Measuring the 3-30-300 rule to help cities meet nature access thresholds.

The 3-30-300 rule offers benchmarks for cities to promote equitable nature access. It dictates that individuals should see three trees from their dwelling, have 30 % tree canopy in their neighborhood, and live within 300 m of a high-quality green space. Implementing this demands thorough measurement, monitoring, and evaluation methods, yet little guidance is currently available to pursue these actions. To overcome this gap, we employed an expert-based consensus approach to review the available ways to measure 3-30-300 as well as each measure's strengths and weaknesses. We described seven relevant data and processes: vegetation indices, street level analyses, tree inventories, questionnaires, window view analyses, land cover maps, and green space maps. Based on the reviewed strengths and weaknesses of each measure, we presented a suitability matrix to link recommended measures with each component of the rule. These recommendations included surveys and window-view analyses for the '3 component', high-resolution land cover maps for the '30 component', and green space maps with network analyses for the '300 component'. These methods, responsive to local situations and resources, not only implement the 3-30-300 rule but foster broader dialogue on local desires and requirements. Consequently, these techniques can guide strategic investments in urban greening for health, equity, biodiversity, and climate adaptation.

Progressive hyperpigmentation in a Taiwanese child due to an inborn error of vitamin B12 metabolism (cblJ).

The physiology of human skin pigmentation is varied and complex, with an extensive melanogenic paracrine network involving mesenchymal and epithelial cells, contributing to the regulation of melanocyte survival and proliferation and melanogenesis. Mutations in several genes, involving predominantly the KIT ligand/c-Kit and Ras/mitogen-activated protein kinase signalling pathways, have been implicated in a spectrum of diseases in which there is hyperpigmentation, hypopigmentation or both. Here, we report on a 12-year-old girl from Taiwan with a 6-year history of diffuse progressive skin hyperpigmentation resulting from a different aetiology: an inborn metabolic disorder of vitamin B12 (cobalamin), designated cblJ. Using whole-exome sequencing we identified a homozygous mutation in ABCD4 (c.423C>G; p.Asn141Lys), which encodes an ATP-binding cassette transporter with a role in the intracellular processing of cobalamin. The patient had biochemical and haematological evidence of cobalamin deficiency but no other clinical abnormalities apart from a slight lightening of her previously black hair. Of note, she had no neurological symptoms or signs. Treatment with oral cobalamin (3 mg daily) led to metabolic correction and some reduction in the skin hyperpigmentation at the 3-month follow-up. This case demonstrates that defects or deficiencies of cobalamin should be remembered in the differential diagnosis of diffuse hyperpigmentary skin disorders.

Activated STING in a vascular and pulmonary syndrome.

BACKGROUND: The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS: We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-ß, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS: We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors. CONCLUSIONS: STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; ClinicalTrials.gov number, NCT00059748.).

The feasibility of QR-code prescription in Taiwan.

WHAT IS KNOWN AND OBJECTIVE: An ideal Health Care Service is a service system that focuses on patients. Patients in Taiwan have the freedom to fill their prescriptions at any pharmacies contracted with National Health Insurance. Each of these pharmacies uses its own computer system. So far, there are at least ten different systems on the market in Taiwan. To transmit the prescription information from the hospital to the pharmacy accurately and efficiently presents a great issue. METHODS: This study consisted of two-dimensional applications using a QR-code to capture Patient's identification and prescription information from the hospitals as well as using a webcam to read the QR-code and transfer all data to the pharmacy computer system. Two hospitals and 85 community pharmacies participated in the study. RESULTS AND DISCUSSION: During the trial, all participant pharmacies appraised highly of the accurate transmission of the prescription information. The contents in QR-code prescriptions from Taipei area were picked up efficiently and accurately in pharmacies at Taichung area (middle Taiwan) without software system limit and area limitation. The QR-code device received a patent (No. M376844, March 2010) from Intellectual Property Office Ministry of Economic Affair, China. WHAT IS NEW AND CONCLUSION: Our trial has proven that QR-code prescription can provide community pharmacists an efficient, accurate and inexpensive device to digitalize the prescription contents. Consequently, pharmacists can offer better quality of pharmacy service to patients.

Viral hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Despite recent advances in the diagnosis and treatment of HCC, its prognosis remains dismal. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factors for HCC. Although both are hepatotropic viral infections, there are important differences between the oncogenic mechanisms of these two viruses. In addition to the oncogenic potential of its viral proteins, HBV, as a DNA virus, can integrate into host DNA and directly transform hepatocytes. In contrast, HCV, an RNA virus, is unable to integrate into the host genome, and viral protein expression has a more critical function in hepatocarcinogenesis. Both HBV and HCV proteins have been implicated in disrupting cellular signal transduction pathways that lead to unchecked cell growth. Most HCC develops in the cirrhotic liver, but the linkage between cirrhosis and HCC is likely multifactorial. In this review, we summarize current knowledge regarding the pathogenetic mechanisms of viral HCC.

Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices.

BACKGROUND: Very early rebleeding is frequently encountered in patients with acute oesophageal variceal bleeding. A trial was designed to assess the efficacy and safety in patients with no active bleeding at endoscopy, receiving banding ligation association with terlipressin to prevent very early rebleeding. METHODS: Patients with no active variceal bleeding at endoscopy were evaluated. Eligible patients were randomised to receive terlipressin infusion alone for 5 days (Terlipressin group) or banding ligation plus terlipressin infusion for 2 days (Combined group). Primary endpoints were treatment failure and very early rebleeding. RESULTS: The terlipressin group was composed of 46 patients and the Combined group was composed of 47 patients. Both groups were comparable in terms of baseline data. Forty-eight-hour haemostasis was achieved in 91% in the Terlipressin group and 98% in the Combined group (p = 0.20). Very early rebleeding within 48-120 h occurred in 7 patients (15%) in the Terlipressin group but not in any patients (0%) in the Combined group (p = 0.006). Treatment failure was 24% in the Terlipressin group and 2% in the Combined group (p = 0.002). Multivariate analysis revealed that treatment (OR 0.081; 95% CI 0.010 to 0.627) was the only predictive factor of very early rebleeding. Blood requirement was significantly lower in the Combined group than in the Terlipressin group. Complications and 6-week survival were similar in both groups. CONCLUSIONS: Combination of banding ligation and terlipressin infusion for 2 days was superior to only infusion of terlipressin for 5 days in the reduction of very early rebleeding and treatment failure in patients with inactive variceal bleeding at endoscopy. TRIAL REGISTRATION NUMBER: ISRCTN28353453.

Distinguishing between two sympatric Acanthopagrus species from Dapeng Bay, Taiwan, using morphometric and genetic characters.

Morphometric and genetic data were used to compare two sympatric and morphologically similar species, Acanthopagrus berda and Acanthopagrus taiwanensis, in Dapeng Bay, South-western Taiwan. A principle component analysis of morphological data indicated a distinction between the two species, with pectoral fin length and eye diameter accounting for 32.27% of the variation. Interspecific sequence divergence, based on mtDNA cytochrome b (0.118 +/- 0.01), was larger than intraspecific divergences between haplotypes (0.007 for A. taiwanensis and 0.003 for A. berda). Individuals of the two species clustered into different groups in three phylogenetic trees with 100% bootstrap support. The mean observed heterozygosity for eight microsatellite loci was 0.471 +/- 0.202 for A. taiwanensis and 0.637 +/- 0.145 for A. berda. Nei's unbiased measure of interspecific genetic distance (D(S)) was 1.334. F(ST) (0.134) and R(ST) (0.404) values indicated significant differentiation between species. An unrooted neighbour-joining tree was constructed by allele-sharing distances and the factorial correspondence analysis split all specimens into two distinct clusters. The results of morphometric, mtDNA and microsatellite analyses indicated the presence of two species, A. taiwanensis and A. berda.

Clinical trial: percutaneous acetic acid injection vs. percutaneous ethanol injection for small hepatocellular carcinoma--a long-term follow-up study.

BACKGROUND: The long-term outcome of percutaneous acetic acid injection (PAI) and percutaneous ethanol injection (PEI) for treating small hepatocellular carcinoma (HCC) remains unclear. AIM: To compare the long-term outcome of PAI vs. PEI for treating small HCC. METHODS: From July 1998 to July 2004, 125 patients with small HCC were enrolled. Seventy patients receiving PAI and 55 patients receiving PEI were enrolled. There were no significant differences in the clinical characteristics between the two groups. Tumour recurrence and survival rates were assessed. RESULTS: Mean follow-up time was 43 months. The local recurrence rate and new tumour recurrence rate were similar between the PAI and PEI groups. The PAI group had significantly better survival than the PEI group (P = 0.027). Multivariate analysis revealed that PAI was the significant factor associated with overall survival [PAI vs. PEI, RR: 0.639, 95% CI: (0.419-1.975), P = 0.038]. The treatment sessions required to achieve complete tumour necrosis were significantly fewer in the PAI group than in the PEI group (2.4 +/- 1.0 vs. 2.9 +/- 1.3, P = 0.018). CONCLUSION: Percutaneous acetic acid injection required fewer treatment sessions than PEI and provided better survival after long-term follow-up.

Prostacyclin protects renal tubular cells from gentamicin-induced apoptosis via a PPARalpha-dependent pathway.

To study the protective effect of prostacyclin (PGI2) we increased PGI2 production by infected NRK-52E cells with an adenovirus carrying cyclooxygenase-1 and prostacyclin synthase. PGI2 overexpression protected these cells from gentamicin-induced apoptosis by reducing cleaved caspase-3 and caspase-9, cytochrome c, and decreasing generation of reactive oxygen species. Expression of the nuclear receptor of PGI2, peroxisome proliferator-activated receptor-alpha (PPARalpha), was reduced during gentamicin treatment of the cells, while its overexpression significantly inhibited gentamicin-induced apoptosis and the amount of cleaved caspase-3. Transformation with PPARalpha short interfering RNA abolished the protective effect of PGI2 overproduction in gentamicin-treated cells. The PPARalpha activator docosahexaenoic acid given to gentamicin-treated mice significantly reduced the number of apoptotic cells in renal cortex, but this protective effect was not seen in PPARalpha knockout mice. Our study suggests that increased endogenous PGI2 production protects renal tubular cells from gentamicin-induced apoptosis through a PPARalpha-signaling pathway.

Role of breast tumour kinase in the in vitro differentiation of HaCaT cells.

BACKGROUND: Breast tumour kinase (BRK) is a newly identified non-receptor protein tyrosine kinase from a metastatic breast tumour. Its biological functions are still under extensive investigation. The mouse homologue Sik (Src-related intestinal kinase) has been implicated in mouse keratinocyte differentiation; however, not much is known about the functions of BRK in human cutaneous biology. OBJECTIVES: Using HaCaT cells as an experimental model, to explore the mutual relationships between BRK and differentiation of human keratinocytes. METHODS: Archival paraffin blocks of normal and pathological skin were retrieved for examining the in vivo distribution of BRK. Its expression and subcellular localization were examined via indirect immunofluorescence, and quantitative changes were analysed by Northern and Western blots. The kinase activity of BRK was determined by its autophosphorylation and phosphorylation of exogenous substrate in the in vitro kinase assay. Using a retroviral infection method, we established stably transfected HaCaT cells expressing vector, wild-type BRK or a kinase-defective mutant (K219M). Expression of the differentiation marker keratin 10 (K10) was compared among these cells using semiquantitative reverse transcription-polymerase chain reaction. Results Histochemical examination showed that BRK was expressed exclusively in suprabasal keratinocytes. Its distribution was both cytoplasmic and intranuclear. An enhanced regional suprabasal expression pattern was observed in the confluent areas of cell cultures. The expression of BRK transcript and protein was up-regulated in prolonged confluence culture in a serum-dependent manner. Its kinase activity was activated shortly after the addition of calcium and ionomycin and returned to the basal level within 30 min. Overexpression of wild-type BRK moderately promoted the expression of K10 transcript while the kinase-defective BRK mutant exerted a prominent suppressive effect. CONCLUSIONS: The in vivo distribution of BRK and its up-regulation during in vitro differentiation of HaCaT cells, together with the activation of its kinase activity by calcium/ionomycin and its influence on K10 expression, all indicate a role for BRK in the complex process of keratinocyte differentiation.

Imaging cells and tissues with refractive index radiology.

Can individual cells, including live cells, be imaged using hard x rays? Common wisdom until now required sophisticated staining techniques for this task. We show instead that individual cells and cell details can be detected in culture solution and tissues with no staining and no other contrast-enhancing preparation. The sample examined can be much thicker than for many other microscopy techniques without sacrificing the capability to resolve cells. The key factor in our approach is the use of a coherent synchrotron source and of contrast mechanisms based on the refractive index. The first successful tests were conducted on a variety of cell systems including skin and internal leaf cells, mouse neurons, rabbit fibroblast cells, and human tumor cells.

Synchrotron microangiography with no contrast agent.

Coherent x-rays from synchrotron sources are increasingly used in non-conventional radiological techniques ('phase-contrast' radiology). Our experiments demonstrate that by using white (unmonochromatic) radiation and a time-resolving system, it is possible to image microscopic details of moving blood vessels in different live animals without using any contrast agent. The images have excellent contrast plus unprecedented spatial resolution for microangiography (< 10 microm). This result is likely to impact many different areas of biological and medical research and of diagnostic radiology.

Endoscopic balloon dilatation is a safe method in the management of common bile duct stones.

BACKGROUNDS AND AIMS: Endoscopic sphincterotomy is a widely accepted treatment for patients with common bile duct stones. Despite improvement in this technique, endoscopic sphincterotomy is still associated with some biliary complications. Endoscopic balloon dilatation is a less traumatic and sphincter preserving method for removal of common bile duct stones. However, the results of controlled studies in comparison with these two methods are contradictory. The aim of this study is to compare the safety and efficacy of endoscopic balloon dilatation and endoscopic sphincterotomy in Chinese patients. PATIENTS AND METHODS: A total of 104 patients with common bile duct stones on endoscopic retrograde cholangiopancreatography were enrolled. They were randomly assigned to endoscopic balloon dilatation or endoscopic sphincterotomy. Endoscopic balloon dilatation was performed by using a balloon dilator to dilate the sphincter for 5 min. The common bile duct stones were then removed by a Dormia basket after endoscopic balloon dilatation or endoscopic sphincterotomy. Mechanical lithotripsy was performed if the stones were difficult to remove by Dormia basket. After discharge, patients were regularly followed up for biliary complications. RESULTS: The successful bile duct stone clearance rate was 94.1% in endoscopic balloon dilatation group and 100% in endoscopic sphincterotomy group. Post-procedural significant haemorrhage was higher in endoscopic sphincterotomy group than in endoscopic balloon dilatation group (14/53 versus 1/48, P < 0.001). The bleeding patient from endoscopic balloon dilatation group was a case of uremia and bleeding occurred 48 h after endoscopic balloon dilatation. All the patients with post-procedural haemorrhage were controlled endoscopically. The post-procedural serum amylase level showed no significant difference in both groups and none of them developed clinical pancreatitis. After a mean 16 months follow-up, three patients (6.3%) in endoscopic balloon dilatation group and four patients (7.5%) in endoscopic sphincterotomy group developed recurrent common bile duct stones. The recurrent common bile duct stones were multiple and muddy in consistency. They were successfully removed endoscopically. CONCLUSION: Both endoscopic balloon dilatation and endoscopic sphincterotomy are safe and effective techniques for the treatment of common bile duct stones. Endoscopic balloon dilatation can be safely applied in patients with coagulopathy and does not increase the incidence of pancreatitis or bleeding.

The phosphotidyl inositol 3-kinase/Akt signal pathway is involved in interleukin-6-mediated Mcl-1 upregulation and anti-apoptosis activity in basal cell carcinoma cells.

Dysregulation of interleukin-6 has been reported to be associated with various types of tumors, and interleukin-6 plays an important part in regulating apoptosis in many types of cells. Previously, Mcl-1 was shown to be significantly increased in interleukin-6-overexpressed basal cell carcinoma cells and conferred on them anti-apoptotic activity. The aim of this study was to investigate which signaling pathway is involved in the anti-apoptotic effect of interleukin-6 on basal cell carcinoma cells. Here we show that the addition of recombinant 100 ng per ml interleukin-6 to basal cell carcinoma cells induced a 2.3-fold increase in the level of Mcl-1 protein in basal cell carcinoma cells. Transfection with dominant-negative STAT3 (STAT3F) into inter-leukin-6-treated basal cell carcinoma cells caused a decrease of phosphotyrosyl STAT3 but did not alter Mcl-1 protein levels; however, AG490, a Janus tyrosine kinase inhibitor, was capable of inhibiting the interleukin-6-induced elevation of Mcl-1 protein. Next, interleukin-6 stimulation elicited extracellular signal-regulated kinase activation in basal cell carcinoma cells, and the mitogen-activated protein kinase inhibitor, PD98059, could affect this response without affecting the interleukin-6-medi-ated Mcl-1 upregulation. Use of the two phosphotidyl inositol 3-kinase inhibitors, LY294002 and wortmannin, to check whether this pathway is involved in Mcl-1 upregulation by interleukin-6, we found that the phosphotidyl inositol 3-kinase inhibitors completely attenuated the interleukin-6-induced Mcl-1 upregulation. Furthermore, in the interleukin-6-overexpressing basal cell carcinoma cell clone, dominant-negative Akt also significantly reduced the increased level of Mcl-1. Interestingly, Janus tyrosine kinase inhibitor, AG490, treatment strongly blocked the phosphotidyl inositol 3-kinase pathway activation, as evidenced by the decrease in phospho-Akt level. Blockage of phosphotidyl inositol 3-kinase/Akt pathway abolished the interleukin-6-mediated anti-apoptotic activity in ultraviolet B treated cells. Unexpectedly, without ultraviolet B irradiation, STAT3F transfection also induced a significant apoptosis in basal cell carcinoma/interleukin-6 cells. Taken together, our data suggest that both the phosphotidyl inositol 3-kinase/Akt and STAT3 pathways are potentially involved in interleukin-6-mediated cell survival activity in basal cell carcinoma cells; however, the upregulation of the anti-apoptotic Mcl-1 protein by interleukin-6 is mainly through the Janus tyrosine kinase/phosphotidyl inositol 3-kinase/Akt, but not the STAT3 pathway.

Risk factors for ulcer development in patients with non-ulcer dyspepsia: a prospective two year follow up study of 209 patients.

BACKGROUND AND AIMS: A subset of non-ulcer dyspepsia (NUD) disorders can evolve into peptic ulcer disease. This prospective study attempted to determine the independent risk factors for ulcer formation in NUD patients, and compared the natural history of Helicobacter pylori positive and negative NUD subjects. METHODS: From May 1997 to April 1999, consecutive NUD patients were enrolled into the study. Endoscopy was performed routinely on enrolment, at the end of the second and 12th months, and whenever there was a dyspepsia attack. Patients were prospectively followed up for two years. RESULTS: Peptic ulcers occurred in 16 of 209 NUD patients during the two year follow up period. Multivariate analysis of 13 host and bacterial factors demonstrated that advanced age (odds ratio 2.90), H pylori infection (odds ratio 3.59), and use of non-steroidal anti-inflammatory drugs (NSAID; odds ratio 4.46) were independently significant in predicting subsequent peptic ulcer development. NUD patients with all three risk factors had a 75% (3/4) risk of developing peptic ulcer but the ulcer incidence in patients without any of the risk parameters was only 1.2% (1/84). The resolution rate of symptoms in the H pylori positive NUD patients was similar to the H pylori negative patients (57.9% v 49.1%; 95% confidence interval (CI) -5 to 22). However, rates for subsequent peptic ulcer and erosion development were significantly higher in H pylori positive patients than in H pylori negative patients (ulcer 12.6% v 3.5%, 95% CI 1-16; erosion 23.2% v 12.3%, 95% CI 1-21). CONCLUSION: A small but significant proportion of NUD patients develop peptic ulcer after long term follow up. H pylori infection, NSAID use, and advanced age are independent risk factors for subsequent ulcer formation. Follow up endoscopy is strongly indicated for an NUD patient with multiple risk factors for ulcer formation when symptoms recur.

Electrochemistry: building on bubbles in metal electrodeposition.

In the electrodeposition of metals, a widely used industrial technique, bubbles of gas generated near the cathode can adversely affect the quality of the metal coating. Here we use phase-contrast radiology with synchrotron radiation to witness directly and in real time the accumulation of zinc on hydrogen bubbles. This process explains the origin of the bubble-shaped defects that are common in electrodeposited coatings.

Psychiatric morbidity and post-traumatic symptoms among survivors in the early stage following the 1999 earthquake in Taiwan.

This study reports the clinical psychiatric presentations and post-traumatic symptoms among 525 survivors at Yu-Chyr District in Nantou County who sought psychiatric service in the first month following the devastating earthquake that struck the central area of Taiwan. All subjects received psychiatric interviews and assessments using the 12-item Chinese Health Questionnaire (CHQ-12) and a checklist for post-traumatic symptoms. The most common psychiatric symptoms reported were insomnia, palpitations, nervousness, and dizziness with headache. Eleven percent of the subjects reported having thought of death or having suicidal ideation. The mean score on the CHQ-12 was 6.43 (S.D.=2.89). The rate of probable psychiatric morbidity as defined by a CHQ-12 score > or =3 was 89.9%. Post-traumatic symptoms were very prevalent, particularly symptoms of re-experiencing the earthquake and hyper-arousal. Factors significantly associated with high psychiatric morbidity were being female, serious destruction of property and house, and personality characteristics of nervousness and obsessiveness. Findings of this study suggest that early psychiatric intervention, including pharmacological treatment for acute stress disorder, is indicated during the early stages following a disastrous earthquake.

First trimester diagnosis of holoprosencephaly and cyclopia with triploidy by transvaginal three-dimensional ultrasonography.

We present the prenatal three-dimensional (3D) ultrasound findings in a case of holoprosencephaly and cyclopia at 11 weeks gestation. Only holoprosencephaly with missing cyclopia were initially diagnosed because suboptimal views of the fetal face were obtained with transvaginal two-dimensional (2D) ultrasonography due to fetal position. Chromosomes identified by analysis of a fluid sample from early amniocentesis demonstrated a triploidy (69, XXX), spontaneous fetal demise occurred at 12 weeks and the pregnancy was terminated. This case demonstrated the usefulness of transvaginal 3D ultrasonography in establishing the final diagnosis.

Implications of quantitative tumor and nodal regression rates for nasopharyngeal carcinomas after 45 Gy of radiotherapy.

PURPOSE: To quantitatively investigate the clinical implications of tumor regression rate (TRR-45) and nodal regression rate (NRR-45) of nasopharyngeal carcinomas (NPC) after receiving 45 Gy of radiotherapy (RT). The values, predictive values, and associated factors of TRR-45 and NRR-45 in NPC are analyzed. METHODS AND MATERIALS: One hundred one patients with newly diagnosed NPC and who were curatively treated by RT alone were included in the study. Tumor volume and nodal volume before treatment and after 45 Gy were obtained from computed tomographic (CT) scans performed at those times and calculated with the assistance of a computer-based imaging analyzing system. TRR-45 (NRR-45) was defined as the ratio of reduced tumor (nodal) volume after 45 Gy to the initial tumor (nodal) volume. TRR-45 (NRR-45) values were stratified into three groups of slow (below 50%), moderate (between 50% and 75%), and rapid (above 75%) change. After conventional RT with 45 Gy, conformal RT for primary tumors was boosted to 70.2-72 Gy for T1-2 tumors, and 75.6-81 Gy for T3-T4 tumors. RT for residual neck masses was boosted by electron beam to 61-75 Gy. RESULTS: The mean value of TRR-45 for all patients was lower than that of NRR-45 for the 78 patients with metastatic neck nodes (70% +/- 4.8% vs. 81% +/- 5%, p = 0.003). The 3-year actuarial neck control rate was better than the primary tumor control rate with statistical significance (98% vs. 85%, p = 0.009). No significant statistical differences concerning local control probability, nodal control probability, or survival rate were found among patients with slow, moderate, or rapid TRR-45 or NRR-45. T-stage was the only significant prognostic factor for locoregional control after multivariate analysis. Tumor volume and T-stage were found to have a statistically significant negative correlation with TRR-45. No associated factor was found to be significantly correlated with NRR-45. CONCLUSION: Slow regression rates of the primary tumor or neck nodes in NPC after receiving 45 Gy of irradiation do not mean ultimately poor radiocurability, but may merely imply slow clearance of the cells damaged during irradiation. The different radiobiological behaviors of the regression rates during treatment, ultimate control probabilities, or associated factors for regression rates of NPC between primary tumors and neck nodes need to be further investigated.

Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency.

Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the diverse functions of cells such as acute phase responses and inflammation. Excessive or insufficient production of IL-6 may contribute to certain diseases of the skin. The aim of this study was to investigate the possible role of IL-6 in the tumorigenesis of basal cell carcinoma (BCC). Initially, we transfected IL-6 expression vector, under the control of a CMV promoter, into human BCC cells and successfully obtained IL-6-overexpressing clones (BCC/IL-6-c1 and BCC/IL-6-c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using (3)H-thymidine pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much higher DNA synthesis rate than the neo control or parental BCC cells. We also detected a greater abundance of IL-6-expressing cell colonies formed in soft agar than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector control cells, were resistant to UV and photodynamic therapy (PDT)-induced apoptosis, as confirmed using DNA fragmentation and morphologic change analyses. Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was specifically up-regulated IL-6 transfectants but not in the control cells. Transient transfection of IL-6 transfectants with antisense mcl-1 greatly enhanced their apoptosis frequency by UV treatment. In tumorigenesis assay, IL-6 transfected clones formed tumors in nude mice more rapidly than the control cells. These tumors appeared to be highly vascularized using pathological examination. Supportive of this finding, we found that IL-6 transfected cells expressed elevated levels of two angiogenic factors, cyclooxygenase (Cox)-2 and vascular endothelial growth factor (VEGF). These results suggest that overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both suppressing apoptosis and actively promoting angiogenesis.