Genetic profile of naïve untreated primary cutaneous melanomas with a negative sentinel lymph node.

Sentinel lymph node (SLN) biopsy is typically offered to patients with primary cutaneous melanomas (PCMs) of ≥ 1 mm depth, but not all SLNs are positive using this cutoff. To ascertain whether positivity is genetically regulated, genetic analysis was performed using an augmented enrichment-based next-generation DNA and RNA sequencing assay in SLN-negative (Group 1, n = 8, mean depth 1.3 mm) and SLN-positive PCMs (controls, Group 2, n = 4, mean depth 1.4 mm). In Group 1, the mean number of mutations was 21 (range 3-48) with the most frequent mutations occurring in NF1 (75%) followed by TP53 (63%), CDKN2A and BRAF (38%), and NRAS (25%), while in Group 2, the ean number of mutations was 9.5 (range 5-18) with mutations in NRAS and BRAF being the most frequent (50%) followed by those in ATM, CDKN2A, CDKN2B, and NOTCH1 (25%). Increased frequency of NF1-inactivating mutations in Group 1 provides provocative early data that the presence of NF1 mutations might confer a less aggressive phenotype.

Bathroom greywater recycling using polyelectrolyte-complex bilayer membrane: Advanced study of membrane structure and treatment efficiency.

Polyelectrolyte-complex bilayer membrane (PCBM) was fabricated using biodegradable chitosan and alginate polymers for subsequent application in the treatment of bathroom greywater. In this study, the properties of PCBMs were studied and it was found that the formation of polyelectrolyte network reduced the molecular weight cut-off (MWCO) from 242kDa in chitosan membrane to 2.71kDa in PCBM. The decrease in MWCO of PCBM results in better greywater treatment efficiency, subsequently demonstrated in a greywater filtration study where treated greywater effluent met the household reclaimed water standard of <2 NTU turbidity and <30ppm total suspended solids (TSS). In addition, a further 20% improvement in chemical oxygen demand (COD) removal was achieved as compared to a single layer chitosan membrane. Results from this study show that the biodegradable PCBM is a potential membrane material in producing clean treated greywater for non-potable applications.

The orally active urotensin receptor antagonist, KR36676, attenuates cellular and cardiac hypertrophy.

BACKGROUND AND PURPOSE: Blockade of the actions of urotensin-II (U-II) mediated by the urotensin (UT) receptor should improve cardiac function and prevent cardiac remodelling in cardiovascular disease. Here, we have evaluated the pharmacological properties of the recently identified UT receptor antagonist, 2-(6,7-dichloro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-methyl-N-(2-(pyrrolidin-1-yl)-1-(4-(thiophen-3-yl)phenyl) ethyl)acetamide (KR36676). EXPERIMENTAL APPROACH: Pharmacological properties of KR36676 were studied in a range of in vitro assays (receptor binding, calcium mobilization, stress fibre formation, cellular hypertrophy) and in vivo animal models such as cardiac hypertrophy induced by transverse aortic constriction (TAC) or myocardial infarction (MI). KEY RESULTS: KR36676 displayed high binding affinity for the UT receptor (Ki : 0.7 nM), similar to that of U-II (0.4 nM), and was a potent antagonist at that receptor (IC50 : 4.0 nM). U-II-induced stress fibre formation and cellular hypertrophy were significantly inhibited with low concentrations of KR36676 (≥0.01 µM). Oral administration of KR36676 (30 mg·kg(-1) ) in a TAC model in mice attenuated cardiac hypertrophy and myocardial fibrosis. Moreover, KR36676 restored cardiac function and myocyte size in rats with MI-induced cardiac hypertrophy. CONCLUSIONS AND IMPLICATIONS: A highly potent UT receptor antagonist exerted anti-hypertrophic effects not only in infarcted rat hearts but also in pressure-overloaded mouse hearts. KR36676 could be a valuable pharmacological tool in elucidating the complicated physiological role of U-II and UT receptors in cardiac hypertrophy.

Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development.

The effects of DNA repair and transcription gene abnormalities in human pre-natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10(-6)) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (n = 24) with respect to abnormalities during their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (n = 18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Small for gestational age (SGA) <10th percentile [Relative risk (RR ) = 9.3, 95% CI = 1.4-60.5, p = 0.02], SGA <3rd percentile (RR = 7.2, 95% CI = 1.1-48.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.4-29.5, p = 0.02) occurred more frequently among TTD-affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD-affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.6-92.5, p = 0.0002), elevated mid-trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.0-16.6, p < 0.0001), SGA <3rd percentile (RR = 13.9, 95% CI = 7.4-21.1, p < 0.0001), pre-term delivery (<32 weeks) (RR = 12.0, 95% CI = 4.9-21.6, p < 0.0001), pre-eclampsia (RR = 4.0, 95% CI = 1.6-7.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.6-5.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development.

Occurrence and intake of deoxynivalenol in cereal-based products marketed in Korea during 2007-2008.

The occurrence of deoxynivalenol (DON) was investigated in 514 cereal-based products (corn-based, n = 125; barley-based, n = 96; wheat-based, n = 94; rice-based, n = 199) marketed in Korea during 2007-2008, and estimates of DON intake were determined. Samples were analysed by high-performance liquid chromatography (HPLC) with ultraviolet light (UV) detection after immunoaffinity clean-up. The limits of detection (LOD) and limits of quantification (LOQ) were 2.2 and 5.6 µg kg(-1), respectively. Recoveries and repeatability expressed as coefficients of variation (CV) were 82.3-100% and 2.4-15.3% in beer, bread and dried corn. The incidences and mean levels of DON were 56% and 68.9 µg kg(-1) for corn-based products, 49% and 24.1 µg kg(-1) for wheat-based products, 43% and 7.5 µg kg(-1) for barley-based products, and 16% and 3.4 µg kg(-1) for rice-based products, respectively. The estimated daily intake of DON from the consumption of rice-based, wheat-based, barley-based and corn-based products were 0.0038 µg kg(-1) bw day(-1), 0.0032 µg kg(-1) bw day(-1), 0.0015 µg kg(-1) bw day(-1) and 0.0002 µg kg(-1) bw day(-1), respectively. These values represent 0.38%, 0.32%, 0.25% and 0.01% of the provisional maximum tolerable daily intake (PMTDI) of 1 µg kg(-1) bw day(-1). These results indicate that rice-based products are major contributors to DON exposure in Korea, even though the current exposure level is unlikely to cause adverse health effects.

Hyperthermal neutral beam sources for material processing.

Hyperthermal neutral beams have a great potential for material processes, especially for etching and thin film deposition for semiconductor and display fabrication as well as deposition for various thin film applications. Plasma-induced damage during plasma etching is a serious problem for manufacturing deep submicron semiconductor devices and is expected to be a problem for future nanoscale devices. Thermal and plasma-induced damage is also problematic for thin film depositions such as transparent conductive oxide films on organic light emitting diodes or flexible displays due to high temperature processes in plasma environments. These problems can be overcome by damage-free and low-temperature processes with hyperthermal neutral beams. We will present the status of the hyperthermal neutral beam development and the applications, especially, in semiconductor and display fabrication and introduce potential applications of thin film growing for optoelectronic devices such as light emitting diodes.

The elevation of the constructed auricle with a temporoparietal fascial flap wrapping a resorbable plate.

During the second stage reconstruction of the auricle in patients with microtia, we modified Nagata's method and two technical improvements were possible. After the implanted auricle was separated from the bed, we harvested the temporoparietal fascial flap through helical rim incision instead of incising the temporal scalp. So the surgical scar over the temporal region was avoided. Thereafter, a costal cartilage wedge was carved and grafted to the posterior aspect of the conchal region to get a firm projection. But in cases of unavailable costal cartilage wedge graft, we used a resorbable plate composed of polylactic and polyglycolic acid as a substitute for the former so that we could create firm elevation and sufficient ear projection. Between June 2002 and May 2004, 28 patients underwent this operation with the temporoparietal fascial flap and resorbable plating system. There was no complication resulting from our technique. It was possible to create firm elevation and good frontal projection even if there was no available cartilage wedge. Additionally, by harvesting the temporoparietal fascia through helical rim incision, we avoid creating additional scars on the scalp.

Developmental toxicity assessment of the new fluoroquinolone antibacterial DW-116 in rabbits.

DW-116 is a newly developed fluoroquinolone antibacterial with a broad spectrum against both Gram-positive and Gram-negative bacteria. We have reported recently that DW-116 is embryotoxic and teratogenic in rats. The present study was conducted to investigate the teratogenicity of DW-116, together with maternal toxicity and developmental toxicity using New Zealand White rabbits. The test chemical was administered by gavage to pregnant rabbits from gestational day (GD) 6 through to GD 18 at dose levels of 0, 5, 19.5 and 76.1 mg kg(-1) day(-1). All does were subjected to caesarean section on day 28 of gestation and their foetuses were examined for external, visceral and skeletal abnormalities. In the 76.1 mg kg(-1) group, a minimal maternal toxicity, as evidenced by decreased body weight gain during treatment period, was observed in pregnant rabbits. Significant embryo-foetal toxicity, including increased number of foetal deaths and delayed foetal ossification, was seen. However, no treatment-related morphological changes were detected in foetal external, visceral and skeletal examinations. There were no adverse effects on either pregnant dams or embryo-foetal development at 19.5 and 5 mg kg(-1). It was concluded that administration of DW-116 during the major organogenetic period in rabbits produced decreased maternal body weight gain, increased number of foetal deaths and foetal developmental delay but no evidence of teratogenicity. The no-observed-adverse-effect levels (NOAELs) of DW-116 are considered to be 19.5 mg kg(-1) day(-1) for does and embryo-foetuses, respectively.

Peri- and postnatal developmental toxicity of the fluoroquinolone antibacterial DW-116 in rats.

DW-116 is a fluoroquinolone antibacterial developed by Dong-Wha Pharmaceutical Industry Co. The aim of this study is to determine the potential adverse effects of this chemical on pregnancy, delivery and lactation of dams and on peri- and postnatal development of F1 offspring. The test chemical was orally administered to pregnant rats from day 16 of pregnancy, through parturition and throughout the period of lactation up to weaning (postnatal day 21) at dose levels of 0, 10, 50, or 250 mg/kg/day. The progeny were examined at birth and subsequently to weaning. Mortality, body weight change, physical signs of postnatal development (pinna detachment, incisor eruption, fur development, eye opening, testis descent and vaginal opening) and behavioral function (righting reflex, negative geotaxis, grip-strength, pupillary reflex, acoustic startle response, rotating rod test, open field test and water-filled T-maze test) were evaluated. When the exposed offspring reached maturity (11 weeks old) their reproductive capacity was assessed. Maternal toxicity was observed only in the highest dose group and was limited to decreased food consumption during the late stage of pregnancy. However, this change was not observed during the lactation period. There were no adverse effects on mortality, clinical signs, body weight, necropsy findings, organ weight of dams in any treatment group. No adverse effects on the offspring were seen with the low and middle doses tested, but the highest dose increased postnatal mortality. The number of stillborn was also increased at the highest dose but the difference was not statistically significant. Meanwhile, no treatment-related effects were observed in clinical sign, developmental and behavioral landmarks and necropsy findings at any dose levels tested. There were no treatment-related effects on the mating of the F1 generation and resulting F2 offspring. The results of this study indicate that the peri- and postnatal administration of DW-116 to female rats results in an increase in postnatal mortality at a minimally maternotoxic dose, i.e., 250 mg/kg/day. Under the experimental conditions, the no-observed-adverse-effect level for peri- and postnatal developmental toxicity was considered to be 50 mg/kg/day.

Mechanistic insight into the inactivation of carboxypeptidase A by alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid, a novel type of irreversible inhibitor for carboxypeptidase A with no stereospecificity.

On the basis of the active site topology and enzymic catalytic mechanism of carboxypeptidase A (CPA), a prototypical zinc-containing proteolytic enzyme, alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (1), was designed as a novel type of mechanism-based inactivator of the enzyme. All four possible stereoisomers of the inhibitor were synthesized in an enantiomerically pure form starting with optically active aspartic acid, and their CPA inhibitory activities were evaluated to find that surprisingly all of the four stereoisomers inhibit CPA in a time dependent manner. The inhibited enzyme did not regain its enzymic activity upon dialysis. The inactivations were prevented by 2-benzylsuccinic acid, a competitive inhibitor that is known to bind the active site of the enzyme. These kinetic results strongly support that the inactivators attach covalently to the enzyme at the active site. The analysis of ESI mass spectral data of the inactivated CPA ascertained the conclusion from the kinetic results. The values of second-order inhibitory rate constants (k(obs)/[I](o)) fall in the range of 1.7-3.6 M(-1) min(-1). The lack of stereospecificity shown in the inactivation led us to propose that the ring cleavage occurs by the nucleophilic attack at the 2-position rather than at the 5-position and the ring opening takes place in an addition-elimination mechanism. The tetrahedral transition state that would be generated in this pathway is thought to be stabilized by the active site zinc ion, which was supported by the PM3 semiemprical calculations. In addition, alpha-benzyl-2-oxo-1,3-oxazolidine-5-acetic acid (18), a structural isomer of 1 was also found to inactivate CPA in an irreversible manner, reinforcing the nucleophilic addition-elimination mechanism. The present study demonstrates that the transition state for the inactivation pathway plays a critical role in determining stereochemistry of the inactivation.

The need for scoliosis screening in Malaysia.

Conflicting recommendations exist on the issue of scoliosis screening in the general population. Worldwide, opponents cite the relative inaccuracy of screening tests, cost-ineffectiveness and psychosocial effect of 'labelled' patients but advocates quote the successes in many centres and the advantages of timely intervention. We studied 205 patients with idiopathic scoliosis and found they presented at relatively later ages and with curves that showed rapid annual progression. We suggest that screening in Malaysia may identify patients early for treatment besides promoting health awareness.

An audit of the Scoliosis Service at Hospital Kuala Lumpur.

This is a study of patients referred to the Scoliosis Service of Hospital Kuala Lumpur. Three hundred and thirty five (335) consecutive patients who were seen between 1985 and 2000 were reviewed to determine the presentation of scoliosis, the treatment received and the compliance to follow up. Data were determined by measuring the frontal spinal radiographs. Two hundred and ninety eight (298) patients met inclusion criteria. Idiopathic scoliosis accounted for 203 patients (68.1%), 31 (10.4%) were neuromuscular scoliosis; and 44 (14.8%) had congenital scoliosis. Twenty-five point five percent of patients had surgery, 10.4% were treated with brace, while the remaining 69.1% of patients were observed, or had no treatment at all. Congenital scoliosis patients had better compliance compared to idiopathic or neuromuscular scoliosis patients.

The natural history of scoliosis: curve progression of untreated curves of different aetiology, with early (mean 2 year) follow up in surgically treated curves.

We studied the curve progression of untreated curves presenting to the Scoliosis Service of Hospital Kuala Lumpur. One hundred and fifty-two (152) patients were included in this study. The median rate of curve progression of idiopathic scoliosis curves was 7.03 degrees per year, for neuromuscular scoliosis curves was 17.39 degrees per year; and congenital scoliosis curves were 3.67 degrees per year. These rates are similar to the reported rates in the literature. Data for sixty-one (61) surgically treated patients were reviewed to determine the early curve correction of the curves of different aetiology. The mean age of surgery was 14.15 years old, the mean preoperative curve size was 71.61 degrees; and the mean postoperative curve size was 43.78 degrees. The mean duration of follow up after surgery was 2.44 years. The revision and removal of instrumentation rate was 8.3%.

Role of catalytic residues in enzymatic mechanisms of homologous ketosteroid isomerases.

Ketosteroid isomerase (KSI) is one of the most proficient enzymes catalyzing an allylic isomerization reaction at a diffusion-controlled rate. In this study of KSI, we have detailed the structures of its active site, the role of various catalytic residues, and have explained the origin of the its fast reactivity by carrying out a detailed investigation of the enzymatic reaction mechanism. This investigation included the X-ray determination of 15 crystal structures of two homologous enzymes in free and complexed states (with inhibitors) and extensive ab initio calculations of the interactions between the active sites and the reaction intermediates. The catalytic residues, through short strong hydrogen bonds, play the role of charge buffer to stabilize the negative charge built up on the intermediates in the course of the reaction. The hydrogen bond distances in the intermediate analogues are found to be about 0.2 A shorter in the product analogues both experimentally and theoretically.

Inhibition of nicotinic receptor-mediated catecholamine secretion by Dryobalanops aromatica in bovine adrenal chromaffin cells.

Effect of the aqueous extract from a medicinal plant Dryobalanops aromatica(Dipterocarpaceae) on catecholamine secretion was investigated in bovine adrenal chromaffin cells. The aqueous extract inhibited [(3)H]norepinephrine ([(3)H]NE) secretion induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic acetylcholine receptor (nAChR) agonist, with a half-maximal inhibitory concentration (IC(50)) of 8.4 +/- 1.7 microgml(-1). Increases in cytosolic calcium ([Ca(2+)](i)) and sodium ([Na(+)](i)) induced by DMPP were also inhibited by the extract. However, the binding of [(3)H]nicotine to nAChRs was not affected by the addition of the extract in receptor binding competition analysis, suggesting that active components in the extract and nicotine do not share the binding site in the nAChR. On the other hand, [Ca(2+)](i)increases induced by high K(+), ionomycin, bradykinin, angiotensin II, and thapsigargin were not inhibited by the extract. The data suggest that the extract from D. aromatica specifically inhibits catecholamine secretion by blocking nAChR in a noncompetitive manner.

Origin of the high affinity and selectivity of novel receptors for NH4+ over K+: charged hydrogen bonds vs cation-pi interaction.

[structure: see text]Given the recent report of a novel pyrazole receptor exhibiting a high selectivity for NH4+ over K+, it would be interesting to investigate the origin of this selectivity and affinity so that better receptors could be designed. On the basis of extensive theoretical studies, we conclude that the origin arises from a subtle interplay of charged H-bonds and cation-pi interactions. The approach employed herein would be very useful in the rational design of novel functional molecular systems.

Catalytic role of enzymes: short strong H-bond-induced partial proton shuttles and charge redistributions.

A two-step reaction mechanism (catalyzed alternatively by acid and base) with partial proton shuttles and charge redistributions promoted by short strong H bonds (SSHBs) (playing a dual role as an amphi-acid/base catalyst) is proposed to explain the enormous rate enhancement observed in enzymatic reactions involving carbanion intermediates. The SSHBs in the two-step reactions are found to be responsible for enhancing enzyme-substrate interactions in favor of the transition state structure over that of reactant. The detailed quantum theoretical studies of ketosteroid isomerase provide evidence of assisting roles of SSHB in enzymatic activity. The understanding of the two-step reaction mechanism would be a useful aid in designing novel functional enzymes and abzymes.

Expression of protein kinase C genes in normal (+/+) and W mutant alleles (Wsh/Wsh, W/Wv) mice testes.

In the present study, we investigated the expression of mRNA of protein kinase C (PKC) isoenzymes (alpha, beta, gamma, delta, epsilon, zeta, eta, and theta) in normal (+/+) and W mutant alleles mice testes. In +/+ mice testes, abundant expression of PKCdelta and PKCtheta was observed, while other PKCs (alpha, beta, gamma, epsilon, zeta, and eta) generally were not detected by Northern blotting. The PKCdelta and PKCtheta isoenzymes demonstrated a distinctive cellular distribution when evaluated by in situ hybridization. We have previously shown that PKCdelta gene was selectively expressed in spermatid of +/+ testes. Here we show that PKCdelta gene is also present in spermatid of Wsh/Wsh mice testes and PKCtheta gene was present in interstitial cells of +/+, Wsh/Wsh, and W/Wv mice testes. These studies provide the evidence of selective cell distributions of the PKC isoenzymes and suggest that PKC has the functional significance in testes.

High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion.

OBJECTIVE: The enzymes cyclooxygenase (COX)-1 and -2 are necessary for the synthesis of prostaglandins. COX-2 is usually absent in normal cells and is upregulated and expressed as a product of the "immediate early" gene during inflammatory processes. In previous studies, the expression of COX-2 has been shown to be induced by proinflammatory cytokines, and suggestions have been made that overexpression of COX-2 suppresses apoptosis and is directly related to tumor growth. We have attempted to determine a relationship between tumor invasion and metastasis of uterine cervical cancer and COX and apoptosis by comparing the protein expression of apoptosis, COX-1, and COX-2 in tumor tissues. METHODS: The subjects were 36 patients who were FIGO stage IB uterine cervical cancer patients who underwent surgery at Ajou University Hospital. There were 12 cases with lymph node or parametrial involvement. All tissues were subjected to immunohistochemical staining for COX-1, -2, and TUNEL method for apoptosis detection, and the following results were obtained. RESULTS: Tumor tissues confirmed by cytokeratin were separated into tumor surface, tumor stroma, and invasion site portions, in which decreased apoptosis was observed in the invasion sites. COX-2 expression was observed in all tumor tissues and was especially strong in the tumor invasion site. Therefore, it is suggested that COX-2 expression may suppress cell apoptosis at the tumor invasion site. When COX-2 expression was investigated according to the groups with regard to the presence of lymph node or parametrial involvement, there was a statistically significant (Mann-Whitney U test) COX-2 expression difference in the tumor invasion site (P value = 0.040) and the tumor stroma (P value = 0. 028). CONCLUSIONS: In surgically treated stage IB cervical cancer patients, COX-2 was significantly expressed when lymph node or parametrial involvement was present. These results suggest that the expression of COX-2 in stage IB cervical cancer may downregulate apoptotic processes and thus enhance tumor invasion and metastasis.

Expression of TRAIL (TNF-related apoptosis-inducing ligand) receptors in cervical cancer.

Apoptosis is an intrinsic and fundamental biologic process that plays a critical role in the normal development of multicellular organisms and in the maintainance of tissue homeostasis. Some of the well known regulators of apoptosis are cytokines of the tumor necrosis factor (TNF) ligand family, such as Fas ligand (Fas L) and TNF, which induce apoptosis by activation of their corresponding receptors, Fas and TNFR-1. Recently, a new member of the TNF family known as TRAIL (TNF-related apoptosis-inducing ligand) was identified and shown to induce p53-independent apoptosis in a variety of tumor cell lines but not in normal cells. Four human receptors for TRAIL were also recently identified and designated TRAIL-R1, -R2, -R3, and -R4. The aim of this study is to examine whether TRAIL and TRAIL receptors (-R1, -R2, -R3) are expressed in uterine cervical cancer and whether it is correlated with apoptosis, TRAIL, and TRAIL receptors. The subjects were 20 patients who were diagnosed with cervical cancer. Western blotting was performed in nine cases and immunohistochemical staining for TRAIL and TRAIL receptors (-R1, -R2, -R3) and TUNEL method for detection of apoptosis was performed in 11 cases. There were proteins for TRAIL, TRAIL-R1, -R2, and -R3 in tissues from cervical cancer. All TRAIL receptors were expressed in both normal cervical epithelium and tumor cells, and TRAIL-R1 and -R2 were more strongly expressed in tumor cells than normal epithelium (P < 0.05). Apoptosis correlated with expression of TRAIL-R1 and -R2 (P < 0.05). This study suggests that TRAIL induces apoptosis in cervical cancer through its receptors.