Oxaliplatin (L-OHP): a new reality in colorectal cancer

Bleiberg, Harry

doi:10.1038/bjc.1998.427

Cited by 54 publications

(33 citation statements)

References 8 publications

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“…Tumors were excised and weighed. Animal experiments were performed in accordance with the regulations of the institutional ethical commission (Shimane University) and those of the United Kingdom Coordinating Committee on Cancer Research Guidelines [12]. …”

Section: Methodsmentioning

confidence: 99%

Functional and Clinicopathological Analysis of Loss of MKK4 Expression in Endometrial Cancer

Ishikawa

Nakayama²,

Rahman³

et al. 2010

Oncology

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Objective: In the current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase-4 (MKK4) expression to the development of endometrial cancer. Methods: MKK4 expression in endometrial cancer was assessed by immunohistochemistry using 87 paraffin-embedded tissue specimens, and clinical data was collected via a retrospective chart review. MKK4 gene knockdown using silencing RNA and an MKK4 gene transfection system was used to assess MKK4 function in tissue samples of endometrial cancer. Results: Lower expression of MKK4 immunointensity was observed in 63.2% (55/87) of the analyzed tumors. High-grade endometrioid adenocarcinoma (G2 and G3) (p = 0.024), postmenopausal status (p = 0.018), and patient age (≧60) (p = 0.012) were significantly correlated with lower MKK4 expression. Patients with lower MKK4 expression in endometrial cancer tissues tended to have a shorter overall survival (p = 0.197). Using cell growth and anchorage-independent assays, we determined that both the growth and colony-forming ability of MKK4-transfected HEC1B cells, a line with a low endogenous expression of MKK4, were significantly reduced compared to control vector-transfected cells. Overexpression of the MKK4 gene in HEC1B cells resulted in reduced cell migration activity in a simulated wound healing assay. To confirm that MKK4 expression is related to tumor suppressor function, we used 2 independent but complementary approaches. MKK4 gene knockdown in JHEM1 cells, which overexpressed MKK4, increased proliferation activity. Additionally, the engineered expression of MKK4 in Ishikawa cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of HEC1B. Similar results were produced in tumor xenografts in nude mice. Conclusion: These results indicate that MKK4 acts as a tumor suppressor, and reduced expression of MKK4 may contribute to the development of endometrial cancer.

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Section: Methodsmentioning

confidence: 99%

Functional and Clinicopathological Analysis of Loss of MKK4 Expression in Endometrial Cancer

Ishikawa

Nakayama²,

Rahman³

et al. 2010

Oncology

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“…There are now several therapeutic drugs that have shown efficiency in colorectal cancer, although metastatic disease remains mostly incurable (1). One of the more potent drugs used in this disease is oxaliplatin, a third-generation platinum compound that forms intrastrand links between two adjacent quinine residues or a guanine and adenine, hence disrupting DNA replication and transcription (2). Oxaliplatin has significant antitumor activity in colorectal cancer and has been approved for this indication (3).…”

Section: Introductionmentioning

confidence: 99%

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer

Lan

Ahmed

Mehta

et al. 2007

Molecular Cancer Therapeutics

307

153

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The role of curcumin (diferuloylmethane), a proapoptotic compound, for the treatment of cancer has been an area of growing interest. Curcumin in its free form is poorly absorbed in the gastrointestinal tract and therefore may be limited in its clinical efficacy. Liposome encapsulation of this compound would allow systemic administration. The current study evaluated the preclinical antitumor activity of liposomal curcumin in colorectal cancer. We also compared the efficacy of liposomal curcumin with oxaliplatin, a standard chemotherapy for this malignancy. In vitro treatment with liposomal curcumin induced a dose-dependent growth inhibition [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt] and apoptosis [poly(ADP-ribose) polymerase] in the two human colorectal cancer cell lines tested (LoVo and Colo205 cells). There was also synergism between liposomal curcumin and oxaliplatin at a ratio of 4:1 in LoVo cells in vitro. In vivo, significant tumor growth inhibition was observed in Colo205 and LoVo xenografts, and the growth inhibition by liposomal curcumin was greater than that for oxaliplatin (P < 0.05) in Colo205 cells. Tumors from animals treated with liposomal curcumin showed an antiangiogenic effect, including attenuation of CD31 (an endothelial marker), vascular endothelial growth factor, and interleukin-8 expression by immunohistochemistry. This study establishes the comparable or greater growth-inhibitory and apoptotic effects of liposomal curcumin with oxaliplatin both in vitro and in vivo in colorectal cancer. We are currently developing liposomal curcumin for introduction into the clinical setting.

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“…Despite the recent development of drugs such as irinotecan, oxaliplatin, bevacitumab and cetuximab, 5-Xuorouracil (5-FU) continues to have an important role in the management of advanced colorectal cancer (Douillard et al 2000;Bleiberg 1998;Punt 1998). Uracil-tegafur (UFT) is a preparation combining uracil and tegafur in a Wxed molar ratio of 4:1 .…”

Section: Introductionmentioning

confidence: 99%

Clinical identification of colorectal cancer patients benefiting from adjuvant uracil–tegafur (UFT): a randomized controlled trial

Fujii

Takayama

Kochi

2008

J Cancer Res Clin Oncol

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Purpose A randomized controlled trial was conducted to determine whether pathologic necrosis in response to preoperative treatment with uracil-tegafur(UFT) could be used to identify patients with colorectal cancer most likely to beneWt from postoperative adjuvant therapy with the drug. Patients and methods The 152 patients with colorectal cancer who received preoperative UFT at a dose of 600 mg/ day for at least 10 days were classiWed into two groups according to the pathologic necrosis in resected tumor specimens: 90% or more necrosis (sensitive) versus less than 90% necrosis (insensitive). After excluding 13 ineligible patients, the remaining 139 were then randomly assigned to receive postoperative adjuvant UFT (400 mg/day) for 12 months or no treatment. Results Preoperative and postoperative UFT produced no serious toxicity in any of the patients. Among the 22 patients with sensitive tumors, overall survival was signiWcantly better in the UFT group (n = 12) than in the control (n = 10) (100 vs. 70.0%; P = 0.023). Among the 117 patients with insensitive tumors, there was no signiWcant diVerence between the two groups (n = 60, 68.1% vs. n = 57, 76.6%; P = 0.373). Conclusion Our method involving neoadjuvant UFT can identify patients most likely to beneWt from postoperative UFT, as well as those unlikely to beneWt from such treatment.

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Oxaliplatin (L-OHP): a new reality in colorectal cancer

Cited by 54 publications

References 8 publications

Functional and Clinicopathological Analysis of Loss of MKK4 Expression in Endometrial Cancer

Functional and Clinicopathological Analysis of Loss of MKK4 Expression in Endometrial Cancer

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer

Clinical identification of colorectal cancer patients benefiting from adjuvant uracil–tegafur (UFT): a randomized controlled trial

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