Comparative Study between Sentinel Lymph Node Biopsy and Axillary Dissection in Patients with One or Two Lymph Node Metastases / 한국유방암학회지

PURPOSE: Sentinel lymph node biopsy (SLNB) is a standard axillary surgery in early breast cancer. If the SLNB result is positive, subsequent axillary lymph node dissection (ALND) is a routine procedure. In 2011, the American College of Surgeons Oncology Group Z0011 trial revealed that ALND may not be necessary in early breast cancer with one or two positive sentinel lymph nodes. The purpose of this study was to compare outcomes among Korean patients with one or two positive axillary lymph nodes in the final pathology who did and did not undergo ALND. METHODS: A total of 131,717 patients from the Korea Breast Cancer Society registry database received breast cancer surgery from January 1995 to December 2014. Inclusion criteria were T stage 1 or 2, one or two positive lymph nodes, and having received breast-conserving surgery (BCS), whole breast radiation therapy, and no neoadjuvant therapy. We analyzed the differences in disease-specific survival (DSS) and overall survival (OS) between patients who received SLNB only and those who underwent SLNB+ALND. RESULTS: A total 4,442 patients met the inclusion criteria, with 1,268 (28.6%) in the SLNB group and 3,174 (71.4%) in the SLNB+ALND group. There were no differences in DSS and OS between the two groups (p=0.378 and p=0.925, respectively). The number of patients who underwent SLNB alone for one or two positive lymph nodes increased continuously from 2004 to 2014. CONCLUSION: Korean patients with early breast cancer and 1 or 2 positive axillary lymph nodes who received BCS plus SLNB showed no significant difference in DSS and OS regardless of whether they received ALND. The findings of this retrospective study demonstrate that omitting ALND can be considered when treating selected patients with early breast cancer who have one or two positive lymph nodes.

Basic Facts of Breast Cancer in Korea in 2014: The 10-Year Overall Survival Progress / 한국유방암학회지

We, the Korean Breast Cancer Society (KBCS), present the facts and the trends of breast cancer in Korea in 2014. Data on the total number of newly diagnosed patients was obtained from the Korea Central Cancer Registry database, other data were collected from the KBCS online registry database, and the overall survival data of patients were updated from Statistics Korea. A total of 21,484 female patients were newly diagnosed with breast cancer in 2014. The crude incidence rate and the age-standardized incidence rate (ASR) of breast cancer in female patients, including carcinoma in situ, were 83.4 cases and 63.9 cases per 100,000 women, respectively. The ASR showed an annual increase of 6.1% from 1999 to 2014; however, although the increase of the ASR had slowed since 2008, the incidence rate itself continuously increased. The proportion of early breast cancer increased consistently, and the pathological features changed accordingly. While breast-conserving surgery was mainly performed, the proportion of total mastectomy was slightly increased. The total number of breast reconstruction surgeries increased rapidly. The 5-year and 10-year overall survival rates for all stages of breast cancer patients were 91.2% and 84.8%, respectively. The overall survival rate of Korean patients with breast cancer was extremely high, compared with other developed countries. Thus, we consider that the clinical characteristics of breast cancer have changed over the past decade. A nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea.

Primary osteosarcoma of the breast: a case report

Primary osteosarcomas of the breast are extremely uncommon. Here we describe a case of a 77-year-old woman who presented with a hard mass on her right breast. Mammography and breast ultrasound demonstrated a round-shaped calcified mass on the right breast but the features were not definitely diagnostic. For diagnostic purposes, an excisional biopsy was performed and the mass proved to be a primary osteosarcoma of the breast by pathologic findings. PET-CT and whole body bone scan showed neither evidence of metastasis nor underlying bone lesions. Wide excision without axillary lymph node dissection was performed after diagnosis. Further treatment such as adjuvant chemotherapy or radiation therapy was not performed. We discuss proper treatment of this rare type of breast cancer.

The Basic Facts of Korean Breast Cancer in 2013: Results of a Nationwide Survey and Breast Cancer Registry Database / 한국유방암학회지

The Korean Breast Cancer Society (KBCS) has reported a nationwide breast cancer data since 1996. We present a comprehensive report on the facts and trends of breast cancer in Korea in 2013. Data on the newly diagnosed patients in the year 2013 were collected from 99 hospitals by using nationwide questionnaire survey. Clinical characteristics such as stage of cancer, histologic types, biological markers, and surgical management were obtained from the online registry database. A total of 19,316 patients were newly diagnosed with breast cancer in 2013. The crude incidence rate of female breast cancer including carcinoma in situ was 76.2 cases per 100,000 women. The median age at diagnosis was 50 years, and the proportions of postmenopausal women with breast cancer accounted for more than half of total patients. The proportion of early breast cancer increased consistently, and the pathologic features have changed accordingly. Breast-conserving surgery was performed in more cases than total mastectomy in the year. The total number of breast reconstruction surgeries markedly increased approaching 3-fold in last 11 years. According to annual percentile change of invasive cancer incidence, the incidence increased rapidly until 2010. And thereafter the increase of it became steadier. For ductal carcinoma in situ, the incidence consistently increased during the same period without any joinpoint. Analysis of nationwide registry data will contribute to defining of the trends and characteristics of breast cancer in Korea.

The Basic Facts of Korean Breast Cancer in 2012: Results from a Nationwide Survey and Breast Cancer Registry Database / 한국유방암학회지

The Korean Breast Cancer Society has constructed a nationwide breast cancer database through utilization of an online registration program. We have reported the basic facts about breast cancer in Korea in 2012, and analyzed the changing patterns in the clinical characteristics and management of breast cancer in Korea over the last 10 years. Data on patients newly diagnosed with breast cancer were collected for the year 2012 from 97 hospitals and clinics nationwide using a questionnaire survey, and from the online registry database. A total of 17,792 patients were newly diagnosed with breast cancer in 2012. The crude incidence rate of female breast cancer, including invasive cancer and in situ cancer, was 70.7 cases per 100,000 women. The median age at diagnosis was 51 years, and the proportion of postmenopausal women was higher than that of premenopausal women among those diagnosed with breast cancer. The proportion of cases of early breast cancer increased continuously, and breast-conserving surgery was performed in more cases than total mastectomy in that same year. The total number of breast reconstruction surgeries increased approximately 3-fold over last 10 years. The 5-year overall survival rate for all stages of breast cancer patients was extremely high. The clinical characteristics of breast cancer have changed in ways that resulted in high overall survival over the past 10 years in Korea, and the surgical management of the disease has changed accordingly. Analysis of nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea.

Erratum: The Basic Facts of Korean Breast Cancer in 2011: Results of a Nationwide Survey and Breast Cancer Registry Database / 한국유방암학회지

The funding source should be added.

The Basic Facts of Korean Breast Cancer in 2011: Results of a Nationwide Survey and Breast Cancer Registry Database / 한국유방암학회지

Breast cancer is the second most frequent malignancy in Korean women, with a continuously increasing incidence. The Korean Breast Cancer Society has constructed a nationwide breast cancer database through an online registration program. The aim of the present study was to report the fundamental facts on Korean breast cancer in 2011, and to analyze the changing patterns in clinical characteristics and breast cancer management in Korea over the last 10 years. Data on newly diagnosed breast cancer patients, including the total number of cases, age, stage, and type of surgery, for the year 2011 were collected from 84 hospitals and clinics nationwide using a questionnaire survey. Additional data relating to the changing patterns of breast cancer in Korea were collected from the online breast cancer registry database and analyzed. According to nationwide survey data, a total of 16,967 patients were newly diagnosed with breast cancer in 2011. The crude incidence of female breast cancer, including invasive cancer and in situ cancer, was 67 cases per 100,000 women. Analysis of the survey and registry data gave equivalent results in terms of age distribution, stage, and type of surgery. The median age at diagnosis was 50 years, and the proportion of postmenopausal women (51.3%) was higher than that of premenopausal women (48.7%) with breast cancer. The incidence of stage 0 and stage I breast cancer increased continuously over the last 10 years (56.3% in 2011), and breast conserving surgery (65.7%) was performed more frequently than total mastectomy (33.8%). The total number of breast reconstruction surgeries increased approximately 8-fold. We conclude that the clinical characteristics of breast cancer have changed over the past 10 years in Korea, and surgical management has changed accordingly. Analysis of nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea.

The Feasibility of Lateral Minimal Invasive Open Thyroid Lobectomy / 대한내분비외과학회지

PURPOSE: Minimal invasive open thyroidectomy is one option for minimal invasive surgery. The population of planned unilateral lobectomy is on the rise in parallel to the increased incidence of confined papillary thyroid microcarcinomas in Korea. In contrast to other minimal invasive modalities, few studies have examined the surgical outcome of minimal invasive open thyroidectomy. This study compared the lateral minimal invasive open thyroid lobectomy with conventional surgery and endoscopic surgery in terms of the feasibility and safety. METHODS: A retrospective study was performed on 197 patients undergoing a thyroid lobectomy between January 2001 and December 2010. One hundred and three patients underwent a lateral minimal invasive open thyroid lobectomy, 42 patients underwent conventional surgery, and 44 patients underwent endoscopic surgery. RESULTS: The hospitalization period with endoscopic surgery was 6.2 days, which was longer than the 5.3 days with a lateral minimal invasive open thyroid lobectomy (P=0.000). The surgical time was lower in those who underwent a lateral minimal invasive open thyroid lobectomy (88.2 minutes) than in those who underwent conventional surgery (107 minutes, P=0.000) or endoscopic surgery (124.1 minutes, P=0.000). In the patients with a diagnosis of malignancy, the mean number of retrieved LNs was similar in the three groups. CONCLUSION: A lateral minimal invasive open thyroid lobectomy offers advantages, such as a shorter surgical time and hospitalization period than others. This procedure can be a feasible alternative to the conventional or endoscopic approach in selected patients undergoing thyroid lobectomy.

The Prevalence of Ovarian Cancer in Korean Women at High-Risk for Hereditary Breast-Ovarian Cancer / 한국유방암학회지

PURPOSE: Few studies have reported ovarian cancer risks in Korean patients with the BRCA1/2 mutation. We investigated the prevalence of ovarian cancer in Korean women at high risk for hereditary breast-ovarian cancer (HBOC) syndrome and reviewed the clinicopathological factors of ovarian cancer. METHODS: Female subjects who were enrolled in the Korean Hereditary Breast Cancer study were included. The questionnaire included a personal and family history of cancer. The BRCA1/2 mutation and CA-125 level were tested at the time of enrollment. A transvaginal ultrasonogram (TVUS) was recommended for subjects with an elevated CA-125 level. RESULTS: A total of 1,689 patients were included. No ovarian cancer was newly diagnosed by CA-125 level or TVUS during the enrollment. The prevalence of ovarian cancer was 1.71% in BRCA1/2 mutation carriers and 0.39% in non-carriers. Among 11 patients with ovarian cancer, five had the BRCA1 mutation and one had the BRCA2 mutation. The most common histopathological type was serous cystadenocarcinoma. No difference in clinicopathological findings between BRCA1/2 mutation carriers and non-carriers was observed. CONCLUSION: The prevalence of ovarian cancer was 58-fold elevated in women at high-risk for HBOC syndrome and 146-fold elevated in the BRCA1 subgroup, compared with the Korean general population. Further investigation with a long-term follow-up is required to evaluate BRCA1/2 gene penetrance.

Central Lumpectomy with Resection of the Nipple-areolar Complex for Retroareolar or Central Breast Cancers

PURPOSE: This study was conducted to evaluate the outcome of central lumpectomy for breast conservation including nipple-areolar resection and postoperative radiation therapy in patients with central breast cancers. METHODS: 19 patients with central breast cancers, aged 39 to 72 years, operated on from May 2004 to March 2010 were identified. Recurrence, survival, and cosmesis were analyzed. Treatment was undertaken as complete excision of the nipple-areolar complex (NAC), followed by external radiation to the whole breast and tumor bed. The mean follow-up period was 37.9 (1 to 71) months. RESULTS: At pathology, 13 had invasive ductal carcinoma; 5 had ductal carcinoma in situ. 1 had neuroendocrine cancer. Only 1 had atypical ductal hyperplasia at resection margin; the remaining 18 were free margins. The mean tumor size was 1.6 cm (range, 0.8~4 cm) and the distance from the nipple was 0~1 cm. 37.5% had positive axillary nodes. Adjuvant chemotherapy was given for 12 patients, followed by radiation therapy. All 15 patients, who were hormone receptor positive, were given tamoxifen or aromatase inhibitors. With a mean follow up of 37.9 months, all 19 patients are alive and free of disease. Cosmetic results ranged from good to excellent in 18 (94.7%) patients, as judged by both the patients and the surgeons. CONCLUSION: Although this study needs further evaluation and long-term follow up, subareolar or central breast cancers can be successfully treated with breast conserving therapy using nipple-areolar resection and postoperative radiation therapy, along with acceptable cosmesis.

The Surgical Management of Papillary Thyroid Microcarcinoma / 대한내분비외과학회지

PURPOSE: There has been a rapid rise in the incidence of thyroid cancer, particularly papillary thyroid microcarcinoma (PTMC). However, there is a lack of consensus of treatment guidelines or follow-up strategies. METHODS: A retrospective analysis of 606 patients who underwent operation due to thyroid cancer from March 2000 to December 2008 was conducted. Of these patients, 587 with pure papillary carcinomas were studied, of whom 392 (67%) presented with PTMC. RESULTS: Only 23% of patients were symptomatic, but 75% of patients were positive using the imaging techniques ultrasonography or positron emission tomography. When the microcarcinoma patient group (G1) was compared with the group of remaining patients (G2), less aggressive operations were chosen for G1. A lobectomy was performed in 63.8% of G1 versus in 14% of G2, and the central compartment neck dissection was omitted in 30% of G1 versus 16% of G2. During the follow-up period (mean 37.9±25.2 months), there were 11 recurrences. Two patients developed contralateral cancers 42 and 49 months after lobectomy. One patient had recurrences on central compartment lymph nodes 34 months post-operatively. Eight patients had lateral neck lymph nodes metastases 13~52 months postoperatively. Three of these eight patients had concomitant central neck lymph node metastases. CONCLUSION: Less aggressive treatments can be chosen for PTMC patients compared to non-PTMC patients. To clarify these results, longer follow up and larger and multi-institutional data are needed.

Breast Cancer Screening: A Medical Audit of the Screening Mammography Performed at One Institution for 10 Years / 한국유방암학회지

PURPOSE: Screening for breast cancer has constantly been increasing since the benefit of screening for breast cancers was established. The purpose of this study was to investigate the efficacy of annual breast cancer screening at one institution for 10 years by conducting a medical audit. METHODS: From March 1995 to July 2004, we performed 110,588 annual clinical examinations and mammographies on 58,024 women, who wanted to undergo breast cancer screening. Two hundred fourteen breast cancers were detected during screening, and one hundred sixty one of these patients were operated on. We then compared these results with the ideal rates for medical audits. RESULTS: Of the 110,588 cases that were screened, the recall rate for further examination was 12.1% (n=13,423). The biopsy rate was 1.01% (n=1,116). Two hundred fourteen breast cancers were detected for a detection rate of 0.19%. The percent of stage 0 cancer among all the cancer was 23.6%, stage I was 40.4%, stage IIa was 19.9%, stage IIb and IIIa were a combined 6.2%, stage IIIc was 3.1%, and stage IV was 0.6%. The positive predictive value (PPV) based on the abnormal findings on the screening examinations was 1.6% (PPV1). The PPV when a biopsy or surgical consultation was recommended was 15.1% (PPV2). The percent of tumor found as stage 0 or I was 64% (103/161). The tumor found as minimal cancer (stage 0 or tumor lesser than 1 cm) was 38.5% (62/161). There were 38 cases of axillary lymph node metastasis (23.6%). The number of cases of cancers found per 1,000 cases was 1.7. The prevalence of cancer found per 1,000 first examinations was 2.3. The incidental cancer found per 1,000 follow-up examinations was 1.2. The recall rate for further evaluation was 12.1%. These results were compatible with the ideal rates for medical audits, except for the recall rate, the PPV1, the PPV2, and the cancers found per 1,000 cases. CONCLUSION: On the base of these results, breast cancer screening was properly performed in this institution. Breast cancer screening using a clinical examination and a mammography is effective for the early detection of breast cancer.

The Effect of Tumor Characteristics on the Repeated Nondiagnostic Fine-needle Aspiration Biopsy Results in Thyroid Nodules / 대한내분비외과학회지

PURPOSE: The management of nondiagnostic fine-needle as-piration biopsy (FNAB) of thyroid nodules has not been determined because the significance of persistent nondiagnostic FNAB has been underestimated. The purposes of the present study were to estimate the likelihood of malignancy in patients with nondiagnostic FNAB results and to evaluate whether tumor factors could affect the nondiagnostic FNAB results. METHODS: 2,400 FNABs were performed for thyroid nodules at our institution from 2001 to 2005. A total 294 patients who had initial nondiagnostic results were the subjects of this study. We retrospectively reviewed the age, gender, tumor size, the sonographic findings, the FNAB results and the pathologic reports. RESULTS: The initial nondiagnostic rate was 12.3% (294/2,400). Among the 294 initial nondiagnosted patients, FNAB was secondarily performed in only 99 patients. Seventy patients (70.7%) were diagnostic and 29 (29.3%) remained nondiagnosed. Twenty of seventy diagnosed patients had malignant FNAB results, including atypical cells, and the other 50 patients were benign. The causes of nondiagnostic FNAB results by pathologic descriptions were 43.1%: scanty cellularity, 29.2%: blood, 13.2%: fluid or colloid, 11.1%: inconclusive, and 3.5%: dry artifact. There are no differences in the nondiagnostic rate according to tumor size (P=0.2) and calcification (P=0.7). When the sonographic results could predict the pathologic results, no difference was noted according to the sonographic findings that determined malignancy (P=0.4). Ten percent of the initial nondiagnostic FNAB results were finally reported as malignancy. CONCLUSION: Scanty cellularity and blood aspiration were the major causes of nondiagnostic FNAB results (43.1% and 29.2%, respectively). Tumor characteristics such as tumor size, the presence of calcification and sonographic findings did not predict nondiagnostic FNAB results. Reaspiration biopsy for the initially nondiagnostic FNAB in the thyroid nodules had a high probability of achieving a nondiagnositc result. Because nondiagnostic FNAB of the thyroid nodules may be associated with a relatively high probability of thyroid malignancy, a nondiagnostic FNAB should not be considered as benign. So, if reaspiration biopsy is nondiagnostic, it should be the subject of concern or the patient might be considered for surgery with taking into account the other characteristics, in particularily malignant sonographic findings.

Diagnosis and Treatment Outcome of Idiopathic Granulomatous Mastitis: Clinical Analysis on 35 Cases of Granulomatous Mastitis

PURPOSE: Idiopathic granulomatous mastitis (GM) is an uncommon breast disease that mimics carcinoma in terms of the clinical and radiological findings. Its unknown etiology makes the management difficult. Although surgical excision with or without steroid therapy has been the mainstay of the treatment, the efficacy of this treatment has been inconsistent. This study was performed to evaluate the diagnostic methods and the treatment outcomes. METHODS: This retrospective study included 31 patients with the diagnosis of GM and 4 patients had bilateral disease. They were found from the database of the pathology laboratory at Cheil General Hospital between January 1999 and December 2004. We reviewed the clinical, radiological, and pathological information, and we finally evaluated the treatment outcomes according to the surgical and medical treatments. RESULTS: The mean age at diagnosis was 34.2 years (range: 27~57). All the patients were parous except one, and 82% of patients were within 5 years from their last delivery. Four patients had bilateral involvement. Only three patients used oral contraceptives and 54% of patients had a history of breast feeding. Most patients (91%) presented with mass and the remainder (9%) presented with fistula. The confirmative diagnosis was made by FNAB (fine needle aspiration biopsy), debridement, CNB (core needle biopsy) or excision. Surgical excision or debridement was successful in 13 cases (39.4%) of 33 cases. Anti-tuberculosis medications were successful in 85% (11/13). Steroid treatment was successful in only two patients (29%). CONCLUSION: Surgical excision provided not only the definite diagnosis, but also treatment of GM for the cases in which a clear surgical margin was obtained. Anti-tuberculosis medication can be considered if fistula or abscess is intractable after excision, even with failure to identify tuberculosis.

Kasai Operation for Extrahepatic Biliary Atresia - Survival and Prognostic Factors

The prognostic factors for extrahepatic biliary atresia (EHBA) after Kasai portoenterostomy include the patient's age at portoenterostomy (age), size of bile duct in theporta hepatis (size), clearance of jaundice after operation (clearance) and the surgeon's experience. The aim of this study is to examine the most significant prognostic factor of EHBA after Kasai portoenterostomy. This retrospective study was done in 51 cases of EHBA that received Kasai portoenterostomy by one pediatric surgeon. For the statistical analysis, Kaplan-Meier method, Logrank test and Cox regression test were used. A p value of less than 0.05 was considered to be significant. Fifteen patients were regarded as dead in this study, including nine cases of liver transplantation. There was no significant difference of survival to age. The age is also not a significant risk factor for survival in this study (Cox Regression test; p = 0.63). There was no significant difference in survival in relation to the size of bile duct. However, bile duct size was a significant risk factor for survival (Cox Regression test; p = 0.002). There was a significant difference in relation to survival and clearance (Kaplan-Meier method; p = 0.02). The clearing was also a significant risk factor for survival (Cox Regression test; p = 0.001). The clearance of jaundice is the most significant prognostic factor of EHBA after Kasai portoenterostomy.

Continuous Administration of Human Endostatin in Xenografted Human Neuroblastoma

PURPOSE: The purpose of this study was to examine whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against a human neuroblastoma cell line (designated TNB9). We employed a human neuroblastoma xenograft model, and we investigated whether continuous infusion is more effective than an intermittent administration. METHODS: In the first experiment, when the tumors on the backs of nude mice reached a weight of 90 mg, rhEndostatin was administered subcutaneously to the mice (n=5) every day for 10 consecutive days. In the second experiment, the same daily dose of rhEndostatin was administered continuously to the TNB9- bearing mice (n=6) via subcutaneous infusion pumps for 3 consecutive days with the total dose being 30% of the dose given in the first experiment. Nestin and factor VIII expression levels were assessed immunohistochemically to elucidate whether the effects of rhEndostatin was present according to the histologic evidence at day 4 in the second experiment. RESULTS: In the first experiment, the relative tumor weight in treated mice (n=5) was significantly less than that in the controls (n=12) on day 2 after treatment initiation only (P<.05). The maximum inhibition rate (MIR) of TNB9 xenograft growth by rhEndostatin was 46.4%, indicating the lack of efficacy. In the second experiment, the effects of rhEndostatin were much more marked than those noted in the first experiment, with the MIR being 60.7%. The mean relative tumor weight in the treated group (n=6) in the second experiment was significantly less than that in the controls (n=10) on days 2, 4 and 6 (P<.01), as well as on days 8 and 10 (P<.05). The nestin staining in the endothelium of the control tumors (n=2) was remarkable, whereas the nestin staining showed as a loss of fibrillar structure in the rhEndostatin-treated tumors (n=2). The number of vessels immunostained with antifactor VIII antibody was markedly reduced in the tumors (n=2) from the rhEndostatin-treated mice compared with that from the control mice (n=2). CONCLUSION: Continuous administration of rhEndostatin resulted in more significant tumor regression than an intermittent administration of the agent. This result suggests that the continuous infusion of rhEndostatin is an effective agent and administration method for treating patients with neuroblastoma in the future.

Effects of Mycophenolic Acid, Rapamycin, and Carvedilol on the PDGF-induced Fibronectin Secretion by Rat Vascular Smooth Muscle Cells: Implication of MAP Kinase / 대한이식학회지

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation and extra-cellular matrix (ECM) protein accumulation play important roles in transplant vascular sclerosis and re- stenosis after balloon vascular injury. Mycophenolic acid (MPA), rapamycin (RPM), and carvedilol (CA) were proven to inhibit the proliferation of VSMC. Fibronectin is a multifunctional ECM protein and induces tissue fibrosis. Since mitogen-activated protein kinases (MAPK) are upstream signaling molecules of VSMC proliferation and fibronectin production, this study examined the effects of MPA, RPM, and CA on the fibronectin secretion and MAPK activation in rat VSMC stimulated by platelet derived growth factor (PDGF). METHODS: VSMC was isolated from the aorta of male Sprague-Dawley rat, weighing 200-250 g and cultured with EMEM containing 10% fetal bovine serum and insulin/transferrin supplement. Near confluent VSMC were incubated with serum-free media for 48 hours to arrest and synchronize the cell growth. Test drugs were administered 15 minutes before the addition of PDGF 10 ng/mL. Cell proliferation, fibronectin secretion, and MAPK activation in VSMCs were measured by Western blot analysis. RESULTS: PDGF induced cell proliferation, fibronectin secretion, and extracellular- regulatary protein kinase 1/2 (ERK 1/2) and p38 MAPK activation by 1.7-, 1.5-, 3.3-, 3.9-fold, respectively, compared to control. MPA (>1 microM), CA (>100 nM), PD98059 (>30 microM), and p38 MAPK inhibitor (>10 nM) effectively inhibited PDGF-induced proliferation and fibronectin secretion. RPM, up to 100 nM, effectively inhibited cell proliferation, but did not inhibit fibronectin secretion. MPA and CA, but not RPM, inhibited PDGF-induced ERK 1/2 and p38 MAPK activation. CONCLUSION: The present study demonstrates that MPA and CA inhibit both cell proliferation and fibronectin secretion in rat VSMC stimulated by PDGF. Inhibition of both ERK 1/2 and p38 molecules are significantly associated with these events. Even though, it has a significant anti-proliferative effect on the rat VSMC, RPM neither affected the phosphorylation of ERK 1/2 and p38 nor secretion of fibronectin. These data suggest that ERK 1/2- and p38 MAPK-independent, more proximal pathway may exist for PDGF-induced proliferation of rat VSMC.