Streptococcus sanguinis Noncoding cia-Dependent Small RNAs Negatively Regulate Expression of Type IV Pilus Retraction ATPase PilT and Biofilm Formation.

Small noncoding RNAs (sRNAs) have been identified as important regulators of gene expression in various cellular processes. cia-dependent small RNAs (csRNAs), a group of sRNAs that are controlled by the two-component regulatory system CiaRH, are widely conserved in streptococci, but their targets have been identified only in Streptococcus pneumoniaeStreptococcus sanguinis, a pioneer colonizer of teeth and one of the most predominant bacteria in the early oral biofilm, has been shown to have six csRNAs. Using computational target prediction and the luciferase reporter assay, we identified pilT, a constituent of the type IV pilus operon, as a negative regulatory target for one of the csRNAs, namely, csRNA1-1, in S. sanguinis RNA-RNA electrophoretic mobility shift assay using a nucleotide exchange mutant of csRNA1-1 revealed that csRNA1-1 binds directly to pilT mRNA. In addition, csRNA1-1 and csRNA1-2, a putative gene duplication product of csRNA1-1 that is tandemly located in the S. sanguinis genome, negatively regulated S. sanguinis biofilm formation. These results suggest the involvement of csRNAs in the colonization step of S. sanguinis.

Photodynamic Therapy With Resveratrol and an Nd:YAG Laser for Enterococcus faecalis Elimination.

BACKGROUND/AIM: Enterococcus faecalis is the leading cause of endodontic treatment failures. Despite various conventional disinfection approaches, microorganisms often persist in root canals. Photodynamic therapy (PDT) is an adjunct antimicrobial strategy employing a nontoxic photosensitizer (PS) and light source. This study evaluated the antimicrobial effect of PDT using an Nd:YAG laser and resveratrol (RSV) with or without pigment, and confirmed that RSV is nontoxic as a PS. MATERIALS AND METHODS: We employed laser irradiation at a 3W output power, using RSV and red pigment as the PS, on an E. faecalis bacterial solution. Subsequently, colony-forming units were quantified. The impact of RSV on osteoblasts was measured using an MTT assay. RESULTS: E. faecalis counts declined after laser irradiation. The combined application of laser irradiation with RSV, red pigment, or both showed a reduction compared to no irradiation and control groups without RSV and red pigment. The 50% cytotoxic concentration against osteoblast cells from mice incubated with RSV for 48 h was 162 µM. The value with RSV and laser was 201 µM and that with RSV and red pigment was 199 µM. The value with RSV, laser and red pigment was 357 µM. CONCLUSION: The combination of Nd:YAG laser irradiation and RSV as the PS with pigment was efficacious for E. faecalis elimination without inducing any toxic effects on osteoblasts. This combination holds potential as a root canal irrigation strategy.

Stromal CD73 Expression in Breast Cancer: Subtype-specific Expression and its Prognostic Significance.

BACKGROUND/AIM: Invasive ductal carcinoma (IDC) is classified into distinct subtypes with varying prognoses and treatment sensitivities. For instance, triple-negative breast cancer (TNBC) is associated with poorer outcomes than other subtypes. We have previously reported the role of interstitial CD73 in tumor invasion and its correlation with prognosis in other cancers. This study aimed to investigate the expression of stromal CD73 (sCD73) in IDC and its potential prognostic significance. PATIENTS AND METHODS: We analyzed 61 cases of human epidermal growth factor receptor 2-negative IDC, including TNBC and hormone receptor-positive (luminal-type) cases, treated surgically at our institution from 2005 to 2010. Cases that received preoperative drug therapy were excluded. CD73 expression was evaluated by immunostaining of the tumor stroma. RESULTS: sCD73 expression was observed in 70% of all cases, with a significantly higher rate in TNBC (93%) compared with luminal breast cancer (48%). High sCD73 expression was associated with poor prognosis in terms of overall survival (OS) and disease-free survival (DFS) across all cases. In patients with luminal breast cancer, high sCD73 expression was also indicative of poor prognosis with respect to both OS and DFS. CONCLUSION: High expression of sCD73 is associated with poor prognosis in IDC, particularly in luminal breast cancer. Further research is needed to establish sCD73 as an independent prognostic factor.

Factors related to post-thoracotomy pain following robotic-assisted thoracic surgery.

BACKGROUND: Robotic-assisted thoracic surgery (RATS) is a minimally invasive procedure; however, some patients experience persistent postoperative pain. This study aimed to investigate factors related to postoperative pain following RATS. METHODS: The data of 145 patients with lung cancer, who underwent RATS with a four-port (one in the sixth intercostal space [ICS] and three in the eighth ICS) lobectomy or segmentectomy between May 2019 and December 2022, were retrospectively analyzed. Factors associated with analgesic use for at least 2 months following postoperative pain (PTP group) were analyzed. RESULTS: Patients who underwent preoperative pain control for any condition or chest wall resection were excluded. Among the 138 patients, 45 (32.6%) received analgesics for at least 2 months after surgery. Patient height and transverse length of the thorax correlated with PTP in the univariate analysis (non-PTP vs. PTP; height, 166 vs. 160 cm; p < .001; transverse length of the thorax, 270 vs. 260 mm, p = .016). In the multivariate analysis, height was correlated with PTP (p = .009; odds ratio, 0.907; 95% confidence interval, 0.843-0.976). Height correlated with the transverse length of the thorax (r = .407), anteroposterior length of the thorax (r = .294), and width of the eighth ICS in the middle axillary line (r = .210) using Pearson's correlation coefficients. When utilizing a 165-cm cutoff value for height to predict PTP using receiver operating characteristic curve analysis, the area under the curve was 0.69 (95% confidence interval, 0.601-0.779). CONCLUSION: Short stature is associated with a high risk of postoperative pain following RATS.

[Lung resection for lung cancer in patient with situs inversus totalis].

Situs inversus, which occurs in 1-2 of every 10,000 births, is a congenital malformation in which the thoracic and abdominal viscera are arranged in partial on complete mirror image of the normal anatomy. In the case of situs inversus, special attention must be taken in performing surgery. We present a surgical case of primary lung cancer in an 81-year-old patient with situs inversus totalis. During surgery, we used the Univent bronchial tube for one-lung ventilation. The appearance of the right lung and the arrangement of the pulmonary vessels and the bronchi corresponded to those normally found on the right side was noted at left thoracotomy. Left middle lobectomy and partial resection of left upper lung were successfully performed. In lung resection for situs inversus, it is important to be aware the mirrorimage anatomy. The three dimensional computed tomography (3D-CT) images were useful for preoperative evaluation of vessel variation.

[Resected case of pulmonary mucormycosis].

A 62-year-old man, with chronic renal failure and receiving hemodialysis, pointed out to have an abnormal shadow on a chest X-ray. A chest computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET) examination showed a 6 cm size mass lesion in the middle of left thoracic cavity. Confirmed diagnosis was not obtained by needle biopsies. Left upper lobectomy was performed on suspicion of a lung cancer. Histopathologically, fungal hyphae were detected in these surgical specimens and it was diagnosed as pulmonary mucormycosis caused by Rhizopus species.

Adhesiveness of various glass ionomer cements in cavities treated with Carisolv.

OBJECTIVE: The purpose of this study was to investigate the adhesion of glass ionomer cements to dentin and the effect of pretreatment using Carisolv. STUDY DESIGN: Forty extracted permanent teeth with caries were used for this study. All lesions were removed using the Carisolv system and teeth were divided into eight groups. Groups 1 to 4 were filled with three types of conventional glass ionomer cements and a resin modified glass ionomer cement. Group 8 was restored with composite resin. In the remaining three groups (Groups 5 to 7), several pretreatment procedures, including EDTA and dentin primer application and a combination of these, were performed before restoring with resin modified glass ionomer cement. All restorations were thermocycled, and microleakage tests were performed on all teeth. RESULTS: There were no statistical differences among Groups 1, 2 and 3 or between Groups 4 and 8. However Groups 1 to 3 had higher microleakage levels than Groups 4 and 8. Groups 5 to 7 showed similar leakage levels as Group 4. CONCLUSION: Pretreatment with EDTA or dentin primer did not improve bonding ability. Combination of caries removal using Carisolv and a resin modified glass ionomer cement restoration without pretreatment seems to be an acceptable method for caries treatment.

Histological examination of experimentally infected root canals after preparation by Er:YAG laser irradiation.

The influence of Er:YAG laser irradiation on periodontal tissues along the root surface and apical region during root canal preparation was histologically evaluated using experimentally infected root canals of rats. Eighty experimentally mesial infected root canals of mandibular first molars in rats were divided into four groups. In three groups, root canals were irradiated using an Er:YAG laser at 2 Hz with 34, 68, or 102 mJ/pulse for 30 s. Non-irradiated canals served as controls. The influence of laser irradiation on periodontal tissues along the root surface and apical area was evaluated histologically under light microscopy at 0 (immediately after), 1, 2, 4, and 8 weeks after irradiation. At all periods, no inflammation or resorption on the root surfaces caused by laser irradiation was observed in any cases in the control or 34 mJ/pulse-irradiated groups. However, mild to severe inflammation with resorption of root surfaces was observed in some cases in the 68- and 102-mJ/pulse-irradiated groups. No significant difference was apparent between control and laser-irradiated groups at the apical area for all experimental periods (p > 0.05). These results suggest that thermal influences on periodontal tissues of experimentally infected root canals during root canal preparation by Er:YAG laser irradiation are minimal if appropriate parameters are selected. Er:YAG laser irradiation is thus a potential therapy for human infected root canals.

Simultaneous surgical resection of cardiac myxoma and atypical thymic carcinoid: a case report.

BACKGROUND: Cardiac myxoma is the most common type of primary cardiac tumor, and thymic carcinoid is a rare neuroendocrine tumor. No previous reports have described surgical management of concomitant occurrence of these neoplasms. We report a case of simultaneous surgical resection in a patient with coexisting cardiac myxoma and atypical thymic carcinoid. CASE PRESENTATION: A 44-year-old Japanese woman underwent chest roentgenography revealing an abnormality in the mediastinum. Computed tomography revealed a 100 mm mass in the anterior mediastinum and also a 30 mm mass in the left atrium. The mediastinal tumor was diagnosed as atypical carcinoid by biopsy. Having completed resection of atypical thymic carcinoid, cardiac mass was successfully resected with careful consideration of minimizing operation time and optimizing patient safety and oncological treatment. The histopathological diagnosis of the cardiac mass was myxoma. No adjuvant chemotherapy was administered, and no recurrence was seen as of the 45 month follow-up. CONCLUSIONS: The simultaneous surgery of cardiac myxoma and atypical thymic carcinoid was feasible and effective. To the best of our knowledge, this is the first case report to describe one-stage treatment of these neoplasms.

Comprehensive study on potent and selective carbonic anhydrase inhibitors: Synthesis, bioactivities and molecular modelling studies of 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl) benzenesulfonamides.

In this research, rational design, synthesis, carbonic anhydrases (CAs) inhibitory effects, and cytotoxicities of the 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl)benzenesulfonamides 1-20 were reported. Compound 18 (Ki = 7.0 nM) was approximately 127 times more selective cancer-associated hCA IX inhibitor over hCA I, while compound 17 (Ki = 10.6 nM) was 47 times more selective inhibitor of hCA XI over hCA II compared to the acetazolamide. Compounds 11 (CC50 = 5.2 µM) and 20 (CC50 = 1.6 µM) showed comparative tumor-specificity (TS= > 38.5; >128.2) with doxorubicin (TS > 43.0) towards HSC-2 cancer cell line. Western blot analysis demonstrated that 11 induced slightly apoptosis whereas 20 did not induce detectable apoptosis. A preliminary analysis showed that some correlation of tumor-specificity of 1-20 with the chemical descriptors that reflect hydrophobic volume, dipole moment, lowest hydrophilic energy, and topological structure. Molecular docking simulations were applied to the synthesized ligands to elucidate the predicted binding mode and selectivity profiles towards hCA I, hCA II, and hCA IX.

Effect of glypican-1 gene on the pulp cells during the reparative dentine process.

GPC-1 (glypican-1) is a cell surface heparan sulfate proteoglycan that acts as a co-receptor for heparin-binding growth factors and members of the TGF-ß (transforming growth factor beta-1) family. The function of cell-surface proteoglycans in the reparative dentine process has been under investigation. Gpc-1 was detected with similar frequency as tgf-ß1 in the cDNA library using mRNA from the odontoblast-like cell-enriched pulp of rat incisors. The aim of this study was to test our hypothesis that gpc-1 may be related to reparative dentine formation. We examined the expression of this gene during the reparative dentine process, as well as the effect of gpc-1 on odontoblast-like cell differentiation using siRNA (small interfering RNA) to down-regulate gpc-1 expression. Immunohistological examination showed that GPC-1 was expressed in pulp cells entrapped by fibrodentine and odontoblast-like cells as well as TGF-ß1. The mRNAs for gpc-1, -3 and -4, except for gpc-2, were expressed during odontoblast-like cell differentiation in pulp cells. The relative levels of gpc-1 mRNA were increased prior to the differentiation stages and were decreased during the secretory and maturation stages of pulp cells. Down-regulation of gpc-1 expression resulted in a 3.9-fold increase in tgf-ß1 expression in pulp cells and a 0.3-fold decrease in dspp (dentine sialophosphoprotein) expression compared with control. These results suggested that gpc-1 and tgfß-1 expression are necessary for the onset of differentiation, but should be down-regulated before other molecules are implicated in the formation of reparative dentine. In conclusion, gpc-1 expression in odontoblast-like cells is associated with the early differentiation but not with the formation of reparative dentine.

Removal of organic debris from occlusal fissures: advantage of Carisolv system over sodium hypochlorite.

OBJECTIVE: The purpose of this in vitro study was to evaluate and compare the removal of artificial debris from pits and fissures using the Carisolv system and sodium hypochlorite. STUDY DESIGN: Forty artificial fissures prepared on extracted human teeth were filled with artificial organic debris. Debris was removed using either Carisolv or 10% sodium hypochlorite gel. After stereoscopic observation, samples were filled with a sealant and subjected to microleakage test. RESULTS: Both Carisolv and sodium hypochlorite demonstrated adequate cleaning ability and prevention of microleakage. Although both Carisolv and 10% sodium hypochlorite are effective at removing debris from fissures, Carisolv presents greater advantages in terms of safety and antibacterial properties. CONCLUSION: Fissure cleaning using Carisolv might be an effective approach to improve the retention of fissure sealants.

Effect of Small-molecule GSK3 Antagonist on Differentiation of Rat Dental Pulp Cells into Odontoblasts.

BACKGROUND: It has been reported that glycogen synthase kinase 3 (GSK3) antagonist promoted the reparative formation of dentin. The aim of the present study was to evaluate whether treatment schedule of Tidegrusib® (TG), a small-molecule GSK3 antagonist, affected in vitro differentiation of dental pulp cells toward odontoblast-like cells. MATERIALS AND METHODS: Pulp cells isolated from rat incisors were repeatedly exposed to TG for the first 6 h (intermittent exposure) or the full 48 h (continuous exposure) of each 48-h incubation cycle. Histological analysis of alkaline phosphatase and von Kossa staining were performed. The expression of dentin sialophosphoprotein (Dspp) and osteocalcin (Ocn) mRNA were examined by real-time polymerase chain reaction. Western blotting assays were used to monitor the expression of ß-catenin and its phosphorylated form. RESULTS: When pulp cells were intermittently exposed to TG for only the first 6 h of each incubation cycle, pulp cells differentiated into odontoblast-like cells, characterized by an increase in alkaline phosphatase activity, nodule formation, and mRNA expression of Dspp. and Ocn; this did not occur under the continuous exposure. Phosphorylation of ß-catenin was enhanced by continuous exposure to TG compared with intermittent exposure. CONCLUSION: These results suggest that the TG-induced odontoblast-like cell differentiation reflects in vivo reparative dentin formation and depends on the exposure time.

Possible role of semaphorin 3F, a candidate tumor suppressor gene at 3p21.3, in p53-regulated tumor angiogenesis suppression.

Although the regulation of tumor angiogenesis is believed to be one of the core functions of p53, the mechanism still remains to be elucidated. Here, we report that semaphorin 3F (SEMA3F), an axon guidance molecule, is involved in p53-regulated antiangiogenesis. The expression level of SEMA3F mRNA was increased by both exogenous and endogenous p53. Chromatin immunoprecipitation assay indicated that a potent p53-binding sequence in intron 1 of SEMA3F interacts with p53 and that it has a p53-responsive transcriptional activity. Overexpression of SEMA3F inhibited in vitro cell growth of the lung cancer cell line H1299. In nude mice assay, the size of the H1299 tumors expressing SEMA3F was much smaller, and they showed lesser number of blood vessels as compared with the control tumors. Moreover, tumors derived from the p53-knockdown colorectal cancer cell line LS174T displayed a remarkable enhancement of tumor vessel formation as compared with control tumors containing normal levels of p53. The expression levels of SEMA3F and neuropilin-2 (NRP2), the functional receptor for SEMA3F, in p53-knockdown LS174T tumors were lower than those in the control tumors. Adenovirus-mediated SEMA3F gene transfer induced the remarkable in vitro growth suppression of the stable transformant of H1299 cells, which express high levels of NRP2. These results suggest that p53 negatively regulates tumor vessel formation and cell growth via the SEMA3F-NRP2 pathway.

Establishment of a Primary Culture System of Human Periodontal Ligament Cells that Differentiate into Cementum Protein 1-expressing Cementoblast-like Cells.

BACKGROUND/AIM: A better understanding of cementogenesis and cementoblast differentiation would be useful for periodontal therapy. The aim of this study was to establish a cell culture system that reflects cementum formation in periodontal tissue and determine whether or not isolated and cultured primary human periodontal ligament (PDL) cells could be used for the study of the differentiation of cementoblast. MATERIALS AND METHODS: PDL cells were isolated from the outgrowths of tissue fragments of human PDL. PDL cells were incubated for up to 21 days in differentiation medium containing ß-glycerophosphate and ascorbic acid. The changes in the cells were detected by alkaline phosphatase (ALP) and von Kossa staining. Real-time polymerase chain reaction was also performed for cementum protein 1 (CEMP1), which is a specific marker of cementoblasts and their progenitors. RESULTS: On day 5, a small number of PDL cells, which were fibrous, were positive for ALP. On day 7, almost all cells were positive for ALP. On day 14, mineralization nodules appeared, as seen by positive von Kossa staining; the nodules increased in number and size by day 21. The expression of CEMP1 was detected on day 5, and its expression level increased gradually by day 7, reached a peak on day 14, and decreased by day 21. CONCLUSION: Human PDL cells were used to establish a culture system that reflects cementum formation. Our results suggested that this culture method is convenient and useful for the study of cementogenesis and cementoblast differentiation.

Analysis of surface roughness and microleakage of fissure sealants following organic debris removal with Carisolv.

OBJECTIVE: The objective of the present study was to improve fissure sealing by pre-treatment with Carisolv in order to remove organic debris. The surface morphology and roughness of fissure cavities and the degree of microleakage after Carisolv application were compared with those after bristle brush treatment in vitro. METHODS: Fifty extracted human teeth were used in this study. The teeth were randomly divided into two groups of 25 each. Artificial fissures were prepared in all teeth into which artificial organic debris was placed. The debris in 25 teeth of one group was removed using Carisolv applied for 30s and excavation was performed with a dental explorer until the gel was clear. The remaining 25 teeth were then cleaned using bristle brush with prophylaxis paste. Surface roughness was analyzed in five samples from each group by color laser three-dimensional (3D) microscopy and by scanning electron microscopic examination. The remaining samples were filled with sealant and subjected to a microleakage test under thermocycling. Statistical analysis was performed using the Mann-Whitney U-test; a value of p<0.05 was considered significant. RESULTS: Morphologically, most of the debris in the fissures was removed by Carisolv treatment, whereas some fissures were not cleaned by bristle brush. Carisolv-treatment with acid-etching resulted in removal of debris-like smear layer leaving enamel prisms open, and 3D laser microscopy demonstrated that the roughness values increased after acid-etching. However, microleakage test of both Carisolv and brush methods showed similar results. CONCLUSIONS: Carisolv-treated surfaces especially when subjected to acid-etching might facilitate good adaptation of sealant to enamel, because of an increase in surface roughness and favorable surface characteristics.

Synergistic inhibition of anaerobic ammonium oxidation (anammox) activity by phenol and thiocyanate.

Coke-oven wastewater discharged from the steel-manufacturing process is phenol and thiocyanate (SCN)-rich wastewater, which inhibits microbial activities in biological wastewater treatment processes. In the present study, synergistic inhibition of anaerobic ammonium oxidation (anammox) activity by phenol and SCN was examined by batch incubation and continuous operation of an anammox reactor. The comparison of anammox activities determined in the batch incubation, in which the anammox biomass was anoxically incubated with 10-250 mg L-1 of i) phenol, ii) SCN, or iii) both phenol and SCN, showed that synergistic inhibition by phenol and SCN was greater than the inhibitions by phenol or SCN alone. The synergistic inhibition by phenol and SCN was further investigated by operating an up-flow column anammox reactor for 262 d. The removal efficiencies of NH4+ and NO2- deteriorated when phenol and SCN concentrations in the influent increased to 16 and 32 mg L-1, respectively, and the inhibition of anammox activity was further investigated by a15NO2- tracer experiment. Addition of phenol and SCN resulted in a population shift of anammox bacteria, and the dominant species changed from "Candidatus Kuenenia stuttgartiensis" to "Ca. Brocadia sinica". The relative abundance of Azoarcus and Thiobacillus 16S rRNA gene reads increased during the operation, suggesting that they were responsible for the anaerobic phenol and SCN degradation. The present study is the first to document the synergistic inhibition of anammox activity by phenol and SCN and the microbial consortia involved in the nitrogen removal as well as the phenol and SCN degradations.

Photodynamic Therapy with Pyoktanin Blue and Diode Laser for Elimination of Enterococcus faecalis.

BACKGROUND/AIM: Enterococcus faecalis is responsible for most cases of endodontic treatment failure. Despite various conventional disinfection methods, root canals are not completely free of microorganisms. Photodynamic therapy (PDT) is a new antimicrobial strategy that involves the use of a non-toxic photosensitizer (PS) and a light source. The aim of this study was to evaluate the antimicrobial effect of PDT using diode laser and pyoktanin blue (PB) and confirm the nontoxicity of PB as a PS. MATERIALS AND METHODS: Laser irradiation with an output power of 3 W was performed with PB as the PS to a bacterial solution containing E. faecalis. Then, the number of colony-forming units was counted. PB cytotoxicity was also assessed by the MTT assay. RESULTS: E. faecalis counts were reduced after laser irradiation, laser irradiation with PB, or the combination thereof compared to the control, non-irradiation or water. The 50% cytotoxic concentration value for adult human dermal fibroblasts incubated with PB for 1 min was 108 µg/ml. CONCLUSION: Diode laser irradiation in combination with PB as the PS is efficacious for the elimination of E. faecalis without toxic effects to human dermal fibroblasts. This strategy might be useful for root canal irrigants.

Protection of Differentiating Neuronal Cells from Amyloid ß Peptide-induced Injury by Alkaline Extract of Leaves of Sasa senanensis Rehder.

BACKGROUND/AIM: We have previously reported the protection of doxorubicin-induced keratinocyte toxicity by alkaline extract of the leaves of Sasa senanensis Rehder (SE). In order to extend the generality of the cell protective effect of SE, we investigated whether it also protects rat PC12 and human SH-SY5Y neuron model cells from amyloid ß-peptide (Aß)-induced injury. MATERIALS AND METHODS: Viability of cells was determined by the MTT method. Cytotoxicity was evaluated by the concentration that reduces the cell viability by 50% (CC50). Protection from Aß-induced cytotoxicity was evaluated by the concentration that reversed the Aß-induced reduction of viability by 50% (EC50). The selectivity index (SI) of neuroprotective activity was defined as the ratio of EC50 to CC50 Aß1-42 aggregation was assayed using Aß1-42 ammonium hydroxide. RESULTS: SE showed hormetic growth stimulation at lower concentrations in both neuron precursors and differentiated cells. SE reproducibly inhibited Aß-induced cytotoxicity against both undifferentiated and differentiated neuron cells. Both the extent of differentiation induction and viability depended on the cell density, suggesting the release of growth and differentiation stimulation substances into culture supernatant. Higher concentrations of SE partially reduced the Aß1-42 aggregation. CONCLUSION: Hormetic growth stimulation and inhibition of aggregation may be involved in the neuroprotective activity of SE.

Survivin expression predicts early recurrence in early-stage breast cancer.

BACKGROUND: The apoptosis inhibitor survivin is one of the most specific proteins in breast cancer patients. The role of this protein in predicting prognosis is still controversial. PATIENTS AND METHODS: Survivin mRNA was measured using quantitative TaqMan reverse transcription-PCR in 76 samples, including 48 early-stage breast cancer tissues and adjacent normal tissues, from patients with operable tumors, and was tested for correlation with established clinicopathological factors, or disease-free survival (DFS). RESULTS: Comparing the survivin expression in 78 breast cancer patients with the clinicopathological factors (age, menopausal status, nodal category, tumor histology, tumor size, histological grade, ER and PgR status, and type of operation), T factor (T1-T4) was significantly associated with a high survivin mRNA ratio (p=0.0104). The proportion of tumors with a high survivin mRNA ratio was greater in node-positive than in node-negative tumors (p=0.0001), and in grade III tumors compared to grade I or grade II tumors (p =0.0001). Patients with low survivin expression showed significantly better disease-free survival than patients with high survivin expression in stage I and II breast cancer (p<0.0001, log-rank). Survivin expression alone is a powerful prognostic factor for disease-free survival of breast cancer patients without nodal involvement (HR: 0.024, 95% CI: 0.001-0.446, p=0.0123) using Cox multivariate regression analysis. CONCLUSION: Survivin is an indicator of the recurrence of early-stage breast cancer. Survivin might be used as a new marker to stratify early-stage breast cancer patients for more optimal treatment modalities, or it could be a promising target for therapy.