BACKGROUND: In the majority of melanomas, the RAS/RAF/MEK/ERK signaling pathway is constitutively activated, due to oncogenic mutations in the BRAF and NRAS genes. The BRAF mutation has been mainly described in Caucasian melanomas. However, there is a lack of study evaluating the status, and the clinical significance, of BRAF mutation in the Asian population. OBJECTIVE: This study was aimed to determine the frequency of BRAF mutation, and to evaluate the correlation of BRAF status with clinicopathologic features and outcomes, in Korean primary acral lentiginous melanoma (ALM) patients. METHODS: ALM samples (n=36) were analyzed for the BRAF V600E mutation, by dual-priming oligonucleotide (DPO) based real-time polymerase chain reaction. The clinicopathologic features and prognosis of the patients were analyzed with BRAF mutation status. RESULTS: The incidence of BRAF V600E mutation was 19.4% (7/36). The BRAF V600E mutations were not associated with clinicopathologic features, except for the age factor. All of the BRAF-mutant patients survived without recurrence or metastasis, and have a better clinical outcome than BRAF wild-type patients. CONCLUSION: In Korean primary ALM, a low frequency of BRAF mutation was shown; and BRAF mutation presented with a favorable prognosis. These results indicate that other distinctive genetic mechanisms may have more important roles in the development and progression of disease. Further multicenter study with large sample size is firmly needed, to confirm the results of our preliminary study.
Age Factors ; Asian Continental Ancestry Group ; Humans ; Incidence ; Melanoma* ; Neoplasm Metastasis ; Prognosis ; Real-Time Polymerase Chain Reaction ; Recurrence ; Sample Size

BACKGROUND/AIMS: To determine the efficacy and toxicity of docetaxel as a third-line therapy for patients with relapsed gastric cancer who have undergone modified oxaliplatin-fluorouracil (m-FOLFOX)-4 and modified irinotecan-fluorouracil (m-FOLFIRI) regimens. METHODS: We analyzed 33 patients who had been histologically diagnosed with adenocarcinoma of the stomach and who had progressed after m-FOLFOX-4 and m-FOLFIRI regimens. Patients were treated with cycles of 75 mg/m2 docetaxel on day 1 every 3 weeks. RESULTS: The median age of the patients was 56.0 years (range, 31.0 to 74.0), and 73% of the patients (24/33) had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients were evaluated in terms of tumor response: five (15%), nine (27%), and 19 (58%) patients experienced a partial response, stable disease, and progressive disease, respectively. The median time to progression was 2.1 months (95% confidence interval [CI], 1.63 to 2.58), and overall survival was 4.7 months (95% CI, 3.20 to 6.20), from the start of the docetaxel regimen. Assessing patients' toxicity profiles, the median number of cycles was 2.0 (range, 1.0 to 12.0). The major hematologic toxicities included grade 3 to 4 neutropenia (19/33, 58%), grade 3 to 4 thrombocytopenia (2/33, 6%), and grade 3 to 4 anemia (5/33, 15%). Neutropenic fever developed in three patients (3/33, 9%). The nonhematological toxicities were nausea and vomiting (10/33, 30%), abdominal pain (4/33, 12%), skin rash (1/33, 3%), and fluid retention (3/33, 9%). CONCLUSIONS: Docetaxel is a feasible third-line therapy regimen for patients with advanced gastric cancer after m-FOLFIRI and m-FOLFOX-4 regimens.
Adenocarcinoma/*drug therapy/mortality ; Adult ; Aged ; Antineoplastic Agents/adverse effects/*therapeutic use ; Antineoplastic Protocols ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Republic of Korea/epidemiology ; Salvage Therapy ; Stomach Neoplasms/*drug therapy/mortality ; Taxoids/adverse effects/*therapeutic use

PURPOSE: Patients with triple-negative breast cancer (TNBC) are known to carry an increased risk of distant metastasis and poor survival. The principal objective of this study was to investigate survival after brain metastases in patients with TNBC. METHODS: The authors retrospectively evaluated clinical data obtained from 66 patients who had been diagnosed with breast cancer and brain metastasis from 2003 to 2009. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were determined via immunohistochemical staining. TNBCs were defined as those that were ER-negative, PR-negative, and HER2-negative. The time interval from initial diagnosis to brain metastasis and overall survival after brain metastasis was evaluated via the Kaplan-Meier method. RESULTS: Twenty four (40.0%) of 60 patients were diagnosed with TNBC. The clinicopathologic characteristics did not differ between the TNBC and non-TNBC patients. The disease-free survival durations of the TNBC and non-TNBC subjects were 17.9 and 25.6 months, respectively (p=0.135). The time intervals from initial diagnosis to brain metastasis were 25.5 and 43.7 months, respectively (p=0.027). The time intervals from distant metastasis to brain metastasis were 8.4 and 19.5 months, respectively (p=0.006). Overall survival durations from brain metastasis to death were 4.3 and 7.6 months, respectively (p=0.046). CONCLUSION: Patients with TNBC were more likely to develop brain metastasis earlier, and exhibit poor overall survival. Triple receptor status may be utilized as a prognostic marker for breast cancer patients with brain metastasis.
Brain ; Breast ; Breast Neoplasms ; Disease-Free Survival ; Estrogens ; Humans ; Neoplasm Metastasis ; Receptors, Progesterone ; Retrospective Studies

Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by its dual differentiation into luminal cells and myoepithelial cells. In most cases these tumors have a benign clinical course, but distant metastases have been reported. We present the case of a 51-year-old woman diagnosed with malignant AME. The patient underwent a right modified radical mastectomy, and pathological examination confirmed the diagnosis of malignant AME. Ten months after the operation, multiple hepatic, pleural, and abdominal wall metastases were detected. A number of palliative chemotherapeutic agents were tried, including anthracycline and taxanes. However, the disease continued to progress, and superior vena cava syndrome developed as a result of direct tumor invasion. The patient received salvage eribulin monotherapy. After two cycles of this treatment, her clinical symptoms were ameliorated, and a computed tomography scan showed a partial response. Eribulin chemotherapy was thus effective in treating malignant AME in this case.
Abdominal Wall ; Adenomyoepithelioma* ; Breast* ; Diagnosis ; Drug Therapy ; Female ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Metastasis ; Phenobarbital ; Superior Vena Cava Syndrome ; Taxoids

PURPOSE: Metastatic breast cancer patients are usually exposed to taxane and anthracycline as neoadjuvant, adjuvant and palliative chemotherapeutic agents. This study was designed to determine the efficacy and safety of the use of a gemcitabine and cisplatin (GP) combination treatment in patients with metastatic breast cancer that were pretreated with anthracycline and taxane. MATERIALS AND METHODS: We evaluated the use of a GP regimen (1,000 mg/m2 gemcitabine administered on days 1 and 8 plus 60 mg/m2 cisplatin administered on day 1 every 3 weeks) in 38 breast cancer patients who had received prior chemotherapy with anthracycline and taxane as an adjuvant or neoadjuvant therapy, or as a palliative therapy. RESULTS: The median patient age was 49 years (age range, 35~69 years). The overall response rate was 28.9% in 11 patients (95% confidence interval [CI], 14~44%). The median time to progression was 5.2 months (95% CI, 3.6~6.8 months). Median survival was 19.5 months (95% CI, 11.2~27.8 months). Major grade 3/4 hematological toxicity was due to leukopenia (36 of 157 cycles, 23.1%). Non-hematological toxicity was rarely severe; grade1/2 nausea and vomiting were observed in 37.8% of the patients. There were no treatment related deaths. CONCLUSIONS: Our results suggest that the use of gemcitabine plus cisplatin appears to be effective and has an acceptable toxicity profile in patients with advanced breast cancer that have been pretreated with anthracycline and taxane.
Breast ; Breast Neoplasms ; Bridged Compounds ; Cisplatin ; Deoxycytidine ; Humans ; Leukopenia ; Nausea ; Neoadjuvant Therapy ; Taxoids ; Vomiting

BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD. RESULTS: Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB. CONCLUSION: DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.
Anemia, Refractory ; Anemia, Refractory, with Excess of Blasts ; Bone Marrow ; Cell Cycle ; Disease Progression ; DNA Methylation ; Epigenomics ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute ; Methylation ; Myelodysplastic Syndromes ; Polymerase Chain Reaction ; Prognosis

Side effects of rituximab are mild in most cases, but there have been a few cases of severe pulmonary toxicity reported in elderly patients. Here we report a case of interstitial pneumonitis following rituximab treatment in a young patient. A 35-year-old woman with diffuse large B-cell lymphoma was admitted complaining of dry cough and dyspnea without fever after the 3 treatments with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Her chest CT with high-resolution CT scanning confirmed the presence of bilateral diffuse ground-glass opacities. The analysis of arterial blood gases indicated hypoxemia. The pulmonary function testing showed a restrictive pattern. There were no other findings suggesting an infection. The findings were compatible with a rituximab-induced interstitial pneumonitis. After the patient was treated with prednisolone, the symptoms resolved. Cases with rituximab-induced interstitial pneumonitis develop principally in elderly patients. However, the condition also can occur in young patients.
Adult ; Aged ; Anoxia ; Cough ; Doxorubicin ; Drug Therapy ; Dyspnea ; Female ; Fever ; Gases ; Humans ; Lung Diseases, Interstitial* ; Lymphoma, B-Cell ; Prednisolone ; Respiratory Function Tests ; Tomography, X-Ray Computed ; Vincristine ; Rituximab

BACKGROUND/AIMS: Bortezomib-based chemotherapy has proven to be an effective salvage regimen for refractory/relapsed multiple myeloma patients in many clinical trials. However, few reports have shown the outcomes and adverse events of bortezomib-based salvage chemotherapy in clinical practice. METHODS: From April 2006 to September 2011, 37 patients were retrospectively analyzed. A total of 19 patients received bortezomib therapy and 18 patients received bortezomib plus dexamethasone therapy. RESULTS: The median follow-up duration was 18.13 months (range, 0.97-87.20 months). The median number of cycles administered was four (range, 1-13). The overall response rate by International Myeloma Working Group (IMWG) 2006 criteria was 64.9%, including six complete responses (16.2%). The median number of cycles to best response was three (95% confidence interval [CI], 1.36-4.64). Six patients achieved their best responses after four cycles of bortezomib therapy. The median time to progression and overall survival were 5.10 (95% CI 4.03-6.17), and 23.10 (95% CI, 9.24-36.96) months, respectively. The incidence of grade 3/4 neutropenia and thrombocytopenia was 29.7% and 64.9%, respectively. A total of 27.0% patients experienced grade 3 peripheral neuropathy. Herpes zoster developed in 11 patients (29.7%). Treatment was stopped in 22 patients (59.5%) due to adverse events after bortezomib-based therapy, and treatment-related mortality occurred in 4 of 25 deaths in total. CONCLUSIONS: Bortezomib-based therapy is a very effective salvage regimen in real clinical practice, although patients relapse after multiple chemotherapies. Despite intolerable in some patients, management of toxicities and extended cycles of therapy could benefit more patients, resulting in higher response rates.
Dexamethasone ; Drug Therapy* ; Follow-Up Studies ; Herpes Zoster ; Humans ; Incidence ; Mortality ; Multiple Myeloma* ; Neutropenia ; Peripheral Nervous System Diseases ; Recurrence ; Retrospective Studies ; Salvage Therapy ; Thrombocytopenia

PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARgamma or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). MATERIALS AND METHODS: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARgamma and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. RESULTS: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARgamma and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARgamma positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARgamma and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). CONCLUSION: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARgamma and TRAP220 represents a biomarker for good prognosis in CRC patients.
Colorectal Neoplasms* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lipid Metabolism ; Lymph Nodes ; Mediator Complex Subunit 1* ; Multivariate Analysis ; Neoplasm Metastasis ; Peroxisomes* ; PPAR gamma* ; Prognosis ; Thyroid Gland

PURPOSE: To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy. MATERIALS AND METHODS: Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful. RESULTS: The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant). CONCLUSION: Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.
Adenosine ; Adenosine Triphosphate ; Chemotherapy, Adjuvant ; Fluorouracil ; Humans ; Recurrence ; Retrospective Studies ; Stomach Neoplasms