Functional characterisation of two phytochelatin synthases in rice (Oryza sativa cv. Milyang 117) that respond to cadmium stress.

Cadmium (Cd) is one of the most toxic heavy metals and a non-essential element to all organisms, including plants; however, the genes involved in Cd resistance in plants remain poorly characterised. To identify Cd resistance genes in rice, we screened a rice cDNA expression library treated with CdCl2 using a yeast (Saccharomyces cerevisiae) mutant ycf1 strain (DTY167) and isolated two rice phytochelatin synthases (OsPCS5 and OsPCS15). The genes were strongly induced by Cd treatment and conferred increased resistance to Cd when expressed in the ycf1 mutant strain. In addition, the Cd concentration was twofold higher in yeast expressing OsPCS5 and OsPCS15 than in vector-transformed yeast, and OsPCS5 and OsPCS15 localised in the cytoplasm. Arabidopsis thaliana plants overexpressing OsPCS5/-15 paradoxically exhibited increased sensitivity to Cd, suggesting that overexpression of OsPCS5/-15 resulted in toxicity due to excess phytochelatin production in A. thaliana. These data indicate that OsPCS5 and OsPCS15 are involved in Cd tolerance, which may be related to the relative abundances of phytochelatins synthesised by these phytochelatin synthases.

Effects of triethylene glycol dimethacrylate and hydroxyethyl methacrylate on macrophage polarization.

AIM: To evaluate the effects of hydrophilic dental resin monomers, triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA), on the polarization of a human monocyte cell line (THP-1). METHODOLOGY: THP-1 cells were treated with resin monomers at noncytotoxic concentrations for 48 h and were analysed for CD86 and CD206 expressions using flow cytometry. The cells were stimulated for polarization in the presence of resin monomers (co-treatment) or after treatment with monomers (pre-treatment). CD86 and CD206 mRNA in co-treated cells was evaluated using quantitative real-time polymerase chain reaction. The release of TNF-α and TGF-ß by pre-treated and co-treated cells was assessed using enzyme-linked immunosorbent assay. Morphological changes of macrophages during polarization were observed using bright-field microscopy. One-way analysis of variance was used for statistical analysis. RESULTS: TEGDMA (1 mmol L-1 ) and HEMA (2 mmol L-1 ) did not induce CD86 and CD206 expressions in THP-1 cells but rather inhibited their expressions in the co-treated cells. The inhibitory effects also appeared at the transcription level. However, the expression of surface markers was not affected by pre-treatment with resin monomers. The release of TNF-α and TGF-ß by M1- and M2-stimulated cells, respectively, was suppressed by co-treatment (P < 0.05). Microscopic studies revealed that co-treatment with resin monomers suppressed polarization-associated morphological changes such as cell volume increase. CONCLUSIONS: TEGDMA and HEMA inhibited macrophage polarization to both M1 and M2 at the transcription level, and the inhibitory effects disappeared upon the removal of resin monomers from the cell culture.

Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis.

BACKGROUND: Uncomplicated appendicitis may resolve spontaneously or require treatment with antibiotics or appendicectomy. The aim of this randomized trial was to compare the outcome of a non-antibiotic management strategy with that of antibiotic therapy in uncomplicated appendicitis. METHODS: Patients presenting to a university teaching hospital with CT-verified uncomplicated simple appendicitis (appendiceal diameter no larger than 11 mm and without any signs of perforation) were randomized to management with a no-antibiotic regimen with supportive care (intravenous fluids, analgesia and antipyretics as necessary) or a 4-day course of antibiotics with supportive care. The primary endpoint was rate of total treatment failure, defined as initial treatment failure within 1 month and recurrence of appendicitis during the follow-up period. RESULTS: Some 245 patients were randomized within the trial, and followed up for a median of 19 months. The duration of hospital stay was shorter (mean 3·1 versus 3·7 days; P < 0·001) and the medical costs lower (€1181 versus 1348; P < 0·001) among those randomized to therapy without antibiotics. There was no difference in total treatment failure rate between the groups: 29 of 124 (23·4 per cent) in the no-antibiotic group and 25 of 121 (20·7 per cent) in the antibiotic group (P = 0·609). Eighteen patients (9 in each group) had initial treatment failure, 15 of whom underwent appendicectomy and three received additional antibiotics. Thirty-six patients (20 in the no-antibiotic group, 16 in the antibiotic group) experienced recurrence, of whom 30 underwent appendicectomy and six received further antibiotics. CONCLUSION: Treatment failure rates in patients presenting with CT-confirmed uncomplicated appendicitis appeared similar among those receiving supportive care with either a no-antibiotic regimen or a 4-day course of antibiotics. Registration number: KCT0000124 ( http://cris.nih.go.kr).

Everolimus-Induced Systemic Serositis After Simultaneous Liver and Kidney Transplantation: A Case Report.

Although everolimus, a mammalian target of rapamycin inhibitor, has been used as a potent immunosuppressive agent in organ transplantation, data regarding its adverse effect profile compared with that of sirolimus in clinical circumstances are limited. A 50-year-old man who underwent simultaneous liver and kidney transplantation 14 months previously was admitted with large pleural effusion, pericardial effusion, and ascites. Laboratory findings and cultures for possible infectious causes were all negative. Pericardial window surgery with drainage of the pericardial fluid was performed on day 3. Pleural and pericardial biopsy revealed non-specific inflammation without evidence of malignant cells. Everolimus was discontinued and replaced by mycophenolate mofetil on day 4. Significant clinical improvement was observed after discontinuation of everolimus, and follow-up echocardiography and chest radiography showed no recurrence of the pericardial or pleural effusion after discharge.

API5 confers cancer stem cell-like properties through the FGF2-NANOG axis.

Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity. Critically, these CSC-like properties mediated by API5 are dependent on FGFR1 signaling, which is triggered by E2F1-dependent FGF2 expression. Furthermore, we uncovered the FGF2-NANOG molecular axis as a downstream component of API5 signaling that is conserved in cervical cancer patients. Finally, we found that the blockade of FGFR signaling is an effective strategy to control API5high human cancer. Thus, our findings reveal a crucial role of API5 in linking immune resistance and CSC-like properties, and provide the rationale for its therapeutic application for the treatment of API5+ refractory tumors.

Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration.

Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration.

Protective role of quercetin against cisplatin-induced hair cell damage in zebrafish embryos.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the protective effects of quercetin on cisplatin-induced hair cell damage in transgenic zebrafish embryos. MATERIALS AND METHODS: Five days postfertilization zebrafish embryos were exposed to 1 mM cisplatin and quercetin at 10, 50, 100, or 200 µM for 4 h. Hair cells within neuromasts of the supraorbital, otic, and occipital lateral lines were analyzed by fluorescent microscopy (n = 10). Survival of hair cells was calculated as the average number of hair cells in the control group that were not exposed to cisplatin. Ultrastructural changes were evaluated using scanning electron microscopy. RESULTS: Hair cell damage in neuromasts was decreased by co-treatment of quercetin and cisplatin (quercetin 100 µM: 8.6 ± 1.1 cells; 1 mM cisplatin only: 5.0 ± 0.5 cells; n = 10, p < 0.05); apoptosis of hair cells examined by special stain was also decreased by quercetin. The ultrastructure of hair cells within neuromasts was preserved in zebrafish by the combination of quercetin (100 µM) and cisplatin (1 mM). CONCLUSION: In conclusion, quercetin showed protective effects against cisplatin-induced toxicity in a zebrafish model. The results of this study suggest the possibility of a protective role of quercetin against cisplatin-induced apoptotic cell death in zebrafish.

Development of the dual SMART micro-surgical system using common-path swept source optical coherence tomography.

Manual micro-surgical tasks are fundamentally divided into grasping, cutting and injecting maneuvers performed on biological tissues. Efficient dissection of fibrous tissue from the surface of the retina often requires grasping and cutting maneuvers carried out simultaneously. True bimanual surgery requires that the surgeon contend with the innate hand tremor of two hands at once as well as unpredicted patient's movement. In this study, we develop and test a dual SMART micro-surgical system to suppress bimanual hand tremor during micro-surgical dissection.

Utility of QuantiFERON-TB assay for prediction of tuberculosis development in kidney transplant patients in an intermediate-tuberculosis-burden country: lack of evidence for enhanced prediction for short-term tuberculosis development.

INTRODUCTION: Although a latent tuberculosis (TB) infection is a risk factor for active TB, the diagnosis of latent TB infection is difficult in end-stage renal disease patients. PATIENTS AND METHODS: We retrospectively compared the results of the QuantiFERON-TB (QFT) test and the tuberculin skin test in patients on the waiting list for kidney transplantation (KT), and investigated whether the QFT test can predict TB development in KT recipients in an intermediate-TB-burden country. RESULTS: The incidence of post-KT TB was 283 cases/100,000 patient-years among 1274 KT recipients at the Seoul National University Hospital. The overall standardized incidence ratio of TB was 4.358 compared with the general population. A past history of TB infection, smoking history, myocardial infarction after KT, and pneumocystis infection were significant predictors of subsequent TB development (adjusted odds ratios were 3.618, 2.959, 9.993, and 5.708, respectively). Among the 129 recipients who had the QFT test, 42 patients (32.5%) had positive a QFT. At a median follow-up of 8.4 ± 6.8 months, 1 patient with positive QFT results developed TB after KT, and 1 of the 87 patients with negative QFT results developed TB after KT. In both of these 2 cases, active TB developed despite isoniazid prophylaxis. Among 272 patients on the waiting list for KT, the tuberculin skin test and QFT were positive in 22.8% and 35.3%, respectively. The degree of agreement between the 2 tests was poor (κ = 0.352). CONCLUSIONS: The QFT test did not predict subsequent short-term TB development. Furthermore, a long-term and larger-scale study is needed to confirm our results.

Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma.

PURPOSE: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT). PATIENTS AND METHODS: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the ≥ grade 2 GD toxicity were investigated. RESULTS: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V25 for stomach and V35 for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for ≥ grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V25 ≤ 6.3 % and 57.1 % for V25 > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V35 ≤ 5.4 % and 45.9 % for V35 > 5.4 %. By multivariate analysis including the clinical factors, V25 for stomach and V35 for duodenum were the significant factors. CONCLUSION: EGD revealed that GD toxicity is common following RT for HCC. V25 for the stomach and V35 for the duodenum were the significant factors to predict ≥ grade 2 GD toxicity.

Within-visit blood pressure variability: relevant factors in the general population.

The objective of this study was to use a nationwide epidemiological survey to investigate the factors that affect within-visit blood pressure (BP) variability. We analyzed the Korean National Health and Nutrition Examination Survey (KNHNES) data for 2005 (n=5488). We examined three within-visit BP variability parameters that include the following: the alarm reaction (AR), defined as the first BP reading minus the third BP reading; the BP discrepancy, defined as the maximal BP reading minus the minimal BP reading (ΔBPmax); and the s.d. (BPSD). Age, fasting glucose, eGFR, total cholesterol, LDL cholesterol, and the metabolic syndrome (MetS) score were the relevant factors that affected the systolic AR, ΔSBPmax and SBPSD. Multiple linear regression models revealed that age (P<0.0001), the office systolic BP (SBP) level (P<0.0001), the MetS score (P<0.0001), the female gender (P=0.007) and the eGFR (P=0.049) were independently associated with the systolic AR, whereas age (P<0.0001), the office SBP level (P<0.0001), and the female gender (P=0.024 and 0.022) were independently associated with ΔSBPmax and SBPSD, respectively. Within-visit BP variability, especially the variability associated with the SBP, was significantly associated with increased age, female gender and cardiovascular risk factors, such as hypertension, low eGFR and adverse glucose and lipid profiles. In addition, increased age, female gender, the eGFR and the MetS score were independently relevant factors that affected the systolic AR. Systolic within-visit BP variability and systolic AR are associated with cardiovascular risk factors.

Evaluation of anatomical landmark position differences between respiration-gated MRI and four-dimensional CT for radiation therapy in patients with hepatocellular carcinoma.

OBJECTIVE: To measure the accuracy of position differences in anatomical landmarks in gated MRI and four-dimensional CT (4D-CT) fusion planning for radiation therapy in patients with hepatocellular carcinoma (HCC). METHODS: From April to December 2009, gated MR and planning 4D-CT images were obtained from 53 inoperable HCC patients accrued to this study. Gated MRI and planning 4D-CT were conducted on the same day. Manual image fusions were performed by matching the vertebral bodies. Liver volumes and three specific anatomical landmarks (portal vein conjunction, superior mesenteric artery bifurcation, and other noticeable points) were contoured from each modality. The points chosen nearest the centre of the four landmark points were compared to measure the accuracy of fusion. RESULTS: The average distance differences (±standard deviation) of four validation points were 5.1 mm (±4.6 mm), 5.6 mm (±6.2 mm), 5.4 mm (±4.5 mm) and 5.1 mm (±4.8 mm). Patients who had ascites or pulmonary disease showed larger discrepancies. MRI-CT fusion discrepancy was significantly correlated with positive radiation response (p<0.05). CONCLUSIONS: Approximately 5-mm anatomical landmark positional differences in all directions were found between gated MRI and 4D-CT fusion planning for HCC patients; the gap was larger in patients with ascites or pulmonary disease. ADVANCES IN KNOWLEDGE: There were discrepancies of approximately 5 mm in gated MRI-CT fusion planning for HCC patients.

Management of patients on the waiting list for deceased donor kidney transplantation.

BACKGROUND: Although the number of wait-listed patients for deceased donor kidney transplantation has been continuously increasing in Korea, no standard guidelines exist for their management. METHODS: We retrospectively analyzed the medical records of our 1,231 wait-listed patients between 2000 and 2010. RESULTS: The time to transplantation of the 201 recipients was 51.9 ± 31.2 months. Ninety-seven patients died while waiting. Diabetic or older patients have increased among new registrants; however, <50% of them have undergone regular screening for malignancy or cardiovascular diseases. Patients with regular screening were more likely to get a chance to receive a transplant (P = .016). Malignancy was newly diagnosed in 26 patients (2.1%) and reversible cardiac ischemia was detected in 9.7%. The presence of anti-HLA antibodies was strongly associated with a lower transplantation rate, whereas blood type O was not. Although use of expanded criteria donor (ECD) kidneys increased, many patients avoided them. CONCLUSION: It is necessary to improve management programs for wait-listed patients by establishing comorbidity screening and ECD education.

Volumetric response evaluation after intensity modulated radiotherapy in patients with supratentorial gliomas.

Radiotherapy is frequently indicated to treat cerebral gliomas. Accurate response evaluation after radiotherapy is essential to determine the efficacy of treatment. We retrospectively analyzed the volumetric tumor response after simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in patients with gliomas. Thirty-five patients (Grade II, 7 patients; Grade III, 12; and Grade IV, 16) were treated with SIB-IMRT with a median total dose of 55.9 Gy/26 fractions for Grade II and 60 Gy/25 fractions for Grade III-IV tumors. Tumor responses were evaluated for enhancing volume on post-gadolinium T1-weighted images (Vgd) and hyper-intensity volume on T2-weighted FLAIR images (V(fl)) on serial MRIs. With the median follow-up of 24.0 months, overall response rates (RRs) were 57% for V(gd) and 51% for V(fl). Tumor grade was predictive of response favoring the lower grade in Vfl with RRs of 86% for Grade II, 75% for Grade III, and 19% for Grade IV tumors (p = 0.004). Time to 50% or greater volume reduction (T50) in Vgd was 8 months for grade III. The T50 in V(fl) was approximately 24 months both for Grade II and III tumors. Majority of Grade IV tumors continued to progress and never reached the T50 in Vgd or Vfl. Responders survived longer than non-responders for V(gd) and V(fl). Volume response after radiotherapy was dependent upon tumor grade and time. LGGs are very responsive to radiotherapy with the RRs of 86% in V(fl). The response of Vfl is more protracted compared to V(gd). Further investigation is needed to determine the clinical significance of volumetric response evaluation.

9-cis retinoic acid improves developmental competence and embryo quality during in vitro maturation of bovine oocytes through the inhibition of oocyte tumor necrosis factor-α gene expression.

Retinoic acid (RA; all-trans RA and 9-cis RA) enhances embryo developmental competence and quality through multiple mechanisms affecting the oocyte and preimplantation embryo. Folliculogenesis and oocyte maturation are influenced by tumor necrosis factor-α (TNF-α) via inhibition of aromatase activity and estradiol secretion in granulosa cells. Retinoic acid inhibits TNF-α production in various cell lines. The aim of the present study was to determine whether oocyte TNF-α concentrations regulate developmental competence and embryo quality and if the beneficial effects of 9-cis RA are mediated through attenuation of oocyte TNF-α production. Bovine cumulus oocyte complexes collected from abattoir ovaries were matured in maturation medium in the absence (control) or presence of 5 nM 9-cis RA (RA), 100 ng/mL of recombinant bovine TNF-α (TNF), or 5 nM 9-cis RA + 100 ng/mL of recombinant bovine TNF-α (RA+TNF). Oocytes were subsequently collected for gene expression analysis or subjected to in vitro fertilization and culture. Apoptosis and gene expression were analyzed in d-8 blastocysts. Results indicated that 9-cis RA downregulated (P < 0.01) both basal and TNF-α-induced TNF-α mRNA in oocytes (1.0-fold in control, 0.4-fold in RA, 2.1-fold in TNF, and 0.7-fold in RA+TNF). The 9-cis RA increased (P < 0.001) blastocyst development rates (37.1 ± 6.9 vs. 23.6 ± 8.0%) and total cell number (138.4 ± 19.2 vs. 120.2 ± 24.5) and reduced (P < 0.001) the percentage of apoptotic cells (3.3 ± 2.0 vs. 5.6 ± 2.3%) compared with controls. Expression of caspase 3 (0.4- vs. 1.0-fold) and TNF-α (0.4- vs. 1.0-fold) mRNA was downregulated (P < 0.05) in RA-treated blastocysts compared with controls. Moreover, 9-cis RA rescued (P < 0.001) development rates (24.5 ± 11.1 vs. 15.6 ± 9.0%), increased total cell number (124.6 ± 36.5 vs. 106.9 ± 31.1), and reduced apoptosis (5.8 ± 2.0 vs. 8.1 ± 3.1%) in blastocysts exposed to TNF-α (TNF group). Caspase 3 (0.8-fold in RA+TNF vs. 2.2-fold in TNF) and TNF-α (0.3-fold in RA+TNF vs. 2.8-fold in TNF) mRNA expression was attenuated (P < 0.05) in TNF-α-treated blastocysts. In conclusion, the present study suggests that 9-cis RA exerts its beneficial roles on oocyte developmental competence and embryo quality by attenuating oocyte TNF-α mRNA expression.

Postobstructive regeneration of kidney is derailed when surge in renal stem cells during course of unilateral ureteral obstruction is halted.

Unilateral ureteral obstruction (UUO), a model of tubulointerstitial scarring (TIS), has a propensity toward regeneration of renal parenchyma after release of obstruction (RUUO). No information exists on the contribution of stem cells to this process. We performed UUO in FVB/N mice, reversed it after 10 days, and examined kidneys 3 wk after RUUO. UUO resulted in attenuation of renal parenchyma. FACS analysis of endothelial progenitor (EPC), mesenchymal stem (MSC) and hematopoietic stem (HSC) cells obtained from UUO kidneys by collagenase-dispersed single-cell suspension showed significant increase in EPC, MSC, and HSC compared with control. After RUUO cortical parenchyma was nearly restored, and TIS score improved by 3 wk. This reversal process was associated with return of stem cells toward baseline level. When animals were chronically treated with nitric oxide synthase (NOS) inhibitor at a dose that did not induce hypertension but resulted in endothelial dysfunction, TIS scores were not different from control UUO, but EPC number in the kidney decreased significantly; however, parenchymal regeneration in these mice was similar to control. Blockade of CXCR4-mediated engraftment resulted in dramatic worsening of UUO and RUUO. Similar results were obtained in caveolin-1-deficient but not -overexpressing mice, reflecting the fact that activation of CXCR4 occurs in caveolae. The present data show increase in EPC, HSC, and MSC population during UUO and a tendency for these cells to decrease to control level during RUUO. These processes are minimally affected by chronic NOS inhibition. Blockade of CXCR4-stromal cell-derived factor-1 (SDF-1) interaction by AMD3100 or caveolin-1 deficiency significantly reduced the UUO-associated surge in stem cells and prevented parenchymal regeneration after RUUO. We conclude that the surge in stem cell accumulation during UUO is a prerequisite for regeneration of renal parenchyma.

Phase II study with oxaliplatin and S-1 for patients with metastatic colorectal cancer.

BACKGROUND: To evaluate the efficacy and safety of the combination of oxaliplatin and S-1 (OS) in treating metastatic colorectal cancer. PATIENTS AND METHODS: Eligible patients were those with measurable lesions, no previous history of chemotherapy (except adjuvant chemotherapy), an age of 18-70 years, and an Eastern Cooperative Oncology Group performance status of zero to two. Oxaliplatin 130 mg/m(2) was administered i.v. on day 1, and S-1 40 mg/m(2) b.i.d. was administered orally on days 1-14, every 3 weeks. RESULTS: Forty-eight patients (median age, 56 years) were enrolled: 23 had colon cancer, seven rectosigmoid colon cancer; and 18 rectal cancer. Of the 48 patients, 31 were diagnosed with metastatic cancer and 17 had relapsed cancer after surgery, with adjuvant chemotherapy or chemoradiotherapy. In total, 413 cycles were administered (median 6 per patient; range 2-24). Toxicity was evaluated in 48 patient and response in 46. Major toxic effects were grade 3/4 thrombocytopenia (13%) and neutropenia (10%). The overall response rate was 54% [95% confidence interval (CI) 40% to 68%]. The median time to progression and median survival time were 8.5 (95% CI 6.2-10.9) months and 27.2 (95% CI 20.3-34.0) months, respectively. CONCLUSIONS: These data indicate that the OS regimen is effective and well tolerated in patients with advanced colorectal cancer.

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.

Cold accumulation of SCOF-1 transcripts is associated with transcriptional activation and mRNA stability.

Cold acclimation enhances the transcription of several cold regulated (COR) genes. However, little is known about whether the elevation of the transcriptional level of the COR genes is due to transcriptional activation, or mRNA stability by a low temperature. Recently, we cloned a novel cold-inducible zinc finger protein gene from soybean, SCOF-1, which may function as a positive regulator of the COR gene expression . Here we report that the elevation of the SCOF-1 transcript level by cold stress is associated with both transcriptional activation and post-transcriptional mRNA stability under a low temperature. A nuclear run-on assay reveals that cold acclimation elevates the SCOF-1 transcript about three-fold compared to that of non-acclimated soybean nuclei. Furthermore, SCOF-1 transcripts increased substantially by a low temperature in transgenic tobacco plants that constitutively expressed SCOF-1 under the control of a constitutive cauliflower mosaic virus (CaMV) 35S promoter. When a transcription inhibitor, cordycepin, was treated with the deacclimating soybean cell, the decay level of the SCOF-1 transcripts was delayed significantly. This suggests that it may affect de novo protein synthesis, which degrades the SCOF-1 mRNA at room temperature. In addition, a secondary structure may be involved in the mRNA stability of SCOF-1 under a low temperature.