Liver Cancer News 2010
HLA-DRB1 allele polymorphisms have been reported to be associated with liver cancer susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to explore whether specific HLA-DRB1 alleles (DRB1*07, DRB1*12, DRB1*15) confer susceptibility to liver cancer.
Hepatologists at the University of Florida have begun a new clinical trial in search of a better way to treat patients who have advanced, inoperable primary liver cancer but have trouble tolerating standard doses of the only drug available to help them.
Black Americans with early-stage liver cancer are more likely to die of the disease than Asian, Hispanic or white patients, say researchers. The team at the University of Michigan, Ann Arbor, analyzed U.S. National Cancer Institute data about 13,244 patients diagnosed with stage 1 or 2 liver cancer between 1995 and 2006.
Researchers from Italy determined that radiofrequency ablation (RFA) is a safe and effective therapy for managing liver cancer in cirrhotic patients. The high repeatability of RFA is advantageous in controlling recurrences of cancerous tumors in the liver. Results of this 10-year retrospective study are available in the January 2011 issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).
Liver transplants are now standard therapy for selected liver cancer patients, but members of the UM/Jackson team know too well that about 20 percent of transplant patients – 15 percent at the Miami Transplant Institute – with primary liver cancer end up dying from a recurrence of the cancer in the replacement liver. The reason, they believe, is that cancer cells remain in the bloodstream even when the tumors are removed or destroyed, or the diseased organ replaced. So Andreas Tzakis, M.D., Ph.D., professor of surgery and director of the Institute’s Liver/GI Transplant Program, said the team was intrigued by the clinical trial in Japan led by Masahiro Ohira, M.D., Ph.D., that showed naturally occurring NK cells extracted from a healthy liver and enhanced to four times their potency in the lab act like smart bombs. When injected into the bloodstream, they hone in on and destroy any lingering cancer cells. They also have the added bonus of being 10 times more aggressive against the hepatitis C virus.
Ligands of Peroxisome proliferator-activated receptor gamma (PPARg) can inhibit growth and promote apoptosis in various cancer cells, and thus have the potential to be utilized as anticancer drugs. This potential however, has been seriously challenged by observations that they can lead to tumor promotion in some cancer models, possibly due to activation of different signaling mechanisms in various tumor environments.
Peregrine Pharma Begins Phase I/II Investigator-Sponsored Trial in Liver Cancer
1 December 2010
Peregrine Pharmaceuticals is a clinical-stage biopharmaceutical company. Their Phase I/II trial will treat patients with Peregrine’s investigational monoclonal antibody bavituximab in combination with sorafenib. Approximately 50 patients will be enrolled in this trial to determine the maximum tolerated dose of bavituximab in patients with advanced liver cancer who were treated with sorafenib, and the radiographic median time to progression.
Studies Reconfirm Significant Benefits Regarding the Use of SIR-Spheres(R) Microspheres for the Treatment of Inoperable Liver Tumors
30 November 2010
Selective Internal Radiation Therapy (SIRT), also known as radioembolization, is a minimally-invasive treatment using millions of radioactive microspheres, used to target liver tumors. Studies reconfirmed evidence from earlier research that established “significant clinical benefits from the use of targeted radioactive SIR-Spheres microspheres as an effective option for patients. SIRFLOX is the first prospective randomized study looking at SIR-Spheres microspheres in combination with standard therapy for first line treatment, FOLFOX6 with or without bevacizumab.
Cutting Edge Liver Cancer Treatment Comes to Toledo
30 November 2010
Liver radioembolization, an innovative technology, is being used in the fight against liver cancer. “The procedure requires getting into the hepatic artery in the liver and injecting small particles with high levels of radiation directly into the tumors and destroying the tumors from the inside out,” explains Dr. Wade Banker, an interventional radiologist from University of Mississippi. The procedure takes about half an hour, and it can be done multiple times.
FDA Approves Merit Medical’s High Quality Clinical Trial Protocol for the Treatment of Primary Liver Cancer
29 November 2010
The FDA has approved Merit Medical Systems, Inc.’s phase 3 clinical trial protocol to treat primary liver cancer with QuadraSphere™ Microspheres (hqTACE) for delivery of doxorubicin. Drug-eluting embolization treats liver cancer through the dual action of delivering chemotherapy into the tumors while also cutting off the blood supply that supports them. QuadraSphere adds to embolization therapy by ionically binding the doxorubicin throughout the microspheres and eluting it into the cancer in a sustained manner. This way, more drugs can be delivered into the tumor, with less escaping into peripheral circulation.
Alpha-1-acid Glycoprotein as Potential Biomarker for Alpha-fetoprotein-low Liver Cancer
23 November 2010
The outcome of patients with liver cancer remains poor because of late diagnosis so researchers determined to test the performances of alpha -1-acid glycoprotein (AAG) and des-gamma-carboxy prothrombin (DCP) for the diagnosis of liver cancer, especially for alpha-fetoprotein (AFP)-low liver cancer. When all patients with liver cancer were evaluated, the area under receiver operating characteristic (ROC) curves for AAG and DCP were similar. Higher sensitivity was obtained from DCP in discriminating liver cancer patients with low AFP than that in high AFP.
EDDA Technology Introduces IQQA(R)-Liver Suite to Provide Dedicated Total Solutions for Liver Cancer Diagnosis and Treatment Management
23 November 2010
EDDA Technology, Inc. is an innovative clinical computer solution provider in healthcare imaging and analysis. For better healthcare and patient management, the IQQA®-Liver Suite aims to enhance efficiency and precision in liver disease diagnosis, pre-operative treatment planning, intra-operative guidance, post-surgical assessment and follow-up. At the core of the suite is an advanced 4-D image quantitative evaluation system.
Using Lasers to Treat Kidney and Liver Tumors
22 November 2010
Doctors at the Mayo Clinic are using a process known as MRI-guided laser ablation to fight kidney and liver tumors. Eric Walser is an interventional radiologist with the Mayo Clinic in Florida, and says the process makes it possible for doctors to target and destroy tumors without damaging the rest of the organ. The MRI machine can measure the temperature inside the tumor, heating it to the point of destruction.
Symptoms of Liver Cancer
22 November 2010
Research points out that the symptoms of liver cancer are visible only in the advanced stage. Symptoms include, lack of bile and digestive enzymes that causes nausea and vomiting, loss of appetite and unintended weight loss, and the abdomen of liver cancer patients swells.
Apricus, FDA Agree on Liver Cancer Drug Study
22 November 2010
Apricus is testing a drug candidate called PrevOnco as a treatment for advanced, inoperable liver cancer. One of the components in PrevOnco is lansoprazole, the main ingredient in the heartburn drug Prevacid. Apricus said it will conduct a one- to two-year study on around 218 patients with advanced liver cancer. If the study is successful, it will be the basis of Apricus’ application for marketing approval.
Less Invasive Surgery Works for Liver Too
18 November 2010
People who undergo surgery to remove benign or cancerous tumors in their liver appear to fare better when they receive a newer type of surgery that makes only small incisions. Two research teams tried to gauge how laparoscopy, type of surgery in which doctors make a few small incisions, compared with traditional surgery, in which they make one long cut to enter the body. Many surgeons continue to rely on larger incisions that enable them to visualize the liver directly, but that is often because they aren’t trained in laparoscopy, said Dr. David Geller, who led the University of Pittsburgh team. Patients who received it spent two to three days less recovering in the hospital.
Combination Therapy Improves Survival Time for Patients with Advanced Liver Cancer
16 November 2010
Ghassan K. Abou-Alfa, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues conducted a randomized, phase 2 study of doxorubicin plus sorafenib and doxorubicin plus placebo in patients with advanced LIVER CANCER. Median overall survival was 13.7 months among patients treated with doxorubicin plus sorafenib vs. 6.5 months among those who received doxorubicin plus placebo.
Pain Linked with Poorer Prognosis in Liver Cancer
12 November 2010
Pain at presentation may indicate a worse prognosis for patients with liver cancer. Brian I. Carr, M.D., and Lynette A. Pujol, Ph.D., of Thomas Jefferson University in Philadelphia, examined patients with unresectable cancer to determine prognostic and clinical correlations. The researchers found 760 patients with pain and 2,657 without pain, and determined that those with pain at presentation had a worse prognosis and more adverse tumor characteristics than those who did not have pain.
Study Suggests Way to Treat Liver Cancer
11 November 2010
Researchers at the Emory University School of Medicine have shown that adiponectin, a hormone produced by fat cells to regulate the body’s metabolic processes, can help detect and cure liver cancer. The researchers found that adiponectin levels can help predict tumor development and size. Treatments that imitate the effects of adiponectin, such as those found in green tea, could help increase chances of survival for obese liver cancer patients.
For Liver Cancer Patients, PGI Offers Ray of Hope in Nuclear Therapy
11 November 2010
The departments of the Post-Graduate Institute of Medical Education and Research (PGIMER), will start treating liver cancer patients in a combined way. The procedure, called ‘intra arterial radio nuclear therapy’, will treat even those patients whose liver cancer has reached an advanced stage. Radioactive material will be deposited directly into the tumor sparing the healthy surrounding tissue.
Celsion Receives COMP Recommendation for Orphan Drug Designation in Europe for ThermoDox(R) to Treat Primary Liver Cancer
11 November 2010
The European Medicines Agency (EMA) has issued a positive opinion on the application for Orphan Drug Designation for ThermoDox® for the treatment of liver cancer. This delivery technology enables high concentrations of doxorubicin to be deposited directly in a targeted tumor. ThermoDox® is currently being evaluated under a Special Protocol Assessment with the FDA in a 600 patient, Phase III trial.
JNM: PET/CT + 18F-fluorocholine bests 18F-FDG for Liver Cancer Detection
10 November 2010
PET/CT with 18F-fluorocholine was significantly more sensitive that 18F-FDG at detecting liver cancer. Jean-Noël MD, PhD, from the department of nuclear medicine, Hopital Tenon, AP-HP and Universite´ Pierre et Maris Curie in Paris, and colleagues performed the prospective study to compare the diagnostic performance of PET/CT with 18F-fluorocholine and 18F-FDG for detecting and staging liver cancer. Eighty-one patients were recruited for the study and standard of truth was determined in 59 cases.
Locally advanced (pT3-4N0M0) liver cancer is a heterogeneous group of tumors. Scientists retrospectively reviewed 298 patients with pT3-4N0M0 HCC who underwent hepatic resection from 1993 to 2000 in an academic tertiary hospital, and cumulative recurrence rate (CRR) and the overall survival (OS) of the liver cancer patients were compared. No significant differences were observed in OS or CRR between the latter three groups of patients. There is a need to redefine the T classification and to stratify locally advanced liver cancer.
Celsion Corporation, a leading oncology drug development company has a Phase III study underway called the HEAT study, involving its investigational drug, ThermoDox®, in combination with radiofrequency ablation (RFA). ThermoDox, a proprietary heat-activated liposomal encapsulation of doxorubicin, is currently being evaluated under a Special Protocol Assessment (SPA) agreement with the FDA in this global Phase III trial in patients with non-resectable liver cancer. Their plan is to enroll a total of 600 patients to fully complete the study.
A research team led by Hanning You, M.D., Ph.D., postdoctoral fellow working in the laboratory of C. Bart Rountree, M.D., at the Pennsylvania State University College of Medicine, Hershey, Pa. presented study results at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development which showed that targeting c-Met may be a promising personalized treatment method for approximately 45 percent of patients with liver cancer who have c-Met-positive tumors. c-Met inhibitor stopped proliferation and tumor growth of metastatic HCC cell. They also found that results of a separate meta-analysis of six studies and 1,051 patients showed that c-Met activation is associated with poor prognosis in HCC.
Researchers led by Andrew Duncan, Ph.D., principal investigator and postdoctoral researcher at the Children’s Hospital at Oregon Health & Science University have discovered that a form of cell division typically associated with cancer called multipolar mitosis can yield diverse, viable cells capable of protecting the liver from injury and poisonous substances. Duncan and colleagues’ work suggests that in response to liver injury that is toxic to most hepatocytes, a subset of select hepatocytes may respond favorably, thereby preventing liver failure and ensuring survival of the organism.
Scientists have observed and have assessed a serum protein, vascular adhesion protein-1 (VAP-1), as a newly postulant biomarker for hepatocellular cancer in patients with a history of alcoholic and non-alcoholic fatty liver diseases. After sampling 55 patients with liver cancer they found that there was a significant difference in mean VAP-1 levels between groups. Serum VAP-1 levels were found higher in patients with hepatocellular cancer (primary liver cancer). Thus, the serum level of sVAP-1 might be a beneficial marker of disease activity in chronic liver diseases.
Hepatoma-derived growth factor (HDGF) is involved in the beginning growth of liver cancer. A study that examined the HDGF expression in HCC, the signs and symptoms of HCC survival patients, and the biological processes regulated by HDGF found that the level of HDGF was much higher in HCC tissues than in normal liver tissues. In addition, patients with higher HDGF expression showed shorter overall survival time that those with low HDGF expression.
A pilot trial enrolled nine patients to be treated with a combination of JX-594 and sorafenib and presented positive results. Jennerex developed JX-594, and it works by targeting and destroying cancer cells through the blood supply to the tumors. It has shown to induce tumor shrinkage and necrosis, and be well tolerated in Phase I and Phase II clinical trials. When used in conjunction with sorafenib a majority of the patients saw a stabilization with the tumors and both drugs were well tolerated.
Kowa Company, Ltd. reported results of a Phase II/III trial showed that high dose peretinoin (NIK-333) which showed to reduce the recurrence of primary liver cancer aka hepatocellular carcinoma (HCC) after surgical resection or ablation in hepatitis C virus (HCV) positive patients when compared to placebo. Peretinoin is the oral acyclic retinoid with vitamin A-like structure, and its main targeting molecule is the retinoid nuclear receptor. Based on the results of the trial, Kowa is moving forward to obtain regulatory approval to produce and market peretinoin.
Researchers with the UC Davis School of Medicine found that among Asian-Americans living in California, Laotian/Hmong-Americans have the lowest survival rates for the most common type of liver cancer. The study used California Cancer Registry data from more than 6,000 Asian-American patients diagnosed with HCC between 1988 and 2007. The Laotian-Hmong have the worst survival rates for liver cancer, between one to two times greater than the aggregate of the Asian-American groups. Researchers also discovered that Laotian/Hmong were far more likely to be diagnosed with cancer at later stages of the disease.
Jennerex, a biotherapeutics company has developed JX-594 for the treatment of solid tumors. JX-594 is an engineered oncolytic virus that is designed to selectively target and destroy cancer cells. Jennerex has given Transgene, a bio-pharmaceutical company specialized in the development of immunotherapeutic products, the rights to develop and commercialize JX-594 in Europe, the CIS, and the Middle East. The development plan will focus initially on liver cancer, both in first line and in second line.
An innovative therapy called radioembolization, precisely targets the tumor with radiation. It was developed over 18 months ago by doctors at the Radiology and Imaging Diagnostics Unit of the Ministry of Internal Affairs and Administration’s Central Research Hospital in Warsaw. The therapy involves the use of radioactive isotopes, specifically the yttrium isotope (90Y), but now doctors are experimenting with rhenium (188Re). The radioactive material is injected directly to the vessels supplying the tumor with blood without destroying the surrounding healthy tissues.
Thymostimulin is a peptide that is toxic to liver cancer (HCC) and palliative efficacy, or any form of medical care or treatment that concentrates on reducing the severity of the disease, rather than striving to stop progression. IN two independent phase II trials thymostimulin was found effective, however in a phase III trial no evidence of any benefiting the treatment of advanced HCC was found.
Scientist We investigated in vitro the effect of salirasib on cell growth as well as its mechanism of action in human hepatoma cell lines. Salirasib induced growth inhibition in hepatocarcinoma cells through inhibition of proliferation and partially through induction of apoptosis. In vivo, salirasib reduced tumor growth from the fifth day and onwards. After 12 days of treatment, mean tumor weight was diminished by 56 percent in the treated animals. The therapeutic potential of salirasib in human liver cancer was further confirmed in a subcutaneous xenograft model.
Many studies have shown that obesity is associated with liver cancer aka hepatocellular carcinoma (HCC). This study investigated the biological actions regulated by leptin, the obesity biomarker molecule, and its receptors in HCC and the correlation between leptin and the human telomerase reverse transcriptase (hTERT), a known mediator of cellular immortalization. It was found that leptin could affect HCC progression and invasion.
The National Health Service (NHS), a publicly funded healthcare system in England, is being urged to offer a free pharmacy test for hepatitis B and C. Death rates from hepatitis are rising, said Charles Gore, chief executive of the Hepatitis C Trust. The trust, with the Royal Pharmaceutical Society, is calling for primary care trusts to find the necessary funds to pay pharmacies to offer the tests to customers.
A recent study investigates the distribution and significance of mobilized endothelial progenitor cells (EPCs), which are a population of rare cells that circulate in the blood and have the ability to differentiate into cells that make up the lining of blood vessels. EPCs are important in tumor growth and metastasis. Both liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT.
A research team from the Massachusetts General Hospital said that the protein called merlin, which is encoded by the NF2 gene, controls the activity of adult stem cells that give rise to the two major types of liver cells. Merlin, a protein that is involved in a rare hereditary cancer syndrome is now thought to regulate the development of liver cancer. After a liver transplant, the recipient’s body would normally produce liver cells to grow the new liver to a functioning size. In was found that mice lacking functioning NF2 in their livers developed dramatic overgrowth of liver stem cells, leading to the development of liver cancer.
Liver Cancer Clinical Trial Priorities Assessed NCI Clinical Trials Planning Meeting Urges Research on First-line Therapies, Prognostic Indicators
Melanie B. Thomas, M.D., of the Medical University of South Carolina in Charleston, and colleagues believe that new prognostic indicators and effective therapies should be a priority as recommended of the National Cancer Institute Clinical Trials Planning Meeting. Dr. Thomas and associates evaluated current staging, prognostic, and treatment approaches and were able to identify key knowledge gaps. Their recommendations included using sorafenib as a first-line drug in clinical trials.
A New Role of Glypican-3 in Hepatocellular Carcinoma
The research team led by Dr. Hiroyuki Yamamoto of Sapporo Medical University in Japan analyzed glypican-3 (GPC3) expression, a highly expressed growth molecule in HCC. It is thought that GPC3 joins a multiprotein complex, which is composed of the ligand, receptor, GPC3, and probably other proteins. This is the first study to report that GPC3, in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.
Liver Cancer Treatments
A treatment called percutaneous hepatic perfusion (PHP) allows doctors to give very high doses of chemotherapy localized at the liver. Dr. Mark Faries, director of translational tumor immunology at the John Wayne Cancer Institute in Santa Monica, uses catheters to deliver ten times the normal amount of chemotherapy to the liver. Two balloons block the chemo from flowing through the rest of the body. In one study, 80 percent of patients saw their tumors shrink or stabilize.
‘Ablate and Wait’ Effective for Hepatocellular Carcinoma Ablation
John P. Roberts, M.D., of the University of California in San Francisco and colleagues write of the “ablate and wait” strategy for improving the five-year recurrence-free outcome of liver transplantation in patients with liver cancer (HCC) compared to rapid transplantation. The researchers write that using “downstaging,” which involves radiofrequency ablation, chemoembolization, or both, and a period of waiting, for patients with a tumor burden outside the Milan criteria who make it to transplantation results in excellent outcomes.
Hospital Now Offers Almost Complete Liver Care
Dr. Shannon Kauffman, interventional radiologist, and other doctors of the Miami Valley Hospital began targeting liver tumors that could not be surgically removed. They used millions of microscopic resin beads loaded with high dose of radiation (yttrium 90), which invade the tumor through their blood supply. “It’s a minimally invasive treatment that is generally very well tolerated, and it’s proven to extend life and extend quality of life,” Kauffman said. When used in combination with chemotherapy, the median survival rate two years after treatment was 39 percent, compared to 29 percent for those undergoing only a chemotherapy regimen.
Low Temperature of Radiofrequency Ablation at the Target Sites can Facilitate Rapid Progression of Residual Hepatic VX2 Carcinoma
Scientists have seen that there can be rapid progression of residual tumor after radiofrequency ablation (RFA) of liver cancer. After implanting VX2 carcinoma into rabbits, and using RFA at 55, 70, and 85 degrees C, they found the greatest differences between the control group and that which was given RFA at 55 degrees C. These results confirmed that low temperature RFA facilitated rapid progression of residual hepatic VX2 carcinoma.
Can-Fite Biopharma LTD is a biotechnology company founded by Prof. Pnina Fishman, an investigator from Rabin Medical Center and patent attorney Dr. Ilan Cohen. So far 3 patients with hepatocellular carcinoma (HCC), who had been treated with the company’s pipeline drug, CF102, have seen a significant decrease in HCV viral load. They are part of an ongoing Phase ½ clinical trial. Researchers found that CF102 triggered programmed cell death of liver cancer cells.
Rapid Induction of Orthotopic Hepatocellular Carcinoma in Immune-competent Rats by Non-invasive Ultrasound-guided Cells Implantation
Researchers used a non-invasive approach to establish an orthotopic HCC model in immune-competent rats by implanting cancer cells with the guidance of ultrasound, to evaluate therapeutic efficacy of short-term and low-dose epirubicin chemotherapy. As a result, they found that the treatment had disturbed tumor progression by inducing apoptosis and neovasculatization blockade.
Up-regulation and Subcellular Localization of hnRNP A2/B1 in the Development of Hepatocellular Carcinoma
Scientists analyzed a single-chain antibody scFv N14 that they found to be a new biomarker that can diagnose liver cancer and monitor its treatment. They later found that the up-regulation of hnRNP A2/B1 measured transcriptional and translational levels in rat HCC cells. They concluded that the increased expression and localization of hnRNP A2/B1 can be used as a diagnostic biomarker to assess the risk of human liver cancer.
Researchers at Banaras Hindu University have developed a drug that could be a potential cure for liver cancer from the extract of the bark of Acacia nilotica tree, or Babool. Professor H B Singh at the Mycology and Plant Pathology Department of the BHU said they found that Indian Babool can prevent HCC. The tree has strong chemo-preventive potential in the form of six compounds present in the methanolic extract that play an essential role in prevention and therapy of cancer by inducing antioxidant defense system.
Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma
The study aimed to assess the efficacy and safety of repeat hepatectomy for recurrent HCC. Thirty-seven patients who underwent a curative repeat hepatectomy were retrospectively studied. Repeat hepatectomy can be performed safely and is associated with long-term survival in a subset of patients with recurrent HCC.
Physicians at the University of Rochester Medical Center have performed upstate New York’s first radioembolization, or TheraSphere, procedure for primary liver cancer. This procedure is used for patients with inoperable tumors that are awaiting organ transplant. After extensive imaging to determine the exact location of the tumor and the arteries leading to the lesion, TheraSphere, the outpatient procedure, involves injecting millions of microscopic radioactive glass beads into the vascular system near the tumor, which then attack cancerous cells.
Bayer’s treatment for advanced liver cancer, Nexavar, is to be tested against a radiotherapy made by Sortex Medical Ltd. A total of 360 patients with inoperable liver cancer will receive either Nexavar or Sydney-based Sirtex’s SIR-Spheres, Singapore’s National Cancer Centre. SIR-Spheres are injectable microscopic polymer beads designed to shrink tumors by carrying a radiotherapy drug directly to them, avoiding damage to healthy tissue that is caused by conventional radiotherapy.
A study shows that cyclosporine treatment is a significant risk factor for the development of de novo cancer in liver transplant recipients. The goal of the study was to clarify the role of different calcineurin inhibitor regimens in the occurrence of de novo cancer after liver transplant. Herold Metselaar, MD, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands, and colleagues performed retrospective analyses in 385 liver transplant recipients. They observed that cyclosporine, in comparison with tacrolimus, is the most important risk factor for de novo malignancy after liver transplant. This higher cancer risk was not, however, found in all cyclosporine treated patients, but cyclosporine specifically enhanced development of de novo cancer.
According to Singapore’s National Cancer Centre, a study being held by the Asia-Pacific Hepatocellular Carcinoma Trials Group, found that patients who have been suffering from liver cancer or HCC may live up to another nine months longer. Their aim was to carry out precautionary and therapeutic trials in HCC. One such trial included systemic therapy and selective internal radiation therapy, which were giving in combination to a group of 35 patients that were shown to have a mean survival of 11.75 months.
Six clinical scientists received funding support for translational and clinical research. Prof. Chow, Senior Consultant at the Department of General Surgery will be conducting a Phase III clinical trial to compare the outcomes of two known therapies for primary liver cancer to analyze which is more beneficial. Dr Mei Wang, Assistant Professor at Duke-NUS Graduate Medical School will be studying the actions of a class of experimental molecules, which help block the effects of cancer-causing proteins produced by oncogenes.
Lawmakers on the House Oversight panel urged Congress to pass legislation to boost the detection and treatment of viral hepatitis, the leading cause of liver cancer. An Institute of Medicine report included two dozen expert recommendations for improvement. The bill would have the secretary of Health and Human Services develop and implement a plan for the prevention, control, and medical management of hepatitis B and C. an independent study found that without federal leadership, the cost of treating hepatitis C alone could more than triple to $85 billion a year by 2024.
Radiomicrosphere therapy is offered to patients with inoperable or unresectable hepatic metastases. Tiny microbeads with yttrium-emitting radioisotope have been shown to be cancer-killing. After the beads have been injected, instead of going to meld with the cancer, they are infused in a nearby region and then carried through the circulatory system to the tumor. An initial run is done with the microbeads carrying technetium while a single photon emission computed tomography, or a SPECT/CT, which is a tomographic imaging technique using gamma rays, tracks them to document the flow ensuring a beneficial treatment when the microspheres with the yttrium isotope are sent.
More than 100 patients with inoperable liver cancer have been successfully treated with a revolutionary therapy discovered by surgeon Bruce Gray, called selective internal radiation therapy, or SIRT. These patients were part of a Melbourne-led international human trial of SIRT along with the chemotherapy drug sorafenib. SIRT involves the injection of tiny radioactive beads, which lodge themselves in the liver and release radiation over several days to shrink the tumor.
Researchers developed a rat model of liver regeneration post-hepatectomy to identify the distinct molecular mechanisms for early HCC. After completing cross-species comparative analysis to identify critical regulatory modules conserved across species, the researchers found 35 signature genes that were conserved and shared among different types of early human HCC. These findings may lead to distinct biomarkers for the detection of early HCC.
A study conducted by researchers at the Baylor College of Medicine found that fewer than 20% of patients with HCC preceded by cirrhosis were monitored for the development of cancer. The study team evaluated HCC surveillance in 1,873 patients diagnosed with HCC who had a prior diagnosis of cirrhosis during 1994-2002. Patients who were younger, Asian, diagnosed during more recent years, living in zip codes with higher income or education or in urban areas, and women were more likely to have received regular surveillance than other groups.
An experimental treatment using Vitamin A analog peretinoin for the treatment of recurrent liver cancer failed to meet its primary endpoint in showing a progression-free survival benefit over a placebo. Researchers believe the drug may still have promising results in the treatment of HCC. In the trial, only 43.7% of patients on peretinoin had maintained progression-free survival after 3 years of therapy compared with 29.3% of patients on placebo. Researchers are now considering increasing the doses of peretinoin from 300mg a day to 900mg a day.
Kinase Inhibitors, Linifanib, is a small, oral molecule that provides potent and specific inhibition of the VEGFR and PDGFR families. Inhibiting the appropriate kinases can suppress tumor growth by preventing the formation and spread of new blood vessels that supply the tumor with nutrients, oxygen, and inhibiting key angiogenic signaling pathways, which signals the body to begin a process of developing new blood vessels resulting in vascularisation of a tissue. Linifanib is in a Phase III clinical trial for HCC.
Researchers at the Baylor College of Medicine in Texas, try to understand how the tumor suppressor protein C/EBP alpha is reduced in aging livers. This information could lead to important clues to the mechanism by which cancer occurs in that organ and the discovery of new therapies and prevention. Dr. Nikolai A. Timchenko, professor at the Huffington Center on Aging studied a variant of C/EBP alpha called the S193-ph isoform, which is a powerful tumor suppressor protein that must be eliminated before liver cancer can occur. Researchers also found that the C/EBP alpha suppressor prevents generation of new liver tissue, which is an advantage because uncontrolled growth is a hallmark of cancer.
The Bureau of National Health Insurance said it is encouraging hospitals to see to it that high-risk patients have regular checkups to ensure early detection of cirrhosis and liver cancer. In Taiwan, 1,000 people are participating in a government project aimed at fighting liver cancer. Bureau statistics show that 685,000 Taiwanese have been diagnosed with hepatitis or cirrhosis but only 91,000 received abdominal sonography and liver function tests every six months. The Bureau set up a reward system to encourage hospitals that enroll and routinely monitor high-risk patients.
The purpose of the study was to compare the impact of the type of resection on HCC recurrence in patients with solitary HCC and preserved liver function. Among 53 patients who underwent curative liver resection, 28 underwent anatomic resection of at least one liver segment and 25 patients underwent limited resection. No difference was detected in recurrence rates. Concluding, that the choice of the type of resection for HCC should be based on the maintenance of adequate amount of liver left to perform basic functions.
The purpose of the study was to compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) in patients with HCC. The results showed that HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques.
HCC lines were used for an in vitro study in an orthotopic nude mouse model. Scientists assessed the metastatic potential, or the potential spread of a disease from the organ or tissue of origin to another part of the body, of surviving tumor cells after oxaliplatin treatment, a chemotherapy drug that kills cancer cells. The Chinese herbal extract SongyouYin that is composed of five herbs and its effects on the metastatic potential of oxaliplatin-treated cancer cells was investigated. Results showed that the cells that survived oxaliplatin treatment showed increased metastatic potential.
ArQule Inc. is a clinical-stage biotechnology company pursuing innovative approaches to cancer therapy. The company’s lead product, ARQ 197, is under Phase II development. ARQ 197 was shown to be well tolerated in the patient population and showed no drug-related worsening of liver function. A Phase I trial evaluating ARQ 197 in combination with sorafenib was dosed last June. ARQ 197 was evaluated in patients with HCC in Phase I and enrollment in Phase II was in last September.
The Data Monitoring Committee (DMC) has reviewed data from 294 patients that were enrolled in the Phase III ThermoDox clinical study (HEAT study) for primary liver cancer and recommend that Celsion continue to enroll patients. The DMC for the HEAT study is comprised of medical and scientific experts who are responsible for reviewing and evaluating patient safety and efficacy. The HEAT study plans to enroll 600 patients and is designed to evaluate efficacy of ThermoDox in combination with radiofrequency ablation (RFA) as compared to patients who receive RFA alone.
BioSphere develops embolotherapeutic products, which are bioengineered microspheres that are administered intravenously to targets drug delivery. The merger of Merit Medical Systems and BioSphere Medical provides a platform technology applicable to multiple therapeutic areas, with immediate application for embolotherapy for uterine fibroids and primary liver cancer (HCC).
Researchers in Taiwan found a male sex hormone that may explain why men who suffer from hepatitis B are more likely to develop liver cancer than women. They found that the hepatitis B virus attaches itself to receptors of the male sex hormone, androgen, before going on to damage liver tissue and cause cancer. This makes men up to seven times more likely to develop liver cancer than women. Researchers said, “Targeting the androgen receptor rather an androgen could be a promising therapy for liver cancer.”
The best option to cure HCC is surgical resection, although surgery on a cirrhotic liver may increase the risk of bleeding. At this time, there are no guidelines on the administration of anti-thromboembolic prophylaxis, or an anti-clotting preventative treatment for patients undergoing hepatic resection. A research team in Italy found that the incidence of venous thrombosis, or a blood clot, in patients who have not undergone prophylaxis was low, as compared to an increased risk of bleeding in patients who received heparin, an anti-clotting medication.
A research team in Hong Kong reported on a patient who presented with a recurrence of HCC in the right kidney after 12 years of the initial diagnosis. Based on this incident, they discuss the importance of considering late recurrence in patients with a history of HCC. This case showed that the diagnosis of extra-hepatic metastasis should always be suspected.
Health officials attribute the rise of hepatocellular carcinoma in the US to the untreated hepatitis infections. The rate of HCC has increased from 2.7 per 100,000 persons in 2001 to 3.2 in 2006, which is an average annual increase of 3.5 %. The Center for Disease Control researchers report that the highest rates are seen among Asian Pacific Islanders and Blacks.
Zeid Kayali, M.D. and researchers of Loma Linda University Medical Center found that proton beam radiation therapy is a safe and effective treatment for advanced, inoperable HCC. Proton beam radiation works by delivering a high dose of radiation to the tumor while sparing the surrounding healthy tissue. The study included 18 patients who received 15 treatments over a three-week period. After treatment all patients we able to receive liver transplants. Of the group, 6 patients had no sign of residual tumor, 7 patients had microscopic evidence of residual tumor, and 5 patients had major residual tumor of the liver.
Pfizer Inc. is discontinuing its SUN 1170 Phase 3 study Sutent® for HCC. This decision was based on a higher incidence occurrence of serious adverse side effects as compared to the trial with sorafenib. More than 82,000 patients have been treated with Sutent®. It works by blocking multiple molecular targets implicated in the growth, and proliferation of cancer. The two important targets of Sutent were the vascular endothelial growth factor (VEGFR) and the platelet-derived growth factor receptor (PDGFR). Sutent is currently approved for gastrointestinal stromal tumors (GIST) and advanced metastic renal cell carcinoma (RCC).
Delcath Systems Inc., a medical research firm said that the preliminary results from a study of its liver cancer treatment device exceeded expectations. Clinical trials for its percutaneous hepatic perfusion (PHP) System, which uses catheters to isolate the liver from a patient’s circulatory system before delivering a concentrated drug to the organ. Clinical data shows the device outperformed the best available care options by keeping the patient’s cancer from worsening and keeping the patient alive longer. Patients treated with the PHP system went almost three times longer without progression of their cancer than the control group who received other treatments.
AngioDynamics’ novel treatment NanoKnife ® that uses irreversible electroportion (IRE) system treats the early stages of HCC. The clinical trial is being conducted under the supervision of Professor Jordi Bruix of the Barcelona Clinic Liver Cancer Group of the University of Barcelona and Professor Riccardo Lencioni of the University of Pisa School of Medicine. As of March 31, 2010, physicians have treated a total of 154 patients in 11 centers on many different organs, including prostate, liver, lung, and pancreas. NanoKnife ® has been cleared by the FDA in the United States for surgical ablation of soft tissue.
Researchers gathered 54 HCC sample liver tissue from West China Hospital of Sichuan University to validate the expression of Phosohoglycerate Mutase 1 (PGAM1). After doing immunoblot and immunohistochemistry using the clinical samples, they found a total of 63 dysregulated proteins, including 51 up-regulated proteins and 12 down-regulated proteins. PGAM1 was found markedly up-regulated. Researchers concluded that PGAM may play an important role in hepatocarcinogenesis and could be a potential biomarker, as well as a therapeutic target for HCC.
Researchers at the Virginia Commonwealth University Massey Cancer Center and the VCU Institute of Molecular Medicine hope the findings could lead to an effective therapy to target and inhibit the expression of this gene and result in inhibition of cancer growth. The team found that LSF plays an important role in the development and progression of HCC, and that inhibiting LSF can reverse the aggressive properties of human liver cancer cells. “We show a novel mechanism of HCC development by LSF that provides us with fresh insight into the complex etiology and mechanism of carcinogenesis process. Because LSF is increased in such a high percentage of patients, it could be a potential target for therapeutic intervention,” said Devanand Sarkar, Ph.D., MBBS, assistant professor in the Department of Human and Molecular Genetics in the VCU School of Medicine.
IXICO Ltd. was granted Phase III for a proprietary drug in combination with transcatheter arterial chemoembolization (TACE) in the treatment of unresectable HCC. The study will recruit 400 patients over a three-year period. “The award of this Phase III, oncology study demonstrates that our customers recognize the value of IXICO’s innovative imaging solutions, which provide higher image quality and shorter timelines,” notes Derek Hill, CEO. “Our solution combines the latest release of our image management technology with rigorous application of well established radiological endpoints to provide the study flexibility that the investigators require.”
Members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. The aim of this study is to investigate the expression of CXCR7 in HCC tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Researchers evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human HCC tissues and CD31 in tumor of mice, and the effect of VEGF stimulation on expression of CXCR7. In addition, they also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo.
The current blood test used to screen for early tumors in people at high risk for liver cancer involves a protein called alpha-fetoprotein (AFP), explained Dr. Claus Fimmel, a hepatologist who is involved in an international study of a protein that is shaping up as a promising basis for the development of an effective liver-cancer screening test for high-risk patients. The protein being studied is known as Golgi Protein-73 (GP73), which was first discovered in Dr. Fimmel’s lab in 1998. Subsequent studies have shown that the blood levels of GP73 are consistently higher in patients with liver cancer than in healthy individuals. For far, the blood samples of more than 1,000 patients with various stages of liver and non-liver disease have been tested for the presence of GP73 in several studies around the world.
Dr. Mark Faries, an associate member of the John Wayne Cancer Institute in Santa Monica, Ca is experimenting with a new treatment called percutaneous hepatic perfusion (PHP) which allows much higher doses of chemotherapy, but being confined to the liver. In one study, 80% of patients saw tumors shrink in size or stabilize. The treatment utilizes three catheters to isolate the liver and deliver targeted chemotherapy directly to the liver instead of throughout the body. Two balloons block the chemo from flowing through the rest of the body. PHP is in the final phase of testing.
Cancer treatment typically involves surgery, radiation therapy, chemotherapy, hormone therapy, or biological therapy. At Georgia Tech, researchers are pursuing many different directions toward improving existing cancer treatment methods and developing new therapeutic techniques including attacking cancer stem cells, improving radiation therapy, including motion and biological information in planning treatment, assessing a tumor’s ability to create new blood vessels, developing a new approach to targeted cancer therapy, increasing responses to chemotherapy, enabling personalized drug delivery, and analyzing gene expression data to predict responses to drugs. The article goes on to expand on each of these methods.
A new treatment called Irreversible Electroportion (IRE) is performed by interventional radiologists. Guided by CT scans, radiologists use thin needles to insert probes around the tumor. Then, high-voltage is passed through the probes killing the tumor. Lasting for 45 seconds, the electrical pulses create multiple holes in the membrane of the cancer cells. Then, the body naturally removes the cell structures that are left behind. No large incisions are required so no scarring is caused and patients can be sent home the next day.
NexMed Inc. has filed for a Phase II trial of its newest cancer drug PrevOnco ™ in combination with doxorubicin in patients with unresectable HCC. PrevOnco is the anti-ulcer compound, lansoprazole, approved under the name Prevacid ®. The FDA has 30 days to comment on the IND before NexMed can proceed with human testing. In vitro and in vivo pre-clinical data generated has demonstrated the ability of lansoprazole to inhibit tumor cell growth and enhance survival in mouse models of cancer alone and in combination with doxorubicin.
A recent study found that sirolimus-based immunosuppression following liver transplantation in patients with non-resectable HCC significantly increases survival rates for this patient population. Researchers evaluated 2,491 adult recipients of isolated liver transplantation for HCC. In a multivariate analysis, only anti-CD25 antibody induction and sirolimus-based maintenance therapy were associated with improved survivals after transplantation for HCC.
Genetic polymorphism has been reported to be a factor increasing the risk of HCC. Phase II enzymes such as glutathione s-transferases (GSTP1, GSTA1) play important roles in protecting cells against damage induced by carcinogens. The aim of this study was to estimate the relationship of the GSTP1 and GSTA1 gene polymorphisms to HCC risk and clinico-pathological status. No association between the GSTA1 gene polymorphism and HCC susceptibility was found.
Researchers found that giving bevacizumab (Avastin) concurrently with transarterial chemoembolization (TACE) is reasonably well tolerated and appears to be effective in patients with inoperable HCC. About 58% of patients had grade 3 or 4 toxicity, and median survival was 13.5 months. The combination has been investigated in other trials, and a phase III study is currently enrolling patients. Researchers have explored the combination because there has been evidence that TACE stimulates angiogenic activity, a physiological process involving the growth of new blood vessels from pre-existing vessels.
A new interventional radiology treatment combines the radioactive isotope Y-90 with microspheres to deliver radiation to tumors, while sparing healthy cells. Each microsphere is about the five red blood cells in width. They are delivered to the tumor through a catheter in the groin that is threaded into the artery supplying it.
In a study of 291 patients, most benefitted from the Y-90 treatment. It took a median of 7.9 months for the tumors to regrow after treatment, and some patients survived more than 20 months, which researchers say are very promising numbers.
Patients treated with locorefional chemotherapy or radiotherapy for HCC, assessment of changes to the largest tumor targeted in the first round of treatment, the “primary index lesion” is a useful biomarker of response to treatment. The three most commonly used treatment response guidelines are Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization (WHO), and European Association for Study of the Liver (EASL). A study of 245 HCC patients and 1,065 scans of the primary index lesion were analyzed. There was a high degree of concurrence in classification of treatment response between the WHO and RECIST guidelines, the investigators found. However, both sets of guidelines had a low correlation with the EASL guidelines.
BioSphere, Medical, a medical device company that develops and manufactures minimally invasive treatments of tumors, announced that its doxorubicin delivery embolotherapy microspheres HepaSphere(TM) were featured in a scientific session on the advances in minimally invasive treatments for liver cancer. Dr. Maleux, an interventional radiologist at the University Hospitals Leuven, Belgium presented a study, which demonstrated the safety of HepaSphere(TM) drug delivery chemoembolization (hqTACE). Patients treated with HepaSphere(TM), compared to patients who received conventional transarterial chemoembolization (cTACE), had lower circulating levels of doxorubicin, which significantly reduced drug toxicity and serious side effects. The hqTACE patients also had better preserved liver function.
The AP-1 transcription factor plays a major role in cell proliferation, apoptosis, differentiation and developmental processes. AP-1 proteins are primarily considered to be oncogenic, or capable of the process of malignant transformation JDP2-transgenic mice display normal liver function. JDP2-transgenic mice displayed potentiation of liver cancer, higher mortality and increased number and size of tumors. The expression of JDP2 at the promotion stage was found to be the most critical for enhancing liver cancer severity.
A national gathering of 180 transplant experts reached a consensus that priority scores for transplantation in patients with hepatocellular carcinoma should rank candidates based on the Model for End stage Liver Disease (MELD) score, alpha-fetoprotein level, tumor size, and rate of tumor growth, according to Elizabeth A. Pomfret, MD, of the Lahey Clinic in Burlington, Mass., and colleagues. The Milan criteria for hepatocellular carcinoma, one nodule ≤5 cm or two to three nodules each <3 cm has generally been considered an acceptable risk of recurrence after transplantation.
Medical research developments over recent years have allowed researchers to explore water molecule motion between cells using diffusion-weighted imaging (DWI) to indirectly measure cellular density within a tissue. This has provided a new and continuously evolving tool in oncologic imaging for lesion detection, characterization, and therapy assessment. Current problems in DWI technology, such as low signal-to-noise ratio (SNR) and limited spatial resolution, are likely to be overcome in part through the more widespread use of higher magnetic field strengths, such as 3T.
The frequency of post-operative complications following surgery for liver cancer is associated with a hospital having a low volume of liver surgery. A recent survey analyzed 9,289 cases between 1998 and 2007 of patients who underwent surgical removal of a portion of their liver. Results showed that more patients at low-volume hospitals experienced complications such as hemorrhaging, sepsis, and lung problems. Also, a patient was 1.4 times more likely to die having a procedure done at a low-volume hospital as compared to a high-volume one.
Transgene BioTek has filed two patients for its cancer drug technologies based on its RNAi platform. The liver cancer drug showed excellent results from the latest animal studies. The technology expressed specific microRNA that silence particular metastisis-promoting gene in liver cancer cells. It uses an Adeno-associated virus (AAV) vector system. AAV is small virus that can infect humans and some primates and make it a good candidate for gene therapy.
Hereditary hemochromatosis (HH) is an autosomal recessive disorder mainly associated with homozygosity for the C282Y and H63D mutations in the hemochromatosis (HFE) gene. To clarify the relationship between C282Y and H63D mutations and hepatocellular carcinoma (HCC), a meta-analysis including nine studies (1102 HCC cases and 3766 controls) was performed. Meta-analysis of nine studies with all controls showed that Y allele of C282Y was associated with HCC risk. H63D mutation did not show evidence of the association with HCC.
A well-known treatment for liver cancer called ablation may have just gotten better. Ablation involves destroying a tumor without removing it, so it is typically used on patients with a few small tumors that cannot be removed with surgery. A new type of ablation is based on a technique called electrophoresis, which involves using electrical energy to alter cell membranes and allow chemotherapy drugs to enter more freely. The technique used in the past to deliver chemotherapy is called reversible electrophoresis. It allowed the cell membranes to close up again. In a new treatment called irreversible electrophoresis, interventional radiologists use a higher voltage to cause permanent damage to cancer cells. The radiologists place proves thru two or three millimeter incisions around a cancerous tumor and connects them to a generator. The generator is turned on and fires an electrical pulse that travels to the tumor cells.
Celsion Corp. is moving into the second phase of clinical trials for its drug to treat liver cancer. The Columbia biotechnology company said Monday that testing for ThermoDox will begin in at least three medical research centers throughout the world, including New York’s Albert Einstein College of Medicine, during the second half of this year. The trials will further study the impacts of ThermoDox when combined with a radiofrequency treatment on liver cancer and tumors, Michael Tardugno, Celsion’s CEO, said in a statement. “The safety experience and dose response relationship we witnessed in the Phase I study was evident in both primary and metastic tumors,” he said. “Building upon this data, we have made the decision to pursue a randomized Phase II study.”
Two biomarkers used to complement ultrasound in the early detection of hepatocellular carcinoma, or liver cancer, are not ideal, according to Anna S. Lok, M.D., professor of internal medicine at the University of Michigan Medical School. The study analyzed the use of des-gamma-carboxy prothrombin (DCP) and the most widely used biomarker, alpha-fetoprotein (AFP). Biomarkers are found in patient’s blood and are used to indicate whether a disease or condition is present. DCP was not superior to AFP in the early detection of HCC in patients with advanced hepatitis C and neither AFP alone, DCP alone, nor the combination of AFP and DCP was sufficiently accurate to be used for HCC surveillance.
To complete a more thorough search for potential biomarkers for HCC invasion and metastasis, a proteomic approach was applied, where they look particularly at a protein’s structure and function. Membrane proteins were extracted from MHCC97L and HCCLM9 cells and compared by SDS-PAGE analyses. A total of 14 differentially expressed proteins were identified by ESI-MS/MS. Coronin-1C, a promising candidate, was found to be overexpressed in HCCLM9 cells.
Top-line data from a phase III study of Delcath’s Percutaneous Hepatic Perfusion (PHP) system will be announced in April, according to CEO Eamonn Hobbs. Positive results will lead quickly to an approval filing with the U.S. Food and Drug Administration. PHP is a system that lets doctors isolate the liver from the rest of the blood supply, allowing tumors in the liver to be treated with very high doses of chemotherapy without causing significant toxicity in the rest of the body. Delcath’s current phase III study enrolled patients with melanoma (skin cancer) that spread or metastasized to the liver. The primary endpoint is hepatic progression-free survival. Delcath designed the study assuming that PHP could reduce the risk of tumor progression or death by about 50% compared to best alternative care. Expectations are that the phase III PHP study will be a success.
Schoolgirl cancer victim Chloe Oldfield was determined to prove doctors wrong when they said she might have just six months to live. The three-year fight finally came to an end. Her parents, Catherine and Philip, were at her bedside at the family home when she died at the age of 16. Chloe was diagnosed with hepatocellular carcinoma—an aggressive form of liver cancer—in March 2007 and underwent a 12-week course of intensive chemotherapy at The Royal Manchester Children’s Hospital in Pendlebury.
Karin and team investigated mice prone to develop HCC. The study showed that mice on a high fat diet developed more liver cancer. They also found that mice on a normal diet but carried a gene that made them obesity prone also developed more cancer.
The DMC for the HEAT study is comprised of an independent group of medical and scientific experts who are responsible for reviewing and evaluating patient safety and efficacy data. The study design and statistical plan for the Phase III ThermoDox trial also incorporates a pre-planned interim efficacy analysis by the DMC. The study for primary liver cancer is enrolling 600 patients and is being conducted under a FDA Special Protocol Assessment. ThermoDox® is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers including breast cancer. ThermoDox® is administered intravenously delivering high concentrations of doxorubicin to be deposited preferentially in a targeted tumor.
MDS Nordion, a global leader in providing products and services for medical imaging and radiotherapeutics, today announced that two of the largest health insurers in the United States have recently approved coverage of radioembolization to treat unresectable liver cancer, which includes the use of MDS Nordion’s TheraSphere(R) treatment. The two insurance companies and their affiliates together serve more than one-quarter of Americans and do business in all 50 states. Radioembolization refers to a process by which small beads or microspheres, containing the radioactive element yttrium-90, are delivered directly to the tumor using the tumor’s own blood supply. TheraSphere is one form of radioembolization. Another name for this type of treatment is selective internal radiation therapy (SIRT).
The group, the Asia-Pacific Hepatocellular Carcinoma Trials Group, was set up in 1997 and involves institutes from 11 countries. Singapore’s National Cancer Centre (NCC) is its secretariat, and the database of trial results will be managed by the Singapore Clinical Research Institute (SCRI). That latest trial treated 35 liver cancer sufferers, who were unsuitable for surgery, with a novel therapy of radioactive microspheres that target the tumors, and the liver cancer drug sorafenib.
The University of Hawai‘i at Manoa’s Cancer Research Center of Hawai‘i has successfully recruited five noted cancer researchers to join its faculty. Three of the researchers—Drs. Clayton Chong, Naoky Tsai and Linda Wong—are well-known cancer specialists in Hawaii. Chong and Wong will join the Center as recipients of two federal ARRA grants that were awarded in December to fund “translational” research that spans the continuum from lab study to patient care. Two additional recruits come from the mainland: Wen-Ming Chu, MD, PhD, formerly of Brown University’s department of molecular microbiology and immunology; and Toshihiko Kawamori, MD, PhD, from the University of South Carolina’s department of pathology and laboratory medicine.
The use of laparoscopy in hepatectomy, while technically demanding, reduces surgical invasiveness and stressfulness but still achieves complete resection with adequate margins. Compared with conventional hepatectomy, laparoscopic hepatectomy provides a better chance and situation for further surgery in the case of recurrence of HCC. The report also describes techniques of the operation and displays characteristic results of laparoscopic hepatectomy such as smaller wounds, less blood loss, less pain, less scars and adhesion, shorter postoperative hospital stay, and faster recovery.
Aegera, a clinical stage biotechnology company focused on developing novel targeted therapies that address major unmet medical needs has begun a new study titled “A Phase 2, Open-Label Study of The X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination with Sorafenib in Patients With Advanced Hepatocellular Carcinoma” is being conducted in Hong Kong. AEG35156 targets XIAP; it is designed to lower the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy, without harming healthy cells.
Avo Artinyan, M.D., of City of Hope in Duarte, California, and colleagues examined the association between race and survival in 20,920 patients with hepatocellular carcinoma (HCC) and 4,735 patients who underwent liver transplantation. The researchers found that survival improved over time regardless of race, ethnicity or income. After adjusting for various factors, survival in patients with HCC was worst for African-Americans.
Kiwamu Okita, MD, professor in the department of gastroenterology and hepatology with Shimonoseki Kohsei Hospital in Shimonoseki, Japan, presented the results and said further analysis leads investigators to believe sorafenib (Nexavar, Bayer) may yet have a role to play in the treatment of these patients. Median time to progression was 5.4 months in the sorafenib group compared with 3.7 months in the placebo group. In the sorafenib group, 41% of patients discontinued treatment due to adverse events.
In the Phase I study, ThermoDox was assessed for safety, pharmacokinetics and tumor response in 12 liver cancer patients, including 3 with hepatocellular carcinoma (HCC). Conclusions from the Phase I study provided support for Celsion’s global Phase III trial in patients with HCC. ThermoDox in combination with hyperthermia has the potential to provide local tumor control and improve quality of life. ThermoDox is a proprietary, heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially in a targeted tumor.
Glucose regulated protein 78, or Grp78 is involved in the invasion and metastasis in many human cancers. The Grp78 and FAK expression levels in 44 patients with HCC were examined using immunohistochemistry. Grp78 was negatively correlated with tumor grading, but positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 promoted the invasion of cancer cells and accelerated the process of cell spreading.
Regulus Therapeutics is a biopharmaceutical company focused on the discovery and development of innovative medicines based on microRNAs. Regulus presented in vivo data demonstrating delivery of miR mimics and microRNA target repression in an orthotopic liver tumor mouse model. Using lipid nanoparticles developed by collaborators at Alnylam Pharmaceuticals, Regulus scientists demonstrated effective delivery of a miR-34a mimic to both the normal liver cells and human hepatocellular carcinoma cells growing as tumors within the liver. Within the tumors, scientists saw a similar down-regulation of messenger RNA targets. When with further analysis, they saw the down-regulated messenger RNAs for functional significance, it was discovered that several cell cycle progression and cellular division genes were over represented. This demonstrates the potential utility of a miR-34a mimic delivered by lipid nanoparticles for the treatment of liver cancer.
Researchers have identified two cellular proteins that are important factors in hepatitis C virus infection, a finding that may result in the approval of new and less toxic treatments for the disease, which can lead to liver cancer and cirrhosis. Samuel French, an assistant professor of pathology and senior author of the study, and his team found the two heat shock proteins (HSP) 40 and 70 that are involved in hepatitis C replication. They also showed the natural compound Quercetin, which inhibits the synthesis of these proteins, also significantly inhibits viral infection in tissue culture. A Phase I clinical trial will done at UCLA to determine safety and efficacy of Quercetin. French and his team used Quercetin in an attempt to block HSP 40 and 70, and found that the compound “reduced infectious particle production at non-toxic concentrations,” according to the study.
The genetic inactivation of tumor suppressor genes is considered a crucial event in the development and progression of tumors. Chromosome 8p, one of the regions most frequently involved in the loss of heterozygosity (LOH), is thought to be closely associated with HCC oncogenesis, progression, venous permeation, and metastasis of HCC. These findings suggest that one or more novel tumor suppressor genes reside in the loci implicated in these cases with allelic deletion. To screen tumor suppressor genes in HCC cells that are silenced by epigenetic modification, scientists tested all currently available 15 human HCC cell lines. Clustering of the gene-expression changes indicated that some common genes were markedly unregulated in these HCC cell lines following demethylating treatment, implying that the transcription of these genes was silenced by hypermethylation of CpG islands in their regulatory elements. Interestingly, 9 unregulated genes were mapped to chromosome 8p. Also, ANGPT2 was shown to be highly overexpressed in hypervascular HCCs, resulting in rapid tumor growth and hemorrhage in an animal model of HCC.
Ze-Guang Han and colleagues at the Chinese National Human Genome Centerat Shanghai People’s Republic of China have identifies SCARA5 as a candidate tumor suppressor gene in human HCC. Their study found SCARA5 resulted in genetic loss and epigenetic silencing, or influencing the behavior of a cell without directly affecting its DNA or other genetic machinery. Further analysis in HCC cells lines in vitro and after transplantation into mice matched with SCARA 5 being a tumor suppressor gene.