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A new chemotherapeutic target for hepatocellular carcinoma
October 25, 2007Hepatocellular carcinoma (HCC) is a major health problem worldwide. Currently, the only chance for obtaining a cure in patients with HCC is by either a surgical resection or liver transplantation. However, many HCCs with scattered tumors cannot be operated on. In such patients, effective alternative therapies need to be discovered in order to treat patients in the early stages of this disease.
An article to be published on 28 October in the World Journal of Gastroenterology proposes a new target for therapy. A study was conducted by Dr. Satoshi Mamori, of Jikei University, in which he evaluated tumor biopsies in order to confirm the diagnosis of HCC.
The immunohistochemical expression of survivin in liver tumor specimens obtained from 17 patients was studied. In addition, to determine the survivin expression in response to anti-cancer drugs in early stage HCC, the survivin expression was determined after treating HCC cells with anti-cancer drugs under hypoxic culture conditions.
Survivin is a member of a family of inhibitors of apoptosis protein (IAP), which has been implicated in both the control of cell division and the inhibition of apoptosis. Survivin is selectively expressed in most common human neoplasms and it also appears to be involved in tumor cell resistance to some anticancer agents and ionizing radiation. Several preclinical studies have demonstrated a down-regulation of the survivin expression/function by the use of anti-sense oligonucleotide, dominant negative mutants, ribozymes, small interfering RNAs and cyclin-dependent kinase inhibitors to increase the rate of apoptosis, while also reducing the tumor growth potential and sensitized tumor cells to various chemotherapeutic drugs and ƒ×-irradiation using both in vitro and in vivo models of various types of human tumors.
The results and conclusions demonstrated survivin protein to be expressed in 64.7% of the cells in early HCC specimens (median). In early stage HCC with a tumor size > 10 mm, the expression rate ranged for 67.7 to 83.7%. Moreover, the survivin protein concentration in HCC cells increased with a combination of hypoxia and anti cancer drugs. With TACE, the conditions of hypoxia are maintained by embolisation over a long period of time. Therefore, this study suggests that survivin could be used as a potential useful therapeutic target for early HCC.
World Journal of Gastroenterology
Survivin is a member of a family of inhibitors of apoptosis protein (IAP), which has been implicated in both the control of cell division and the inhibition of apoptosis. Survivin is selectively expressed in most common human neoplasms and it also appears to be involved in tumor cell resistance to some anticancer agents and ionizing radiation. Several preclinical studies have demonstrated a down-regulation of the survivin expression/function by the use of anti-sense oligonucleotide, dominant negative mutants, ribozymes, small interfering RNAs and cyclin-dependent kinase inhibitors to increase the rate of apoptosis, while also reducing the tumor growth potential and sensitized tumor cells to various chemotherapeutic drugs and ƒ×-irradiation using both in vitro and in vivo models of various types of human tumors.
The results and conclusions demonstrated survivin protein to be expressed in 64.7% of the cells in early HCC specimens (median). In early stage HCC with a tumor size > 10 mm, the expression rate ranged for 67.7 to 83.7%. Moreover, the survivin protein concentration in HCC cells increased with a combination of hypoxia and anti cancer drugs. With TACE, the conditions of hypoxia are maintained by embolisation over a long period of time. Therefore, this study suggests that survivin could be used as a potential useful therapeutic target for early HCC.
World Journal of Gastroenterology
Hepatocellular Carcinoma News and Current Hepatocellular Carcinoma Events RSSTo protect against liver disease, body puts cells 'under arrest'
A stable form of cell-cycle arrest known to offer potent protection against cancer also limits liver fibrosis, a condition characterized by an excess of fibrous tissue, according to a new report in the August 22nd Cell, a Cell Press publication.
Senescence in liver cells is found by CSHL scientists to help limit acute tissue damage
Although post-reproductive life in humans is often associated with decline and a loss of powers, an analogous state in certain cells -- called senescence -- is proving to be one of ironic potency. Scientists at Cold Spring Harbor Laboratory (CSHL) today reported that a particular class of senescent liver cells orchestrates a sequence of events in living mice that can limit fibrosis, a natural response of the liver to acute damage.
New study shows potential to treat or prevent viral cancers
A new study, presented at the SNM 55th Annual Meeting, shows that radioimmunotherapy (RIT) targeting viral antigens offers a novel option to treat-or even prevent-many viral cancers by targeting cancer cells expressing viral antigens or infected cells before they convert into malignancy.
CSHL scientists trace causal link between a tumor suppressor gene and liver cancer
Scientists at Cold Spring Harbor Laboratory (CSHL) have taken the search for cancer-causing genes an important step forward. In a newly published paper, they confirm that a gene called DLC1 is a tumor suppressor. They have demonstrated in living mice that its deletion, inactivation or loss precipitates events culminating in an aggressive type of liver cancer closely related to common human epithelial cancers of the liver (also known as hepatocellular carcinoma, or HCC).
Synergistic growth inhibitory effect of herbal extracts against HCC and lung cancer cells
Several herbs with diversified pharmacological properties are known to be rich sources of chemical constituents that may have potential for the treatment of several human cancers. Data from the Department of Preclinical Science, Faculty of Medicine, Thammasat University, demonstrates that the growth inhibitory activity of doxorubicin or cisplatin, as single agents, may be modified in combination with emblic myrobalan or belleric myrobalan extracts and may be synergistically enhanced in some cases.
Anti-HBe may play a role in the progression of the disease of hepatitis B
Genotype D is found to be the only detected type in different clinical forms of HBV infections, including cirrhosis, among residents of southwestern Iran. A significant association between the presence of anti-HBe antibody and increasing ALT levels among either HBeAg-negative or HBeAg-positive individuals was also determined.
High circulating D-dimers are associated with presence of ascites
The liver is the production site of most of the proteins which favour and inhibit the process of coagulation and fibrinolysis.
Study shows positive findings in treating patients with advanced hepatitis C
The hepatitis C therapy peginterferon alfa-2b, when given as low-dose maintenance therapy, can prevent disease progression in certain patients who failed previous interferon-based hepatitis C therapies and have advanced liver disease, according to findings from a large, four-year study presented today at the 43rd annual meeting of the European Association for the Study of the Liver (EASL).
What change does prokineticin 2/Bv8 have in human hepatocellular carcinoma?
Liver hepatocarcinoma is a highly vascularized cancer, and more and more research is focused on the molecules controlling angiogenesis.
New Jefferson Trial to Test Radiation-Emitting Beads Against Advanced Liver Cancer
Liver cancer specialists at Jefferson's Kimmel Cancer Center in Philadelphia are beginning an 18-month study of a new treatment for liver cancer. The therapy entails injecting tiny beads that emit small amounts of radiation into the liver's main artery while also blocking the blood supply feeding the cancer's growth.
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