A phase II study of bevacizumab with modified OPTIMOX1 as first-line therapy for metastatic colorectal cancer: the TCOG-GI 0802 study.

Background: Although bevacizumab plus FOLFOX is a standard treatment for metastatic colorectal cancer, oxaliplatin must be withdrawn in many patients because of cumulative neurotoxicity. We postulated that a reduced dose of oxaliplatin and modified treatment schedule would prolong the time to treatment failure and evaluated bevacizumab combined with a modified OPTIMOX1 regimen (mOPTIMOX1, oxaliplatin dose: 85 mg/m(2)).

Methods: Eligible patients had a histologically confirmed diagnosis of metastatic colorectal cancer and a performance status of 0-1.

Serum vimentin methylation as a potential marker for colorectal cancer.

Aims: The present study aimed to examine the feasibility of detecting vimentin (VIM) methylation in the serum of patients with colorectal cancer (CRC) and to determine the effectiveness of a relatively simple, inexpensive, and non-invasive test performed in combination with the conventional carcinoembryonic antigen analysis.

Materials And Methods: VIM methylation in the serum DNA of 242 patients with CRC was measured by a quantitative methylation-specific polymerase chain reaction.

Results: A significantly higher positive rate was obtained for VIM methylation than for carcinoembryonic antigen or carbohydrate antigen 19-9 in stage 0, I, and II patients.

p16 Methylation is frequently detected in the serum of metastatic colorectal cancer patients.

For the purpose of detection of colorectal cancers, we tried to detect p16 methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP). Out of 211 serum samples derived from colorectal cancer patients, 14 (7%) exhibited p16 methylation in their serum DNA by qMSP. After completion of qMSP analysis in all specimens, clinicopathological data were correlated with the molecular analysis.

[Efficacy and safety of cetuximab+irinotecan for unresectable advanced or recurrent colorectal cancer].

Background: In July 2008, cetuximab treatment for unresectable advanced or recurrent colorectal cancer was approved in Japan, but there have been few reports on this therapy in Japan.

Purpose: We retrospectively analyzed the efficacy and safety of cetuximab(Cmab)+irinotecan(CPT-11)for unresectable advanced or recurrent colorectal cancer from October 2008 to April 2010 at 5 centers in the Kanagawa region.

Patients And Methods: The number of patients enrolled was 38, all of whom were treated after second-line therapy.

Methylation of the HACE1 gene is frequently detected in hepatocellular carcinoma.

Background/aims: Recently, it has been reported that HACE1, the E3 ubiquitin ligase, is epigenetically inactivated in human Wilms' tumors and HACE 1 expression was also down-regulated in colorectal and gastric carcinomas.

Methodology: In this study, methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 27 patients with HCC using quantitative methylation-specific PCR (qMSP).

Results: Methylation of the HACE1 gene was detected in 18 out of the 27 (67%) HCCs, suggesting that the methylation of HACE1 was frequently observed in HCC.

Methylation of the WNT5A gene is frequently detected in early gastric carcinoma.

Background/aims: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown.

Methodology: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated.

Methylation of the UNC5C gene is frequently detected in hepatocellular carcinoma.

Background/aims: Recently, we detected that UNC5C expression was downregulated in colon and gastric cancer.

Methodology: In the present study, the methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 42 patients with HCC.

Results: Methylation of the UNC5C gene was detected in 11 out of the 42 (26%) HCCs, suggesting that the methylation of UNC5C was frequently observed in HCCs.

FBN2 methylation is detected in the serum of colorectal cancer patients with hepatic metastasis.

Background, Materials And Methods: For the purpose of colorectal cancer detection, we investigated fibrillin-2 (FBN2) methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP).

Results: Out of 78 patients with colorectal cancer, 49 (63%) exhibited methylation of FBN2 in their tumor tissue DNA, suggesting that FBN2 methylation frequently exists in colorectal cancer. We next examined the methylation status of FBN2 in the serum DNA of patients with colorectal cancer.

Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum.

Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare disease, and many cases are either benign neoplasms or low-graded malignancies; however, a few cases show rapid progressive clinical courses. No effective therapy has yet been established for WDPMP, and the molecular basis of WDPMP tumorigenesis has never been reported. This study shows the malignant transformation of WDPMP in a Japanese female patient, who was alive for 54 months after the initial diagnosis by a laparoscopic biopsy.

Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase in patients with colorectal cancer.

Background: Predictors of the response of colorectal cancer to chemotherapy remain poorly understood. We analyzed the mRNA expression levels of enzymes related to sensitivity to 5-fluorouracil derivatives in patients with colorectal cancer.

Patients And Methods: Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer.

Methylation of the DFNA5 gene is frequently detected in colorectal cancer.

Background: Recently, the human deafness, autosomal dominant 5 gene, DFNA5, has frequently been detected in cancer tissues. The methylation status of the DFNA5 gene in colorectal cancer was examined and was compared to the clinocopathological findings.

Materials And Methods: Eighty-five tumor samples and corresponding normal tissues were obtained from patients with colorectal cancer who underwent surgery at our hospital.

Detection of vimentin methylation in the serum of patients with gastric cancer.

Aim: Detection of gastric cancer using serum assay of vimentin methylation.

Methods: A quantitative methylation-specific polymerase chain reaction assay was used to detect vimentin gene (VIM) methylation in the serum of 71 patients with gastric cancer.

Results: Mean VIM methylation in cancer patients (0.

Methylation of TFPI2 no longer detected in the serum DNA of colorectal cancer patients after curative surgery.

In our previous study, we used quantitative methylation-specific polymerase chain reaction (qMSP) to examine the methylation status of tissue factor pathway inhibitor 2 (TFPI2) in the preoperative serum DNA of 215 colorectal cancer patients and found that TFPI2 was methylated in serum DNA from 39 of these patients. In this study, we examined postoperative serum DNA, obtained within one month after surgery from 38 out of the 39 patients and found that TFPI2 was methylated in the serum DNA of only 18 (47%) of these patients, suggesting that TFPI2 methylation in the serum of the remaining colorectal cancer patients was abolished by surgical tumor reduction. Next, we examined the correlation between the presence of TFPI2 methylation in postoperative serum DNA and residual cancer status after surgery.

[Significance of Onodera's prognostic nutritional index for treating unresectable or recurrent colorectal cancer with chemotherapy].

We analyzed the relationship between Onodera's prognostic nutritional index(PNI), classified by serum albumin level, lymphocyte level, and clinicopathological features, in 46 patients with unresectable or recurrent colorectal cancer being treated with chemotherapy.Onodera 's PNI was distributed between 29.7 and 56.

Detection of TFPI2 methylation in the serum of gastric cancer patients.

Background: Methylation of tissue factor pathway inhibitor-2 (TFPI2) has been detected in the stool of colorectal cancer patients. Using quantitative methylation-specific polymerase chain reaction (qMSP), 39 out of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that a significant number of methylated TFPI2 existed in colorectal cancer patients' sera.

Materials And Methods: Methylation status of the TFPI2 gene was examined in sera derived from 73 patients with gastric cancer using qMSP and the correlation between the methylation status and the clinicopathological findings was evaluated.

Down-regulation of EGFL8: a novel biomarker for advanced gastric cancer.

Background: Recently, we have reported an important role of epidermal growth factor-like domain 8 (EGFL8) in the progression of colorectal cancer (CRC) and documented EGFL8 to be a novel prognostic biomarker for this malignancy. However, the function of EGFL8 in the other human gastroenterological malignancies such as gastric cancer remains largely unknown.

Patients And Methods: EGFL8 expression in 53 cases of gastric cancer and the corresponding normal tissues were determined by quantitative real-time PCR and the EGFL8 down-regulation score for each patient was calculated.

Methylation of the homeobox gene, HOPX, is frequently detected in poorly differentiated colorectal cancer.

Background: Homeodomein only protein x (HOPX) gene methylation has frequently been detected in cancer tissues. The methylation status of the HOPX gene in colorectal cancer was examined and compared to the clinocopathological findings.

Materials And Methods: Eighty-nine tumor samples and corresponding normal tissues were obtained from colorectal cancer patients who underwent surgery at our hospital.

Detection of TFPI2 methylation in the serum of colorectal cancer patients.

We examined whether TFPI2 methylation can be used as a molecular marker for colorectal cancers by detecting TFPI2 methylation in colorectal cancer patients' sera by using quantitative methylation-specific polymerase chain reaction (qMSP). The qMSP analysis showed that 39 of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that TFPI2 methylation frequently existed in colorectal cancer patients' sera. After completion of qMSP analysis, clinicopathological data were correlated with molecular data.

[Complete response to S-1/CDDP combination in a patient with obstructive jaundice secondary to lymph node metastasis by gastric cancer - a case report].

A 55-year-old woman was found to have a type-4 lesion centered on the greater curvature of the lower portion of her stomach during an upper gastrointestinal endoscopic examination.A diagnosis of inoperable advanced gastric carcinoma [type 4, tub 2/por, T3 (SE), N3, H0, P1, cStage IV], complicated by pyloric stenosis, liver dysfunction, and obstructive jaundice untreatable by bile drainage, was made.After obtaining the informed consent of the patient and her family and explain- ing that under the circumstances surgery was not indicated, chemotherapy [S-1 (granules) 80 mg/m2, CDDP 60 mg/m2] was selected.

Down-regulation of EGFL8: a novel prognostic biomarker for patients with colorectal cancer.

Background: In a previous study, we reported a critical role of epidermal growth factor-like domain 7 (EGFL7) in the metastasis of hepatocellular carcinoma (HCC) and documented it to be a prognostic biomarker as well as a potential therapeutic target for HCC. However, the role of EGFL8, the only known paralog of EGFL7, in human malignancies is currently unclear.

Patients And Methods: EGFL8 expression in 101 cases of colorectal cancer (CRC) patients was determined by quantitative reverse transcription-polymerase chain reaction and the clinicopathological features of the CRC patients were correlated with the EGFL8 down-regulation scores.

Methylation of OSMR gene is frequently observed in non-invasive colorectal cancer.

Background: Recently, it has been reported that oncostatin M receptor-β (OSMR) is frequently methylated in primary colon cancer tissues, but not in normal tissues. We examined the methylation status of the OSMR gene in primary carcinomas and the corresponding normal tissues derived from 56 patients with colorectal cancer.

Patients And Methods: The methylation status of the OSMR gene was examined in primary carcinomas and corresponding normal tissues derived from 56 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP), and the correlation between the methylation status and the clinicopathological findings was evaluated.

Aberrant methylation of the Vimentin gene in hepatocellular carcinoma.

Background: Recently, it was shown that the Vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma.

Materials And Methods: The methylation status of the Vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 43 patients with hepatocellular carcinoma (HCC) using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated.

Results: Aberrant methylation of the Vimentin gene was detected in 24 out of the 43 (56%) primary HCC.

MACC 1 as a marker for vascular invasive hepatocellular carcinoma.

Background: Recently, metastasis associated with colon cancer 1 (MACC1) gene was identified by genome-wide search for differentially expressed genes in human colon cancer tissues and metastases. Previously, MACC1 expression was examined in colorectal carcinomas and gastric carcinomas and was found to show significant correlation with peritoneal dissemination.

Patients And Methods: In this study, MACC1 expression was analyzed in 60 samples (tumor and the surrounding non-tumorous liver tissue) collected from 30 patients with hepatocellular carcinoma (HCC) using quantitative real-time polymerase chain reaction (QRT-PCR).

TIP60 as a potential marker for the malignancy of gastric cancer.

Background: Recently, it has been shown that the loss of the human histone acetyl transferase, TIP60, led to an accumulation of double-strand DNA breaks and has been linked to a growing number of cancer types.

Materials And Methods: TIP60 expression levels were examined in 46 gastric cancer samples using a quantitative real-time polymerase chain reaction (QRT-PCR). Subsequently, clinicopathological data were correlated with the TIP60 expression score.