Overexpression of S100A4 is closely associated with progression of colorectal cancer

AIM: To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS: A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS: Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 (55.6%) of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 (69.4%) of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes' stage and lymph node metastasis. Nuclear staining was also observed in 24 (19.4%) of 124 samples and dosely associated with Dukes' stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION: Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.     

Incidence and risk factors of delayed pneumothorax after transthoracic needle biopsy of the lung

STUDY OBJECTIVES: To evaluate the incidence and clinical significance of delayed pneumothorax, and to analyze the influence of multiple variables on the rate of delayed pneumothorax associated with transthoracic needle biopsy (TTNB) of the lung. STUDY DESIGN: Prospective study. SETTING: Tertiary care university hospital. STUDY SUBJECTS: Adult patients underwent TTNB from June 2001 to June 2002. MEASUREMENTS AND RESULTS: Among the 458 patients included in this study, 280 fluoroscopic-guided, 21 CT-guided, and 157 ultrasonography-guided lung biopsies were performed. A follow-up chest radiograph was obtained immediately, and 3 h, 8 h, and 24 h after the biopsy procedure. Pneumothorax that had not developed up to 3 h but developed later was defined as a delayed pneumothorax. Patients with a symptomatic or enlarged pneumothorax were treated using a pigtail catheter or chest tube. Variables such as age, gender, lesion size, location, presence of an emphysematous change, biopsy guidance methods, and biopsy devices were analyzed. Pneumothorax developed in 100 of the 458 patients (21.8%), and delayed pneumothorax developed in 15 patients (3.3%). Seventeen patients, including 3 patients with delayed pneumothorax, required a pigtail catheter or a chest tube insertion. The pigtail catheter or chest tube insertion rate in delayed pneumothorax was 20% (3 of 15 patients). Female gender and the absence of an emphysematous change correlated with an increased rate of delayed pneumothorax (p < 0.05). Lesion size, location, biopsy guidance methods, devices, and underlying diseases were not correlated with the delayed pneumothorax rate. CONCLUSIONS: The incidence of delayed pneumothorax was 3.3% of all TTNBs. Female gender and the absence of an emphysematous change were identified as risk factors for delayed pneumothorax. Delayed pneumothorax is clinically important because of its considerable incidence and the necessity for pigtail catheterization or chest tube insertion in these patients.     

Evaluation of the CombiChip Mycobacteria Drug-Resistance detection DNA chip for identifying mutations associated with resistance to isoniazid and rifampin in Mycobacterium tuberculosis

The CombiChip Mycobacteriatrade mark Drug-Resistance Detection DNA chip, recently developed by GeneIn (Pusan, South Korea), is an oligonucleotide microchip coupled with polymerase chain reaction for the detection of mutations associated with resistance to isoniazid (INH) and rifampin (RIF). This oligonucleotide chip was compared with DNA sequencing and phenotypic drug susceptibility testing with 69 INH- and/or RIF-resistant and 27 all tested drug-susceptible Mycobacterium tuberculosis isolates. Two selected codons (the katG codon 315 and inhA15) allowed identification of 84.1% of INH-resistant isolates and 100% of RIF resistance were detected by screening for 7 codons: rpoB511, rpoB513, rpoB516, rpoB522, rpoB526, rpoB531, and rpoB533. The overall specificity of this oligonucleotide chip for detecting INH and RIF resistance were 100 and 95.3%, respectively. This level of sensitivity and specificity is concordant with that from the determination of M. tuberculosis drug resistance by DNA sequencing. This oligonucleotide chip is a rapid and reliable genotypic method capable of detecting multiple mutations associated with INH and RIF resistance simultaneously in a single microchip slide.     

Calculation of crystalline lens power using a modification of the Bennett method

We present a method for measuring lens power from extended depth OCT biometry, corneal topography, and refraction using an improvement on the Bennett method. A reduced eye model was used to derive a formula for lens power in terms of ocular distances, corneal power, and objective spherical equivalent refraction. An error analysis shows that the formula predicts relaxed lens power with a theoretical accuracy of ± 0.5 D for refractive error ranging from −10 D to + 10 D. The formula was used to calculate lens power in 16 eyes of 8 human subjects. Mean lens power was 24.3 D ± 1.7 D.OCIS codes: (170.4500) Optical coherence tomography, (170.4580) Optical diagnostics for medicine, (330.7325) Visual optics, metrology, (330.7326) Visual optics, modeling     

Low efficacy of entecavir therapy in adefovir‐refractory hepatitis B patients with prior lamivudine resistance

Summary. We determined the virologic response, incidence of entecavir resistance, and evolution of lamivudine and adefovir‐resistant mutants during entecavir (ETV) therapy in adefovir‐refractory patients with prior lamivudine resistance. Forty adefovir‐refractory chronic hepatitis B patients with prior lamivudine resistance who had received entecavir for ≥6 months were included and monitored for virologic response and entecavir resistance. Ten per cent of patients achieved HBV DNA < 50 copies/mL by PCR after 24 weeks of ETV therapy, and an initial virologic response was observed in 12 of 40 patients (30%). Higher pretreatment ALT (P = 0.039) and the presence of the rtL180M mutation (P = 0.038) were associated with an initial virologic response. During a mean follow‐up of 11.4 months, four patients (10%) experienced virologic breakthrough, while ETV‐resistant mutants were detected in six patients (15%). YMDD and adefovir‐resistant mutants were detected in 57 and 35% of patients at baseline, respectively. At 48 weeks of therapy, 96 and 4% of patients had YMDD and adefovir‐resistant mutants, respectively. These data suggest an early development of ETV resistance and low antiviral response during ETV therapy in adefovir‐refractory patients with prior lamivudine resistance.     

High FDG uptake in PET/CT predicts worse prognosis in patients with metastatic gastric adenocarcinoma

Purpose

We evaluated the role of FDG-PET/CT in patients with metastatic gastric adenocarcinoma before palliative chemotherapy to predict prognosis and chemotherapeutic response.

Methods

The study included 35 consecutive newly diagnosed patients with metastatic gastric adenocarcinoma who underwent FDG-PET/CT before palliative chemotherapy. Maximum standardized uptake value (SUVmax) of the primary tumor was assessed to evaluate survival and chemotherapeutic response. Survival analysis was performed for time to progression and overall survival using the Kaplan–Meier method. Cox proportional hazard models were used to determine independent prognostic factors.

Results

All primary tumors were visualized using FDG-PET/CT (mean SUVmax = 8.1 ± 4.5, range 2.5–22.1). Sensitivity, specificity, and accuracy of FDG-PET/CT in detection of solid organ metastasis were 95.2% (20/21), 100% (14/14), and 97.1% (34/35), respectively. No significant difference of primary tumor SUVmax was found among the chemotherapeutic response groups. Univariate survival analysis demonstrated ECOG performance status (≥2), presence of solid organ metastasis, number of organs involved in distant metastasis (≥2), and SUVmax of the primary tumor (>8) as significant predictors for poor overall survival. Multivariate survival analysis showed SUVmax of the primary tumor (P = 0.048), presence of solid organ metastasis (P = 0.015), and ECOG performance status (P = 0.002) as significant independent prognostic predictors for overall survival.

Conclusions

High FDG uptake of the primary tumor in patients with metastatic gastric adenocarcinoma is associated with poor overall survival. Assessment of tumor FDG uptake has limited value for prediction of chemotherapeutic response, but provides useful information regarding prognosis.     

The common exon 3 polymorphism of the growth hormone receptor gene and the effect of growth hormone therapy on growth in Korean patients with Turner syndrome

Objective Recombinant human growth hormone (GH) can achieve final adult height gain in girls with Turner syndrome (TS), but its efficacy varies widely across individuals. The exon 3‐deleted polymorphism of growth hormone receptor (d3‐GHR) has been reported to be associated with responsiveness to GH therapy. The short‐term growth response of Turner patients to GH therapy was analysed according to their GHR‐exon 3 polymorphism genotype. Design and patients This was a retrospective study of 175 TS patients. Auxological and endocrine parameters were measured, and the GHR‐exon 3 genotype was analysed. Allelic frequencies of GHR‐exon 3 genotype were compared between patients with TS and control individuals. GH had been administered to 147 patients, 115 of which remained pre‐pubertal after the first follow‐up year. Changes in height standard deviation score (SDS), height velocity (HV), body mass index (BMI), IGF‐1 and IGF binding protein‐3 (IGFBP‐3) concentrations were compared between these patients, grouped according to genotype, after the first follow‐up year. Results There was no difference in GHR‐exon 3 genotype frequency between the TS and control groups of Koreans. According to the GHR‐exon 3 genotype (fl/fl group vs. d3/fl and d3/d3 group), HV gain and height SDS gain did not differ significantly at the first year of GH therapy. Moreover, changes in IGF‐1, IGFBP‐3 concentration and BMI showed no significant difference between the groups with and without d3‐GHR after 1 year of GH therapy. Conclusion The distribution of the GHR‐exon 3 genotype was similar in the TS and control groups in a Korean population. The growth promotion efficacy of GH therapy did not differ significantly between TS patients with and without the d3‐GHR allele. These findings indicate that the GHR‐exon 3 genotype may not be a major factor to affect the GH response in Korean Turner patients.     

Gastrokine 1 functions as a tumor suppressor by inhibition of epithelial–mesenchymal transition in gastric cancers

Purpose  

Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. The specific aim of this study was to determine the molecular mechanisms underlying GKN1 tumor suppressor activity in the progression of gastric cancers.