Does SAPHO syndrome exist in dermatology?

In the late 1960s, palmoplantar pustulosis (PPP) with sternocostoclavicular arthropathy was first described in Japan, predominantly affecting women in the perimenopausal age. In the 1970s, the chronic non-bacterial osteomyelitis and chronic recurrent multifocal osteomyelitis were initially observed in paediatric patients with approximately 70% girls. Acne fulminans accompanied by polyarthralgia have been observed since early 1970s, which almost exclusively occurs in adolescent boys. Report on spondyloarthropathy associated with hidradenitis suppurativa can be traced back to 1982. The SAPHO syndrome was coined in 1987 to lump together synovitis, acne, pustulosis, hyperostosis and osteitis to conceptualize a group of inflammatory osteocutaneous diseases of unclear etiopathogenesis and ill-defined associations spanning disparate age and gender groups. From historical view, Sasaki syndrome is proposed to replace SAPHO syndrome to represent PPP with sternocostoclavicular arthropathy in the absence of other skin manifestations. Hidradenitis suppurativa is folliculitis in pathogenesis and no longer classified as acne. PPP accompanied by psoriasis vulgaris is more likely psoriasis pustulosa palmoplantaris in dermatological aspect, and the associated arthritis is part of psoriatic arthropathy. Pathophysiology of these disorders is incompletely understood. To echo the advancement of high-throughput sequencing, splitting but not lumping of clinical findings would be a better strategy to decipher these multigenic complex inflammatory disorders.

[Study of coenzyme Q10 in the liver of preeclampsia pregnant rats].

OBJECTIVE: To investigate the protective effect of coenzyme Q10 (CoQ10) in the liver of preeclampsiapregnant rats and the potential etiology. METHODS: Fifty pregnant SD rats were equally divided into the normal pregnant (NP) group (n=10) and the preeclampsia (PE) group (n=40) randomly. The PE rats (n=40) were equally divided into four groups randomly, distilled water (DW) group, CoQ10 group, CoQ10 combined magnesium(CM) group and magnesium (Mg) group were established by treating the preeclampsia rats on day 15 to 21 of gestation with different measures. As for all the 50 rats, systolic blood pressure (SBP) of rat tail was detected on day 10, 15 and 21 of gestation respectively, 24 hours proteinuria analysis were detected on day 10, 15 and 21 of gestation respectively, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in blood andsuperoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), caspase-3, Bcl-2 and Bax protein expression in liver tissue were detected by western blot assay on day 21 of gestation. RESULTS: (1) SBP and 24 hours proteinuria analysis: there was no statistic difference among all the five groups on day 10 of gestation (P>0.05). Whereas, SBP and 24 hours proteinuria analysis were significantly higher in CoQ10 group, CoQ10 combined CM group, CM group and DW group than that in NP group on day 15, 21 of gestation (P<0.05). And SBP and 24 hours proteinuria analysis were significantly lower in CoQ10 group, CoQ10 combined CM group and CM group than that in DW group on day 21 of gestation (P<0.05). (2) Liver function: among CoQ10 group, CoQ10 combined CM group, CM group, DW group and NP group, serum levels of ALT were respectively (52±7) , (34±9) , (49±10) , (70±19) , (30±7) U/L; and serum levels of AST were respectively (169±25) , (84±11) , (159±20) , (281±26) and (78±18) U/L. ALT and AST serum levels were significantly higher in CoQ10 group, CM group and DW group than that in NP group (P<0.05). ALT and AST serum levels were significant lower in CoQ10 combined CM group than those in CoQ10 group, CM group and DW group, respectively (P<0.05). ALT and AST serum levels were significant lower in CoQ10 group and CM group than that in DW group, respectively (P<0.05). (3) SOD, GSH-PX, MDA, caspase-3, Bcl-2 and Bax expression in liver tissue of rats: SOD expression was significant higher in CoQ10 group, CoQ10 combined CM group than thoes in CM group, DW group and NP group (P<0.05) ; SOD expression was significant lower in CM group, DW grouo than thoes in NP group (P<0.05) ; and SOD expression was significant higher in CM group than that in DW group (P<0.05) . Compared with CoQ10 group, CoQ10 combined CM group, CW group and DW group respectively, the GSH-PX and Bcl-2 protein expressions were significant higher in NP group (P<0.05) , while MDA, caspase-3 and Bax protein expressions were significant lower in NP group (P<0.05) ; compared with CoQ10 group, CoQ10 combined CM group and CW group respectively, the GSH-PX and Bcl-2 protein expressions were significant lower in DW group (P<0.05) , while MDA, caspase-3 and Bax protein expressions were significant higher in DW group (P<0.05) . CONCLUSIONS: Oxidative stress and apoptosis levles were upregulated in PE pregnant liver tissues. CoQ10 could effectively protect the liver by improving the liver functions and decreasing the apoptosis of liver cells in PE pregnant rats, and markedly decrease the oxidative stress and apoptosis in the livers. The protective roles of CoQ10 in liver might through its function of anti-oxidative stress and inhibiting cell apoptosis by regulating the balance of Bcl-2/Bax.

Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.

Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer.

BACKGROUND: RNA-binding proteins have an important role in messenger RNA (mRNA) regulation during tumour development and carcinogenesis. In the present study, we examined the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; hereafter refered to as IMPs) and Lin28 family expressions in epithelial ovarian carcinoma (EOC) patients and correlated their expression levels with the response to chemotherapy, hCTR1 expression and patient survival. METHODS: Patients clinical information, real-time RT-PCR, immunohistochemistry, western blot, Transwell migration invasion assays, and cytotoxicity assays were used. RESULTS: From 140 EOC patients, high expression of IMP3 or Lin28B was associated with poor survival, and women diagnosed at advanced stages with elevated IMP3 and Lin28B were at higher risk of developing chemoresistance. High IMP3 levels combined with high Lin28B levels significantly correlated with the poorest 5-year survival rates. Knockdown of IMP3 or Lin28B decreased cell proliferation, migration, and invasion, and increased the platinum sensitivity, but not taxol sensitivity, of ovarian cancer cells through increased expression of hCTR1, a copper transporter involved in platinum uptake. High expression of hCTR1 correlated with low expression of IMP3/Lin28B and better progression-free survival in advanced-stage EOC patients. CONCLUSION: Testing for a combination of elevated IMP3 and Lin28B levels could further facilitate the identification of a patient subgroup with the worst prognosis.

Minor physical anomalies and craniofacial measures in patients with treatment-resistant schizophrenia.

BACKGROUND: Schizophrenia patients have higher rates of minor physical anomalies (MPAs) than controls, particularly in the craniofacial region; this difference lends support to the neurodevelopmental model of schizophrenia. Whether MPAs are associated with treatment response in schizophrenia remains unknown. The aim of this case-control study was to investigate whether more MPAs and specific quantitative craniofacial features in patients with schizophrenia are associated with operationally defined treatment resistance. METHOD: A comprehensive scale, consisting of both qualitatively measured MPAs and quantitative measurements of the head and face, was applied in 108 patients with treatment-resistant schizophrenia (TRS) and in 104 non-TRS patients. Treatment resistance was determined according to the criteria proposed by Conley & Kelly (2001; Biological Psychiatry 50, 898-911). RESULTS: Our results revealed that patients with TRS had higher MPA scores in the mouth region than non-TRS patients, and the two groups also differed in four quantitative measurements (facial width, lower facial height, facial height, and length of the philtrum), after controlling for multiple comparisons using the false discovery rate. Among these dysmorphological measurements, three MPA item types (mouth MPA score, facial width, and lower facial height) and earlier disease onset were further demonstrated to have good discriminant validity in distinguishing TRS from non-TRS patients in a multivariable logistic regression analysis, with an area under the curve of 0.84 and a generalized R 2 of 0.32. CONCLUSIONS: These findings suggest that certain MPAs and craniofacial features may serve as useful markers for identifying TRS at early stages of the illness.

Quantum-mechanical approach to predissociation of water dimers in the vibrational adiabatic representation: Importance of channel interactions.

The results of application of the quantum-mechanical adiabatic theory to vibrational predissociation (VPD) of water dimers, (H2O)2 and (D2O)2, are presented. We consider the VPD processes including the totally symmetric OH mode of the dimer and the bending mode of the fragment. The VPD in the adiabatic representation is induced by breakdown of the vibrational adiabatic approximation, and two types of nonadiabatic coupling matrix elements are involved: one provides the VPD induced by the low-frequency dissociation mode and the other provides the VPD through channel interactions induced by the low-frequency modes. The VPD rate constants were calculated using the Fermi golden rule expression. A closed form for the nonadiabatic transition matrix element between the discrete and continuum states was derived in the Morse potential model. All of the parameters used were obtained from the potential surfaces of the water dimers, which were calculated by the density functional theory procedures. The VPD rate constants for the two processes were calculated in the non-Condon scheme beyond the so-called Condon approximation. The channel interactions in and between the initial and final states were taken into account, and those are found to increase the VPD rates by 3(1) orders of magnitude for the VPD processes in (H2O)2 ((D2O)2). The fraction of the bending-excited donor fragments is larger than that of the bending-excited acceptor fragments. The results obtained by quantum-mechanical approach are compared with both experimental and quasi-classical trajectory calculation results.

Quantifying midbrain serotonin transporter in depression: a preliminary study of diagnosis and naturalistic treatment outcome.

INTRODUCTION: Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain. METHODS: In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment. RESULTS: A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT. DISCUSSION: The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.

Role of the CKIP1 gene in proliferation and apoptosis of the human lung cancer cell line H1299.

Casein kinase 2 interacting protein 1 (CKIP1) is a specific interacting protein of the casein kinase 2 (CK2) α subunit, and, by binding CK2 and other proteins, functions as an adaptor to regulate a series of cellular functions. Previous studies suggested that CKIP1 might play an important role in regulating oncogenic activities. However, few studies examining the function of CKIP1 in cancer cells have been performed. The present study aimed to investigate the role of CKIP1 in lung cancer. CKIP1 mRNA expression was detected in 5 human lung cancer cell lines (H-125, H1299, LTEP-A-2, SPC-A-1, and NCL-H446) by semi-quantitative RT-PCR, and in 10 noncancerous lung tissues and 30 non-small lung cancer tissues by real-time quantitative PCR. A lentivirus-mediated small interfering RNA (siRNA) was used to knock down CKIP1 expression in the H1299 cell line. To elucidate the impact of CKIP1 downregulation on H1299 cells, cell proliferation, DNA synthesis, and cell cycle distribution and apoptosis were measured by high content screening assay, BrdU incorporation, and flow cytometric analyses, respectively. CKIP1 mRNA was highly expressed both in H1299 cells and lung cancer tissues. We found that downregulation of CKIP1 resulted in suppression of proliferation and colony-forming ability of H1299 cells, and led to S phase cell cycle arrest and G2 phase promotion, as well as a significant enhancement of H1299 cell apoptosis. Our study indicated that high expression levels of CKIP1 were associated with the development of lung cancer, and that CKIP1 knockdown may block tumor cell growth mainly by promoting cell apoptosis.

Efficacy of percutaneous radiofrequency ablation for the treatment of hepatocellular carcinoma.

In this study, we sought to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA; experimental group) versus RFA treatment (control group) in patients receiving palliative treatment for hepatocellular carcinoma. To summarize the available evidence, we used the Review Manager 5.1 software to perform a meta-analysis of English-language articles published in public databases prior to 2014. Based on 6 studies that met the inclusion criteria, a total of 531 (experimental group, 272; control group, 259) patients with hepatocellular carcinoma were included in the meta-analysis. The meta-analysis demonstrated that the experimental group had a higher 3-year survival rate [risk ratios (RRs) = 1.41; 95% confidence interval (CI) = 1.03-1.94; P < 0.05] and a higher 2-year survival rate (RR = 1.11; 95%CI = 1.01-1.23; P < 0.05) than the control group. In the overall meta-analysis, the overall RRs were 2.02 (95%CI = 1.40-2.91; P < 0.05) and 1.63 (95%CI = 1.06-2.51; P < 0.05) for 3- and 5-year recurrence-free survival, respectively. Furthermore, the overall meta-analysis showed an overall RR of 0.75 (95%CI = 0.60-0.93; P < 0.05) for the incidence of tumor progression and an overall RR of 1.19 (95%CI = 0.33-4.33; P > 0.05) for the major complication rate. In a sensitivity analysis, the above mentioned meta-analytic estimates were unchanged by the removal of 1 study at a time. The meta-analysis suggested that the experimental group had a higher survival rate, a higher recurrence-free survival rate, and a lower incidence of tumor progression than the corresponding control group.

First Report of Corn Kernel Brown Spot Disease Caused by Mucor irregularis in China.

In October 2012, a brown spot disease was found on corn kernels during a field survey in Nanyang city (33°01' N, 112°29' E), China. The incidences of affected ears and kernels were 2 to 10% (n = 600) and 0.08 to 0.4% (n = 25,000), respectively. Symptoms first appeared as circular or irregular brown spots on the endosperm. These spots subsequently enlarged or coalesced, resulting in the formation of a large light-brown or light-yellow irregular speckle commonly surrounded by a dark-brown edge. Pure fungal cultures with similar morphological characteristics were obtained from surface-disinfected symptomatic kernels using a conventional method for isolation of culturable microbes. The isolated fungal cultures were purified by single-spore isolation (3). A representative isolate F1 was randomly selected, used for pathogenicity tests, and identified using morphological and molecular methods. Colonies on PDA were circular with abundant villiform aerial mycelia. The color of colonies was white-gray at first and turned to light yellow or became ochraceous after 3 days of incubation at 28°C. Hyphae were hyaline and less septate, with rectangular branches. Sporangiophores were erect and unbranched or branched, with globose sporangia formed on their tips. Sporangiospores were elliptical to round, 3.6 to 7.3 × 1.6 to 3.7 µm (n = 100) in size. Two gene regions were amplified for multilocus sequence typing. The D1/D2 region of the nuclear large subunit ribosomal RNA gene (nucLSU) was amplified with primers NL1 and NL4 and the rDNA internal transcribed spacer (ITS) with primers ITS1 and ITS4. PCR products were purified using an Axygen nucleic acid purification kit for sequencing. Both rDNA D1/D2 and rDNA-ITS sequences were submitted to GenBank with accession numbers KM093834 and KM203872, respectively. The isolate F1 showed 98% identity with two isolates of Mucor irregularis (KC524427 and KC461926) in rDNA-ITS sequences and 99% identity with multiple isolates (JX976221, JX976203, and JX976219) of M. irregularis in rDNA D1/D2 sequences. Pathogenicity tests of isolate F1 were conducted based on Koch's postulates. Thirty kernels of fresh ears (milk stage) were pricked by sterilized toothpicks and separately inoculated with a sporangiospore suspension (1 × 106 spores/ml) and 5-day-old mycelial plugs (5 × 5 mm) of isolate F1. Kernels on ears that were inoculated with sterilized water and pure PDA plugs were separately used as controls. After 7 days of incubation, brown spot symptoms developed on the F1-inoculated kernels, which were similar to those observed on the naturally infected ears from the field samples. The control ears remained symptomless during the inoculation tests. Fungal cultures showing the same morphological characteristics as those of isolate F1 were consistently recovered from the diseased cobs inoculated by isolate F1, indicating that M. irregularis was responsible for corn kernel brown spot disease. M. irregularis was reported as a pathogen causing human skin diseases in China (5), America (1), and India (2) and as a phytopathogen causing fruit rot on durian (4). This is the first report of M. irregularis causing corn kernel brown spot disease in China. References: (1) M. M. Abuali et al. J. Clin. Microbiol. 47:4176, 2009. (2) B. M. Hemashettar et al. J. Clin. Microbiol. 49:2372, 2011. (3) S. L. Huang and K. Kohmoto. Bull. Fac. Agric., Tottori Univ. 44:1, 1991. (4) W. F. Wang et al. Plant Quarant. l23:60, 2009. (5) Y. Zhao et al. Mycopathologia 168:243, 2009.

First Report of Fusarium Head Blight of Wheat Caused by Fusarium sacchari in China.

Fusarium head blight (FHB), or scab, caused by Fusarium species, is an economically devastating disease of wheat and other cereal crops worldwide. FHB epidemics in wheat occur frequently in China, especially along the middle and lower reaches of the Yangtze River, including Jiangsu and Shanghai. In 2013, wheat spikes showing clear FHB symptoms were collected from fields in Jiangsu and Shanghai. Symptomatic seeds were surface-sterilized for 1 min with a 5% sodium hypochlorite solution and dipping in 70% ethanol for 30 s, then rinsed three times in sterile distilled water and dried. They were placed onto potato dextrose agar (PDA) and incubated for 3 to 5 days at 28°C in the dark. Fungal colonies displaying morphological characteristics of Fusarium spp. (1,2) were purified by the single-spore technique and characterized at the species level by morphological observations (1,2) and translation elongation factor 1-α (TEF) gene sequencing. The results indicated that members of the Fusarium graminearum clade were predominant on wheat, while the morphological characteristics of 16 isolates were found to be identical to those of F. sacchari (1,2). Colonies on PDA were densely cottony, initially pale but becoming violet with age. The average growth rate was 6 to 8 mm per day at 25°C in the dark. Reverse pigmentation was brownish red to violet-brown. Microconidia, abundant in the aerial mycelium and formed in false heads, were oval to ellipsoidal in shape, primarily zero-septate, measuring 5.7 to 18.8 (average 10.6) µm in length. Macroconidia were slender, three- to five-septate, with a curved apical cell and a poorly developed basal cell, 26.3 to 68.9 (average 44.0) µm in length. No chlamydospores were observed. Two F. sacchari strains (Y37 and S43), isolated from Jiangsu and Shanghai, respectively, were investigated by sequence comparison of their partial TEF gene sequences (Accession Nos. KM233195 and KM233196). BLASTn analysis of the TEF sequences obtained with sequences available in the GenBank database revealed 99.8 and 99.5% sequence identity to F. sacchari (GenBank Accession Nos. JF740708 and JF740709). Pathogenicity tests were conducted by injecting 10 µl of a spore suspension (5 × 105 spores/ml) into wheat florets (20 per isolate of cv. Yangmai16), which were then grown under field conditions in Shanghai. Control plants were inoculated with sterile distilled water. Spikes were harvested and evaluated 14 days post-inoculation. Reddish white mold was observed on inoculated wheat spikes; in addition, spikelets adjacent to the inoculation point and the infected florets were brown. No symptoms were observed on water controls. Koch's postulates were fulfilled by reisolating the pathogen from infected florets and identifying them by TEF gene sequencing. F. sacchari is the cause of an important disease of sugar cane, pokkah boeng (1), and has been reported to produce the mycotoxin beauvericin, which causes toxicosis in human and other animals (3). To our knowledge, this is the first report of F. sacchari causing wheat head blight in China. The report contributes to an improved understanding of the composition of Fusarium species on wheat in the lower reaches of the Yangtze River in China, which will be useful for exploring appropriate disease management strategies in this region. References: (1) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Publishing, Ames, IA, 2006. (2) J. F. Leslie et al. Mycologia 97:718, 2005. (3) A. Moretti et al. Int. J. Food Microbiol. 118:158, 2007.

Mycobacterial bone marrow infections at a medical centre in Taiwan, 2001-2009.

Mycobacterial bone marrow (BM) infection is the most common diagnosis established by BM examinations for fever of unknown origin. In this study, clinical features and outcomes of patients who fulfilled the criteria for BM infection due to Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) at a medical centre in Taiwan from 2001 to 2009 were investigated. The BM histopathological findings were also analysed. A total of 24 patients (16 men, eight women) with mycobacterial BM infections were found. Of these, nine (38%) were positive for human immunodeficiency virus (HIV) and six (25%) had no pre-existing immunocompromised conditions. MTB isolates were obtained from 11 (46%) patients and NTM species were isolated from 10 (42%) patients, including M. avium complex (MAC, n = 7) and M. kansasii (n = 3). Patients with MTB infections were significantly older than those with NTM infections (60·5 vs. 47·7 years, P = 0·043) and were less likely to have a positive BM culture (45% vs. 100%, P = 0·012). The 90-day survival rates for MTB and NTM BM infections were 68% and 60%, respectively (P = 0·61). In addition, the presence of BM granulomas was significantly more common in patients with MTB BM infections than in those with NTM infections (82% vs. 30%, P = 0·030). In Taiwan, the importance of NTM was not inferior to MTB and besides MAC, M. kansasii might be an important pathogen in non-HIV-infected patients. The presence of BM granulomas and caseation provides valuable information regarding early treatment pending culture results.

Changing aetiology of healthcare-associated bloodstream infections at three medical centres in Taiwan, 2000-2011.

This multicentre surveillance study was conducted to investigate the trends in incidence and aetiology of healthcare-associated bloodstream infections (HCA-BSIs) in Taiwan. From 2000 to 2011 a total of 56 830 HCA-BSIs were recorded at three medical centres, and coagulase-negative staphylococci (CoNS) were the most common pathogens isolated (n = 9465, 16·7%), followed by E. coli (n = 7599, 13·4%). The incidence of all HCA-BSIs in each and all hospitals significantly increased over the study period owing to the increase of aerobic Gram-positive cocci and Enterobacteriaceae by 4·2% and 3·6%, respectively. Non-fermenting Gram-negative bacteria, Bacteroides spp. and Candida spp. also showed an increase but there was a significant decline in the numbers of methicillin-resistant S. aureus. In conclusion, the incidence of HCA-BSIs in Taiwan is significantly increasing, especially for Enterobacteriaceae and aerobic Gram-positive cocci.

MiR-99a exerts anti-metastasis through inhibiting myotubularin-related protein 3 expression in oral cancer.

OBJECTIVE: We aimed at studying the role of the most deregulated miR-99a, identifying its downstream targets, and exploring the clinical potential of miR-99a and its target(s) in oral cancer. SUBJECTS AND METHODS: Following confirmation of miR-99a deregulation in nine oral lines and 26 pairwise clinical specimens, miR-99a-manipulated oral cancer cells were subjected to cell proliferation, migration, invasion, and in vivo murine metastasis assays. We characterized putative miR-99a target(s) using luciferase reporter assays and genetic manipulation. The inverse relation of miR-99a and its target(s) was examined in clinical specimens using real-time PCR and Western blot analysis. RESULTS: MiR-99a down-regulation was confirmed both in tested oral cancer cell lines and clinical specimens. Ectopic miR-99a expression inhibited oral cancer cell migration and invasion. Anti-miR-99a, silencing miR-99a functions, had the opposite effect. Myotubularin-related protein 3 (MTMR3) with one evolutionarily conserved seed region in the 3'-untranslated region was a novel miR-99a target. Depleting MTMR3 expression significantly reduced cell proliferation, migration, or invasion. There was an inverse expression of miR-99a and MTMR3 protein in oral cancer lines and clinical specimens. CONCLUSION: miR-99a repressed oral cancer cell migration and invasion partly through decreasing MTMR3 expression. MTMR3 may serve as a therapeutic target for oral cancer treatment.

Low/negative expression of DDX3 might predict poor prognosis in non-smoker patients with oral cancer.

OBJECTIVE: DDX3 has diverse biological functions in translation control, cell growth regulation, and tumor progression. Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide with a poor clinical prognosis. The impact of DDX3 expression in OSCC is seldom discussed. MATERIALS AND METHODS: Tumor tissues and adjacent normal tissues were obtained from 324 patients with OSCC. In this study, we used immunohistochemical staining methods to investigate the associations between DDX3 expression and the clinicopathological characteristics of OSCC. RESULTS: Low/negative DDX3 expression in tumor cells was significantly associated OSCC patient characteristics including male gender (P < 0.001), smoking (P < 0.001), alcohol consumption (P < 0.001), betel quid chewing (P = 0.002), poor relapse-free survival (P = 0.001), and poor overall survival (OS) (P = 0.001). Patients with low/negative DDX3 expression, and particularly non-smoker OSCC patients, had significantly worse OS as defined by the log-rank test (P = 0.020 for all cases; P = 0.008 for non-smoker patients). In non-smoker patients with OSCC, low/negative DDX3 expression in tumor cells was associated with poor prognosis (P = 0.024) and a 3.802-fold higher death risk, as determined by Cox regression. CONCLUSIONS: Low/negative DDX3 expression in tumor cells was significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in non-smoker patients with OSCC.

Obesity and outcomes in patients treated with chemoradiotherapy for esophageal carcinoma.

Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. It was hypothesized that obesity status affects disease outcomes and treatment-related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). From March 2002 to April 2010, 405 patients with non-metastatic esophageal carcinoma at MD Anderson Cancer Center treated with either definitive or neoadjuvant CRT were retrospectively analyzed. Patients were categorized as either obese (BMI ≥ 25 kg/m(2) ) or nonobese (BMI < 25 kg/m(2) ). Progression-free survival and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. One hundred fifteen (28.4%) patients were classified as nonobese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (P < 0.001), adenocarcinoma located distally (P < 0.001), and have undergone surgery (P = 0.004). Obesity was not associated with either worse operative morbidity/mortality (P > 0.05) or worse positron emission tomography tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (P = 0.98) on multivariate analysis. There was also no difference in overall survival, locoregional control, or metastasis-free survival between obese and nonobese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation-induced high-grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high-grade hematologic toxicity (P < 0.001). In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, data suggest it may be associated with decreased risk of acute chemotherapy- and radiotherapy-related treatment toxicities.

Risk factors and surgical interventions associated with primary postpartum haemorrhage unresponsive to first-line therapies.

The aim of this study was to investigate risk factors and surgical interventions associated with primary postpartum haemorrhage (PPH) unresponsive to first-line therapies. A retrospective analysis was performed of 212 women who experienced primary PPH (blood loss ≥ 500 ml). Logistic regression analysis identified that caesarean section (odds ratio [OR] 2.745; 95% confidence interval [CI], 1.063-7.085; p = 0.037) and abnormal placental adhesion (OR 3.823; 95% CI, 1.333-10.963; p = 0.013) were risk factors for PPH unresponsive to first-line therapies. There was no significant difference in blood loss, blood transfusion and success rate among intrauterine tamponade, B-Lynch suture and uterine artery ligation. Intrauterine tamponade is the least invasive and most rapid approach, so it should be taken as the first choice for surgical management after unresponsiveness to first-line therapies.

Risk factors for local and regional recurrence in patients with resected N0-N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy.

BACKGROUND: The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. PATIENTS AND METHODS: Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. RESULTS: Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. CONCLUSION: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.