Crystal Engineering with the New Linker Tolanedisulfonic Acid (H2 TDS): Helical Chains in Zn(TDS)(DMA)3 , Linear Chains in Zn(TDS)(NMP)3 , and Complex Anions in [HDMA]2 [Zn(TDS)2 (DMA)3 ](DMA)2.

Reaction of 4,4'-tolanedisulfonic acid, H2 TDS, with zinc hydroxide in dimethylacetamide, DMA, under solvothermal conditions led to the coordination polymer Zn(TDS)(DMA)3 (I). In the crystal structure [trigonal, P32 21, Z=3, a=1175.0(1) pm, c=1949.5(1) pm, R1 ; wR2 (Io > 2σ(Io ))=0.0393; 0.0921] the disulfonate anions linked the Zn(2+) ions into helical chains according to ∞ (1) [Zn(DMA)3/1 (TDS)2/2 ] (I) causing the chirality of the compound. By using higher concentrations of H2 TDS in the starting mixture the compound [HDMA]2 [Zn(TDS)2 (DMA)3 ](DMA)2 (II) was formed. The structure [monoclinic, Cc, Z=4, a=1201.5(1) pm, b=1996.0(1) pm, c=2749.2(2) pm, ß=101.897(2)°, R1 ; wR2 (Io > 2σ(Io ))=0.0699; 0.2017] displayed the complex anion [Zn(TDS)2 (DMA)3 ](2-) which was a perfect cut-off of the helical chain in I. Charge compensation was achieved by protonated DMA molecules. If N-methylpyrrolidone, NMP, was chosen as a solvent, the sulfonate Zn(TDS)(NMP)3 (III) [monoclinic, I2/a, Z=4, a=1575.7(1) pm, b=1077.3(1) pm, c=1870.0(1) pm, ß=101.189(9)°, R1 ; wR2 (Io > 2σ(Io ))=0.0563; 0.1320] was obtained. Similarly to the findings for I, the formation of chains according to ∞ (1) [Zn(NMP)3/1 (TDS)2/2 ] was observed. However, due to the more bulky NMP molecules these chains were no longer helical but straight instead.

Drought-resistant cereals: impact on water sustainability and nutritional quality.

This review uses production and climate data to examine global and local production trends that can be related to events such as drought. UK grain quality data is also available and provides an overview of trends in protein content. Literature surveys show a consistent reduction in grain size due to the effects of temperature and/or drought. A review of gene expression studies showed that most genes involved in starch synthesis are down regulated under heat stress. Net protein production is also reduced under heat and/or drought stress but apparently to a lesser degree as the reduction in grain mass is larger, resulting in an increase in protein concentration. Modelling has suggested that adaptation could be achieved by moving production to more extreme latitudes but other research suggests that simply transferring germplasm from one region to another is unlikely to be successful. Another review has identified drought tolerance phenotypes that could be used to breed more drought tolerant crops. At the time of the review, the authors concluded that phenotypic selection was generally preferable to forms of marker-assisted breeding and have used the approach to produce drought tolerant wheat cultivars. Transgenic approaches have also been shown to improve drought tolerance under controlled environment conditions but there are no results to show how well these results translate into improved crop performance under field conditions. The recent advances in genomic data and detecting marker-trait associations suggest that marker-assisted breeding will play a much more important role in breeding drought tolerant cereals in the future.

Surgeon-Performed Ultrasound-Guided Fine-Needle Aspiration Cytology (SP-US-FNAC) Shortens Time for Diagnosis of Thyroid Nodules.

INTRODUCTION: Ultrasound-guided fine-needle aspiration cytology (US-FNAC) of thyroid nodules is an important diagnostic procedure. In most hospitals, patients are referred to radiologists for US-FNAC, but this often results in a long waiting time before results are available. Surgeon-performed US-FNAC (SP-US-FNAC) during the initial patient consultation attempts to reduce the waiting time but it is not known whether this is as accurate as radiologist-performed US-FNAC (RP-US-FNAC). The aim of this study is to compare the clinical efficiency between SP-US-FNAC and RP-US-FNAC. MATERIALS AND METHODS: A retrospective study was performed on patients from the Department of General Surgery, Tan Tock Seng Hospital (TTSH) who underwent an US-FNAC from August 2011 to May 2012. All cases of SP-US-FNAC were performed by a single surgeon. This study compared the rates of positive diagnoses achieved by SP-US-FNAC and RPUS- FNAC as well as the time interval to reach a cytological diagnosis by each group. RESULTS: A total of 40 cases of SP-US-FNAC and 72 cases of RP-US-FNAC were included in the study. SP-US-FNAC resulted in 28 (70%) positive diagnoses and 12 (30%) nondiagnoses while RP-US-FNAC resulted in 47 (65.3%) positive diagnoses and 25 (34.7%) non-diagnoses. These results were comparable (P=0.678). The median time taken to reach a cytological diagnosis was 1 working day for SP-US-FNAC and 29.5 working days for RP-US-FNAC resulting in a shorter interval to reaching a cytological diagnosis for SP-US-FNAC (P<0.001). CONCLUSION: In the workup of thyroid nodules, SP-US-FNAC is as accurate as RP-US-FNAC but significantly reduces the time taken to reach a cytological diagnosis. This leads to greater clinical efficiency in the management of patients with thyroid nodules, which in turn leads to other benefits such as decreased patient anxiety and increased patient satisfaction.

Surgeon-Performed Ultrasound-Guided Fine-Needle Aspiration Cytology (SP-US-FNAC) Shortens Time for Diagnosis of Thyroid Nodules

<p><b>INTRODUCTION</b>Ultrasound-guided fine-needle aspiration cytology (US-FNAC) of thyroid nodules is an important diagnostic procedure. In most hospitals, patients are referred to radiologists for US-FNAC, but this often results in a long waiting time before results are available. Surgeon-performed US-FNAC (SP-US-FNAC) during the initial patient consultation attempts to reduce the waiting time but it is not known whether this is as accurate as radiologist-performed US-FNAC (RP-US-FNAC). The aim of this study is to compare the clinical efficiency between SP-US-FNAC and RP-US-FNAC.</p><p><b>MATERIALS AND METHODS</b>A retrospective study was performed on patients from the Department of General Surgery, Tan Tock Seng Hospital (TTSH) who underwent an US-FNAC from August 2011 to May 2012. All cases of SP-US-FNAC were performed by a single surgeon. This study compared the rates of positive diagnoses achieved by SP-US-FNAC and RPUS- FNAC as well as the time interval to reach a cytological diagnosis by each group.</p><p><b>RESULTS</b>A total of 40 cases of SP-US-FNAC and 72 cases of RP-US-FNAC were included in the study. SP-US-FNAC resulted in 28 (70%) positive diagnoses and 12 (30%) nondiagnoses while RP-US-FNAC resulted in 47 (65.3%) positive diagnoses and 25 (34.7%) non-diagnoses. These results were comparable (P=0.678). The median time taken to reach a cytological diagnosis was 1 working day for SP-US-FNAC and 29.5 working days for RP-US-FNAC resulting in a shorter interval to reaching a cytological diagnosis for SP-US-FNAC (P<0.001).</p><p><b>CONCLUSION</b>In the workup of thyroid nodules, SP-US-FNAC is as accurate as RP-US-FNAC but significantly reduces the time taken to reach a cytological diagnosis. This leads to greater clinical efficiency in the management of patients with thyroid nodules, which in turn leads to other benefits such as decreased patient anxiety and increased patient satisfaction.</p>

Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres.

PURPOSE: Selective internal radiotherapy (SIRT) with yttrium-90 ((90)Y) resin microspheres can improve the clinical outcomes for selected patients with inoperable liver cancer. This technique involves intra-arterial delivery of ß-emitting microspheres into hepatocellular carcinomas or liver metastases while sparing uninvolved structures. Its unique mode of action, including both (90)Y brachytherapy and embolization of neoplastic microvasculature, necessitates activity planning methods specific to SIRT. METHODS AND MATERIALS: A panel of clinicians experienced in (90)Y resin microsphere SIRT was convened to integrate clinical experience with the published data to propose an activity planning pathway for radioembolization. RESULTS: Accurate planning is essential to minimize potentially fatal sequelae such as radiation-induced liver disease while delivering tumoricidal (90)Y activity. Planning methods have included empiric dosing according to degree of tumor involvement, empiric dosing adjusted for the body surface area, and partition model calculations using Medical Internal Radiation Dose principles. It has been recommended that at least two of these methods be compared when calculating the microsphere activity for each patient. CONCLUSIONS: Many factors inform (90)Y resin microsphere SIRT activity planning, including the therapeutic intent, tissue and vasculature imaging, tumor and uninvolved liver characteristics, previous therapies, and localization of the microsphere infusion. The influence of each of these factors has been discussed.

Utilization of thyroidectomy for benign disease in the United States: a 15-year population-based study.

BACKGROUND: Recent recommendations suggest that total thyroidectomy (TT) is the preferred treatment for benign thyroid disease. This approach remains controversial because of the increased risk of morbidity compared with a partial thyroidectomy (PT). The aim of this study was to determine the use of thyroidectomy for benign disease over a 15-year period. METHODS: One hundred nineteen thousand eight hundred eighty-five patients from the Nationwide Inpatient Sample database (1993-2007) underwent surgery for benign thyroid disease. Logistic regression was used to assess the relation between extent of thyroidectomy and the year of admission, hospital volume, and surgical outcomes. RESULTS: The use of TT increased from 17.6% (1993-1997) to 39.6% (2003-2007) compared with 82.4% and 60.4% for PT over the same periods (P < .0001). A greater proportion of TTs was performed in high-volume centers in which the rates of postoperative complications were lower than low-volume centers. CONCLUSIONS: The use of TT for benign thyroid disease has increased over the last 15 years in the United States. This pattern of practice is in keeping with the trends reported in recent literature.

para-Benzene disulfonic acid and its tetrachloro and tetrafluoro derivatives--studies towards polyhalogenated metal-organic-frameworks with sulfo analogues of terephthalic acid.

We developed convenient synthetic routes for the preparation of para-benzene disulfonic acid (H(2)BDS) and its tetrachloro (H(2)BDSCl(4)) and tetrafluoro (H(2)BDSF(4)) derivatives. The reaction of these acids with zinc nitrate in DMF led to single crystals of [Zn(BDS)(DMF)(2)] (triclinic, P ̄1[combining macron], Z=2, a=976.62(4), b=986.85(4), c=1014.40(4), α=69.106(2)°, ß=68.746(2)°, γ=86.295(2)°, wR(2)=0.0627), [Zn(BDSCl(4))(DMF)(4)] (triclinic, P ̄1[combining macron], Z=1, a=831.5(1), b=905.2(1), c=989.6(1), α=90.44(2)°, ß=91.41 (2)°, γ=106.72(2)°, wR(2)=0.0635), and [Zn(BDSF(4))(DMF)(4)] (monoclinic, P2(1)/c, Z=2, a=889.01(3), b=968.91(3), c=1633.07(5) pm, ß=106.524(2)°, wR(2)=0.0948). While [Zn(BDS)(DMF)(2)] exhibits a layer structure, the disulfonate linkers connect the zinc ions into chains in the crystal structures of [Zn(BDSCl(4))(DMF)(4)] and [Zn(BDSF(4))(DMF)(4)]. Thermoanalytical investigations revealed that desolvation of the compounds occurs in a temperature range between 100 and 200 °C. The solvent free sulfonates show remarkably high stabilities, [Zn(BDS)(DMF)(2)] is stable up to nearly 600 °C. The halogenated acids were also used to prepare copper salts from aqueous solutions and Cu(2)(OH)(2)(CO(3)) (malachite) as a copper source. The crystal structure of [Cu(H(2)O)(6)](BDSF(4)) (triclinic, P ̄1[combining macron], Z=1, a=510.45(2), b=744.68(3), c=1077.77(4) pm, α=85.627 (2)°, ß=77.449 (2)°, γ=76.015 (2)°) exhibits complex cations and uncoordinated sulfonate anions, while in [Cu(BDSCl(4))(H(2)O)(4)] (orthorhombic, Pnma, Z=4, a=721.27(2), b=2147.81(6), c=979.42(3) pm) the Cu(2+) ions are linked to infinite chains in the crystal structure. The most interesting structural feature of [Cu(BDSCl(4))(H(2)O)(4)] is the significant deviation from planarity of the disulfonate dianion. Theoretical investigations revealed that a boat conformation is favoured due to steric hindrance in cases where a syn coordination of the sulfonate groups occurs. The thermal behaviour of the copper compounds was also investigated by DTA/TG measurements and X-ray powder diffraction.

Mixed model association scans of multi-environmental trial data reveal major loci controlling yield and yield related traits in Hordeum vulgare in Mediterranean environments.

An association panel consisting of 185 accessions representative of the barley germplasm cultivated in the Mediterranean basin was used to localise quantitative trait loci (QTL) controlling grain yield and yield related traits. The germplasm set was genotyped with 1,536 SNP markers and tested for associations with phenotypic data gathered over 2 years for a total of 24 year × location combinations under a broad range of environmental conditions. Analysis of multi-environmental trial (MET) data by fitting a mixed model with kinship estimates detected from two to seven QTL for the major components of yield including 1000 kernel weight, grains per spike and spikes per m(2), as well as heading date, harvest index and plant height. Several of the associations involved SNPs tightly linked to known major genes determining spike morphology in barley (vrs1 and int-c). Similarly, the largest QTL for heading date co-locates with SNPs linked with eam6, a major locus for heading date in barley for autumn sown conditions. Co-localization of several QTL related to yield components traits suggest that major developmental loci may be linked to most of the associations. This study highlights the potential of association genetics to identify genetic variants controlling complex traits.

Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population.

BACKGROUND AND AIM: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems. METHODS: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor-node-metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared. RESULTS: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow-up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child-Pugh-stage, alpha-fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3-month survival while CLIP performed better in predicting the outcome of 6- and 12-month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance. CONCLUSION: We have validated CUPI in a population composed of predominant HBV-related HCC. CUPI is an appropriate staging system for HBV-related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification.

Current role of selective internal irradiation with yttrium-90 microspheres in the management of hepatocellular carcinoma: a systematic review.

PURPOSE: This article reviews the role of selective internal irradiation (SIR) with yttrium-90 ((90)Y) microspheres for hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Studies were identified by searching Medline and PubMed databases for articles from 1990 to 2009 using the keywords "selective internal irradiation," "hepatocellular carcinoma," "therapeutic embolization," and "yttrium-90." RESULTS: (90)Y microspheres are a safe and well-tolerated therapy for unresectable HCC (median survival range, 7 -21.6 months). The evidence was limited to cohort studies and comparative studies with historical control. (90)Y microspheres have been reported to downstage unresectable HCC to allow for salvage treatments with curative intent, act as a bridging therapy before liver transplantation, and treat HCC with curative intent for patients who are not surgical candidates because of comorbidities. CONCLUSIONS: (90)Y microsphere is recommended as an option of palliative therapy for large or multifocal HCC without major portal vein invasion or extrahepatic spread. It can also be used for recurrent unresectable HCC, as a bridging therapy before liver transplantation, as a tumor downstaging treatment, and as a curative treatment for patients with associated comorbidities who are not candidates for surgery.

Patterns of genetic diversity and linkage disequilibrium in a highly structured Hordeum vulgare association-mapping population for the Mediterranean basin.

Population structure and genome-wide linkage disequilibrium (LD) were investigated in 192 Hordeum vulgare accessions providing a comprehensive coverage of past and present barley breeding in the Mediterranean basin, using 50 nuclear microsatellite and 1,130 DArT((R)) markers. Both clustering and principal coordinate analyses clearly sub-divided the sample into five distinct groups centred on key ancestors and regions of origin of the germplasm. For given genetic distances, large variation in LD values was observed, ranging from closely linked markers completely at equilibrium to marker pairs at 50 cM separation still showing significant LD. Mean LD values across the whole population sample decayed below r (2) of 0.15 after 3.2 cM. By assaying 1,130 genome-wide DArT((R)) markers, we demonstrated that, after accounting for population substructure, current genome coverage of 1 marker per 1.5 cM except for chromosome 4H with 1 marker per 3.62 cM is sufficient for whole genome association scans. We show, by identifying associations with powdery mildew that map in genomic regions known to have resistance loci, that associations can be detected in strongly stratified samples provided population structure is effectively controlled in the analysis. The population we describe is, therefore, shown to be a valuable resource, which can be used in basic and applied research in barley.

Thiopurines, a previously unrecognised cause for fatigue in patients with inflammatory bowel disease.

BACKGROUND: Active inflammatory bowel disease, anaemia, iron deficiency and depression, alone or in combination, are known contributing factors of fatigue in inflammatory bowel disease. However, in some patients, fatigue cannot be attributed to known causes. Thiopurines are not a recognized cause. AIM: To describe the clinical scenario of a series of patients where thiopurines were the likely cause of fatigue. METHOD: The clinical scenario of 5 patients was examined with specific reference to the temporal association of thiopurine therapy with fatigue, the effect of its withdrawal and rechallenge, and drug specificity. RESULTS: The onset of severe fatigue was related to the introduction of azathioprine or 6-mercaptopurine, rapid relief was experienced on its withdrawal in all patients, and fatigue rapidly occurred on rechallenge. The speed of onset was rapid in two patients and in the context of gradual withdrawal of moderate steroid dose, but recurred rapidly on rechallenge when not on steroids. CONCLUSIONS: Marked fatigue is a previously unrecognized adverse effect of thiopurines. It does not appear to be drug-specific. Its onset might be masked by concurrent steroid therapy.

Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival.

OBJECTIVE: In this prospective randomized trial, we attempted to find out if 1 dose of postoperative adjuvant intra-arterial iodine-131-labeled lipiodol could reduce the rate of local recurrence, and increase disease-free and overall survival for patients with hepatocellular carcinoma (HCC). This study evaluated the long-term outcome. BACKGROUND: Resection of HCC is potentially curative, but local recurrence is common. However, there is currently no effective adjuvant therapy. Early results after closing the trial (Lau et al. Lancet 1999;353:797-801) showed that 1 dose of intra-arterial I-lipiodol given after curative resection significantly decreased the rate of recurrence, and increased disease-free and overall survival. METHODS: Patients who underwent curative resection for HCC and recovered within 6 weeks were randomly assigned one 1850 MBq dose of I-lipiodol or no further treatment (controls). We compared rates of recurrence, and long-term disease-free and overall survival (the primary endpoints) between the 2 groups by intention-to-treat. RESULTS: Between April 1992 and August 1997, we recruited 43 patients: 21 were randomized to receive intra-arterial I-lipiodol and 22 to receive no adjuvant treatment. I-lipiodol had no significant toxic effects. During a median follow-up of 66 (range, 3-198) months, there were 10 (47.6%) recurrences among the 21 patients in the adjuvant treatment group, compared with 14 (63.6%) in the control group (P = 0.29). The actuarial 5-year disease-free survival in the treatment and control groups was 61.9% and 31.8%, respectively (P = 0.0397). The actuarial 5-year overall survival in the treatment and control groups was 66.7% and 36.4%, respectively (P = 0.0433). The actuarial 7-year disease-free survival in the treatment and control groups was 52.4% and 31.8%, respectively (P = 0.0224). The actuarial 7-year overall survival in the treatment and control groups was 66.7% and 31.8%, respectively (P = 0.0243). The actuarial 10-year disease-free survival in the treatment and control groups was 47.6% and 27.3%, respectively (P = 0.0892). The actuarial 10-year overall survival in the treatment and control groups was 52.4% and 27.3%, respectively (P = 0.0905). CONCLUSIONS: In patients with HCC, adjuvant intra-arterial I-lipiodol after curative liver resection provided survival benefit on the disease-free survival and overall survival, although the difference became statistically insignificant at 8 years after randomization.

Panmucositis and chemosensitisation associated with betel quid chewing during dose-dense adjuvant breast cancer chemotherapy.

PURPOSE: The severity of chemotherapy-induced oral mucositis has previously been reported to be greater in patients who chew betel quid (areca), an addictive habit shared by hundreds of millions of individuals worldwide. Here, we report a case of fulminant panmucositis complicating dose-dense adjuvant breast cancer treatment in a betel-chewing patient without evidence of other risk factors. METHODS: Grade IV mucositis was triggered by the initial use of standard-dose anthracycline chemotherapy, and involved not only the mouth but also the genital and anal mucosa, as well as other severe non-mucosal toxicities. RESULTS: Despite subsequent treatment with dose-reduced CMF and docetaxel regimens-which are seldom associated with mucosal toxicity at these dose intensities in the absence of neutropenia-high-grade oral mucositis continued to complicate the therapeutic course. CONCLUSION: These observations suggest that the potentiation of chemotherapy-induced mucositis by quid chewing may not be mediated solely by local effects on the oral epithelium, but also involves the systemic absorption of toxic chemosensitising molecules.

A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma.

BACKGROUND: Single-agent doxorubicin has been widely used to treat unresectable hepatocellular carcinoma (HCC), but the response rate is low (< 20%) and there is no convincing evidence for improved survival. Cisplatin, interferon, doxorubicin, and fluorouracil (PIAF) used in combination, by contrast, has shown promise in a phase II study. We compared doxorubicin to PIAF in patients with unresectable HCC in a phase III trial. METHODS: Patients with histologically confirmed unresectable HCC were randomly assigned to receive either doxorubicin or PIAF every 3 weeks, for up to six cycles. The primary endpoint was overall survival, and secondary endpoints were response rate and toxicity. Survival differences were calculated using the Kaplan-Meier method. Treatment groups were compared for differences in the incidence of adverse events using chi-square tests. All statistical tests were two-sided. RESULTS: The median survival of the doxorubicin and PIAF groups was 6.83 months (95% confidence [CI] = 4.80 to 9.56) and 8.67 months (95% CI = 6.36 to 12.00), respectively (P = 0.83). The hazard ratio for death from any cause in the PIAF compared with the doxorubicin groups was 0.97 (95% CI = 0.71 to 1.32). Eighty-six of the 94 patients receiving doxorubicin and 91 of the 94 receiving PIAF were assessable for response. The overall response rates in the doxorubicin and PIAF groups were 10.5% (95% CI = 3.9% to 16.9%) and 20.9% (95% CI = 12.5% to 29.2%), respectively. Neutropenia, thrombocytopenia, and hypokalemia were statistically significantly more common in patients treated with PIAF than in patients treated with doxorubicin. CONCLUSION: Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin, the differences were not statistically significant. PIAF was also associated with increased treatment-related toxicity. The prognosis of patients with unresectable HCC remains poor.

Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma.

This phase III randomized study compared concurrent cisplatin-radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m(2) weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.

Karyotypic imbalances and differential gene expressions in the acquired doxorubicin resistance of hepatocellular carcinoma cells.

Administration of doxorubicin has been shown to prolong survival of patients with hepatocellular carcinoma (HCC). However, treatment regimen is often complicated by the emergence of drug resistance. The goal of our study is to enhance our understanding on the genetic changes that confer cellular chemoresistance to doxorubicin. To model this insensitive response, we established five doxorubicin-resistant (DOR) sublines through repeated exposure of escalating doses of doxorubicin to HCC cell lines (HKCI-2, -3, -4, -C1 and -C2). The DOR sublines developed displayed an average approximately 17-fold higher IC(50) value than their sensitive parental cell lines. The resistant phenotype displayed was investigated by the genome-wide analyses of comparative genomic hybridization (CGH) and complementary DNA microarray for the affected genomic anomalies and deregulated genes expressed, respectively. Over-representations of regional chr. 7q11-q21, 8q22-q23 and 10p13-pter were indicated in the DOR sublines from CGH analysis. Of particular interest was the finding of amplicon augmentations from regional or whole chromosome gains during the clonal expansion of resistant sublines. Most notably, recurring amplicon 7q11.2-q21 identified coincided with the location of the multi-drug-resistant gene, MDR1. The potential involvement of MDR1 was examined by quantitative reverse transcription-polymerase chain reaction RT-PCR (qRT-PCR), which indicated an upregulation in all DOR sublines (P=0.015). Consistent overexpression of the translated MDR1 gene, P-glycoprotein, in all five DOR sublines was further confirmed in Western blot analysis. Two distinct cluster dendrograms were achieved between the DOR sublines and their sensitive parental counterparts in expression profiling. Within the doxorubicin-resistant group, distinct features of candidate genes overexpressions including ABC transporting proteins, solute carriers and TOP2A were suggested. Further assessment of TOP2A messenger RNA levels by qRT-PCR confirmed array findings and pinpointed to a common up-regulation of TOP2A in DOR sublines. Our present study highlighted areas of genomic imbalances and candidate genes in the acquired doxorubicin-resistance behavior of HCC cells.