Expression of the candidate tumor suppressor gene hSRBC is frequently lost in primary lung cancers with and without DNA methylation

Recently, the human SRBC (hSRBC) gene, a candidate tumor suppressor gene (TSG), has been mapped to the chromosomal region 11p 15.5--p15.4 where frequent allele loss has been described in lung cancer. Aberrant methylation (referred to as methylation) of the promoter region of TSGs has been identified as an important mechanism for gene silencing. Loss of hSRBC protein expression occurs frequently in lung cancer cell lines and sodium bisulfite sequencing of the promoter region of hSRBC in several lung cancer cell lines suggested that methylation plays an important role in inactivating hSRBC. To determine the methylation status of hSRBC in a large collection of primary lung cancer samples, corresponding nonmalignant lung tissues and lung cancer cell lines (N=52), we designed primers for a methylation-specific PCR assay. Methylation was detected in 41% of primary non-small-cell lung cancers (NSCLC) (N=107) and in 80% of primary small-cell lung cancers (SCLC) (N=5), but was seen only in 4% of corresponding nonmalignant lung tissues (N=103). In all, 79% of lung cancer cell lines were methylated and the frequency of hSRBC methylation was significantly higher in SCLC (100%) than in NSCLC (58%) cell lines. Normal hSRBC protein expression was detected in only 18% of primary NSCLCs (N=93) by immunostaining and a significant association between loss of protein expression and methylation was found. hSRBC re-expression was observed after treatment of lung cancer cells with the demethylating agent 5-aza-2'-deoxycytidine. In addition, 45% of the 76 hSRBC immunostaining-negative NSCLCs did not have hSRBC promoter methylation, indicating that other mechanisms of hSRBC expression silencing also exist. Both hSRBC immunostaining and methylation results did not correlate with clinicopathological characteristics of these patients. Our findings suggest that hSRBC is a candidate TSG involved in lung cancer pathogenesis, where expression is frequently inactivated by methylation and other mechanisms.     

Fruits and dietary phytochemicals in bone protection

Osteoporosis is a disease of bone characterized by loss of bone matrix and deterioration of bone microstructure that leads to an increased risk of fracture. Cross-sectional studies have shown a positive association between higher fruit intake and higher bone mineral density. In this review, we evaluated animal and cellular studies of dried plum and citrus and berry fruits and bioactive compounds including lycopene, phenolics, favonoids, resveratrol, phloridzin, and pectin derived from tomato, grapes, apples, and citrus fruits. In addition, human studies of dried plum and lycopene were reviewed. Animal studies strongly suggest that commonly consumed antioxidant-rich fruits have a pronounced effect on bone, as shown by higher bone mass, trabecular bone volume, number, and thickness, and lower trabecular separation through enhancing bone formation and suppressing bone resorption, resulting in greater bone strength. Such osteoprotective effects seem to be mediated via antioxidant or anti-inflammatory pathways and their downstream signaling mechanisms, leading to osteoblast mineralization and osteoclast inactivation. In future studies, randomized controlled trials are warranted to extend the bone-protective activity of fruits and their bioactive compounds. Mechanistic studies are needed to differentiate the roles of phytochemicals and other constitutes in bone protection offered by the fruits. Advanced imaging technology will determine the effective doses of phytochemicals and their metabolites in improving bone mass, microarchitecture integrity, and bone strength, which is a critical step in translating the benefits of fruit consumption on osteoporosis into clinical data.     

Beta2-adrenoceptor polymorphisms and obstructive airway diseases: important issues of study design

1. Asthma and chronic obstructive pulmonary disease (COPD) are chronic airway diseases characterized by airflow obstruction. The beta(2)-adrenoceptor mediates bronchodilatation in response to exogenous and endogenous beta-adrenoceptor agonists. 2. Single nucleotide polymorphisms in the beta(2)-adrenoceptor gene (ADRB2) cause amino acid changes (e.g. Arg16Gly, Gln27Glu) that potentially alter receptor function. Recently, a large cohort study found no association between asthma susceptibility and beta(2)-adrenoceptor polymorphisms. In contrast, asthma phenotypes, such as asthma severity and bronchial hyperresponsiveness, have been associated with beta(2)-adrenoceptor polymorphisms. Of importance to asthma management, coding region polymorphisms may alter the response to short-acting and long-acting beta-adrenoceptor agonists, which are commonly prescribed asthma treatments. 3. Optimizing study design would enhance the robustness of genetic association studies of ADRB2 polymorphisms in airway diseases. Characteristics of high-quality studies include suitable study design and subject selection, optimal study of polymorphisms and haplotypes, disease outcomes of relevance, adequate sample size, adjustment for confounding factors, supportive functional data and appropriate analysis, interpretation and replication. Enhancing these study design factors will provide high-quality evidence regarding the biological and clinical importance of beta(2)-adrenoceptor pharmacogenomics in asthma and COPD.     

A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease

In Saccharomyces cerevisiae, transport of arginine into the vacuole has previously been shown to be facilitated by a putative H+/arginine antiport. We confirm that transport of arginine into isolated yeast vacuoles requires ATP and we demonstrate a requirement for a functional vacuolar H+-ATPase. We previously reported that deletion of BTN1 (btn1-delta), an ortholog of the human Batten disease gene CLN3, resulted in a decrease in vacuolar pH during early growth. We report that this altered vacuolar pH in btn1-delta strains underlies a lack of arginine transport into the vacuole, which results in a depletion of endogenous vacuolar arginine levels. This arginine transport defect in btn1-delta is complemented by expression of either BTN1 or the human CLN3 gene and strongly suggests a function for transport of, or regulation of the transport of, basic amino acids into the vacuole or lysosome for yeast Btn1p, and human CLN3 protein, respectively. We propose that defective transport at the lysosomal membrane caused by an absence of functional CLN3 is the primary biochemical defect that results in Batten disease.     

Intrahepatic cholangiocarcinoma in Korea

We reviewed surgically treated patients with intrahepatic cholangiocarcinoma to evaluate the clinical and pathologic features of intrahepatic cholangiocarcinoma that may affect long-term survival in Korean patients with the disease. Between 1990 and 1997, 28 patients with intrahepatic cholangiocarcinoma underwent laparotomy. Resection was performed in 25 patients, and wedge resection alone in 3 patients. The liver resections consisted of right lobectomy in 5 patients, right trisegmentectomy in 1, left lobectomy in 7, extended left lobectomy in 3, hepatopancreatoduodenectomy in 2, and segmentectomy in 7. Curative resection was performed in 15 patients. Histological sections of all resected specimens were immunohistochemically stained with p53 and Ki-67 monoclonal antibodies to assess the biological behavior of the tumor cells. Cumulative survival rate and clinicopathological factors that may influence the prognosis, including biological markers (p53, Ki-67), were analyzed statistically. Patients who underwent curative resection survived significantly longer than patients who underwent noncurative resection. The median survival time of the patients who underwent curative resection was 24 months (mean, 34 ± 8 months), with 1-, 2-, and 3-year survival rates of 66.6%, 44.4%, and 35.6%, respectively. The median survival time of the patients who underwent noncurative resection was 3 months (mean, 8 ± 3 months), with 1- and 2-year survival rates of 26.7% and 13.4%, respectively. Univariate analysis showed that positive regional lymph nodes correlated significantly with poor outcome (P = 0.004) and that curative resection significantly correlated with better prognosis (P = 0.001). Age, sex, tumor size, degree of cell differentiation, gross type of tumor, and p53 and Ki-67 labeling index were not significantly correlated with outcome. Our findings support the concept that aggressive liver resection, along with regional lymph node dissection, be recommended for long-term survival. The validity of molecular biologic tumor markers (p53, Ki-67) as prognostic factors has not yet been clearly demonstrated.     

Photodynamic therapy: current evidence and applications in dermatology

Photodynamic therapy (PDT) involves the activation of a photosensitizing drug, which preferentially localizes to diseased skin, by irradiation with light to cause selective cytotoxic damage. Since its discovery in the early 20th century and the development of topical photosensitizers 2 decades ago, PDT is increasingly being used in dermatology for a wide range of neoplastic, inflammatory, and infectious cutaneous conditions. Topical 5-aminolevulinic acid and methyl aminolevulinic acid, the most commonly used agents in PDT, have received Food and Drug Administration approval for the treatment of actinic keratoses, and many second-generation photosensitizers are under investigation. Compared with conventional therapies, PDT has the advantage of being noninvasive and capable of field treatment. It is also associated with quicker recovery periods and excellent cosmetic results. Because of these benefits, PDT is being evaluated as a potential treatment option for many dermatologic conditions and has been shown to be effective for certain nonmelanoma skin cancers. Although research is still limited, PDT might also have a therapeutic benefit for cutaneous T-cell lymphoma, acne, psoriasis, leishmaniasis, and warts, among others. This article is a review of the clinical applications of PDT in dermatology and summarizes the current evidence in literature describing its efficacy, safety, and cosmetic outcome.     

Replacement of n-type layers with a non-toxic APTES interfacial layer to improve the performance of amorphous Si thin-film solar cells

Hydrogenated amorphous Si (a-Si:H) thin-film solar cells (TFSCs) generally contain p/n-type Si layers, which are fabricated using toxic gases. The substitution of these p/n-type layers with non-toxic materials while improving the device performance is a major challenge in the field of TFSCs. Herein, we report the fabrication of a-Si:H TFSCs with the n-type Si layer replaced with a self-assembled monolayer (3-aminopropyl) triethoxysilane (APTES). The X-ray photoelectron spectroscopy results showed that the amine groups from APTES attached with the hydroxyl groups (–OH) on the intrinsic Si (i-Si) surface to form a positive interfacial dipole towards i-Si. This interfacial dipole facilitated the decrease in electron extraction barrier by lowering the work function of the cathode. Consequently, the TFSC with APTES showed a higher fill factor (0.61) and power conversion efficiency (7.68%) than the reference device (without APTES). This performance enhancement of the TFSC with APTES can be attributed to its superior built-in potential and the reduction in the Schottky barrier of the cathode. In addition, the TFSCs with APTES showed lower leakage currents under dark conditions, and hence better charge separation and stability than the reference device. This indicates that APTES is a potential alternative to n-type Si layers, and hence can be used for the fabrication of non-toxic air-stable a-Si:H TFSCs with enhanced performance.

Hydrogenated amorphous Si (a-Si:H) thin-film solar cells (TFSCs) generally contain p/n-type Si layers, which are fabricated using toxic gases.