PURPOSE: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. MATERIALS AND METHODS: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. RESULTS: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. CONCLUSION: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.
Adenocarcinoma/*drug therapy/*genetics/mortality ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/pharmacology/*therapeutic use/toxicity ; Female ; Glutamates/pharmacology/*therapeutic use/toxicity ; Guanine/*analogs & derivatives/pharmacology/therapeutic use/toxicity ; Humans ; Lung Neoplasms/*drug therapy/*genetics/mortality ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Middle Aged ; Pharmacogenetics ; Phosphoribosylglycinamide Formyltransferase/genetics ; *Polymorphism, Single Nucleotide ; Tetrahydrofolate Dehydrogenase/genetics ; Thymidylate Synthase/genetics

Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and in the constitutive activation of nuclear factor kappa B (NF-kappaB). We investigated the association of non-small cell lung cancer (NSCLC) treatment efficacy with TG2 and NF-kappaB expression in 120 patients: 102 with adenocarcinoma and 18 with other histologic types. All patients underwent surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based doublet chemotherapy as first-line treatment and 29 receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and NF-kappaB expression values were calculated semiquantitatively. The median TG2 value was 50 (range, 0-300) and the median NF-kappaB value was 20 (range, 0-240). Disease-free survival did not differ between the low- and high-TG2 groups. Among patients who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0 months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI, PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013). TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR-TKI.
Adenocarcinoma/*drug therapy/mortality/surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/surgery ; Disease-Free Survival ; Female ; GTP-Binding Proteins/*biosynthesis ; Humans ; Lung Neoplasms/*drug therapy/mortality/surgery ; Male ; Middle Aged ; NF-kappa B/biosynthesis ; Protein Kinase Inhibitors/therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/genetics ; Transglutaminases/*biosynthesis ; Treatment Outcome

No abstract available.

PURPOSE: The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. MATERIALS AND METHODS: Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. RESULTS: Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. CONCLUSION: h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma.
Adenocarcinoma ; Biomarkers ; Carcinoembryonic Antigen* ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Erlotinib Hydrochloride* ; Female ; Humans ; Keratin-19* ; Prognosis ; Receptor, Epidermal Growth Factor

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) have been confirmed as predictors of the efficacy of treatment with EGFR-tyrosine kinase inhibitors (TKIs). We investigated whether polymorphisms of the EGFR gene were associated with clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. MATERIALS AND METHODS: A polymorphic dinucleotide repeat in intron 1 [CA simple sequence repeat in intron 1(CA-SSR1)] in intron 1 and single nucleotide polymorphisms (SNP-216) in the promoter region of the EGFR gene were evaluated in 71 NSCLC patients by restriction fragment length polymorphism and DNA sequencing. The relationship between genetic polymorphisms and clinical outcomes of treatment with EGFR-TKIs was evaluated. RESULTS: SNP-216G/T polymorphisms were associated with the efficacy of EGFR-TKI. The response rate for the SNP-216G/T tended to be higher than that for G/G (62.5% vs. 27.4%, p=0.057). The SNP-216G/T genotype was also associated with longer progression-free survival compared with the GG genotype (16.7 months vs. 5.1 months, p=0.005). However, the length of CA-SSR1 was not associated with the efficacy of EGFR-TKI. CONCLUSION: SNP-216G/T polymorphism was a potential predictor of clinical outcomes in NSCLC patients treated with EGFR-TKI.
Adult ; Aged ; Aged, 80 and over ; Female ; Genotype ; Humans ; Introns/genetics ; Kaplan-Meier Estimate ; Lung Neoplasms/*drug therapy/*genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Protein Kinase Inhibitors/*therapeutic use ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/*genetics ; Treatment Outcome

The purpose of this study was to compare radiopacity and radiographic discriminability of various FRC-Posts. Six FRC-Posts were investigated ; 1) FRC Postec Plus (Ivoclar Vivadent AG, Schaan, Liechtenstein), 2) Snowlight (Carbotech, Lewis center, OH, USA), 3) Dentin Post (Komet Brasseler, Lamgo, Germany), 4) Rely-X Fiber Post (3M ESPE, St.paul, MN, USA), 5) D.T.-Light Post (BISCO, Schaumburg, IL,USA), 6) Luxapost (DMG, Hamburg, Germany) The radiographs of each post with a reference 1 mm / 2 mm aluminum step-wedge was taken using digital sensor. The optical density were calculated by gray value of 10 x 10 pixel and compared in mm Al equivalent at five points. Six maxillary incisors of similar radiopacity were used. Radiographs of posts in Mx. incisors of lingual side of dry mandible were taken. We showed radiographs and asked the questionnaire to 3 radiologists, 3 endodontists, 3 general practitioners. The questionnaire was comprised of choices of the highest, lowest radiopaque individual post and the choices of best discriminable post at apical, coronal area. The following results were obtained. 1. Each post system showed various radiopacity. 2. There was change of discriminability between each post and simulated specimens regardless of examiner. Although each post showed various radiopacity, the difference of radiopacity did not affect on discriminability.
Acrylic Resins ; Aluminum ; Composite Resins ; Dentin ; General Practitioners ; Humans ; Incisor ; Mandible ; Polyurethanes ; Resin Cements ; Surveys and Questionnaires

Splenic rupture is a frequent surgical emergency in blunt abdominal trauma patients. There are several treatment options, including conservative treatment, a partial splenectomy, splenorrhaphy, and a splenectomy for splenic injury. Although reports on the safety and the efficacy of an elective laparoscopic splenectomy are abundant in the literature, a laparoscopic splenectomy for a ruptured spleen has only been reported in a few cases. We report a case of a laparoscopic splenectomy in the patient with Grade III traumatic splenic injury. To our knowledge, this is the first report in which a laparoscopic splenectomy was performed in Korea for the treatment of a traumatic splenic injury.
Emergencies ; Humans ; Korea ; Spleen ; Splenectomy ; Splenic Rupture

PURPOSE: Although cardiac toxicity is a key parameter of significant toxicity, in antidepressant intoxication, there are few studies on the cardiac toxicity of serotonin reuptake inhibitor and the intoxication with the new generation of antidepressants. The aim of this study is to investigate the relative cardiac toxicity of serotonin reuptake inhibitor and intoxication with the new generation of antidepressants as compared with that of tricyclic antidepressant intoxication. METHODS: We retrospectively reviewed the medical records of 109 antidepressant intoxicated patients who visited the Emergency Department from January, 2005 to December, 2009 to collect and analyze the demographic and clinical data. Sixteen patients were excluded. The enrolled seventy eight patients were classified into three groups: the tricyclic antidepressant group (TCA) (n=32), the selective serotonin reuptake inhibitor subgroup (SSRI) (n=28) and the new generation antidepressant subgroup (NGA) (n=18). RESULTS: The demographic and clinical data of the SSRI and NGA groups were not significantly different from that of the TCA group. The QRS duration of the SSRI subgroup (86.4+/-12.0 msec) and the NGA subgroup (91.8+/-11.9 msec) was not significantly different from that of the TCA group (90.0+/-13.5msec) (p=0.598). CONCLUSION: Intoxication with SSRI and the new generation antidepressants seemed to show significant cardiac toxicity, like what is seen in tricyclic antidepressant intoxication. Clinicians must pay attention to SSRI and new generation antidepressant intoxication.
Antidepressive Agents ; Emergencies ; Humans ; Medical Records ; Retrospective Studies ; Serotonin

PURPOSE: With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies. MATERIALS AND METHODS: Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks. RESULTS: Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed. CONCLUSION: The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy* ; Febrile Neutropenia ; Humans ; Neutropenia ; Platinum ; Small Cell Lung Carcinoma ; Thrombocytopenia

PURPOSE: The PTEN gene, a novel tumor suppressor, is localized to chromosome 10q23.3 and shares extensive homology with the cytoskeletal protein, tensin. A high frequency of mutations at the PTEN locus has been described in a variety of neoplasms including breast cancer and Cowden Disease. However, the role of PTEN alterations and its association with clinicopathological factors have not been well established. We investigated the relationship between the PTEN expression and clinicopathological factors. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissues from 105 women with breast cancer were evaluated for the PTEN expression and were scored semi-quantitatively based on staining intensity and distribution. Results were statistically compared with clinicopathological factors. RESULTS: Forty-seven (45%) of the 105 breast cancers had a loss of the PTEN expression. In the recurrent group, 19 of 32 (59%) patients showed a loss of the PTEN expression, whereas in the non-recurrent group, only 28 of 73 (38%) patients showed a loss of the PTEN expression. The loss of PTEN expression correlated with estrogen receptors (ER) (p=0.027), recurrence (p=0.046), HER-2/neu overexpression (p=0.016), disease-free survival (p=0.0163), and overall survival (p=0.0357). In particular, when HER-2/ neu was overexpressed, the overall survival rate correlated with the loss of PTEN expression statistically (p=0.0454), whereas when HER-2/neu was negative, there was no correlation (p=0.9808). Progesterone receptor (PR) and disease stage had no relationship with the PTEN expression. CONCLUSION: Our results support that PTEN plays a role as a tumor suppressor in breast cancer and is a prognostic factor in predicting recurrence.
Breast Neoplasms ; Breast* ; Disease-Free Survival ; Female ; Genes, vif ; Hamartoma Syndrome, Multiple ; Humans ; Receptors, Estrogen ; Receptors, Progesterone ; Recurrence ; Survival Rate