The COMET Open-label Phase II Study of Neoadjuvant FOLFOX or XELOX Treatment Combined with Molecular Targeting Monoclonal Antibodies in Patients with Resectable Liver Metastasis of Colorectal Cancer.

BACKGROUND: Advantages of neoadjuvant chemotherapy combined with monoclonal antibodies for treating patients with resectable colorectal cancer liver metastasis (CLM) have not been established. The purpose of this study was to evaluate the efficacy and safety of oxaliplatin-based regimen (FOLFOX or XELOX) plus monoclonal antibodies (cetuximab or bevacizumab) treatment in patients with resectable CLM. METHODS: A single-arm, open-label, multicenter, phase II trial was conducted for patients aged ≥ 20 years with resectable and untreated CLM. Patients received preoperative FOLFOX (6 cycles) or XELOX (4 cycles). Cetuximab or bevacizumab was administered to patients with wild-type or mutated KRAS codons 12 and 13, respectively. The primary endpoint was progression-free survival (PFS). RESULTS: Between January 2010 and June 2012, 47 patients were enrolled from 12 institutions. Wild-type or mutant KRAS sequences were examined in 32 and 15 patients, respectively. Twenty-one (45 %) patients experienced Grades 3/4 adverse events, and 55 % of all patients responded to therapy. The sizes of tumors of patients in the wild-type KRAS group were significantly reduced compared with those of the mutant KRAS group. The overall rates of liver resection and postoperative morbidity were 83 and 14 %, respectively, and the median PFS was 15.6 months. The median PFS times of the KRAS wild-type and mutant groups were 22.5 months and 10.5 months, respectively. CONCLUSIONS: Neoadjuvant therapy using FOLFOX/XELOX combined with monoclonal antibodies did not improve PFS, although it was administered safely and had less adverse effects after liver resection.

Inflammatory pseudotumor of the liver diagnosed as metastatic liver tumor in a patient with a gastrointestinal stromal tumor of the rectum: report of a case.

BACKGROUND: Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion. A case of IPT of the liver found in association with a malignant gastrointestinal stromal tumor (GIST) is reported. CASE REPORT: A 74-year-old man was admitted to our hospital for a liver tumor. He previously underwent rectal amputation for a malignant GIST. Computed tomography (CT) revealed a low-density area in the liver and dynamic contrast-enhanced MRI (EOB-MRI) showed that the tumor was completely washed out in the delayed phase. 18Fluorine-fluorodeoxyglucose positron emission tomography (FDG-PET) showed strong uptake in the liver. A diagnosis of liver metastasis was made and partial hepatectomy was performed. Microscopic examination showed that the tumor was an IPT. CONCLUSION: Differential diagnosis between IPT and malignant neoplasms is difficult. Moreover, FDG-PET revealed strong uptake in the tumor. To our knowledge, this is the first patient reported to have an IPT in association with a rectal GIST. This patient is discussed along with a review of the literature.

Comparative analysis of MRSA strains isolated from cases of mupirocin ointment treatment in which eradication was successful and in which eradication failed.

Nasal decolonization in methicillin-resistant Staphylococcus aureus (MRSA) carriers using mupirocin (MUP) is a strategy that complements barrier precautions and contact isolation. However, eradication failure cases have been observed despite isolates being susceptible to MUP. This would suggest that the minimum inhibitory concentration (MIC) alone is not the only determinant of successful eradication. In this study, we undertook a comparative analysis of MRSA isolates from cases of successful and unsuccessful MUP-eradication treatment. The analyses we carried out were: determination of mupirocin MICs, sequencing of the isoleucyl-tRNA synthetase (ileS) gene, staphylococcal cassette chromosome mec typing, and the assessment of slime production. MICs for all 14 of the successful nasal decolonization cases showed susceptibility to MUP, whereas 21 (87.5 %) of the 24 unsuccessful cases were MUP-susceptible, with low-level resistance seen in 3 (12.5 %) strains. In the analysis of mutations in the ileS gene, one strain with an MIC of 4 µg/ml exhibited a G1778A point mutation that has not been previously reported. In the 14 successful nasal decolonization cases, only 1 strain (7.1 %) was an MRSA slime-producer, compared with 19 (79.7 %) of the 24 MRSA strains that could not be eradicated after MUP treatment (p < 0.05). For the eradication of MRSA by MUP, it is possible that slime may affect drug penetration. In conclusion, slime production was the only significant difference between isolates recovered from successful and unsuccessful eradication cases.

Multicenter phase II study of modified FOLFOX6 as neoadjuvant chemotherapy for patients with unresectable liver-only metastases from colorectal cancer in Japan: ROOF study.

BACKGROUND: Neoadjuvant chemotherapy for unresectable colorectal liver metastases can reduce tumor size, which sometimes leads to curative resection. The aim of the present study was to identify and describe patients with initially unresectable liver-only metastases from colorectal cancer who obtained sufficient chemotherapeutic benefit that eventually lead to the removal of the metastatic diseases in the liver. METHODS: A phase II multicenter cooperative study was conducted in 38 medical institutions using modified FOLFOX6 (mFOLFOX6) as neoadjuvant chemotherapy from January 2008 to June 2009. Patients with liver-only metastases from colorectal cancer that was deemed not optimally resectable by liver surgeons received mFOLFOX6 as preoperative neoadjuvant chemotherapy for 6-8 cycles. Patients were reassessed for resectability after 6 cycles of mFOLFOX6. Surgery was carried out 3-6 weeks after chemotherapy. The primary endpoint was the rate of macroscopic curative surgery including liver resection. RESULTS: 36 patients (23 male/13 female, ECOG performance status 0-1) were enrolled. The median age of the patients was 62.5 years; 78% (28 patients) had 5 or more metastatic tumors, and 50% (18 patients) had metastatic tumors over 5 cm diameter. The mFOLFOX6 regimen was safety administered resulting in 18 partial responses (50%), 12 stable disease, and 4 progressive disease. There was no grade 3/4 neurotoxicity. Fourteen patients (38.9%) underwent surgery (R0: 13; R1: 1). Of these, thirteen patients (36.1%) underwent R0 surgery. CONCLUSIONS: Our data suggest that mFOLFOX6 has a high response rate in patients with liver-only metastases from colorectal cancer, allowing for R0 resection of liver metastases in a proportion of patients initially not judged to be optimally resectable.

Carcinoembryonic antigen elevation in post-hepatectomy patients with colorectal cancer liver metastasis indicates recurrence with high accuracy.

BACKGROUND/AIMS: We aimed to retrospectively determine the accuracy of postoperative serum carcinoembryonic antigen (CEA) monitoring to detect or rule out recurrence in post-hepatectomy colorectal cancer patients by using a new statistical technique, likelihood ratio and post-test probability. METHODS: A total of 110 colorectal cancer patients who underwent curative hepatectomy were enrolled. A serum CEA assay and radiological examination were performed routinely for 5 years after surgery or until recurrence was detected. Yearly recurrence rates, sensitivities, specificities, and likelihood ratios were calculated. Post-test probabilities were calculated using these values. RESULTS: All episodes of recurrence occurred within 3 years after hepatectomy. The most frequent recurrence site was the liver, with a recurrence rate of 61.4% of all recurrence. The post-test probabilities of recurrence in post-hepatectomy colorectal cancer patients with positive and negative serum CEA were approximately 70-90% and 10%, respectively. CONCLUSIONS: CEA elevation in colorectal cancer patients who underwent curative resection indicated recurrence with high accuracy because of the high recurrence rate in the liver, in which CEA elevation is more frequent than in other recurrent sites. The elevation of CEA in post-hepatectomy patients necessitates frequent examination using imaging techniques to reveal undetected metastasis as soon as possible.

Curatively resected isolated inguinal lymph node metastasis from cecum cancer: report of a case.

We herein report the case of a curatively resected solitary inguinal lymph node metastasis from cecum cancer. Our patient was a 67-year-old male with cecum cancer with abdominal wall invasion. Three years after surgery, inguinal lymph node swelling was detected by a computed tomography examination. Further examination revealed no other metastases. Surgical resection was performed to remove the lesion, and microscopic examination revealed that cancer cells had metastasized. No recurrence was detected 3 years after the salvage surgery. Inguinal lymph node metastasis of cecum cancer has not been reported in the literature, but in our case salvage surgery resulted in a good outcome.

Transvaginal resection of a rectal gastrointestinal stromal tumor.

We herein report a case in which a rectal gastrointestinal stromal tumor (GIST) was resected transvaginally. The patient, a 45-year-old female, had a rectal GIST on the anterior wall of the lower rectum. The tumor was within 6 cm of the anal verge, a location which would normally require performing an ultra-low anterior resection using the Double Staple Technique, and a diverting stoma. To minimize the invasiveness of treatment and to reduce the postoperative morbidity, a transvaginal resection was performed. Under general anesthesia, the posterior vaginal mucosa was incised vertically. The tumor was then excised en bloc with the overlying rectovaginal septum and rectal mesenchymal tissue. The defect was repaired primarily, and a diverting stoma was not required. The procedure was uncomplicated, and the patient was discharged home with an intact anal sphincter function and no abdominal incisions. In female patients, transvaginal resection of low anterior rectal lesions may provide a minimally invasive alternative to the traditional ultra-low anterior resection.

Accuracy of monitoring serum carcinoembryonic antigen levels in postoperative stage III colorectal cancer patients is limited to only the first postoperative year.

PURPOSE: The aim of the present study was to determine the accuracy of yearly postoperative monitoring of serum tumor markers to either detect or rule out recurrence in colorectal cancer patients. METHODS: A total of 127 colorectal cancer patients who underwent curative surgery were enrolled. The serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were assayed, and radiological examinations were performed routinely for 5 years after surgery or until recurrence was detected. Yearly recurrence rates (number of recurrences/number of patients assessed in a given year), sensitivities, specificities, and likelihood ratios were calculated. Post-test probabilities were calculated from these values. RESULTS: Recurrences tended to show almost the same frequencies in the first and second year after surgery (20 of 127 patients and 18 of 107 patients, respectively). However, the post-test probability of recurrence in patients with positive and negative serum CEA levels was significantly lower in the second year than in the first year (test positive: 40.0% and 76.0%; test negative: 9.3% and 0.5%, respectively). CONCLUSIONS: Measuring CEA can help to identify patients likely to demonstrate recurrence with high accuracy only within the first year after surgery. Another examination, such as imaging, is therefore necessary for monitoring patients at 2 or more years after surgery.

IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells.

BACKGROUND: Type-1 insulin-like growth factor (IGF-1) up-regulates cell proliferation and invasiveness through activation of PI3K/Akt signaling pathway. IGF-1 also down-regulates the tumor suppressor chromosome 10 (PTEN). We investigated the mechanism by which IGF-1 affects cell proliferation and invasion by suppression of PTEN phosphorylation and interaction with PI3K/PTEN/Akt/NF-small ka, CyrillicB signaling pathway in pancreatic cancer. MATERIALS AND METHODS: The expression of IGF-1 receptor (IGF-1R) and PTEN in five pancreatic cancer cell lines was determined by RT-PCR and Western blot. Proliferation and invasion were investigated by WST-1 assay and Matrigel-double chamber assay. Pancreatic cancer cells were transfected with PTEN siRNA to investigate which signaling pathway correlates in regulation of cancer cell proliferation and invasion. RESULTS: Five pancreatic cancer cell lines expressed PTEN and IGF-1R in mRNA and protein levels. Suppression of PTEN phosphorylation strongly enhanced cell proliferation and invasion stimulated with IGF-1 via activation of PI3K/Akt/NF-small ka, CyrillicB signaling pathway. In addition, knockdown of PTEN by siRNA transfection also enhanced activation of PI3K/Akt/NF-small ka, CyrillicB pathway, subsequently up-regulating cell invasiveness and proliferation. CONCLUSIONS: The IGF-1/PI3K/PTEN/Akt/NF-small ka, CyrillicB cascade may be a key pathway stimulating metastasis of pancreatic cancer cells. We suggest that interfering with the functions of IGF-1/PI3K/Akt/NF-small ka, CyrillicB might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer.

Does serum carcinoembryonic antigen elevation in patients with postoperative stage II colorectal cancer indicate recurrence? Comparison with stage III.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the accuracy of postoperative monitoring of serum carcinoembryonic antigen (CEA) to detect or rule out recurrence in patients with stage II colorectal cancer (CRC) by comparing results with stage III. METHODS: A total of 303 patients with CRC who underwent curative surgery were enrolled. Serum CEA was assayed, and radiological examination was performed routinely for 5 years after surgery. Yearly recurrence rates, sensitivities, specificities, likelihood ratios, and posttest probabilities were calculated. RESULTS: Sensitivity and specificity of CEA monitoring in stage II patients are almost same as those in stage III. Whereas recurrences occurred early in stage III, they occurred almost as frequently in both early and late stage II. The obtained posttest probability of recurrence in stage II patients with CEA elevation was significantly lower (only 30% or less) than those in stage III (approximately 80%). CONCLUSION: Elevation of CEA in patients with stage II CRC does not represent recurrence with high probability. One of the reasons for the unreliability of CEA monitoring was its high false-positive rate. Another tumor marker with a lower false-positive rate is necessary to follow-up stage II CRC patients.

Interleukin-1alpha enhances angiogenesis and is associated with liver metastatic potential in human gastric cancer cell lines.

BACKGROUND: To better understand the underlying mechanism of liver metastasis formation in human gastric cancer, we evaluated the angiogenic capabilities of human gastric cancer cell lines with different metastatic potentials as well as the role of interleukin (IL)-1alpha in the angiogenic process. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction was used to detect the expression of IL-1alpha and vascular endothelial growth factor (VEGF) mRNA in gastric cancer cell lines with different liver metastatic potentials. Levels of VEGF secreted by human gastric cancer cells were measured by enzyme-linked immunosorbent assay. We also examined how gastric cancer cells with different metastatic potentials influence the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the Premix WST-1 cell proliferation assay system and an angiogenesis assay, respectively. RESULTS: IL-1alpha expression levels were significantly correlated with liver metastatic potential in gastric cancer cell lines. Levels of VEGF secreted by gastric cancer cells appear to be regulated by IL-1alpha through IL-1 receptor Type 1 and were correlated with liver metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with high liver-metastatic gastric cancer cells and were enhanced to a similar extent by culture in the presence of IL-1alpha. In contrast, blockade of IL-1alpha inhibited both HUVEC proliferation and angiogenesis. CONCLUSIONS: IL-1alpha may play a role in liver metastasis of gastric cancer via enhanced vascular endothelial cell proliferation and angiogenesis.

Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival.

BACKGROUND: The tumour suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. To evaluate the correlation between PTEN expression and clinicopathological characteristics of colorectal cancer patients with and without liver metastases, we investigated PTEN expression in primary colorectal cancer and colorectal cancer liver metastases. METHODS: Sixty-nine pairs of primary colorectal cancer and corresponding liver metastasis specimens were analyzed immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. Seventy primary colorectal cancer specimens from patients without liver metastases were used as controls. RESULTS: PTEN was strongly expressed in 44 (62.9%) colorectal cancer specimens from patients without liver metastases. In contrast, PTEN was weakly expressed in 52 (75.4%) primary colorectal cancer specimens from patients with liver metastases, and was absent in liver metastases. Weak PTEN expression in colorectal cancer tissues was significantly associated with advanced TNM stage (p < 0.01) and lymph node metastasis (p < 0.05). PTEN expression was significantly stronger in primary colorectal cancer specimens from patients without liver metastases. Furthermore, among colorectal cancer patients with liver metastases, the 5-year survival rate was significantly higher in patients with positive PTEN expression compared to those with negative PTEN expression (p = 0.012). CONCLUSION: Our results suggest that loss of PTEN expression is involved with colorectal cancer aggressive capacity and that diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for colorectal cancer patients.

Antiproteases in preventing the invasive potential of pancreatic cancer cells.

The process of tumor progression and metastasis involves degradation of the extracellular matrix and is governed by an intricate balance of proteases, their activators and their inhibitors, in which malignant cells are permitted to infiltrate the adjacent structures and gain access to lymph and blood vessels. These proteases can be broadly categorized into three families: matrix metalloproteinases, serine proteinases and cysteine proteinases, all of which have all been implicated in these processes. The presence of neural invasion is often considered to be a poor prognostic sign; however, the cellular mechanisms underlying this propensity for perineural invasion are unknown. We recently researched the relationship between the glial cell line-derived neurotrophic factor and perineural invasion by human pancreatic cancer cells. We also confirmed that NF-kappa B is a part of the signaling pathway from the glial cell line-derived neurotrophic factor in human pancreatic cancer cells, and documented the inhibitory effect of gabexate mesilate, a well-known non-physiological synthetic serine protease inhibitor, for pancreatic cancer invasion. Recent studies on the role of proteases and protease inhibitors in pancreatic cancer invasion are also reviewed.

Successful paclitaxel-based chemotherapy for an alpha-fetoprotein-producing gastric cancer patient with multiple liver metastases.

BACKGROUND: Alpha-fetoprotein (AFP)-producing gastric cancer is known to frequently cause multiple liver metastases and to have an extremely poor prognosis. CASE PRESENTATION: A 64-year-old Japanese man admitted to our hospital was diagnosed with gastric cancer with liver metastases. He underwent a total gastrectomy with splenectomy, and pathological stage IV disease according to the classification proposed by the Japanese Gastric Cancer Association was assigned. The histological diagnosis was poorly differentiated adenocarcinoma, and tumor production of AFP was confirmed by immunohistochemical staining. Following surgery, the patient received combination chemotherapy consisting of TS-1 and paclitaxel. Initially, AFP levels decreased dramatically and computed tomography (CT) revealed regression of liver metastases. However, multiple new liver metastases appeared and serum AFP levels increased after 5 months. A regimen of 5-FU plus paclitaxel followed by paclitaxel monotherapy was used next. Serum AFP levels once again decreased and CT showed regression or disappearance of liver metastases. The patient currently has a very good quality of life, and is receiving weekly paclitaxel monotherapy as an outpatient. No progression of liver metastases has been observed to date. CONCLUSION: We consider this rare case to have significant value with respect to treatment of AFP-producing gastric cancer with multiple liver metastases, and propose that combining surgery with chemotherapeutic agents such as paclitaxel may lead to a better prognosis in such cases.

The relationship between GDNF and integrins in human colorectal cancer cell activity.

BACKGROUND/AIMS: This study was performed to determine whether GDNF influences the expression of integrins in colorectal cancer cell lines and to elucidate the mechanisms of adhesion to and invasion of extracellular matrix (ECM) proteins. METHODOLOGY: The expression of integrin subunits and alteration of this expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in four human colorectal cancer cell lines. Assays to evaluate adhesion and invasion of cancer cells toward ECM proteins were conducted to investigate whether increased integrin expression affects the interaction between cancer cells and putative integrin ECM ligands. RESULTS: The RET/GFRalpha-1 receptor complex for GDNF was expressed in all four colorectal cancer cell lines. The expression of the Beta1 integrin subunit in these cells was significantly enhanced by GDNF. The enhancement and associated increase in adhesion and invasion abilities in response to by GDNF were inhibited by blocking the GDNF receptor or the integrin P1 subunit. CONCLUSIONS: In colorectal cancer, the enhancement of integrin expression by signaling through the GDNF receptor strongly influences adhesion to and invasion of ECM proteins.

The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells.

BACKGROUND: The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST), small-cell lung cancer and chronic myelogenous leukemia (CML). KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF)-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. RESULTS: RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2). 5 muM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 muM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. We propose that inhibitors of c-kit tyrosine kinase receptor have the potential to slow the progression of KIT-positive pancreatic cancers.

Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients.

Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6) in colorectal cancer (CRC). Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS) and disease-free survival (DFS) rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP) and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

Expression of glial cell line-derived neurotrophic factor family members and their receptors in pancreatic cancers.

BACKGROUND: The glial cell line-derived neurotrophic factor (GDNF) is a member of neurotrophic polypeptide family, which promotes survival and rescue of various neural cells in the central and peripheral nerve systems. We previously reported that GDNF promotes tumor cell invasion in pancreatic cancer cell lines. The purpose of this study was to investigate GDNF family expression and the status of related receptors in actual cancer tissues, and assess correlations with clinicopathologic behavior. METHODS: Immunohistochemical assessment of GDNF, neurturin, persephin, artemin, GDNF family receptor alpha-1 and alpha-2, and RET was performed for 51 cases of surgically resected pancreatic cancer. RESULTS: In all intrapancreatic nerves, GDNF and artermin were expressed strongly. In pancreatic cancer tissues. The expression of RET was stronger than that seen in normal ductal cells and was significantly related to the survival rate after resection (P = .026) and lymphatic invasion (P = .014). Intrapancreatic neural invasion was significantly related to the expression of GDNF (P = .047). CONCLUSIONS: We conclude that the expression of RET in pancreatic cancer tissues may be a useful prognostic marker and GDNF may play an important role in neural invasion.

Biological effect of irradiation on adhesion molecules in human colon cancer cells in vitro.

BACKGROUND: Carbohydrate antigens, such as sialyl Lewis(a) antigen (s-Le(a)) and sialyl Lewis(x) antigen (s-Le(x)), play an important role in cancer metastasis in vitro and in vivo. Currently, preoperative radiotherapy is used to prevent local recurrence of rectal cancer. We investigated the effects of X-ray irradiation on the carbohydrate antigens s-Le(a) and s-Le(x) in vitro. MATERIALS AND METHODS: The cell surface expressions of s-Le(a) and s-Le(x) were determined by flow cytometric analysis at 24 hours after X-ray irradiation of 4 human cancer cell lines. s-Le(a) and s-Le(x) functions were quantitated using a monolayer cell adhesion assay with human umbilical vein endothelial cells (HUVECs). RESULTS: The cell surface expressions of s-Le(a) and s-Le(x) decreased at 24 hours after irradiation. s-Le(a) adhesion to HUVECs monolayers similarly decreased at 24 hours after irradiation. CONCLUSION: These results may indicate a role for X-ray irradiation in the reduction of liver metastasis in patients with colon cancer.