Ulmus davidiana Nakai induces apoptosis and autophagy on non-small cell lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus davidiana Nakai (UDN) is frequently used in the treatment of cancer in traditional oriental medicine. Although several reports indicate that UDN has inhibitory effects in some cancers, there has been no report on the inhibitory effects of UDN via both autophagy and apoptosis. MATERIALS AND METHODS: Cytotoxicity induced by UDN in human non-small cell lung cancer (NSCLC) H-1299 and H-460 cell lines was evaluated using the 2, 3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay and trypan blue exclusion assay. Induction of apoptosis was also investigated using Hoechst staining and annexin-V binding assay and was confirmed with western blot analysis. Induction of autophagy was investigated through observation of autophagy vacuoles under inverted phase-contrast microscopy and was confirmed by observing the formation of autophagy vacuoles under a fluorescence microscope using monodansylcadaverine (MDC) staining and western blot analysis. The in vivo anti-tumorigenic effect of UDN was investigated in an athymic nude mouse xenograft model using H-1299 NSCLC cells. RESULTS: UDN exhibited a marked inhibitory effect on cell growth in H-1299 and H-460 human NSCLC cell lines in a dose- and time-dependent manner in vitro and in vivo. It induced not only apoptosis, but also autophagy in both H-1299 and H-460 cells in a dose-dependent manner. UDN-mediated autophagy led to the accumulation of autophagosome, resulting in apoptosis induction and cell death. CONCLUSIONS: From our current knowledge, we are the first to demonstrate that UDN has the potential to induce both autophagy and apoptosis in H-1299 and H-460 human NSCLC cell lines. We suggest that UDN can be considered a potential candidate for lung cancer-specific chemotherapy with efficacy as a cytotoxic agent.

Is noncurative gastrectomy always a beneficial strategy for stage IV gastric cancer?

PURPOSE: The purpose of this study is to suggest a treatment strategy for stage IV gastric cancer by investigating the behavioral difference between initially and recurrent metastatic disease. METHODS: We reviewed the medical records of the patients who underwent chemotherapy alone for metastatic gastric cancer between January 2006 and September 2013. Patients were divided into those who underwent chemotherapy for metastatic disease since initial diagnosis (IM group) and for metastatic recurrence after curative surgery (RM group). Survival and causes of death were compared between the 2 groups, and significant prognostic factors were also investigated. RESULTS: A total of 170 patients were enrolled in this study. Of these patients, 104 were included in the IM group and 66 in the RM group. Overall survival of the IM group did not differ from that of RM (P = 0.569). In the comparison of the causes of death, the IM group had a greater tendency to die from bleeding (P = 0.054) and pneumonia (P = 0.055). In multivariate analysis, bone metastasis (P < 0.001; HR = 2.847), carcinoma peritonei (P = 0.047; HR = 1.766), and the frequency of chemotherapy (P < 0.001; HR = 0.777) were significantly associated with overall survival of IM group. CONCLUSION: Disease-burden mainly contributes to the prognosis of metastatic gastric cancer, although noncurative gastrectomy may be helpful in reducing the mortality of initially metastatic disease. Therefore, disease-burden should be also prioritized in determining the treatment strategies for stage IV gastric cancer.

Imatinib Mesylate Dose Adjustment Based on Body Surface Area for CML Chronic Phase Patients Intolerant to Standard Dosage.

AIM: Chronic myelogenous leukemia (CML) chronic phase (CP) patients cannot tolerate a standard dose (400 mg/day) of imatinib mesylate (IM), sometimes needing a reduced dose. This study aimed to find convenient clinical indexes, rather than plasma trough levels of IM, to define the appropriate IM dosage. METHODS: Seventy CML CP patients who experienced an IM dose reduction, or a temporary cessation, were enrolled from 2002 to 2010. The IM treatment was resumed and maintained at either ≥400 mg in 25 patients (35.7%; group ≥400 mg) or at ≤300 mg in 45 patients (64.3%; group ≤300 mg). The various clinical characteristics of these patients were evaluated. The plasma trough level of IM was monitored in 20 patients from group ≤300 mg. RESULTS: Via multivariate analysis, the IM dosage divided by the body surface area (BSA) was an important index, presupposing a complete cytogenetic response at 12 months (CCyR12). Patients with IM/BSA >206.7 mg/m2 showed a higher probability of CCyR12 than others. The IM/BSA (221.7 mg/m2) in group ≤300 mg was higher than in group ≥400 mg (207.6 mg/m2). The sustained response and survival rate of group ≤300 mg was comparable to that of group ≥400 mg. The plasma trough level of IM was significantly correlated with the IM/BSA. CONCLUSION: Our study suggests that IM dose adjustments, based on IM/BSA, could improve the clinical outcomes in CML CP patients.

Influence of socioeconomic status on survival and clinical outcomes in patients with advanced gastric cancer after chemotherapy.

BACKGROUND: Socioeconomic inequalities are known to influence the survival of cancer patients due to differences in treatment modalities and disease extent at diagnosis. However, there are few studies regarding the influence of socioeconomic status on patient survival, especially after palliative chemotherapy for advanced gastric cancer. PATIENTS AND METHODS: This retrospective study was performed on 138 advanced gastric cancer patients who received palliative chemotherapy. Demographic, socioeconomic, and cancer-related variables were analyzed according to education level. Effects of socioeconomic factors and cancer-related variables on patient survival were also evaluated. RESULTS: In our study, higher education level (> 6 years of schooling; p = 0.01), disease control (p < 0.01), and a greater number of chemotherapeutic agents (≥ 5 drugs; p < 0.01) were associated with a significant increase in median survival. Multivariate analysis showed that a higher education level (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.35-0.82; p < 0.01), disease control (HR 0.21; 95% CI 0.13-0.34), and total number of chemotherapeutic agents used (HR 0.44; 95% CI 0.26-0.73) were significantly associated with prolonged survival. CONCLUSIONS: Among socioeconomic factors, only higher education level was associated with better survival. Increase in survival was also associated with clinical outcomes, including total number of chemotherapeutic agents used and disease control after chemotherapy.

Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment.

PURPOSE: There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC. MATERIALS AND METHODS: We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy. RESULTS: The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death. CONCLUSION: Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.

Combination of gemcitabine and carboplatin as first line treatment in elderly patients or those unfit for cisplatin-based chemotherapy with advanced transitional cell carcinoma of the urinary tract.

PURPOSE: Although cisplatin-based chemotherapy is the standard of care for advanced transitional cell carcinoma, tolerability is a challenging issue in unfit patients. This study was conducted to evaluate the efficacy, toxicity, and tolerability of the combination of gemcitabine and carboplatin in unfit patients with advanced transitional cell carcinoma. METHODS: Thirty-one patients who had advanced transitional cell carcinoma and one of the following clinical features were evaluated: Eastern Cooperative Oncology Group performance status equal or greater than 2, age older the 75 years or estimated glomerular filtration rate less than 60 ml/min. The patients were treated with carboplatin and gemcitabine delivered every 4 weeks. RESULTS: Of the 31 patients, 71 % had an estimated glomerular filtration rate of less than 60 ml/min, and the remaining patients were treated by this protocol due to poor performance status or age older than 75. The median age of the patients was 74 years old. A total of 162 cycles of treatment were delivered to the patients. The overall response rate was 45.1 %. After the median follow-up of 15 months, the median progression-free survival time was 9.4 months (95 % CI 7.3-11.4) and overall survival time was 20 months (95 % CI 14.9-25.0). Grades 3 and 4 anemia, thrombocytopenia, and neutropenia were observed in 22.6, 6.45, and 6.45 % of patients, respectively. There was no treatment-related mortality in our patient series. CONCLUSION: The combination of gemcitabine and carboplatin is effective in elderly patients with advanced transitional cell carcinoma or those unfit for cisplatin-based chemotherapy, with manageable toxicity.

The relationship between Helicobacter pylori infection and the effects of chemotherapy in patients with advanced or metastatic gastric cancer.

PURPOSE: Several reports have shown a better prognosis in gastric cancer patients who are positive for Helicobacter pylori (HP) infection compared with negative cases. However, there are currently no studies that investigate the relationship between HP infection and the effects of chemotherapy in gastric cancer patients. In this study, we report the relationship between HP infection and chemotherapy effects in patients with advanced or metastatic gastric cancer. METHODS: Sixty-one patients with advanced or metastatic gastric cancer were enrolled in this study. Biopsies were conducted around the tumor site to determine HP status. Patients were then treated with combination 5-FU and cisplatin-based chemotherapy. And we compared chemotherapy response rate and overall survival rate between HP infection group and without HP infection group. RESULTS: Twelve of 18 patients with HP infection (66.7 %) and 9 of 42 patients without HP infection (21.4 %) showed a partial response to chemotherapy (Chi square P = 0.001). Patients with HP infection had a median survival time of 13 months (95 % CI, 6.9-19.1 months), which was significantly longer than that of patients without HP infection (9 months; P = 0.027, log-rank test). CONCLUSIONS: Patients with advanced or metastatic gastric cancer with concomitant HP infection had a better response to chemotherapy and had an improved overall prognosis compared with patients without HP infection. Further studies are warranted to confirm these findings.

Mitomycin-C, 5-fluorouracil, and leucovorin as a salvage therapy in patients with metastatic colorectal adenocarcinoma.

AIM: There is no further treatment option for metastatic colon patients who are refractory to standard chemotherapy and to whom novel biological agents are not available. We evaluated the outcomes of mitomycin-C, 5-fluorouracil (5-FU) and leucovorin in patients with metastatic colon cancer previously treated with oxaliplatin/5-FU/leucovorin and irinotecan/5-FU/leucovorin. METHODS: We retrospectively analyzed 46 patients who had received mitomycin-C/5FU/leucovorin between March 2008 and December 2009. All patients had failed prior first-line and second-line therapy containing oxaliplatin, irinotecan, and 5-FU. RESULTS: The median age of the patients was 57.0 years (range, 34.0-76.0) and their median Eastern Cooperative Oncology Group performance status was 1 (0-2). A complete or partial response was not observed in any patient and stable disease was observed in 19 patients (41.3%). The median duration of follow up was 29 weeks (range 8-87 weeks). Median progression-free survival was 10 weeks (95% CI 8-12) and median overall survival was 38 weeks (95% CI 32-44). Grade 3 and 4 hematological toxicities included neutropenia in five patients (10.8%) and thrombocytopenia in four patients (8.8%). Grade 3 or 4 non-hematologic toxicities included nausea and vomiting in two patients. There were no treatment-related deaths. CONCLUSION: The combination regimen of mitomycin-C/5-FU/leucovorin showed marginal activity and tolerable toxicity profiles in heavily pretreated metastatic colorectal cancer patients.

Concurrent chemoradiation followed by adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma in Korea.

PURPOSE: Concomitant approach using cisplatin and 5-fluorouracil (5-FU) has shown an excellent local control rate and significantly reduced distant metastasis in patients with locally advanced nasopharyngeal carcinoma (NPC). However, optimal schedule and dosing of chemotherapy still need to be developed to reduce distant metastasis. This retrospective study was conducted to evaluate the efficacy, toxicity, and tolerability of a concurrent chemoradiation therapy (CCRT) regimen using cisplatin and 5-FU followed by adjuvant chemotherapy (AC) in patients with locoregionally advanced NPC. METHODS: Forty-three NPC patients who had AJCC stage T3/T4 or N2/N3 and M0 disease were evaluated. The chemotherapy during CCRT consisted of cisplatin (75 mg/m(2) on day 1) plus 5-FU (750 mg/m(2)/day on day 1-5), delivered every 4 weeks for two cycles. Three cycles of AC were given with cisplatin (75 mg/m(2)), epirubicin (37.5 mg/m(2)) on day 1, and bleomycin (7.5 mg/m(2) bolus iv. on day 1 followed by 9 mg/m(2) on day 1-5 by continuous infusion) every 3 weeks. RESULTS: The overall response rate after CCRT was 95% (22 CRs and 19 PRs in 43) and 100% (16 CRs and 8 PRs in 24) after AC. Grade 3/4 neutropenia, mucositis, and weight loss were observed during CCRT phase in 18, 44, and 26% of patients, respectively. AC caused grade 3/4 neutropenia and emesis in 12.5 and 20.8% of patients, respectively. CONCLUSIONS: CCRT regimen using cisplatin and 5-FU followed by three cycles of BEC chemotherapy was effective in locally advanced NPC patients, with acceptable and reversible acute toxicities.

The suggestion of a risk stratification system for febrile neutropenia in patients with hematologic disease.

We analyzed the prognostic factors from 259 cases of febrile neutropenia occurring in 137 patients with hematologic disease. Based on multivariate analysis, significant prognostic factors are recovery of neutropenia, respiratory infection, baseline serum albumin, baseline bicarbonate, baseline CRP, and CRP on the fifth day after antibiotic treatment. From these variables, we derived a predictive model for the prognosis of febrile neutropenia using baseline serum albumin, bicarbonate, and CRP, which could be easily checked before chemotherapy. Further studies in prospective setting are needed for the validation of this model.

Treatment results including more than third-line chemotherapy for patients with advanced non-small cell lung cancer.

Recently, third-line chemotherapy for advanced non-small cell lung cancer (NSCLC) was accepted as a reasonable therapeutic option in patients with a favorable performance status. In practice, however, palliative chemotherapy has been performed for patients with a favorable performance status, even after third-line chemotherapy. Although multiple cycles of palliative chemotherapy were performed for these patients, there are little data of observation for courses of treatment from first-line to the last chemotherapy. We reviewed the courses of treatment for 82 patients with advanced NSCLC that had been admitted for platinum-based chemotherapy as a first-line treatment. Additional cycles of palliative chemotherapy were provided as monotherapy, based on the attending physician's decision considering patient performance status and toxicity after disease progression for previous chemotherapy. The median number of chemotherapy lines and cycles were 2 and 7, respectively, from first-line to the last chemotherapy. The median overall survival was 24 months in the response group of first-line chemotherapy, compared to 15 months for the entire study group. In the response group, the median number of chemotherapy cycles was 15 and patients received a median of 3 lines of chemotherapy. A total of 33 patients were candidate third-line chemotherapy or more. The median survival was 23 months for patients treated with more than third-line chemotherapy, compared to 7 months for patients treated with less than second-line chemotherapy. We conclude that long-standing chemotherapy is not beneficial to all NSCLC patients. However, patients with a favorable response to first-line chemotherapy tend to receive a higher number and more cycles of chemotherapy than the non-response group. Furthermore, multi-line chemotherapy appears to increase survival in the response group. Further studies will be needed to confirm these results.

A multicenter phase II study of gemcitabine and S-1 combination chemotherapy in patients with unresectable pancreatic cancer.

PURPOSE: To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer. METHODS: Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, with at least one measurable lesion were eligible for the study. Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days 1 and 8, while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1 to 14, and the cycle was repeated every 3 weeks. The objective response rate, which was assessed according to RECIST criteria, was the primary end point. RESULTS: A total of 38 patients were enrolled between June 2006 and June 2007. The median number of treatment courses was 5.5 (range 1-22). Thirty-four patients were evaluable for response. Although no complete response was seen, partial responses were achieved in 11 patients, resulting in an overall response rate of 32% [95% confidence interval (CI) 17-48%]. The median response duration was 6.0 months (95% CI 4.6-8.3 months), the median time-to-progression was 5.4 months (95% CI 2.9-8.0 months), and the median overall survival was 8.4 months (95% CI 5.7-11.1 months). The major grade 3/4 hematologic toxicities were neutropenia (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%). CONCLUSIONS: Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer.

Absolute CD4+ cell count using a plastic microchip and a microscopic cell counter.

We have designed and evaluated the performance of a simple, rapid, and affordable method for counting CD4(+) T-cells with the use of plastic microchips. This new system is an adaptation of a "no-lyse, no-wash," volumetric single platform assay, and absolute CD4(+) counts are determined with the use of a microscopic scanning cell counter. To assess the CD4(+) count test precision and linearity of the system, measured CD4(+) counts were compared with two other reference assays (single and dual platform flow cytometry) with the use of 123 clinical samples including samples obtained from 35 HIV-infected patients, and artificially diluted samples. A correlation between the results from the use of the new method and from the use of the two other reference assays was r = 0.98 for the clinical samples. A dilution test of the new method demonstrated a linearity of r >or= 0.99, with coefficients of variation

Treatment outcomes of oxaliplatin, 5-FU, and leucovorin as salvage therapy for patients with advanced or metastatic gastric cancer: a retrospective analysis.

PURPOSE: We performed a single-institution retrospective study to evaluate the efficacy and toxicities of oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) combination chemotherapy as salvage treatment in patients with metastatic or advanced gastric cancer. METHODS: Sixty-two patients with advanced gastric cancer previously treated were eligible for the study. Patients received oxaliplatin 100 mg/m(2) and LV 100 mg/m(2) (2-h intravenous infusion) followed by 5-FU 2,400 mg/m(2) (46-h continuous infusion) every 2 weeks, and responses were assessed after every three cycles. RESULTS: Fifty-nine out of 62 patients were assessable for response. Among them, 46 patients had previously been treated with cisplatin based chemotherapy. Patients had a median age of 57 years (range 32-76 years), 72.6% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Total 296 courses of chemotherapy were administered as second-line (67.7%) or third-line (27.4%), and the median courses per patient was three cycles. Out of 59 evaluable patients, 14 partial responses were observed (overall response rate, 22.6%). Stable disease was observed in 22 patients (35.5%), and progressive disease in 23 patients (37.1%). The median response duration, time to progression, and overall survival were 2.3, 3.0, and 8.0 months, respectively. The major toxicities were neutropenia, mucositis, and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in nine patients (14.5%) and thrombocytopenia in one patient (1.6%). Other grade 3 or 4 toxicities included mucositis in one patient (1.6%) and vomiting in two patients (3.2%). Grade 1 or 2 peripheral neuropathy were observed in 18 patients (29.0%), however there were no cases of grade 3 or 4 peripheral neuropathy and no treatment-related deaths. CONCLUSION: The combination of oxaliplatin, 5-FU and LV was effective and safe salvage chemotherapy in advanced gastric cancer patients.

Docetaxel and epirubicin salvage regimen in relapsed anthracycline-sensitive metastatic breast cancer patients after anthracycline-containing adjuvant therapy.

Our aim in this paper is to verify the efficacy and safety of a epirubicin and docetaxel salvage regimen for anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy. Thirty-two metastatic breast cancer patients were treated with epirubicin and docetaxel every 21 days. Of the 31 evaluable patients, there were 13/31 (41.9%) partial responses and no complete responses. Median time to progression was 12 months (95% CI, 4-60 months) and median survival duration was 41 months (95% CI, 1.2-80.8 months). According to the Cox model, ECOG performance and response group were statistically significant variables, and visceral metastasis was a borderline significant variable with regards to overall survival. Although this salvage regimen showed a high rate of hematologic toxicities, it was a relatively active regimen with manageable toxicities and no cardiac dysfunction. We propose that this salvage regimen could be carefully used in anthracycline sensitive metastatic breast cancer patients who have relapsed after anthracycline-containing adjuvant therapy.

Single nucleotide polymorphisms of IGFBP-3 gene and lung cancer risk in a Korean population.

Insulin-like growth factor binding protein-3 (IGFBP-3) is a putative tumor suppressor and inhibits the mitogenic and antiapoptotic activity of insulin-like growth factor (IGF) by blocking the binding to its receptors or by IGF-independent manner. Epidemiological studies have suggested that serum level of IGFBP-3 is associated with lung cancer risk. The present study was conducted to evaluate the association between single nucleotide polymorphisms (SNPs) of the IGFBP-3 gene and susceptibility to lung cancer and the effect of the SNPs on the serum levels of IGFBP-3, total IGF-I and free IGF-I in a Korean population. After a preliminary study for polymorphism screening of the promoter region of the IGFBP-3 gene in randomly selected 41 lung cancer patients, two polymorphisms (-1590 C>A; -202 A>C) were identified with PCR-based restriction fragment length polymorphism (PCR-RFLP) and SNaPshot primer extension assay in 415 Korean lung cancer patients and 415 matched normal controls. Although the genotype and allele frequency distribution of each SNP did not differ significantly between cases and controls in the single-locus analysis, we found that the polymorphisms of -1590A and -202C were associated with increased risk for lung cancer in females (-1590 C>A; adjusted OR=2.11, 95% CI=1.08-4.12, -202 A>C; adjusted OR=1.96, 95% CI=1.02-3.75, respectively) and never-smokers (-1590 C>A; adjusted OR=2.06, 95% CI=1.12-3.78, -202 A>C; adjusted OR=1.99, 95% CI=1.10-3.62, respectively) in a dominant model after stratification for gender and smoking history. Haplotype analysis showed that carriers of A-C had significantly higher risk for lung cancer in females (dominant aOR=2.05, 95% CI=1.14-3.68) and in never-smokers (codominant aOR=1.71, 95% CI=1.11-2.64 and dominant aOR=1.99, 95% CI=1.17-3.40). Functional analysis in H1703 cell line using DNA fragments containing A-C haplotype of the promoter region showed significantly decreased transcriptional activity. Furthermore, there was a negative correlation between the number of polymorphic alleles in -1590/-202 loci and serum levels of IGFBP-3 in lung cancer patients, but it was not statistically significant in the test for linear trend. These results suggest that IGFBP-3 promoter polymorphisms of -1590 C>A and -202 A>C might be a genetic risk factor for lung cancer by means of decreased IGFBP-3 expression among females or never-smoking Koreans.

Putative association of the single nucleotide polymorphisms in RASSF1A promoter with Korean lung cancer.

SUMMARY: The RASSF1 gene, a putative tumor suppressor gene located on human chromosome 3p21, has attracted a great deal of attention because of frequent allelic loss and gene silencing via promoter hypermethylation in a variety of human malignancies. To evaluate the role of RASSF1A gene in lung cancer risk, genotypes of the RASSF1A promoter region (-710 C>T and -392T>C) were determined in 410 lung cancer patients and 410 normal subjects. Furthermore, to examine potential effects of the common haplotypes (C-C, T-T and C-T haplotypes) on RASSF1A transcription, luciferase reporter assays were performed in H2009 and H358 non-small cell lung cancer (NSCLC) cell lines. We found that ht2 C-T haplotype was associated with susceptibility to the risk of lung cancer in dominant (odds ratio (OR): 0.69; 95% CI: 0.46-0.99) model. In particular, we found that C-T haplotype showed a decreased risk of lung cancer in males (codominant OR: 0.59; 95% CI: 0.38-0.93 and dominant OR: 0.58; 95% CI: 0.35-0.96) and in smokers (codominant OR: 0.58; 95% CI: 0.36-0.93 and dominant OR: 0.56; 95% CI: 0.33-0.96). Interestingly, C-T haplotype induced transcriptional activity by 50-60% compared with other haplotypes in NSCLC cell lines. These results suggest that RASSF1A promoter polymorphisms affect RASSF1A expression, further contributing to the genetic susceptibility to lung cancer.

Clinical factors related to suspected second primary lung cancer development in patients with head and neck cancer.

PURPOSE: The rate of second primary lung cancer development for patients with head and neck cancer (HNC) has been noted. The aim of our study was to evaluate the incidence and clinical features of suspected second primary lung cancer that developed in patients with primary HNC. MATERIALS AND METHODS: We conducted a retrospective study of 469 patients who were newly diagnosed with HNC at the Korea University Medical Center between January 2000 and December 2006. RESULTS: A total of 469 patients were included (389 men and 80 women). Eighteen patients (3.8%) had suspected second primary lung cancers. Statistically significant clinical variables for lung cancer development included the origin site for the primary HNC (oro-hypopharynx and larynx) (p=0.048), abnormal chest x-ray findings (p=0.027) and the histological HNC type (squamous cell carcinoma) (p=0.032). When the second primary lung cancers were combined with HNCs, the adjusted overall survival of patients with a second primary lung cancer was 16 months (p<0.001). CONCLUSIONS: Considering the relative risk factors for a second primary lung cancer developing in patients with HNC, advanced diagnostic tools, such as chest CT or PET CT scan, should be applied for the early detection of a second primary lung cancer.

Association of single nucleotide polymorphisms in PIM-1 gene with the risk of Korean lung cancer.

PURPOSE: The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population. MATERIALS AND METHODS: To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects. RESULTS: We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24 approximately 12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75 approximately 34.98, p-value: 0.007). CONCLUSIONS: The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.