Analysis of patient-dropouts from the critical pathways for gastric cancer

PURPOSE: This study was designed to determine the factors affecting completion of critical pathway for elective gastrectomy. METHODS: Since 2008, a critical pathway has been applied for elective gastrectomy at Chosun University Hospital. We retrospectively analyzed 252 patients who underwent elective gastrectomies from January 2009 to April 2013. The completion rate was determined, and risk factors for patient dropout were examined. RESULTS: The completion rate of the critical pathway was 45.6% (115/252). Mean length of stay was 11.7 +/- 8.6 days (8-59 days). Readmission rates were 4.4% (11/252). Causes of failure for clinical pathway were systemic complications (21/137, 15.3%), intra-abdominal complications (44/137, 32.8%), patient factors (41/137, 29.9%), and wound complications (30/137, 21.9%). There were no significant differences between the two groups in age, sex, American Society of Anesthesiologists (ASA) score, operation time, readmission, and underlying disease (P > 0.05). Body mass index (P = 0.008) and pathologic stage (P = 0.001) were significantly different between the two groups. In multivariate analysis, the conventional approach (odds ratio, 2.0), and total gastrectomy (odds ratio, 5.3) were determined to be independent risk factors to drop the critical pathway. But there were no significant differences between total and distal gastrectomy groups in age, gender, underlying diseases, ASA score, readmission, operation time, and cause of dropout (P > 0.05). CONCLUSION: We concluded that total gastrectomy may not be suitable for the critical pathway. We suggest that the critical pathway for elective distal gastrectomy is divided 2 subgroups, according to the surgical approach.

Ewing's Sarcoma of the Stomach; Rare Case of Ewing's Sarcoma and Suggestion of New Treatment Strategy

Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months.

Ewing's Sarcoma of the Stomach; Rare Case of Ewing's Sarcoma and Suggestion of New Treatment Strategy

Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months.

Consideration of Cardia Preserving Proximal Gastrectomy in Early Gastric Cancer of Upper Body for Prevention of Gastroesophageal Reflux Disease and Stenosis of Anastomosis Site

PURPOSE: The aim of this study is to evaluate the feasibility and safety of cardia preserving proximal gastrectomy, in early gastric cancer of the upper third. MATERIALS AND METHODS: A total of 10 patients were diagnosed with early gastric cancer of the upper third through endoscopic biopsy. The operation time, length of resection free margin, number of resected lymph nodes and postoperative complications, gastrointestinal symptoms, nutritional status, anastomotic stricture, and recurrence were examined. RESULTS: There were 5 males and 5 females. The mean age was 56.5+/-0.5 years. The mean operation time was 188.5+/-0.5 minutes (laparoscopic operation was 270 minutes). Nine patients were T1 stage (T2 : 1), and N stage was all N0. The mean number of resected lymph nodes was 25.2+/-0.5. The length of proximal resection free margin was 3.1+/-0.1 cm and distal was 3.7+/-0.1 cm. Early complications were surgical site infection (1), bleeding (1), and gastro-esophageal reflux disease (1) (this symptom was improved with medication). Late complications were dyspepsia (3) (this symptom was improved without any treatment), and others were nonspecific results of endoscopy or symptom. CONCLUSIONS: Cardia preserving proximal gastrectomy was feasible for early gastric cancer of the upper third. Further evaluation and prospective research will be required.

Impacts of Cytosolic Phospholipase A2, 15-Prostaglandin Dehydrogenase, and Cyclooxygenase-2 Expressions on Tumor Progression in Colorectal Cancer

PURPOSE: In addition to cyclooxygenase-2 (COX-2) which is related to prostaglandin E2 synthesis, other enzymes such as cytosolic phospholipase A2 (cPLA2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH) have been suggested to be related to carcinogenesis of colorectal cancer (CRC). The aim of this study was to investigate the roles of cPLA2, COX-2, mPGES-1, and 15-PGDH in tumor progression. MATERIALS AND METHODS: cPLA2, COX-2, mPGES-1, 15-PGDH, and vascular endothelial growth factor (VEGF) expressions were immunohistochemically examined in 89 CRC, and their expressions were compared with each other or clinicopathologic parameters as well as VEGF as tumor progression parameters. RESULTS: cPLA2 was expressed in 54.5%, COX-2 in 80.5%, mPGES-1 in 96.4%, 15-PGDH in 46.1%, and VEGF in 65.9%. The expression of cPLA2 correlated with VEGF expression. COX-2 expression was correlated with the depth of invasion, tumor stage, cPLA2, and VEGF expressions. Moreover, VEGF revealed the highest expression in the tissues positive for both cPLA2 and COX-2. Furthermore, 15-PGDH expression was inversely correlated with VEGF expression. CONCLUSION: The present study demonstrates that cPLA2 and mPGES-1, in addition to COX-2, are constitutively overexpressed, and that 15-PGDH might be attenuated in colorectal cancer. Furthermore, cPLA2 and 15-PGDH as well as COX-2 could have an important role in tumor progression.

The Clinicopathologic Features of Synchronous and Metachronous Cancer in Patients with Gastric Cancer

PURPOSE: With the development of diagnostic techniques, second primary neoplasms such as synchronous or metachronous cancers in gastric cancer patients are being increasingly found. In this study, we investigated the clinicopathological features and clinical significance of gastric neoplasms combined with synchronous and metachronous cancers. MATERIALS AND METHODS: 1,048 patients who were diagnosed with gastric cancer in Chosun University Hospital from January 1998 to March 2008 were retrospectively reviewed. RESULTS: 38 of the 1,048 patients with gastric cancer (3.6%) had synchronous and metachronous cancers. Of the 38 patients, 16 patients (42.1%) had synchronous cancer and 22 patients (57.9%) had metachronous cancer. The average time interval between gastric cancer and the secondary primary cancer was 27.08+/-31.25 months. The most common second primary neoplasm was lung cancer (8/38, 21.1%), followed by colorectal cancer (8/38, 21.1%). Among the 27 patients who underwent surgical resection for gastric cancer, 5 patients (18.5%) were in the synchronous group and 22 patients (81.5%) were in the metachronous group. The mean survival time of the 38 patients was 49.8 months. The mean survival time was 24.6 months for the synchronous cancer patients and 68.1 month for the metachronous cancer patients. The 3 year survival rate of the synchronous group and the metachronous group was 33.3% and 81.1%, respectively. CONCLUSION: We must pay attention on the preoperative workup for synchronous cancer and on the postoperative follow-up for metachronous cancer in gastric cancer patients.

Clinicopathologic Findings of Micropapillary Carcinomas, according to Tumor Size

PURPOSE: Papillary thyroid microcarcinomas (PTMC), which are not palpable and have no clinical symptoms are 1.0 cm or less in diameter. The optimal extent of thyroid tumor resection has been controversial. We investigated clinicopathological findings of PTMC of 5 mm or less in diameter for reasonable therapeutic approach. METHODS: From, Jan. 2002 to Dec. 2006, 366 patients underwent thyroidectomy for thyroid papillary carcinoma at our institution. Among these patients, 62 patients with a mass measuring less than 5 mm and 103 patients with a mass 5 mm to 1.0 cm were selected. We retrospectively reviewed their medical records. RESULTS: There was no significant difference on the clinical characteristics except multifocality. We performed more unilateral lobectomy, near total thyroidectomy with or without neck node dissection in patients with PTMC of less than 5 mm (P=0.13). In permanent biopsy, lymph node metastasis more frequently occurred in patients with PTMC of less than 5 mm (P=0.03). There were no differences in capsular invasion, distant metastasis or recurrence. CONCLUSION: In papillary thyroid microcarcinoma less than 0.5 cm, it is very uncommon for capsular invasion, distant metastasis and locoregional metastasis to exist. The extent of tumor resection may be limited less than near total thyroidectomy for suitable cases, because there was no locoregional metastasis or distant metastasis in the follow-up period. Longer follow-up periods would be required to confirm that limited surgery is sufficient for tumors less than 0.5 cm in size.

Expression of Vascular Endothelial Growth Factor in Colorectal Cancer

PURPOSE: The neovascularization is an essential factor for the growth of solid organ cancer and especially vascular endothelial growth factor (VEGF) has been known to the very important mediator of neovascularization. Thus, this study was searching that expression of VEGF in colorectal cancer correlate to clinicopathologic factors. METHODS: We analyzed 93 patients with sporadic colorectal cancer who underwent colectomy and their specimens were studied immunohistochemistry at Chosun University hospital from March, 2002 to November, 2005. RESULTS: The expression rate of VEGF was 61 cases of all (65.6%). There were no significant relation VEGF expression to age, sex and lymph node metastasis. But, VEGF expression in colon cancer was 80.5% rather than 53.8% in rectal cancer (P=0.010). Correlation with T staging, expression of VEGF was 10.0% in pT0, 62.5% in pT1, pT2 and 77.2% in pT3, pT4 (P<0.0001), and correlation with TNM staging, expression of VEGF was 10.0% in stage 0, 63.2% in stage I, 72.0% in stage II, 73.3% in stage III and 100.0% in stage IV (P=0.001). CONCLUSIONS: Expression of VEGF in colorectal cancer closely correlates with cancer progression and VEGF was more expressed in colon cancer than rectum.

The Risk Factors Associated with Surgical Site Infection after an Abdominal Operation

PURPOSE: Surgical site infection (SSI) is the most common nosocomial infection in surgical patients, and this accounts for 38% of all patients with nosocomial infections. Despite the advances in techniques and knowledge to prevent infection, SSI remains a significant source of postoperative morbidity and mortality, and it results in a prolonged hospital stay and increased cost. This study aims to assess the incidence of SSI and to identify the risk factors associated with SSI for patients who undergo abdominal operation. METHODS: The data on 347 abdominal operations that were done under general anesthesia from 1 August 2005 to 31 July 2006 was collected and reviewed. RESULTS: The overall incidence of SSI was 4.9%. Comorbidity was the independent risk factor for the development of SSI (P=0.011). The development of SSI was related with the American Society of Anesthesiologists (ASA) preoperative assessment score (P=0.025). The duration of the operation had a statistically significant association with an increased risk of SSI on univariate analysis. The wound classification was not associated with SSI. Staphylococcus aureus was the most frequently isolated organism, and all of the cases were methcillin-resistant Staphylococcus aureus. CONCLUSION: This study demonstrate that comorbidity is a significant independent risk factor for SSI.

A Case of Gastroduodenal Fistula Caused byIngested Magnetic Foreign Bodies / 대한소아소화기영양학회지

If multiple magnets are ingested, the potential exists for the magnets attracting one another across the gastrointestinal tract and inducing pressure necrosis, perforation, fistula formation, or intestinal obstruction. We report the case of a 12-year-old boy who suffered from a fistulous communication between the lesser curvature of the mid-body of the stomach and the duodenal bulb, caused by 4 ingested magnets (Singing Magnets, China). The patient presented with moderate mental retardation, a one-year history of cyclic vomiting, and abdominal discomfort. We present the findings of simple abdominal radiography, esophagogastroduodenoscopy, computed tomography, and upper gastrointestinal series. An emergency exploratory laparotomy was performed, which revealed a gastroduodenal fistula. Fistula repair and the removal of 4 magnetic toys were subsequently performed. We emphasize that clinicians who care for children should be aware of the hazards of magnetic toy ingestion.

Clinical Features of Patients with Stage IV Gastric Cancer

PURPOSE: The early detection of gastric cancer and accuracy of preoperative staging has currently been on the increase due to the development of endoscopy and imaging techniques, but there are still many cases of advanced gastric cancer detected at the first diagnosis and there are also many cases of stage IV gastric cancer diagnosed after a postoperative pathological examination. Although the prognosis of stage IV gastric cancer is very poor, this study was performed to determine the value of the use of aggressive treatment determined after a clinical analysis. MATERIALS AND METHODS: We retrospectively analyzed 150 patients that were diagnosed with stage IV gastric cancer among 1376 patients who underwent a laparotomy for gastric cancer from January 1994 to December 2006. RESULTS: Of the 150 patients with stage IV gastric cancer who underwent a laparotomy, there were 104 men and 46 women. The mean patient age was 57.8 years (age range, 28~93 years). A subtotal gastrectomy or total gastrectomy was performed in 119 patients and 31 patients underwent an explorative laparotomy. The mean survival time of patients that underwent a gastrectomy and patients that did not undergo a gastrectomy was 722 days (range, 14~4,559 days) and 173 days (range, 16~374 days), respectively this result was statistically significant. When patients that underwent a gastrectomy were classified according to the TNM stage, the mean survival time of 33 patients with stage T4 disease was 534 days (range, 17~3,378 days) and the mean survival time of 63 patients with stage N3 disease was 521 days (range, 14~4,190 days), but there was no statistical significance. Chemotherapy was administered to 98 patients and 52 patients did not receive chemotherapy. The mean survival time of patients that received chemotherapy was 792 days (range, 36~4,559 days) and the mean survival time of patients that did not receive chemotherapy was 243 days (range, 14~2,413 days), with statistical significance. CONCLUSION: If there is no evidence of distant metastasis in stage IV gastric cancer, one can expect improvement of the survival rate by the use of aggressive treatment, including curative gastric resection with radical lymph node dissection and chemotherapy.

Primary Squamous Cell Carcinoma of the Stomach that was Misdiagnosed as a Submucosal Tumor

Squamous cell carcinoma (SCC) of the stomach is relatively rare. We report a patient with a primary SCC of the stomach that was initially misdiagnosed as a submucosal tumor. The patient was a 64-year-old male who had a large submucosal tumor in the gastric fundus. Gastric endoscopy, endoscopic ultrasonography and abdominal computed tomography indicated a malignant submucosal tumor with multiple lymph node metastases. The patient underwent a total gastrectomy and a regional lymph node dissection. Histologically, the tumor was identified as a primary SCC of the stomach.

Clinicopathologic Characteristics and the Prognosis of Gastric Cancer Patients at Both Extremes of Age

PURPOSE: There have been several comparative studies that have focused on elderly groups of patients with gastric cancer. However, new criteria are needed for this elderly group because of the longer life span of Korean people. The diagnosis of gastric cancer has sometimes been missed in the young age group. The perioperative risk is high in the elderly age group because of their combined diseases. This study was designed to determine the differences of the clinicopathologic features and the prognosis between young and elderly patients with gastric cancer. MATERIALS AND METHODS: Eighty patients were divided in two groups and these patients were selected for making comparison between young and elderly groups of patients with gastric cancer. The young age group consisted of 31 patients who were aged 35 years old or less. The elderly age group was made up of 49 patients who were aged 75 years old or above. RESULTS: For the clinicopathologic features, the young age group was characterized by a high incidence of the poorly differentiated type of adenocarcinoma and the diffuse type too, according to the Lauren classification. On the other hand, the elderly group was characterized by a high incidence of poorly to moderate differentiated adenocarcinoma and also the intestinal type according to the Lauren classification. The other clinical differences were unremarkable. Additionally, there was no survival advantage in the young age group compared to the elderly group. CONCLUSION: There were no clinicopathologic and prognostic differences between both extreme age groups. So, active surgical treatment is recommended even for the elderly patients group.

Recurrent Colonic Perforation after Successful Conservative Treatment of Colonoscopic Perforation

Although the management of a colonic perforation after a colonoscopy is still controversial, conservative therapy is commonly used in those whose colonoscopy reveals a small perforation, those whose condition is relatively good, those who were diagnosed belatedly, or those who have not developed the symptoms of generalized peritonitis. We encountered a case of recurrent colonic perforation after successful conservative treatment for a colonoscopic perforation of the sigmoid colon in a 69-year-old female, who was treated with tube sigmoidostomy.

Expression of Cyclooxygenase-2 and its Relationship to p53 Accumulation in Colorectal Cancers

PURPOSE: Cyclooxygenase (COX)-2 is an inducible isoform responsive to cytokines, mitogens, and growth factors, and is believed to be an important enzyme related to colorectal cancer (CRC). Existing evidence suggests that COX-2 expression is normally suppressed by wild-type p53 but not mutant p53, suggesting that loss of p53 function may result in the induction of COX-2 expression. The aim of this study was to determine the relationship between COX-2 expression and p53 levels in CRC. MATERIALS AND METHODS: Patients with sporadic colorectal adenocarcinoma (n=161) who underwent curative surgery in Chosun University Hospital were enrolled in this study. Expression of COX-2 and p53 proteins was examined by immunohistochemistry in paraffin-embedded cancer tissue blocks, and the relationship between COX-2 and/or p53 expression with clinicopathologic parameters was analyzed. RESUTLS: Expression of COX- 2 was positive in 47.8% of colorectal cancers, and significantly associated with the depth of tumor invasion (p= 0.042). In contrast, p53 was positive in 50.3% of the cases, and was associated with both age (p=0.025) and the depth of tumor invasion (p=0.014). There was no correlation between COX-2 expression and p53 expression (p=0.118). CONCLUSION: These results suggest that COX-2 expression might play an important role in the progression of colorectal cancer. However, COX-2 expression was not associated with mutational p53. Further studies are needed to clarify the regulatory mechanisms governing COX-2 overexpression in colorectal cancers.

Operative Treatment of Patients Over 75 Years Old with Gastric Cancer

PURPOSE: The incidence of gastric neoplasms is increasing in the elderly population, and a rational method of treatment for gastric cancer in the elderly is needed to improve survival. The purpose of the present study was to clarify whether the patient's age is an independent prognostic factor and to determine clinicopathological characteristics in the elderly. MATERIAL AND METHODS: Curative or palliative surgery for gastric cancer was carried out on 706 patients in Chosun University Hospital from March 1995 to February 2002. They were divided into the following two groups: elderly group (75 years or older) and control group (under 74 years old). The clinicopathologic features of these patients were reviewed retrospectively, and a multivariate analysis was performed. RESULTS: There was no difference in clinicopathological appearances between the two groups, and the postoperative morbidity and mortality rates were similar in the two groups. The two groups showed similar survival rates. CONCLUSION: In this study, age was not a prognostic factor in surgery for gastric cancer. In the elderly, an oncologically correct surgical procedure can safely be prosecuted with satisfactory early and late results.

The Significance of CD24 Expression in Gastric Adenocarcinoma

PURPOSE: CD24 is a small heavily glycosylated glycosyl- phosphatidylinositol-linked cell surface protein expressed in hematological malignancies as well as a large variety of solid tumors. It appears to function as a ligand of P-selectin, an adhesion molecule present in activated platelets and endothelial cells. The authors aimed to evaluate the expression of CD24 in adenomas and adenocarcinomas of the stomach and its correlation to clinicopathological data. METHODS: A series of 48 adenocarcinoma cases (advanced gastric carcinoma: 24 cases, early gastric carcinoma: 24 cases) and 12 adenoma cases of the stomach were immunohistochemically stained for correlation with the clinicopathological data. The staining was evaluated as stainability (negative, weak-, moderate-, strong-positive) and staining patterns (membranous vs. intracytoplasmic), which were used for statistical analyses. RESULTS: The present study clearly demonstrated that the stainability of CD24 expression increased with positive nodal status in advanced gastric carcinomas (P<0.005). The stainability of CD24 in the adenocarcinoma group was much higher than in the adenoma group, but this was not statistically significant. Intracytoplasmic CD24 expression was demonstrated only in the adenocarcinoma group, with the exception of the adenoma group, but this also was not statistically significant. CONCLUSION: The authors conclude that the stainability of CD24 could be a molecular marker for gastric adenocarcinomas which could help to predict lymphogenous metastasis.

Expression and Function of ABC Transporters as Multidrug Resistance Mechansims in Gastric Cancer Cells

PURPOSE: Multidrug resistance (MDR) is a phenomenon whereby tumor cell acquire resistance to a broad range of structurally and functionally diverse chemotherapeutic drugs. The most widely implicated mechanism of MDR is that of altered membrane transporter in tumor cells. P-glycoprotein (Pgp), multidrug resistance protein (MRP), and breast cancer-resistance protein (BCRP) are well known membrane transporters, which pump out antitumor agents via an ATP-dependent process, the so called ATP-binding cassette (ABC) superfamily or transporter. This study was undertaken to test the prevalence of each ABC transporter, and which of then exhibit functional activity in various gastric cancer cells. METHODS: The expressions of Pgp, MRP, and BCRP mRNA were determined by RT-PCR assay on 10 gastric cancer cells. The sensitivity to anticancer agents, substrates for each ABC transporter in the gastric cancer cells was determined using the MTT assay. The intracellular accumulation of fluorescent compounds for the functional detection of each ABC transporter was determined using flow cytometry. RESULTS: The Pgp mRNA was expressed at various levels in 9 out of the 10 gastric cancer cells tested, but significantly low. MRP mRNA was constitutively expressed in all the cells. BCRP mRNA was differentially expressed in 5 of the gastric cancer cells. There was no relation between the expressions of Pgp and MRP and the cytotoxicity to each substrate. It was observed that the accumulations of paclitaxel and VP-16 were significantly increased on the additions of PSC833 and probenecid, respectively, in all tested cells. The reversal effect of drug accumulation by each inhibitor was much higher in the MRP than Pgp. With BCRP, the observed cytotoxic effect and amount of mitoxanthrone accumulation were less than in the cells expressing the highest levels of BCRP compared to those that did not. However the mitoxanthrone accumulation was not increased on the addition of FTC in the either cell type. CONCLUSION: This study suggests that of the ABC transporters, MRP has primarily functional activity, whereas that of Pgp is only slight, in the gastric cancer cells. Other possible MDR mechanisms involved will have to be explored in further studies.

Adjuvant Effect of NSAIDs on the Cytotoxicity of Colon Cancer Cells to 5-FU

PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the conversion of arachidonic acid to prostaglandins, is believed to be an important enzyme related to colorectal cancer. A large number of studies have supported the concept that non-steroidal anti-inflammatory drugs (NSAIDs) targeting COX alter the biologic processes of colon carcinogenesis. Although COX-2 inhibitors generally reduce the growth rate of established tumors, tumor regression is rarely observed. Hence, it is reasonable that COX-2 inhibitors be given in conjunction with standard anti-cancer therapy in treating cancer. We investigated whether aspirin and meloxicam not only are cytotoxic but also potentiate the antitumor effect of 5-Fluorouracil (5-FU) against colon cancer cells. METHODS: Expressions of COX-1 and COX-2 were determined by using the reverse transcriptase-polymerase chain reaction (RT-PCR) & Western blotting assay in 9 colon cancer cell lines. The cytotoxicities of NSAIDs and/or 5-FU were determined by using a microculture tetrazolium dye (MTT) assay. RESULTS: COX-1 mRNA and protein, as well as COX-2 mRNA, were variably expressed in all the cell lines tested whereas COX-2 protein was expressed in HT-29 and to a lesser extent in HCT-8, but not in the other cell lines. We selected two representative cell lines, HT-29 expressing COX-2 protein and SNU-C1 not expressing it. The dose-dependent cytotoxicity was observed in both cell lines treated with aspirin and with meloxicam. A combination treatment of aspirin or meloxicam with 5-FU revealed some additive effect, rather than a synergistic effect, for both cells lines. This additive effect was remarkable even for low concentrations of the drugs. Furthermore, the additive effect was highest when the combination was adminstered sequentially, 5-FU followed by aspirin or meloxicam, in both cell lines. CONCLUSIONS: These results suggest that a combination therapy using NSAIDs and 5-FU might be useful in the treatment of colon cancer cells not expressing COX-2, as well as in colon cancer cells expressing COX-2.

Expression and Function of ABC Transporters as Multidrug Resistance Mechansims in Colon Cancer Cells

PURPOSE: Multidrug resistance (MDR) is a phenomenon whereby tumor cells acquire resistance to a broad range of structurally and functionally diverse chemotherapeutic drugs. The most widely implicated mechanism of MDR is that concerned with altered membrane transporters in tumor cells. P-glycoprotein (Pgp), multidrug resistance protein (MRP), and breast-cancer-resistance protein (BCRP) are well-known membrane transporters that pump out antitumor agents by using an ATP-dependent process, the so-called ATP-binding cassette (ABC) superfamily or transporter. This study was undertaken to test the prevalence of each ABC transporter and to determine which transporter has functional acitivity in various colon cancer cells. METHODS: Expressions of Pgp, MRP, and BCRP mRNA were determined in 9 colon-cancer cell lines by using an RT-PCR assay. The sensitivity to anticancer agents substrate for each ABC transporter in the colon cancer cells determined using an MTT assay. The accumulation of fluorescent compounds for functional detection of each ABC transporter was determined by using flow cytometry. RESULTS: Pgp mRNA was variably expressed in 6 of 9 colon cancer cells lines. MRP and BCRP mRNA were expressed in all the 9 cell lines. A smaller cytotoxic effect to paclitaxel and a smaller amount of rhodamine123 accumulation were observed in Colo 320HSR expressing the highest levels of Pgp than in SNU-C5 not expressing Pgp. These effects in Colo320HSR were reversed with the addition of various Pgp inhibitors, but such a reversal did not occur in SNU-C5. The cytotoxic effect to VP-16 was not related to the expression levels of MRP in Colo320HSR and SNU-C, but the amount of calcein-AM accumulation was reversed with addition of probenecid, MRP inhibitor. The cytotoxic effect and the drug accumulation of mitoxantrone were not related to the expression levels of BCRP. CONCLUSIONS: This study suggests that of the ABC transporters, primarily Pgp and MRP have functional activity in colon cancer cell lines.