Chemotherapy for advanced hepatocellular carcinoma

Han, Kwang Hyub; Park, Jun Yong

doi:10.1111/j.1440-1746.2008.05444.x

Cited by 14 publications

(11 citation statements)

References 16 publications

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“…So far, adverse events from cisplatin and 5-FU appear to be mostly manageable with conservative care (Ando et al 2002;Han and Park 2008;Park et al 2007). Physicians must still exercise care with HAIC, however, because higher concentration of drugs are delivered directly to the liver.…”

Section: Discussionmentioning

confidence: 98%

Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma

Kim

Park

Choi

et al. 2010

J Cancer Res Clin Oncol

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Section: Discussionmentioning

confidence: 98%

Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma

Kim

Park

Choi

et al. 2010

J Cancer Res Clin Oncol

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“…Systemic therapy with conventional cytotoxic agents is ineffective or marginally effective in those cases. [3][4][5][6][7] HCC is a tumor entity with a high rate of resistance to chemotherapy administered either alone or in combination. Chemotherapy for advanced HCC has limited response rates and provides a marginal survival benefit.…”

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confidence: 99%

“…These include abscess, bleeding from the fistulous tract, and sepsis secondary to abscess formation; the latter is usually associated with high fistulous output, and mortality in such complicated cases is 13%-36%. [3][4][5] In patients afflicted with low fistulous output EPF, conservative management is appropriate. This includes nil by mouth, total parenteral nutrition, and administration of inhibitors of pancreatic secretion, such as somatostatin or its analog.…”

mentioning

confidence: 99%

“…The reason why there is a wide reported range for the successful achievement of EPF closure might be because studies have been based on small case numbers and have employed several therapeutic modalities. 5 Conservative therapy is aimed at decreasing endogenous pancreatic secretion so that flow through the fistula will diminish, allowing the fistula to close. However, some EPF cases are refractory to conservative treatment.…”

mentioning

confidence: 99%

“…Even with complex forms of EPF, endotherapy can be attempted instead of surgery. 4,5,[7][8][9] There are two opposite premises in endotherapy: one is that most ductal disruptions will close and heal if ductal continuity is re-established and the pressure gradient is abolished through pancreatic sphincterotomy, stone removal, stricture dilation, and pancreatic stenting; the other is that ductal disruption might never heal without correction of the downstream obstruction. 10 While existing data are limited to a few studies, the results of pancreatic endotherapy for EPF to date are encouraging.…”

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confidence: 99%

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Systemic treatment in advanced/metastatic hepatocellular carcinoma in the era of targeted therapy

Han

Park

2010

J of Gastro and Hepatol

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1 Recent advances in imaging modalities have permitted the detection of HCC at an early stage. However, despite extensive efforts to improve early diagnosis and treatment, only 10-30% of patients diagnosed with HCC are eligible for curative treatments. A majority of HCC patients present with unresectable status, and approximately 80% have associated cirrhosis, making effective therapy difficult. The tumor biology of HCC and the co-existing cirrhosis have presented major obstacles to HCC treatments.2,3 The prognosis is extremely very poor in patients with advanced HCC, especially with extrahepatic metastasis. Systemic therapy with conventional cytotoxic agents is ineffective or marginally effective in those cases. [3][4][5][6][7] HCC is a tumor entity with a high rate of resistance to chemotherapy administered either alone or in combination. Chemotherapy for advanced HCC has limited response rates and provides a marginal survival benefit. Thus, a meta-analysis evaluating the results of 37 randomized clinical trials of systemic and hepatic arterial infusion chemotherapy in 2803 HCC patients concluded that non-surgical therapies were ineffective or minimally effective at best. 7Among several chemotherapeutic agents, combined chemotherapy with 5-fluorouracil (5-FU) and interferon (IFN) was reported as one effective strategy for advanced HCC. [8][9][10] In particular, for the use of intra-arterial 5-FU combined with subcutaneous interferon therapy (FAIT), several studies have reported beneficial effects against HCC, with response rates ranging from 47% to 73%. Recent advances in implantable port drug delivery systems have facilitated repeated hepatic arterial infusions of anticancer agents. [10][11][12] Because the blood supply to HCC comes mostly through the hepatic artery, hepatic arterial infusion chemotherapy (HAIC) results in high local drug concentrations, and HAIC also reduces systemic side-effects.5-FU is the most frequently-used chemotherapeutic agent for HAIC. 5-FU has been reported to exhibit its anticancer effects via two major mechanisms: (i) the inhibition of DNA synthesis through the inhibition of the activity of thymidylate synthase (TS) by 5-fluoro-2′-deoxyuridine 5′-monophosphate, which is synthesized from 5-FU; and (ii) interference with RNA metabolism by incorporating the 5-FU metabolite into DNA and RNA.

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Tripartite motif protein 25 is associated with epirubicin resistance in hepatocellular carcinoma cells via regulating PTEN/AKT pathway

Yuan¹,

Zheng²,

Tang³

2020

Cell Biology International

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Tripartite motif protein 25 (TRIM25) expression was altered in various human cancers. Herein, we found that the expression of TRIM25 was elevated in hepatocellular carcinoma (HCC) tissues and cell lines. Knockdown of TRIM25 increased the sensitivity of HCC HepG2 cells to epirubicin (EPI), as indicated by reduced cell viability, enhanced cell apoptosis, and downregulated P‐glycoprotein (P‐gp) and multiple drug‐resistance protein 1 (MRP1). Moreover, TRIM25 knockdown strengthened the effects of EPI on phosphatase and tensin homolog (PTEN) and phosphorylated (p)‐AKT. However, overexpression of TRIM25 exerted an opposite effect, weakening the sensitivity of Huh7 to EPI, and obviously increasing PTEN and reducing p‐AKT. Most important, all the changes induced by TRIM25 overexpression in Huh7 were reversed with additional treatment of LY294002 (an AKT pathway inhibitor). Notably, coimmunoprecipitation experiments confirmed the interaction between TRIM25 and PTEN. Knockdown of TRIM25 resulted in reduced ubiquitination of PTEN protein. Collectively, our data suggested that TRIM25 enhanced EPI resistance via modulating PTEN/AKT pathway, and targeting TRIM25 may enhance the sensitivity of HCC cells toward chemotherapy drugs.

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Chemotherapy for advanced hepatocellular carcinoma

Cited by 14 publications

References 16 publications

Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma

Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma

Systemic treatment in advanced/metastatic hepatocellular carcinoma in the era of targeted therapy

Tripartite motif protein 25 is associated with epirubicin resistance in hepatocellular carcinoma cells via regulating PTEN/AKT pathway

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