Nosocomial infection with rotavirus vaccine strain in paediatric patients with immunodeficiency.

In infants with immunodeficiency, rotavirus (RV) vaccines can be continuously excreted in stool. We analysed nosocomial infection with RV vaccine strain in immunodeficient paediatric patients. RV1 RNAs were detected in stool and serum samples from case A, who was vaccinated with RV1, and case B, who was not. PAGE analysis of serial stool samples of case A revealed several rearrangements of the RV genome. In case B, the only band pattern detected was the same as a rearrangement detected in case A at the same time. In summary, RV vaccination of infants with immunodeficiency poses a risk of nosocomial infections.

Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation.

OBJECTIVES: The surface of pure titanium (Ti) shows decreased histocompatibility over time; this phenomenon is known as biological ageing. UV irradiation enables the reversal of biological ageing through photofunctionalisation, a physicochemical alteration of the titanium surface. Ti implants are sterilised by UV irradiation in dental surgery. However, orthopaedic biomaterials are usually composed of the alloy Ti6Al4V, for which the antibacterial effects of UV irradiation are unconfirmed. Here we evaluated the bactericidal and antimicrobial effects of treating Ti and Ti6Al4V with UV irradiation of a lower and briefer dose than previously reported, for applications in implant surgery. MATERIALS AND METHODS: Ti and Ti6Al4V disks were prepared. To evaluate the bactericidal effect of UV irradiation, Staphylococcus aureus 834 suspension was seeded onto the disks, which were then exposed to UV light for 15 minutes at a dose of 9 J/cm2. To evaluate the antimicrobial activity of UV irradiation, bacterial suspensions were seeded onto the disks 0, 0.5, one, six, 24 and 48 hours, and three and seven days after UV irradiation as described above. In both experiments, the bacteria were then harvested, cultured, and the number of colonies were counted. RESULTS: No colonies were observed when UV irradiation was performed after the bacteria were added to the disks. When the bacteria were seeded after UV irradiation, the amount of surviving bacteria on the Ti and Ti6Al4V disks decreased at 0 hours and then gradually increased. However, the antimicrobial activity was maintained for seven days after UV irradiation. CONCLUSION: Antimicrobial activity was induced for seven days after UV irradiation on both types of disk. Irradiated Ti6Al4V and Ti had similar antimicrobial properties.Cite this article: T. Itabashi, K. Narita, A. Ono, K. Wada, T. Tanaka, G. Kumagai, R. Yamauchi, A. Nakane, Y. Ishibashi. Bactericidal and antimicrobial effects of pure titanium and titanium alloy treated with short-term, low-energy UV irradiation. Bone Joint Res 2017;6:108-112. DOI: 10.1302/2046-3758.62.2000619.

Neuropeptide Y loses its orexigenic effect in rats with lesions of the hypothalamic paraventricular nucleus.

BACKGROUND: Both neuropeptide Y (NPY) and ghrelin can enhance the feeding behavior. The purpose of this study was to determine whether NPY and ghrelin are involved in hyperphagia and obesity induced by lesions of the hypothalamic paraventricular nucleus (PVN). METHODS: Sham-operated control rats and rats subjected to bilateral electrolytic lesions of the PVN were administered NPY (5 µg/rat) by intracerebroventricular infusion or ghrelin (20 µg/kg) by intraperitoneal (i.p.) injection. Control rats were administered the appropriate vehicle by the same route as the drug. We measured the cumulative food intake (FI) for 2 h after infusion of NPY and for 4 h after ghrelin injection. RESULTS: NPY significantly increased the cumulative FI in sham-operated rats. In PVN-lesioned rats, however, the cumulative FI at each time point (15 min, 30 min, 1 h, and 2 h) after NPY infusion was not significantly different from vehicle infusion, showing that NPY lost its orexigenic effect in PVN-lesioned rats. Following ghrelin injection, the cumulative FI was greater in PVN-lesioned rats than sham-operated rats, indicating that PVN lesions enhanced the orexigenic effects of ghrelin. CONCLUSION: These results suggest that the hyperphagia and obesity induced by PVN lesions may be related to an increased orexigenic action of ghrelin, but not NPY.

Calcium influx through the TRPV1 channel of endothelial cells (ECs) correlates with a stronger adhesion between monocytes and ECs.

PURPOSE: Atherosclerosis is thought to be initiated by the transendothelial migration of monocytes. In the early stage of this process, the adhesion of monocytes to endothelial cells is supported by an increase in the intracellular concentration of calcium ion ([Ca(2+)]i) in endothelial cells. However, the main source of Ca(2+) has been unclear. In this study, the changes in ionic transmittance and [Ca(2+)]i due to the adhesion of monocytes were continuously measured by an electrophysiological technique and fluorescent imaging. Especially, we focused on transient receptor potential vanilloid channel 1 (TRPV1) as a Ca(2+) channel that could influence the adhesion of monocytes. MATERIAL AND METHODS: Whole-cell current was continuously recorded in human umbilical vein endothelial cells (HUVECs) by a patch electrode. RESULTS: The adhesion of monocytes (THP-1) induced a transient inward current in HUVECs, as well as an elevation of [Ca(2+)]i. This inward element was abolished by the application of 100 nM SB366,791, a selective antagonist of TRPV1 channel. Furthermore, SB366,791 significantly decreased the number of THP-1 cells that adhered to HUVECs (control: 231 ± 38, SB366,791: 96 ± 16 cells/mm2). CONCLUSION: These results suggest that an inward calcium current via the TRPV1 channels of endothelial cells correlates with a stronger adhesion between monocytes and endothelial cells.

Laparoscopy for recurrent Crohn's disease: how do the results compare with the results for primary Crohn's disease?

AIM: To assess the feasibility and outcomes of reoperative laparoscopic-assisted surgery for recurrent Crohn's disease compared with index laparoscopic resections. METHOD: A retrospective analysis of a prospectively maintained database was performed from 2001 to 2008 on patients who had primary laparoscopy (group I) or reoperative laparoscopy for Crohn's disease (group II). Data collection included demographic and surgical data, and postoperative outcomes. RESULTS: One hundred and thirty patients were included in this study, distributed as follows: group I, 80 patients with a mean age of 35 years; and group II, 50 patients with a mean age of 42 years. Preoperative American Society of Anesthesiologists score and body mass index were similar in both groups. Patients in group II had a longer period of disease (15.5 vs 8.9 years in groups I and II, respectively; P = 0.0002). Immunosuppressive therapy had been utilized in 66 (82.5%) and in 42 (84%) patients in groups I and II, respectively. Ileocolic resection was the most commonly performed procedure in both groups (82%), followed by subtotal colectomy. Conversion rates were 18.7 and 32% in groups I and II, respectively (P = 0.09). The mean operative time (182 vs 201 min) and mean blood loss (161 vs 202 ml) were not significantly different (P > 0.05); however, the overall incisional length was significantly longer in group II (6.7 vs 11.4 cm, P = 0.045). A stoma was created in 17 and 16% of patients in groups I and II, respectively. Overall, early postoperative complications were not statistically significantly different between the two groups (P > 0.05); anastomotic leak occurred in four (5%) and one (2%) patients (P = 0.65), and abdominal abscess in three (3.75%) and four (8%) patients (P = 0.56), in groups I and II, respectively. Reoperative rates were 10 and 6% (P = 0.53), and mean hospital stay was similar in groups I and II respectively (6.7 vs 7.5 days, respectively; P = 0.3266). There was no mortality. CONCLUSION: The results of laparoscopic-assisted resection for recurrent Crohn's disease are similar to those for primary resection.

TCEAL7, a putative tumor suppressor gene, negatively regulates NF-kappaB pathway.

We have previously shown that a frequently downregulated gene, transcription elongation factor A-like 7 (TCEAL7), promoted anchorage-independent growth and modulated Myc activity in ovarian surface epithelial cells immortalized with temperature-sensitive large T antigen and human telomerase reverse transcriptase (OSEtsT/hTERT). Analysis of protein/DNA array showed that TCEAL7 downregulation resulted in an approximately twofold increase in nuclear factor (NF)-kappaB binding to its target DNA sequence. In this study we showed that short hairpin RNA (shRNA)-mediated downregulation of TCEAL7 in two different immortalized OSE cells showed higher NF-kappaB activity, as determined using reporter and gel-shift assays. Transient transfection of TCEAL7 inhibited the activation of NF-kappaB in TCEAL7-downregulated clones, IOSE-523 and in other ovarian cancer cell lines (OVCAR8, SKOV3ip and DOV13), suggesting that TCEAL7 negatively regulates NF-kappaB pathway. Consistent with this observation, TCEAL7-downregulated clones showed higher levels of NF-kappaB targets, such as pro-proliferative (cyclin-D1 and cMyc), pro-angiogenic (interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF)), inflammatory (intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase-2 (Cox-2)) and anti-apoptotic (B-cell lymphoma-extra large (Bcl-xl)) genes when compared with vector controls. Inhibition of NF-kappaB by IkappaB kinase (IKK) inhibitor (BMS 345541) attenuated cell survival and proliferation of TCEAL-knockdown clones. Although TCEAL7 inhibited p65 transcriptional activity, it did not modulate the cytoplasmic signaling of the NF-kappaB pathway, by itself or by tumor necrosis factor-alpha (TNF-alpha). Chromatin immunoprecipitation (ChIP) assays revealed increased recruitment of p65 and p300 to the promoters of IL-8 and IL-6 in TCEAL7-downregulated clones. Collectively, these results indicate a novel role for TCEAL7 in the negative regulation of NF-kappaB signaling at the basal level by modulating transcriptional activity of NF-kappaB on its target gene promoters, potentially providing a novel mechanism by which NF-kappaB activity may be deregulated in ovarian cancer cells.

Effort-reward imbalance and depressive state in nurses.

BACKGROUND: The mental health of nurses is an important issue. AIMS: To examine relationships between effort-reward imbalance (ERI) and depression and anxiety in nurses of a Japanese general hospital. METHODS: A self-report survey was conducted among 406 nurses. Work stress was measured using a Japanese version of the ERI scale. Depression and anxiety were assessed by an item of the QOL-26. Logistic regression analysis was used to determine the independent contribution of the effort-reward ratios or overcommitment to the depressive state. RESULTS: Both higher effort-money ratio and higher overcommitment significantly correlated with the depressive state (OR: 2.75; 95% CI: 1.34-5.66 and OR: 1.27; 95% CI: 1.15-1.41, respectively). CONCLUSIONS: These findings suggest that in addition to effort-money ratio, overcommitment at work is an especially important issue that may be able to be managed in health promotion services for nurses in general hospitals.

Phase II study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer.

OBJECTIVE: To determine the efficacy and tolerability of oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced colorectal cancer. METHODS: S-1 was administered orally at 80 mg/m(2)/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at a dose of 80 mg/m(2)/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 282 courses of treatment were administered to 40 patients, achieving complete response in 1 and partial responses in 24 with an overall response rate of 62.5% (95% CI: 47.5-77.5%). Median progression-free survival was 7.8 months (95% CI: 6.7-9.6 months). The rates of grade 3 or 4 toxicities were as follows: neutropenia 12.5%, anorexia 12.5%, fatigue 10%, and diarrhea 7.5%. CONCLUSION: Combined treatment with S-1 and irinotecan is an effective, well-tolerated and convenient regimen in patients with advanced colorectal cancer which is easily maintained.

[Emergency distal arch replacement for traumatic thoracic aortic dissection with subarachnoid hemorrhage].

A 77-year-old woman was transferred as traumatic thoracic aortic dissection with subarachnoid hemorrhage soon after a traffic accident. Her consciousness was slightly compromised and cardiogenic shock was developed. Serial computed tomography (CT) scans revealed an unchanging subarachnoid hemorrhage and a progressive mediastinal hemorrhage and pericardial effusion due to traumatic type B aortic dissection. An emergency distal arch replacement was performed under cardiopulmonary bypass 4 hours after the injury. She woke up 3 days after the operation without progression of subarachnoid hemorrhage on a cerebral CT scan. She was discharged 36 days after the injury.

Interspecies somatic cell nucleus transfer with porcine oocytes as recipients: A novel bioassay system for assessing the competence of canine somatic cells to develop into embryos.

Interspecies somatic cell nucleus transfer (iSCNT) could be a useful bioassay system for assessing the ability of mammalian somatic cells to develop into embryos. To examine this possibility, we performed canine iSCNT using porcine oocytes, allowed to mature in vitro, as recipients. Canine fibroblasts from the tail tips and dewclaws of a female poodle (Fp) and a male poodle (Mp) were used as donors. We demonstrated that the use of porcine oocytes induced blastocyst formation in the iSCNT embryos cultured in porcine zygote medium-3. In Fp and Mp, the rate of blastocyst formation from cleaved embryos (Fp: 6.3% vs. 22.4%; and Mp: 26.1% vs. 52.4%) and the number of cells at the blastocyst stage (Fp: 30.7 vs. 60.0; and Mp: 27.2 vs. 40.1) were higher in the embryos derived from dewclaw cells than in those derived from tail-tip cells (P<0.05). The use of donor cells of any type in later passages decreased the rate of blastocyst formation. Treatment with trichostatin-A did not improve the rate of blastocyst formation from cleaved dewclaw cell-derived embryos but did so in the embryos derived from the tail-tip cells of Fp. Only blastocysts derived from dewclaw cells of Mp developed outgrowths. However, outgrowth formation was retrieved in the embryos derived from dewclaw cells of Fp by aggregation at the 4-cell stage. We inferred that iSCNT performed using porcine oocytes as recipients could represent a novel bioassay system for evaluating the developmental competence of canine somatic cells.

[Local recurrence of Castleman disease].

A rare case of recurrent Castleman disease is reported. A 49-year-old man was referred to our division under the suspicion of mediastinal tumor. We performed tumor resection successfully, and the tumor was shown to be Castleman disease by histology. The patient had a past history of this disease, therefore it was suggested that the tumor recurred at the same site 20-years after removal.

A role for candidate tumor-suppressor gene TCEAL7 in the regulation of c-Myc activity, cyclin D1 levels and cellular transformation.

The pathophysiological mechanisms that drive the development and progression of epithelial ovarian cancer remain obscure. Recently, we identified TCEAL7 as a transcriptional regulatory protein often downregulated in epithelial ovarian cancer. However, the biological significance of such downregulation in cancer is not currently known. Here, we show that TCEAL7 is downregulated frequently in many human cancers and that in immortalized human ovarian epithelial cells this event promotes anchorage-independent cell growth. Mechanistic investigations revealed that TCEAL7 associates with cyclin D1 promoter containing Myc E-box sequence and transcriptionally represses cyclin D1 expression. Moreover, downregulation of TCEAL7 promotes DNA-binding activity of Myc-Max, and upregulates the promoter activity of c-Myc-target gene, ornithine decarboxylase (ODC), whereas enhanced expression of TCEAL7 inhibits Myc-induced promoter activity of ODC. Our findings suggest that TCEAL7 may restrict ovarian epithelial cell transformation by limiting Myc activity. These results also suggest a potential, alternative mechanism by which c-Myc activity may be deregulated in cancer by the downregulation of TCEAL7.

Ghrelin stimulates milk intake by affecting adult type feeding behaviour in postnatal rats.

The influence of ghrelin on feeding behaviour during infancy is unknown. To determine whether ghrelin influences milk intake in rat pups, newborn rats received a single i.p. injection of either rat ghrelin (100 microg/kg) or rabbit anti-ghrelin immunoglobulin G (100 microg/kg) every 5 days from postpartum day 5 to day 30 (P5-P30). Milk intake was then assessed by body weight gain following a 2-h suckling period. Ghrelin significantly increased weight gain relative to vehicle-injected controls in P20, P25 and P30 pups, but not in younger animals. Similarly, after 8 h of milk restriction, anti-ghrelin injections significantly decreased weight gain in P25 and P30, but not in younger pups. Interestingly, however, ghrelin did increase independent feeding in P10 and P15 pups using a paradigm in which pups consumed milk from a milk-soaked paper towel. We therefore conclude that ghrelin stimulates milk intake at an early postnatal stage, primarily by affecting adult-type feeding behaviour.

Effects of ghrelin, corticotrophin-releasing hormone, and melanotan-II on food intake in rats with paraventricular nucleus lesions.

Bilateral lesions of the hypothalamic paraventricular nuclei (PVN) induce hyperphagia and obesity, and ghrelin stimulates appetite in rodents and humans. Conversely, corticotrophin-releasing hormone (CRH) and melanotan-II (MT-II, a synthetic structural homologue of alpha-melanocyte-stimulating hormone, alphaMSH) inhibit feeding behavior. The purpose of the present study was to determine whether these peptides are involved in the hyperphagia and obesity induced by PVN lesions. After bilateral electrolytic lesions of the PVN, rats were given ghrelin intraperitoneally (i. p.), or intracerebroventricular (i. c. v.) infusion of CRH or MT-II. We measured the cumulative food intake (FI) for 4 h after ghrelin injection in rats fed AD LIB, and the changes in FI at 15 min, 30 min, 1 h, and 2 h after infusion of CRH and MT-II in rats fasted for 24 h. Ghrelin significantly increased cumulative FI, with maximal response 3 h and 4 h after injection, and at these times, the FI of PVN-lesioned rats was greater than that of sham-operated rats. CRH significantly decreased FI in all experimental animals, but at 1 h, there was a more powerful inhibitory effect on FI in the PVN-lesioned group than in the sham-operated group. MT-II decreased FI in sham-operated, but not in PVN-lesioned rats. Thus, ghrelin and CRH showed more potent orexigenic and anorectic effects in PVN-lesioned rats, respectively, but MT-II lost its inhibitory action on feeding behavior. These results suggest that the hyperphagia and obesity induced by PVN lesions may be related to an increased orexigenic action of ghrelin due to the destruction of endogenous CRH and alphaMSH receptors.

Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer.

PURPOSE: To determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan plus S-1 in advanced colorectal cancer. PATIENTS AND METHODS: S-1 was administered orally at 80 mg/m2/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 60 mg/m2/day, stepping up to 80, 100, 120 or 140 mg/m2/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 20 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 100 mg/m2, because 2 of 3 patients developed dose-limiting toxicities, such as anorexia, fatigue and diarrhea. Therefore, the recommended dose of CPT-11 was set at 80 mg/m2. Tumor responses were seen in 8 of 14 patients with measurable lesions. CONCLUSION: A combination of S-1 with CPT-11 is safe and can be recommended for further phase II studies in patients with advanced colorectal cancer.

Contrast-enhanced multi-shot echo-planar FLAIR in the depiction of metastatic tumors of the brain: comparison with contrast-enhanced spin-echo T1-weighted imaging.

BACKGROUND: The usefulness of fast fluid-attenuated inversion-recovery (FLAIR) sequences after administration of contrast medium (f-FLAIR (+)) has been shown in depicting brain tumors including metastases and meningeal carcinomatosis. Contrast-enhanced multi-shot echo-planar FLAIR (Ms-EPI-FLAIR (+)), comprising combined sequences of f-FLAIR (+) and Ms-EPI, may provide the advantages of f-FLAIR (+) along with rapid acquisition. PURPOSE: To compare Ms-EPI-FLAIR (+) with post-contrast spin-echo T1-weighted imaging (SE-T1WI (+)) in the depiction of brain metastases. MATERIAL AND METHODS: In 14 patients with metastatic tumors of the brain, spin-echo precontrast T1-weighted imaging (SE-T1WI (-)), fast spin-echo T2-weighted imaging (FSE-T2WI), fast-FLAIR, SE-T1WI (+), and Ms-EPI-FLAIR (+) were acquired. For qualitative evaluation of SE-T1WI (+) and Ms-EPI-FLAIR (+), receiver operating characteristic (ROC) analysis was performed in two different readers. For quantitative analysis, the intensity ratios (intensity of tumor divided by intensity of peritumoral region) in SE-T1WI (+) and Ms-EPI-FLAIR (+) were compared. RESULTS: Although pre-contrast f-FLAIR detected 84 of 106 tumors, Ms-EPI-FLAIR (+) detected 98 of 106 tumors. In the ROC analysis for observers A and B, Az values in SE-T1WI (+) did not differ from values in Ms-EPI-FLAIR (+). Quantitatively, the intensity ratio in Ms-EPI-FLAIR (+) also did not differ from that in SE-T1WI (+). CONCLUSION: Detectability of brain metastases with Ms-EPI-FLAIR (+) is almost similar to that with SE-T1WI (+). Ms-EPI-FLAIR (+) could be an alternative to SE-T1WI (+) in the depiction of brain metastases.

Using precise data sets on farming and pesticide properties to verify a diffuse pollution hydrological model for predicting pesticide concentration.

Verification of a diffuse pollution model involves comparing results actually observed with those predicted by precise model inputs. Acquisition of precise model inputs is, however, problematic. In particular, when the target catchment is large and substantial estimation uncertainty exists, not only model verification but also prediction is difficult. Therefore, in this study, rice-farming data were collected for all paddy fields from all farmers in a catchment and pesticide adsorption and degradation rates in paddy field soil samples were measured to obtain precise model inputs. The model inputs successfully verified the model's capability to predict pesticide concentrations in river water. Sensitivity analyses of the model inputs elucidated the processes significantly affecting pesticide runoff from rice farms. Pesticide adsorption and degradation rates of the soil did not significantly affect pesticide concentrations, although pesticide discharge to river water accounted for less than 50% of the total quantity of pesticide applied to fields, possibly owing to pesticide adsorption and degradation. The timing of increases in pesticide concentrations in river water was affected mostly by the farming schedule, including the time of pesticide application and irrigation, and secondarily by rainfall events.

Enhancement of Ca2+-induced Ca2+ release by cyclic ADP-ribose in frog motor nerve terminals.

Ca2+-induced Ca2+ release (CICR) occurs via activation of ryanodine receptors (RyRs) in frog motor nerve terminals after RyRs are primed for activation by repetitive Ca2+ entries, thereby contributing to synaptic plasticity. To clarify how the mechanism of CICR becomes activable by repetitive Ca2+ entries, we studied effects of a RyR modulator, cyclic ADP-ribose (cADPr), on CICR by Ca2+ imaging techniques. Use-dependent binding of fluorescent ryanodine and its blockade by ryanodine revealed the existence of RyRs in the terminals. Repetition of tetani applied to the nerve produced repetitive rises in intracellular Ca2+ ([Ca2+]i) in the terminals. The amplitude of each rise slowly waxed and waned during the course of the stimulation. These slow rises and decays were blocked by ryanodine, indicating the priming, activation and inactivation of CICR. Uncaging of caged-cADPr loaded in the terminals increased the amplitude of short tetanus-induced rises in [Ca2+]i and the amplitude, time to peak and half decay time of the slow waxing and waning rises in [Ca2+]i evoked by repetitive tetani. A cADPr blocker, 8-amino-cADPr, loaded in the terminals decreased the slow waxing and waning component of rises and blocked all the actions of exogenous cADPr. It is concluded that cADPr enhances the priming and activation of CICR. The four-state model for RyRs suggests that cADPr inhibits the inactivation of CICR and increases the activation efficacy of RyR.

Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance.

To investigate the mechanism by which HSulf-1 expression is downregulated in ovarian cancer, DNA methylation and histone acetylation of HSulf-1 was analysed in ovarian cancer cell lines and primary tumors. Treatment of OV207 and SKOV3 by 5-aza-2'-deoxycytidine resulted in increased transcription of HSulf-1. Sequence analysis of bisulfite-modified genomic DNA from ovarian cell lines and primary tumors without HSulf-1 expression revealed an increase in the frequency of methylation of 12 CpG sites in exon 1A. Chromatin immunoprecipitation assays showed an increase in histone H3 methylation in cell lines without HSulf-1 expression. To assess the significance of HSulf-1 downregulation in ovarian cancer, OV167 and OV202 cells were transfected with HSulf-1 siRNA. Downregulation of HSulf-1 expression in OV167 and OV202 cells lead to an attenuation of cisplatin-induced cytotoxicity. Moreover, patients with ovarian tumors expressing higher levels of HSulf-1 showed a 90% response rate (27/30) to chemotherapy compared to a response rate of 63% (19/30) in those with weak or moderate levels (P=0.0146, chi(2) test). Collectively, these data indicate that HSulf-1 is epigenetically silenced in ovarian cancer and that epigenetic therapy targeting HSulf-1 might sensitize ovarian tumors to conventional first-line therapies.