Hyun; Suh, Sung-Ock

    2016-01-01

    Purpose The aim of this study was to find risk factors for early recurrence (ER) and early death (ED) after liver resection for colorectal cancer liver metastasis (CRCLM). Methods Between May 1990 and December 2011, 279 patients underwent liver resection for CRCLM at Korea University Medical Center. They were assigned to group ER (recurrence within 6 months after liver resection) or group NER (non-ER; no recurrence within 6 months after liver resection) and group ED (death within 6 months after liver resection) or group NED (alive > 6 months after liver resection). Results The ER group included 30 patients (10.8%) and the NER group included 247 patients (89.2%). The ED group included 18 patients (6.6%) and the NED group included 253 patients (93.4%). Prognostic factors for ER in a univariate analysis were poorly differentiated colorectal cancer (CRC), synchronous metastasis, ≥5 cm of liver mass, ≥50 ng/mL preoperative carcinoembryonic antigen level, positive liver resection margin, and surgery alone without perioperative chemotherapy. Prognostic factors for ED in a univariate analysis were poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy. Multivariate analysis showed that poorly differentiated CRC, ≥5-cm metastatic tumor size, positive liver resection margin, and surgery alone without perioperative chemotherapy were independent risk factors related to ER. For ED, poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy were risk factors in multivariate analysis. Conclusion Complete liver resection with clear resection margin and perioperative chemotherapy should be carefully considered when patients have the following preoperative risk factors: metastatic tumor size ≥ 5 cm and poorly differentiated CRC. PMID:27186570

  9. Increased Porphyrins in Primary Liver Cancer Mainly Reflect a Parallel Liver Disease

    PubMed Central

    Kaczynski, Jerzy; Hansson, Göran; Wallerstedt, Sven

    2009-01-01

    Hepatic porphyries have been associated with an increased risk of primary liver cancer (PLC), which on the other hand may cause an increased porphyrin production. To evaluate the role of an underlying liver disorder we analyzed porphyrins in patients with hepatocellular carcinoma (HCC) (n = 65), cholangiocellular carcinoma (n = 3), or suspected PLC, which turned out to be metastases (n = 18) or a benign disorder (n = 11). None of the patients had a family history of porphyry or clinical signs of porphyry. Increased aminolevulinic acid or porphyrin values were common not only in patients with PLC (43%) but also in metastatic (50%) and benign (64%) liver disorders. The corresponding proportion for HCC patients with liver cirrhosis (55%) was higher (P < .05) than in those without cirrhosis (17%). We conclude that symptomatic porphyries are unusual in PLC, whereas elevated urinary and/or faecal porphyrins are common, primarily reflecting a parallel liver disease and not the PLC. PMID:19841684

  10. [A case of sigmoid colon cancer liver metastasis accompanied by multiple liver abscesses].

    PubMed

    Murakami, Masakazu; Miyake, Yasuhiro; Uemura, Hisashi; Okada, Kaoru; Nakane, Shigeru; Higaki, Naozumi; Hayashida, Hirohito; Oka, Yoshio; Nezu, Riichiro

    2014-11-01

    We describe the case of a patient with sigmoid colon cancer liver metastasis accompanied by multiple liver abscesses. The 59-year-old female patient presented with a fever at a body temperature of 39.0°C. On abdominal computed tomography (CT), multiple liver abscesses were detected, and percutaneous transhepatic abscess drainage (PTAD) was performed. The day after the PTAD, the patient's fever subsided and her inflammatory response abated. A lower gastrointestinal examination, performed to identify the origin of her symptoms, revealed a type 1 tumor in the sigmoid colon. A biopsy indicated a moderately differentiated adenocarcinoma. Prior to surgery, a second abdominal CT scan was performed, and a single liver metastasis was detected. Laparoscopic sigmoidectomy and partial liver resection were simultaneously performed. The histopathological diagnosis of the colon cancer was tub2, pN1, pH1, P0, ly1, v1, stage IV. To date, the patient remains free from hepatic abscess and colon cancer recurrence. Gastrointestinal examinations should be performed as early as possible to identify the cause of hepatic abscesses. Moreover, therapeutic decisions should only be made after imaging and examinations have been performed, which will be sufficient to identify the presence of liver metastases. PMID:25731285

  11. Importance of surgical margins in rectal cancer.

    PubMed

    Mukkai Krishnamurty, Devi; Wise, Paul E

    2016-03-01

    Distal resection margin (DRM) and circumferential resection margin (CRM) are two important considerations in rectal cancer management. Although guidelines recommend a 2 cm DRM, studies have shown that a shorter DRM is adequate, especially in patients receiving neoadjuvant chemoradiation. Standardization of total mesorectal excision has greatly improved quality of CRM. Although more patients are undergoing sphincter-saving procedures, abdominoperineal resection is indicated for very distal tumors, and pelvic exenteration is often necessary for tumors involving pelvic organs. PMID:27094456

  12. PCDH8 is Frequently Inactivated by Promoter Hypermethylation in Liver Cancer: Diagnostic and Clinical Significance

    PubMed Central

    Zhang, Cheng; Peng, Yunfei; Yang, Fan; Qin, Ruixi; Liu, Wenjun; Zhang, Cuijuan

    2016-01-01

    AIM: Protocadherin-8 (PCDH8) plays an important role in signaling pathways of cell adhesin, proliferation, and migration. It has been reported that PCDH8 is mutated or methylated in several human cancers. However, little is known about PCDH8 in liver cancer. The aim of this study was to investigate the protein expression and promoter methylation status of PCDH8 in liver cancer and evaluate the association between PCDH8 methylation and the clinicopathological features. METHODS: The methylation status of PCDH8 in 42 hepatocellular carcinoma (HCC), 8 Cholangiocarcinoma (CC) and 50 normal liver tissues were examined using methylation-specific PCR (MSP) and the protein expression of PCDH8 was detected by immunohistochemistry. The relationships between PCDH8 methylation and clinicopathological features as well as overall survival of patients were evaluated. RESULTS: The PCDH8 methylation was more frequent in liver cancer tissues than that in the normal liver tissues (88% vs. 32%, P < 0.001), and is significantly associated with loss of its protein expression (P = 0.004). Moreover, there is a significant correlation between PCDH8 methylation and the alpha-fetoprotein (AFP) level (P = 0.008). Kaplan-Meier survival analysis revealed that patients with PCDH8 methylation have shorter OS and PFS than those without PCDH8 methylation (P = 0.041 and P = 0.028, respectively). CONCLUSION: PCDH8 is often inactivated by promoter methylation in liver cancer. PCDH8 methylation can serve as a valuable diagnostic biomarker for early detection of liver cancer and might be useful to predict an unfavorable clinical feature. PMID:26918058

  13. 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. PMID:27258482

  14. Application of stereotactic body radiation therapy to cancer liver metastasis.

    PubMed

    Zhang, Si-Yuan; Zhu, Guang-Ying; Li, Gong; Zhang, Yi-Bao; Geng, Jian-Hao

    2016-09-01

    As an accurate external beam irradiation method, stereotactic body radiotherapy (SBRT) has been increasingly used to deliver high dose in less fractions. The liver is one of the most common organs for cancer metastasis. Recently, there have been several trials applying SBRT to cancer liver metastasis and have proved to be effective and safe with local control (LC) rates ranging from 70% to 100% within one or two years and 2-year overall survival (OS) rates ranging from 30% to 38%. Many published studies indicate that SBRT for cancer liver metastasis results in good outcomes without severe toxicities. However, the validated contribution of SBRT to an improved progression-free survival is still missing and more randomized trials should be conducted. PMID:26704306

  15. A fresh liver agar substrate for rearing small numbers of forensically important blow flies (Diptera: Calliphoridae)

    USGS Publications Warehouse

    Gruner, Susan V.; Slone, Daniel H.

    2014-01-01

    Forensically important calliphorids can be reared on a mixture of beef liver and agar. Small pieces of meat, especially fresh or frozen beef liver, will desiccate in 2–6 h, but this simple-to-make feeding substrate remains moist for at least 12 h at 25 and 30°C without desiccation, even in small (5 g) amounts. We determined the survivorship of small numbers of Chrysomya megacephala (F.) (first-instar larvae to adult eclosion) raised on 5 g of liver agar and fresh beef liver. We found that all larvae raised on 5 g of liver died due to desiccation, but survivorship on 5 g of liver agar was equivalent to that on larger (50 g) pieces of either liver agar or beef liver.

  16. Complete and rapid response to FOLFIRI plus bevacizumab in a patient presenting with impaired liver function and poor performance status from colon cancer liver metastases.

    PubMed

    Belda-Iniesta, Cristóbal; Sáenz, Enrique Casado; de Castro-Carpeño, Javier; Hernández, Elena; Barón, Manuel González

    2009-04-01

    Impaired liver function is a final complication of hepatic metastases from colon cancer. This disease status is of critical importance at first clinical presentation because of the tight therapeutic window for chemotherapy. A rapid response to treatment is required as other means of supportive care for hepatic function are limited. New targeted therapies including monoclonal antibodies directed against several proteins with key roles in colon cancer biology are now available, allowing new treatment options for this group of patients. Here, we present a patient with highly impaired liver function secondary to hepatic metastases from colon cancer that showed clinical and radiological improvement after systemic treatment including bevacizumab. PMID:19352108

  17. Do We Know What Causes Liver Cancer?

    MedlinePlus

    ... only partially understood. Cancers develop when a cell’s DNA is damaged. DNA is the chemical in each of our cells ... tumor suppressor genes . Cancers can be caused by DNA changes that turn on oncogenes or turn off ...

  18. Clinical Features of Liver Cancer with Cerebral Hemorrhage

    PubMed Central

    Lu, Qiuhong; Chen, Li; Zeng, Jinsheng; Huang, Gelun; Qin, Chao; Cheng, Daobin; Yu, Lixia; Liang, Zhijian

    2016-01-01

    Background Cerebral hemorrhage is common in patients with cancer, but the clinical features and pathogenesis of liver cancer patients with cerebral hemorrhage are not well known. Material/Methods Liver cancer patients who developed cerebral hemorrhage were recruited from the First Affiliated Hospital of Guangxi Medical University between January 2003 and December 2014. We retrospectively analyzed clinical presentations, results of laboratory tests, and imaging examinations. The clinical features and pathogenesis were summarized. Results Among 11133 patients with liver cancer, 9 patients (0.08%), including 3 females and 6 males met the inclusion criteria. The age range was 48–73 years and the average age was 61.67±8.97 years. Five patients did not have traditional hemorrhage risk factors and 4s had the risk factors; however, all had developed hepatocellular carcinoma, and 3 had developed metastasis. All 9 patients showed elevated tumor markers: an increased AFP level was detected in 6 patients, coagulation dysfunctions in 8 patients, and abnormal liver functions in 6 patients. Five patients had developed cerebral hemorrhagic lesions in the lobes of their brains, while hemorrhagic lesions in the basal ganglia occurred in 3 patients and in the brainstem in only 1 patient. Four patients had clear consciousness, while 5 patients were in coma and showed poor prognosis. Conclusions Patients who have liver cancer complicated with cerebral hemorrhage usually lack traditional risk factors of cerebral hemorrhage. The site of cerebral hemorrhage is often detected in the lobes of the brain. Coagulation dysfunctions might be the main pathogenesis of liver cancer complicated with cerebral hemorrhage. PMID:27209058

  19. Clinical Features of Liver Cancer with Cerebral Hemorrhage.

    PubMed

    Lu, Qiuhong; Chen, Li; Zeng, Jinsheng; Huang, Gelun; Qin, Chao; Cheng, Daobin; Yu, Lixia; Liang, Zhijian

    2016-01-01

    BACKGROUND Cerebral hemorrhage is common in patients with cancer, but the clinical features and pathogenesis of liver cancer patients with cerebral hemorrhage are not well known. MATERIAL AND METHODS Liver cancer patients who developed cerebral hemorrhage were recruited from the First Affiliated Hospital of Guangxi Medical University between January 2003 and December 2014. We retrospectively analyzed clinical presentations, results of laboratory tests, and imaging examinations. The clinical features and pathogenesis were summarized. RESULTS Among 11133 patients with liver cancer, 9 patients (0.08%), including 3 females and 6 males met the inclusion criteria. The age range was 48-73 years and the average age was 61.67±8.97 years. Five patients did not have traditional hemorrhage risk factors and 4s had the risk factors; however, all had developed hepatocellular carcinoma, and 3 had developed metastasis. All 9 patients showed elevated tumor markers: an increased AFP level was detected in 6 patients, coagulation dysfunctions in 8 patients, and abnormal liver functions in 6 patients. Five patients had developed cerebral hemorrhagic lesions in the lobes of their brains, while hemorrhagic lesions in the basal ganglia occurred in 3 patients and in the brainstem in only 1 patient. Four patients had clear consciousness, while 5 patients were in coma and showed poor prognosis. CONCLUSIONS Patients who have liver cancer complicated with cerebral hemorrhage usually lack traditional risk factors of cerebral hemorrhage. The site of cerebral hemorrhage is often detected in the lobes of the brain. Coagulation dysfunctions might be the main pathogenesis of liver cancer complicated with cerebral hemorrhage. PMID:27209058

  20. Liver macrophages contribute to pancreatic cancer-related cachexia.

    PubMed

    Martignoni, Marc E; Dimitriu, Corneliu; Bachmann, Jeaninne; Krakowski-Rosen, Holger; Ketterer, Knut; Kinscherf, Ralf; Friess, Helmut

    2009-02-01

    Cachexia is a devastating process especially in pancreatic cancer patients and contributes to their poor survival. We attempted to clarify the pathological and molecular changes that occur in the liver during the development of cachexia. Using immunohistochemistry we investigated the infiltration of inflammatory mononuclear cells in liver biopsies of pancreatic cancer patients with or without cachexia, and the potential relevance of the cells for the nutritional and inflammatory status. Additionally, these findings were compared with the patients' clinical parameters. We found a significantly higher amount of CD68 immunoreactive macrophages in liver cross sections of patients with pancreatic cancer and cachexia. The number of CD68-positive macrophages was significantly inversely correlated with the nutritional status. Additionally, in these CD68-positive areas a significant increase in IL-6 and IL-1 immunoreactive cells was localized. Moreover, we found significantly increased areas of CD68-positive macrophages in liver biopsies of patients with a more dedifferentiated (aggressive) grading of the tumor. In conclusion, these results suggest that a crucial interaction between the tumor, PBMCs, and the liver may play a central role in the development and regulation of cachexia. Furthermore, pancreatic cancer may be able to alter systemic organ function even without obvious metastatic disease. PMID:19148509

  1. 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

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

    PubMed

    Thoppil, Roslin J; Bishayee, Anupam

    2011-09-27

    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

  3. 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

  4. Liver Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... ung thư gan - Tiếng Việt (Vietnamese) PDF Stanford University, Asian Liver Center Characters not displaying correctly on this page? See language display issues . Return to the MedlinePlus Health Information ...

  5. 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

    2011-11-01

    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.

  6. 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.

  7. New Insights into Orphan Nuclear Receptor SHP in Liver Cancer

    PubMed Central

    Zou, An; Lehn, Sarah; Magee, Nancy; Zhang, Yuxia

    2015-01-01

    Small heterodimer partner (SHP; NR0B2) is a unique orphan nuclear receptor (NR) that contains a putative ligand-binding domain but lacks a DNA-binding domain. SHP is a transcriptional corepressor affecting diverse metabolic processes including bile acid synthesis, cholesterol and lipid metabolism, glucose and energy homeostasis, and reproductive biology via interaction with multiple NRs and transcriptional factors (TFs). Hepatocellular carcinoma (HCC) is one of the most deadly human cancers worldwide with few therapeutic options and poor prognosis. Recently, it is becoming clear that SHP plays an antitumor role in the development of liver cancer. In this review, we summarize the most recent findings regarding the new SHP interaction partners, new structural insights into SHP’s gene repressing activity, and SHP protein posttranslational modifications by bile acids. We also discuss the pleiotropic role of SHP in regulating cell proliferation, apoptosis, DNA methylation, and inflammation that are related to antitumor role of SHP in HCC. Improving our understanding of SHP’s antitumor role in the development of liver cancer will provide new insights into developing novel treatments or prevention strategies. Future research will focus on developing more efficacious and specific synthetic SHP ligands for pharmaceutical applications in liver cancer and several metabolic diseases such as hypercholesterolemia, obesity, diabetes, and fatty liver disease. PMID:26504773

  8. 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,...

  9. The Rainbow Trout Liver Cancer Model: Response to Environmental Chemicals and Studies on Promotion and Chemoprevention✰

    PubMed Central

    Williams, David E.

    2011-01-01

    Rainbow trout (Oncorhynchus mykiss) are an outstanding model of liver cancer induction by environmental chemicals and development of strategies for chemoprevention. Trout have critical and unique advantages allowing for cancer studies with 40,000 animals to determine dose-response at levels orders of magnitude lower than possible in rodents. Examples of two promoters in this model, the dietary supplement dehydroepiandrosterone (DHEA) and industrial chemical perfluorooctanoic acid (PFOA), are presented. In addition, indole-3-carbinol (I3C) and chlorophyllin (CHL) inhibit initiation following exposure to potent human chemical carcinogens (e.g., aflatoxin B1 (AFB1). Two “ED001” cancer studies have been conducted, utilizing approximately 40,000 trout, by dietary exposure to AFB1 and dibenzo[d,e,f,p]chrysene (DBC). These studies represent the two largest cancer studies ever performed and expand the dose-response dataset generated by the 25,000 mouse “ED01” study over an order of magnitude. With DBC, the liver tumor response fell well below the LED10 line, often used for risk assessment, even though the biomarker (liver DBC-DNA adducts) remained linear. Conversely, the response with AFB1 remained relatively linear throughout the entire dose range. These contributions to elucidation of mechanisms of liver cancer, induced by environmental chemicals and the remarkable datasets generated with ED001 studies, make important contributions to carcinogenesis and chemoprevention. PMID:21704190

  10. 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

  11. Bimodal role of Kupffer cells during colorectal cancer liver metastasis.

    PubMed

    Wen, Shu Wen; Ager, Eleanor I; Christophi, Christopher

    2013-07-01

    Kupffer cells (KCs) are resident liver macrophages that play a crucial role in liver homeostasis and in the pathogenesis of liver disease. Evidence suggests KCs have both stimulatory and inhibitory functions during tumor development but the extent of these functions remains to be defined. Using KC depletion studies in an orthotopic murine model of colorectal cancer (CRC) liver metastases we demonstrated the bimodal role of KCs in determining tumor growth. KC depletion with gadolinium chloride before tumor induction was associated with an increased tumor burden during the exponential growth phase. In contrast, KC depletion at the late stage of tumor growth (day 18) decreased liver tumor load compared with non-depleted animals. This suggests KCs exhibit an early inhibitory and a later stimulatory effect. These two opposing functions were associated with changes in iNOS and VEGF expression as well as T-cell infiltration. KC depletion at day 18 increased numbers of CD3 (+) T cells and iNOS-expressing infiltrating cells in the tumor, but decreased the number of VEGF-expressing infiltrating cells. These alterations may be responsible for the observed reduction in tumor burden following depletion of pro-tumor KCs at the late stage of metastatic growth. Taken together, our results indicate that the bimodal role of KC activity in liver tumors may provide the key to timing immunomodulatory intervention for the treatment of CRC liver metastases. PMID:23792646

  12. Changing Rates for Liver and Lung Cancer in Qidong, China

    PubMed Central

    Chen, Jian-Guo; Kensler, Thomas W.

    2013-01-01

    Residents of Qidong, China are undergoing a rapid fluctuation in cancer incidence rates at many organ sites, reflecting a dynamic interplay of socio-behavioral, economic and environmental factors. This Perspective On Statistical Trends examines the China age-standardized incidence rates (CASR), as tracked by the Qidong Cancer Registry for the past 40 years, for the two leading cancer killers in Qidong, liver and lung. Both cancer types are strongly influenced by environmental factors. The CASR for liver cancer has dropped nearly 50% in the last 4 decades, in part from access to deep-well drinking water in the 1970s with consequent diminished exposure to tumor promoting microcystins produced by blue-green algae. There have also been substantive reductions in exposures to dietary aflatoxins, as economic reform in the mid-1980s fostered a wholesale change in dietary staple from maize to rice. In men, lung cancer CASR has trebled over this period, likely driven by a high prevalence of smokers (~65%) and an ever increasing smoking frequency in this population. Qidong women, by contrast, rarely smoke and have exhibited a flat CASR until the last decade where lung cancer rates have now doubled. This upturn may reflect an increasing burden of indoor and outdoor air pollution. PMID:24215631

  13. Changing rates for liver and lung cancers in Qidong, China.

    PubMed

    Chen, Jian-Guo; Kensler, Thomas W

    2014-01-21

    Residents of Qidong, China are undergoing a rapid fluctuation in cancer incidence rates at many organ sites, reflecting a dynamic interplay of socio-behavioral, economic, and environmental factors. This Perspective On Statistical Trends examines the China age-standardized incidence rates (CASR), as tracked by the Qidong Cancer Registry for the past 40 years, for the two leading cancer killers in Qidong, liver and lung. Both cancer types are strongly influenced by environmental factors. The CASR for liver cancer has dropped nearly 50% in the last 4 decades, in part from access to deep-well drinking water in the 1970s with consequent diminished exposure to tumor promoting microcystins produced by blue-green algae. There have also been substantive reductions in exposures to dietary aflatoxins, as economic reform in the mid-1980s fostered a wholesale change in dietary staple from maize to rice. In men, lung cancer CASR has trebled over this period, likely driven by a high prevalence of smokers (∼65%) and an ever increasing smoking frequency in this population. Qidong women, by contrast, rarely smoke and have exhibited a flat CASR until the past decade where lung cancer rates have now doubled. This upturn may reflect an increasing burden of indoor and outdoor air pollution. PMID:24215631

  14. miR-449a promotes liver cancer cell apoptosis by downregulation of Calpain 6 and POU2F1

    PubMed Central

    Liu, Yonglei; Wang, Yutong; Sun, Xiangjun; Mei, Chuanzhong; Wang, Liying; Li, Zengxia; Zha, Xiliang

    2016-01-01

    Our previous study shows that Calpain 6 (CAPN6) expression is regulated by PI3K-Akt in liver cancer through POU2F1 and CAPN6 which promote cell proliferation and inhibit apoptosis of liver cancer cells. microRNAs (miRNAs) plays important roles in regulation of gene expression. However, whether miRNAs regulates CAPN6 expression and its cellular function is still unknown. This study aims to investigate how miRNAs regulate liver cancer apoptosis through POU2F1-CAPN6. It was verified that POU2F1 could promote cell proliferation and inhibit apoptosis through CAPN6. Using methods of bioinformatics, miR-449a was predicted as a potential regulator of both CAPN6 and POU2F1. It was verified that CAPN6 and POU2F1 were the target genes of miR-449a by luciferase assay. CAPN6 and POU2F1 protein and mRNA levels decreased in liver cancer cells with miR-449a overexpression using western blot and real time RT-PCR assays. miR-449a expression was lower in liver cancer tissues compared with their normal ones, so did the cells. Overexpression of miR-449a inhibited cell proliferation, induced G1 phase arrest and cell apoptosis in liver cancer. Further research demonstrated that miR-449a inhibited cancer cell proliferation and induced apoptosis via suppressing both POU2F1 and CAPN6. The study indicated that miR-449a functions as a tumor inhibitor in liver cancer by decreasing POU2F1 and CAPN6 expression in liver cancer. PMID:26375440

  15. Distinguishing Cancerous Liver Cells Using Surface-Enhanced Raman Spectroscopy.

    PubMed

    Huang, Jing; Liu, Shupeng; Chen, Zhenyi; Chen, Na; Pang, Fufei; Wang, Tingyun

    2016-02-01

    Raman spectroscopy has been widely used in biomedical research and clinical diagnostics. It possesses great potential for the analysis of biochemical processes in cell studies. In this article, the surface-enhanced Raman spectroscopy (SERS) of normal and cancerous liver cells incubated with SERS active substrates (gold nanoparticle) was measured using confocal Raman microspectroscopy technology. The chemical components of the cells were analyzed through statistical methods for the SERS spectrum. Both the relative intensity ratio and principal component analysis (PCA) were used for distinguishing the normal liver cells (QSG-7701) from the hepatoma cells (SMMC-7721). The relative intensity ratio of the Raman spectra peaks such as I937/I1209, I1276/I1308, I1342/I1375, and I1402/I1435 was set as the judge boundary, and the sensitivity and the specificity using PCA method were calculated. The results indicated that the surface-enhanced Raman spectrum could provide the chemical information for distinguishing the normal cells from the cancerous liver cells and demonstrated that SERS technology possessed the possible applied potential for the diagnosis of liver cancer. PMID:25432931

  16. Radionuclide liver cancer therapies: from concept to current clinical status.

    PubMed

    Vente, Maarten A D; Hobbelink, Monique G G; van Het Schip, Alfred D; Zonnenberg, Bernard A; Nijsen, Johannes F W

    2007-07-01

    Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery. These internal radiation techniques consist of injecting either yttrium-90 ((90)Y) microspheres, or iodine-131 ((131)I) or rhenium-188 ((188)Re) labeled lipiodol into the hepatic artery. Radioactive lipiodol is used exclusively for treatment of primary liver cancer, whereas (90)Y microsphere therapy is applied for treatment of both primary and metastatic liver cancers. Favorable clinical results have been achieved, particularly when (90)Y microspheres were used in conjunction with systemic chemotherapy. The main advantages of radiolabeled lipiodol treatment are that it is relatively inexpensive (especially (188)Re-HDD-lipiodol) and that the administration procedure is somewhat less complex than that of the microspheres. Holmium-166 ((166)Ho) loaded poly(L-lactic acid) microspheres have also been developed and are about to be clinically introduced. Since (166)Ho is a combined beta-gamma emitter and highly paramagnetic as well, it allows for both (quantitative) scintigraphic and magnetic resonance imaging. PMID:17630919

  17. Efficiency of Non-Contrast-Enhanced Liver Imaging Sequences Added to Initial Rectal MRI in Rectal Cancer Patients

    PubMed Central

    Kwon, Gene-hyuk; Kim, Kyung Ah; Hwang, Seong Su; Park, Soo Youn; Kim, Hyun A.; Choi, Sun Young; Kim, Ji Woong

    2015-01-01

    Purpose The purpose of this study was to estimate the value of addition of liver imaging to initial rectal magnetic resonance imaging (MRI) for detection of liver metastasis and evaluate imaging predictors of a high risk of liver metastasis on rectal MRI. Methods We enrolled 144 patients who from October 2010 to May 2013 underwent rectal MRI with T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) (b values = 50, 500, and 900 s/mm2) of the liver and abdominopelvic computed tomography (APCT) for the initial staging of rectal cancer. Two reviewers scored the possibility of liver metastasis on different sets of liver images (T2WI, DWI, and combined T2WI and DWI) and APCT and reached a conclusion by consensus for different analytic results. Imaging features from rectal MRI were also analyzed. The diagnostic performances of CT and an additional liver scan to detect liver metastasis were compared. Multivariate logistic regression to determine independent predictors of liver metastasis among rectal MRI features and tumor markers was performed. This retrospective study was approved by the Institutional Review Board, and the requirement for informed consent was waived. Results All sets of liver images were more effective than APCT for detecting liver metastasis, and DWI was the most effective. Perivascular stranding and anal sphincter invasion were statistically significant for liver metastasis (p = 0.0077 and p = 0.0471), while extramural vascular invasion based on MRI (mrEMVI) was marginally significant (p = 0.0534). Conclusion The addition of non-contrast-enhanced liver imaging, particularly DWI, to initial rectal MRI in rectal cancer patients could facilitate detection of liver metastasis without APCT. Perivascular stranding, anal sphincter invasion, and mrEMVI detected on rectal MRI were important imaging predictors of liver metastasis. PMID:26348217

  18. Donor transmitted and de novo cancer after liver transplantation.

    PubMed

    Desai, Rajeev; Neuberger, James

    2014-05-28

    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

  19. The importance of serine metabolism in cancer.

    PubMed

    Mattaini, Katherine R; Sullivan, Mark R; Vander Heiden, Matthew G

    2016-08-01

    Serine metabolism is frequently dysregulated in cancers; however, the benefit that this confers to tumors remains controversial. In many cases, extracellular serine alone is sufficient to support cancer cell proliferation, whereas some cancer cells increase serine synthesis from glucose and require de novo serine synthesis even in the presence of abundant extracellular serine. Recent studies cast new light on the role of serine metabolism in cancer, suggesting that active serine synthesis might be required to facilitate amino acid transport, nucleotide synthesis, folate metabolism, and redox homeostasis in a manner that impacts cancer. PMID:27458133

  20. Radiofrequency Ablation of Liver Metastases from Colorectal Cancer: A Literature Review

    PubMed Central

    Kudo, Masatoshi

    2013-01-01

    Liver metastases occur in up to 60% of patients with colorectal cancer, and the control of liver metastases is considered to be of primary importance because it is a critical factor in determining prognosis. Radiofrequency ablation (RFA) therapy is one of the least invasive techniques for unresectable hepatic malignancies and can be performed safely using percutaneous, laparoscopic, or open surgical techniques. The local tumor progression rates after RFA for colorectal liver metastases range from 8.8% to 40.0%, and 5-year survival rates range from 20.0% to 48.5%. No prospective, randomized trials comparing the efficacy of RFA with that of surgical resection for colorectal liver metastases are currently available. However, some retrospective studies have reported that patients who received RFA had a survival rate similar to that observed in surgically treated groups, while other studies have reported better survival among patients who underwent surgical resection. The use of a laparoscopic or open surgical approach allows the repeated placement of RFA electrodes at multiple sites to ablate larger tumors. An accurate evaluation of treatment response is very important for the success of RFA therapy because a sufficient safety margin (at least 0.5 cm) can prevent local tumor progression. This review critically summarizes the current status of RFA for liver metastases from colorectal cancer. PMID:23422905

  1. Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system.

    PubMed

    Zhang, Q-B; Zhang, B-H; Zhang, K-Z; Meng, X-T; Jia, Q-A; Zhang, Q-B; Bu, Y; Zhu, X-D; Ma, D-N; Ye, B-G; Zhang, N; Ren, Z-G; Sun, H-C; Tang, Z-Y

    2016-08-01

    Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-β1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-β1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer. PMID:26686088

  2. 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. PMID:25921181

  3. The importance of registries in cancer control.

    PubMed

    Leal, Yelda A; Fernández-Garrote, Leticia M; Mohar-Betancourt, Alejandro; Meneses-García, Abelardo

    2016-04-01

    Cancer is one of the major causes of morbidity and mortality in the world, with 14.1 million new cases and 8.2 million deaths annually. A marked disparity exists between developed countries and developing countries, with 57% of new cases and 65% of deaths in 2012 occurring in developing countries. This global picture can only be obtained because of data obtained from population-based cancer registries, which allow cancer estimations for different geographic areas. Our objective is to perform a review of different types of registries and their role in the control of cancer. These types of registries are lacking in developing countries. In Central and South America, only 6% of the population is included in cancer registries versus 83% in North America. It is necessary to increase the coverage of cancer registries to obtain more reliable data that will more appropriately guide control programs. PMID:27557391

  4. [Diagnosis and therapy of liver metastasis of breast cancer].

    PubMed

    Voznyĭ, E K; Meshcheriakova, N G; Buianov, S S; Dobrovol'skaia, N I

    1994-01-01

    Thirty seven patients received different modalities of chemotherapy for breast cancer disseminated to the liver. Apparent effect was registered in 9 (24.3%) patients (full effect--3 (8.1%), stabilization--23 (62.1%) and tumor progression--5 (13.5%). The ECE modality proved the most effective. Treatment efficacy was relatively higher in cases of breast tumor removal. The study established a correlation between effectiveness of therapy and size and number of metastatic nodes. PMID:7610636

  5. Deleted in liver cancer protein family in human malignancies (Review)

    PubMed Central

    Lukasik, D.; Wilczek, E.; Wasiutynski, A.; Gornicka, B.

    2011-01-01

    The Deleted in Liver Cancer (DLC) protein family comprises proteins that exert their function mainly by the Rho GTPase-activating protein (GAP) domain and by regulation of the small GTPases. Since Rho GTPases are key factors in cell proliferation, polarity, cytoskeletal remodeling and migration, the aberrant function of their regulators may lead to cell transformation. One subgroup of these proteins is the DLC family. It was found that the first identified gene from this family, DLC1, is often lost in hepatocellular carcinoma and may be involved as a tumor suppressor in the liver. Subsequent studies evaluated the hypothesis that the DLC1 gene acts as a tumor suppressor, not only in liver cancer, but also in other types of cancer. Following DLC1, two other members of the DLC protein family, DLC2 and DLC3, were identified. However, limited published data are available concerning the role of these proteins in malignant transformation. This review focuses on the structure and the role of DLC1 and its relatives in physiological conditions and summarizes data published thus far regarding DLC function in the neoplastic process. PMID:22866123

  6. Suppressing Cancer: The Importance of Being Senescent

    SciTech Connect

    Campisi, Judith

    2005-07-01

    Cellular senescence permanently arrests the cell division cycle, and has long been thought to prevent the growth of cells at risk for transformation into cancer cells. Four new papers now provide evidence that cellular senescence indeed limits the development of malignant cancers in mice and humans.

  7. What Happens After Treatment for Liver Cancer?

    MedlinePlus

    ... to treat or help control the infection. Keeping health insurance and copies of your medical records Even after treatment, it’s very important to keep health insurance . Tests and doctor visits cost a lot, and ...

  8. LiverCancerMarkerRIF: a liver cancer biomarker interactive curation system combining text mining and expert annotations

    PubMed Central

    Dai, Hong-Jie; Wu, Johnny Chi-Yang; Lin, Wei-San; Reyes, Aaron James F.; dela Rosa, Mira Anne C.; Syed-Abdul, Shabbir; Tsai, Richard Tzong-Han; Hsu, Wen-Lian

    2014-01-01

    Biomarkers are biomolecules in the human body that can indicate disease states and abnormal biological processes. Biomarkers are often used during clinical trials to identify patients with cancers. Although biomedical research related to biomarkers has increased over the years and substantial effort has been expended to obtain results in these studies, the specific results obtained often contain ambiguities, and the results might contradict each other. Therefore, the information gathered from these studies must be appropriately integrated and organized to facilitate experimentation on biomarkers. In this study, we used liver cancer as the target and developed a text-mining–based curation system named LiverCancerMarkerRIF, which allows users to retrieve biomarker-related narrations and curators to curate supporting evidence on liver cancer biomarkers directly while browsing PubMed. In contrast to most of the other curation tools that require curators to navigate away from PubMed and accommodate distinct user interfaces or Web sites to complete the curation process, our system provides a user-friendly method for accessing text-mining–aided information and a concise interface to assist curators while they remain at the PubMed Web site. Biomedical text-mining techniques are applied to automatically recognize biomedical concepts such as genes, microRNA, diseases and investigative technologies, which can be used to evaluate the potential of a certain gene as a biomarker. Through the participation in the BioCreative IV user-interactive task, we examined the feasibility of using this novel type of augmented browsing-based curation method, and collaborated with curators to curate biomarker evidential sentences related to liver cancer. The positive feedback received from curators indicates that the proposed method can be effectively used for curation. A publicly available online database containing all the aforementioned information has been constructed at http

  9. Liver scan

    MedlinePlus

    ... hyperplasia or adenoma of the liver Abscess Budd-Chiari syndrome Infection Liver disease (such as cirrhosis or ... Amebic liver abscess Cirrhosis Hepatic vein obstruction (Budd-Chiari) Hepatitis Liver cancer - hepatocellular carcinoma Liver disease Splenic ...

  10. TGF-β signaling in liver and gastrointestinal cancers.

    PubMed

    Katz, L H; Likhter, M; Jogunoori, W; Belkin, M; Ohshiro, K; Mishra, L

    2016-09-01

    Transforming Growth Factor-β (TGF-β) plays crucial and complex roles in liver and gastrointestinal cancers. These include a multitude of distinct functions, such as maintaining stem cell homeostasis, promoting fibrosis, immune modulating, as a tumor suppressor and paradoxically, as a tumor progressor. However, key mechanisms for the switches responsible for these distinct actions are poorly understood, and remain a challenge. The Cancer Genome Atlas (TCGA) analyses and genetically engineered mouse models now provide an integrated approach to dissect these multifaceted and context-dependent driving roles of the TGF-β pathway. In this review, we will discuss the molecular mechanisms of TGF-β signaling, focusing on colorectal, gastric, pancreatic, and liver cancers. Novel drugs targeting the TGF-β pathway have been developed over the last decade, and some have been proven effective in clinical trials. A better understanding of the TGF-β pathway may improve our ability to target it, thus providing more tools to the armamentarium against these deadly cancers. PMID:27039259

  11. Aberrant expression of peroxiredoxin 1 and its clinical implications in liver cancer

    PubMed Central

    Sun, Yu-Lin; Cai, Jian-Qiang; Liu, Fang; Bi, Xin-Yu; Zhou, Lan-Ping; Zhao, Xiao-Hang

    2015-01-01

    AIM: To investigate the expression characteristics of peroxiredoxin 1 (PRDX1) mRNA and protein in liver cancer cell lines and tissues. METHODS: The RNA sequencing data from 374 patients with liver cancer were obtained from The Cancer Genome Atlas. The expression and clinical characteristics of PRDX1 mRNA were analyzed in this dataset. The Kaplan-Meier and Cox regression survival analysis was performed to determine the relationship between PRDX1 levels and patient survival. Subcellular fractionation and Western blotting were used to demonstrate the expression of PRDX1 protein in six liver cancer cell lines and 29 paired fresh tissue specimens. After bioinformatics prediction, a putative post-translational modification form of PRDX1 was observed using immunofluorescence under confocal microscopy and immunoprecipitation analysis in liver cancer cells. RESULTS: The mRNA of PRDX1 gene was upregulated about 1.3-fold in tumor tissue compared with the adjacent non-tumor control (P = 0.005). Its abundance was significantly higher in men than women (P < 0.001). High levels of PRDX1 mRNA were associated with a shorter overall survival time (P = 0.04) but not with recurrence-free survival. The Cox regression analysis demonstrated that patients with high PRDX1 mRNA showed about 1.9-fold increase of risk for death (P = 0.03). In liver cancer cells, PRDX1 protein was strongly expressed with multiple different bands. PRDX1 in the cytosol fraction existed near the theoretical molecular weight, whereas two higher molecular weight bands were present in the membrane/organelle and nuclear fractions. Importantly, the theoretical PRDX1 band was increased, whereas the high molecular weight form was decreased in tumor tissues. Subsequent experiments revealed that the high molecular weight bands of PRDX1 might result from the post-translational modification by small ubiquitin-like modifier-1 (SUMO1). CONCLUSION: PRDX1 was overexpressed in the tumor tissues of liver cancer and served as an

  12. The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography

    PubMed Central

    Chew, Cindy; O’Dwyer, Patrick J

    2016-01-01

    INTRODUCTION 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). METHODS 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. RESULTS 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. CONCLUSION The results of the present study indicate that MR imaging improves the staging of disease in patients with resectable pancreatic cancer. PMID:27353741

  13. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

    PubMed Central

    Hu, Yang; Wu, Xiaoliang; Ma, Rui

    2016-01-01

    Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer. PMID:27429976

  14. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data.

    PubMed

    Zhang, Tianjiao; Hu, Yang; Wu, Xiaoliang; Ma, Rui; Jiang, Qinghua; Wang, Yadong

    2016-01-01

    Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer. PMID:27429976

  15. Lipid peroxidation may not be important in an early stage of alcohol-induced liver injury

    SciTech Connect

    Inomata, T.; Rao, G.A.; Tsukamoto, H.

    1986-03-01

    Role of lipid peroxidation (LP) in alcoholic liver injury (ALI) is still controversial. The authors have previously described a rat model which produced the sequential injury from alcoholic fatty liver to liver necrosis and fibrosis. In the present study, the authors have examined the degree of LP and GSH/GSSG ratio in the liver to investigate whether the LP can be identified in an early stage of progressive ALI. Six pairs of male Wistar rats were continuously infused intragastrically for 30 days with a high fat diet (25% total calories) plus either ethanol or isocaloric amount of dextrose. Following intoxication, the content of diene conjugates in mitochondrial and microsomal lipids as well as the liver GSH/GSSG ratio were determined by the diene difference spectrum and fluorometry, respectively. The UV absorption at 234nm by mitochondrial lipid from alcoholic rats (0.668 +/- 0.023 OD/mg) was significantly (p<0.05) lower than that of controls (0.977 +/- 0.102 OD/mg). The microsomal lipid, however, exhibited a similar absorbance in the two groups (0.986 +/- 0.086 vs 1.149 +/- 0.091 OD/mg0. Similarly, no difference in the ratio of GSH/GSSG was found (6.05 +/- 0.27 vs 5.35 +/- 0.44). These results do not support a concept that LP is an important pathogenetic factor for the progression of alcoholic fatty liver to liver necrosis.

  16. Obesity and liver cancer mortality in Asia: The Asia Pacific Cohort Studies Collaboration.

    PubMed

    Batty, G David; Barzi, Federica; Huxley, Rachel; Chang, Charissa Y; Jee, Sun Ha; Jamrozik, Konrad; Kim, Hyeon Chang; Fang, Xianghua; Lam, Tai H; Woodward, Mark

    2009-12-01

    While obesity is associated with liver cancer in studies from western societies, the paucity of data from Asia limits insights into its aetiological role in this population. We examined the relationship between body mass index (BMI) and liver cancer mortality using data from the Asia Pacific Cohort Studies Collaboration. In 309,203 Asian study members, 4 years of follow-up gave rise to 11,135 deaths from all causes, 420 of which were ascribed to liver cancer. BMI, whether categorised according to current guidelines for Asian groups or World Health Organisation recommendations, was not associated with liver cancer in any of our analyses. PMID:19900847

  17. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2016-06-17

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  18. [Comparison of serum trace element spectrum of liver cancer patients and healthy adults].

    PubMed

    Yin, D Z

    1990-05-01

    The contents of 15 trace elements in the sera of 30 liver cancer patients and 30 healthy adults were assayed by ICP-AES method. The data obtained were analysed by routine statistical tests, multi-variate discrimination analysis, multi-variate stepwise regression analysis and non-linear mapping algorithm. The results showed that the contents of copper, vanadium, cadmium, stannum, cobalt, nickel in liver cancer patients were significantly higher than those in healthy adults. The serum trace element spectrum of liver cancer patients was different from that of healthy adults. Hence, the liver cancer patients could be differentiated from healthy adults by serum trace element spectrum. PMID:2249593

  19. A case of leptospirosis simulating colon cancer with liver metastases

    PubMed Central

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco B.

    2004-01-01

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α - fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal. PMID:15285043

  20. Important drugs for cough in advanced cancer.

    PubMed

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management. PMID:11762966

  1. [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. PMID:27431631

  2. An alternatively spliced variant of CXCR3 mediates the metastasis of CD133+ liver cancer cells induced by CXCL9

    PubMed Central

    Ding, Qiang; Xia, Yujia; Ding, Shuping; Lu, Panpan; Sun, Liang; Liu, Mei

    2016-01-01

    Metastasis of liver cancer is closely linked to tumor microenvironment, in which chemokines and their receptors act in an important role. The CXCR3, the receptor of chemokine CXCL9, belongs to a superfamily of rhodopsin-like seven transmembrane GPCRs and CXCR subfamily. In HCC tissues, CXCR3 was frequently upregulated and correlated with tumor size, tumor differentiation, portal invasion and metastasis. In the study, CXCR3-A isoform that was bound by CXCL9 was found to cause significant change of ERK1/2 phosphorylation level in the MAPK signaling pathway, consequently upregulating the MMP2 and MMP9 expression and promoting invasion and metastasis of CD133+ liver cancer cells. Also, CXCR3-A suppressed the adhesion ability of CD133+ liver cancer cells that stimulated by CXCL9 for 24h. These findings suggest that CXCR3 and its ligand CXCL9 could promote the metastasis of liver cancer cells and might be a potential target for the intervention of liver cancer metastasis. PMID:26883105

  3. Association of serum α-tocopherol, β-carotene, and retinol with liver cancer incidence and chronic liver disease mortality

    PubMed Central

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

    2014-01-01

    Background: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, β-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. Methods: Baseline and 3-year follow-up serum were available from 29 046 and 22 805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. Results: Higher β-carotene and retinol levels were associated with less liver cancer (β-carotene: 0.35, 0.22–0.55, P-trend <0.0001; retinol: 0.58, 0.39–0.85, P-trend=0.0009) and CLD mortality (β-carotene: 0.47, 0.30–0.75, P-trend=0.001; retinol: 0.55, 0.38–0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40–0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64–1.74, P-trend=0.77). Participants with higher levels of β-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. Conclusions: Our findings suggest that higher concentrations of β-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases. PMID:25314058

  4. Cancer

    MedlinePlus

    ... Leukemia Liver cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer ... have any symptoms. In certain cancers, such as pancreatic cancer, symptoms often do not start until the disease ...

  5. Mouse Monoclonal Antibodies for Liver Cancer Research | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute Laboratory of Molecular Biology seeks parties for collaborative research to co-develop and commercialize antibody drug/toxin conjugates as liver cancer therapy and diagnostics.

  6. Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells.

    PubMed

    Kwon, Taeho; Bak, Yesol; Park, Young-Ho; Jang, Gyu-Beom; Nam, Jeong-Seok; Yoo, Jeong Eun; Park, Young Nyun; Bak, In Seon; Kim, Jin-Man; Yoon, Do-Young; Yu, Dae-Yeul

    2016-05-01

    Redox regulation in cancer stem cells (CSCs) is viewed as a good target for cancer therapy because redox status plays an important role in cancer stem-cell maintenance. Here, we investigated the role of Peroxiredoxin II (Prx II), an antioxidant enzyme, in association with maintenance of liver CSCs. Our study demonstrates that Prx II overexpressed in liver cancer cells has high potential for self-renewal activity. Prx II expression significantly corelated with expression of epithelial-cell adhesion molecules (EpCAM) and cytokerain 19 in liver cancer tissues of hepatocellular carcinoma (HCC) patients. Downregulation of Prx II in Huh7 cells with treatment of siRNA reduced expression of EpCAM and CD133 as well as Sox2 in accordance with increased ROS and apoptosis, which were reversed in Huh7-hPrx II cells. Huh7-hPrx II cells exhibited strong sphere-formation activity compared with mock cells. Vascular endothelial growth factor (VEGF) exposure enhanced sphere formation, cell-surface expression of EpCAM and CD133, and pSTAT3 along with activation of VEGF receptor 2 in Huh7-hPrx II cells. The result also emerged in Huh7-H-ras(G12V) and SK-HEP-1-H-ras(G12V) cells with high-level expression of Prx II. Prx II was involved in regulation of VEGF driving cancer stem cells through VEGFR-2/STAT3 signaling to upregulate Bmi1 and Sox2. In addition, knockdown of Prx II in Huh7-H-ras(G12V) cells showed significant reduction in cell migration in vitro and in tumorigenic potential in vivo. Taken together, all the results demonstrated that Prx II plays a key role in the CSC self-renewal of HCC cells through redox regulation. Stem Cells 2016;34:1188-1197. PMID:26866938

  7. Liver Cancer Detection by a Simple, Inexpensive and Effective Immunosensor with Zinc Oxide Nanoparticles

    PubMed Central

    Ching, Congo Tak-Shing; van Hieu, Nguyen; Cheng, Teng-Yun; Fu, Lin-Shien; Sun, Tai-Ping; Liu, Ming-Yen; Huang, Su-Hua; Yao, Yan-Dong

    2015-01-01

    Regular monitoring of blood α-fetoprotein (AFP) and/or carcino-embryonic antigen (CEA) levels is important for the routine screening of liver cancer. However, AFP and CEA have a much lower specificity than des-γ-carboxyprothrombin (DCP) to detect liver cancer. Therefore, the study reported here was designed, to develop a screen-printed DCP immunosensor incorporating zinc oxide nanoparticles, for accurate determination of DCP. The designed immunosensor shows low detection limits for the detection of DCP: 0.440 ng/mL (based on impedance measurement), 0.081 ng/mL (based on real part of impedance measurement) and 0.078 ng/mL (based on imaginary part of impedance measurement), within the range of 3.125 ng/mL to 2000 ng/mL. In addition, there was little interference to DCP determination by molecules such as Na+, K+, Ca2+, Cl−, glucose, urea, and uric acid. It is therefore concluded that the DCP immunosensor developed and reported here is simple, inexpensive and effective, and shows promise in the rapid screening of early-stage liver cancer at home with a point-of-care approach. PMID:26610504

  8. Cytoglobin deficiency promotes liver cancer development from hepatosteatosis through activation of the oxidative stress pathway.

    PubMed

    Thuy, Le Thi Thanh; Matsumoto, Yoshinari; Thuy, Tuong Thi Van; Hai, Hoang; Suoh, Maito; Urahara, Yuka; Motoyama, Hiroyuki; Fujii, Hideki; Tamori, Akihiro; Kubo, Shoji; Takemura, Shigekazu; Morita, Takashi; Yoshizato, Katsutoshi; Kawada, Norifumi

    2015-04-01

    This study was conducted to clarify the role of cytoglobin (Cygb), a globin expressed in hepatic stellate cells (HSCs), in the development of liver fibrosis and cancer in nonalcoholic steatohepatitis (NASH). Cygb expression was assessed in patients with NASH and hepatocellular carcinoma. Mouse NASH model was generated in Cygb-deficient (Cygb(-/-)) or wild-type (WT) mice by giving a choline-deficient amino acid-defined diet and, in some of them, macrophage deletion and N-acetyl cysteine treatment were used. Primary-cultured mouse HSCs isolated from WT (HSCs(Cygb-wild)) or Cygb(-/-) (HSCs(Cygb-null)) mice were characterized. As results, the expression of CYGB was reduced in patients with NASH and hepatocellular carcinoma. Choline-deficient amino acid treatment for 8 weeks induced prominent inflammation and fibrosis in Cygb(-/-) mice, which was inhibited by macrophage deletion. Surprisingly, at 32 weeks, despite no tumor formation in the WT mice, all Cygb(-/-) mice developed liver cancer, which was ameliorated by N-acetyl cysteine treatment. Altered expression of 31 genes involved in the metabolism of reactive oxygen species was notable in Cygb(-/-) mice. Both HSCs(Cygb-null) and Cygb siRNA-transfected-HSCs(Cygb-wild) exhibited the preactivation condition. Our findings provide important insights into the role that Cygb, expressed in HSCs during liver fibrosis, plays in cancer development with NASH. PMID:25665792

  9. Liver Cancer Detection by a Simple, Inexpensive and Effective Immunosensor with Zinc Oxide Nanoparticles.

    PubMed

    Ching, Congo Tak-Shing; van Hieu, Nguyen; Cheng, Teng-Yun; Fu, Lin-Shien; Sun, Tai-Ping; Liu, Ming-Yen; Huang, Su-Hua; Yao, Yan-Dong

    2015-01-01

    Regular monitoring of blood α-fetoprotein (AFP) and/or carcino-embryonic antigen (CEA) levels is important for the routine screening of liver cancer. However, AFP and CEA have a much lower specificity than des-γ-carboxyprothrombin (DCP) to detect liver cancer. Therefore, the study reported here was designed, to develop a screen-printed DCP immunosensor incorporating zinc oxide nanoparticles, for accurate determination of DCP. The designed immunosensor shows low detection limits for the detection of DCP: 0.440 ng/mL (based on impedance measurement), 0.081 ng/mL (based on real part of impedance measurement) and 0.078 ng/mL (based on imaginary part of impedance measurement), within the range of 3.125 ng/mL to 2000 ng/mL. In addition, there was little interference to DCP determination by molecules such as Na⁺, K⁺, Ca(2+), Cl(-), glucose, urea, and uric acid. It is therefore concluded that the DCP immunosensor developed and reported here is simple, inexpensive and effective, and shows promise in the rapid screening of early-stage liver cancer at home with a point-of-care approach. PMID:26610504

  10. Oxidative stress is important in the pathogenesis of liver injury induced by sulindac and lipopolysaccharide cotreatment

    PubMed Central

    Zou, Wei; Roth, Robert A.; Younis, Husam S.; Burgoon, Lyle D.; Ganey, Patricia E.

    2010-01-01

    Among all the nonsteroidal anti-inflammatory drugs, sulindac (SLD) is associated with the greatest incidence of idiosyncratic hepatotoxicity in humans. Previously, an animal model of SLD-induced idiosyncratic hepatotoxicity was developed by cotreating rats with a nonhepatotoxic dose of LPS. Tumor necrosis factor-alpha (TNF) was found to be critically important to the pathogenesis. In this study, the mechanism of liver injury induced by SLD/LPS cotreatment was further explored. Protein carbonyls, products of oxidative stress, were elevated in liver mitochondria of SLD/LPS-cotreated rats. The results of analyzing gene expression in livers of rats before the onset of liver injury indicated that genes associated with oxidative stress were selectively regulated by SLD/LPS cotreatment. Antioxidant treatment with either ebselen or dimethyl sulfoxide attenuated SLD/LPS-induced liver injury. The role of oxidative stress was further investigated in vitro. SLD sulfide, the toxic metabolite of SLD, enhanced TNF-induced cytotoxicity and caspase 3/7 activity in HepG2 cells. SLD sulfide also increased dichlorofluorescein fluorescence, suggesting generation of reactive oxygen species (ROS). Hydrogen peroxide and TNF cotreatment of HepG2 cells caused greater cytotoxicity than either treatment alone. Either antioxidant tempol or a pancaspase inhibitor Z-VAD-FMK decreased cell death as well as caspase 3/7 activity induced by SLD sulfide/TNF coexposure. These results indicate that SLD/LPS treatment causes oxidative stress in livers of rats and suggest that ROS are important in SLD/LPS-induced liver injury in vivo. Furthermore, ROS contribute to the cytotoxic interaction of SLD and TNF by activating caspase 3/7. PMID:20371263

  11. Reproducibility of liver position using active breathing coordinator for liver cancer radiotherapy

    SciTech Connect

    Eccles, Cynthia; Brock, Kristy K.; Bissonnette, Jean-Pierre; Hawkins, Maria; Dawson, Laura A. . E-mail: laura.dawson@rmp.uhn.on.ca

    2006-03-01

    Purpose: To measure the intrabreath-hold liver motion and the intrafraction and interfraction reproducibility of liver position relative to vertebral bodies using an active breathing coordinator (ABC) in patients with unresectable liver cancer treated with hypofractionated stereotactic body radiation therapy (SBRT). Methods: Tolerability of ABC and organ motion during ABC was assessed using kV fluoroscopy in 34 patients. For patients treated with ABC, repeat breath-hold CT scans in the ABC breath-hold position were acquired at simulation to estimate the volumetric intrafraction reproducibility of the liver relative to the vertebral bodies. In addition, preceding each radiation therapy fraction, with the liver immobilized using ABC, repeat anteroposterior (AP) megavoltage verification images were obtained. Off-line alignments were completed to determine intrafraction reproducibility (from repeat images obtained before one treatment) and interfraction reproducibility (from comparisons of the final image for each fraction with the AP) of diaphragm position relative to vertebral bodies. For each image set, the vertebral bodies were aligned, and the resultant craniocaudal (CC) offset in diaphragm position was measured. Liver position during ABC was also evaluated from kV fluoroscopy acquired at the time of simulation, kV fluoroscopy at the time of treatment, and from MV beam's-eye view movie loops acquired during treatment. Results: Twenty-one of 34 patients were screened to be suitable for ABC. The average free breathing range of these patients was 13 mm (range, 5-1 mm). Fluoroscopy revealed that the average maximal diaphragm motion during ABC breath-hold was 1.4 mm (range, 0-3.4 mm). The MV treatment movie loops confirmed diaphragm stability during treatment. For a measure of intrafraction reproducibility, an analysis of 36 repeat ABC computed tomography (CT) scans in 14 patients was conducted. The average mean difference in the liver surface position was -0.9 mm, -0

  12. The state of regional therapy in the management of metastatic colorectal cancer to the liver.

    PubMed

    Cho, May; Gong, Jun; Fakih, Marwan

    2016-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality in the United States. Most colorectal cancer patients die from advanced disease, and two-thirds of CRC deaths are due to liver metastases. Liver resection provides the best curative option for patients with colorectal liver metastases (CRLM), yet only 20% of those patients are eligible for liver metastases resection for curative intent. Loco-regional treatment of CRLM may provide additional benefits in terms of down-staging for resection and prolonged hepatic disease control. This review focusses on hepatic arterial infusion, radioembolization and chemoembolization. PMID:26652741

  13. Factors predicting early postoperative liver cirrhosis-related complications after lung cancer surgery in patients with liver cirrhosis.

    PubMed

    Iwata, Takashi; Inoue, Kiyotoshi; Nishiyama, Noritoshi; Nagano, Koshi; Izumi, Nobuhiro; Tsukioka, Takuma; Hanada, Shoji; Suehiro, Shigefumi

    2007-12-01

    We aimed to determine the factors predicting liver cirrhosis-related complications in the early postoperative period after lung cancer surgery in patients with liver cirrhosis. We retrospectively reviewed the medical records of patients who underwent curative surgery for primary lung cancer in our institute from January 1990 to March 2007, finding 37 cases with comorbid liver cirrhosis. These patients were divided into two groups, according to whether liver failure, bleeding, and critical infection had occurred postoperatively. Various clinical parameters were analyzed statistically between the bigeminal groups. Liver cirrhosis-related complications occurred in seven of the 37 patients (18.9%). Transient liver failure occurred in two patients (5.4%) after pulmonary resection. Acute intrathoracic bleeding occurred in four cases (10.8%). Two patients died (5.4%) in both cases due to sepsis. Preoperative total bilirubin (P<0.05), and indocyanine green retention rate at 15 min (P<0.05) were significantly higher in patients with liver failure. Only serum value of total bilirubin was an independent risk factor (P<0.05) by multivariate analysis. In predicting death from infection, only preoperative nutritional status was a significant risk factor (P<0.05). To avoid postoperative cirrhosis-related complications, preoperative preparation to improve their liver function and nutrition status is essential. PMID:17766277

  14. Cantilever with immobilized antibody for liver cancer biomarker detection

    NASA Astrophysics Data System (ADS)

    Shuaipeng, Wang; Jingjing, Wang; Yinfang, Zhu; Jinling, Yang; Fuhua, Yang

    2014-10-01

    A novel cantilever array-based bio-sensor was batch-fabricated with IC compatible MEMS technology for precise liver cancer bio-marker detection. A micro-cavity was designed in the free end of the cantilever for local antibody-immobilization, thus the adsorption of the cancer biomarker takes place only in the local region of the cantilever instead of the whole lever, and the effect of adsorption-induced k variation can be dramatically reduced. These structural features offer several advantages: high sensitivity, high throughput, high mass detection accuracy, and a portable system. In addition, an analytical model has been established to eliminate the effect of the adsorption-induced lever stiffness change and has been applied to the precise mass detection of the cancer biomarker AFP; the experimentally detected AFP antigen mass by the sensor (7.6 pg/mL) is quite close to the calculated one (5.5 pg/mL), two orders of magnitude better than those of the fully antibody-immobilized cantilever sensor. These approaches can promote real applications of the cantilever sensors in cancer diagnosis.

  15. 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.

  16. Potential use of Doppler perfusion index in detection of occult liver metastases from colorectal cancer

    PubMed Central

    Patrlj, Leonardo; Bušić, Željko; Kolovrat, Marijan; Rakić, Mislav; Kliček, Robert; Židak, Marcel; Stipančić, Igor

    2014-01-01

    Many clinical and preclinical studies demonstrated that measurements of liver hemodynamic [Doppler perfusion index (DPI)] may be used to accurately diagnose and predict liver metastases from primary colorectal cancer in a research setting. However, Doppler measurements have some serious limitations when applied to general population. Ultrasound is very operator-dependent, and requires skilled examiners. Also, many conditions may limit the use of Doppler ultrasound and ultrasound in general, such as the presence of air in digestive tract, cardiac arrhythmias, vascular anomalies, obesity and other conditions. Therefore, in spite of the results from clinical studies, its value may be limited in everyday practice. On the contrary, scientific research of the DPI in detection of liver metastases is of great importance, since current research speaks strongly for the presence of systemic vasoactive substance responsible for observed hemodynamic changes. Identification of such a systemic vasoactive substance may lead to the development of a simple and reproducible laboratory test that may reliably identify the presence of occult liver metastases and therefore increase the success of adjuvant chemotherapy through better selection of patients. Further research in this subject is therefore of great importance. PMID:25392837

  17. Cetuximab and/or Dasatinib in Patients With Colorectal Cancer and Liver Metastases That Can Be Removed by Surgery

    ClinicalTrials.gov

    2014-05-07

    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

  18. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    ClinicalTrials.gov

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  19. Capecitabine-related liver lesions: sinusoidal dilatation mimicking liver metastasis.

    PubMed

    Groom, Katherine; Penna, Marta; Arul, Dhili; Steward, Michael; Leonard, Pauline; Wilson, Jonathan

    2016-06-01

    A 30-year-old lady treated with capecitabine for primary colon adenocarcinoma developed liver lesions suspicious for metastasis. Liver biopsies showed sinusoidal dilatation thought to be secondary to capecitabine. This case highlights the importance of differentiating between benign and malignant liver lesions during cancer surveillance preventing unnecessary liver resections for benign disease. PMID:27398193

  20. 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.

  1. Important predictor of mortality in patients with end-stage liver disease

    PubMed Central

    Lee, Hyun Woong

    2013-01-01

    Prognosis is an essential part of the baseline assessment of any disease. For predicting prognosis of end-stage liver disease, many prognostic models were proposed. Child-Pugh score has been the reference for assessing the prognosis of cirrhosis for about three decades in end-stage liver disease. Despite of several limitations, recent large systematic review showed that Child-Pugh score was still robust predictors and it's components (bilirubin, albumin and prothrombin time) were followed by Child-Pugh score. Recently, Model for end-stage liver disease (MELD) score emerged as a "modern" alternative to Child-Pugh score. The MELD score has been an important role to accurately predict the severity of liver disease and effectively assess the risk of mortality. Due to several weakness of MELD score, new modified MELD scores (MELD-Na, Delta MELD) have been developed and validated. This review summarizes the current knowledge about the prognostic factors in end-stage liver disease, focusing on the role of Child-Pugh and MELD score. PMID:23837134

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

    PubMed Central

    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. PMID:27196400

  3. 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. PMID:26383527

  4. 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

  5. Surveillance, Diagnosis, Treatment, and Outcome of Liver Cancer in Japan

    PubMed Central

    Kudo, Masatoshi

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the third leading cause of cancer-related death worldwide. HCC is most common in Asia, but its prevalence is rapidly increasing in Western countries; consequently, HCC is a global medical issue that urgently needs to be addressed. Japan is the only developed country that has experienced both hepatitis B-related and hepatitis C-related HCC and has a long history of innovation when it comes to new diagnostic and therapeutic modalities, such as computed tomography angiography, anatomical resection, ablation, and transarterial chemoembolization. Among these innovations, a nationwide surveillance program was well established by the 1980s, and such a long-term national program does not exist anywhere else in the world. Summary More than 60% of the initially detected HCCs in Japan are Barcelona Clinic Liver Cancer stage 0 or A, which can undergo curative therapies such as resection, ablation, or transplantation. The recent 5-year survival rate of HCC patients in Japan was 43% and the median survival time was 50 months. In addition, both incidence and mortality rates are drastically declining as a result of the successful surveillance program, careful diagnostic flow, and extensive repeated treatments. Key Message Japan's successful model in the surveillance, diagnosis, and treatment of HCC should be adopted as widely as possible to improve the survival of HCC patients worldwide. PMID:26020028

  6. Liver Label Retaining Cancer Cells Are Relatively Resistant to the Reported Anti-Cancer Stem Cell Drug Metformin

    PubMed Central

    Xin, Hong-Wu; Ambe, Chenwi M.; Miller, Tyler C.; Chen, Jin-Qiu; Wiegand, Gordon W.; Anderson, Andrew J.; Ray, Satyajit; Mullinax, John E.; Hari, Danielle M.; Koizumi, Tomotake; Godbout, Jessica D.; Goldsmith, Paul K.; Stojadinovic, Alexander; Rudloff, Udo; Thorgeirsson, Snorri S.; Avital, Itzhak

    2016-01-01

    Background & Aims: Recently, we reported that liver Label Retaining Cancer Cells (LRCC) can initiate tumors with only 10 cells and are relatively resistant to the targeted drug Sorafenib, a standard of practice in advanced hepatocellular carcinoma (HCC). LRCC are the only cancer stem cells (CSC) isolated alive according to a stem cell fundamental function, asymmetric cell division. Metformin has been reported to preferentially target many other types of CSC of different organs, including liver. It's important to know if LRCC, a novel class of CSC, are relatively resistant to metformin, unlike other types of CSC. As metformin inhibits the Sorafenib-Target-Protein (STP) PI3K, and LRCC are newly described CSC, we undertook this study to test the effects of Metformin on Sorafenib-treated HCC and HCC-derived-LRCC. Methods: We tested various STP levels and phosphorylation status, associated genes' expression, proliferation, viability, toxicity, and apoptosis profiles, before and after treatment with Sorafenib with/without Metformin. Results: Metformin enhances the effects of Sorafenib on HCC, and significantly decreased viability/proliferation of HCC cells. This insulin-independent effect was associated with inhibition of multiple STPs (PKC, ERK, JNK and AKT). However, Metformin increased the relative proportion of LRCCs. Comparing LRCC vs. non-LRCC, this effect was associated with improved toxicity and apoptosis profiles, down-regulation of cell death genes and up-regulation of cell proliferation and survival genes in LRCC. Concomitantly, Metformin up-regulated pluripotency, Wnt, Notch and SHH pathways genes in LRCC vs. non-LRCC. Conclusions: Metformin and Sorafenib have enhanced anti-cancer effects. However, in contradistinction to reports on other types of CSC, Metformin is less effective against HCC-derived-CSC LRCC. Our results suggest that combining Metformin with Sorafenib may be able to repress the bulk of tumor cells, but as with other anti-cancer drugs, may

  7. Effect of Combined Treatment Using Wilfortrine and Paclitaxel in Liver Cancer and Related Mechanism

    PubMed Central

    Li, Shuzhen; Zheng, Lei

    2016-01-01

    Background Liver cancer is a common malignant tumor with high mortality. Currently, effective medicines against liver cancer are still lacking. Paclitaxel is a wide-spectrum anti-tumor agent, while wilfortrine has been shown to have an inhibitory effect on the proliferation of liver cancer cells. This study thus investigated the potential effect of paclitaxel combined with wilfortrine on cultured liver cancer cells and related mechanisms, in order to provide evidence for pathogenesis and treatment of liver cancer. Material/Methods Liver cancer cell line HpeG2 was divided into control, paclitaxel, wilfortrine, and combined treatment groups. Cell proliferation was tested by MTT, while invasion was detected in Transwell chamber assay. Apoptotic protein Bcl-2 and Bax expression levels were further quantified using real-time PCR and Western blotting. Results Both of those 2 drugs can effectively inhibit cancer cell proliferation, depress invasion ability, increase Bcl-2 expression, and elevate Bax expression levels (p<0.05 in all cases). The combined therapy had better treatment efficacy compared to either of those drugs alone (p<0.05). Conclusions The combined treatment using wilfortrine and paclitaxel can inhibit proliferation and invasion of liver cancer cells via down-regulating Bcl-2 and up-regulating Bax, with better efficacy than single use of either drug. PMID:27043783

  8. Constitutive expression of Wnt/β-catenin target genes promotes proliferation and invasion of liver cancer stem cells

    PubMed Central

    CHEN, WEI; ZHANG, YU-WEI; LI, YANG; ZHANG, JIAN-WEN; ZHANG, TONG; FU, BIN-SHENG; ZHANG, QI; JIANG, NAN

    2016-01-01

    Wnt/β-catenin is an important signaling pathways involved in the tumorgenesis, progression and maintenance of cancer stem cells (CSCs). In the present study, the role of Wnt/β-catenin signaling in CSC-mediated tumorigenesis and invasion in liver CSCs was investigated. A small population of cancer stem-like side population (SP) cells (3.6%) from liver cancer samples were identified. The cells were highly resistant to drug treatment due to the enhanced expression of drug efflux pumps, such as ABC subfamily G member 2, multidrug resistance protein 1 and ATP-binding cassette subfamily B member 5. Furthermore, using TOPflash and reverse transcription-quantitative polymerase chain reaction analysis, Wnt/β-catenin signaling and the transcriptional regulation of Wnt/β-catenin target genes including dickkopf Wnt signaling pathway inhibitor 1, axis inhibition protein 2 and cyclin D1 were observed to be markedly upregulated in liver cancer SP cells. As a consequence, SP cells possessed infinite cell proliferation potential and the ability to generating tumor spheres. In addition, upon reducing Wnt/β-catenin signaling, the rates of proliferation, tumor sphere formation and tumor invasion of SP cells were markedly reduced. Therefore, these data suggest that Wnt/β-catenin signaling is a potential therapeutic target to reduce CSC-mediated tumorigenicity and invasion in liver cancer. PMID:26956539

  9. 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.

  10. Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases: A Single Institution Experience

    PubMed Central

    Nace, Gary W.; Steel, Jennifer L.; Amesur, Nikhil; Zajko, Albert; Nastasi, Bryon E.; Joyce, Judith; Sheetz, Michael; Gamblin, T. Clark

    2011-01-01

    Purpose. We sought to evaluate our experience using yttrium-90 (90Y) resin microsphere hepatic radioembolization as salvage therapy for liver-dominant metastatic colorectal cancer (mCRC). Methods. A retrospective review of consecutive patients with unresectable mCRC who were treated with 90Y after failing first and second line systemic chemotherapy. Demographics, treatment dose, biochemical and radiographic response, toxicities, and survival were examined. Results. Fifty-one patients underwent 90Y treatments of which 69% were male. All patients had previously undergone extensive chemotherapy, 31% had undergone previous liver-directed therapy and 24% had a prior liver resection. Using RECIST criteria, either stable disease or a partial response was seen in 77% of patients. Overall median survival from the time of first 90Y treatment was 10.2 months (95% CI = 7.5–13.0). The absence of extrahepatic disease at the time of treatment with 90Y was associated with an improved survival, median survival of 17.0 months (95% CI = 6.4–27.6), compared to those with extrahepatic disease at the time of treatment with 90Y, 6.7 months (95% CI = 2.7–10.6 Conclusion: 90Y therapy is a safe locoregional therapy that provides an important therapeutic option to patients who have failed first and second line chemotherapy and have adequate liver function and performance status. PMID:22312513

  11. The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma.

    PubMed

    Xiang, Yan; Yang, Ting; Pang, Bing-Yao; Zhu, Ying; Liu, Yong-Ning

    2016-01-01

    Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with "stem-like" characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a "global" marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies. PMID:27610139

  12. The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma

    PubMed Central

    Yang, Ting

    2016-01-01

    Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with “stem-like” characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a “global” marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies. PMID:27610139

  13. Liver-directed therapies in metastatic colorectal cancer

    PubMed Central

    Clark, Margaret E.

    2014-01-01

    Colorectal cancer (CRC) is a major health concern in the United States (US) with over 140,000 new cases diagnosed in 2012. The most common site for CRC metastases is the liver. Hepatic resection is the treatment of choice for colorectal liver metastases (CLM), with a 5-year survival rate ranging from 35% to 58%. Unfortunately, only about 20% of patients are eligible for resection. There are a number of options for extending resection to more advanced patients including systemic chemotherapy, portal vein embolization (PVE), two stage hepatectomy, ablation and hepatic artery infusion (HAI). There are few phase III trials comparing these treatment modalities, and choosing the right treatment is patient dependent. Treating hepatic metastases requires a multidisciplinary approach and knowledge of all treatment options as there continues to be advances in management of CLM. If a patient can undergo a treatment modality in order to increase their potential for future resection this should be the primary goal. If the patient is still deemed unresectable then treatments that lengthen disease-free and overall-survival should be pursued. These include chemotherapy, ablation, HAI, chemoembolization, radioembolization (RE) and stereotactic radiotherapy. PMID:25276410

  14. IDH mutations in liver cell plasticity and biliary cancer

    PubMed Central

    Saha, Supriya K; Parachoniak, Christine A; Bardeesy, Nabeel

    2014-01-01

    Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer associated with the bile ducts within the liver. These tumors are characterized by frequent gain-of-function mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes—that are also common in subsets of neural, haematopoietic and bone tumors, but rare or absent in the other types of gastrointestinal malignancy. Mutant IDH acts through a novel mechanism of oncogenesis, producing high levels of the metabolite 2-hydroxyglutarate, which interferes with the function of α-ketoglutarate-dependent enzymes that regulate diverse cellular processes including histone demethylation and DNA modification. Recently, we used in vitro stem cell systems and genetically engineered mouse models (GEMMs) to demonstrate that mutant IDH promotes ICC formation by blocking hepatocyte differentiation and increasing pools of hepatic progenitors that are susceptible to additional oncogenic hits leading to ICC. We found that silencing of HNF4A—encoding a master transcriptional regulator of hepatocyte identity and quiescence—was critical to mutant IDH-mediated inhibition of liver differentiation. In line with these findings, human ICC with IDH mutations are characterized by a hepatic progenitor cell transcriptional signature suggesting that they are a distinct ICC subtype as compared to IDH wild type tumors. The role of mutant IDH in controlling hepatic differentiation state suggests the potential of newly developed inhibitors of the mutant enzyme as a form of differentiation therapy in a solid tumor. PMID:25485496

  15. Glaucocalyxin A inhibits the growth of liver cancer Focus and SMMC-7721 cells

    PubMed Central

    TANG, LISHA; JIN, XIAOFENG; HU, XIAOHUI; HU, XIAODING; LIU, ZULONG; YU, LONG

    2016-01-01

    Liver cancer is one of the most common types of cancer, and hepatoma demonstrates a poor long-term prognosis. The present study reports that glaucocalyxin A (GLA), a natural product isolated from Rabdosia umbrosa, inhibits the growth of the liver cancer Focus and SMMC-7721 cell lines in a dose- and time-dependent manner. The present study revealed that GLA arrested the liver cancer cells at the G2/M stage of the cell cycle and led to decreased expression of caspase 3 and the cleavage of poly(adenosine diphosphate-ribose) polymerase. Overall, the present study demonstrated that GLA inhibits the growth of liver cancer cells by G2/M stage cell-cycle arrest and cell apoptosis. PMID:26893714

  16. Synergistic ablation of liver tissue and liver cancer cells with high-intensity focused ultrasound and ethanol.

    PubMed

    Hoang, Nguyen H; Murad, Hakm Y; Ratnayaka, Sithira H; Chen, Chong; Khismatullin, Damir B

    2014-08-01

    We investigated the combined effect of ethanol and high-intensity focused ultrasound (HIFU), first, on heating and cavitation bubble activity in tissue-mimicking phantoms and porcine liver tissues and, second, on the viability of HepG2 liver cancer cells. Phantoms or porcine tissues were injected with ethanol and then subjected to HIFU at acoustic power ranging from 1.2 to 20.5 W (HIFU levels 1-7). Cavitation events and the temperature around the focal zone were measured with a passive cavitation detector and embedded type K thermocouples, respectively. HepG2 cells were subjected to 4% ethanol solution in growth medium (v/v) just before the cells were exposed to HIFU at 2.7, 8.7 or 12.0 W for 30 s. Cell viability was measured 2, 24 and 72 h post-treatment. The results indicate that ethanol and HIFU have a synergistic effect on liver cancer ablation as manifested by greater temperature rise and lesion volume in liver tissues and reduced viability of liver cancer cells. This effect is likely caused by reduction of the cavitation threshold in the presence of ethanol and the increased rate of ethanol diffusion through the cell membrane caused by HIFU-induced streaming, sonoporation and heating. PMID:24798386

  17. The Role of MicroRNAs in Human Liver Cancers

    PubMed Central

    Braconi, Chiara; Henry, Jon C.; Kogure, Takayuki; Schmittgen, Thomas; Patel, Tushar

    2014-01-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver of global importance. Recent studies of the expression and role of microRNA (miRNA) in HCC are providing new insights into disease pathogenesis. In addition, therapeutic efforts targeting specific miRNAs are being evaluated in animal models of HCC. The potential of miRNAs as biomarkers of disease or prognostic markers is being explored. Herein, we review studies of miRNA expression in human HCC, and discuss recent advances in knowledge about the involvement and role of selected miRNAs in disease pathogenesis, as biomarkers, or as therapeutic targets for HCC. PMID:22082761

  18. The role of microRNAs in human liver cancers.

    PubMed

    Braconi, Chiara; Henry, Jon C; Kogure, Takayuki; Schmittgen, Thomas; Patel, Tushar

    2011-12-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver of global importance. Recent studies of the expression and role of microRNA (miRNA) in HCC are providing new insights into disease pathogenesis. In addition, therapeutic efforts targeting specific miRNAs are being evaluated in animal models of HCC. The potential of miRNAs as biomarkers of disease or prognostic markers is being explored. Herein, we review studies of miRNA expression in human HCC, and discuss recent advances in knowledge about the involvement and role of selected miRNAs in disease pathogenesis, as biomarkers, or as therapeutic targets for HCC. PMID:22082761

  19. Prostate Cancer in Young Men: An Important Clinical Entity

    PubMed Central

    Salinas, Claudia A.; Tsodikov, Alex; Ishak-Howard, Miriam; Cooney, Kathleen A.

    2014-01-01

    Prostate cancer is considered a disease of older men, but today over 10% of new diagnoses occur in U.S. men ≤ 55 years. Early onset prostate cancer, i.e., diagnosed at ≤55 years, differs from prostate cancer in older men in several ways. Among men diagnosed with high grade and stage prostate cancer, men with early onset prostate cancer are more likely to die of their cancer, with higher cause-specific mortality than all others except those diagnosed over age 80. This suggests that important biological differences may exist in early onset disease compared to late onset disease. Furthermore, early onset prostate cancer has been shown to have a more significant genetic component indicating that this group may benefit more than most from evaluation of genetic risk. Clinically, although the majority of cases ≤ 55 years are diagnosed with low risk disease, their extended life expectancy exposes them to long-term risk of disease progression resulting in death from prostate cancer, but also to prolonged impact from treatment-related morbidities. These patients pose unique challenges and opportunities for both the research and clinical communities. We therefore suggest that early onset prostate cancer is a distinct phenotype, from both an etiologic and clinical perspective, that deserves further attention. PMID:24818853

  20. Analysis of liver-directed therapies in U.S. cancer patients

    PubMed Central

    Alese, O.B.; Kim, S.; Chen, Z.; Ramalingam, S.S.; Owonikoko, T.K.; El-Rayes, B.F.

    2015-01-01

    Background The liver is a common site of primary and metastatic cancer. Liver-directed therapies are commonly used to treat cancer involving the liver. We report on the patterns, predictors, and outcomes of liver-directed therapies in hospitalized cancer patients in the United States. Methods Data were obtained from all U.S. states that contributed to the Nationwide Inpatient Sample maintained by the Agency for Healthcare Research and Quality between 2006 and 2010. Univariate and multivariate testing was used to identify factors significantly associated with patient outcome. Results For the 5-year period of interest, 12,540 patient discharges were identified. Mean age in the sample was 60 years. Primary liver lesions (n = 8840) made up 26.9% of the sample; the remaining cases were metastases. Most procedures were performed in large (79%) urban (98%) hospitals and in patients with insurance (97.9%). The most common intervention was partial hepatectomy (42.7%), followed by open (9.9%), percutaneous (7.2%), and laparoscopic (5.04%) ablation of liver lesions; embolization (9.8%); and liver transplantation (2.64%). The incidence of in-hospital mortality was very low (2.4%), and the complication rate was 12.2%. Complications such as acute liver necrosis, ascites, hepatic coma, hepatorenal syndrome, liver abscess, and high number of comorbid illnesses (>8) accounted for 60% of the in-hospital mortality. Conclusions The low rate of morbidity and mortality associated with liver-directed therapies in hospitalized cancer patients supports the continuing utility of such procedures in the management of primary and metastatic liver cancer. The patterns of health disparities observed with respect to the use of liver-directed therapies are concerning. PMID:26715883

  1. The Link Between Hepatitis B and Liver Cancer: The Asian American Community

    Cancer.gov

    Dr. Moon Chen, Professor of the Department of Internal Medicine and Associate Director of Cancer Control at the University of California-Davis Comprehensive Cancer Center, speaks about Hepatitis B and Liver Cancer as a more prevalent problem in the Asian American community.

  2. A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases

    PubMed Central

    Lam, Vincent WT; Laurence, Jerome M; Pang, Tony; Johnston, Emma; Hollands, Michael J; Pleass, Henry CC; Richardson, Arthur J

    2014-01-01

    Background: Since the liver metastases rather than the colorectal cancer itself is the main determinant of patient’s survival, the ‘Liver-First Approach (LFA)’ with upfront chemotherapy followed by a hepatic resection of colorectal liver metastases (CLM) and finally a colorectal cancer resection was proposed. The aim of this review was to analyse the evidence for LFA in patients with colorectal cancer and synchronous CLM. Methods: A literature search of databases (MEDLINE and EMBASE) to identify published studies of LFA in patients with colorectal cancer and synchronous CLM was undertaken focussing on the peri-operative regimens of LFA and survival outcomes. Results: Three observational studies and one retrospective cohort study were included for review. A total of 121 patients with colorectal cancer and synchronous CLM were selected for LFA. Pre-operative chemotherapy was used in 99% of patients. One hundred and twelve of the initial 121 patients (93%) underwent a hepatic resection of CLM. In total, 60% had a major liver resection and the R0 resection rate was 93%. Post-operative morbidity and mortality after the hepatic resection were 20% and 1%, respectively. Ultimately, 89 of the initial 121 (74%) patients underwent a colorectal cancer resection. Post-operative morbidity and mortality after a colorectal resection were 50% and 6%, respectively. The median overall survival was 40 months (range 19–50) with a recurrence rate of 52%. Conclusions: Current evidence suggests that LFA is safe and feasible in selected patients with colorectal cancer and synchronous CLM. Future studies are required to further define patient selection criteria for LFA and the exact role of LFA in the management of synchronous CLM. PMID:23509899

  3. Role of liver stem cells in hepatocarcinogenesis

    PubMed Central

    Xu, Lei-Bo; Liu, Chao

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

  4. Preclinical Evaluation of 4-Methylthiobutyl Isothiocyanate on Liver Cancer and Cancer Stem Cells with Different p53 Status

    PubMed Central

    Lamy, Evelyn; Hertrampf, Anke; Herz, Corinna; Schüler, Julia; Erlacher, Miriam; Bertele, Daniela; Bakare, Adekunle; Wagner, Meike; Weiland, Timo; Lauer, Ulrich; Drognitz, Oliver; Huber, Roman; Rohn, Sascha; Giesemann, Torsten; Mersch-Sundermann, Volker

    2013-01-01

    Isothiocyanates from plants of the order Brassicales are considered promising cancer chemotherapeutic phytochemicals. However, their selective cytotoxicity on liver cancer has been barely researched. Therefore, in the present study, we systematically studied the chemotherapeutic potency of 4-methylthiobutyl isothiocyanate (MTBITC). Selective toxicity was investigated by comparing its effect on liver cancer cells and their chemoresistant subpopulations to normal primary hepatocytes and liver tissue slices. Additionally, in a first assessment, the in vivo tolerability of MTBITC was investigated in mice. Growth arrest at G2/M and apoptosis induction was evident in all in vitro cancer models treated with MTBITC, including populations with cancer initiating characteristics. This was found independent from TP53; however cell death was delayed in p53 compromised cells as compared to wt-p53 cells which was probably due to differential BH3 only gene regulation i. e. Noxa and its antagonist A1. In normal hepatocytes, no apoptosis or necrosis could be detected after repeated administration of up to 50 µM MTBITC. In mice, orally applied MTBITC was well tolerated over 18 days of treatment for up to 50 mg/kg/day, the highest dose tested. In conclusion, we could show here that the killing effect of MTBITC has a definite selectivity for cancer cells over normal liver cells and its cytotoxicity even applies for chemoresistant cancer initiating cells. Our study could serve for a better understanding of the chemotherapeutic properties of isothiocyanates on human liver-derived cancer cells. PMID:23936472

  5. Interaction-based discovery of functionally important genes in cancers

    PubMed Central

    Ghersi, Dario; Singh, Mona

    2014-01-01

    A major challenge in cancer genomics is uncovering genes with an active role in tumorigenesis from a potentially large pool of mutated genes across patient samples. Here we focus on the interactions that proteins make with nucleic acids, small molecules, ions and peptides, and show that residues within proteins that are involved in these interactions are more frequently affected by mutations observed in large-scale cancer genomic data than are other residues. We leverage this observation to predict genes that play a functionally important role in cancers by introducing a computational pipeline (http://canbind.princeton.edu) for mapping large-scale cancer exome data across patients onto protein structures, and automatically extracting proteins with an enriched number of mutations affecting their nucleic acid, small molecule, ion or peptide binding sites. Using this computational approach, we show that many previously known genes implicated in cancers are enriched in mutations within the binding sites of their encoded proteins. By focusing on functionally relevant portions of proteins—specifically those known to be involved in molecular interactions—our approach is particularly well suited to detect infrequent mutations that may nonetheless be important in cancer, and should aid in expanding our functional understanding of the genomic landscape of cancer. PMID:24362839

  6. The combination of FOLFOX4 and bevacizumab may enable salvage surgery of unresectable liver metastases in colon cancer.

    PubMed

    Sereno Moyano, María; Casado Sáenz, Enrique; de Castro-Carpeño, Javier; Belda-Iniesta, Cristóbal

    2009-04-01

    Colorectal cancer treatment has experienced important advances in the last 5 years. New targeted therapies have been included in the classical regimens based on 5-fluorouracil, oxaliplatin, or irinotecan. This new approach has brought great revolution in the treatment of this type of cancer. Bevacizumab (Avastin), a new antivascular endothelial growth factor drug, has been shown to improve overall survival in combination with chemotherapy in first-line and second-line settings as compared with standard chemotherapy regimens alone. This case report demonstrates our experience with bevacizumab in a colon cancer patient with liver, lung, and regional lymph node metastases who had a relapse in the liver after adjuvant treatment with capecitabine (Xeloda). The addition of bevacizumab to the FOLFOX4 regimen resulted in a partial response that provided an opportunity for salvage hepatic surgery. PMID:19352109

  7. Co-migration of colon cancer cells and CAFs induced by TGFβ₁ enhances liver metastasis.

    PubMed

    Gonzalez-Zubeldia, Idoia; Dotor, Javier; Redrado, Miriam; Bleau, Anne-Marie; Manrique, Irene; de Aberasturi, Arrate L; Villalba, Maria; Calvo, Alfonso

    2015-03-01

    Colorectal cancer (CRC) cells often metastatize to the liver. Cancer-associated fibroblasts (CAFs) enhance metastasis by providing cytokines that create a favorable microenvironment and by inducing co-dissemination with tumor cells. However, the mechanisms of co-metastatization remain elusive. The aim of this study is to assess the role of TGFβ1 in CRC cell-CAFs attachment and its impact on liver metastasis. CAFs were obtained after xenotransplantation of Mc38 cells into EGFP-C57BL/6 mice. Attachment experiments with CRC cells and CAFs (with or without TGFβ1 and the inhibitory peptide P17) were carried out, as well as in vivo liver metastasis assays. TGFβ1 induced adhesion of CRC cells to CAFs, whereas exposure to P17 abrogated this effect. Co-injection of Mc38 cells with CAFs intrasplenically increased liver metastasis, as compared to injection of tumor cells alone. Pretreatment of Mc38 cells with TGFβ1 enhanced the metastatic burden, in comparison to untreated Mc38 + CAFs. TGFβ1-pretreated Mc38 cells co-metastatized with CAFs to the liver in a highly efficient way. Importantly, the metastatic burden was significantly reduced (p < 0.001) when P17 was administered in mice. The number of PCNA+ and CD-31+ cells was also reduced by P17 in these animals, indicating a decrease in proliferation and angiogenesis upon TGFβ1 signaling blockade. Through microarray analysis, we identified potential TGFβ1-regulated genes that may mediate cancer cell-stroma interactions to increase metastasis. In conclusion, TGFβ1 promotes co-travelling of CRC cells and CAFs to the liver to enhance metastasis. Our results strongly support the use of TGFβ1 targeted drugs as a novel strategy to reduce liver metastasis in CRC patients. PMID:25557989

  8. Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine.

    PubMed

    Xu, Huarong; Liu, Ran; He, Bosai; Bi, Cathy Wenchuan; Bi, Kaishun; Li, Qing

    2016-01-01

    Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography-tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50) and liver cancer patients (n = 50) were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer. PMID:27517900

  9. Ability of luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 binding to LHRH receptor on human liver cancer cells

    PubMed Central

    Gong, Shou-Liang; Zhao, Gang; Zhao, Hong-Guang; Lü, Wen-Tian; Liu, Guang-Wei; Zhu, Ping

    2004-01-01

    AIM: To explore the ability of recombinant toxin luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40) and LHRH binding to LHRH receptor (LHRHR) on the membrane surface of human liver cancer HEPG cells. METHODS: LHRH was labeled by using 125I with enzymatic reaction. The affinity and receptor volume of LHRH-PE40 and LHRH binding to LHRHR on the membrane surface of human liver cancer cells were measured with radioligand receptor assay. RESULTS: The specific activity of LHRH labeled with 125I was 2.7 × 104 kBq/μL, and its radiochemical purity reached to 99.2%-99.7%. The binding of 125I to LHRH was maximal for 240 min in the warm cultivation, and this binding was stabilized. The inhibiting rates of 125I-LHRH and LHRH on the proliferation of human liver cancer HEPG cells were not significantly different. On the basis of the saturation curve of 125I-LHRH binding to the membrane LHRHR of HEPG cells, 125I-LHRH of 1 × 105 cpm was selected for radioligand receptor assay. The affinity constants (Kd) of LHRH-PE40 and LHRH binding to the membrane LHRHR of HEPG cells were 0.43 ± 0.12 nmol/L and 4.86 ± 1.47 nmol/L, respectively, and their receptor volumes were 0.37 ± 0.15 μmol/g and 0.42 ± 0.13 μmol/g, respectively. The binding of LHRH-PE40 to the membrane protein of normal liver cells was not observed. CONCLUSION: The recombinant toxin LHRH-PE40 binding to the membrane surface of LHRHR of human liver cancer HEPG cells was very strong, while the specific binding of it to normal liver cells was not observed. The results provide an important experimental basis for the clinical application of LHRH-PE. PMID:15334689

  10. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    ClinicalTrials.gov

    2016-07-05

    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

  11. 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

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

    PubMed Central

    Park, Kwan-Kyu; Choi, Yang-Kyu; Nam, Jeong-Seok; Hong, In-Sun

    2016-01-01

    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. PMID:26967248

  13. Stem Cells in Liver Diseases and Cancer: Recent Advances on the Path to New Therapies

    PubMed Central

    Rountree, C. Bart; Mishra, Lopa; Willenbring, Holger

    2011-01-01

    Stem cells have potential for therapy of liver diseases, but may also be involved in the formation of liver cancer. Recently, the AASLD Henry M. and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” brought together a diverse group of investigators to define the status of research on stem cells and cancer stem cells in the liver and identify problems and solutions on the path to clinical translation. This report summarizes the outcomes of the conference and provides an update on recent research advances. Progress in liver stem cell research includes isolation of primary liver progenitor cells (LPC), directed hepatocyte differentiation of primary LPC and pluripotent stem cells, findings of transdifferentiation, disease-specific considerations for establishing a therapeutically effective cell mass, and disease modeling in cell culture. Tumor initiating stem-like cells (TISC) that emerge during chronic liver injury share expression of signaling pathways, including those organized around TGF-β and β-catenin, and surface markers with normal LPC. Recent investigations of the role of TISC in hepatocellular carcinoma have provided insight into the transcriptional and posttranscriptional regulation of hepatocarcinogenesis. Targeted chemotherapies for TISC are in development as a means to overcome cellular resistance and mechanisms driving disease progression in liver cancer. PMID:22030746

  14. Menopausal hormone therapy use and risk of primary liver cancer in the clinical practice research datalink.

    PubMed

    McGlynn, Katherine A; Hagberg, Katrina; Chen, Jie; Braunlin, Megan; Graubard, Barry I; Suneja, Neha; Jick, Susan; Sahasrabuddhe, Vikrant V

    2016-05-01

    Primary liver cancer occurs less commonly among women than men in almost all countries. This discrepancy has suggested that hormone levels and/or exogenous hormone use could have an effect on risk, although prior studies have reached inconsistent conclusions. Thus, the current study was conducted to examine the relationship between menopausal hormone therapy (MHT) use and development of liver cancer. A nested case-control study was conducted within the United Kingdom's Clinical Practice Research Datalink (CPRD). Controls were matched, at a 4-to-1 ratio, to women diagnosed with primary liver cancer between 1988 and 2011. A second match, based on whether the cases and controls had diabetes, was also conducted. Odds ratios (OR) and 95% confidence intervals (95%CI) for associations of MHT with liver cancer were estimated using conditional logistic regression adjusted for known risk factors. In the overall match, 339 women with liver cancer were matched to 1318 controls. MHT use was associated with a significantly lower risk of liver cancer (ORadj  = 0.58, 95%CI = 0.37-0.90) especially among users of estrogen-only MHT (ORadj = 0.44, 95%CI = 0.22-0.88) and among past users (ORadj  = 0.53, 95%CI = 0.32-0.88). Among the matched cases (n = 58) and controls (n = 232) with diabetes, the odds ratios were similar to the overall analysis (ORadj  = 0.57, 95%CI = 0.09-3.53), but did not attain statistical significance. In the current study, MHT use, especially estrogen-only MHT use, was associated with a significantly lower risk of liver cancer. These results support the need of further investigation into whether hormonal etiologies can explain the variation in liver cancer incidence between men and women. PMID:26662112

  15. Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis

    PubMed Central

    Tabariès, Sébastien; Annis, Matthew G.; Hsu, Brian E.; Tam, Christine E.; Savage, Paul; Park, Morag; Siegel, Peter M.

    2015-01-01

    Claudin-2 enhances breast cancer liver metastasis and promotes the development of colorectal cancers. The objective of our current study is to define the regulatory mechanisms controlling Claudin-2 expression in breast cancer cells. We evaluated the effect of several Src Family Kinase (SFK) inhibitors or knockdown of individual SFK members on Claudin-2 expression in breast cancer cells. We also assessed the potential effects of pan-SFK and SFK-selective inhibitors on the formation of breast cancer liver metastases. This study reveals that pan inhibition of SFK signaling pathways significantly elevated Claudin-2 expression levels in breast cancer cells. In addition, our data demonstrate that pan-SFK inhibitors can enhance breast cancer metastasis to the liver. Knockdown of individual SFK members reveals that loss of Yes or Fyn induces Claudin-2 expression; whereas, diminished Lyn levels impairs Claudin-2 expression in breast cancer cells. The Lyn-selective kinase inhibitor, Bafetinib (INNO-406), acts to reduce Claudin-2 expression and suppress breast cancer liver metastasis. Our findings may have major clinical implications and advise against the treatment of breast cancer patients with broad-acting SFK inhibitors and support the use of Lyn-specific inhibitors. PMID:25823815

  16. Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

    ClinicalTrials.gov

    2016-01-22

    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 IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  17. Complement proteins C7 and CFH control the stemness of liver cancer cells via LSF-1.

    PubMed

    Seol, Hyang Sook; Lee, Sang Eun; Song, Joon Seon; Rhee, Je-Keun; Singh, Shree Ram; Chang, Suhwan; Jang, Se Jin

    2016-03-01

    Tumor-initiating cells are important for the formation and maintenance of tumor bulks in various tumors. To identify surface markers of liver tumor-initiating cells, we performed primary tumorsphere culture and analyzed the expression of cluster of differentiation (CD) antigen genes using NanoString. Interestingly, we found significant upregulation of the complement proteins (p = 1.60 × 10(-18)), including C7 and CFH. Further studies revealed that C7 and CFH are required to maintain stemness in liver cancer cells. Knockdown of C7 and CFH expression abrogated tumorsphere formation and induced differentiation, whereas overexpression stimulated stemness factor expression as well as in vivo cell growth. Mechanistically, by studying C7 and CFH-dependent LSF-1 expression and its direct role on stemness factor transcription, we found that LSF-1 is involved in this regulation. Taken together, our data demonstrate the unprecedented role of complement proteins on the maintenance of stemness in liver tumor-initiating cells. PMID:26723877

  18. 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. PMID:27244487

  19. Active targeting docetaxel-PLA nanoparticles eradicate circulating lung cancer stem-like cells and inhibit liver metastasis.

    PubMed

    Yang, Nan; Jiang, Yao; Zhang, Huifeng; Sun, Bo; Hou, Chunying; Zheng, Ji; Liu, Yanyong; Zuo, Pingping

    2015-01-01

    Lung cancer is the major cause of cancer related lethality worldwide, and metastasis to distant organs is the pivotal cause of death for the vast majority of lung cancer patients. Accumulated evidence indicates that lung cancer stem-like cells (CSLCs) play important roles in metastagenesis, and these circulating CSLCs may be important targets to inhibit the subsequent metastasis. The present study was aimed at establishing CSLC-targeting polylactic acid (PLA) encapsulated docetaxel nanoparticles for antimetastatic therapy. Cyclic binding peptides were screened on CSLCs in vitro and the peptide CVKTPAQSC exhibiting high specific binding ability to pulmonary adenocarcinoma tissue was subsequently conjugated to the nanoparticles loaded with docetaxel (NDTX). Antimetastatic effect of CSLC-targeting nanoparticles loaded with docetaxel (TNDTX) was evaluated in a nude mouse model of liver metastasis. Results showed that, in the absence of targeting peptide, NDTX hardly exhibited any antimetastatic effect. However, TNDTX treatment significantly decreased the metastatic tumor area in the nude mouse liver. Histopathological and serological results also confirmed the antimetastatic efficacy of TNDTX. To our knowledge, this is the first report on establishing a CSLC-based strategy for lung cancer metastatic treatment, and we hope this will offer a potential therapeutic approach for management of metastatic lung cancer. PMID:25418453

  20. Role of surgery in colorectal cancer liver metastases

    PubMed Central

    Akgül, Özgür; Çetinkaya, Erdinç; Ersöz, Şiyar; Tez, Mesut

    2014-01-01

    Colorectal carcinoma (CRC) is the third most common cancer, and approximately 35%-55% of patients with CRC will develop hepatic metastases during the course of their disease. Surgical resection represents the only chance of long-term survival. The goal of surgery should be to resect all metastases with negative histological margins while preserving sufficient functional hepatic parenchyma. Although resection remains the only chance of long-term survival, management strategies should be tailored for each case. For patients with extensive metastatic disease who would otherwise be unresectable, the combination of advances in medical therapy, such as systemic chemotherapy (CTX), and the improvement in surgical techniques for metastatic disease, have enhanced prognosis with prolongation of the median survival rate and cure. The use of portal vein embolization and preoperative CTX may also increase the number of patients suitable for surgical treatment. Despite current treatment options, many patients still experience a recurrence after hepatic resection. More active systemic CTX agents are being used increasingly as adjuvant therapy either before or after surgery. Local tumor ablative therapies, such as microwave coagulation therapy and radiofrequency ablation therapy, should be considered as an adjunct to hepatic resection, in which resection cannot deal with all of the tumor lesions. Formulation of an individualized plan, which combines surgery with systemic CTX, is a necessary task of the multidisciplinary team. The aim of this paper is to discuss different approaches for patients that are treated due to CRC liver metastasis. PMID:24876733

  1. Single Nucleotide Polymorphisms of One-Carbon Metabolism and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population

    PubMed Central

    Chang, Shen-Chih; Chang, Po-Yin; Butler, Brendan; Goldstein, Binh Y.; Mu, Lina; Cai, Lin; You, Nai-Chieh Y.; Baecker, Aileen; Yu, Shun-Zhang; Heber, David; Lu, Qing-Yi; Li, Liming; Greenland, Sander; Zhang, Zuo-Feng

    2014-01-01

    One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005) and stomach cancer (posterior homogeneity P = 0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the

  2. Liver cancer immunoassay with magnetic nanoparticles and MgO-based magnetic tunnel junction sensors

    NASA Astrophysics Data System (ADS)

    Lei, Z. Q.; Li, L.; Li, G. J.; Leung, C. W.; Shi, J.; Wong, C. M.; Lo, K. C.; Chan, W. K.; Mak, C. S. K.; Chan, S. B.; Chan, N. M. M.; Leung, C. H.; Lai, P. T.; Pong, P. W. T.

    2012-04-01

    We have demonstrated the detection of alpha-fetoprotein (AFP) labeled with magnetic nanoparticles (MNPs) using MgO-based magnetic tunnel junction (MTJ) sensors. AFP is an important hepatic tumor biomarker and the detection of AFP has significant applications for clinical diagnostics and immunoassay for early-stage liver cancer indications. In this work, MgO-based MTJ sensors and 20-nm iron-oxide magnetic nanoparticles (MNPs) were used for detecting AFP antigens by a sandwich-assay configuration. The MTJ sensors with a sensing area of 4 × 2 μm2 possess tunneling magnetoresistance (TMR) of 122% and sensitivity of 0.95%/Oe at room temperature. The target AFP antigens of three concentrations were successfully detected, and the experimental data indicate that the resistance variations of the MTJ sensor increased with the AFP concentration ratios proportionally. These results demonstrate that MgO-based MTJ sensors together with MNPs are a promising biosensing platform for liver cancer immunoassay.

  3. Oral cancer. The importance of early diagnosis and treatment.

    PubMed

    Sciubba, J J

    2001-01-01

    Oral cancer is an important health issue. The WHO predicts a continuing worldwide increase in the number of patients with oral cancer, extending this trend well into the next several decades. In the US the projected number of new cases of oral and oropharyngeal cancer will exceed 31,000 per year. Mortality due to cancers in this region exceeds the annual death rate is the US caused by either cutaneous melanoma or cervical cancer. Significant agents involved in the etiology of oral cancer in Western countries include sunlight exposure, smoking and alcohol consumption. Use of the areca or betel nut in many cultures is a major etiological factor outside of the USA. Other etiologic factors associated with oral squamous cell carcinoma, but far less significant statistically, include syphilis and sideropenic dysphagia. Recently, strong evidence for an etiological relationship between human papilloma virus and a subset of head and neck cancers has been noted. It is generally accepted that most sporadic tumors are the result of a multi-step process of accumulated genetic alterations. These alterations affect epithelial cell behavior by way of loss of chromosomal heterozygosity which in turn leads to a series of events progressing to the ultimate stage of invasive squamous cell carcinoma. The corresponding genetic alterations are reflected in clinical and microscopic pathology from hyperplasia through invasiveness. A wide range of mucosal alternations fall within the rubric of leukoplakia. Proliferative verrucous leukoplakia represents a relatively new type of leukoplakia that is separate from the more common or less innocuous form of this condition. Erythroplakia is particularly relevant considering its almost certain relationship with dysplasia or invasive carcinoma. Squamous cell carcinoma will develop from antecedent dysplastic oral mucosal lesions if an early diagnosis has not been made and treatment given. Early diagnosis within stages I and II correspond to a vastly

  4. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis.

    PubMed

    Nguyen, Alexander; Loo, Jia Min; Mital, Rohit; Weinberg, Ethan M; Man, Fung Ying; Zeng, Zhaoshi; Paty, Philip B; Saltz, Leonard; Janjigian, Yelena Y; de Stanchina, Elisa; Tavazoie, Sohail F

    2016-02-01

    Colorectal cancer metastasis to the liver is a major cause of cancer-related death; however, the genes and pathways that govern this metastatic colonization event remain poorly characterized. Here, using a large-scale in vivo RNAi screen, we identified liver and red blood cell pyruvate kinase (PKLR) as a driver of metastatic liver colonization. PKLR expression was increased in liver metastases as well as in primary colorectal tumors of patients with metastatic disease. Evaluation of a murine liver colonization model revealed that PKLR promotes cell survival in the tumor core during conditions of high cell density and oxygen deprivation by increasing glutathione, the primary endogenous antioxidant. PKLR negatively regulated the glycolytic activity of PKM2, the major pyruvate kinase isoenzyme known to regulate cellular glutathione levels. Glutathione is critical for metastasis, and we determined that the rate-limiting enzyme of glutathione synthesis, GCLC, becomes overexpressed in patient liver metastases, promotes cell survival under hypoxic and cell-dense conditions, and mediates metastatic liver colonization. RNAi-mediated inhibition of glutathione synthesis impaired survival of multiple colon cancer cell lines, and pharmacological targeting of this metabolic pathway reduced colonization in a primary patient-derived xenograft model. Our findings highlight the impact of metabolic reprogramming within the niche as metastases progress and suggest clinical potential for targeting this pathway in colorectal cancer. PMID:26784545

  5. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis

    PubMed Central

    Nguyen, Alexander; Loo, Jia Min; Mital, Rohit; Weinberg, Ethan M.; Man, Fung Ying; Zeng, Zhaoshi; Paty, Philip B.; Saltz, Leonard; Janjigian, Yelena Y.; de Stanchina, Elisa; Tavazoie, Sohail F.

    2016-01-01

    Colorectal cancer metastasis to the liver is a major cause of cancer-related death; however, the genes and pathways that govern this metastatic colonization event remain poorly characterized. Here, using a large-scale in vivo RNAi screen, we identified liver and red blood cell pyruvate kinase (PKLR) as a driver of metastatic liver colonization. PKLR expression was increased in liver metastases as well as in primary colorectal tumors of patients with metastatic disease. Evaluation of a murine liver colonization model revealed that PKLR promotes cell survival in the tumor core during conditions of high cell density and oxygen deprivation by increasing glutathione, the primary endogenous antioxidant. PKLR negatively regulated the glycolytic activity of PKM2, the major pyruvate kinase isoenzyme known to regulate cellular glutathione levels. Glutathione is critical for metastasis, and we determined that the rate-limiting enzyme of glutathione synthesis, GCLC, becomes overexpressed in patient liver metastases, promotes cell survival under hypoxic and cell-dense conditions, and mediates metastatic liver colonization. RNAi-mediated inhibition of glutathione synthesis impaired survival of multiple colon cancer cell lines, and pharmacological targeting of this metabolic pathway reduced colonization in a primary patient-derived xenograft model. Our findings highlight the impact of metabolic reprogramming within the niche as metastases progress and suggest clinical potential for targeting this pathway in colorectal cancer. PMID:26784545

  6. Analysis of histone modifications at human ribosomal DNA in liver cancer cell

    PubMed Central

    Yu, Feng; Shen, Xingyong; Fan, Li; Yu, Zhaocai

    2015-01-01

    Human liver cancer is the cancer commonly seen clinically. The transcription of ribosomal DNA (rDNA) is a critical step for cells, and epigenetic marks such as post-translational histone modifications have been involved in the regulation of rDNA transcription. But less is known about the pathogenesis of the liver cancers concerning the rDNA transcription regulation. Here we aligned the ChIP-seq data of histone modification markers and CTCF to the human genome assembly which contains a single rDNA repeat in human liver cancer cell and validated their distribution with ChIP-QPCR. Human liver cancer cell possesses a higher enrichment of H3K4me1 and H3K27me3 at ~28 kb within the intergenic spacer (IGS) of rDNA and a higher enrichment of H3K4me3 and H3K27ac upstream of TSS. Furtherly, we studied whether UBF could affect histone modification markers and CTCF at rDNA in human liver cancer cell. UBF depletion leads to a decrease of gene activation mark H3K4me3 across the rDNA promoter. And other histone modification marks and CTCF were not altered after UBF depletion. Taken together, our data showed a high resolution map of histone modification marks at rDNA in human liver cancer cell and provide novel evidence to decipher chromatin-mediated regulation of rDNA in liver cancer. PMID:26657029

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

    PubMed Central

    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. PMID:27010735

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

    PubMed

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

    2016-03-21

    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. 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

  10. Prevalence of aflatoxin M1 in milk and its potential liver cancer risk in Taiwan.

    PubMed

    Peng, Kai-Yao; Chen, Chia-Yang

    2009-05-01

    Pasteurized milk may contain the liver carcinogen aflatoxin M1 (AFM1) if the cows that produce the milk ingest feed contaminated with aflatoxin B1. In this study, we collected 144 milk samples of three main brands in Taiwan twice a month over a 1-year period and purchased two samples each of eight domestic and imported brands of infant formula at two different times in 2005. Samples underwent solid-phase extraction, cleaning in immunoaffinity columns, and quantification by liquid chromatography-tandem mass spectrometry. We found autumn and winter levels of AFM1 to be higher than those in the spring and the summer. We also found higher concentrations of AFM1 in low-fat milk than in whole-fat milk. We were able to detect trace amounts of AFM1 (1.17 to 54.7 ng/liter) in all of our milk samples, but there was only one sample in which the level of AFM1 slightly exceeded the regulatory limit of the European Union (50 ng/liter). We were unable to detect AFM1 in any of the infant formulae. Using a World Health Organization method of evaluating risk of liver cancer, the group we found to be at greatest risk was 6- to 9-year-old girls (average, 12.2 additional cases per billion); the group with the lowest risk was men of 45 to 64 years of age (average, 3.45 additional cases per billion), the latter consuming less milk than all other groups. Consequently, the risk for liver cancer due to ingestion of milk contaminated with AFM1 was estimated to be low in Taiwan. PMID:19517730

  11. Effects of α-tocopherol and β-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study

    PubMed Central

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

    2014-01-01

    Background: Recent data suggest the possible benefits of α-tocopherol and β-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. Methods: We evaluated the efficacy of supplemental 50 mg day−1 α-tocopherol and 20 mg day−1 β-carotene on incident liver cancer and CLD mortality in a randomised trial of 29 105 Finnish male smokers, who received supplementation for 5–8 years and were followed for 16 additional years for outcomes. Results: Supplemental α-tocopherol, β-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. Conclusions: Long-term supplemental α-tocopherol or β-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up. PMID:25314069

  12. Comparison of anamnestic history, alcohol intake and smoking, nutritional status, and liver dysfunction between thorotrast patients who developed primary liver cancer and those who did not

    SciTech Connect

    Kiyosawa, K.; Imai, H.; Sodeyama, T.; Franca, S.T.; Yousuf, M.; Furuta, S.; Fujisawa, K.; Kido, C. )

    1989-08-01

    In order to clarify the differences in past history, nutritional condition and, consumption of alcohol and tobacco, and liver dysfunction between the thorotrast patients who developed primary liver cancer and those who did not, 103 persons who had no primary liver cancer in January 1980 were studied. All subjects were military men who had undergone angiography with thorotrast between 1943 and 1946. Twenty persons developed hepatocellular carcinoma and 16 developed intrahepatic bile duct carcinoma by April 1987, whereas 67 are still alive without any cancer. There was no difference in age or period after thorotrast infusion between those two groups of patients in January 1980. A difference in history of hepatitis and/or jaundice and presence of hepatic dysfunction was found between the subjects who developed primary liver cancers and those who did not. These findings suggest that an anamnestic history of hepatitis and liver dysfunction are risks for development of thorotrast-induced liver cancer. On the basis of the above findings, early detection of liver dysfunction offers a possibility of early diagnosis of primary liver cancer.

  13. The importance of early detection of lip cancer risk groups

    NASA Astrophysics Data System (ADS)

    Fratila, M.; Rosu, S.

    2014-03-01

    Oral maxillo-facial region cancer carries major importance in the tumour pathology of the organism being characterized by a high frequency as well as by the variety of the clinical anatomical and topographic forms through which it is presented. Over 60% of labial carcinoma begins as an asymptomatic ulceration, therefore patients do not pay due attention, considering it a "rebellious thrush" and they make a specialized medical appointment in an advanced stage of the tumor. In this study we pursued the frequency of the lip cancer pathology compared to the total CMF; the distribution the lip cancer by sex and age in patients who submitted to the specialized service; the originating environment of the patient with lip cancer; the anatomical location of the lip cancer; the frequency of relapses after treatment; the presence of adenopathy in the first consultation. The study was performed at the Clinic of Cranio-Maxillofacial Surgery, University of Medicine and Pharmacy "Victor Babes" Timişoara and pursued statistical aspects of the lip cancer incidence over a period of five years (2007-2012). Pre- and postoperative patients were monitored constantly, registering in individual sheets the evolution of the disease, monitoring the relapses after treatment and the presence of adenopathy in the first consultation. As shown in the statistics made in the last five years (2007-2012), from a total of 8135 cases with CMF pathology hospitalized in the Timisoara surgery clinic, 163 cases, or 2%, were cancer of the lip. Analyzing the gender distribution shows that males represent 81% of cases while the remaining 19% were found in women. From the study of age distribution, we found that the number of cases increases with age: 153 cases over 60 years old and 58 cases between 20 - 60 years. Personal statistics from the 212 cases of cancer of the lip reveal that 143 (67%) patients were from the rural areas and 69 (33%) from urban areas. Neoplastic pathology is constantly increasing both

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

    SciTech Connect

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

    2015-05-15

    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 ribosome 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.

  15. Reciprocal regulation between O-GlcNAcylation and tribbles pseudokinase 2 (TRIB2) maintains transformative phenotypes in liver cancer cells.

    PubMed

    Yao, Bingjie; Xu, Yanli; Wang, Jiayi; Qiao, Yongxia; Zhang, Yue; Zhang, Xiao; Chen, Yan; Wu, Qi; Zhao, Yinghui; Zhu, Guoqing; Sun, Fenyong; Li, Zhi; Yuan, Hong

    2016-11-01

    TRIB2 has been identified as an onco-protein, and O-GlcNAcylation of target proteins has been reported to stimulate transformative phenotypes in liver cancer cells. However, the relationships between TRIB2 and O-GlcNAcylation are still unknown. The aim of this study was to investigate whether and how O-GlcNAcylation and TRIB2 regulate each other. We found that stimulation of O-GlcNAcylation elevates TRIB2 by enhancing its protein stability. TRIB2 can be O-GlcNAcylated by the hexosamine biosynthesis pathway (HBP). Also, O-GlcNAcylation boosting of transformative phenotypes of liver cancer cells might occur in a TRIB2-dependent manner. Interestingly, TRIB2 stimulated the metabolism of HBP, demonstrating that TRIB2 has positive feedback on O-GlcNAcylation. Notably, TRIB2 was found to maintain the stability of guanylate cyclase 1 alpha 3 (GUCY1A3), a key component of HBP, by interacting GUCY1A3 and reducing its ubiquitination. Importantly, TRIB2-dependent regulation of metabolism, transformative phenotypes, and O-GlcNAcylation all rely on GUCY1A3. Mouse experiments demonstrate that O-GlcNAcylation of TRIB2 is much higher in the livers of diabetic mice compared to control mice, suggesting that O-GlcNAcylation of TRIB2 might be critical for diabetes-associated liver cancer. Collectively, we have uncovered a positive auto-regulatory feedback between O-GlcNAcylation and TRIB2, which might be regarded as a promising therapeutic target for liver cancer. PMID:27515988

  16. The importance of exercise in lung cancer treatment

    PubMed Central

    2016-01-01

    There is emerging evidence that exercise can help in a variety of different ways for people with lung cancer. Exercise can be beneficial at any stage of the patient journey through increasing strength, endurance and decreasing emotional issues. A recovery fitness program is described and provides guidance on breathing, stretching, aerobic exercise and strength training. There are more people surviving lung cancer with services needing to cater for the varying requirements of each patient. Promoting physical activity is an important facet of health care management and collaboration between providers of services is required. PMID:27413700

  17. Sex Difference of Egfr Expression and Molecular Pathway in the Liver: Impact on Drug Design and Cancer Treatments?

    PubMed

    Wang, Lishi; Xiao, Jianqi; Gu, Weikuan; Chen, Hong

    2016-01-01

    Epidermal growth factor receptor (EGFR) has been used as the target in drug design for cancer treatment including the liver cancer. Men and women have different levels of EGFR expression during the life. The whole genome expression profiles of livers of recombinant inbred (RI) strains derived from C57BL/6J (B6) X DBA/2J (D2) were used to compare three major molecular aspects of Egfr gene: the relative expression levels, gene network and eQTLs that regulate the expression of Egfr between female and male mice. Our data suggest that there is a significant difference in the expression levels in the liver between female and male mice. Several important genes in the gene network of Egfr are differentially expressed between female and male mice. The regulatory elements for the expression levels of Egfr between female and male mice are also different. In summary, our data reveals an important sex difference in the Egfr pathways in the liver of the mice. These data may have substantial impact on drug development and dosage determinant for women and men in the clinical trials. PMID:27076848

  18. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  19. Stable isotope dimethyl labeling combined with LTQ mass spectrometric detection, a quantitative proteomics technology used in liver cancer research

    PubMed Central

    TANG, BO; LI, YANG; ZHAO, LIANG; YUAN, SHENGGUANG; WANG, ZHENRAN; LI, BO; CHEN, QIAN

    2013-01-01

    Liver cancer is a common malignant disease, with high incidence and mortality rates. The study on the proteomics of liver cancer has attracted particular attention. The quantitative study method of proteomics depends predominantly on two-dimensional (2D) gel electrophoresis. In the present study we reported a rapid and accurate proteomics quantitative study method of high repeatability that includes the use of stable isotope labeling for the extraction of proteins and peptides via enzymolysis to achieve new type 2D capillary liquid chromatography-mass spectrometry separation using the separation mode of cation-exchange chromatography in conjunction with reversed-phase chromatography. LTQ OrbiTrap mass spectrometry detection was also performed. A total of 188 differential proteins were analyzed, including 122 upregulating [deuterium/hydrogen ratio (D/H) >1.5)] and 66 downregulating proteins (D/H<0.67). These proteins may play an important role in the occurrence, drug resistance, metastasis and recurrence of cancer or other pathological processes. Such a proteomics technology may provide biological data as well as a new methodological basis for liver cancer research. PMID:24648984

  20. A holistic approach to study the effects of natural antioxidants on inflammation and liver cancer.

    PubMed

    Costantini, Susan; Colonna, Giovanni; Castello, Giuseppe

    2014-01-01

    The limited effectiveness of chemotherapy and the high recurrence rate of cancers highlight the urgent need to identify new molecular targets and to develop new treatments. Numerous epidemiological studies have recently highlighted the existence of an inverse association between fruit and vegetable consumption, natural antioxidants, and cancer risk; in fact, antioxidant intake through diet or supplements of plant origin is strongly recommended for cancer prevention and cure. In general, antioxidants are substances of vegetable, mineral, or animal origin that neutralize free radicals and protect the body from their negative actions on the plasma membrane, proteins, and DNA. Hence, cancer can be prevented by the stimulation of the immune system to destroy cancer cells or to block their proliferation. Since living organisms may be studied as a whole complex system by the "omics sciences" which tend toward understanding and describing the global information of genes, mRNA, proteins, and metabolites, our aim is to use bioinformatics and systems biology to study cytokinome, which plays an important role in the evolution of inflammatory processes and is also a key component in the evolution of cancer, a disease recognized as depending on chronic inflammation and also with the concomitant presence of type 2 diabetes and obesity. On the whole, we define cytokinome as the totality of these proteins and their interactions in and around biological cells. Understanding the complex interaction network of cytokines in patients affected by cancers should be very useful both to follow the evolution of cancer from its early stages and to define innovative therapeutic strategies by using systems biology approaches. In this paper, we review some results of our group in the light of the "omics" logic, and in particular (1) the need for a global approach to study complex systems such as multifactorial cancer and, in particular, hepatocellular carcinoma, (2) the correlation between

  1. Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer

    PubMed Central

    Lee, Sung Hwan; Kim, Sung Hyun; Lim, Jin Hong; Kim, Sung Hoon; Lee, Jin Gu; Kim, Dae Joon; Choi, Gi Hong; Choi, Jin Sub

    2016-01-01

    Backgrounds/Aims Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases. PMID:27621747

  2. Radioembolization in the treatment of unresectable liver tumors: experience across a range of primary cancers.

    PubMed

    Coldwell, Douglas; Sangro, Bruno; Salem, Riad; Wasan, Harpreet; Kennedy, Andrew

    2012-04-01

    Radioembolization is a proven treatment to slow disease progression and improve survival in patients with colorectal cancer liver metastases and hepatocellular carcinoma. Accumulating evidence supports its use in metastases from neuroendocrine tumors and breast cancer. Cancers with radiobiologic profiles similar to those of colorectal and breast cancer, including melanoma, lung cancer, and nodular cholangiocarcinoma, are being studied as candidates for radioembolization. This treatment modality has also been shown to downsize hepatic tumors for potentially curative ablation in patients with breast, pancreatic, and colorectal cancer. Radioembolization using either yttrium-90 ((90)Y)-labeled resin or glass microspheres represents a promising therapy for liver-only or liver-predominant tumors in patients with 1 or more variables, including adequate or sufficient functional liver reserve, good performance status, and absence of other significant comorbidities. Therapeutic efficacy and safety can be best achieved by use of careful dosimetric techniques and treatment planning. Radioembolization could be considered after progression of liver metastases during treatment hiatus, at an early therapeutic line in tumors that respond poorly to chemotherapy, or in treatment-refractory disease. PMID:21127414

  3. Circulating cancer stem cells: the importance to select

    PubMed Central

    Yang, Ming-Hsin; Imrali, Ahmet

    2015-01-01

    It has been demonstrated that even localized tumors without clinically apparent metastasis give rise to circulating tumor cells (CTCs). A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients’ outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, ‘liquid biopsy’, which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis-initiating capabilities based on their stemness properties and invasiveness and thus are critical for the patients’ clinical outcome. As compared to non-tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and

  4. Hydrodynamic Transfection for Generation of Novel Mouse Models for Liver Cancer Research

    PubMed Central

    Chen, Xin; Calvisi, Diego F.

    2015-01-01

    Primary liver cancers, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, are leading causes of cancer-related death worldwide. Recent large-scale genomic approaches have identified a wide number of genes whose deregulation is associated with hepatocellular carcinoma and intrahepatic cholangiocarcinoma development. Murine models are critical tools to determine the oncogenic potential of these genes. Conventionally, transgenic or knockout mouse models are used for this purpose. However, several limitations apply to the latter models. Herein, we review a novel approach for stable gene expression in mouse hepatocytes by hydrodynamic injection in combination with Sleeping Beauty–mediated somatic integration. This method represents a flexible, reliable, and cost-effective tool to generate preclinical murine models for liver cancer research. Furthermore, it can be used as an in vivo transfection method to study biochemical cross talks among multiple pathways along hepatocarcinogenesis and to test the therapeutic potential of drugs against liver cancer. PMID:24480331

  5. [Vitamin D as an important steroid hormone in breast cancer].

    PubMed

    Obermannova, R; Demlová, R; Drábová, K; Melichárková, K; Greplová, K; Mrkvicová, M; Zdražilová-Dubská, L; Vyzula, R; Valík, D

    2014-01-01

    Vitamin D is the third steroid hormone playing important bio-logical roles in the development of breast cancer. Decreased plasma levels of its 25- hydroxyderivative, 25OHD, display robust associations with higher incidence of breast cancer and shorter overall survival. Although no consensus exists, most authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas levels higher than 375 nmol/ l can be potentially toxic with higher risk of hypercalcemia. To date, no data are available on the optimal levels of vitamin D related to the risk of breast cancer development, its phenotype features and the course of the disease. Published studies mostly describe associations among higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be associated with higher disease incidence and also be of negative prognostic significance in breast cancer. This review presents an overall summary of the current knowledge and publications on vitamin D and breast cancer. PMID:24945552

  6. 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

  7. PTTG: an important target gene for ovarian cancer therapy

    PubMed Central

    Panguluri, Siva Kumar; Yeakel, Casey; Kakar, Sham S

    2008-01-01

    Pituitary tumor transforming gene (PTTG), also known as securin is an important gene involved in many biological functions including inhibition of sister chromatid separation, DNA repair, organ development, and expression and secretion of angiogenic and metastatic factors. Proliferating cancer cells and most tumors express high levels of PTTG. Overexpression of PTTG in vitro induces cellular transformation and development of tumors in nude mice. The PTTG expression levels have been correlated with tumor progression, invasion, and metastasis. Recent studies show that down regulation of PTTG in tumor cell lines and tumors in vivo results in suppression of tumor growth, suggesting its important role in tumorigenesis. In this review, we focus on PTTG structure, sub-cellular distribution, cellular functions, and role in tumor progression with suggestions on possible exploration of this gene for cancer therapy. PMID:19014669

  8. Use of multiphoton microscopy to diagnose liver cancer and lung metastasis in an orthotopic rat model.

    PubMed

    Yan, Jun; Zhuo, Shuangmu; Chen, Gang; Tan, Changjun; Zhu, Weifeng; Lu, Jianping; Fan, Jia; Chen, Jianxin; Zhou, Jian

    2012-01-01

    Liver or lung biopsy for suspicious lesions has several disadvantages such as bleeding, bile leak or pneumothorax, needle track seeding, and time-consuming histopathological procedure. The ability to directly observe cellular and subcellular details and then perform "optical biopsy" is a major goal in the development of new interventional techniques. Multiphoton microscopy (MPM) enables real-time noninvasive visualization of tissue architecture and cell morphology in live tissue. We performed a study to evaluate whether MPMcan make real-time optical diagnosis for liver cancer and lung metastasis using an orthotopic rat model with Morris hepatoma. We found that real-time high-resolution MPMimaging could clearly show tissue architecture and cell morphology. In the normal liver tissue, MPMimaging clearly revealed the blood-filled sinusoids and cords of hepatocytes. In the cancerous tissue, MPMimaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. MPMimages were comparable to golden standard hematoxylin-eosin staining images. Moreover, MPMimaging had deep penetration with the capability of optical sectioning. In short, MPMcan make real-time optical diagnosis for liver cancer and lung metastasis. This study provides the groundwork for further using multiphoton endoscopy to perform real-time noninvasive "optical biopsy" for liver cancer and lung metastasis in the near future. PMID:22331704

  9. Silymarin in the prevention and treatment of liver diseases and primary liver cancer.

    PubMed

    Féher, János; Lengyel, Gabriella

    2012-01-01

    In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and chemical-induced hepatic toxicity), the antioxidant medicines such as silymarin can have beneficial effect. Liver cirrhosis, non-alcoholic fatty liver and steatohepatitis are risk factors for hepatocellular carcinoma (HCC). Insulin resistance and oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore it reduces the inflammatory reaction, and inhibits the fibrogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of patients with alcohol induced liver cirrhosis. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumor cell proliferation, angiogenesis as well as insulin resistance. Furthermore, it exerts an anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression due to adhesion molecules. The chemopreventive effect of silymarin on HCC has been established in several studies using in vitro and in vivo methods; it can exert a beneficial effect on the balance of cell survival and apoptosis by interfering cytokines. In addition to this, anti-inflammatory activity and inhibitory effect of silymarin on the development of metastases have also been detected. In some neoplastic diseases silymarin can be administered as adjuvant therapy as well. PMID:21466434

  10. PDGFRα in Liver Pathophysiology: Emerging Roles in Development, Regeneration, Fibrosis, and Cancer

    PubMed Central

    Kikuchi, Alexander; Monga, Satdarshan Pal

    2015-01-01

    Platelet-derived growth factor receptor α (PDGFRα) is an isoform of the PDGFR family of tyrosine kinase receptors involved in cell proliferation, survival, differentiation, and growth. In this review, we highlight the role of PDGFRα and the current evidence of its expression and activities in liver development, regeneration, and pathology—including fibrosis, cirrhosis, and liver cancer. Studies elucidating PDGFRα signaling in processes ranging from profibrotic signaling, angiogenesis, and oxidative stress to epithelial-to-mesenchymal transition point toward PDGFRα as a potential therapeutic target in various hepatic pathologies, including hepatic fibrosis and liver cancer. Furthermore, PDGFRα localization and modulation during liver development and regeneration may lend insight into its potential roles in various pathologic states. We will also briefly discuss some of the current targeted treatments for PDGFRα, including multireceptor tyrosine kinase inhibitors and PDGFRα-specific inhibitors. PMID:25700367

  11. High prevalence of diabetes mellitus and impaired glucose tolerance in liver cancer patients: A hospital based study of 4610 patients with benign tumors or specific cancers

    PubMed Central

    Roujun, Chen; Yanhua, Yi; Bixun, Li

    2016-01-01

    Objective: The prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were hypothesised to be different among different tumor patients. This study aimed to study the association between the prevalence of DM, IGT and IFG and liver cancer, colorectal cancer, breast cancer, cervical cancer, nasopharyngeal cancer and benign tumor. Methods:  A hospital based retrospective study was conducted on 4610 patients admitted to the Internal Medical Department of the Affiliated Tumor Hospital of Guangxi Medical University, China. Logistic regression was used to examine the association between gender, age group, ethnicity , cancer types or benign tumors and prevalence of DM, IFG, IGT. Results: Among 4610 patients, there were 1000 liver cancer patients, 373 breast cancer patients, 415 nasopharyngeal cancer patients, 230 cervical cancer patients, 405 colorectal cancer patients, and 2187 benign tumor patients. The prevalence of DM and IGT in liver cancer patients was 14.7% and 22.1%, respectively. The prevalence of DM and IGT was 13.8% and 20%, respectively, in colorectal cancer patients, significantly higher than that of benign cancers. After adjusting for gender, age group, and ethnicity, the prevalence of DM and IGT in liver cancers patients was 1.29 times (CI :1.12-1.66) and 1.49 times (CI :1.20-1.86) higher than that of benign tumors, respectively. Conclusion: There was a high prevalence of DM and IGT in liver cancer patients. PMID:27610222

  12. Combination of internal radiation therapy and hyperthermia to treat liver cancer

    SciTech Connect

    Grady, E.D.; McLaren, J.; Auda, S.P.; McGinley, P.H.

    1983-09-01

    Sixteen patients were treated for liver cancer (primary and metastatic) by a combination of internal radiation therapy with intra-arterial yttrium 90 microspheres and regional hyperthermia with electromagnetic radiation. Four patients have their liver disease apparently controlled; two had a partial regression of more than 50%; and two had a partial regression of less than 50%. The complications consisted of one case of radiation hepatitis and one of peptic ulcer.

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

    PubMed Central

    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. PMID:25938802

  14. An integrated genomic and pharmacoepigenomic approach predicts therapeutic response of zebularine in human liver cancer*

    PubMed Central

    Andersen, Jesper B.; Factor, Valentina M.; Marquardt, Jens U.; Raggi, Chiara; Lee, Yun-Han; Seo, Daekwan; Conner, Elizabeth A.; Thorgeirsson, Snorri S.

    2010-01-01

    Epigenomic changes such as aberrant hypermethylation and subsequent atypical gene silencing are characteristic features of human cancer. Here, we report a comprehensive characterization of epigenomic modulation caused by zebularine, an effective DNA methylation inhibitor, in human liver cancer. Using transcriptomic and epigenomic profiling, we identified a zebularine signature that classified liver cancer cell lines into two major subtypes with different drug-responses. In drug-sensitive cell lines, zebularine caused inhibition of proliferation coupled with increased apoptosis, whereas drug-resistant cell lines were associated with upregulation of oncogenic networks (e.g. E2F1, MYC, and TNF) driving liver cancer growth in vitro and in preclinical mouse models. Assessment of zebularine-based therapy in xenograft mouse models demonstrated potent therapeutic effects against tumors established from zebularine-sensitive but not zebularine-resistant liver cancer cells leading to increased survival and decreased pulmonary metastasis. Integration of zebularine gene expression and demethylation response signatures differentiated patients with HCC according to their survival and disease recurrence and identified a subclass of patients within the poor survivors likely to benefit from therapeutic agents that target the cancer epigenome. PMID:20962331

  15. 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.

  16. Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis.

    PubMed

    Nielsen, Sebastian R; Quaranta, Valeria; Linford, Andrea; Emeagi, Perpetua; Rainer, Carolyn; Santos, Almudena; Ireland, Lucy; Sakai, Takao; Sakai, Keiko; Kim, Yong-Sam; Engle, Dannielle; Campbell, Fiona; Palmer, Daniel; Ko, Jeong Heon; Tuveson, David A; Hirsch, Emilio; Mielgo, Ainhoa; Schmid, Michael C

    2016-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is a devastating metastatic disease for which better therapies are urgently needed. Macrophages enhance metastasis in many cancer types; however, the role of macrophages in PDAC liver metastasis remains poorly understood. Here we found that PDAC liver metastasis critically depends on the early recruitment of granulin-secreting inflammatory monocytes to the liver. Mechanistically, we demonstrate that granulin secretion by metastasis-associated macrophages (MAMs) activates resident hepatic stellate cells (hStCs) into myofibroblasts that secrete periostin, resulting in a fibrotic microenvironment that sustains metastatic tumour growth. Disruption of MAM recruitment or genetic depletion of granulin reduced hStC activation and liver metastasis. Interestingly, we found that circulating monocytes and hepatic MAMs in PDAC patients express high levels of granulin. These findings suggest that recruitment of granulin-expressing inflammatory monocytes plays a key role in PDAC metastasis and may serve as a potential therapeutic target for PDAC liver metastasis. PMID:27088855

  17. [Stereotactic Body Radiotherapy with CyberKnife®for Liver Metastases from Colorectal Cancer].

    PubMed

    Mihara, Koki; Kaihara, Masaki; Sunahori, Sayaka; Yamashiro, Naotsugu; Nishiya, Shin; Ito, Yasuhiro; Funakoshi, Kazuto; Egawa, Tomohisa; Tsukamoto, Nobuhiro; Nagashima, Atsushi

    2015-10-01

    For treatment of colorectal liver metastases, liver resection is recommended for resectable cases in the clinical guidelines for colorectal cancer. On the other hand, there are currently no data supporting the efficacy of radiation therapy as a topical treatment, and this treatment can therefore not presently be recommended. With CyberKnife®, it is possible to perform stereotactic radiation therapy using a linear accelerator with high accuracy, even for lesions in the trunk area such as liver metastases. Between December 2009 and September 2014 in our hospital, we performed radiation treatment using CyberKnife® for 14 cases with 22 colorectal liver metastases. As a result, we obtained response and local control rates of 76.2%and 81.0%, respectively. Moreover, no advanced adverse events were observed. Thus, we consider that CyberKnife® treatment for colorectal liver metastases is effective as a topical treatment, with low invasiveness and high safety. PMID:26489566

  18. Pooled analysis of the surgical treatment for colorectal cancer liver metastases.

    PubMed

    Veereman, G; Robays, J; Verleye, L; Leroy, R; Rolfo, C; Van Cutsem, E; Bielen, D; Ceelen, W; Danse, E; De Man, M; Demetter, P; Flamen, P; Hendlisz, A; Sinapi, I; Vanbeckevoort, D; Ysebaert, D; Peeters, M

    2015-04-01

    Liver metastases in colorectal cancer patients decreases the expected 5 year survival rates by a factor close to nine. It is generally accepted that resection of liver metastases should be attempted whenever feasible. This manuscript addresses the optimal therapeutic plan regarding timing of resection of synchronous liver metastases and the use of chemotherapy in combination with resection of synchronous metachronous liver metastases. The aim is to pool all published results in order to attribute a level of evidence to outcomes and identify lacking evidence areas. A systematic search of guidelines, reviews, randomised controlled, observational studies and updating a meta-analysis was performed. Data were extracted and analysed. Data failed to demonstrate an effect of timing of surgery or use of chemotherapy on overall survival. Concomitant resection of liver metastases and the primary tumour may result in lower postoperative morbidity. Systemic peri-operative chemotherapy may improve progression free survival compared to surgery alone. PMID:25666309

  19. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

  20. Liver transplantation and subsequent risk of cancer: findings from a Canadian cohort study.

    PubMed

    Jiang, Ying; Villeneuve, Paul J; Fenton, Stanley S A; Schaubel, Douglas E; Lilly, Les; Mao, Yang

    2008-11-01

    Characterization of the long-term cancer risks among liver transplant patients has been hampered by the paucity of sufficiently large cohorts. The increase over time in the number of liver transplants coupled with improved survival underscores the need to better understand associated long-term health effects. This is a cohort study whose subjects were assembled with data from the population-based Canadian Organ Replacement Registry. Analyses are based on 2034 patients who received a liver transplant between June 1983 and October 1998. Incident cases of cancer were identified through record linkage to the Canadian Cancer Registry. We compared site-specific cancer incidence rates in the cohort and the general Canadian population by using the standardized incidence ratio (SIR). Stratified analyses were performed to examine variations in risk according to age at transplantation, sex, time since transplantation, and year of transplantation. Liver transplant recipients had cancer incidence rates that were 2.5 times higher than those of the general population [95% confidence interval (CI) = 2.1, 3.0]. The highest SIR was observed for non-Hodgkin's lymphoma (SIR = 20.8, 95% CI = 14.9, 28.3), whereas a statistically significant excess was observed for colorectal cancer (SIR = 2.6, 95% CI = 1.4, 4.4). Risks were more pronounced during the first year of follow-up and among younger transplant patients. In conclusion, our findings indicate that liver transplant patients face increased risks of developing cancer with respect to the general population. Increased surveillance in this patient population, particularly in the first year following transplantation, and screening for colorectal cancer with modalities for which benefits are already well recognized should be pursued. PMID:18975293

  1. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers.

    PubMed

    Sanna, Claudia; Rosso, Chiara; Marietti, Milena; Bugianesi, Elisabetta

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas) and extra-intestinal sites (kidney in men, and breast in women). Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC), but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites. PMID:27187365

  2. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

    PubMed Central

    Sanna, Claudia; Rosso, Chiara; Marietti, Milena; Bugianesi, Elisabetta

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas) and extra-intestinal sites (kidney in men, and breast in women). Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC), but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites. PMID:27187365

  3. 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

  4. MiR-15b mediates liver cancer cells proliferation through targeting BCL-2

    PubMed Central

    Zhang, Yuping; Huang, Feizhou; Wang, Jian; Peng, Lin; Luo, Hongwu

    2015-01-01

    The incidence and mortality of liver cancer increased year by year. Our country presents high incidence of liver cancer. MicroRNAs have tissue sensitivity as tumor biomarkers that play a role by promoting tumor growth as oncogenes or inhibit malignant cell growth as tumor suppressor genes. Studies showed that miR-15b abnormal expression in the tumor and can be treated as one of the tumor molecular markers. However, miR-15b expression and role in the liver cancer cells have not been elucidated. This study intended to explore the mechanism of miR-15b effect on liver cancer occurrence and development. Liver cancer cell line HepG2 was transfected with miR-15b mimic or inhibitor. Real-time PCR was applied to detect miR-15b expression. MTT was used to test cell proliferation. Transwell assay was performed to determine cell invasive ability. Real-time PCR and Western blot were used to detect BCL2 expression. MiR-15b mimic transfection promoted miR-15b overexpression and inhibited HepG2 cell proliferation significantly (P < 0.05). MiR-15b overexpression downregulated BCL2 mRNA and protein expression obviously (P < 0.05). On the contrary, miR-15b inhibitor transfection markedly reduced miR-15b expression in liver cancer cells (P < 0.05), promoted tumor cell proliferation, and increased BCL2 mRNA and protein expression. MiR-15b expression changes did not affect cell invasion (P > 0.05). MiR-15b can inhibit HepG2 cell proliferation and down-regulate BCL2 mRNA and protein expression. PMID:26884837

  5. 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. PMID:27087003

  6. 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.

  7. Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

    NASA Astrophysics Data System (ADS)

    Zhou, Fang; Wei, Huajiang; Ye, Xiangping; Hu, Kun; Wu, Guoyong; Yang, Hongqin; He, Yonghong; Xie, Shusen; Guo, Zhouyi

    2015-02-01

    In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues.

  8. Incidental biliary cystadenoma mimicking liver metastasis in a gastric cancer patient

    PubMed Central

    Yazıcı, Pınar; Aydın, Ünal

    2016-01-01

    Biliary cystadenoma represents a rare benign cystic hepatic neoplasm with premalignant potential. The diagnosis is usually difficult, and imaging methods may not be possible to clarify the pathology. It can be hard to determine, particularly in patients with a previous cancer history that has high metastatic potential in the liver. We presented a 53-year-old man with a newly diagnosed liver mass that was suspicious for metastasis 2 years after gastric cancer surgery and histological analysis confirmed the diagnosis of biliary cystadenoma. PMID:27528806

  9. 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

  10. 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

    2016-01-01

    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. PMID:27618777

  11. Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefractory liver metastases from colorectal cancer

    PubMed Central

    Yu, Jeong Il; Choi, Doo Ho; Noh, Jae Myoung; Oh, Dongryul; Park, Jun Su; Chang, Ji Hyun; Kim, Seung Tae; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki

    2016-01-01

    Purpose A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Materials and Methods Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. Results A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Conclusion Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer. PMID:27104165

  12. Increased childhood liver cancer mortality and arsenic in drinking water in Northern Chile

    PubMed Central

    Liaw, Jane; Marshall, Guillermo; Yuan, Yan; Ferreccio, Catterina; Steinmaus, Craig; Smith, Allan H.

    2009-01-01

    Arsenic in drinking water is an established cause of lung, bladder and skin cancers in adults, and may also cause adult kidney and liver cancer. Some evidence for these effects originated from Region II of Chile which had a period of elevated arsenic levels in drinking water, in particular from 1958 to 1970. This unique exposure scenario provides a rare opportunity to investigate the effects of early-life arsenic exposure on childhood mortality; to our knowledge, this is the first study of childhood cancer mortality and high concentrations of arsenic in drinking water. In this paper, we compare cancer mortality rates under the age of 20 in Region II during 1950–2000 with those of unexposed Region V, dividing subjects into those born before, during or after the peak exposure period. Mortality from the most common childhood cancers, leukemia and brain cancer, were not increased in the exposed population. However, we found childhood liver cancer mortality occurred at higher rates than expected; for those exposed as young children liver cancer mortality between ages 0–19 was especially high: the relative risk (RR) for males born during this period was 8.9 (95% CI 1.7–45.8; p=0.009), for females the corresponding RR was 14.1 (95% CI 1.6–126; p=0.018), and for males and females pooled, the RR was 10.6 (95% CI 2.9–39.2; p<0.001). These findings suggest exposure to arsenic in drinking water during early childhood may result in an increase in childhood liver cancer mortality. PMID:18708388

  13. Effective Dose from Stray Radiation for a Patient Receiving Proton Therapy for Liver Cancer

    SciTech Connect

    Taddei, Phillip J.; Krishnan, Sunil; Mirkovic, Dragan; Newhauser, Wayne D.; Yepes, Pablo

    2009-03-10

    Because of its advantageous depth-dose relationship, proton radiotherapy is an emerging treatment modality for patients with liver cancer. Although the proton dose distribution conforms to the target, healthy tissues throughout the body receive low doses of stray radiation, particularly neutrons that originate in the treatment unit or in the patient. The aim of this study was to calculate the effective dose from stray radiation and estimate the corresponding risk of second cancer fatality for a patient receiving proton beam therapy for liver cancer. Effective dose from stray radiation was calculated using detailed Monte Carlo simulations of a double-scattering proton therapy treatment unit and a voxelized human phantom. The treatment plan and phantom were based on CT images of an actual adult patient diagnosed with primary hepatocellular carcinoma. For a prescribed dose of 60 Gy to the clinical target volume, the effective dose from stray radiation was 370 mSv; 61% of this dose was from neutrons originating outside of the patient while the remaining 39% was from neutrons originating within the patient. The excess lifetime risk of fatal second cancer corresponding to the total effective dose from stray radiation was 1.2%. The results of this study establish a baseline estimate of the stray radiation dose and corresponding risk for an adult patient undergoing proton radiotherapy for liver cancer and provide new evidence to corroborate the suitability of proton beam therapy for the treatment of liver tumors.

  14. 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

  15. Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer.

    PubMed

    Fujimoto, Akihiro; Furuta, Mayuko; Totoki, Yasushi; Tsunoda, Tatsuhiko; Kato, Mamoru; Shiraishi, Yuichi; Tanaka, Hiroko; Taniguchi, Hiroaki; Kawakami, Yoshiiku; Ueno, Masaki; Gotoh, Kunihito; Ariizumi, Shun-Ichi; Wardell, Christopher P; Hayami, Shinya; Nakamura, Toru; Aikata, Hiroshi; Arihiro, Koji; Boroevich, Keith A; Abe, Tetsuo; Nakano, Kaoru; Maejima, Kazuhiro; Sasaki-Oku, Aya; Ohsawa, Ayako; Shibuya, Tetsuo; Nakamura, Hiromi; Hama, Natsuko; Hosoda, Fumie; Arai, Yasuhito; Ohashi, Shoko; Urushidate, Tomoko; Nagae, Genta; Yamamoto, Shogo; Ueda, Hiroki; Tatsuno, Kenji; Ojima, Hidenori; Hiraoka, Nobuyoshi; Okusaka, Takuji; Kubo, Michiaki; Marubashi, Shigeru; Yamada, Terumasa; Hirano, Satoshi; Yamamoto, Masakazu; Ohdan, Hideki; Shimada, Kazuaki; Ishikawa, Osamu; Yamaue, Hiroki; Chayama, Kazuki; Miyano, Satoru; Aburatani, Hiroyuki; Shibata, Tatsuhiro; Nakagawa, Hidewaki

    2016-05-01

    Liver cancer, which is most often associated with virus infection, is prevalent worldwide, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 liver cancers from Japanese individuals. Our comprehensive analysis identified point mutations, structural variations (STVs), and virus integrations, in noncoding and coding regions. We discovered mutational signatures related to liver carcinogenesis and recurrently mutated coding and noncoding regions, such as long intergenic noncoding RNA genes (NEAT1 and MALAT1), promoters, CTCF-binding sites, and regulatory regions. STV analysis found a significant association with replication timing and identified known (CDKN2A, CCND1, APC, and TERT) and new (ASH1L, NCOR1, and MACROD2) cancer-related genes that were recurrently affected by STVs, leading to altered expression. These results emphasize the value of whole-genome sequencing analysis in discovering cancer driver mutations and understanding comprehensive molecular profiles of liver cancer, especially with regard to STVs and noncoding mutations. PMID:27064257

  16. 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. PMID:26735868

  17. Effective Dose from Stray Radiation for a Patient Receiving Proton Therapy for Liver Cancer

    NASA Astrophysics Data System (ADS)

    Taddei, Phillip J.; Krishnan, Sunil; Mirkovic, Dragan; Yepes, Pablo; Newhauser, Wayne D.

    2009-03-01

    Because of its advantageous depth-dose relationship, proton radiotherapy is an emerging treatment modality for patients with liver cancer. Although the proton dose distribution conforms to the target, healthy tissues throughout the body receive low doses of stray radiation, particularly neutrons that originate in the treatment unit or in the patient. The aim of this study was to calculate the effective dose from stray radiation and estimate the corresponding risk of second cancer fatality for a patient receiving proton beam therapy for liver cancer. Effective dose from stray radiation was calculated using detailed Monte Carlo simulations of a double-scattering proton therapy treatment unit and a voxelized human phantom. The treatment plan and phantom were based on CT images of an actual adult patient diagnosed with primary hepatocellular carcinoma. For a prescribed dose of 60 Gy to the clinical target volume, the effective dose from stray radiation was 370 mSv; 61% of this dose was from neutrons originating outside of the patient while the remaining 39% was from neutrons originating within the patient. The excess lifetime risk of fatal second cancer corresponding to the total effective dose from stray radiation was 1.2%. The results of this study establish a baseline estimate of the stray radiation dose and corresponding risk for an adult patient undergoing proton radiotherapy for liver cancer and provide new evidence to corroborate the suitability of proton beam therapy for the treatment of liver tumors.

  18. Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells

    PubMed Central

    Kanthimathi, MS; Haerian, Batoul Sadat

    2016-01-01

    The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liver cancer cells with an IC50 value of 6.98 ± 0.11 µM and 7.76 ± 0.45 µM against SNU-475 and SNU-423 respectively after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of this study suggest that PCC is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PMID:27019772

  19. Changes in Normal Liver and Spleen Volume after Radioembolization with {sup 90}Y-Resin Microspheres in Metastatic Breast Cancer Patients: Findings and Clinical Significance

    SciTech Connect

    Paprottka, Philipp M. Schmidt, G. P.; Trumm, C. G.; Hoffmann, R. T.; Reiser, M. F.; Jakobs, T. F.

    2011-10-15

    Purpose: In clinical trials with yttrium-90-resin-microspheres for the management of colorectal cancer liver metastases, it was observed that radioembolization might result in splenomegaly and an increase in portal vein size. Subclinical hepatitis in normal liver tissue as well as the effects of radioembolization and prior chemotherapy are suspected to be responsible for this phenomenon. The purpose of this study was to quantify the changes in liver and spleen volume and portal vein diameter after radioembolization. Methods: Twenty-seven patients with liver-dominant metastatic disease from breast cancer who had not responded to chemotherapy or had to abandon chemotherapy because of its toxic effects were evaluated. Changes in liver and spleen volume and portal vein diameter as well as liver tumor volume and diameter were quantified using computed tomography scans. Results: Radioembolization was associated with a significant mean decrease in the whole liver volume of 10.2% (median 16.7%; P = 0.0024), mainly caused by a reduction in the right lobe volume (mean 16.0%; P < 0.0001). These changes were accompanied by a significant increase in the diameter of the main portal vein (mean 6.8%; P < 0.0001) as well as splenic volume (mean 50.4%; P < 0.0001). Liver-tumor volume and diameter decreased by a median of 24 and 39.7%. Conclusions: Radioembolization is an effective treatment for tumor size reduction in patients with breast cancer liver metastases. Treatment is associated with changes of hepatic parenchymal volume, splenic volume, and portal vein size that appear not to represent clinically important sequelae in this patient cohort.

  20. N-acetylcysteine improves antitumoural response of Interferon alpha by NF-kB downregulation in liver cancer cells

    PubMed Central

    2012-01-01

    Background Liver cancer is one of the most common malignancies in the world and at the moment, there is no drug intervention effective for the treatment of liver tumours. Investigate the effect of N-acetylcysteine (NAC), which has been studied for its antitumoural properties, on the toxicity of hepatocarcinoma (HCC) cells in vitro when used with the drug interferon alpha-2A (IFN), which is used clinically to treat HCC. Results NAC, IFN and NAC plus IFN reduced cell viability, as determined by MTT assay. More importantly, NAC potentiates the cytotoxic effect of IFN, with the best response achieved with 10 mM of NAC and 2.5 x 104 of IFN. These results were confirmed by Annexin/PI staining through flow cytometry and morphologic analyses. Co-treatment reduced the expression of the nuclear transcription factor kappa-B (NF-kB). In a similar way to NAC, RNAi against p65 potentiated the toxic effect of IFN, suggesting that, indeed, NAC may be enhancing the effect of IFN through inhibition of NF-kB. Conclusions Our results support the notion that NAC may be an important drug for the treatment of liver tumours as primary or adjuvant therapy. IFN has a limited clinical response, and therefore, the anti-proliferative properties of NAC in the liver should be explored further as an alternative for non-responders to IFN treatment. PMID:23206959

  1. Application of an in silico liver model to determine nuclear receptor mediated pathways in liver cancer

    EPA Science Inventory

    Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs in rodents can result in increased incidence of liver tumors. These are generally thought to develop through a non-genotoxic mechanism with...

  2. Locally ablative therapies for primary and metastatic liver cancer.

    PubMed

    Li, David; Kang, Josephine; Madoff, David C

    2014-08-01

    Locally ablative therapies have an increasing role in the effective multidisciplinary approach towards the treatment of both primary and metastatic liver tumors. In patients who are not considered surgical candidates and have low volume disease, these therapies have now become established into consensus practice guidelines. A large range of therapeutic options exist including percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, percutaneous laser ablation (PLA), irreversible electroporation (IRE), stereotactic body radiation therapy (SBRT) and high intensity focused ultrasound (HIFU); each having benefits and drawbacks. The greatest body of evidence supporting clinical utility in the liver currently exists for RFA, with PEI having fallen out of favor. MWA, IRE, SBRT and HIFU are relatively nascent technologies, and outcomes data supporting their use is promising. Future directions of ablative therapies include tandem approaches to improve efficacy in the treatment of liver tumors. PMID:24746315

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

    PubMed

    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

  4. Intrapancreatic bile duct metastasis from colon cancer after resection of liver metastasis with intrabiliary growth: a case report.

    PubMed

    Kawakatsu, Shoji; Kaneoka, Yuji; Maeda, Atsuyuki; Takayama, Yuichi; Fukami, Yasuyuki; Onoe, Shunsuke

    2015-01-01

    An extremely rare case of intrapancreatic bile duct metastasis from sigmoid colon adenocarcinoma is herein presented. Sigmoid colon cancer (T3, N0, M0, stage IIA) had been diagnosed and treated by sigmoidectomy in October 1993. In December 2002, a liver metastasis with intrabiliary growth was found, and this was treated by extended right hepatic lobectomy and caudate lobectomy with extrahepatic bile duct resection. In February 2014, intrapancreatic bile duct metastasis was found, and this was treated by subtotal stomach-preserving pancreatoduodenectomy. The intrapancreatic metastasis was judged to have arisen from cancer cell implantation, either by spontaneous shedding of cancer cells or as a complication of percutaneous transhepatic biliary drainage. Twelve months have passed since the last surgical intervention, and there has been no sign of local recurrence or distant metastasis. Differential diagnosis between intrahepatic cholangiocarcinoma and intrabiliary growth of a liver metastasis originating from colorectal adenocarcinoma is difficult but very important for determining the therapeutic strategy. Careful examination is needed to diagnose intrahepatic biliary dilatation, especially for patients with a history of carcinoma in the digestive tract and even if years have passed since curative resection of the digestive tract cancer. Aggressive surgical management for localized recurrence of a hepatic metastasis from colorectal adenocarcinoma may improve patient survival. PMID:26293132

  5. PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

    PubMed Central

    Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

    2014-01-01

    Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

  6. Folate metabolism-related gene polymorphisms and susceptibility to primary liver cancer in North China.

    PubMed

    Cui, Lian-Hua; Song, Yang; Si, Hongzong; Shen, Fangzhen; Shin, Min-Ho; Kim, Hee Nam; Choi, Jin-Su

    2012-09-01

    Genetic factors may contribute to individual differences in cancer susceptibility. This study was designed to investigate the effects of the polymorphisms of methylenetetrahydrofolate reductase 677 C → T (MTHFR 677 C → T), methylenetetrahydrofolate reductase 1298 A → C (MTHFR 1298A → C), thymidylate synthase (TYMS 3R → 2R), and methionine synthase 2756 A → G (MTR 2756 A → G) on the risk of primary liver cancer (PLC). We conducted a case-control study involving 356 PLC cases and 641 healthy controls in North China. Compared with the MTHFR 677CC genotype, the MTHFR 677TT genotype showed an increased risk for PLC (TT vs. CC: adjusted odds ratio (OR) = 1.56; 95% confidence interval (CI): 1.02-2.40; P = 0.043) after adjusting for gender and age, whereas the MTHFR 1298CC genotype showed a significantly decreased risk for PLC (CC vs. AA: adjusted OR = 0.23; 95% CI: 0.08-0.70; P = 0.010). However, no significant association was found between the TYMS 3R → 2R or the MTR 2756 A → G polymorphism and the risk of PLC. Our results suggest that the MTHFR 677 C → T and the MTHFR 1298A → C genetic polymorphisms might play important role in hepatic carcinogenesis. Further studies with larger sample sizes are required to validate this association. PMID:21956592

  7. Analysis of clinical effect of high-intensity focused ultrasound on liver cancer

    PubMed Central

    Li, Chuan-Xing; Xu, Guo-Liang; Jiang, Zhen-You; Li, Jian-Jun; Luo, Guang-Yu; Shan, Hong-Bo; Zhang, Rong; Li, Yin

    2004-01-01

    AIM: To evaluate the clinical effect of high-intensity focused ultrasound (HIFU) in the treatment of patients with liver cancer. METHODS: HIFU treatment was performed in 100 patients with liver cancer under general anesthesia and by a targeted ultrasound. Evaluation of efficacy was made on the basis of clinical symptoms, liver function tests, AFP, MRI or CT before and after the treatment. RESULTS: After HIFU treatment, clinical symptoms were relieved in 86.6%(71/82) of patients. The ascites disappeared in 6 patients. ALT (95 ± 44) U/L and AST (114 ± 58) U/L before HIFU treatment were reduced to normal in 83.3%(30/36) and 72.9%(35/48) patients, respectively, after the treatment. AFP was lowered by more than 50% in 65.3%(32/49) patients. After HIFU treatment, MRI or CT findings indicated coagulation necrosis and blood supply reduction or disappearance of tumor in the target region. CONCLUSION: HIFU can efficiently treat the patients with liver cancer. It will offer a significant noninvasive therapy for local treatment of liver tumor. PMID:15259065

  8. A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness

    PubMed Central

    Yi, Cao; Li, Chen Chen; Yu, Patricia; Arakelian, Ani; Tanvir, Imrana; Khan, Haseeb Ahmed; Rabbani, Shafaat

    2015-01-01

    Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from non-invasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes in cellular invasiveness from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness. SUMMARY Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins that could serve as drug targets. PMID:26427334

  9. Epidemiology and early diagnosis of primary liver cancer in China

    SciTech Connect

    Yen, F.S.; Shen, K.N.

    1986-01-01

    Epidemiological studies in different areas in China have revealed several outstanding risk factors of PLC, i.e., HBV infection, pollution of drinking water, contamination of food by AFB1 and/or nitrosamines, and family predisposition. Accordingly, a program of HBV vaccination, improved supply of drinking water, better preservation and storage of food, and possibly chemoprevention for high-risk populations should be effective preventive measures. Studies have shown that frequent AFP screening in high-risk populations is highly recommended to detect early cases of PLC. According to research in Qidong, careful follow-up of the dynamic changes of AFP in individuals with persistent low levels of positive AFP is important for distinguishing other conditions from true PLC. Newer means for the localization of small-size PLC (under 5 cm), such as type B ultrasonography, nuclide scanning, computerized tomography, and hepatoangiography, represent remarkable progress in improving markedly the success of surgery and hence the survival rate of PLC patients. The advances in knowledge of PLC have been encouraging. Although much work remains to be done on the etiological agents and the mechanism of oncogenesis, it is time that larger scale control measures be put into effect in high-incidence areas to discover if one of the most common cancers in the world can be controlled. 62 references.

  10. Identification of two functional nuclear localization signals mediating nuclear import of liver receptor homologue-1.

    PubMed

    Yang, Feng-Ming; Lin, Yu-Chi; Hu, Meng-Chun

    2011-04-01

    Liver receptor homologue-1 (LRH-1) is a member of the nuclear receptor superfamily. We characterized two functional nuclear localization signals (NLSs) in LRH-1. NLS1 (residues 117-168) overlaps the second zinc finger in the DNA binding domain. Mutagenesis showed that the zinc finger structure and two basic clusters on either side of the zinc finger loop are critical for nuclear import of NLS1. NLS2 (residues 169-204) is located in the Ftz-F1 box that contains a bipartite signal. In full-length LRH-1, mutation of either NLS1 or NLS2 had no effect on nuclear localization, but disruption of both NLS1 and NLS2 resulted in the cytoplasmic accumulation of LRH-1. Either NLS1 or NLS2 alone was sufficient to target LRH-1 to the nucleus. Both NLS1 and NLS2 mediate nuclear transport by a mechanism involving importin α/β. Finally, we showed that three crucial basic clusters in the NLSs are involved in the DNA binding and transcriptional activities of LRH-1. PMID:20853131

  11. Hospital stays for hepatitis B or C virus infection or primary liver cancer among immigrants: a census-linked population-based cohort study

    PubMed Central

    Ng, Edward; Myers, Robert P.; Manuel, Doug; Sanmartin, Claudia

    2016-01-01

    Background: The recent increase in the incidence of primary liver cancer in Canada has been attributed to a higher proportion of immigrants from countries endemic for hepatitis B virus (HBV) and hepatitis C virus (HCV). We examined hospital discharges for liver disease in Canada, focusing on those for all liver-related diseases, HBV infection, HCV infection and primary liver cancer, by 3 immigration-related variables: immigration status, duration of residence in Canada and risk level of the source country. Methods: We calculated annualized crude and age-standardized rates of a hospital stay in Canada for HBV infection, HCV infection, primary liver cancer and all liver-related diseases using data from the 2006 Canadian census (long form) linked to the Canadian Institute for Health Information Discharge Abstract Database for fiscal years 2006/07 to 2008/09. We estimated the odds of a hospital stay using logistic regression for the 3 immigration-related variables, adjusting for sociodemographic indicators. Results: Immigrants were less likely than Canadian-born residents to be discharged with a diagnosis of any liver-related condition (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.78-0.89); however, they were more likely to be discharged with a diagnosis of HBV infection (OR 2.02, 95% CI 1.57-2.60) and primary liver cancer (OR 1.43, 95% CI 1.22-1.68). There was a clear association between a hospital stay for HBV infection and immigration from HBV-endemic countries (OR 5.15, 95% CI 3.87-6.84) and between a stay for HCV infection and immigration from HCV-endemic countries (OR 2.98, 95% CI 1.74-5.11). Adjustment for low income status and urban residence did not change the results. Interpretation: Although the odds of a liver-related hospital stay were lower among immigrants than among those born in Canada, immigrants from countries at high risk for HBV infection, HCV infection and primary liver cancer were more likely than Canadian-born residents to have a

  12. Assessment of residual error in liver position using kV cone-beam computed tomography for liver cancer high-precision radiation therapy

    SciTech Connect

    Hawkins, Maria A.; Brock, Kristy K.; Eccles, Cynthia; Moseley, Douglas; Jaffray, David; Dawson, Laura A. . E-mail: laura.dawson@rmp.uhn.on.ca

    2006-10-01

    Purpose: To evaluate the residual error in liver position using breath-hold kilovoltage (kV) cone-beam computed tomography (CT) following on-line orthogonal megavoltage (MV) image-guided breath-hold liver cancer conformal radiotherapy. Methods and Materials: Thirteen patients with liver cancer treated with 6-fraction breath-hold conformal radiotherapy were investigated. Before each fraction, orthogonal MV images were obtained during exhale breath-hold, with repositioning for offsets >3 mm, using the diaphragm for cranio-caudal (CC) alignment and vertebral bodies for medial-lateral (ML) and anterior posterior (AP) alignment. After repositioning, repeat orthogonal MV images, orthogonal kV fluoroscopic movies, and kV cone-beam CTs were obtained in exhale breath-hold. The cone-beam CT livers were registered to the planning CT liver to obtain the residual setup error in liver position. Results: After repositioning, 78 orthogonal MV image pairs, 61 orthogonal kV image pairs, and 72 kV cone-beam CT scans were obtained. Population random setup errors ({sigma}) in liver position were 2.7 mm (CC), 2.3 mm (ML), and 3.0 mm (AP), and systematic errors ({sigma}) were 1.1 mm, 1.9 mm, and 1.3 mm in the superior, medial, and posterior directions. Liver offsets >5 mm were observed in 33% of cases; offsets >10 mm and liver deformation >5 mm were observed in a minority of patients. Conclusions: Liver position after radiation therapy guided with MV orthogonal imaging was within 5 mm of planned position in the majority of patients. kV cone-beam CT image guidance should improve accuracy with reduced dose compared with orthogonal MV image guidance for liver cancer radiation therapy.

  13. 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

  14. Erythema, papules, and arthralgia associated with liver cancer: report of a rare case of multicentric reticulohistiocytosis

    PubMed Central

    Hu, Liang; Mei, Jun-Hua; Xia, Jin; Hao, Quan-Shui; Cheng, Li-Ping; Wu, Yao-Hua

    2015-01-01

    We report a rare case of multicentric reticulohistiocytosis (MRH) associated with liver carcinoma. A 36-year-old man who had been diagnosed as having liver carcinoma for 2 years presented with a 2-month history of multiple papulonodules on the face, ears, neck, and upper chest, accompanied by progressive polyarthralgia of the hands, wrists, elbows and knee joints without fever or chills. Skin histology revealed well defined dermal infiltrate consisting of multinucleated giant cells and macrophages having abundant eosinophilic finely granular cytoplasm with ground glass appearance. Further immunohistochemical studies characterized the lesions as positive for CD68, CD45 and Vimentin. A diagnosis of MRH that was associated with liver cancer was made. Treatment with prednisolone for 2 months resulted in a significant improvement of the skin and joint symptoms, but was discontinued due to his significant enlargement and extensive metastases of the liver carcinoma. PMID:26045857

  15. Inhibition of diethylnitrosamine-induced liver cancer in rats by Rhizoma paridis saponin.

    PubMed

    Liu, Jing; Man, Shuli; Li, Jing; Zhang, Yang; Meng, Xin; Gao, Wenyuan

    2016-09-01

    Rhizoma Paridis saponin (RPS) had been regarded as the main active components responsible for the anti-tumor effects of the herb Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. In the present research, we set up a rat model of diethylnitrosamine (DEN) induced hepatoma to evaluate antitumor effect of RPS. After 20 weeks treatment, rats were sacrificed to perform histopathological examinations, liver function tests, oxidative stress assays and so forth. As a result, DEN-induced hepatoma formation. RPS alleviated levels of liver injury through inhibiting liver tissues of malondialdehyde (MDA) and nitric oxide (NO) formation, increasing superoxide dismutases (SOD) production, and up-regulating expression of GST-α/μ/π in DEN-induced rats. All in all, RPS would be a potent agent inhibiting chemically induced liver cancer in the prospective application. PMID:27451357

  16. 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

  17. Metabolic Profiles are Principally Different between Cancers of the Liver, Pancreas and Breast

    PubMed Central

    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. PMID:25210494

  18. 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

  19. A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer.

    PubMed

    O'Donnell, Kathryn A; Keng, Vincent W; York, Brian; Reineke, Erin L; Seo, Daekwan; Fan, Danhua; Silverstein, Kevin A T; Schrum, Christina T; Xie, Wei Rose; Mularoni, Loris; Wheelan, Sarah J; Torbenson, Michael S; O'Malley, Bert W; Largaespada, David A; Boeke, Jef D

    2012-05-22

    The Sleeping Beauty (SB) transposon mutagenesis system is a powerful tool that facilitates the discovery of mutations that accelerate tumorigenesis. In this study, we sought to identify mutations that cooperate with MYC, one of the most commonly dysregulated genes in human malignancy. We performed a forward genetic screen with a mouse model of MYC-induced liver cancer using SB-mediated mutagenesis. We sequenced insertions in 63 liver tumor nodules and identified at least 16 genes/loci that contribute to accelerated tumor development. RNAi-mediated knockdown in a liver progenitor cell line further validate three of these genes, Ncoa2/Src-2, Zfx, and Dtnb, as tumor suppressors in liver cancer. Moreover, deletion of Ncoa2/Src-2 in mice predisposes to diethylnitrosamine-induced liver tumorigenesis. These findings reveal genes and pathways that functionally restrain MYC-mediated liver tumorigenesis and therefore may provide targets for cancer therapy. PMID:22556267

  20. A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death.

    PubMed

    Catrysse, L; Farhang Ghahremani, M; Vereecke, L; Youssef, S A; Mc Guire, C; Sze, M; Weber, A; Heikenwalder, M; de Bruin, A; Beyaert, R; van Loo, G

    2016-01-01

    An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-κB (NF-κB) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF-κB-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor. PMID:27253414

  1. Jagged1 DNA Copy Number Variation Is Associated with Poor Outcome in Liver Cancer.

    PubMed

    Kawaguchi, Kazunori; Honda, Masao; Yamashita, Taro; Okada, Hikari; Shirasaki, Takayoshi; Nishikawa, Masashi; Nio, Kouki; Arai, Kuniaki; Sakai, Yoshio; Yamashita, Tatsuya; Mizukoshi, Eishiro; Kaneko, Shuichi

    2016-08-01

    Notch signaling abnormalities are reported to be involved in the acceleration of malignancy in solid tumors and stem cell formation or regeneration in various organs. We analyzed specific genes for DNA copy number variations in liver cancer cells and investigated whether these factors relate to clinical outcome. Chromosome 20p, which includes the ligand for Notch pathways, Jagged1, was found to be amplified in several types of hepatoma cells, and its mRNA was up-regulated according to α-fetoprotein gene expression levels. Notch inhibition using Jagged1 shRNA and γ-secretase inhibitors produced significant suppression of cell growth in α-fetoprotein-producing cells with suppression of downstream genes. Using in vivo hepatoma models, the administration of γ-secretase inhibitors resulted in reduced tumor sizes and effective Notch inhibition with widespread apoptosis and necrosis of viable tumor cells. The γ-secretase inhibitors suppressed cell growth of the epithelial cell adhesion molecule-positive fraction in hepatoma cells, indicating that Notch inhibitors could suppress the stem cell features of liver cancer cells. Even in clinical liver cancer samples, the expression of α-fetoprotein and Jagged1 showed significant correlation, and amplification of the copy number of Jagged1 was associated with Jagged1 mRNA expression and poor survival after liver cancer surgical resection. In conclusion, amplification of Jagged1 contributed to mRNA expression that activates the Jagged1-Notch signaling pathway in liver cancer and led to poor outcome. PMID:27315779

  2. NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project.

    PubMed

    Petrick, Jessica L; Sahasrabuddhe, Vikrant V; Chan, Andrew T; Alavanja, Michael C; Beane-Freeman, Laura E; Buring, Julie E; Chen, Jie; Chong, Dawn Q; Freedman, Neal D; Fuchs, Charles S; Gaziano, John Michael; Giovannucci, Edward; Graubard, Barry I; Hollenbeck, Albert R; Hou, Lifang; Jacobs, Eric J; King, Lindsay Y; Koshiol, Jill; Lee, I-Min; Linet, Martha S; Palmer, Julie R; Purdue, Mark P; Rosenberg, Lynn; Schairer, Catherine; Sesso, Howard D; Sigurdson, Alice J; Wactawski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Campbell, Peter T; McGlynn, Katherine A

    2015-12-01

    Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. PMID:26391917

  3. Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice

    PubMed Central

    Fu, Min; Song, Yang; Wen, Zhaoxia; Lu, Xingyi; Cui, Lianhua

    2016-01-01

    Inositol hexaphosphate (IP6) and inositol (Ins), naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti-metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC) in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group). IP6 and/or Ins (80 mg/kg each, 0.2 mL/day) were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin-β1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies. PMID:27187454

  4. Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice.

    PubMed

    Fu, Min; Song, Yang; Wen, Zhaoxia; Lu, Xingyi; Cui, Lianhua

    2016-01-01

    Inositol hexaphosphate (IP6) and inositol (Ins), naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti-metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC) in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group). IP6 and/or Ins (80 mg/kg each, 0.2 mL/day) were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin-β1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies. PMID:27187454

  5. 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. PMID:27571956

  6. What You Need to Know about Liver Cancer

    MedlinePlus

    ... Currents Blog Research Findings Drug Approvals Precision Medicine Leadership Views All Press Releases 2016 2015 2014 2013 ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ...

  7. Liver dysfunction in pregnancy: an important cause of maternal and perinatal morbidity and mortality in Pakistan

    PubMed Central

    Hossain, N; Shamsi, T; Kuczynski, E; Lockwood, C J; Paidas, M J

    2009-01-01

    The objective of this study was to evaluate the maternal and perinatal outcome of women with liver dysfunction during pregnancy. The study involved a prospective observational study design and was carried out at the Dow University of Health Sciences and Civil Hospital Karachi, Pakistan. A total of 800 women, who delivered during the study period from January 2006 to September 2006, constituted the study population. Pregnant women with liver dysfunction underwent evaluation for the aetiology of their liver dysfunction, including screening for hepatitis E. Thirty-five women were identified with liver dysfunction. Fourteen (40%) presented in the second trimester and 21 (60%) presented in the third trimester. Twenty-two of the 35 women (63%) had isolated acute hepatitis E; five (14%) had HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome; two (6%) had intrahepatic cholestasis of pregnancy (IHCP), two had acute fatty liver of pregnancy (AFLP) and two women had hepatitis A. A specific diagnosis was not reached in two women who died prior to delivery. In women with hepatitis E, the mean values of bilirubin and alanine transaminase were 12 mg/dL and 675 U/L, respectively. Abnormal coagulation parameters were present in 20 (57%) of the women and in 18 of 22 (82%) with hepatitis E. Fulminant hepatic failure (FHF) was seen in four patients. Seven women (20%) underwent caesarean section, 26 (74%) delivered vaginally and two women died undelivered. There were six maternal deaths in the study population; two were due to hepatitis E, one each from HELLP and AFLP, and two remained undiagnosed. The overall perinatal mortality within the group was 43%. Hepatitis E was the most common cause of FHF and maternal death in pregnant women with liver dysfunction.

  8. Biology and clinical implications of CD133{sup +} liver cancer stem cells

    SciTech Connect

    Ma, Stephanie

    2013-01-15

    Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, accounting for 80%–90% of all liver cancers. The disease ranks as the fifth most common cancer worldwide and is the third leading cause of all cancer-associated deaths. Although advances in HCC detection and treatment have increased the likelihood of a cure at early stages of the disease, HCC remains largely incurable because of late presentation and tumor recurrence. Only 25% of HCC patients are deemed suitable for curative treatment, with the overall survival at just a few months for inoperable patients. Apart from surgical resection, loco-regional ablation and liver transplantation, current treatment protocols include conventional cytotoxic chemotherapy. But due to the highly resistant nature of the disease, the efficacy of the latter regimen is limited. The recent emergence of the cancer stem cell (CSC) concept lends insight into the explanation of why treatment with chemotherapy often may seem to be initially successful but results in not only a failure to eradicate the tumor but also possibly tumor relapse. Commonly used anti-cancer drugs in HCC work by targeting the rapidly proliferating and differentiated liver cancer cells that constitute the bulk of the tumor. However, a subset of CSCs exists within the tumor, which are more resistant and are able to survive and maintain residence after treatment, thus, growing and self-renewing to generate the development and spread of recurrent tumors in HCC. In the past few years, compelling evidence has emerged in support of the hierarchic CSC model for solid tumors, including HCC. And in particular, CD133 has drawn significant attention as a critical liver CSC marker. Understanding the characteristics and function of CD133{sup +} liver CSCs has also shed light on HCC management and treatment, including the implications for prognosis, prediction and treatment resistance. In this review, a detailed summary of the recent progress

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

    SciTech Connect

    Klein, Jonathan; Dawson, Laura A.; Jiang, Haiyan; Kim, John; Dinniwell, Rob; Brierley, James; Wong, Rebecca; Lockwood, Gina; Ringash, Jolie

    2015-09-01

    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 also 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 warrants

  10. Lessons Learnt from Evidence-Based Approach of Using Chinese Herbal Medicines in Liver Cancer

    PubMed Central

    Zheng, Zhan; Cho, William Chi-Shing; Xu, Ling; Wang, Juyong; Sze, Daniel Man-Yuen

    2013-01-01

    This paper is a systematic review of evidence-based studies of the effectiveness of Chinese herbal medicine (CHM) in the treatment of liver cancer. After a detailed analysis of the literature, five animal studies and four human clinical trials met the criteria for inclusion. Analysis revealed that results of the clinical trials, whilst encouraging, need to be interpreted with caution as problems with study designs may lead to apparent benefits being attributable to various forms of bias. However, as each of the CHM agents used in these studies appeared to be potentially beneficial, further well-designed and controlled randomized clinical trials are warranted. The second part of this review focused on the lessons learned from the relationships between Traditional Chinese Medicine (TCM) theory, TCM Syndrome Differentiation, and modern scientific understanding of mechanisms of action of CHM agents. The understanding of TCM Syndrome Differentiation may allow identification of different patterns of disharmony and may provide important guidance to the prescription of CHM. Furthermore, quality control using both biological and chemical fingerprinting of CHM is important to ensure batch-to-batch consistency to deliver sustained therapeutic benefit. Also, careful assessment of herb-drug interactions is paramount for safety and integrative use of western chemotherapeutic and CHM agents. PMID:23818930

  11. [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. PMID:26805157

  12. Oxaliplatin-induced sinusoidal obstruction syndrome mimicking metastatic colon cancer in the liver

    PubMed Central

    CHOI, JUNG-HYE; WON, YOUNG-WOONG; KIM, HYUN SUNG; OH, YOUNG-HA; LIM, SANGHYEOK; KIM, HAN-JOON

    2016-01-01

    Oxaliplatin is an effective chemotherapeutic agent for the treatment of colorectal cancer; however, it may cause liver injury, particularly sinusoidal obstruction syndrome (SOS). Although SOS does not usually present with focal lesions on radiological images, the present study describes the case of a 22-year-old woman with oxaliplatin-induced SOS mimicking metastatic colon cancer in the liver. An abdominal computed tomography revealed a novel 1 cm, low-density lesion in segment 1 of the liver following the administration of the fourth round of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer. Since the lesion was indistinguishable from metastasis, even with detailed imaging studies, including magnetic resonance imaging and positron emission tomography-computed tomography, an isolated caudate lobectomy was planned. The cut surface of the resected liver showed a localized reddish congested lesion measuring 1.4 cm in diameter. The adjacent hepatic parenchyma also demonstrated diffuse sinusoidal congestion with a nutmeg-like appearance. Histologically, the lesion exhibited severe sinusoidal congestion with peliosis hepatis-like features. The widened sinusoidal space was outlined by markedly attenuated hepatic cords and filled with erythrocytes. The final diagnosis was oxaliplatin-induced SOS. The patient recovered completely and was relapse-free at the time of writing. PMID:27073565

  13. An analysis of content in comprehensive cancer control plans that address chronic hepatitis B and C virus infections as major risk factors for liver cancer.

    PubMed

    Momin, Behnoosh; Richardson, Lisa

    2012-08-01

    Chronic hepatitis B and hepatitis C virus (HBV and HCV) infections are among the leading causes of preventable death worldwide. Chronic viral hepatitis is the cause of most primary liver cancer, which is the third leading cause of cancer deaths globally and the ninth leading cause of cancer deaths in the United States. The extent to which comprehensive cancer control (CCC) programs in states, tribal governments and organizations, territories, and Pacific Island jurisdictions address chronic hepatitis B and/or hepatitis C infections as risk factors for liver cancer or recommend interventions for liver cancer prevention in their CCC plans remains unknown. We searched CCC plans for this information using the search tool at http://www.cdc.gov/cancer/ncccp/ to access the content of plans for this information. A combination of key search terms including "liver cancer", "hepatitis", "chronic alcohol", and "alcohol abuse" were used to identify potential content regarding liver cancer risk factors and prevention. Relevant content was abstracted for further review and classification. Of 66 (Although CDC funds 65 programs, one of the Pacific Island Jurisdiction grantees is the Federated States of Micronesia (FSM). This national program supports four FSM states, each of which submits a cancer plan to CDC for a total of 69 plans. During this time period, 66 plans were available on the website.) CCC plans, 27% (n = 18) addressed liver cancer using the above-mentioned search terms. In the 23 plans that addressed HBV and/or HCV, there were 25 goals, objectives, strategies, and outcomes aimed at reducing the incidence or prevalence of HBV and/or HCV infection. While nearly a third of CCC programs identify at least one goal, objective, strategy, outcome, or prevention program to reduce cancer burden in their CCC plans, few plans discuss specific actions needed to reduce the burden of liver cancer. PMID:22160788

  14. Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens

    PubMed Central

    Fox, J G; Feng, Y; Theve, E J; Raczynski, A R; Fiala, J L A; Doernte, A L; Williams, M; McFaline, J L; Essigmann, J M; Schauer, D B; Tannenbaum, S R; Dedon, P C; Weinman, S A; Lemon, S M; Fry, R C; Rogers, A B

    2013-01-01

    Background and aims Hepatocellular carcinoma (HCC) frequently results from synergism between chemical and infectious liver carcinogens. Worldwide, the highest incidence of HCC is in regions endemic for the foodborne contaminant aflatoxin B1 (AFB1) and hepatitis B virus (HBV) infection. Recently, gut microbes have been implicated in multisystemic diseases including obesity and diabetes. Here, the hypothesis that specific intestinal bacteria promote liver cancer was tested in chemical and viral transgenic mouse models. Methods Helicobacter-free C3H/HeN mice were inoculated with AFB1 and/or Helicobacter hepaticus. The incidence, multiplicity and surface area of liver tumours were quantitated at 40 weeks. Molecular pathways involved in tumourigenesis were analysed by microarray, quantitative real-time PCR, liquid chromatography/mass spectrometry, ELISA, western blot and immunohistochemistry. In a separate experiment, C57BL/6 FL-N/35 mice harbouring a full-length hepatitis C virus (HCV) transgene were crossed with C3H/HeN mice and cancer rates compared between offspring with and without H hepaticus. Results Intestinal colonisation by H hepaticus was sufficient to promote aflatoxin- and HCV transgene-induced HCC. Neither bacterial translocation to the liver nor induction of hepatitis was necessary. From its preferred niche in the intestinal mucus layer, H hepaticus activated nuclear factor-κB (NF-κB)-regulated networks associated with innate and T helper 1 (Th1)-type adaptive immunity both in the lower bowel and liver. Biomarkers indicative of tumour progression included hepatocyte turnover, Wnt/β-catenin activation and oxidative injury with decreased phagocytic clearance of damaged cells. Conclusions Enteric microbiota define HCC risk in mice exposed to carcinogenic chemicals or hepatitis virus transgenes. These results have implications for human liver cancer risk assessment and prevention. PMID:19850960

  15. Non-Coding RNAs in Primary Liver Cancer

    PubMed Central

    Ghidini, Michele; Braconi, Chiara

    2015-01-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with poor prognosis and limited therapeutic options. Over the past few years, many studies have evaluated the role of non-coding RNAs (ncRNAs) in hepatocarcinogenesis and tumor progression. ncRNAs were shown to have diagnostic, prognostic, and therapeutic potential in HCC. In this manuscript, we review the latest major discoveries concerning microRNAs and long ncRNAs in HCC pathogenesis, and discuss the potentials and the limitations for their use in clinical practice. PMID:26131450

  16. Non-Coding RNAs in Primary Liver Cancer.

    PubMed

    Ghidini, Michele; Braconi, Chiara

    2015-01-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with poor prognosis and limited therapeutic options. Over the past few years, many studies have evaluated the role of non-coding RNAs (ncRNAs) in hepatocarcinogenesis and tumor progression. ncRNAs were shown to have diagnostic, prognostic, and therapeutic potential in HCC. In this manuscript, we review the latest major discoveries concerning microRNAs and long ncRNAs in HCC pathogenesis, and discuss the potentials and the limitations for their use in clinical practice. PMID:26131450

  17. Deranged liver function tests in pregnancy: the importance of postnatal follow-up

    PubMed Central

    Stone, Sophia; Girling, Joanna C

    2009-01-01

    We report an asymptomatic 40-year-old woman with persistently deranged liver function tests found incidentally in the first trimester of her second pregnancy. No cause was apparent clinically, serologically or with imaging studies until a new finding of hepatomegaly led to a repeat ultrasound scan six weeks following delivery. A mass in the region of the common hepatic duct was confirmed to be a cholangiocarcinoma, with vascular invasion precluding curative surgical resection. This case highlights the need for close vigilance of patients with unexplained and persistently abnormal liver function tests, antenatally and postdelivery.

  18. 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.

  19. Importance of ABCC1 for cancer therapy and prognosis.

    PubMed

    Kunická, Tereza; Souček, Pavel

    2014-08-01

    Multidrug resistance presents one of the most important causes of cancer treatment failure. Numerous in vitro and in vivo data have made it clear that multidrug resistance is frequently caused by enhanced expression of ATP-binding cassette (ABC) transporters. ABC transporters are membrane-bound proteins involved in cellular defense mechanisms, namely, in outward transport of xenobiotics and physiological substrates. Their function thus prevents toxicity as carcinogenesis on one hand but may contribute to the resistance of tumor cells to a number of drugs including chemotherapeutics on the other. Within 48 members of the human ABC superfamily there are several multidrug resistance-associated transporters. Due to the well documented susceptibility of numerous drugs to efflux via ABC transporters it is highly desirable to assess the status of ABC transporters for individualization of treatment by their substrates. The multidrug resistance associated protein 1 (MRP1) encoded by ABCC1 gene is one of the most studied ABC transporters. Despite the fact that its structure and functions have already been explored in detail, there are significant gaps in knowledge which preclude clinical applications. Tissue-specific patterns of expression and broad genetic variability make ABCC1/MRP1 an optimal candidate for use as a marker or member of multi-marker panel for prediction of chemotherapy resistance. The purpose of this review was to summarize investigations about associations of gene and protein expression and genetic variability with prognosis and therapy outcome of major cancers. Major advances in the knowledge have been identified and future research directions are highlighted. PMID:24670052

  20. The important application of thioridazine in the endometrial cancer

    PubMed Central

    Meng, Qiong; Sun, Xiao; Wang, Jing; Wang, Yudong; Wang, Lihua

    2016-01-01

    Background: Endometrial cancer (ECa) is one of the serious healthy burden for female worldwide. The treatments of ECa focus on the application of endocrine therapy and aberrant signaling proteins expression recently years. Medroxyprogesterone acrtate (MPA) plays crucial role in the endocrine therapy for ECa patients. However, the outcomes are still not ideal in the advanced stage tumor, especially in the progesterone-resistant ECa. Thioridazine (THIO) is an anti-psychotic agent, which has been reported to suppress the development of several human cancers. In this study, we aimed at to explore the clinical significant of THIO in the treatment of ECa. Methods: Two ECa cell lines (ISK and KLE) were enrolled in this study, and were grouped into fore groups based on the treatment with different agents. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to analyze the viability of ECa cell lines. The apoptosis of ECa cells was examined by using the flow cytometer. To investigate the expression of important proteins, we applied the quantitative real-time RT-PCR (qRT-PCR) method and western blot analysis. Results: The viability of ECa cells was downregulated, and the apoptosis of ECa cells was upregulated after treating with the THIO plus MPA. The expression of progesterone receptor B (PRB) and dopamine receptor D2 (DRD2) were increased, and epidermal growth factor receptor (EGFR) and p-AKT were decreased in the THIO+MPA group. All these results suggested that the THIO could promote MPA to inhibit the growth of cells in ECa, especially in the progesterone-resistant ECa. Conclusion: Taken together, all the data in the present study suggested that the THIO plus MPA might act as the suppressor of tumor growth in ECa by inhibiting the PI3K/AKT signal transduction pathway, which was mediated by PRB, DRD2 and EGFR. PMID:27398159

  1. Evaluation of porcine mesenchymal stem cells for therapeutic use in human liver cancer.

    PubMed

    Groth, Ariane; Ottinger, Sabine; Kleist, Christian; Mohr, Elisabeth; Golriz, Mohammad; Schultze, Daniel; Bruns, Helge; Mehrabi, Arianeb; Schemmer, Peter; Büchler, Markus W; Herr, Ingrid

    2012-02-01

    Mesenchymal stem cell (MSC) transplantation is suggested for therapy of end-stage liver disease, due to e.g. liver cancer and metastasis. Liver transplantation is the only therapeutic option so far but donor organs are short. Also, the availability of allogeneic human MSCs for liver regeneration is limited. Therefore, we evaluated the suitability of porcine bone marrow MSCs from semi-adult pigs and found that morphology, surface expression pattern and multilineage differentiation are similar to those of human MSCs. Porcine MSCs differentiated to a hepatocyte-like phenotype and expressed porcine mRNA of typical liver proteins. However, hepatocyte-like MSCs failed to express the corresponding proteins and did not produce glycogen and urea as primary porcine hepatocytes do. Porcine MSCs were immunotolerated, since they did not activate resting human PBMCs, and were not attacked by human activated PBMCs. However, porcine MSCs led to enhanced proliferation of human pre-activated PBMCs suggesting that immunotoleration of porcine MSCs in the human system has limitations. Together, the potential of porcine MSCs for xenogenous use in human liver therapy is promising but needs further evaluation prior to clinical use. PMID:21964567

  2. Hepatic resection beyond barcelona clinic liver cancer indication: When and how

    PubMed Central

    Garancini, Mattia; Pinotti, Enrico; Nespoli, Stefano; Romano, Fabrizio; Gianotti, Luca; Giardini, Vittorio

    2016-01-01

    Hepatocellular carcinoma (HCC) is the main common primary tumour of the liver and it is usually associated with cirrhosis. The barcelona clinic liver cancer (BCLC) classification has been approved as guidance for HCC treatment algorithms by the European Association for the Study of Liver and the American Association for the Study of Liver Disease. According to this algorithm, hepatic resection should be performed only in patients with small single tumours of 2-3 cm without signs of portal hypertension (PHT) or hyperbilirubinemia. BCLC classification has been criticised and many studies have shown that multiple tumors and large tumors, as wide as those with macrovascular infiltration and PHT, could benefit from liver resection. Consequently, treatment guidelines should be revised and patients with intermediate/advanced stage HCC, when technically resectable, should receive the opportunity to be treated with radical surgical treatment. Nevertheless, the surgical treatment of HCC on cirrhosis is complex: The goal to be oncologically radical has always to be balanced with the necessity to minimize organ damage. The aim of this review was to analyze when and how liver resection could be indicated beyond BCLC indication. In particular, the role of multidisciplinary approach to assure a proper indication, of the intraoperative ultrasound for intra-operative restaging and resection guidance and of laparoscopy to minimize surgical trauma have been enhanced. PMID:27099652

  3. Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus.

    PubMed

    Adam, René; de Gramont, Aimery; Figueras, Joan; Kokudo, Norihiro; Kunstlinger, Francis; Loyer, Evelyne; Poston, Graeme; Rougier, Philippe; Rubbia-Brandt, Laura; Sobrero, Alberto; Teh, Catherine; Tejpar, Sabine; Van Cutsem, Eric; Vauthey, Jean-Nicolas; Påhlman, Lars

    2015-11-01

    An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team. PMID:26417845

  4. Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

    PubMed Central

    Morales-Romero, Jaime; Vargas, Gustavo; García-Román, Rebeca

    2014-01-01

    The hepatitis B virus (HBV) represents a worldwide public health problem; the virus is present in one third of the global population. However, this rate may in fact be higher due to occult hepatitis B virus infection (OBI). This condition is characterized by the presence of the viral genome in the liver of individuals sero-negative for the virus surface antigen (HBsAg). The causes of the absence of HBsAg in serum are unknown, however, mutations have been identified that produce variants not recognized by current immunoassays. Epigenetic and immunological host mechanisms also appear to be involved in HBsAg suppression. Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver. In common with open HBV infection, OBI can contribute to the establishment of hepatocellular carcinoma. Epidemiological data regarding the global prevalence of OBI vary due to the use of detection methods of different sensitivity and specificity. In Latin America, which is considered an area of low prevalence for HBV, diagnostic screening methods using gene amplification tests for confirmation of OBI are not conducted. This prevents determination of the actual prevalence of OBI, highlighting the need for the implementation of cutting edge technology in epidemiological surveillance systems. PMID:24717680

  5. ChIP-seq in steatohepatitis and normal liver tissue identifies candidate disease mechanisms related to progression to cancer

    PubMed Central

    2013-01-01

    Background Steatohepatitis occurs in alcoholic liver disease and may progress to liver cirrhosis and hepatocellular carcinoma. Its molecular pathogenesis is to a large degree unknown. Histone modifications play a key role in transcriptional regulations as marks for silencing and activation of gene expression and as marks for functional elements. Many transcription factors (TFs) are crucial for the control of the genes involved in metabolism, and abnormality in their function may lead to disease. Methods We performed ChIP-seq of the histone modifications H3K4me1, H3K4me3 and H3K27ac and a candidate transcription factor (USF1) in liver tissue from patients with steatohepatitis and normal livers and correlated results to mRNA-expression and genotypes. Results We found several regions that are differentially enriched for histone modifications between disease and normal tissue, and qRT-PCR results indicated that the expression of the tested genes strongly correlated with differential enrichment of histone modifications but is independent of USF1 enrichment. By gene ontology analysis of differentially modified genes we found many disease associated genes, some of which had previously been implicated in the etiology of steatohepatitis. Importantly, the genes associated to the strongest histone peaks in the patient were over-represented in cancer specific pathways suggesting that the tissue was on a path to develop to cancer, a common complication to the disease. We also found several novel SNPs and GWAS catalogue SNPs that are candidates to be functional and therefore needs further study. Conclusion In summary we find that analysis of chromatin features in tissue samples provides insight into disease mechanisms. PMID:24206787

  6. Isoquercitrin inhibits the progression of liver cancer in vivo and in vitro via the MAPK signalling pathway.

    PubMed

    Huang, Guihong; Tang, Bo; Tang, Kun; Dong, Xiaomin; Deng, Jungang; Liao, Luqin; Liao, Zengzhen; Yang, Hua; He, Songqing

    2014-05-01

    Liver cancer is a malignant tumour with high morbidity and fatality rates that is common worldwide. At present, the clinical approaches to treating primary liver cancer include partial hepatectomy, systemic or local chemotherapy, radiotherapy, radiofrequency ablative surgery and liver transplantation. However, all of these approaches have shortcomings, including poor prognosis and numerous side-effects. A large number of studies have proven that many effective ingredients in traditional Chinese medicine, particularly the flavonoid compounds extracted from plants, have achieved breakthroughs in terms of enhancing the effects and reducing the toxicity of chemotherapy and radiotherapy, preventing tumour metastasis and relapse after surgery, alleviating the clinical symptoms of advanced tumours, improving the quality of life of the patient with tumours and extending patient long‑term survival. The purpose of the present study was to investigate the impact of isoquercitrin, the flavonoid from Bidens bipinnata L. extract, on the progression of liver cancer and to achieve a deeper understanding of the biological characteristics of isoquercitrin's involvement in the progression of liver cancer. In the in vitro experiments, isoquercitrin was found to strongly inhibit the proliferation of human liver cancer cells, promote the apoptosis of human liver cancer cells, and block the cell cycle in the G1 phase. Isoquercitrin activated caspase-3, -8 and -9, inhibited the expression level of ERK and p38MAPK protein phosphorylation, and promoted the phosphorylation of JNK. Additionally, isoquercitrin reduced the expression level of PKC in human liver cancer cells. In the in vivo experiments, isoquercitrin was also found to significantly inhibit the growth of transplanted tumours in nude mice. The present study confirmed that isoquercitrin could inhibit the progression of human liver cancer in vivo and in vitro, and the molecular mechanism of isoquercitrin may be closely associated

  7. Observations of liver cancer cells in scanning probe acoustic microscope: a preliminary study

    NASA Astrophysics Data System (ADS)

    Chen, Xiaohui; Fang, Xiaoyue; Xi, Qing; Guo, Hua; Zhang, Ning; Ding, Mingyue

    2016-04-01

    Scanning probe acoustic microscope (SPAM) can be used to acquire the morphology image as well as the non-destructive internal structures acoustic image. However, the observations of the morphology image as well as the internal structures acoustic image of liver cancer cells in SPAM are few. In this paper, we cultured 4 different types of liver cancer cells on the silicon wafer and coverslip to observe their morphology images as well as acoustic images in SPAM, and made a preliminary study of the 8 types of cells specimens (hereinafter referred to as the silicon specimens and coverslips specimens). The experimental measurement results showed that some cellular pseudopodium were observed in the morphology images of the coverslip specimens while no such cellular pseupodium were appeared in the morphology images of the silicon specimens, which concluded that the living liver cancer cells were less likely to grow on the silicon wafer. SPAM provides a rapid and sensitive visual method for studying the morphology and internal structures of the cancer cells. The proposed method can be also used to obtain the morphology and internal information in both solid and soft material wafers, such as silicon and cells, with the resolution of nanometer scale.

  8. The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data.

    PubMed

    Sharp, Gerald B

    2002-12-01

    Chronic exposure to high LET radiation has been shown to cause liver cancer in humans based on studies of patients who received Thorotrast, a colloidal suspension of thorium dioxide formerly used as a radiological contrast agent, and on studies of Russian nuclear weapons workers exposed to internally ingested plutonium. Risk estimates for these exposures and specific subtypes of liver cancer have not been previously reported. Combining published data with tumor registry data pertinent to the Thorotrast cohorts in Germany, Denmark, Portugal, and Japan and to Russian workers, we generally found significantly elevated risks of three major histologic types of liver tumors: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and hemangiosarcoma (HS) for Thorotrast exposures. In contrast, HS was the only liver tumor significantly associated with the lower alpha-particle doses experienced by the Russian workers. Excess cases per 1,000 persons exposed to Thorotrast were similar for the three liver cancer subtypes but lower for plutonium exposure. Odds ratios (OR) of HS and CC for Thorotrast were from 26 to 789 and from 1 to 31 times higher than those for HCC, respectively. ORs of liver cirrhosis for Thorotrast exposure ranged from 2.7 (95% confidence interval (CI): 2.2-3.4) to 6.7 (5.1-8.7). PMID:12674201

  9. Complete resection of unresectable liver metastases from colorectal cancer without deterioration of liver function after cetuximab and irinotecan: two case reports.

    PubMed

    Karasaki, Takahiro; Sano, Keiji; Takamoto, Taketumi; Kinoshita, Hiroto; Tateishi, Ryosuke; Takemura, Tamiko; Makuuchi, Masatoshi

    2010-01-01

    Complete resection for colorectal metastases is the only treatment that can provide long-term survival and may lead to cure. Recent reports have shown that liver resection following systemic chemotherapy in patients with initially unresectable metastases from colorectal cancer may also result in a good long-term survival, and rescue surgery after chemotherapy has become a strategy of choice. A 29-year-old male and a 35-year-old female with unresectable liver metastases from colorectal cancer underwent complete resection after administration of third-line combination therapy of cetuximab and irinotecan. Although systemic chemotherapy may decrease liver function, which may make liver resection unfeasible, in the two cases reported, liver function did not deteriorate after cetuximab plus irinotecan. The indocyanine green retention rate at 15 minutes, which is useful in deciding the safe limit of hepatectomy, was optimal after the administration of cetuximab plus irinotecan in both patients. Cetuximab plus irinotecan may be beneficial as neoadjuvant chemotherapy for metastatic colorectal cancer, not only because of its oncological efficacy but also for preservation of liver function. PMID:21443115

  10. Boosting NAD+ for the prevention and treatment of liver cancer

    PubMed Central

    Djouder, Nabil

    2015-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide yet has limited therapeutic options. We recently demonstrated that inhibition of de novo nicotinamide adenine dinucleotide (NAD+) synthesis is responsible for DNA damage, thereby initiating hepatocarcinogenesis. We propose that boosting NAD+ levels might be used as a prophylactic or therapeutic approach in HCC. PMID:27308492

  11. Boosting NAD(+) for the prevention and treatment of liver cancer.

    PubMed

    Djouder, Nabil

    2015-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide yet has limited therapeutic options. We recently demonstrated that inhibition of de novo nicotinamide adenine dinucleotide (NAD(+)) synthesis is responsible for DNA damage, thereby initiating hepatocarcinogenesis. We propose that boosting NAD(+) levels might be used as a prophylactic or therapeutic approach in HCC. PMID:27308492

  12. LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

    PubMed Central

    CORAL, Gabriela P.; ANTUNES, Aline Dal Pozzo; SERAFINI, Ana Paula Almeida; ARAUJO, Fernanda B.; de MATTOS, Angelo Alves

    2016-01-01

    Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts. PMID:26910447

  13. Biallelic inactivation of protoporphyrinogen oxidase and hydroxymethylbilane synthase is associated with liver cancer in acute porphyrias.

    PubMed

    Schneider-Yin, Xiaoye; van Tuyll van Serooskerken, Anne-Moon; Siegesmund, Marko; Went, Philip; Barman-Aksözen, Jasmin; Bladergroen, Reno S; Komminoth, Paul; Cloots, Roy H E; Winnepenninckx, Véronique J; zur Hausen, Axel; Weber, Markus; Driessen, Ann; Poblete-Gutiérrez, Pamela; Bauer, Peter; Schroeder, Christopher; van Geel, Michel; Minder, Elisabeth I; Frank, Jorge

    2015-03-01

    Variegate porphyria (VP) and acute intermittent porphyria (AIP), the two most common types of acute porphyrias (AHPs), result from a partial deficiency of protoporphyrinogen oxidase (PPOX) and hydroxymethylbilane synthase (HMBS), respectively. A rare but serious complication in the AHPs is hepatocellular carcinoma (HCC). However, the underlying pathomechanisms are yet unknown. We performed DNA sequence analysis in cancerous and non-cancerous liver tissue of a VP and an AIP patient, both with HCC. In samples of both cancerous and non-cancerous liver tissues from the patients, we identified the underlying PPOX and HMBS germline mutations, c.1082dupC and p.G111R, respectively. Additionally, we detected a second somatic mutation, only in the cancer tissue i.e., p.L416X in the PPOX gene of the VP patient and p.L220X in the HMBS gene of the AIP patient, both located in trans to the respective germline mutations. Both somatic mutations were not detected in 10 non-porphyria-associated HCCs. Our data demonstrate that in the hepatic cancer tissue of AHP patients, somatic second-hit mutations result in nearly complete inactivation of the enzymes catalyzing major steps in the heme biosynthetic pathway. Both PPOX and HMBS, which might act as tumor suppressors, play a crucial role in the development of HCC in these individuals. PMID:25445397

  14. Liver Stiffness Measurement in Psoriasis: Do Metabolic or Disease Factors Play the Important Role?

    PubMed Central

    Pongpit, Jamrus; Porntharukchareon, Saneerat; Kaewduang, Piyaporn; Promson, Kwannapa; Stitchantrakul, Wasana; Petraksa, Supanna; Thakkinstian, Ammarin; Kositchaiwat, Chomsri; Rajatanavin, Natta; Sobhonslidsuk, Abhasnee

    2016-01-01

    Background. An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment. We evaluated the prevalence of significant liver fibrosis or high liver stiffness measurement (LSM) using the LSM cutoff over 7 kPa and its associated factors in psoriatic patients. Methods. Subjects underwent TE and ultrasonography. Univariate and multivariate analysis were performed for the associated factors. Results. One hundred and sixty-eight patients were recruited. Three patients were excluded due to TE failure. Mean BMI was 24.8 ± 4.7 kg/m2. NAFLD, metabolic syndrome, and diabetes were seen in 105 (63.6%), 83 (50.3%), and 31 (18.8%) patients. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6%) patients. Mean LSM was 5.3 ± 2.9 kPa. High LSM was found in 18 (11.0%) patients. Waist circumference (OR: 1.24; 95% CI: 1.11–1.38; P = 0.0002), diabetes (OR: 12.70; 95% CI: 1.84–87.70; P = 0.010), and AST (OR: 1.08; 95% CI: 1.02–1.16; P = 0.017) were associated with high LSM. Conclusion. 11% of psoriatic patients had significant liver fibrosis by high LSM. Waist circumference, diabetes, and AST level were the independent predictors. PMID:27006950

  15. Liver Stiffness Measurement in Psoriasis: Do Metabolic or Disease Factors Play the Important Role?

    PubMed

    Pongpit, Jamrus; Porntharukchareon, Saneerat; Kaewduang, Piyaporn; Promson, Kwannapa; Stitchantrakul, Wasana; Petraksa, Supanna; Thakkinstian, Ammarin; Kositchaiwat, Chomsri; Rajatanavin, Natta; Sobhonslidsuk, Abhasnee

    2016-01-01

    Background. An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment. We evaluated the prevalence of significant liver fibrosis or high liver stiffness measurement (LSM) using the LSM cutoff over 7 kPa and its associated factors in psoriatic patients. Methods. Subjects underwent TE and ultrasonography. Univariate and multivariate analysis were performed for the associated factors. Results. One hundred and sixty-eight patients were recruited. Three patients were excluded due to TE failure. Mean BMI was 24.8 ± 4.7 kg/m(2). NAFLD, metabolic syndrome, and diabetes were seen in 105 (63.6%), 83 (50.3%), and 31 (18.8%) patients. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6%) patients. Mean LSM was 5.3 ± 2.9 kPa. High LSM was found in 18 (11.0%) patients. Waist circumference (OR: 1.24; 95% CI: 1.11-1.38; P = 0.0002), diabetes (OR: 12.70; 95% CI: 1.84-87.70; P = 0.010), and AST (OR: 1.08; 95% CI: 1.02-1.16; P = 0.017) were associated with high LSM. Conclusion. 11% of psoriatic patients had significant liver fibrosis by high LSM. Waist circumference, diabetes, and AST level were the independent predictors. PMID:27006950

  16. Cholelithiasis and the risk of liver cancer: results from cohort studies of 134,546 Chinese men and women

    PubMed Central

    Vogtmann, Emily; Shu, Xiao-Ou; Li, Hong-Lan; Chow, Wong-Ho; Yang, Gong; Ji, Bu-Tian; Cai, Hui; Yu, Chang; Gao, Yu-Tang; Zheng, Wei; Xiang, Yong-Bing

    2014-01-01

    Background Cholelithiasis and cholecystectomy have been proposed as risk factors for liver cancer, but findings have been inconsistent. We assessed this association using data from the Shanghai Women’s and Men’s Health Studies. Methods History of cholelithiasis and cholecystectomy were reported at baseline and follow-up interviews and liver cancer diagnoses were ascertained from the Shanghai Cancer Registry and Vital Statistics Unit. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated after adjustment for potential confounders. Results A history of cholelithiasis and cholecystectomy was reported by 9.5% and 3.6% of participants at baseline, respectively. After a total of 859,882 person-years of follow-up for women and 391,093 for men, incident liver cancer was detected in 160 women and 252 men. A positive association was observed between a history of cholelithiasis or cholecystectomy and liver cancer in men (aHR 1.46; 95% CI: 1.02, 2.07) and women (aHR 1.55; 95% CI: 1.06, 2.26). Similar results were observed for cholelithiasis only, but cholecystectomy did not reach statistical significance. There was no strong evidence for detection bias of liver cancer due to cholelithiasis or cholecystectomy. Conclusion Our study suggests that cholelithiasis and possibly cholecystectomy may increase the risk of liver cancer. PMID:24574318

  17. The MAPK Pathway Signals Telomerase Modulation in Response to Isothiocyanate-Induced DNA Damage of Human Liver Cancer Cells

    PubMed Central

    Lamy, Evelyn; Herz, Corinna; Lutz-Bonengel, Sabine; Hertrampf, Anke; Márton, Melinda-Rita; Mersch-Sundermann, Volker

    2013-01-01

    4-methylthiobutyl isothiocyanate (MTBITC), an aliphatic, sulphuric compound from Brassica vegetables, possesses in vitro and in vivo antitumor activity. Recently we demonstrated the potent growth inhibitory potential of the DNA damaging agent MTBITC in human liver cancer cells. Here we now show that MTBITC down regulates telomerase which sensitizes cells to apoptosis induction. This is mediated by MAPK activation but independent from production of reactive oxygen species (ROS). Within one hour, MTBITC induced DNA damage in cancer cells correlating to a transient increase in hTERT mRNA expression which then turned into telomerase suppression, evident at mRNA as well as enzyme activity level. To clarify the role of MAPK for telomerase regulation, liver cancer cells were pre-treated with MAPK-specific inhibitors prior to MTBITC exposure. This clearly showed that transient elevation of hTERT mRNA expression was predominantly mediated by the MAPK family member JNK. In contrast, activated ERK1/2 and P38, but not JNK, signalled to telomerase abrogation and consequent apoptosis induction. DNA damage by MTBITC was also strongly abolished by MAPK inhibition. Oxidative stress, as analysed by DCF fluorescence assay, electron spin resonance spectroscopy and formation of 4-hydroxynonenal was found as not relevant for this process. Furthermore, N-acetylcysteine pre-treatment did not impact MTBITC-induced telomerase suppression or depolarization of the mitochondrial membrane potential as marker for apoptosis. Our data therefore imply that upon DNA damage by MTBITC, MAPK are essential for telomerase regulation and consequent growth impairment in liver tumor cells and this detail probably plays an important role in understanding the potential chemotherapeutic efficacy of ITC. PMID:23382840

  18. Clinicopathologic and gene expression parameters predict liver cancer prognosis

    PubMed Central

    2011-01-01

    Background The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model. Methods Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction. Results HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis. Conclusion When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome. PMID:22070665

  19. Preoperative CT versus diffusion weighted magnetic resonance imaging of the liver in patients with rectal cancer; a prospective randomized trial

    PubMed Central

    Løgager, Vibeke B.; Skjoldbye, Bjørn; Møller, Jakob M.; Lorenzen, Torben; Rasmussen, Vera L.; Thomsen, Henrik S.; Mollerup, Talie H.; Okholm, Cecilie; Rosenberg, Jacob

    2016-01-01

    Introduction. Colorectal cancer is one of the most frequent cancers in the world and liver metastases are seen in up to 19% of patients with colorectal cancers. Detection of liver metastases is not only vital for sufficient treatment and survival, but also for a better estimation of prognosis. The aim of this study was to evaluate the feasibility of diffusion weighted MRI of the liver as part of a combined MR evaluation of patients with rectal cancers and compare it with the standard preoperative evaluation of the liver with CT. Methods. Consecutive patients diagnosed with rectal cancers were asked to participate in the study. Preoperative CT and diffusion weighted MR (DWMR) were compared to contrast enhanced laparoscopic ultrasound (CELUS). Results. A total of 35 patients were included, 15 patients in Group-1 having the standard CT evaluation of the liver and 20 patients in Group-2 having the standard CT evaluation of the liver and DWMR of the liver. Compared with CELUS, the per-patient sensitivity/specificity was 50/100% for CT, and for DWMR: 100/94% and 100/100% for Reader 1 and 2, respectively. The per-lesion sensitivity of CT and DWMR were 17% and 89%, respectively compared with CELUS. Furthermore, one patient had non-resectable metastases after DWMR despite being diagnosed with resectable metastases after CT. Another patient was diagnosed with multiple liver metastases during CELUS, despite a negative CT-scan. Discussion. DWMR is feasible for preoperative evaluation of liver metastases. The current standard preoperative evaluation with CT-scan results in disadvantages like missed metastases and futile operations. We recommend that patients with rectal cancer, who are scheduled for MR of the rectum, should have a DWMR of the liver performed at the same time. PMID:26793420

  20. [SURGICAL TREATMENT OUTCOME IN PATIENTS WITH COLORECTAL CANCER AND CONCOMITANT LIVER METASTASES].

    PubMed

    Shchepotin, S B; Kolesnik, O O; Burlaka, A A; Lukashenko, A V; Pryimak, V V

    2015-04-01

    Colorectal cancer with synchronous liver metastasis (sm-CRC) is extremely unfavorable prognostic factor. Surgery remains is most effective method, able to extend the life of these patients. The results of treatment of 126 patients with sm-CRC were analyzed, whom performed simultaneous (group I) or staged (group II) surgery. Simultaneous resection of 3 segments of liver or less with metastases and primary tumor is a safe surgical strategy (complicatios level was 4.8%); simultaneous resection of 3 segments of liver or more increase the complicatios level to 20.9%. Simultaneous resection ensure reduction of hospital stay terms in 58.1% and duration of surgery in 71.3% (p < 0.001). The average cost of treatment patient treating with staged strategy exceeded in simultaneous surgical treatment in 40.9%. PMID:26263637

  1. [A Case of Liver Metastasis of Descending Colon Cancer with a Pathological Complete Response to mFOLFOX6].

    PubMed

    Kawamoto, Yusuke; Ome, Yusuke; Koda, Yusuke; Saga, Kenichi; Kawamoto, Kazuyuki; Ito, Tadashi

    2016-01-01

    A 75-year-old woman presented with right upper quadrant abdominal pain and anorexia. She was diagnosed with descending colon cancer with lymph node and liver metastases. She was treated with preoperative chemotherapy consisting of levofolinate/5-fluorouracil/oxaliplatin (mFOLFOX6). After the completion of 7 courses of chemotherapy, the tumor shrunk remarkably. A left-sided colectomy with radical lymphadenectomy and an extensive posterior segment resection of the liver were performed. Postoperatively, pathological analysis revealed no cancerous cells in the primary tumor, lymph node metastases, or liver metastases. She is currently receiving mFOLFOX6 therapy as adjuvant chemotherapy. In a patient with advanced colon cancer, a complete response of not only the primary tumor but also the lymph node and liver metastases to preoperative chemotherapy is rare. This case demonstrates that mFOLFOX6 therapy is safe and effective as preoperative chemotherapy for advanced colon cancer. PMID:26809540

  2. Bevacizumab with preoperative chemotherapy versus preoperative chemotherapy alone for colorectal cancer liver metastases

    PubMed Central

    Lu, Zhen-Hai; Peng, Jian-Hong; Wang, Fu-Long; Yuan, Yun-Fei; Jiang, Wu; Li, Yu-Hong; Wu, Xiao-Jun; Chen, Gong; Ding, Pei-Rong; Li, Li-Ren; Kong, Ling-Heng; Lin, Jun-Zhong; Zhang, Rong-Xin; Wan, De-Sen; Pan, Zhi-Zhong

    2016-01-01

    Abstract This study aimed to assess the efficacy and safety of bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer in Chinese patients compared with those of preoperative chemotherapy alone. Patients with histologically confirmed liver-only metastatic colorectal cancer were sequentially reviewed, and received either preoperative chemotherapy plus bevacizumab (bevacizumab group, n = 32) or preoperative chemotherapy alone (chemotherapy group, n = 57). Progression-free survival, response rate, liver resection rate, conversion rate, and safety were analyzed. With median follow-up of 28.7 months, progression-free survival was 10.9 months (95% confidence interval: 8.7–13.1 months) in bevacizumab group and 9.9 months (95% confidence interval: 6.8–13.1 months) in chemotherapy group (P = 0.472). Response rates were 59.4% in bevacizumab group and 38.6% in chemotherapy group (P = 0.059). Overall liver resection (R0, R1, and R2) rate was 68.8% in bevacizumab group and 54.4% in chemotherapy group (P = 0.185). Conversion rate was 51.9% in bevacizumab group and 40.4% in chemotherapy group (P = 0.341). No postoperative complication was observed in all patients. Bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer tends to achieve better clinical benefit with controllable safety in Chinese patients. PMID:27583930

  3. The role of the liver in the protection by elemental diets against experimental colon cancer.

    PubMed

    Barton, T; Lewin, M R

    1988-06-01

    This study investigates the mechanism whereby the elemental diet 'Vivonex' protects against experimental colon cancer. A total of 240 Wistar rats were randomly allocated to three dietary groups: (A) Vivonex HN, (B) Vivonex HN with 0.05% added cholesterol and (C) control standard powdered diet. All received a colon cancer-producing regimen of dimethylhydrazine (DMH) at a dose of 40 mg/kg BW, s.c., once weekly for 5 weeks. Ten weeks following the first DMH injection, then at 5 weekly intervals until the 40th week, 10 randomly selected rats from each dietary group were weighed, killed and necropsied. Total liver weights were recorded with samples kept for total lipid extraction and cholesterol and phospholipid assay. Each colon underwent macroscopic examination and all neoplasms were recorded. Results showed that control rats had a constant total liver lipid content over the 40 weeks and an increased incidence, number and development of colonic neoplasms with time. In contrast, Vivonex fed rats had significantly elevated total liver lipids, cholesterol and phospholipids over the 40 weeks compared to controls and a significantly reduced number and rate of development of colonic neoplasms. Rats fed on Vivonex + cholesterol had total liver lipids intermediate and significantly different from both the Vivonex and control groups and a similar result was seen in tumour development with time. This study shows that a Vivonex diet results in an increase in hepatic lipids, this effect being partially reversed with dietary cholesterol. The protective effect of Vivonex feeding in the DMH model of colon cancer may thus be mediated in part by the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3411183

  4. Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer

    SciTech Connect

    Laarhoven, Hanneke W.M. van . E-mail: h.vanlaarhoven@onco.umcn.nl; Kaanders, Johannes; Lok, Jasper; Peeters, Wenny J.M.; Rijken, Paul F.J.W.; Wiering, Bastiaan; Ruers, Theo J.M.; Punt, Cornelis J.A.; Heerschap, Arend; Kogel, Albert J. van der

    2006-02-01

    Purpose: To investigate hypoxia measured by pimonidazole binding, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CA-IX) expression, proliferation, and vascularity in liver metastases of colorectal cancer and to compare GLUT1 and CA-IX expression in corresponding primary tumors. Methods and Materials: Twenty-five patients with liver metastases of colorectal cancer, planned for metastasectomy, were included. The hypoxia marker pimonidazole and proliferation marker iododeoxyuridine were administered before surgery. After immunofluorescent staining of the frozen metastases, pimonidazole binding, vascularity, and proliferation were analyzed quantitatively. Thirteen paraffin-embedded primary tumors were stained immunohistochemically for GLUT1 and CA-IX expression, which was analyzed semiquantitatively in primary tumors and corresponding liver metastases. Results: In liver metastases, pimonidazole binding showed a pattern consistent with diffusion-limited hypoxia. The mean pimonidazole-positive fraction was 0.146; the mean distance from vessels to pimonidazole-positive areas was 80 {mu}m. When expressed, often co-localization was observed between pimonidazole binding and GLUT1 or CA-IX expression, but microregional areas of mismatch were also observed. No correlation between the level of pimonidazole binding and GLUT1 or CA-IX expression was observed. In some patients, a large fraction (up to 30%) of proliferating cells was present in pimonidazole-stained areas. Expression of CA-IX in primary tumors and metastases showed a significant correlation, which was absent for GLUT1 expression. Conclusions: Compared with other tumor types, liver metastases of colorectal cancer contain large amounts of hypoxic cells. The lack of correlation with pimonidazole binding brings into question the value of GLUT1 and CA-IX as endogenous markers of hypoxia.

  5. Clinical short-term results of radiofrequency ablation in liver cancers

    PubMed Central

    Jiang, Hong-Chi; Liu, Lian-Xin; Piao, Da-Xun; Xu, Jun; Zheng, Min; Zhu, An-Long; Qi, Shu-Yi; Zhang, Wei-Hui; Wu, Lin-Feng

    2002-01-01

    AIM: To study local therapeutic efficacy, side effects, and complications of radiofrequency ablation (RFA), which is emerging as a new method for the treatment of patients with hepatocellular carcinoma (HCC) with cirrhosis or chronic hepatitis and metastatic liver cancer. METHODS: Thirty-six patients with primary and secondary liver cancers (21 with primary hepatocellular carcinoma, 12 with colorectal cancer liver metastases and 3 with other malignant liver metastases), which were considered not suitable for curative resection, were include in this study. They were treated either with RFA (RITA2000, Mountain View, California, USA) percutaneously (n = 20) or intraoperatively (n = 16). The procedures were performed using the ultrasound guidance. The quality of RFA were based on monitoring of equipments and subject feeling of the practitioners. Patients treated with RFA was followed according to clinical findings, radiographic images, and tumor markers. RESULTS: Thirty-six patients underwent RFA for 48 nodules. RFA was used to treat an average 1.3 lesions per patient, and the median size of treated lesions was 2.5 cm (range, 0.5-9 cm). The average hospital stay was 5.6 d overall (2.8 d for percutaneous cases and 7.9 d for open operations). Seven patients underwent a second RFA procedure (sequential ablations). Sixteen HCC patients with a high level of alpha fetoprotein (AFP) and 9 colorectal cancer liver metastases patients with a high level of serum carcinoembryonic antigen (CEA) have a great reduction benefited from RFA. Four (11.1%) patients had complications: one skin burn; one postoperative hemorrhage; one cholecystitis and one hepatic abscess associated with percutaneous ablations of a large lesion. There were 4 deaths: 3 patients died from local and system diseases (1 at 7 month, 1 at 9 month, and 1 at 12 month), 1 patients died from cardiovascular shock, but no RFA-related death. At a median follow-up of 10 mo (range, 1-24 mo), 6 patients (16.7%) had

  6. 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.

  7. 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.

  8. Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

    PubMed Central

    Yang, Hua; Qiao, Jingjuan; Pu, Fan; Jiang, Jie; Hubbard, Kendra; Hekmatyar, Khan; Langley, Jason; Salarian, Mani; Long, Robert C.; Bryant, Robert G.; Hu, Xiaoping Philip; Grossniklaus, Hans E.; Liu, Zhi-Ren; Yang, Jenny J.

    2015-01-01

    With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol−1⋅s−1/89.2 mmol−1⋅s−1 per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10–20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery. PMID:25971726

  9. Inhibition effects of Chinese cabbage powder on aflatoxin B1-induced liver cancer.

    PubMed

    Wang, Tuoyi; Li, Chunyan; Liu, Yang; Li, Tiezhu; Zhang, Jie; Sun, Yonghai

    2015-11-01

    In this study, 0.25 μg/ml aflatoxin B1 was used to establish a liver cancer model for assessing the potential anticancer ability of Chinese cabbage powder, which is a complex water-soluble extract from Chinese cabbage by spray-drying at an outlet temperature of 130 °C. We found at least 11 potential anticancer substances in Chinese cabbage powder. A 90-d animal experiment demonstrated that 10% of Chinese cabbage powder in drinking water could improve the plasma micronutrient status, inhibit the formation of aflatoxin B1-DNA adducts in liver cells, and effectively reduce the incidence of liver tumor induced by aflatoxin B1 from 6.67% to 0%. The dose effect experiment revealed that 10% may be the minimal effective dose to prevent the occurrence of early liver tumors. This study will help elucidate the basis of epidemiological observations of dietary cancer prevention in humans, as well as explore related mechanisms. PMID:25976785

  10. Vegetable-based dietary pattern and liver cancer risk: results from the Shanghai Women's and Men's Health Studies

    PubMed Central

    Zhang, Wei; Xiang, Yong-Bing; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ji, Bu-Tian; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao-Ou

    2013-01-01

    Summary 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 (HRs) and 95% confidence intervals (CIs) 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 enrollment. Three dietary patterns were derived by factor analysis. A vegetable-based dietary pattern was inversely associated with liver cancer; HRs (95% CIs) 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); Ptrend=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 Ptrend<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. PMID:23841909

  11. The tumorigenic liver fluke Opisthorchis viverrini –multiple pathways to cancer

    PubMed Central

    Sripa, Banchob; Brindley, Paul J.; Mulvenna, Jason; Laha, Thewarach; Smout, Michael J; Mairiang, Eimorn; Bethony, Jeffrey M.; Loukas, Alex

    2012-01-01

    Liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Thailand and adjacent countries. In addition to infection-associated morbidity, infection with O. viverrini and the related Clonorchis sinensis are unarguable risk factors for cholangiocarcinoma, bile duct cancer. Here we review the pathogenesis of opisthorchiasis and the association of O. viverrini infection and bile duct cancer, focusing on the molecular parallels between wound healing, chronic inflammation and cancer development. We review a schema for human disease progression from fluke infection, chronic opisthorchiasis, advanced periductal fibrosis, and cholangiocarcinogenesis, and present a rationale for biomarker discovery to facilitate early intervention. We conclude by addressing post-genomic advances with a view to developing new control strategies to combat this infectious cancer. PMID:22947297

  12. Electrochemotherapy as a new approach on pancreatic cancer and on liver metastases.

    PubMed

    Tafuto, Salvatore; von Arx, Claudia; De Divitiis, Chiara; Maura, Claire Tracey; Palaia, Raffaele; Albino, Vittorio; Fusco, Roberta; Membrini, Massimo; Petrillo, Antonella; Granata, Vincenza; Izzo, Francesco

    2015-09-01

    Electrochemotherapy is a local non-thermal treatment for cancer ablation. Currently, many studies and case report have investigated the differences in effectiveness of electrochemotherapy with respect to tumor type, chemotherapeutic drug, and route of drug administration. ESOPE trial validated standard operating procedures [SOP] for ECT using the Cliniporator device and demonstrated that ECT is a simple, highly efficacious, and cost-effective treatment of cutaneous and subcutaneous nodules from different primary tumors for cutaneous or superficial lesions. This review has the purpose to summarize current knowledge about clinical effectiveness of electrochemotherapy and future prospects regarding its use on pancreatic cancer and liver metastasis not only. PMID:26123385

  13. Mössbauer studies of hemoglobin of the patients with liver cancer and cirrhosis

    NASA Astrophysics Data System (ADS)

    Ni, Xinlei; Hsia, Yuanfu; Liu, Rongchuan; Lu, Qingyou; Huang, Runsheng; Sun, Yunhan; Wang, Quanxing; Long, Jianxui

    1992-04-01

    Red blood cells (RBC) of the patients with primary liver cancer and with cirrhosis were investigated by using Mössbauer spectroscopy. Control measurements were carried out on RBC from normal adults. The Mössbauer spectra of normal RBC are composed of two doublets corresponding to deoxy-Hb and Oxy-Hb. Besides disappearance or a decrease of the doublets corresponding to deoxy-Hb, no additional peak was detected in the samples from the patients.

  14. Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic Approach

    PubMed Central

    Zender, Lars; Spector, Mona S.; Xue, Wen; Flemming, Peer; Cordon-Cardo, Carlos; Silke, John; Fan, Sheung-Tat; Luk, John M.; Wigler, Michael; Hannon, Gregory J.; Mu, David; Lucito, Robert; Powers, Scott; Lowe, Scott W.

    2010-01-01

    SUMMARY The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both cIAP1 and Yap accelerated tumorigenesis and were required to sustain rapid growth of amplicon-containing tumors. Furthermore, cIAP1 and Yap cooperated to promote tumorigenesis. Our results establish a tractable model of liver cancer, identify two oncogenes that cooperate by virtue of their coamplification in the same genomic locus, and suggest an efficient strategy for the annotation of human cancer genes. PMID:16814713

  15. A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis

    PubMed Central

    Kunawudhi, Anchisa; Promteangtrong, Chetsadaporn; Chotipanich, Chanisa

    2016-01-01

    Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment. PMID:27385894

  16. A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis.

    PubMed

    Kunawudhi, Anchisa; Promteangtrong, Chetsadaporn; Chotipanich, Chanisa

    2016-01-01

    Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment. PMID:27385894

  17. ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

    PubMed Central

    Zhu, Pingping; Wang, Yanying; He, Lei; Huang, Guanling; Du, Ying; Zhang, Geng; Yan, Xinlong; Xia, Pengyan; Ye, Buqing; Wang, Shuo; Hao, Lu; Wu, Jiayi; Fan, Zusen

    2015-01-01

    Liver cancer stem cells (CSCs) have been identified and shown to have self-renewal and differentiation properties; however, the biology of these hepatic CSCs remains largely unknown. Here, we analyzed transcriptome gene expression profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells lines and found that the transcription factor (TF) ZIC2 is highly expressed in liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating OCT4 activation. In HCC patients, expression levels of the NURF complex were consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels positively correlated to the clinicopathological stages of HCC patients. Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex can be detected and used for diagnosis and prognosis prediction of HCC patients. Moreover, these factors may be potential therapeutic targets for eradicating liver CSCs. PMID:26426078

  18. 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.

  19. Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties.

    PubMed

    Samie, Nima; Muniandy, Sekaran; Kanthimathi, M S; Haerian, Batoul Sadat; Raja Azudin, Raja Elina

    2016-01-01

    The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PMID:27072064

  20. Grey zone in the Barcelona Clinic Liver Cancer Classification for hepatocellular carcinoma: Surgeons' perspective.

    PubMed

    Yang, Tian; Lau, Wan-Yee; Zhang, Han; Huang, Bin; Lu, Jun-Hua; Wu, Meng-Chao

    2015-07-21

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer-related deaths worldwide. The Barcelona Clinic Liver Cancer (BCLC) classification has been endorsed as the optimal staging system and treatment algorithm for HCC by the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease. However, in real life, the majority of patients who are not considered ideal candidates based on the BCLC guideline still were performed hepatic resection nowadays, which means many hepatic surgeons all around the world do not follow the BCLC guidelines. The accuracy and application of the BCLC classification has constantly been challenged by many clinicians. From the surgeons' perspectives, we herein put forward some comments on the BCLC classification concerning subjectivity of the assessment criteria, comprehensiveness of the staging definition and accuracy of the therapeutic recommendations. We hope to further discuss with peers and colleagues with the aim to make the BCLC classification more applicable to clinical practice in the future. PMID:26217077

  1. Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties

    PubMed Central

    Samie, Nima; Muniandy, Sekaran; Kanthimathi, M. S.; Haerian, Batoul Sadat; Raja Azudin, Raja Elina

    2016-01-01

    The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PMID:27072064

  2. Mouse models of liver cancer: Progress and recommendations.

    PubMed

    He, Li; Tian, De-An; Li, Pei-Yuan; He, Xing-Xing

    2015-09-15

    To clarify the pathogenesis of hepatocellular carcinoma (HCC) and investigate the effects of potential therapies, a number of mouse models have been developed. Subcutaneous xenograft models are widely used in the past decades. Yet, with the advent of in vivo imaging technology, investigators are more and more concerned with the orthotopic models nowadays. Genetically engineered mouse models (GEM) have greatly facilitated studies of gene function in HCC development. Recently, GEM of miR-122 and miR-221 provided new approaches for better understanding of the in vivo functions of microRNA in hepatocarcinogenesis. Chemically induced liver tumors in animals share many of the morphological, histogenic, and biochemical features of human HCC. Yet, the complicated and obscure genomic alternation restricts their applications. In this review, we highlight both the frequently used mouse models and some emerging ones with emphasis on their merits or defects, and give advises for investigators to chose a "best-fit" animal model in HCC research. PMID:26259234

  3. Understanding the gender disparity in bladder cancer risk: The impact of sex hormones and liver on bladder susceptibility to carcinogens

    PubMed Central

    Zhang, Yuesheng

    2013-01-01

    It has long been known that bladder cancer (BC) incidence is approximately 4-fold higher in men than in women in the US, and a similar disparity also exists in other countries. The reason for this phenomenon is not known, which impedes progress in BC prevention. However, BC incidence is also significantly higher in male animals than in their female counterparts after treatment with aromatic amines, which are principal human bladder carcinogens. These animal studies and related studies in the context of available human data provide significant insight into what may drive the excessive BC risk in men, which is the focus of this article. The carcinogenicity and biotransformation of bladder carcinogens as well as the impact of sex hormones on these processes are discussed, highlighting the novel concept that the gender disparity in BC risk may result primarily from the interplay of androgen, estrogen and liver, with the liver functioning via its metabolic enzymes as the main decider of bladder exposure to carcinogens in the urine and the male and female hormones exerting opposing effects on carcinogenesis in the bladder and likely also on liver enzymes handling bladder carcinogens. The findings may facilitate further investigation into the mechanism of gender disparity in BC risk and may also have important implications for BC prevention. PMID:24171436

  4. Spectrum of De Novo Cancers and Predictors in Liver Transplantation: Analysis of the Scientific Registry of Transplant Recipients Database

    PubMed Central

    Zhou, Jie; Hu, Zhenhua; Zhang, Qijun; Li, Zhiwei; Xiang, Jie; Yan, Sheng; Wu, Jian; Zhang, Min; Zheng, Shusen

    2016-01-01

    Background De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. Aims To describe the overall pattern of de novo cancers in liver transplant recipients. Methods 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. Results 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. Conclusions 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. PMID:27171501

  5. Quality of Life in Patients Undergoing Radiation Therapy for Primary Lung Cancer, Head and Neck Cancer, or Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer

  6. Is clinical breast examination important for breast cancer detection?

    PubMed Central

    Provencher, L.; Hogue, J.C.; Desbiens, C.; Poirier, B.; Poirier, E.; Boudreau, D.; Joyal, M.; Diorio, C.; Duchesne, N.; Chiquette, J.

    2016-01-01

    Background Screening clinical breast examination (cbe) is controversial; the use of cbe is declining not only as a screening tool, but also as a diagnostic tool. In the present study, we aimed to assess the value of cbe in breast cancer detection in a tertiary care centre for breast diseases. Methods This retrospective study of all breast cancers diagnosed between July 1999 and December 2010 at our centre categorized cases according to the mean of detection (cbe, mammography, or both). A cbe was considered “abnormal” in the presence of a mass, nipple discharge, skin or nipple retraction, edema, erythema, peau d’orange, or ulcers. Results During the study period, a complete dataset was available for 6333 treated primary breast cancers. Cancer types were ductal carcinoma in situ (15.3%), invasive ductal carcinoma (75.7%), invasive lobular carcinoma (9.0%), or others (2.2%). Of the 6333 cancers, 36.5% (n = 2312) were detected by mammography alone, 54.8% (n = 3470) by mammography and cbe, and 8.7% (n = 551) by physician-performed cbe alone (or 5.3% if considering ultrasonography). Invasive tumours diagnosed by cbe alone were more often triple-negative, her2-positive, node-positive, and larger than those diagnosed by mammography alone (p < 0.05). Conclusions A significant number of cancers would have been missed if cbe had not been performed. Compared with cancers detected by mammography alone, those detected by cbe had more aggressive features. Clinical breast examination is a very low-cost test that could improve the detection of breast cancer and could prompt breast ultrasonography in the case of a negative mammogram. PMID:27536182

  7. Circulating TGF-β1 and VEGF and risk of cancer among liver transplant recipients.

    PubMed

    Engels, Eric A; Jennings, Linda; Kemp, Troy J; Chaturvedi, Anil K; Pinto, Ligia A; Pfeiffer, Ruth M; Trotter, James F; Acker, Michelle; Onaca, Nicholas; Klintmalm, Goran B

    2015-08-01

    Transplant recipients have elevated cancer risk, perhaps partly due to direct carcinogenic effects of immunosuppressive medications. Experimental evidence indicates that calcineurin inhibitors given to transplant recipients increase cellular expression of transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF), which could promote cancer. To assess the potential role of these pathways in the transplantation setting, we conducted a case-control study nested in a cohort of liver recipients. Cases had nonmelanoma skin cancer (N = 84), cancer of the lung (N = 29), kidney (N = 20), or colorectum (N = 17), or melanoma (N = 3). We selected N = 463 recipients without cancer as controls. TGF-β1 and VEGF levels were measured in sera obtained, on average, approximately 3 years before case diagnosis/control selection. We also measured platelet factor 4 (PF4), a marker of ex vivo platelet degranulation, because TGF-β1 and VEGF can be released from platelets, and we developed a statistical model to isolate the platelet-derived fraction from the remaining circulating component. Compared with controls, lung cancer cases had higher levels of TGF-β1 (median 22.8 vs. 19.4 ng/mL, P = 0.02) and VEGF (277 vs. 186 pg/mL, P = 0.02). However, lung cancer cases also had higher platelet counts (P = 0.08) and PF4 levels (P = 0.02), while residual serum levels of TGF-β1 and VEGF, after accounting for PF4, were unassociated with lung cancer (P = 0.40 and P = 0.15, respectively). Associations were not seen for other cancers. In conclusion, TGF-β1 and VEGF levels were increased in association with lung cancer among transplant recipients, which may be explained by increased platelet counts and platelet degranulation in lung cancer cases. PMID:25919050

  8. Solid cancer incidence other than lung, liver and bone in Mayak workers: 1948–2004

    PubMed Central

    Hunter, N; Kuznetsova, I S; Labutina, E V; Harrison, J D

    2013-01-01

    Background: Cancer incidence in the Mayak Production Association (PA) cohort was analysed to investigate for the first time whether external gamma-ray and internal plutonium exposure are associated with raised incidence of solid cancers other than lung, liver and bone (other solid cancers). Methods: The cohort includes 22 366 workers of both sexes who were first employed between 1948 and 1982. A total of 1447 cases of other solid cancers were registered in the follow-up period until 2004. The Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to plutonium and external gamma-ray. Results: A weak association was found between cumulative exposure to external gamma-ray and the incidence of other solid cancers (ERR/Gy=0.07; 95% confidence intervals (CIs): 0.01–0.15), but this association lost its significance after adjusting for internal plutonium exposure. There was no indication of any association with plutonium exposure for other solid cancers. Among 16 individual cancer sites, there was a statistically significant association with external exposure for lip cancer (ERR/Gy=1.74; 95% CI: 0.37; 6.71) and with plutonium exposure for pancreatic cancer (ERR/Gy=1.58; 95% CI; 0.17; 4.77). Conclusion: This study of Mayak workers does not provide evidence of an increased risk of other solid cancers. The observed increase in the risk of cancer of the lip and pancreas should be treated with caution because of the limited amount of relevant data and because the observations may be simply due to chance. PMID:24022197

  9. Factor VII Light Chain-Targeted Lidamycin Shows Intensified Therapeutic Efficacy for Liver Cancer

    PubMed Central

    Liu, Xiujun; Xu, Shuangshuang; Li, Caihong; Zhang, Yang; Yang, Jie; Zheng, Junnian

    2012-01-01

    Abstract The overexpression of tissue factor (TF) observed in numerous cancer cells and clinical samples of human cancers makes TF an ideal target for cancer therapy. The purpose of this study is to develop a TF-targeting energized fusion protein hlFVII-LDP-AE, which is composed of a human Factor VII light chain (hlFVII) as the targeting domain conjugated to the cytotoxic antibiotic lidamycin (LDM, LDP-AE) as the effector domain. The potential efficacy of hlFVII-LDP-AE for cancer therapy was tested in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays and in vivo with a BALB/c nude mouse xenograft model of human liver cancer line HepG2. The inhibitory concentration (IC50) value of hlFVII-LDP-AE varied from 0.15 to 0.64 nM for the various human tumor lines. hlFVII-LDP-AE showed a tumor growth inhibition rate of 90.6% at the dose of 0.6 mg/kg in in vivo animal experiments. The mechanism through which hlFVII-LDP-AE inhibits tumor growth also was determined by Hoechst 33342 staining and Tdt-mediated dUTP nick-end labeling (TUNEL) assay. hlFVII-LDP-AE causes tumor cell death through inducing chromatin condensation and cleavage of genomic DNA. These findings suggest that the hlFVII-LDP-AE protocol is efficacious and tolerated in the mouse model of human liver cancer HepG2 and has clinical applicability for treating cancer patients. PMID:22651685

  10. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma: a Study of 3843 Patients From Taiwan Liver Cancer Network

    PubMed Central

    Chang, Il-Chi; Huang, Shiu-Feng; Chen, Pei-Jer; Chen, Chi-Ling; Chen, Chao-Long; Wu, Cheng-Chung; Tsai, Cheng-Chung; Lee, Po-Huang; Chen, Miin-Fu; Lee, Chuan-Mo; Yu, Hsien-Chung; Lo, Gin-Ho; Yeh, Chau-Ting; Hong, Chih-Chen; Eng, Hock-Liew; Wang, John; Tseng, Hui-Hwa; Hsiao, Cheng-Hsiang; Wu, Hong-Dar Isaac; Yen, Tseng-Chang; Liaw, Yun-Fan

    2016-01-01

    Abstract Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research. PMID:27082566

  11. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma: a Study of 3843 Patients From Taiwan Liver Cancer Network.

    PubMed

    Chang, Il-Chi; Huang, Shiu-Feng; Chen, Pei-Jer; Chen, Chi-Ling; Chen, Chao-Long; Wu, Cheng-Chung; Tsai, Cheng-Chung; Lee, Po-Huang; Chen, Miin-Fu; Lee, Chuan-Mo; Yu, Hsien-Chung; Lo, Gin-Ho; Yeh, Chau-Ting; Hong, Chih-Chen; Eng, Hock-Liew; Wang, John; Tseng, Hui-Hwa; Hsiao, Cheng-Hsiang; Wu, Hong-Dar Isaac; Yen, Tseng-Chang; Liaw, Yun-Fan

    2016-04-01

    Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research. PMID:27082566

  12. The most important physiological constants among the Volga region long-livers

    NASA Astrophysics Data System (ADS)

    Malinova, L. I.; Shuvalov, S. S.; Denisova, T. P.

    2012-03-01

    In our research we brought out the age difference in the group of long-livers and the continuous character of the biochemical basal metabolism indexes changing. The results allowed us to carry out the polynominal high-powered approximation to study the dynamics of laboratory indexes. We revealed the progressive reduction of the cholesterol, triglycerides, glucose and creatinine levels starting from 90 years of age, and this reduction showed the non-linear character with interchange of local minimums and maximums. During the speed characteristics analysis we revealed the cooccurrence of the speed maximums of all the examined biochemical indexes, except the speed of changing the concentration of cholesterol, which maximum took the lead over the other indexes by four years. The phase-plane portrait analysis of the regulatory systems on the plane "time - speed" showed the unfulfilled attempt of system stabilization by all the searched parameters nearby the special spot - "stable focus". The standard deviation values analysis of the researched parameters showed their progressive reduction in the long-livers. That fact can be considered as the regulatory systems physiological "backlash" reduction among the centenarians.

  13. The most important physiological constants among the Volga region long-livers

    NASA Astrophysics Data System (ADS)

    Malinova, L. I.; Shuvalov, S. S.; Denisova, T. P.

    2011-10-01

    In our research we brought out the age difference in the group of long-livers and the continuous character of the biochemical basal metabolism indexes changing. The results allowed us to carry out the polynominal high-powered approximation to study the dynamics of laboratory indexes. We revealed the progressive reduction of the cholesterol, triglycerides, glucose and creatinine levels starting from 90 years of age, and this reduction showed the non-linear character with interchange of local minimums and maximums. During the speed characteristics analysis we revealed the cooccurrence of the speed maximums of all the examined biochemical indexes, except the speed of changing the concentration of cholesterol, which maximum took the lead over the other indexes by four years. The phase-plane portrait analysis of the regulatory systems on the plane "time - speed" showed the unfulfilled attempt of system stabilization by all the searched parameters nearby the special spot - "stable focus". The standard deviation values analysis of the researched parameters showed their progressive reduction in the long-livers. That fact can be considered as the regulatory systems physiological "backlash" reduction among the centenarians.

  14. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?

    PubMed

    Bhatia, Lokpal S; Curzen, Nicholas P; Calder, Philip C; Byrne, Christopher D

    2012-05-01

    Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease. PMID:22408036

  15. Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements

    PubMed Central

    Abdalla, Eddie K; Bauer, Todd W; Chun, Yun S; D'Angelica, Michael; Kooby, David A; Jarnagin, William R

    2013-01-01

    Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient's care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location. PMID:23297723

  16. Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements.

    PubMed

    Abdalla, Eddie K; Bauer, Todd W; Chun, Yun S; D'Angelica, Michael; Kooby, David A; Jarnagin, William R

    2013-02-01

    Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient's care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location. PMID:23297723

  17. Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer

    PubMed Central

    Chauhan, Arun; Zubair, Swaleha; Tufail, Saba; Sherwani, Asif; Sajid, Mohammad; Raman, Suri C; Azam, Amir; Owais, Mohammad

    2011-01-01

    Background Nanomaterials are considered to be the pre-eminent component of the rapidly advancing field of nanotechnology. However, developments in the biologically inspired synthesis of nanoparticles are still in their infancy and consequently attracting the attention of material scientists throughout the world. Keeping in mind the fact that microorganism-assisted synthesis of nanoparticles is a safe and economically viable prospect, in the current study we report Candida albicans-mediated biological synthesis of gold nanoparticles. Methods and results Transmission electron microscopy, atomic force microscopy, and various spectrophotometric analyses were performed to characterize the gold nanoparticles. The morphology of the synthesized gold particles depended on the abundance of C. albicans cytosolic extract. Transmission electron microscopy, nanophox particle analysis, and atomic force microscopy revealed the size of spherical gold nanoparticles to be in the range of 20–40 nm and nonspherical gold particles were found to be 60–80 nm. We also evaluated the potential of biogenic gold nanoparticles to probe liver cancer cells by conjugating them with liver cancer cell surface-specific antibodies. The antibody-conjugated gold particles were found to bind specifically to the surface antigens of the cancer cells. Conclusion The antibody-conjugated gold particles synthesized in this study could successfully differentiate normal cell populations from cancerous cells. PMID:22072868

  18. Successful multimodal therapy for an α-fetoprotein-producing gastric cancer patient with simultaneous liver metastases

    PubMed Central

    FANG, YU; WANG, LIN; YANG, NINGRONG; GONG, XINLEI; ZHANG, YU; QIN, SHUKUI

    2015-01-01

    α-fetoprotein-producing gastric cancer (AFPGC) is considered to be a special type of stomach cancer, due its features of high malignancy, fast progression, easy transferral and a poor prognosis. No standard therapy is currently available for patients with AFPGC. In the present study, the case of a 59-year-old male diagnosed with AFPGC and simultaneous liver metastases is presented. The patient presented with abdominal bloating and multiple liver lesions were revealed upon imaging. During the course of treatment, the patient's serum AFP level increased to a maximum of 20,624.6 µg/l. The patient survived for 30 months and was ultimately treated with multimodal therapy, including surgery, chemotherapy, interventional therapy and molecular targeted therapy. Treatment with paclitaxel, irinotecan and TS-1, particularly sorafenib as a molecular targeted drug, are effective for such patients. The choice of chemotherapy regimen according to the Lauren classification and the use of oral sorafenib are likely to be novel and effective treatments for this type of stomach cancer. However, investigations should be performed to identify the gastric cancer patient population most receptive to sorafenib treatment. In addition, combined chemotherapy and molecular targeting treatment requires further study in order to determine if a synergistic effect is present. Further investigation in a large-sample study is required to confirm the validity of these results. PMID:26722283

  19. Colorectal cancer with liver metastases: Neoadjuvant chemotherapy, surgical resection first or palliation alone?

    PubMed Central

    Khan, Khurum; Wale, Anita; Brown, Gina; Chau, Ian

    2014-01-01

    Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for > 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease. PMID:25253940

  20. Dietary glycemic load, glycemic index, and carbohydrates on the risk of primary liver cancer among Chinese women and men

    PubMed Central

    Vogtmann, E.; Li, H. L.; Shu, X. O.; Chow, W. H.; Ji, B. T.; Cai, H.; Gao, J.; Zhang, W.; Gao, Y. T.; Zheng, W.; Xiang, Y. B.

    2013-01-01

    Background Dietary glycemic index (GI) and glycemic load (GL) typically have a positive relationship with obesity and diabetes, which are risk factors for liver cancer. However, studies on their association with liver cancer have yielded inconsistent results. Therefore, we assessed the association of GI, GL, and carbohydrates with liver cancer risk. Patients and methods A total of 72 966 women and 60 207 men from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) were included for analysis. Food frequency questionnaire (FFQ) data were used to calculate daily dietary GI, GL, and carbohydrate intake. These values were energy adjusted and categorized into quintiles. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated with adjustment for potential confounders. Results After a median follow-up time of 11.2 years for the SWHS and 5.3 years for the SMHS, 139 and 208 incident liver cancer cases were identified in the SWHS and SMHS, respectively. In multivariable Cox regression models, no statistically significant trends by quintile of GI, GL, or carbohydrate intake were observed. Stratification by chronic liver disease/hepatitis, diabetes, or body mass index (BMI) did not alter the findings. Conclusions There is little evidence that dietary GI, GL, or carbohydrates affect the incidence of liver cancer in this Asian population. PMID:22898034

  1. HPV and oropharyngeal cancer: etiology and prognostic importance.

    PubMed

    Yom, Sue S

    2015-12-01

    HPV is the most common sexually transmitted disease, but the overwhelming majority of individuals clear the infection. A small percentage of individuals develop persistence of oncogenic HPV types, especially HPV-16; and as a result, squamous cell carcinoma can develop in the tonsils and base of the tongue. Over 70% of oropharyngeal cancers are now thought to be associated with oncogenic HPV infection. Immunohistochemistry for p16 protein is often used as a surrogate marker for oncogenic HPV in the oropharyngeal tissues, although alternative HPV DNA testing methods are under intensive study. The clinical profile of patients with HPV-associated oropharyngeal cancer (OPC) differs quite notably from that of traditional head and neck cancer patients, and the prognosis for HPV-associated OPC is significantly better. As a result, experimental clinical trials are focused on de-intensification of therapies with the hope of preserving an improved long-term quality of life for these patients. PMID:26650695

  2. Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells

    PubMed Central

    Derangère, V; Chevriaux, A; Courtaut, F; Bruchard, M; Berger, H; Chalmin, F; Causse, S Z; Limagne, E; Végran, F; Ladoire, S; Simon, B; Boireau, W; Hichami, A; Apetoh, L; Mignot, G; Ghiringhelli, F; Rébé, C

    2014-01-01

    Liver X receptors (LXRs) have been proposed to have some anticancer properties, through molecular mechanisms that remain elusive. Here we report for the first time that LXR ligands induce caspase-1-dependent cell death of colon cancer cells. Caspase-1 activation requires Nod-like-receptor pyrin domain containing 3 (NLRP3) inflammasome and ATP-mediated P2 × 7 receptor activation. Surprisingly, LXRβ is mainly located in the cytoplasm and has a non-genomic role by interacting with pannexin 1 leading to ATP secretion. Finally, LXR ligands have an antitumoral effect in a mouse colon cancer model, dependent on the presence of LXRβ, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXRβ, through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis. PMID:25124554

  3. Na,K-ATPase Isozymes in Colorectal Cancer and Liver Metastases

    PubMed Central

    Baker Bechmann, Marc; Rotoli, Deborah; Morales, Manuel; Maeso, María del Carmen; García, María del Pino; Ávila, Julio; Mobasheri, Ali; Martín-Vasallo, Pablo

    2016-01-01

    The goal of this study was to define Na,K-ATPase α and β subunit isoform expression and isozyme composition in colorectal cancer cells and liver metastases. The α1, α3, and β1 isoforms were the most highly expressed in tumor cells and metastases; in the plasma membrane of non-neoplastic cells and mainly in a cytoplasmic location in tumor cells. α1β1 and α3β1 isozymes found in tumor and metastatic cells exhibit the highest and lowest Na+ affinity respectively and the highest K+ affinity. Mesenchymal cell isozymes possess an intermediate Na+ affinity and a low K+ affinity. In cancer, these ions are likely to favor optimal conditions for the function of nuclear enzymes involved in mitosis, especially a high intra-nuclear K+ concentration. A major and striking finding of this study was that in liver, metastasized CRC cells express the α3β1 isozyme. Thus, the α3β1 isozyme could potentially serve as a novel exploratory biomarker of CRC metastatic cells in liver. PMID:26858653

  4. TM4SF1 Promotes Proliferation, Invasion, and Metastasis in Human Liver Cancer Cells

    PubMed Central

    Huang, Yu-Kun; Fan, Xue-Gong; Qiu, Fu

    2016-01-01

    Transmembrane 4 superfamily member 1 (TM4SF1) is a member of tetraspanin family, which mediates signal transduction events regulating cell development, activation, growth and motility. Our previous studies showed that TM4SF1 is highly expressed in liver cancer. HepG2 cells were transfected with TM4SFl siRNA and TM4SF1-expressing plasmids and their biological functions were analyzed in vitro and in vivo. HepG2 cells overexpressing TM4SF1 showed reduced apoptosis and increased cell migration in vitro and enhanced tumor growth and metastasis in vivo, whereas siRNA-mediated silencing of TM4SF1 had the opposite effect. TM4SF1 exerts its effect by regulating a few apoptosis- and migration-related genes including caspase-3, caspase-9, MMP-2, MMP-9 and VEGF. These results indicate that TM4SF1 is associated with liver tumor growth and progression, suggesting that TM4SF1 may be a potential target for treatment of liver cancer in future. PMID:27153056

  5. Portal vein embolization effect on colorectal cancer liver metastasis progression: Lessons learned

    PubMed Central

    Al-Sharif, Eman; Simoneau, Eve; Hassanain, Mazen

    2015-01-01

    Colorectal liver metastasis (CRLM) is the major cause of death in patients diagnosed with colorectal cancer. The gold standard treatment of CRLM is surgical resection. Yet, in the past, more than half of these patients were deemed unresectable due to the inadequate future liver remnant (FLR). The introduction of efficient portal vein embolization (PVE) preoperatively allowed more resections of metastasis in CRLM patients by stimulating adequate liver hypertrophy. However, several experimental and clinical studies reported tumor progression after PVE which critically influences the subsequent management of these patients. The underlying pathophysiological mechanism of tumor progression post-PVE is still not fully understood. In spite of the adverse effects of PVE, it remains a potentially curative procedure in patients who would remain otherwise unresectable because of the insufficient FLR. Currently, the challenge is to halt tumor proliferation following PVE in patients who require this technique. This could potentially be achieved by either attempting to suppress the underlying oncologic stimulus or by inhibiting tumor growth once observed after PVE, without jeopardizing liver regeneration. More research is still required to better identify patients at risk of experiencing tumor growth post-PVE. PMID:26468450

  6. [A case of surgical resection for liver metastasis of gastric cancer with portal vein tumor thrombus].

    PubMed

    Hata, Tomoki; Wada, Hiroshi; Tomimaru, Yoshito; Tomokuni, Akira; Hama, Naoki; Kawamoto, Koichi; Kobayashi, Shogo; Asaoka, Tadafumi; Marubashi, Shigeru; Eguchi, Hidetoshi; Umeshita, Koji; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro; Nagano, Hiroaki

    2014-11-01

    A 58-year-old man presented with anorexia and weight loss in April 2010. Endoscopic examination revealed a type 3 tumor extending from the gastric cardia to the antrum. Preoperative imaging showed liver metastasis (S8; 2 cm) and direct invasion of the cancer into the pancreas. We administered 4 courses of chemotherapy (DCS) for the unresectable tumor; the impact of the therapy was partial response (PR). We performed total gastrectomy, D2 dissection, splenectomy, distal pancreatectomy, and partial hepatectomy (S8) in April 2011. The patient was treated with 8 courses of adjuvant chemotherapy with S-1. In April 2012, abdominal computed tomography (CT) revealed a solitary recurrent lesion in the liver (S2). After 7 courses of chemotherapy(weekly paclitaxel), abdominal CT and magnetic resonance imaging (MRI) revealed a tumor thrombus in the portal vein extending from P2 to the umbilical portion (UP). We performed left hepatectomy and cholecystectomy due to the absence of new lesions. Histopathological findings revealed that the poorly differentiated adenocarcinoma had metastasized to the liver. Abdominal CT revealed the presence of multiple recurrent metastases in the liver, 4 months after the surgery. The patient died 27 months after the initial surgery and 7 months after the last operation. PMID:25731448

  7. The status of zinc in the development of hepatocellular cancer: an important, but neglected, clinically established relationship.

    PubMed

    Costello, Leslie C; Franklin, Renty B

    2014-04-01

    Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75% of HCC cases result in death generally within one year. The factors responsible for the initiation and progression of HCC remain largely unknown and speculative, thereby impeding advancements in the development of effective therapeutic agents and biomarkers for early detection of HCC. A consistent marked decrease in zinc in HCC tumors compared with normal liver is an established clinical relationship, which occurs in virtually all cases of HCC. However, this relationship has been largely ignored by the contemporary clinical and research community. Consequently, the factors and mechanisms involved in this relationship have not been addressed. Thus, the opportunity and potential for its employment as biomarkers for early identification of malignancy, and for development of a chemotherapeutic approach have been lacking. This presentation includes a review of the literature and the description of important recent and new data, which provide the basis for a concept of the role of zinc in the development of HCC. The basis is presented for characterizing HCC malignancy as ZIP14-deficient tumors, and its requirement to prevent zinc cytotoxic effects on the malignant cells. The potential for an efficacious zinc treatment approach for HCC is described. The involvement of zinc in the predisposition for HCC by chronic liver disease/cirrhosis is presented. Hopefully, this presentation will raise the awareness, interest, and support for the much needed research in the implications of zinc in the development and progression of HCC. PMID:24448510

  8. Assessing tumor response after loco-regional liver cancer therapies: the role of 3D MRI

    PubMed Central

    Chapiro, Julius; Lin, MingDe; Duran, Rafael; Schernthaner, Rüdiger E; Geschwind, Jean-François

    2015-01-01

    Assessing the tumor response of liver cancer lesions after intraarterial therapies is of major clinical interest. Over the last two decades, tumor response criteria have come a long way from purely size-based, anatomic methods such as the Response Evaluation Criteria in Solid Tumors towards more functional, enhancement- and diffusion-based parameters with a strong emphasis on MRI as the ultimate imaging modality. However, the relatively low reproducibility of those one- and 2D techniques (modified Response Evaluation Criteria in Solid Tumors and the European Association for the Study of the Liver criteria) provided the rationale for the development of new, 3D quantitative assessment techniques. This review will summarize and compare the existing methodologies used for 3D quantitative tumor analysis and provide an overview of the published clinical evidence for the benefits of 3D quantitative tumor response assessment techniques. PMID:25371052

  9. Cancer and aging: The importance of telomeres in genome maintenance

    SciTech Connect

    Rodier, Francis; Kim, Sahn-ho; Nijjar, Tarlochan; Yaswen, Paul; Campisi, Judith

    2004-10-01

    Telomeres are the specialized DNA-protein structures that cap the ends of linear chromosomes, thereby protecting them from degradation and fusion by cellular DNA repair processes. In vertebrate cells, telomeres consist of several kilobase pairs of DNA having the sequence TTAGGG, a few hundred base pairs of single-stranded DNA at the 3' end of the telomeric DNA tract, and a host of proteins that organize the telomeric double and single stranded DNA into a protective structure. Functional telomeres are essential for maintaining the integrity and stability of genomes. When combined with loss of cell cycle checkpoint controls, telomere dysfunction can lead to genomic instability, a common cause and hallmark of cancer. Consequently, normal mammalian cells respond to dysfunctional telomeres by undergoing apoptosis (programmed cell death) or cellular senescence (permanent cell cycle arrest), two cellular tumor suppressor mechanisms. These tumor suppressor mechanisms are potent suppressors of cancer, but recent evidence suggests that they can antagonistically also contribute to aging phenotypes. Here, we review what is known about the structure and function of telomeres in mammalian cells, particularly human cells, and how telomere dysfunction may arise and contribute to cancer and aging phenotypes.

  10. Clinical evaluation of cryosurgery in the treatment of primary liver cancer. Report of 60 cases.

    PubMed

    Zhou, X D; Tang, Z Y; Yu, Y Q; Ma, Z C

    1988-05-01

    Cryosurgery with liquid nitrogen was employed for the treatment of 60 patients with primary liver cancer (PLC) at the Liver Cancer Research Unit, Zhong Shan Hospital, Shanghai Medical University, the People's Republic of China, from November 1973 to August 1987. Of 60 patients, subclinical stage amounted to 35% (21/60), moderate stage 55% (33/60) and late stage 10% (6/60). There were 21 cases with small PLC (less than or equal to 5 cm). The postoperative course was uneventful in all of the 60 patients. These was no operative mortality, and there was no complications such as rupture of tumor, secondary bleeding, bile leakage, or abdominal infection. The 1-year, 2-year, 3-year, 4-year, and 5-year survival rates were 51.7% (30/58), 33.9% (19/56), 20.8% (11/53), 15.6% (7/45), and 11.4% (5/44), respectively, for the whole series. Among the 21 patients with tumor nodules less than or equal to 5 cm in diameter, the 1-year, 2-year, 3-year, 4-year, and 5-year survival rates were 76.2% (16/21), 61.9% (13/21), 50.0% (9/18), 41.2% (7/17), and 37.5% (6/16), respectively. These results indicate that hepatic cryosurgery is a promising, safe, and simple treatment for neoplastic disease of liver. Cryosurgery with liquid nitrogen can be considered the surgery of choice for nonresectable PLC in patients without jaundice, ascites, and noncompensated liver function, and the whole tumor mass can be involved in the frozen area. PMID:2833343

  11. Phase I and pharmacokinetic study of IV vinflunine in cancer patients with liver dysfunction.

    PubMed

    Delord, J P; Ravaud, A; Bennouna, J; Fumoleau, P; Favrel, S; Pinel, M C; Ferré, P; Saliba, F

    2013-06-01

    Vinflunine is a novel tubulin-targeted agent that is currently indicated as a monotherapy in bladder cancer patients. The recommended dose of 320 mg/m(2) is given as an intravenous infusion once every 3 weeks. Vinflunine is metabolized through CYP3A4 and mainly eliminated via the feces. A phase I trial was designed to explore the tolerability and pharmacokinetics of vinflunine in cancer patients with ranging degrees of liver dysfunction (LD). A sequential design was used for patient accrual, with the objective of determining the maximum tolerated dose (MTD) and the recommended dose (RD) of vinflunine in 3 groups of increasing LD levels. Vinflunine and its only active metabolite 4-O-deacetylvinflunine were quantified in serial whole blood samples. PK parameters were derived and compared between LD groups and with a reference PK database. Vinflunine and 4-O-deacetylvinflunine PK parameters were not affected in any of the explored LD levels. Geometric mean values for vinflunine total clearance were 47.8, 37.5 and 45.4 L/h in the 3 groups of increasing degrees of LD, as compared to 42.5 L/h in reference patients with no LD. No relationship was found between vinflunine clearance and the presence or absence of cirrhosis, nor was it found with the presence or absence of liver metastasis or with liver-related biochemical parameters. Based on the observed tolerability profile, the recommended doses of i.v. vinflunine are 320 mg/m(2), 250 mg/m(2) or 200 mg/m(2) for patients with increasing degrees of liver dysfunction. PMID:22996801

  12. [A case of sigmoid colon cancer with multiple liver metastases responding to S-1].

    PubMed

    Maruyama, Tsunehiko; Takagaki, Toshiro; Hara, Ken; Ohkohchi, Nobuhiro

    2008-02-01

    A 74-year-old woman was referred to our hospital with complaints of constipation and abdominal distention caused by a sigmoid colon tumor. After examination, she was diagnosed as sigmoid colon cancer with multiple liver metastases. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative days 15, S-1 was started, and she was discharged on postoperative day 26. Each course consisted of daily oral administration S-1 for 4 weeks followed by 2 drug-free weeks. However, because of grade 2 anorexia in the 1st course, the treatment plan was changed to administration for 2 weeks and withdrawal for 1 week. After 7 courses of treatment, computed tomography revealed that the liver metastases were remarkably reduced. Although she experienced an adverse event involving a cutaneous symptom of grade 2, the treatment was continued under ambulatory management. After eight courses, elevation of tumor marker and metastasis at the right femur were found, and she died of the cancer 12 months after the operation. S-1 is expected to be an effective agent for the treatment of advanced colorectal cancer. PMID:18281773

  13. Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer

    PubMed Central

    Harisa, Gamaleldin I.; Badran, Mohamed M.; AlQahtani, Saeed A.; Alanazi, Fars K.; Attia, Sabry M.

    2015-01-01

    Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin–chitosan nanogels (PR–CNG–ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR–CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR–CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR–CNG–ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR–CNG–ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR–CNG–ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR–CNG–ER are promising drug carriers to target liver cancer. PMID:26903771

  14. Update and review of the multidisciplinary management of stage IV colorectal cancer with liver metastases

    PubMed Central

    Abdel-Misih, Sherif Raafat Zikry; Schmidt, Carl R; Bloomston, Paul Mark

    2009-01-01

    Background The management of stage IV colorectal cancer with liver metastases has historically involved a multidisciplinary approach. In the last several decades, there have been great strides made in the therapeutic options available to treat these patients with advancements in medical, surgical, locoregional and adjunctive therapies available to patients with colorectal liver metastases(CLM). As a result, there have been improvements in patient care and survival. Naturally, the management of CLM has become increasingly complex in coordinating the various aspects of care in order to optimize patient outcomes. Review A review of historical and up to date literature was undertaken utilizing Medline/PubMed to examine relevant topics of interest in patients with CLM including criterion for resectability, technical/surgical considerations, chemotherapy, adjunctive and locoregional therapies. This review explores the various disciplines and modalities to provide current perspectives on the various options of care for patients with CLM. Conclusion Improvements in modern day chemotherapy as allowed clinicians to pursue a more aggressive surgical approach in the management of stage IV colorectal cancer with CLM. Additionally, locoregional and adjunctive therapies has expanded the armamentarium of treatment options available. As a result, the management of patients with CLM requires a comprehensive, multidisciplinary approach utilizing various modalities and a more aggressive approach may now be pursued in patients with stage IV colorectal cancer with CLM to achieve optimal outcomes. PMID:19788748

  15. Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer.

    PubMed

    Harisa, Gamaleldin I; Badran, Mohamed M; AlQahtani, Saeed A; Alanazi, Fars K; Attia, Sabry M

    2016-01-01

    Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR-CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer. PMID:26903771

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

    PubMed Central

    Cho, Donghun

    2015-01-01

    Background/Aims 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. Methods 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. Results 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. Conclusions 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. PMID:26523270

  17. Inhibition of Hepatocyte Apoptosis: An Important Mechanism of Corn Peptides Attenuating Liver Injury Induced by Ethanol

    PubMed Central

    Ma, Zhili; Hou, Tao; Shi, Wen; Liu, Weiwei; He, Hui

    2015-01-01

    In this study, the effects of mixed corn peptides and synthetic pentapeptide (QLLPF) on hepatocyte apoptosis induced by ethanol were investigated in vivo. QLLPF, was previously characterized from corn protein hydrolysis, which had been shown to exert good facilitating alcohol metabolism activity. Mice were pre-treated with the mixed corn peptides and the pentapeptide for 1 week and then treated with ethanol. After treatment of three weeks, the biochemical indices and the key ethanol metabolizing enzymes, the serum TNF-α, liver TGF-β1 concentrations and the protein expressions related to apoptosis were determined. We found that the Bcl-2, Bax and cytochrome c expressions in the intrinsic pathway and the Fas, FasL and NF-κB expressions in the extrinsic pathway together with higher TNF-α and TGF-β1 concentrations were reversed compared with the model group by both the mixed corn peptides and the pentapeptide. The activation of caspase3 was also suppressed. Additionally, apoptosis was further confirmed with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the TUNEL assay demonstrated peptides suppressed hepatocyte apoptosis. Our results suggest that apoptosis induced by ethanol is alleviated in response to the treatment of corn peptides, potentially due to reversing the related protein expression. PMID:26378531

  18. Colon cancer metastasis to mediastinal lymph nodes without liver or lung involvement: A case report.

    PubMed

    El-Halabi, Mustapha M; Chaaban, Said A; Meouchy, Joseph; Page, Seth; Salyers, William J

    2014-11-01

    Colon cancer is the second most common type of cancer in females and the third in males, worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this study, an extremely rare case of colon adenocarcinoma with extensive metastasis to the mediastinal lymph nodes without any other organ involvement is presented. A 44-year-old Caucasian male presented with abdominal pain, a change in bowel habits, melena and weight loss. Colonoscopy revealed a large friable, ulcerated, circumferential mass in the ascending colon. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Subsequently, right colon resection was performed, and pathological analysis revealed moderately differentiated adenocarcinoma of the right colon with extensive regional lymph node involvement. Computed tomography (CT) scans of the chest, abdomen and pelvis were performed preoperatively as part of routine staging for colon cancer. No liver or lung pathology was identified; however, multiple pathologically enlarged mediastinal lymph nodes were observed. Endoscopic ultrasound with fine needle aspiration of the largest mediastinal lymph node, which measured 5.2×3.5 cm on CT scans, was performed. The pathology was again consistent with the diagnosis of metastatic colorectal primary adenocarcinoma. At present, no optimum treatment has been identified for metastatic colon cancer to the mediastinal lymph nodes. The patient in the current case received chemotherapy with folinic acid, fluorouracil and oxaliplatin (FOLFOX), as well as with bevacizumab. Initial follow-up CT scans of the chest revealed a positive response to treatment. Physicians, in particular, radiologists, must consider the mediastinum during the first evaluation and further follow-up of patients with colorectal carcinoma even in the absence of metastasis. PMID:25289100

  19. Smyd3 Is a Transcriptional Potentiator of Multiple Cancer-Promoting Genes and Required for Liver and Colon Cancer Development.

    PubMed

    Sarris, Michalis E; Moulos, Panagiotis; Haroniti, Anna; Giakountis, Antonis; Talianidis, Iannis

    2016-03-14

    Smyd3 is a protein methyltransferase implicated in cancer development. Here we show that Smyd3 expression in mice is required for chemically induced liver and colon cancer formation. In these organs Smyd3 functions in the nucleus, stimulating the transcription of several key regulators involved in cell proliferation, epithelial-mesenchymal transition, the JAK/Stat3 oncogenic pathway, as well as the Myc and Ctnnb1 oncogenes. Smyd3 interacts with H3K4Me3-modified histone tails, which facilitates its recruitment to the core promoter regions of most active genes. Smyd3 binding density on target genes positively correlates with increased RNA polymerase-II density and transcriptional outputs. Despite its widespread distribution, the transcription-potentiating function of Smyd3 is restricted to a particular set of genes, whose expression is induced specifically during carcinogenesis. PMID:26908355

  20. 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

  1. 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. PMID:26699805

  2. Autophagy-related cell death by pan-histone deacetylase inhibition in liver cancer.

    PubMed

    Di Fazio, Pietro; Waldegger, Petra; Jabari, Samir; Lingelbach, Susanne; Montalbano, Roberta; Ocker, Matthias; Slater, Emily P; Bartsch, Detlef K; Illig, Romana; Neureiter, Daniel; Wissniowski, Thaddeus T

    2016-05-17

    Autophagy is a homeostatic, catabolic degradation process and cell fate essential regulatory mechanism. Protracted autophagy triggers cell death; its aberrant function is responsible for several malignancies. Panobinostat, a potent pan-deacetylase inhibitor, causes endoplasmic reticulum stress-induced cell death. The aim of this study was to investigate the role of autophagy in deacetylase inhibitor-triggered liver cancer cell death.HepG2 (p53wt) and Hep3B (p53 null) liver cancer cell lines were exposed to panobinostat. RT-qPCR and western blot confirmed autophagic factor modulation. Immuno-fluorescence, -precipitation and -histochemistry as well as transmission electron microscopy verified autophagosome formation. The cytotoxicity of panobinostat and autophagy modulators was detected using a real time cell viability assay.Panobinostat induced autophagy-related factor expression and aggregation. Map1LC3B and Beclin1 were significantly over-expressed in HepG2 xenografts in nude mice treated with panobinostat for 4 weeks. Subcellular distribution of Beclin1 increased with the appearance of autophagosomes-like aggregates. Cytosolic loss of p53, in HepG2, and p73, in Hep3B cells, and a corresponding gain of their nuclear level, together with modulation of DRAM1, were observed. Autophagosome aggregation was visible after 6 h of treatment. Treatment of cells stably expressing GFP-RFPtag Map1LC3B resulted in aggregation and a fluorescence switch, thus confirming autophagosome formation and maturation. Tamoxifen, an inducer of autophagy, caused only a block in cell proliferation; but in combination with panobinostat it resulted in cell death.Autophagy triggers cell demise in liver cancer. Its modulation by the combination of tamoxifen and panobinostat could be a new option for palliative treatment of hepatocellular carcinoma. PMID:27058414

  3. A High Circulating Tumor Cell Count in Portal Vein Predicts Liver Metastasis From Periampullary or Pancreatic Cancer: A High Portal Venous CTC Count Predicts Liver Metastases.

    PubMed

    Tien, Yu Wen; Kuo, Hsun-Chuan; Ho, Be-Ing; Chang, Ming-Chu; Chang, Yu-Ting; Cheng, Mei-Fang; Chen, Huai-Lu; Liang, Ting-Yung; Wang, Chien-Fang; Huang, Chia-Yi; Shew, Jin-Yuh; Chang, Ying Chih; Lee, Eva Y H P; Lee, Wen-Hwa

    2016-04-01

    Circulating tumor cells (CTCs) released from a periampullary or pancreatic cancer can be more frequently detected in the portal than the systemic circulation and potentially can be used to identify patients with liver micrometastases. Aims of this study is to determine if CTCs count in portal venous blood of patients with nonmetastatic periampullary or pancreatic adenocarcinoma can be used as a predictor for subsequent liver metastases. CTCs were quantified in portal and peripheral venous blood samples collected simultaneously during pancreaticoduodenectomy in patients with presumed periampullary or pancreatic adenocarcinoma without image-discernible metastasis. Postoperatively patients were monitored for liver metastasis by abdominal magnetic resonance imaging or computed tomography every 3 months for 1 year. Sixty patients with a pathological diagnosis of periampullary or pancreatic adenocarcinoma were included in the study. Multivariate analysis indicated that portal CTC count was a significant predictor for liver metastases within 6 months after surgery. Eleven of 13 patients with a high portal CTCs count (defined as >112 CMx Platform estimated CTCs in 2 mL blood) developed liver metastases within 6 months after surgery. In contrast, only 6 of 47 patients with a low portal CTC count developed liver metastases (P < 0.0001). A value of 112 CMx Platform estimated CTCs had 64.7% sensitivity and 95.4% specificity to predict liver metastases within 6 months after surgery. We concluded that a high CTC count in portal venous blood collected during pancreaticoduodenectomy in patients with periampullary or pancreatic adenocarcinoma without metastases detected by currently available imaging tools is a significant predictor for liver metastases within 6 months after surgery. PMID:27100430

  4. Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer

    PubMed Central

    Aleksandrova, Krasimira; Boeing, Heiner; Nöthlings, Ute; Jenab, Mazda; Fedirko, Veronika; Kaaks, Rudolf; Lukanova, Annekatrin; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Boffetta, Paolo; Trepo, Elisabeth; Westhpal, Sabine; Duarte-Salles, Talita; Stepien, Magdalena; Overvad, Kim; Tjønneland, Anne; Halkjær, Jytte; Boutron-Ruault, Marie-Christine; Dossus, Laure; Racine, Antoine; Lagiou, Pagona; Bamia, Christina; Benetou, Vassiliki; Agnoli, Claudia; Palli, Domenico; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, Bas; Peeters, Petra H; Gram, Inger Torhild; Lund, Eiliv; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Gavrila, Diana; Barricarte, Aurelio; Dorronsoro, Miren; Ohlsson, Bodil; Lindkvist, Björn; Johansson, Anders; Sund, Malin; Khaw, Kay-Tee; Wareham, Nicholas; Travis, Ruth C; Riboli, Elio; Pischon, Tobias

    2014-01-01

    Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n = 125), GBTC (n = 137), or IBD (n = 34). Using risk-set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL-6, C-peptide, and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95% CI = 1.02-1.46; P = 0.03; 1.90; 95% CI = 1.30-2.77; P = 0.001; 2.25; 95% CI = 1.43-3.54; P = 0.0005; and 2.09; 95% CI = 1.19-3.67; P = 0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95% CI = 1.05-1.42; P = 0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95% CI = 1.25-2.11; P = 0.0003) and IBD (IRR = 10.5; 95% CI = 2.20-50.90; P = 0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide, and non-HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of

  5. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

    Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented. PMID:9752034

  6. [A Case of Colon Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine/Oxaliplatin plus Bevacizumab].

    PubMed

    Suematsu, Yuki; Ishibashi, Yuji; Hiratsuka, Miyuki; Suda, Hiroshi; Takahashi, Miyuki; Saito, Hiroyuki; Omori, Keita; Morita, Akihiko; Wakabayashi, Kazuhiko; Ito, Yutaka

    2015-11-01

    A 69-year-old woman was diagnosed with descending colon cancer with multiple liver metastases, and a left hemicolectomy was performed. The patient was treated with capecitabine/oxaliplatin (CapeOX) plus bevacizumab (Bmab). After 5 courses of chemotherapy, the number and size of liver metastases remarkably reduced, and after the 12th course, because of peripheral neuropathy, a "stop-and-go"fashion of administering oxaliplatin (L-OHP) was initiated. After 14 courses, the liver metastases had disappeared. After the 33rd course of L-OHP treatment, the patient started receiving capecitabine therapy. The patient is recurrence-free 3 years after surgery, 14 months after achieving a complete response (CR). We report a case of long-term CR after surgery for descending colon cancer with multiple liver metastases, followed by a "stop-and-go" method of administering L-OHP or CapeOX plus Bmab therapy. PMID:26805277

  7. Conversion Therapy Using mFOLFOX6 With Panitumumab for Unresectable Liver Metastases From Multiple Colorectal Cancers With Familial Adenomatous Polyposis

    PubMed Central

    Toiyama, Yuji; Inoue, Yasuhiro; Kitajima, Takahito; Okigami, Masato; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

    2014-01-01

    A 39-year-old man received a diagnosis of unresectable multiple liver metastases from multiple colorectal cancers with familial adenomatous polyposis. After construction of an ileostomy, modified FOLFOX6 (mFOLFOX6) with panitumumab was administrated because rectal cancer and sigmoid colon cancer are KRAS wild type. The 13 courses of chemotherapy resulted in a marked reduction in the size of liver metastases and sigmoid colon cancer. Consequently, curative resection with total colectomy, ileal pouch anal anastomosis, and liver metastasis resection with radiofrequency ablation was performed. Progression of KRAS wild-type rectal cancer after chemotherapy suggested that each clone from rectal and sigmoid colon cancer might have a different sensitivity to epidermal growth factor receptor antibody. Immunohistochemical analysis revealed loss of PTEN expression in rectal cancer compared with liver metastases from sigmoid colon cancer, showing that the difference of mFOLFOX6 with panitumumab might be related to activation of the PI3K-AKT pathway. PMID:25437589

  8. N-hydroxylation of 4-aminobiphenyl by CYP2E1 produces oxidative stress in a mouse model of chemically induced liver cancer.

    PubMed

    Wang, Shuang; Sugamori, Kim S; Tung, Aveline; McPherson, J Peter; Grant, Denis M

    2015-04-01

    4-Aminobiphenyl (ABP) is a trace component of cigarette smoke and hair dyes, a suspected human carcinogen and a potent rodent liver carcinogen. Postnatal exposure of mice to ABP results in a higher incidence of liver tumors in males than in females, paralleling the sex difference in human liver cancer incidence. A traditional model of ABP tumorigenesis involves initial CYP1A2-mediated N-hydroxylation, which eventually leads to production of mutagenic ABP-DNA adducts that initiate tumor growth. However, several studies have found no correlation between sex or CYP1A2 function and the DNA-damaging, mutagenic, or tumorigenic effects of ABP. Oxidative stress may be an important etiological factor for liver cancer, and it has also been linked to ABP exposure. The goals of this study were to identify novel enzyme(s) that contribute to ABP N-oxidation, and to investigate a potential role for oxidative stress in ABP liver tumorigenicity. Isozyme-selective inhibition experiments using liver microsomes from wild-type and genetically modified mice identified CYP2E1 as a major ABP N-hydroxylating enzyme. The N-hydroxylation of ABP by transiently expressed CYP2E1 produced oxidative stress in cultured mouse hepatoma cells. In vivo postnatal exposure of mice to a tumorigenic dose of ABP also produced oxidative stress in male wild-type mice, but not in male Cyp2e1(-/-) mice or in female mice. However, a stronger NRF2-associated antioxidant response was observed in females. Our results identify CYP2E1 as a novel ABP-N-oxidizing enzyme, and suggest that sex differences in CYP2E1-dependent oxidative stress and antioxidant responses to ABP may contribute to the observed sex difference in tumor incidence. PMID:25601990

  9. N-Hydroxylation of 4-Aminobiphenyl by CYP2E1 Produces Oxidative Stress in a Mouse Model of Chemically Induced Liver Cancer

    PubMed Central

    Wang, Shuang; Sugamori, Kim S.; Tung, Aveline; McPherson, J. Peter; Grant, Denis M.

    2015-01-01

    4-Aminobiphenyl (ABP) is a trace component of cigarette smoke and hair dyes, a suspected human carcinogen and a potent rodent liver carcinogen. Postnatal exposure of mice to ABP results in a higher incidence of liver tumors in males than in females, paralleling the sex difference in human liver cancer incidence. A traditional model of ABP tumorigenesis involves initial CYP1A2-mediated N-hydroxylation, which eventually leads to production of mutagenic ABP-DNA adducts that initiate tumor growth. However, several studies have found no correlation between sex or CYP1A2 function and the DNA-damaging, mutagenic, or tumorigenic effects of ABP. Oxidative stress may be an important etiological factor for liver cancer, and it has also been linked to ABP exposure. The goals of this study were to identify novel enzyme(s) that contribute to ABP N-oxidation, and to investigate a potential role for oxidative stress in ABP liver tumorigenicity. Isozyme-selective inhibition experiments using liver microsomes from wild-type and genetically modified mice identified CYP2E1 as a major ABP N-hydroxylating enzyme. The N-hydroxylation of ABP by transiently expressed CYP2E1 produced oxidative stress in cultured mouse hepatoma cells. In vivo postnatal exposure of mice to a tumorigenic dose of ABP also produced oxidative stress in male wild-type mice, but not in male Cyp2e1(−/−) mice or in female mice. However, a stronger NRF2-associated antioxidant response was observed in females. Our results identify CYP2E1 as a novel ABP-N-oxidizing enzyme, and suggest that sex differences in CYP2E1-dependent oxidative stress and antioxidant responses to ABP may contribute to the observed sex difference in tumor incidence. PMID:25601990

  10. Exploring important influences on the healthfulness of prostate cancer survivors' diets.

    PubMed

    Coa, Kisha I; Smith, Katherine C; Klassen, Ann C; Thorpe, Roland J; Caulfield, Laura E

    2015-06-01

    A cancer diagnosis is often conceptualized as a teachable moment when individuals might be motivated to make lifestyle changes. Many prostate cancer survivors, however, do not adhere to dietary guidelines. In this article, we explore how cancer affected prostate cancer survivors' diets and identify important influences on diet. Twenty prostate cancer survivors completed three 24-hour dietary recalls and an in-depth dietary interview. We analyzed interviews using a constant comparison approach, and dietary recall data quantitatively to assess quality and qualitatively to identify food choice patterns. Most men reported not making dietary changes following their cancer diagnosis but did express an interest in healthy eating, primarily to facilitate weight loss. Men portrayed barriers to healthy eating that often outweighed their motivation to eat healthy. Public health programs should consider alternative ways of framing healthy eating programs for prostate cancer survivors that might be more effective than a cancer-specific focus. PMID:25857653

  11. Exploring Important Influences on the Healthfulness of Prostate Cancer Survivors’ Diets

    PubMed Central

    Coa, Kisha I.; Smith, Katherine Clegg; Klassen, Ann C.; Thorpe, Roland J.; Caulfield, Laura E.

    2015-01-01

    A cancer diagnosis is often conceptualized as a teachable moment when individuals might be motivated to make lifestyle changes. Many prostate cancer survivors, however, do not adhere to dietary guidelines. In this article, we explore how cancer impacted prostate cancer survivors’ diets and identify important influences on diet. Twenty prostate cancer survivors completed three 24-hour dietary recalls and an in-depth dietary interview. We analyzed interviews using a constant comparison approach, and dietary recall data quantitatively to assess quality and qualitatively to identify food choices patterns. Most men reported not making dietary changes following their cancer diagnosis, but did express an interest in healthy eating, primarily to facilitate weight loss. Men portrayed barriers to healthy eating that often outweighed their motivation to eat healthy. Public health programs should consider alternative ways of framing healthy eating programs for prostate cancer survivors that might be more effective than a cancer-specific focus. PMID:25857653

  12. Sphingosine kinase 1 dependent protein kinase C-δ activation plays an important role in acute liver failure in mice

    PubMed Central

    Lei, Yan-Chang; Yang, Ling-Ling; Li, Wen; Luo, Pan

    2015-01-01

    AIM: To investigate the role of protein kinase C (PKC)-δ activation in the pathogenesis of acute liver failure (ALF) in a well-characterized mouse model of D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced ALF. METHODS: BALB/c mice were randomly assigned to five groups, and ALF was induced in mice by intraperitoneal injection of D-GaIN (600 mg/kg) and LPS (10 μg/kg). Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at different time points within one week were determined using a multiparameteric analyzer. Serum levels of high-mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 as well as nuclear factor (NF)-κB activity were determined by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of PKC-δ in liver tissue and peripheral blood mononuclear cells (PBMCs) was analyzed by Western blot. RESULTS: The expression and activation of PKC-δ were up-regulated in liver tissue and PBMCs of mice with D-GalN/LPS-induced ALF. Inhibition of PKC-δ activation with rottlerin significantly increased the survival rates and decreased serum ALT/AST levels at 6, 12 and 24 h compared with the control group (P < 0.001). Rottlerin treatment also significantly decreased serum levels of HMGB1 at 6, 12, and 24 h, TNF-α, IL-6 and IL-1 β at 12 h compared with the control group (P < 0.01). The inflammatory cell infiltration and necrosis in liver tissue were also decreased in the rottlerin treatment group. Furthermore, sphingosine kinase 1 (SphK1) dependent PKC-δ activation played an important role in promoting NF-κB activation and inflammatory cytokine production in ALF. CONCLUSION: SphK1 dependent PKC-δ activation plays an important role in promoting NF-κB activation and inflammatory response in ALF, and inhibition of PKC-δ activation might be

  13. Liver receptor homolog-1 (LRH-1): a potential therapeutic target for cancer

    PubMed Central

    Nadolny, Christina; Dong, Xiaoqun

    2015-01-01

    Liver receptor homolog-1 (LRH-1) is a nuclear receptor involved in various biological processes. This nuclear receptor has critical functions in embryonic development as well as in adult homeostasis. Although the physiological functions of LRH-1 in normal breast, pancreas, and intestine have been widely investigated, the dysregulation that occurs during pathological conditions is not well understood. LRH-1 has been implicated in pancreatic, breast, and gastrointestinal cancer, where it exerts its effect of initiation and progression by promoting cell proliferation and metastasis. In addition to mechanistic studies, LRH-1 agonists and antagonists are being explored. Identification and development of endogenous and synthetic ligands has been pursued using computational-based structural analysis. Through ligand identification and a thorough understanding of the pathological roles of LRH-1, new therapeutic avenues for cancer treatment based upon LRH-1 may be a desirable focus for further research. PMID:25951367

  14. MSH2 Dysregulation Is Triggered by Proinflammatory Cytokine Stimulation and Is Associated with Liver Cancer Development.

    PubMed

    Eso, Yuji; Takai, Atsushi; Matsumoto, Tomonori; Inuzuka, Tadashi; Horie, Takahiro; Ono, Koh; Uemoto, Shinji; Lee, Kyeryoung; Edelmann, Winfried; Chiba, Tsutomu; Marusawa, Hiroyuki

    2016-08-01

    Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFα stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via NF-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2(-) (/) (-)AID(+), ALB-MSH2(-) (/) (-), and ALB-AID(+) mice, in which MSH2 is deficient and/or activation-induced cytidine deaminase (AICDA) is expressed in cells with albumin-producing hepatocytes. The mutation signatures in the tumors developed in these models, especially ALB-MSH2(-) (/) (-)AID(+) mice, closely resembled those of human hepatocellular carcinoma. Our findings demonstrated that inflammation-mediated dysregulation of MSH2 may be a mechanism of genetic alterations during hepatocarcinogenesis. Cancer Res; 76(15); 4383-93. ©2016 AACR. PMID:27261510

  15. p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer.

    PubMed

    Tschaharganeh, Darjus F; Xue, Wen; Calvisi, Diego F; Evert, Matthias; Michurina, Tatyana V; Dow, Lukas E; Banito, Ana; Katz, Sarah F; Kastenhuber, Edward R; Weissmueller, Susann; Huang, Chun-Hao; Lechel, Andre; Andersen, Jesper B; Capper, David; Zender, Lars; Longerich, Thomas; Enikolopov, Grigori; Lowe, Scott W

    2014-07-31

    The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protein nestin in an Sp1/3 transcription-factor-dependent manner and that Nestin is required for tumor initiation in vivo. Moreover, loss of p53 facilitates dedifferentiation of mature hepatocytes into nestin-positive progenitor-like cells, which are poised to differentiate into hepatocellular carcinomas (HCCs) or cholangiocarcinomas (CCs) in response to lineage-specific mutations that target Wnt and Notch signaling, respectively. Many human HCCs and CCs show elevated nestin expression, which correlates with p53 loss of function and is associated with decreased patient survival. Therefore, transcriptional repression of Nestin by p53 restricts cellular plasticity and tumorigenesis in liver cancer. PMID:25083869

  16. p53 dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer

    PubMed Central

    Tschaharganeh, Darjus F; Xue, Wen; Calvisi, Diego F; Evert, Matthias; Michurina, Tatyana V; Dow, Lukas E; Banito, Ana; Katz, Sarah F; Kastenhuber, Edward R; Weissmueller, Susann; Huang, Chun-Hao; Lechel, Andre; Andersen, Jesper B; Capper, David; Zender, Lars; Longerich, Thomas; Enikolopov, Grigori; Lowe, Scott W

    2014-01-01

    Summary The p53 tumor suppressor coordinates a series of anti-proliferative responses that restrict the expansion of malignant cells and, as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor cell-associated protein nestin in an Sp1/3 transcription factor-dependent manner and that nestin is required for tumor initiation in vivo. Moreover, loss of p53 facilitates dedifferentiation of mature hepatocytes into nestin-positive progenitor-like cells, which are poised to differentiate into hepatocellular carcinomas (HCCs) or cholangiocarcinomas (CCs) in response to lineage-specific mutations that target Wnt and Notch signaling, respectively. Many human HCCs and CCs show elevated nestin expression, which correlates with p53 loss of function and is associated with decreased patient survival. Therefore, transcriptional repression of Nestin by p53 restricts cellular plasticity and tumorigenesis in liver cancer. PMID:25083869

  17. 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. PMID:27194488

  18. Recent progress and clinical importance on pharmacogenetics in cancer therapy

    PubMed Central

    Soh, Thomas I Peng; Yong, Wei Peng; Innocenti, Federico

    2013-01-01

    Recent advances have provided unprecedented opportunities to identify prognostic and predictive markers of efficacy of cancer therapy. Genetic markers can be used to exclude patients who will not benefit from therapy, exclude patients at high risk of severe toxicity, and adjust dosing. Genomic approaches for marker discovery now include genome-wide association studies and tumor DNA sequencing. The challenge is now to select markers for which there is enough evidence to transition them to the clinic. The hurdles include the inherent low frequency of many of these markers, the lengthy validation process through trials, as well as legislative and economic hurdles. Attempts to answer questions about certain markers more quickly have led to an increased popularity of trials with enrichment design, especially in the light of the dramatic phase I results seen in recent months. Personalized medicine in oncology is a step closer to reality. PMID:21950596

  19. Digital mammography, cancer screening: Factors important for image compression

    NASA Technical Reports Server (NTRS)

    Clarke, Laurence P.; Blaine, G. James; Doi, Kunio; Yaffe, Martin J.; Shtern, Faina; Brown, G. Stephen; Winfield, Daniel L.; Kallergi, Maria

    1993-01-01

    The use of digital mammography for breast cancer screening poses several novel problems such as development of digital sensors, computer assisted diagnosis (CAD) methods for image noise suppression, enhancement, and pattern recognition, compression algorithms for image storage, transmission, and remote diagnosis. X-ray digital mammography using novel direct digital detection schemes or film digitizers results in large data sets and, therefore, image compression methods will play a significant role in the image processing and analysis by CAD techniques. In view of the extensive compression required, the relative merit of 'virtually lossless' versus lossy methods should be determined. A brief overview is presented here of the developments of digital sensors, CAD, and compression methods currently proposed and tested for mammography. The objective of the NCI/NASA Working Group on Digital Mammography is to stimulate the interest of the image processing and compression scientific community for this medical application and identify possible dual use technologies within the NASA centers.

  20. Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer

    SciTech Connect

    Tomasi, Maria Lauda; Ryoo, Minjung; Skay, Anna; Tomasi, Ivan; Giordano, Pasquale; Mato, José M.; Lu, Shelly C.

    2013-07-15

    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 apoptosis 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 growth

  1. The Role of Cea and Liver Function Tests in the Detection of Hepatic Metastases From Colo-Rectal Cancer

    PubMed Central

    Bombelli, Luigia; Bozzetti, F.; Doci, R.; Gennari, L.; Koukouras, D.

    1990-01-01

    Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyl-transpeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallable imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases. PMID:2090187

  2. Anti-EGFR and anti-VEGF agents: important targeted therapies of colorectal liver metastases.

    PubMed

    Feng, Qing-Yang; Wei, Ye; Chen, Jing-Wen; Chang, Wen-Ju; Ye, Le-Chi; Zhu, De-Xiang; Xu, Jian-Min

    2014-04-21

    Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, "new" RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into

  3. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan

    PubMed Central

    Kudo, Masatoshi; Matsui, Osamu; Izumi, Namiki; Iijima, Hiroko; Kadoya, Masumi; Imai, Yasuharu; Okusaka, Takuji; Miyayama, Shiro; Tsuchiya, Kaoru; Ueshima, Kazuomi; Hiraoka, Atsushi; Ikeda, Masafumi; Ogasawara, Sadahisa; Yamashita, Tatsuya; Minami, Tetsuya; Yamakado, Koichiro

    2014-01-01

    The Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma proposed by the Japan Society of Hepatology was updated in June 2014 at a consensus meeting of the Liver Cancer Study Group of Japan. Three important items have been updated: the surveillance and diagnostic algorithm, the treatment algorithm, and the definition of transarterial chemoembolization (TACE) failure/refractoriness. The most important update to the diagnostic algorithm is the inclusion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging as a first line surveillance/diagnostic tool. Another significant update concerns removal of the term “lipiodol” from the definition of TACE failure/refractoriness. PMID:26280007

  4. A Novel Multiinstance Learning Approach for Liver Cancer Recognition on Abdominal CT Images Based on CPSO-SVM and IO

    PubMed Central

    Yi, Dehui

    2013-01-01

    A novel multi-instance learning (MIL) method is proposed to recognize liver cancer with abdominal CT images based on instance optimization (IO) and support vector machine with parameters optimized by a combination algorithm of particle swarm optimization and local optimization (CPSO-SVM). Introducing MIL into liver cancer recognition can solve the problem of multiple regions of interest classification. The images we use in the experiments are liver CT images extracted from abdominal CT images. The proposed method consists of two main steps: (1) obtaining the key instances through IO by texture features and a classification threshold in classification of instances with CPSO-SVM and (2) predicting unknown samples with the key instances and the classification threshold. By extracting the instances equally based on the entire image, the proposed method can ignore the procedure of tumor region segmentation and lower the demand of segmentation accuracy of liver region. The normal SVM method and two MIL algorithms, Citation-kNN algorithm and WEMISVM algorithm, have been chosen as comparing algorithms. The experimental results show that the proposed method can effectively recognize liver cancer images from two kinds of cancer CT images and greatly improve the recognition accuracy. PMID:24368931

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

    PubMed

    Huang, Xiongfei; Zeng, Yeting; Wang, Xinrui; Ma, Xiaoxiao; Li, Qianqian; Li, Ningbo; Su, Hongying; Huang, Wendong

    2016-05-27

    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 by 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. PMID:27109477

  6. Development of a Liver-specific Tet-On Inducible System for AAV Vectors and Its Application in the Treatment of Liver Cancer

    PubMed Central

    Vanrell, Lucia; Di Scala, Marianna; Blanco, Laura; Otano, Itziar; Gil-Farina, Irene; Baldim, Victor; Paneda, Astrid; Berraondo, Pedro; Beattie, Stuart G; Chtarto, Abdelwahed; Tenenbaum, Lilianne; Prieto, Jesús; Gonzalez-Aseguinolaza, Gloria

    2011-01-01

    Recombinant adeno-associated virus (rAAV) are effective gene delivery vehicles that can mediate long-lasting transgene expression. However, tight regulation and tissue-specific transgene expression is required for certain therapeutic applications. For regulatable expression from the liver we designed a hepatospecific bidirectional and autoregulatory tetracycline (Tet)-On system (TetbidirAlb) flanked by AAV inverted terminal repeats (ITRs). We characterized the inducible hepatospecific system in comparison with an inducible ubiquitous expression system (TetbidirCMV) using luciferase (luc). Although the ubiquitous system led to luc expression throughout the mouse, luc expression derived from the hepatospecific system was restricted to the liver. Interestingly, the induction rate of the TetbidirAlb was significantly higher than that of TetbidirCMV, whereas leakage of TetbidirAlb was significantly lower. To evaluate the therapeutic potential of this vector, an AAV-Tetbidir-Alb-expressing interleukin-12 (IL-12) was tested in a murine model for hepatic colorectal metastasis. The vector induced dose-dependent levels of IL-12 and interferon-γ (IFN-γ), showing no significant toxicity. AAV-Tetbidir-Alb-IL-12 was highly efficient in preventing establishment of metastasis in the liver and induced an efficient T-cell memory response to tumor cells. Thus, we have demonstrated persistent, and inducible in vivo expression of a gene from a liver-specific Tet-On inducible construct delivered via an AAV vector and proved to be an efficient tool for treating liver cancer. PMID:21364542

  7. Possible action mechanism of the electromagnetic fields in the liver cancer development: A mathematical proposal

    NASA Astrophysics Data System (ADS)

    Jiménez-García, Mónica Noemí; Godina-Nava, Juan José

    2012-02-01

    Currently it is known that electromagnetic field exposure can induce biological changes, although the precise effects and action mechanism of the interaction between the electromagnetic field and biological systems are not well understood. In this work we propose a possible action mechanism, concerning the effect that the extremely low frequency electromagnetic field exposure has on the early stage of liver cancer development. The model is developed studying the phenomena called oxidative stress that it appears after it is applied a carcinogenic agent used to induce hepatic cancer chemically in an experimental animal model. This physical-chemical process involves the movement of magnetic field dependent free charged particles, called free radicals. We will consider the use of the radical pairs theory as a framework, in which we will describe the spin density operator evolution by implementing the stochastic Liouville equation with hyperfine interaction. This describes how the selectivity of the interaction between spin states of the free radicals with the applied electromagnetic field, influences the development of pre-neoplastic lesions in the liver. AIP Publishing is retracting this article due to the substantial use of content in the Results and Conclusions section without proper citation of a previously published paper in Chemical Physics Letters 361 (2012) 219-225. This article is retracted from the scientific record with effect from 15 October 2015.

  8. Sorafenib treatment during partial hepatectomy reduces tumorgenesis in an inflammation-associated liver cancer model.

    PubMed

    Zahavi, Tamar; Lanton, Tali; Divon, Mali Salmon; Salmon, Asher; Peretz, Tamar; Galun, Eithan; Axelrod, Jonathan H; Sonnenblick, Amir

    2016-01-26

    The long-term prognosis after resection of hepatocellular carcinoma (HCC), which is one of the treatment options for early-stage HCC, remains unsatisfactory as a result of a high incidence of disease recurrence. Recent studies performed in murine models revealed a link between liver regeneration under chronic inflammation and hepatic tumorigenesis. Sorafenib is a potent drug for advanced HCC with multikinase inhibition activity. We propose that inhibition of signal transduction pathways which are activated during hepatectomy, using Sorafenib, will reduce accelerated tumorigenesis. To test this hypothesis, we studied the Mdr2-knockout (KO) mouse strain, a model of inflammation-associated cancer, which underwent partial hepatectomy (PHx) at three months of age, with or without Sorafenib.Here we show that Sorafenib treatment during PHx inhibited different signal transduction pathways at the multikinase levels, but did not result in increased morbidity or mortality. At the early stages after PHx, Sorafenib treatment had no effect on the course of proliferation, apoptosis and DNA repair in the regenerating liver, but resulted in decreased stellate cells activation and inflammatory response. Finally, we show that Sorafenib treatment during PHx at three months of age resulted in decreased fibrosis and tumor formation at 8.5 months.In conclusion our study indicates that short-term Sorafenib treatment during PHx is safe and effective in inhibiting inflammation-associated cancer, and is therefore a potential strategy for recurrence prevention in patients with early-stage HCC treated with PHx. PMID:26695439

  9. Sorafenib treatment during partial hepatectomy reduces tumorgenesis in an inflammation-associated liver cancer model

    PubMed Central

    Salmon, Asher; Peretz, Tamar; Galun, Eithan; Axelrod, Jonathan H.; Sonnenblick, Amir

    2016-01-01

    The long-term prognosis after resection of hepatocellular carcinoma (HCC), which is one of the treatment options for early-stage HCC, remains unsatisfactory as a result of a high incidence of disease recurrence. Recent studies performed in murine models revealed a link between liver regeneration under chronic inflammation and hepatic tumorigenesis. Sorafenib is a potent drug for advanced HCC with multikinase inhibition activity. We propose that inhibition of signal transduction pathways which are activated during hepatectomy, using Sorafenib, will reduce accelerated tumorigenesis. To test this hypothesis, we studied the Mdr2-knockout (KO) mouse strain, a model of inflammation-associated cancer, which underwent partial hepatectomy (PHx) at three months of age, with or without Sorafenib. Here we show that Sorafenib treatment during PHx inhibited different signal transduction pathways at the multikinase levels, but did not result in increased morbidity or mortality. At the early stages after PHx, Sorafenib treatment had no effect on the course of proliferation, apoptosis and DNA repair in the regenerating liver, but resulted in decreased stellate cells activation and inflammatory response. Finally, we show that Sorafenib treatment during PHx at three months of age resulted in decreased fibrosis and tumor formation at 8.5 months. In conclusion our study indicates that short-term Sorafenib treatment during PHx is safe and effective in inhibiting inflammation-associated cancer, and is therefore a potential strategy for recurrence prevention in patients with early-stage HCC treated with PHx. PMID:26695439

  10. Simulation and Visualization of Liver Cancer Ablation Focus in Optical Surgical Navigation.

    PubMed

    Cai, Ken; Yang, Rongqian; Chen, Huazhou; Ning, Hai; Ma, Amin; Zhou, Jing; Huang, Wenhua; Ou, Shanxing

    2016-01-01

    Radiofrequency ablation therapy of liver cancer is a local mini-invasive treatment technology with several advantages, such as low trauma, safety, effectiveness, and quick postoperative recovery. The application of the optical surgical navigation system in radiofrequency ablation therapy can realize the real-time positioning of surgical instruments and focus. The positioning results can be displayed on the computer, thereby guiding doctors to accurately insert the radiofrequency electrode into the focus and improving surgical efficiency. Meanwhile, the accurate evaluation of the form and size of the ablation focus by the navigation system is the key to realizing the complete ablation of liver cancer. Therefore, based on the heat conduction equation, this paper simplifies the simulation process of the ablation focus, calculates the volume of the ablation focus by distinguishing boundary points and internal points, achieves the effective simulation of the ablation results in the surgery, and reconstructs the ablation focus by using ray casting algorithm and mobile cube algorithm for 3D visualization processing, thereby providing doctors the convenience of being able to simulate the radiofrequency ablation surgery before the actual surgery. PMID:26525057

  11. Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer

    PubMed Central

    Ranzani, Marco; Cesana, Daniela; Bartholomae, Cynthia C.; Sanvito, Francesca; Pala, Mauro; Benedicenti, Fabrizio; Gallina, Pierangela; Sergi, Lucia Sergi; Merella, Stefania; Bulfone, Alessandro; Doglioni, Claudio; von Kalle, Christof; Kim, Yoon Jun; Schmidt, Manfred; Tonon, Giovanni; Naldini, Luigi; Montini, Eugenio

    2013-01-01

    Transposons and γ-retroviruses have been efficiently used as insertional mutagens in different tissues to identify molecular culprits of cancer. However, these systems are characterized by recurring integrations that accumulate in tumor cells, hampering the identification of early cancer-driving events amongst bystander and progression-related events. We developed an insertional mutagenesis platform based on lentiviral vectors (LVV) by which we could efficiently induce hepatocellular carcinoma (HCC) in 3 different mouse models. By virtue of LVV’s replication-deficient nature and broad genome-wide integration pattern, LVV-based insertional mutagenesis allowed identification of 4 new liver cancer genes from a limited number of integrations. We validated the oncogenic potential of all the identified genes in vivo, with different levels of penetrance. Our newly identified cancer genes are likely to play a role in human disease, since they are upregulated and/or amplified/deleted in human HCCs and can predict clinical outcome of patients. PMID:23314173

  12. HNF1α and SREBP2 are important regulators of NPC1L1 in human liver

    PubMed Central

    Pramfalk, Camilla; Jiang, Zhao-Yan; Cai, Qu; Hu, Hai; Zhang, Sheng-Dao; Han, Tian-Quan; Eriksson, Mats; Parini, Paolo

    2010-01-01

    Niemann-Pick C1-like 1 (NPC1L1), a key regulator of intestinal cholesterol absorption, is highly expressed in human liver. Here, we aimed to gain more insight into mechanisms participating in its hepatic regulation in humans. Correlation analysis in livers from Chinese patients with and without gallstone disease revealed strong positive correlations between NPC1L1 and sterol regulatory element binding protein 2 (SREBP2) (r = 0.74, P < 0.05) and between NPC1L1 and hepatic nuclear factor α (HNF4α) (r = 0.53, P < 0.05) mRNA expression. HNF4α is an upstream regulator of HNF1α; thus, we also tested whether HNF1α participates in the regulation of NPC1L1. We showed a dose-dependent regulation by SREBP2 on the NPC1L1 promoter activity and mRNA expression in HuH7 cells. Chromatin immunoprecipitation assay confirmed the binding of SREBP2 to the promoter in vivo. Surprisingly, HNF4α slightly decreased the NPC1L1 promoter activity but had no effect on its gene expression. By contrast, HNF1α increased the promoter activity and the gene expression, and an important HNF1 binding site was identified within the human NPC1L1 promoter. ChIP assays confirmed that HNF1α can bind to the NPC1L1 promoter in vivo. PMID:20460578

  13. Importance of Breast Cancer Subtype in the Development of Androgen Receptor Directed Therapy

    PubMed Central

    Lim, Elgene; Ni, Min; Cao, Shiliang; Hazra, Aditi; Tamimi, Rulla M.; Brown, Myles

    2014-01-01

    The androgen receptor (AR) has re-emerged as a potential therapeutic target in breast cancer. This stems from recent progress made in preclinical models, that have recognized important differences in the effect of AR expression on patient outcomes among different breast cancer subtypes. In parallel, the clinical development of new generations of AR directed therapies for prostate cancer has begun to mature. The availability of these new agents has translated into new trials to treat breast cancer. It is critical that studies of the effect of AR expression and signaling in breast cancer be context and subtype specific in order to successfully target AR signalling as a therapeutic strategy for breast cancer. We will review developments in preclinical studies, and recent clinical trials targeting AR in breast cancer. PMID:24860642

  14. Comparison of inhibition capability of scutellarein and scutellarin towards important liver UDP-glucuronosyltransferase (UGT) isoforms.

    PubMed

    Ma, Guang-You; Cao, Yun-Feng; Hu, Cui-Min; Fang, Zhong-Ze; Sun, Xiao-Yu; Hong, Mo; Zhu, Zhi-Tu

    2014-03-01

    Scutellarin is an important bioactive flavonoid extracted from Erigeron breviscapus (Vant.) Hand-Mazz, and scutellarein is the corresponding aglycone of scutellarin. The present study aims to compare the inhibition potential of scutellarin and scutellarein towards several important UDP-glucuronosyltransferase (UGT) isoforms, including UGT1A1, UGT1A6, UGT1A9 and UGT2B7. It was demonstrated that scutellarein exerted stronger inhibition towards the tested UGT isoforms than scutellarin. Furthermore, the inhibition kinetic type and parameters (Ki ) were determined for the scutellarein's inhibition towards these UGT isoforms. Competitive inhibition of scutellarein towards all these UGT isoforms was demonstrated, and the Ki values were calculated to be 0.02, 5.0, 5.8 and 35.9 μM for UGT1A1, 1A6, 1A9 and 2B7, respectively. Using in vivo maximum plasma concentration of scutellarein in rat, the in vitro-in vivo extrapolation was performed to predict in vivo situation, indicating the most possible in vivo adverse effects due to the inhibition of scutellarein towards UGT1A1. All these results remind us to monitor the utilization of scutellarin and scutellarein, and the herbs containing these two components. PMID:23620377

  15. Estrogen-related receptor γ is upregulated in liver cancer and its inhibition suppresses liver cancer cell proliferation via induction of p21 and p27

    PubMed Central

    Kim, Ji-Hyun; Choi, Yeon-Kyung; Byun, Jun-Kyu; Kim, Mi-Kyung; Kang, Yu Na; Kim, Seong Heon; Lee, Sungwoo; Jang, Byoung Kuk; Park, Keun-Gyu

    2016-01-01

    Orphan nuclear receptor estrogen-related receptor γ (ERRγ) regulates cell growth and tumorigenesis in various cancers. However, the clinical relevance of ERRγ to hepatocellular carcinoma (HCC) remains unclear. Here we examined the clinical significance of ERRγ in HCC and its potential as a therapeutic target. ERRγ levels in tissues from completely resected specimens from 190 HCC patients were examined immunohistochemically and their association with clinical stage and pathological grade was analyzed. Small interfering RNA (siRNA)-mediated knockdown of ERRγ (siRNA-ERRγ) or an ERRγ inverse agonist, GSK5182, were also used to examine the effects of ERRγ inhibition on the proliferation and growth of a human hepatoma cell line, PLC/PRF/5. Immunohistochemical analysis revealed that tumor tissues showed higher levels of ERRγ-positivity than adjacent non-tumor lesions. Tumors showing high levels of ERRγ immunoreactivity also had advanced tumor node metastasis (TNM) and Barcelona Clinic Liver Cancer stages and a higher Edmondson–Steiner grade. In addition, high-level expression of ERRγ in tumors of advanced TNM stage correlated with poorer overall survival. Treatment of PLC/PRF/5 cells with siRNA-ERRγ or GSK5182 inhibited proliferation through G1 arrest, increased expression of p21 and p27 and decreased expression of phosphorylated retinoblastoma protein. GSK5182-induced reactive oxygen species also suppressed the proliferation of PLC/PRF/5 cells. The present study showed that ERRγ expression is clinically significant in HCC; therefore, it can be considered a biomarker for HCC diagnosis. Moreover, the results provide a rationale for the use of ERRγ inhibitors such as GSK5182 as potential therapeutic agents. PMID:26940882

  16. Multifunctional lactobionic acid-modified dendrimers for targeted drug delivery to liver cancer cells: investigating the role played by PEG spacer.

    PubMed

    Fu, Fanfan; Wu, Yilun; Zhu, Jingyi; Wen, Shihui; Shen, Mingwu; Shi, Xiangyang

    2014-09-24

    We report the development of a lactobionic acid (LA)-modified multifunctional dendrimer-based carrier system for targeted therapy of liver cancer cells overexpressing asialoglycoprotein receptors. In this study, generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers were sequentially modified with fluorescein isothiocyanate (FI) and LA (or polyethylene glycol (PEG)-linked LA, PEG-LA), followed by acetylation of the remaining dendrimer terminal amines. The synthesized G5.NHAc-FI-LA or G5.NHAc-FI-PEG-LA conjugates (NHAc denotes acetamide groups) were used to encapsulate a model anticancer drug doxorubicin (DOX). We show that both conjugates are able to encapsulate approximately 5.0 DOX molecules within each dendrimer and the formed dendrimer/DOX complexes are stable under different pH conditions and different aqueous media. The G5.NHAc-FI-PEG-LA conjugate appears to have a better cytocompatibility, enables a slightly faster DOX release rate, and displays better liver cancer cell targeting ability than the G5.NHAc-FI-LA conjugate without PEG under similar experimental conditions. Importantly, the developed G5.NHAc-FI-PEG-LA/DOX complexes are able to specifically inhibit the growth of the target cells with a better efficiency than the G5.NHAc-FI-LA/DOX complexes at a relatively high DOX concentration. Our results suggest a key role played by the PEG spacer that affords the dendrimer platform with enhanced targeting and therapeutic efficacy of cancer cells. The developed LA-modified multifunctional dendrimer conjugate with a PEG spacer may be used as a delivery system for targeted liver cancer therapy and offers new opportunities in the design of multifunctional drug carriers for targeted cancer therapy applications. PMID:25185074

  17. Linkage Specific Fucosylation of Alpha-1-Antitrypsin in Liver Cirrhosis and Cancer Patients: Implications for a Biomarker of Hepatocellular Carcinoma

    PubMed Central

    Comunale, Mary Ann; Rodemich-Betesh, Lucy; Hafner, Julie; Wang, Mengjun; Norton, Pamela; Di Bisceglie, Adrian M.; Block, Timothy; Mehta, Anand

    2010-01-01

    Background We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT). To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV) induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC). Methodology/Principal Findings Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (α-1,3) fucosylation. Increases in core (α-1,6) fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL), specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific. Conclusions/Significance This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification. PMID:20811639

  18. Clonogenically Culturing and Expanding CD34+ Liver Cancer Stem Cells in Vitro.

    PubMed

    Park, Su Cheol; Zeng, Changjun; Tschudy-Seney, Benjamin; Nguyen, Ngoc Tue; Eun, Jong Ryeol; Zhang, Yanling; Ramsamooj, Rajendra; Zhang, Yanghong; Zhao, Min; Theise, Neil D; Zhou, Huaijun; Zern, Mark A; Duan, Yuyou

    2015-07-01

    A large number of cancer stem cells (CSCs) have been isolated and identified; however, none has been cultured in an unlimited manner in vitro without losing tumorigenicity and multipotency. In this study, we successfully clonogenically cultured a newly identified CD34+ liver CSC (LCSC) on feeder cells up to 22 passages (to date) without losing CSC property. Cloned CD34+ LCSC formed a round packed morphology and it could also be cryopreserved and recultured. Stem cell markers, CD34, CD117, and SOX2; normal liver stem cell markers, alpha fetoprotein, CK19, CK18, and OV6; putative CSC markers, CD44, CD133, EpCAM, and CD90; as well as CD31 were expressed in cloned CD34+ LCSC. SOX2 was the major factor in maintaining this LCSC before colonization, and interestingly, OCT4, SOX2, NAONG, Klf4, c-Myc, and Lin28 were upregulated in association with symmetric self-renewal for colony growth of CD34+ LCSC on feeder cells. Gene expression patterns of in vitro differentiation were consistent with our in vivo finding; furthermore, the tumorigenicity of cloned CD34+ LCSC was not different from uncloned CD34+ LCSC sorted from parental PLC. These results show that our cloned CD34+ LCSC maintained CSC property, including self-renewal, bipotency, and tumorigenicity after long-term culture, demonstrating that this LCSC can be cultured in an unlimited manner in vitro. Thus, establishing pure population of CSCs isolated from the patients will provide an opportunity to explore the mechanisms of tumorigenesis and cancer development, and to identify unique biomarkers presenting potential indicators of drug efficacy against CSCs for establishment of a novel strategy for cancer therapy. PMID:25867583

  19. Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells.

    PubMed

    Liu, Shufeng; Zhao, Ting; Song, BenBen; Zhou, Jianhua; Wang, Tony T

    2016-01-01

    Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection. PMID:26808496

  20. Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells

    PubMed Central

    Song, BenBen; Zhou, Jianhua; Wang, Tony T.

    2016-01-01

    Hepatitis C virus (HCV) poses a global threat to public health. HCV envelop protein E2 is the major component on the virus envelope, which plays an important role in virus entry and morphogenesis. Here, for the first time, we affinity purified E2 complex formed in HCV-infected human hepatoma cells and conducted comparative mass spectrometric analyses. 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners. Subsequent functional characterization demonstrated that gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle. Domain mapping experiments showed that HCV E2-NS4B interaction requires the transmembrane domains of the two proteins. Altogether, our proteomics study has uncovered key viral and cellular factors that interact with E2 and provided new insights into our understanding of HCV infection. PMID:26808496

  1. Liver biopsy

    MedlinePlus

    ... Test is Performed The biopsy helps diagnose many liver diseases . The procedure also helps assess the stage (early, advanced) of liver disease. This is especially important in hepatitis C infection. ...

  2. Cancer incidence among alcoholic liver disease patients in Finland: A retrospective registry study during years 1996-2013.

    PubMed

    Sahlman, Perttu; Nissinen, Markku; Pukkala, Eero; Färkkilä, Martti

    2016-06-01

    Both alcohol abuse and liver cirrhosis are known risk factors for various cancers. This article was aimed to assess the long-term risk of malignancies among patients with severe alcoholic liver disease (ALD), i.e., alcoholic liver cirrhosis and alcoholic hepatitis. A cohort of 8,796 male and 3,077 female ALD patients from 1996 to 2012 was identified from the Finnish National Hospital Discharge Register. This nationwide cohort was combined with the data from the Finnish Cancer Registry for incidence of malignancies during the years 1996-2013. The cancer cases diagnosed were compared with the number of cancers in the general population. The number of malignancies in our cohort was 1,052 vs. 368 expected. There was statistically significant excess of cancers of the liver, (standardized incidence ratio [SIR] 59.20; 95% CI 53.11-65.61), pancreas (SIR 3.71; 95% CI 2.72-4.94), pharynx (SIR 9.25; 95% CI 6.05-13.56), mouth (SIR 8.31; 95% CI 4.84-13,29), oesophagus (SIR 7.92; 95% CI 5.49-11.07), tongue (SIR 7,21; 95% CI 3.60-12.89), larynx (SIR 5.20; 95% CI 2.77-8.89), lung (SIR 2.77; 95% CI 2.27-3.32), stomach (SIR 2.76; 95% CI 1.79-4.07), kidney (SIR 2.69; 95% CI 1.84-3.79) and colon (SIR 2.33; 95% CI 1.70-3.11). There was no decreased risk of any cancer among ALD patients. Severe ALD is associated with markedly increased risk of malignancies. The risk is especially high for hepatocellular carcinoma, but also significantly increased for cancers of the upper aerodigestive tract, pancreas and kidneys, and warrants cancer surveillance in selected cases. PMID:26756434

  3. Lung Dose Calculation With SPECT/CT for {sup 90}Yittrium Radioembolization of Liver Cancer

    SciTech Connect

    Yu, Naichang; Srinivas, Shaym M.; DiFilippo, Frank P.; Shrikanthan, Sankaran; Levitin, Abraham; McLennan, Gordon; Spain, James; Xia, Ping; Wilkinson, Allan

    2013-03-01

    Purpose: To propose a new method to estimate lung mean dose (LMD) using technetium-99m labeled macroaggregated albumin ({sup 99m}Tc-MAA) single photon emission CT (SPECT)/CT for {sup 90}Yttrium radioembolization of liver tumors and to compare the LMD estimated using SPECT/CT with clinical estimates of LMD using planar gamma scintigraphy (PS). Methods and Materials: Images of 71 patients who had SPECT/CT and PS images of {sup 99m}Tc-MAA acquired before TheraSphere radioembolization of liver cancer were analyzed retrospectively. LMD was calculated from the PS-based lung shunt assuming a lung mass of 1 kg and 50 Gy per GBq of injected activity shunted to the lung. For the SPECT/CT-based estimate, the LMD was calculated with the activity concentration and lung volume derived from SPECT/CT. The effect of attenuation correction and the patient's breathing on the calculated LMD was studied with the SPECT/CT. With these effects correctly taken into account in a more rigorous fashion, we compared the LMD calculated with SPECT/CT with the LMD calculated with PS. Results: The mean dose to the central region of the lung leads to a more accurate estimate of LMD. Inclusion of the lung region around the diaphragm in the calculation leads to an overestimate of LMD due to the misregistration of the liver activity to the lung from the patient's breathing. LMD calculated based on PS is a poor predictor of the actual LMD. For the subpopulation with large lung shunt, the mean overestimation from the PS method for the lung shunt was 170%. Conclusions: A new method of calculating the LMD for TheraSphere and SIR-Spheres radioembolization of liver cancer based on {sup 99m}Tc-MAA SPECT/CT is presented. The new method provides a more accurate estimate of radiation risk to the lungs. For patients with a large lung shunt calculated from PS, a recalculation of LMD based on SPECT/CT is recommended.

  4. MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties

    SciTech Connect

    Liu, Angela M.; Poon, Ronnie T.P.; Luk, John M.

    2010-04-09

    Hepatocellular carcinoma (HCC) is a malignant form of liver cancer that ranks the second leading cause of cancer-related deaths in China and many Asia regions. The dismal outcome reflects the need for a better understanding of the transcriptional control of oncogenic signaling pathway. Our recent findings have identified yes-associated protein (YAP) is a potent oncogenic driver and independent prognostic risk factor of HCC. The present study aims to elucidate the transcriptional regulation of YAP targeted by microRNA (miRNA). miR-375 is a putative target and was found significantly down-regulated in the tumor versus adjacent non-tumor tissues of HCC patients (n = 48). As determined by luciferase reporter assay, we found ectopic expression of miR-375 could diminish the transcriptional activity of YAP. Furthermore, immunoblotting revealed miR-375 suppressed endogenous YAP protein level. Functional assays showed that miR-375 was able to inhibit proliferation and invasion of HCC cells. Conclusion: miR-375 is an important regulator of YAP oncogene, implicating a potential therapeutic role in HCC treatment.

  5. Expression and mechanism of microRNA-181A on incidence and survival in late liver metastases of colorectal cancer.

    PubMed

    Li, Zengjun; Wang, Haipeng; Xu, Zhongfa; Sun, Yanlai; Han, Jianjun

    2016-03-01

    The emerging role of microRNA-181A (miR-181A) in CRC patients with late liver metastases was studied. In the present study we investigated the association between expression and mechanism of miRNA-181A, liver metastasis and prognosis of colorectal cancer (CRC). The expression of miR-181A and PTEN in CRC patients with late liver metastases was higher than that of the normal (control) group, whereas the expression of miR-181A and PTEN was lower in all pathological groups (TNM I-TNM IV). Overall survival (OS) of lower expression miR-181A CRC patients with late liver metastases was higher than that of higher expression miR-181A CRC patients with late liver metastases. The expression of miR-181A and PTEN in the colon cell line NCM460 was lower than that of the colon cancer SW620 cell line. Upregulation of miR-181A promoted cell viability and inhibited apoptosis of SW620 cells, suppressed PTEN expression and activated phosphorylation of AKT (p-AKT) in SW620 cells. Additionally, downregulation of miR-181A inhibited cell viability of SW620 cells through promotion of PTEN and inhibition of p-AKT. Together, our results indicate that miR-181A expression is associated with CRC patients with late liver metastases through PTEN/AKT signaling. PMID:26750720

  6. [Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].

    PubMed

    Ooe, Asako; Suganuma, Yasushi

    2016-03-01

    We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients. PMID:27067853

  7. Multicentric Cancer Detected at Breast MR Imaging and Not at Mammography: Important or Not?

    PubMed

    Iacconi, Chiara; Galman, Lanie; Zheng, Junting; Sacchini, Virgilio; Sutton, Elizabeth J; Dershaw, David; Morris, Elizabeth A

    2016-05-01

    ), MR imaging-detected multicentric cancers were potentially more biologically relevant because of the presence of unsuspected invasion or a higher grade. Conclusion Multicentric cancer detected only at MR imaging was invasive in 66 of 87 patients (76%), larger than 1 cm in 18 of 73 patients (25%), larger than the known index cancer in 17 of 73 patients (23%), and more biologically important in four of 73 women (5%). An unsuspected additional multicentric cancer seen only at MR imaging is likely clinically relevant disease. (©) RSNA, 2015. PMID:26605912

  8. 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

  9. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    PubMed Central

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  10. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy.

    PubMed

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  11. Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers

    PubMed Central

    Correia da Costa, José M.; Vale, Nuno; Gouveia, Maria J.; Botelho, Mónica C.; Sripa, Banchob; Santos, Lúcio L.; Santos, Júlio H.; Rinaldi, Gabriel; Brindley, Paul J.

    2014-01-01

    Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture. PMID:25566326

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

    MedlinePlus

    ... 2006 Asian Liver Center What every Asian and Pacific Islander should know about hepatitis B and liver ... or liver failure. » 1 in 10 Asian and Pacific Islanders is living with chronic (life-long) hepatitis ...

  13. [A Case of Unresectable Rectal Cancer with Multiple Liver Metastases Treated Effectively with 22 Courses of XELOX Therapy].

    PubMed

    Tanaka, Masanao; Shibano, Nariyuki

    2016-05-01

    The patient was a 64-year-old man who underwent medical examination for anorexia and hematochezia. An abdominal computed tomography (CT) scan showed a large advanced rectal cancer with multiple metastases to the liver. We judged a radical operation to be impossible and performed a sigmoid colostomy for unresectable rectal cancer with multiple liver metastases. Postoperatively, we started XELOX therapy and confirmed the patient had a complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) after completion of the 5th course. In addition, the multiple liver metastases reduced remarkably in size and were judged as having a partial response (PR). To date, the patient has completed 22 courses and these good effects continue. PMID:27210099

  14. The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus

    PubMed Central

    2013-01-01

    Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer. PMID:25512859

  15. The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus.

    PubMed

    Aubry, Jean-Francois; Pauly, Kim Butts; Moonen, Chrit; Haar, Gail Ter; Ries, Mario; Salomir, Rares; Sokka, Sham; Sekins, Kevin Michael; Shapira, Yerucham; Ye, Fangwei; Huff-Simonin, Heather; Eames, Matt; Hananel, Arik; Kassell, Neal; Napoli, Alessandro; Hwang, Joo Ha; Wu, Feng; Zhang, Lian; Melzer, Andreas; Kim, Young-Sun; Gedroyc, Wladyslaw M

    2013-01-01

    Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer. PMID:25512859

  16. Down-regulation of carboxylesterases 1 and 2 plays an important role in prodrug metabolism in immunological liver injury rats.

    PubMed

    Zhang, Chengliang; Xu, Yanjiao; Gao, Ping; Lu, Jingli; Li, Xiping; Liu, Dong

    2015-02-01

    Liver plays a central role in xenobiotics metabolism, thus affecting the in vivo disposition and therapeutic effects of drugs. Carboxylesterases (CESs), with the main isoforms CES1 and CES2, are important in the metabolism of ester-type prodrugs. However, influences of immunological liver injury on the activity of CES remain undefined. In the present study, we demonstrated treatment with lipopolysaccharide (LPS) suppressed the activities of CES1 and CES2. The decreased activities of CES1 and CES2 were preliminarily assessed by the hydrolysis assay for their common substrate p-nitrophenyl acetate (PNPA) with rat hepatic microsomal enzyme. Subsequently, RT-PCR results showed that the levels of CES1 mRNA and mRNA of CES2 (AB010635) and CES2 (AY034877) in the model group were significantly lower than those of the normal control group (P<0.05). Western blot results showed that the expressions of CES1 and CES2 proteins were decreased (P<0.05). To further clarify the effects of LPS on the metabolic activities of CESs, pharmacokinetic studies were performed in rats by utilizing imidapril and irinotecan (CPT-11) as the specific substrates for CES1 and CES2, respectively. After treatment with LPS, AUC0-∞ and Cmax of imidaprilat were decreased from 2084.86±340.66ng·h(-1)·mL(-1) and 234.66±68.85ng·mL(-1) to 983.87±315.34ng·h(-1)·mL(-1) and 113.1±19.69ng·mL(-1) (P<0.05), respectively. Moreover, AUC0-∞ and Cmax of SN-38 were decreased from 8100±918.6ng·h(-1)·mL(-1) and 144.67±20.28ng·mL(-1) to 3270±500.5ng·h(-1)·mL(-1) and 56.19±10.38ng·mL(-1) (P<0.05), respectively. In summary, immunological liver injury remarkably attenuated the expressions and metabolic activities of CES1 and CES2, which may be associated with the regulatory effects of cytokines under inflammation. PMID:25499727

  17. Effect of saffron on liver metastases in patients suffering from cancers with liver metastases: A randomized, double blind, placebo-controlled clinical trial

    PubMed Central

    Hosseini, Azar; Mousavi, Seyed Hamed; Ghanbari, Anis; Homaee Shandiz, Fatemeh; Raziee, Hamid Reza; Pezeshki Rad, Masoud; Mousavi, Seyed Hadi

    2015-01-01

    Objective: Cancer represents the second cause of mortality in the world. Saffron as a medicinal plant is known for its anti-cancer and anti-depressant properties. In this randomized double blind clinical trial, the effects of saffron on response to treatment in patients suffering from liver metastasis were evaluated. Materials and Methods: Thirteen patients suffering from liver metastases who referred to Ghaem and Imam Reza hospital, Mashhad, Iran were included in this study and then divided into two different groups. Both groups received chemotherapy regimen. Patients in group one were treated with saffron capsule (50 mg, twice daily) during chemotherapy periods whereas patients in group two received placebo. A sum of the longest diameter were calculated and compared for all lesions in IV contrast CT scan before and after the treatment. Results: from 13 patients included in this study, six patients quit and seven continued until the end. In saffron-treated group, two patients showed partial and complete response (50%) whereas in placebo group, no response was seen. Also, two deaths in placebo and one in saffron group occurred. Conclusion: This research suggests that saffron might be useful in patients suffering from liver metastasis. However, further investigations with larger sample size are required. PMID:26468463

  18. Based on surface-enhanced Raman spectroscopy analysis of serum albumin in different stages of liver disease for early screening primary liver cancer

    NASA Astrophysics Data System (ADS)

    Liao, Fadian; Ruan, Qiuyong; Lin, Juqiang; Lin, Jinyong; Zeng, Yongyi; Li, Ling; Huang, Zufang; Liu, Nenrong; Chen, Rong

    2014-09-01

    Despite the introduction of high-technology methods of detection and diagnosis, screening of primary liver cancer (PLC) remains imperfect. To diagnosis PLC earlier, Surface-enhanced Raman spectroscopy (SERS) coupled with cellulose-acetate membrane electrophoresis were introduced to separate human serum albumin and SERS spectra. Three groups (15 normal persons' samples, 17 hepatitis/cirrhosis samples, 15 cases of PLC) of serum albumin were tested. Silver colloid was used to obtain SERS spectra of human serum albumin. Principal component analysis (PCA) and linear discriminant analysis (LDA) were also employed for statistical analysis. The mean Raman spectra of three groups and the difference spectra of any two suggested that the albumin has changed in liver patients. Compared to normal groups, some Raman peaks have shifted or even disappeared in hepatitis/cirrhosis and PLCs groups. The sensitivity and specificity between PLCs and normal groups is 80% and 93.3%. Among hepatitis/cirrhosis and normal groups, the sensitivity is 88.2% and specificity is also 93.3%. Besides, the sensitivity and specificity between PLCs and hepatitis/cirrhosis groups is 86.7% and 76.5%. All the above data and results indicated that early screening of PLC is potential by SERS in different stages of liver disease before cancer occurs.

  19. Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver Abscess

    PubMed Central

    Lindner, Buko; Winau, Florian; Isibasi, Armando; Moreno-Lafont, Martha; Ulmer, Artur J.; Holst, Otto; Tannich, Egbert; Jacobs, Thomas

    2009-01-01

    The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jα18-/- mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using α-galactosylceramide (α-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d−/− mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-γ but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28∶0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-γ production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to α-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess. PMID:19436711

  20. Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess.

    PubMed

    Lotter, Hannelore; González-Roldán, Nestor; Lindner, Buko; Winau, Florian; Isibasi, Armando; Moreno-Lafont, Martha; Ulmer, Artur J; Holst, Otto; Tannich, Egbert; Jacobs, Thomas

    2009-05-01

    The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jalpha18(-/-) mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using alpha-galactosylceramide (alpha-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d(-/-) mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-gamma but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28:0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-gamma production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to alpha-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess. PMID:19436711

  1. Radiation dose dependent risk of liver cancer mortality in the German uranium miners cohort 1946-2003.

    PubMed

    Dufey, F; Walsh, L; Sogl, M; Tschense, A; Schnelzer, M; Kreuzer, M

    2013-03-01

    An increased risk of mortality from primary liver cancers among uranium miners has been observed in various studies. An analysis of the data from a German uranium miner cohort (the 'Wismut cohort') was used to assess the relationship with ionising radiation. To that end the absorbed organ dose due to high and low linear energy transfer radiation was calculated for 58 987 miners with complete information on radiation exposure from a detailed job-exposure matrix. 159 deaths from liver cancer were observed in the follow-up period from 1946 to 2003. Relative risk models with either linear or categorical dependence on high and low linear energy transfer radiation liver doses were fitted by Poisson regression, stratified on age and calendar year. The linear trend of excess relative risk in a model with both low and high linear transfer radiation is -0.8 (95% confidence interval (CI): -3.7, 2.1) Gy(-1) and 48.3 (95% CI: -32.0, 128.6) Gy(-1) for low and high linear energy transfer radiation, respectively, and thus not statistically significant for either dose. The increase of excess relative risk with equivalent liver dose is 0.57 (95% CI: -0.69, 1.82) Sv(-1). Adjustment for arsenic only had a negligible effect on the radiation risk. In conclusion, there is only weak evidence for an increase of liver cancer mortality with increasing radiation dose in the German uranium miners cohort considered. However, both a lack of statistical power and potential misclassification of primary liver cancer are issues. PMID:23295324

  2. Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women

    PubMed Central

    Yang, Yang; Gao, Jing; Li, Hong-Lan; Zheng, Wei; Yang, Gong; Zhang, Wei; Ma, Xiao; Tan, Yu-Ting; Rothman, Nat; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-Ou; Xiang, Yong-Bing

    2016-01-01

    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) to 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. PMID:26990915

  3. 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. PMID:26990915

  4. Adjuvant therapy of Dukes' C colon cancer by intra-arterial P-32 colloid for internal radiation therapy of the liver

    SciTech Connect

    Grady, E.D.

    1984-09-01

    To prevent probable occult metastatic liver cancer from progressing to clinical disease, the author used internal radiation therapy as an effective adjuvant to surgical excision of primary Dukes' C colonic cancer. A calculated radiation dose of 5000 rads was delivered to the liver by injecting radioactive 32-P chromic phosphate colloid through the superior mesenteric and celiac arteries. When this was done, the colloid passed through the intestines and was mixed thoroughly with the blood and delivered to the liver by the portal vein. The Kupffer cells in the liver trapped the colloid, and a minimum amount passed through the liver and got into the general circulation. This kept the amount of colloid deposited in the bone marrow to a minimum. In a phase-I pilot study in which nine patients were treated, no serious side effects were noted. In eight patients, the liver has remained free of cancer for more than 1 year.

  5. Focal Hepatic Fluorodeoxyglucose Uptake Mimics Liver Metastasis Following External Beam Radiation for Gastroesophageal Cancers: A Case and Review of the Literature

    PubMed Central

    Wei, Randy; Chaurasia, Avinash; Yu, Suhong; Lall, Chandana; Klempner, Samuel J

    2016-01-01

    Patients with locally advanced gastroesophageal cancers frequently undergo concurrent chemotherapy and radiation (CRT). 18-fluorodeoxyglucose-positron emission tomography (18FDG-PET) in combination with computed tomography is used for disease staging and assessing response to therapy. 18FDG-PET interpretation is subject to confounding influences including infectious/inflammatory conditions, serum glucose, and concurrent medications. Radiotherapy induces tissue damage, which may be associated with FDG-avidity; however, few reports have described the focal areas of hepatic uptake following concurrent chemoradiation (CRT). Distinguishing hepatic FDG uptake from disease progression represents an important clinical scenario. Here, we present two cases of unexpected FDG uptake in the liver after CRT and review the literature describing incidental liver uptake on FDG-PET. PMID:27625896

  6. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors

    PubMed Central

    Kanas, Gena P; Taylor, Aliki; Primrose, John N; Langeberg, Wendy J; Kelsh, Michael A; Mowat, Fionna S; Alexander, Dominik D; Choti, Michael A; Poston, Graeme

    2012-01-01

    Background Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. Methods Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. Results Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7–7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5–1.7); carcinoembryonic antigen level, 1.9 (1.1–3.2); extrahepatic disease, 1.9 (1.5–2.4); poor tumor grade, 1.9 (1.3–2.7); positive margin, 2.0 (1.7–2.5); >1 liver metastases, 1.6 (1.4–1.8); and >3 cm tumor diameter, 1.5 (1.3–1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. Conclusion The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival. PMID:23152705

  7. Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer.

    PubMed

    Misra, Santosh K; Ghoshal, Goutam; Gartia, Manas R; Wu, Zhe; De, Arun K; Ye, Mao; Bromfield, Corinne R; Williams, Emery M; Singh, Kuldeep; Tangella, Krishnarao V; Rund, Laurie; Schulten, Klaus; Schook, Lawrence B; Ray, Partha S; Burdette, Everette C; Pan, Dipanjan

    2015-11-24

    Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we repurposed FDA-approved topical agent bexarotene (Targretin), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physico-chemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell internalization capability, and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach. PMID:26435333

  8. The Tower of Babel of liver metastases from colorectal cancer: are we ready for one language?

    PubMed

    Bittoni, Alessandro; Scartozzi, Mario; Giampieri, Riccardo; Faloppi, Luca; Maccaroni, Elena; Del Prete, Michela; Bianconi, Maristella; Cascinu, Stefano

    2013-03-01

    Advances in surgical and medical treatments have significantly changed the management of colorectal cancer liver metastases (CRCLMs). In particular, new drugs and modern combination chemotherapy regimens, together with the improvement of surgical techniques, allow a potentially curative approach in an increasing number of patients. Nevertheless, there is no strong evidence for an optimal treatment strategy for CRCLMs, mainly because of the extensive heterogeneity in the patients. In fact, although we consider them a population, they represent different clinical and biological subtypes requiring different approaches. Furthermore, results from different studies in this setting may be difficult to interpret, also because the definitions of different patient subgroups are unclear and overlapping. In this review we discuss the results of clinical trials evaluating the role of chemotherapy in the multimodal management of CRCLMs, in either the pre- or postoperative setting. Then we identify three main categories of CRCLM patients, providing clinical recommendations for each. PMID:22964298

  9. Synthesis and evaluation of hydroxycamptothecin-encapsulated chitosan nanospheres for the treatment of liver cancer.

    PubMed

    Han, J; Hou, Z Q; Wang, Y G; Guo, X

    2015-02-01

    Hydroxycamptothecin-encapsulated chitosan (HC) nanospheres were prepared by Shirasu porous glass (SPG) membrane emulsification technique. The properties and morphology of HC nanospheres were characterized. The diameter of the nanospheres could be controlled within a narrow distribution according to the pore-size of SPG membrane. Hydroxycamptothecin (HCPT) encapsulation efficiency could reach to 81.3%. The long-term drug release of HCPT could be presented by an accumulated drug release of 85.4% in 15 days with an initial burst effect. In vitro study, HC showed its anti-tumor ability to human hepatoma (HepG2) cells. In vivo study, HC could reduce tumor weight and growth rate. The results indicated that HC nanospheres prepared by SPG had potential application as a sustained drug delivery system for the treatment of liver cancer. PMID:24593290

  10. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    SciTech Connect

    Lazarus, Kyren A.; Zhao, Zhe; Knower, Kevin C.; To, Sarah Q.; Chand, Ashwini L.; Clyne, Colin D.

    2013-08-30

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E{sub 2}), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E{sub 2}, showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E{sub 2} treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer.

  11. How I do it: Cone-beam CT during transarterial chemoembolization for liver cancer.

    PubMed

    Tacher, Vania; Radaelli, Alessandro; Lin, MingDe; Geschwind, Jean-François

    2015-02-01

    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. PMID:25625741

  12. 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

  13. MicroRNA-224 Induces G1/S Checkpoint Release in Liver Cancer

    PubMed Central

    An, Fangmei; Olaru, Alexandru V.; Mezey, Esteban; Xie, Qing; Li, Ling; Piontek, Klaus B.; Selaru, Florin M.

    2015-01-01

    Profound changes in microRNA (miR) expression levels are frequently found in liver cancers compared to the normal liver. In this study, we evaluate the expression of miR-224 in human HCC and CCA, as well as its downstream targets and affected pathways. We show that miR-224 is upregulated in a large cohort of human CCA, similar to its upregulation in human HCC. For the purpose of studying the roles of miR-224 in HCC and CCA, we enforced miR-224 expression in cells. mRNA arrays followed by Ingenuity Pathway Analysis (IPA)-identified putative molecules and pathways downstream of miR-224. Phenotypically, we report that enforced expression of miR-224 increases the growth rate of normal cholangiocytes, CCA cell lines, and HCC cell lines. In addition, we identified, in an unbiased fashion, that one of the major biologic processes affected by miR-224 is Gap1 (G1) to Synthesis (S) transition checkpoint release. We next identified p21, p15, and CCNE1 as downstream targets of miR-224 and confirmed the coordinated downregulation results in the increased phosphorylation of Retinoblastoma (Rb) with resulting G1/S checkpoint release. Our data suggest that miR-224 is a master regulator of cell cycle progression, and that its overexpression results in G1/S checkpoint release followed by accelerated cell growth. PMID:26343737

  14. Management of a Patient with Metastatic Colorectal Cancer and Liver Metastases

    PubMed Central

    Saif, Muhammad Wasif

    2014-01-01

    Liver metastases are commonly encountered in patients presenting with metastatic colorectal cancer (mCRC); resection is the treatment of choice. A number of systemic treatment options are currently available for such patients, including the use of 5-fluorouracil-based chemotherapies and oxaliplatin (e.g., FOLFOX) in combination with biologic agents that target angiogenesis (e.g., bevacizumab). For patients with progression following first-line treatment, current second-line options include a change in chemotherapy with bevacizumab (for patients who did or did not receive prior bevacizumab) or FOLFIRI in combination with aflibercept, a more recently approved antiangiogenesis therapy. Neurotoxicity is a well-established adverse event of oxaliplatin-based therapy. The current case details an mCRC patient with liver metastases who was treated with a capecitabine and oxaliplatin regimen (XELOX), and experienced two episodes of transient cortical blindness possibly related to oxaliplatin. After disease progression, the patient was switched to a regimen of FOLFIRI and aflibercept and did well on this second-line regimen. PMID:24744930

  15. 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. PMID:27174600

  16. microRNA 21-mediated suppression of Sprouty1 by Pokemon affects liver cancer cell growth and proliferation.

    PubMed

    Jin, Xiu-Li; Sun, Qin-Sheng; Liu, Feng; Yang, Hong-Wei; Liu, Min; Liu, Hong-Xia; Xu, Wei; Jiang, Yu-Yang

    2013-07-01

    Transcriptional repressor Pokemon is a critical factor in embryogenesis, development, cell proliferation, differentiation, and oncogenesis, thus behaving as an oncogene. Oncomine database suggests a potential correlation between the expressions of Pokemon and Sprouty1. This study investigated the regulatory role of Pokemon in Sprouty1 expression and the effect on liver cancer cell growth and proliferation, revealing a novel miR-21-mediated regulatory circuit. In normal (HL-7702) and cancer (QGY-7703) liver cell lines, Sprouty1 expression is inversely correlated with Pokemon levels. Targeted expression or siRNA-mediated silencing showed that Pokemon is a repressor of Sprouty1 expression at both mRNA and protein levels, but Pokemon cannot affect the promoter activity of Sprouty1. Sprouty1 is a target of miR-21 and interestingly, we found that miR-21 is up-regulated by Pokemon in liver cancer cells. Luciferase reporter assays showed that Pokemon up-regulated miR-21 transcription in a dose-dependent manner, and ChIP assay exhibited a direct binding of Pokemon to the miR-21 promoter at -747 to -399 bp. Site-directed mutagenesis of the GC boxes at -684 to -679 bp and -652 to -647 bp of miR-21 promoter abolished the regulatory activity by Pokemon. Furthermore, we found that the modulation of Pokemon and miR-21 expression affected the growth and proliferation of liver cancer cells QGY-7703. In summary, our findings demonstrate that Pokemon suppresses Sprouty1 expression through a miR-21-mediated mechanism, affecting the growth and proliferation of liver cancer cells. This study recognized miR-21 and Sprouty1 as novel targets of the Pokemon regulatory network. PMID:23355454

  17. Yttrium-90 radioembolization stops progression of targeted breast cancer liver metastases after failed chemotherapy

    PubMed Central

    Gordon, Andrew C.; Gradishar, William J.; Kaklamani, Virginia G.; Thuluvath, Avesh J.; Ryu, Robert K.; Sato, Kent T.; Gates, Vanessa L.; Salem, Riad; Lewandowski, Robert J.

    2016-01-01

    PURPOSE The purpose of this open-label, retrospective report was to determine the safety and effectiveness of locoregional therapy with yttrium-90 (90Y) radioembolization for patients with progressing breast cancer liver metastases (BCLM) despite polychemotherapy. MATERIALS & METHODS Seventy-five patients with progressing BCLM and stable extrahepatic disease were treated with radioembolization at our institution. Retrospective review of a prospectively collected database was performed to evaluate clinical and biochemical toxicities, tumor response, overall survival (OS), and time to progression (TTP). Radiologic response assessments included Response Evaluation Criteria in Solid Tumors in primary index lesions and metabolic activity on positron emission tomography. Univariate and multivariate analyses were performed. RESULTS 30-day mortality was 4% (n=3). Grade 3+ clinical toxicity and hyperbilirubinemia occurred in 7.6% (n=5) and 5.9% (n=4), respectively. The rate of partial response was 35.3% (n=24), 63.2% (n=43) had stable disease, and progressive disease occurred in 1.5% (n=1). PET imaging was available in 25 patients and 21 (84%) had a complete or partial response or stable disease. The median OS was 6.6mo (95% CI, 5.0 to 9.2mo). The hazard ratio (HR) for OS was .39 (95% CI, .23 to .66) for tumor burden <25% compared to greater tumor burden in multivariate analysis. Elevated bilirubin reduced OS. The HR for hepatic progression was .22 (95% CI, .05 to .98) for solitary compared to multifocal disease. CONCLUSIONS Locoregional therapy with 90Y radioembolization is safe and stops or delays the progression of targeted chemorefractory breast cancer liver metastases. Adverse prognosticators are identified. PMID:25156827

  18. Hong Kong Liver Cancer Staging System Is Associated With Better Performance for Hepatocellular Carcinoma

    PubMed Central

    Liu, Po-Hong; Hsu, Chia-Yang; Lee, Yun-Hsuan; Su, Chien-Wei; Hsia, Cheng-Yuan; Huang, Yi-Hsiang; Chiou, Yi-You; Lin, Han-Chieh; Huo, Teh-Ia

    2015-01-01

    Abstract Hong Kong Liver Cancer (HKLC) staging system was developed for prognostic and treatment evaluation for hepatocellular carcinoma (HCC) but is not externally validated. We aimed to evaluate and compare HKLC system with Barcelona Clínic Liver Cancer (BCLC) staging system. The prognostic performance, discriminatory ability, and efficacy of treatment recommendations were compared between the BCLC and HKLC systems. Significant differences in survival were found across all stages of BCLC and across stages I to IV of HKLC systems (P < 0.01). HKLC system was associated with higher homogeneity in prognostic accuracy. The survival was similar between patients treated according to the HKLC or BCLC system (P = 0.07). However, more patients were treated according to HKLC recommendations than to BCLC recommendations (57% vs. 47%, P < 0.001). In a hypothetical cohort created by random sampling, patients treated according to the HKLC scheme had better survival compared with patients treated according to the BCLC system (P < 0.001). Subgroup analyses between hepatitis B virus (HBV) and hepatitis C virus (HCV)-related HCC were performed. More HCV-related HCC were at earlier BCLC or HKLC stages (both P < 0.001). The HKLC system was more informative with greater homogeneity in predicting survival in both HBV and HCV cohorts. However, HKLC treatment recommendations were associated with better long-term survival only in HBV-related HCC but not in HCV-related HCC (P < 0.001 and P = 0.79, respectively). In conclusion, we provided external validation of the HKLC system. Compared with the BCLC system, the HKLC system has better prognostic accuracy and therapeutic efficacy in the entire cohort and in HBV-related HCC but not in HCV-related HCC. Due to high heterogeneity among patients of various etiologies, staging and treatment strategies tailored to specific HCC etiology are required. PMID:26469917

  19. Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases

    PubMed Central

    Raff, Evan J.; Kakati, Donny; Bloomer, Joseph R.; Shoreibah, Mohamed; Rasheed, Khalid; Singal, Ashwani K.

    2015-01-01

    Background and Aims Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease. Diabetes mellitus (DM) is a common comorbidity among NAFLD patients. We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD. Methods Medical charts of 480 patients with ALD or NAFLD (2004–2011) managed at a tertiary center were retrospectively reviewed. NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d. ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5 years. Results Of 480 patients (307 NAFLD), 200 diabetics differed from nondiabetics for: age (52±11 vs. 49±11 years; p=0.004); male gender (48% vs. 57%; p=0.03); metabolic syndrome (49% vs. 30%; p=0.0002); NAFLD (80% vs. 56%; p<0.0001); cirrhosis (70% vs. 59%; p=0.005); and hepatocellular carcinoma (HCC; 8% vs. 3%; p=0.009). Over a 3 year median follow-up period, diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs. 41%; p=0.022) and HCC (27% vs. 10%; p=0.045). There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs. 39%; p=0.053), and there was no difference between the two groups in survival or other liver disease complications. Conclusions DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD. Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics. PMID:26356325

  20. The Nlrp3 Inflammasome Suppresses Colorectal Cancer Metastatic Growth in the Liver by Promoting Natural Killer Cell Tumoricidal Activity.

    PubMed

    Dupaul-Chicoine, Jeremy; Arabzadeh, Azadeh; Dagenais, Maryse; Douglas, Todd; Champagne, Claudia; Morizot, Alexandre; Rodrigue-Gervais, Ian Gaël; Breton, Valérie; Colpitts, Sara L; Beauchemin, Nicole; Saleh, Maya

    2015-10-20

    The crosstalk between inflammation and tumorigenesis is now clearly established. However, how inflammation is elicited in the metastatic environment and the corresponding contribution of innate immunity pathways in suppressing tumor growth at secondary sites are poorly understood. Here, we show that mice deficient in Nlrp3 inflammasome components had exacerbated liver colorectal cancer metastatic growth, which was mediated by impaired interleukin-18 (IL-18) signaling. Control of tumor growth was independent of differential cancer cell colonization or proliferation, intestinal microbiota effects, or tumoricidal activity by the adaptive immune system. Instead, the inflammasome-IL-18 pathway impacted maturation of hepatic NK cells, surface expression of the death ligand FasL, and capacity to kill FasL-sensitive tumors. Our results define a regulatory signaling circuit within the innate immune system linking inflammasome activation to effective NK-cell-mediated tumor attack required to suppress colorectal cancer growth in the liver. PMID:26384545

  1. Volume change of segments II and III of the liver after gastrectomy in patients with gastric cancer

    PubMed Central

    Ozutemiz, Can; Obuz, Funda; Taylan, Abdullah; Atila, Koray; Bora, Seymen; Ellidokuz, Hulya

    2016-01-01

    PURPOSE We aimed to evaluate the relationship between gastrectomy and the volume of liver segments II and III in patients with gastric cancer. METHODS Computed tomography images of 54 patients who underwent curative gastrectomy for gastric adenocarcinoma were retrospectively evaluated by two blinded observers. Volumes of the total liver and segments II and III were measured. The difference between preoperative and postoperative volume measurements was compared. RESULTS Total liver volumes measured by both observers in the preoperative and postoperative scans were similar (P > 0.05). High correlation was found between both observers (preoperative r=0.99; postoperative r=0.98). Total liver volumes showed a mean reduction of 13.4% after gastrectomy (P = 0.977). The mean volume of segments II and III showed similar decrease in measurements of both observers (38.4% vs. 36.4%, P = 0.363); the correlation between the observers were high (preoperative r=0.97, P < 0.001; postoperative r=0.99, P < 0.001). Volume decrease in the rest of the liver was not different between the observers (8.2% vs. 9.1%, P = 0.388). Time had poor correlation with volume change of segments II and III and the total liver for each observer (observer 1, rseg2/3=0.32, rtotal=0.13; observer 2, rseg2/3=0.37, rtotal=0.16). CONCLUSION Segments II and III of the liver showed significant atrophy compared with the rest of the liver and the total liver after gastrectomy. Volume reduction had poor correlation with time. PMID:26899148

  2. Overexpression of eIF4E in colorectal cancer patients is associated with liver metastasis

    PubMed Central

    Xu, Tao; Zong, Yuanyuan; Peng, Lipan; Kong, Shuai; Zhou, Mingliang; Zou, Jianqiang; Liu, Jinglei; Miao, Ruizheng; Sun, Xichao; Li, Leping

    2016-01-01

    Purpose Liver metastasis is one of the leading causes of death in colorectal cancer (CRC) patients. The present study aimed to evaluate the value of eIF4E as a prognostic marker of colorectal liver metastasis (CLM) and identify the functional role of eIF4E in CRC metastasis. Patients and methods The expression level of eIF4E in CRC tissues was analyzed by immunohistochemical staining and Western blot. Expression of eIF4E in CRC cell lines was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Cell Counting Kit-8 (CCK-8) and Transwell assays were performed to assess the effects of eIF4E on cell proliferation, migration, and invasion. Western blot was further used to investigate the mechanism of eIF4E in tumor metastasis. Results The upregulation frequency of eIF4E in the CLM group (82.5%) was higher than that in the non-CLM group (65.0%). Of the 80 patients recruited for the follow-up study, 23 were in the low eIF4E group (ratio of tumor to nontumor tissue liver metastasis (47.4%) than the group exhibiting low eIF4E expression (13.0%). In CRC cell lines, the expression of eIF4E was higher than in the normal cells. In vitro functional studies indicated that eIF4E knockdown inhibited the proliferation, migration, and invasion of Lovo and SW480 cells, and suppressed the expression of cyclin D1, VEGF, MMP-2, and MMP-9. Conclusion The results of the present study indicated that high eIF4E levels in CRC patients predicted a high risk of liver metastasis. Knockdown of eIF4E inhibited CRC cell metastasis in part through regulating the expression of cyclin D1, VEGF, MMP-2, and MMP-9. PMID:26929650

  3. The Oncosurgery Approach to Managing Liver Metastases from Colorectal Cancer: A Multidisciplinary International Consensus

    PubMed Central

    De Gramont, Aimery; Figueras, Joan; Guthrie, Ashley; Kokudo, Norihiro; Kunstlinger, Francis; Loyer, Evelyne; Poston, Graeme; Rougier, Philippe; Rubbia-Brandt, Laura; Sobrero, Alberto; Tabernero, Josep; Teh, Catherine; Van Cutsem, Eric

    2012-01-01

    An international panel of multidisciplinary experts convened to develop recommendations for the management of patients with liver metastases from colorectal cancer (CRC). The aim was to address the main issues facing the CRC hepatobiliary multidisciplinary team (MDT) when managing such patients and to standardize the treatment patients receive in different centers. Based on current evidence, the group agreed on a number of issues including the following: (a) the primary aim of treatment is achieving a long disease-free survival (DFS) interval following resection; (b) assessment of resectability should be performed with high-quality cross-sectional imaging, staging the liver with magnetic resonance imaging and/or abdominal computed tomography (CT), depending on local expertise, staging extrahepatic disease with thoracic and pelvic CT, and, in selected cases, fluorodeoxyglucose positron emission tomography with ultrasound (preferably contrast-enhanced ultrasound) for intraoperative staging; (c) optimal first-line chemotherapy—doublet or triplet chemotherapy regimens combined with targeted therapy—is advisable in potentially resectable patients; (d) in this situation, at least four courses of first-line chemotherapy should be given, with assessment of tumor response every 2 months; (e) response assessed by the Response Evaluation Criteria in Solid Tumors (conventional chemotherapy) or nonsize-based morphological changes (antiangiogenic agents) is clearly correlated with outcome; no imaging technique is currently able to accurately diagnose complete pathological response but high-quality imaging is crucial for patient management; (f) the duration of chemotherapy should be as short as possible and resection achieved as soon as technically possible in the absence of tumor progression; (g) the number of metastases or patient age should not be an absolute contraindication to surgery combined with chemotherapy; (h) for synchronous metastases, it is not advisable to

  4. Curative two-stage resection for synchronous triple cancers of the esophagus, colon, and liver: Report of a case

    PubMed Central

    Akiyama, Yuji; Iwaya, Takeshi; Konosu, Masafumi; Shioi, Yoshihiro; Endo, Fumitaka; Katagiri, Hirokatsu; Nitta, Hiroyuki; Kimura, Toshimoto; Otsuka, Koki; Koeda, Keisuke; Kashiwaba, Masahiro; Mizuno, Masaru; Kimura, Yusuke; Sasaki, Akira

    2015-01-01

    Introduction Cases of synchronous triple cancers of the esophagus and other organs curatively resected are rare. Presentation of case A 73-year-old man was admitted to our hospital with bloody feces. He was diagnosed with synchronous triple cancers of the esophagus, colon, and liver. We selected a two-stage operation to safely achieve curative resection for all three cancers. The first stage of the operation comprised a laparoscopy-assisted sigmoidectomy and partial liver resection via open surgery. The patient was discharged without complications. Thirty days later, he was readmitted and thoracoscopic esophagectomy was performed. Although pneumonia-induced pulmonary aspiration occurred as a postoperative complication, it was treated conservatively. The patient was discharged on postoperative day 24. Discussion Esophagectomy is a highly invasive procedure; thus, simultaneous surgery for plural organs, including the esophagus, may induce life-threatening, severe complications. Two-stage surgery is useful in reducing surgical stress in high-risk patients. For synchronous multiple cancers, the planning of two-stage surgery should be considered for each cancer to maintain organ function and reduce the stress and difficulty of each stage. Conclusion We successfully treated synchronous triple cancers, including esophageal cancer, by a two-stage operation. PMID:26074482

  5. Involvement of serum retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers in Hungary

    PubMed Central

    Mózsik, Gyula; Rumi, György; Dömötör, András; Figler, Mária; Gasztonyi, Beáta; Papp, Előd; Pár, Alajos; Pár, Gabriella; Belágyi, József; Matus, Zoltán; Melegh, Béla

    2005-01-01

    AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers. METHODS: The changes in serum levels of retinoids (vitamin A, α- and β-carotene, α- and β-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in matched groups) for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used. RESULTS: The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of α- and β-carotene, α- and β-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer. CONCLUSION: Retinoids (as environmental factors) are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer. PMID:16437692

  6. Differential TGFβ pathway targeting by miR-122 in humans and mice affects liver cancer metastasis

    PubMed Central

    Yin, Shenyi; Fan, Yu; Zhang, Hanshuo; Zhao, Zhihua; Hao, Yang; Li, Juan; Sun, Changhong; Yang, Junyu; Yang, Zhenjun; Yang, Xiao; Lu, Jian; Xi, Jianzhong Jeff

    2016-01-01

    Downregulation of a predominantly hepatocyte-specific miR-122 is associated with human liver cancer metastasis, whereas miR-122-deficient mice display normal liver function. Here we show a functional conservation of miR-122 in the TGFβ pathway: miR-122 target site is present in the mouse but not human TGFβR1, whereas a noncanonical target site is present in the TGFβ1 5′UTR in humans and other primates. Experimental switch of the miR-122 target between the receptor TGFβR1 and the ligand TGFβ1 changes the metastatic properties of mouse and human liver cancer cells. High expression of TGFβ1 in human primary liver tumours is associated with poor survival. We identify over 50 other miRNAs orthogonally targeting ligand/receptor pairs in humans and mice, suggesting that these are evolutionarily common events. These results reveal an evolutionary mechanism for miRNA-mediated gene regulation underlying species-specific physiological or pathological phenotype and provide a potentially valuable strategy for treating liver-associated diseases. PMID:26987776

  7. [Hepatic Resection of Multiple Liver Metastases from Gastric Cancer after Molecular Targeted Chemotherapy(S-1 plus Cisplatin plus Trastuzumab)].

    PubMed

    Kim, Yongkook; Hosoda, Yohei; Nishino, Masaya; Okano, Miho; Kawada, Junji; Yamasaki, Masaru; Nagai, Ken-ichi; Yasui, Masayosi; Okuyama, Masaki; Tsujinaka, Toshimasa

    2015-11-01

    A 62-year-old man was diagnosed with gastric cancer and underwent distal gastrectomy, and D1+b lymph node dissection. He was diagnosed postoperatively with T1b (sm2) N0M0, StageⅠA gastric adenocarcinoma and did not receive any adjuvant chemotherapy after surgery. One year and 6 months after gastrectomy, blood analysis indicated high levels of carcinoembryonic antigen (CEA 262.1 ng/mL) while abdominal computed tomography (CT) revealed multiple liver tumors (S7: 15 mm, S7/8: 20 mm). The patient was diagnosed with metachronous multiple liver metastases from gastric cancer. Chemotherapy, combined with molecular targeted therapy (S-1 plus cisplatin [CDDP] plus trastuzumab), was administered because of overexpression of the human epidermal growth factor receptor 2 (HER2) protein in the primary tumor as assessed by immunohistochemistry, the CEA levels decreased immediately after 2 cycles of the chemotherapy, and the liver metastases shrank markedly with no evidence of new lesions on abdominal CT. However, after treatment, Grade 3 neutropenia and diarrhea were observed. Chemotherapy was suspended and hepatic resection was performed. After hepatic resection, the liver tumors were histologically evaluated as Grade 2 metastatic gastric adenocarcinoma, and the HER2 expression of remnant carcinoma cells was established. The patient has been in good health and remained free of recurrences in the 2 years and 3 months after the liver resection. Surgery with preoperative chemotherapy (S-1 plus CDDP plus trastuzumab) can be an effective treatment for liver metastasis from HER2-positive gastric cancer. PMID:26805121

  8. Zhx2 and Zbtb20: Novel regulators of postnatal alpha-fetoprotein repression and their potential role in gene reactivation during liver cancer

    PubMed Central

    Peterson, Martha L.; Ma, Chunhong; Spear, Brett T.

    2012-01-01

    The mouse alpha-fetoprotein (AFP) gene is abundantly expressed in the fetal liver, normally silent in the adult liver but is frequently reactivated in hepatocellular carcinoma. The basis for AFP expression in the fetal liver has been studied extensively. However, the basis for AFP reactivation during hepatocarcinogenesis is not well understood. Two novel factors that control postnatal AFP repression, Zhx2 and Zbtb20, were recently identified. Here, we review the transcription factors that regulate AFP in the fetal liver, as well as Zhx2 and Zbtb20, and raise the possibility that the loss of these postnatal repressors may be involved in AFP reactivation in liver cancer. PMID:21216289

  9. Serum Starvation Induces DRAM Expression in Liver Cancer Cells via Histone Modifications within Its Promoter Locus

    PubMed Central

    Chen, Changqiang; Wang, Jiayi; Liu, Xiangfan; Hu, Yiqun; Fan, Qishi; Hou, Zhaoyuan; Lu, Yang

    2012-01-01

    DRAM is a lysosomal membrane protein and is critical for p53-mediated autophagy and apoptosis. DRAM has a potential tumor-suppressive function and is downregulated in many human cancers. However, the regulation of DRAM expression is poorly described so far. Here, we demonstrated that serum deprivation strongly induces DRAM expression in liver cancer cells and a core DNA sequence in the DRAM promoter is essential for its responsiveness to serum deprivation. We further observed that euchromatin markers for active transcriptions represented by diacetyl-H3, tetra-acetyl-H4 and the trimethyl-H3K4 at the core promoter region of DRAM gene are apparently increased in a time-dependent manner upon serum deprivation, and concomitantly the dimethyl-H3K9, a herterochromatin marker associated with silenced genes, was time-dependently decreased. Moreover, the chromatin remodeling factor Brg-1 is enriched at the core promoter region of the DRAM gene and is required for serum deprivation induced DRAM expression. These observations lay the ground for further investigation of the DRAM gene expression. PMID:23251372

  10. Low-density lipoprotein-mediated delivery of docosahexaenoic acid selectively kills murine liver cancer cells

    PubMed Central

    Reynolds, Lacy; Mulik, Rohit S.; Wen, Xiaodong; Dilip, Archana; Corbin, Ian R.

    2014-01-01

    Aim The natural omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has recently been credited for possessing anticancer properties. Herein, we investigate the cytotoxic actions of DHA-loaded low-density lipoprotein (LDL) nanoparticles in normal and liver cancer cells. Materials & methods LDL-DHA nanoparticles were prepared and subjected to extensive biophysical characterization. The therapeutic utility of LDL-DHA nanoparticles was evaluated in normal and malignant murine hepatocyte cell lines, TIB-73 and TIB-75, respectively. Results & discussion The engineered LDL-DHA nanoparticles possessed enhanced physical and oxidative stabilities over native LDL and free DHA. Dose–response studies showed that therapeutic doses of LDL-DHA nanoparticles that completely killed TIB-75 were innocuous to TIB-73. The selective induction of lipid peroxidation and reactive oxygen species in the cancer cells was shown to play a central role in LDL-DHA nanoparticle-mediated cytotoxicity. Conclusion In summary, these findings indicate that LDL-DHA nanoparticles show great promise as a selective anticancer agent against hepatocellular carcinoma. PMID:24397600

  11. New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges.

    PubMed

    Cong, Wen-Ming; Wu, Meng-Chao

    2015-11-01

    Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional