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Biomedical subjects

Bo Lu

Publications and source records attributed to Bo Lu.

36 records · Page 2Linked to original sources
PubMed2005

Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation.

An association between epidermal growth factor receptor (EGFR) signaling pathway and response of cancer cells to ionizing radiation has been reported. Recently, a polymorphic variant in the EGFR gene that leads to an arginine-to-lysine substitution in the extracellular domain at codon 497 within subdomain IV of EGFR has been identified. The variant EGFR (HER-1 497K) may lead to attenuation in ligand binding, growth stimulation, tyrosine kinase activation, and induction of proto-oncogenes myc, fos, and jun. A (CA)(n) repeat polymorphism in intron 1 of the EGFR gene that alters EGFR expression in vitro and in vivo has also been described. In the current pilot study, we assessed both polymorphisms in 59 patients with locally advanced rectal cancer treated with adjuvant or neoadjuvant chemoradiation therapy using PCR-RFLP and a 5'-end [gamma-(33)P]ATP-labeled PCR protocol. We tested whether either polymorphism alone or in combination can be associated with local recurrence in the setting of chemoradiation treatment. We found that patients with HER-1 497 Arg/Arg genotype or lower number of CA repeats (both alleles <20) tended to have a higher risk of local recurrence (P = 0.24 and 0.31, respectively). Combined analysis showed the highest risk for local recurrence was seen in patients who possessed both a HER-1 497 Arg allele and <20 CA repeats (P = 0.05, log-rank test). Our data suggest that the HER-1 R497K and EGFR intron 1 (CA)(n) repeat polymorphisms may be potential indicators of radiosensitivity in patients with rectal cancer treated with chemoradiation.

Adult↗
PubMed2005

Propensity score matching with time-dependent covariates.

In observational studies with a time-dependent treatment and time-dependent covariates, it is desirable to balance the distribution of the covariates at every time point. A time-dependent propensity score based on the Cox proportional hazards model is proposed and used in risk set matching. Matching on this propensity score is shown to achieve a balanced distribution of the covariates in both treated and control groups. Optimal matching with various designs is conducted and compared in a study of a surgical treatment, cystoscopy and hydrodistention, given in response to a chronic bladder disease, interstitial cystitis. Simulation studies also suggest that the statistical analysis after matching outperforms the analysis without matching in terms of both point and interval estimations.

Cohort Studies↗
PubMed2005

Endostatin polymorphism 4349G/A(D104N) is not associated with aggressiveness of disease in prostate [corrected] cancer.

Endostatin is an important inhibitory molecule which mediates the sequential steps involved in angiogenesis. Lower level or impaired function of endostatin is associated with a higher risk of developing malignant solid tumors and with a worse prognosis of the disease. The endostatin N104 polymorphism might be associated with an impaired ability to inhibit angiogenesis. We analyzed the tissues from 98 Caucasian prostate cancer patients for the presence of D104N polymorphism. The frequencies of homozygous 4349G/G(104D/D), and heterozygous 4349G/A(104D/N) were 83.67%(82/98) and 16.33%(16/98), respectively; no individuals were homozygous 4349A/A(104N/N). With the Fisher's exact test we found the genotype of D104N was not significantly related to age, tumor grade, PSA and clinical stage (P > 0.05). There was no difference in relapse free survival(RFS) or overall survival(OS) between patients with 104D/N and those with 104D/D (P = 0.8283, 0.3713 respectively). We concluded that endostatin polymorphism was not associated with the aggressiveness of prostate cancer in Caucasian patients.

Aged↗
PubMed2005

Murine double minute 2 as a therapeutic target for radiation sensitization of lung cancer.

Murine double minute 2 (MDM2) inhibits p53-mediated functions, which are essential for therapies using DNA-damaging agents. The purpose of this study was to determine whether MDM2 inhibition enhances the radiosensitivity of a lung cancer model. The effects of MDM2 inhibition on tumor vasculature were also studied. Transient transfection of H460 lung cancer cells and human umbilical vascular endothelial cells (HUVEC) with antisense oligonucleotides (ASODN) against MDM2 resulted in a reduced level of MDM2 and increased levels of p21 and p53. Clonogenic assays showed that inhibition of MDM2 greatly decreased cell survival following irradiation. Quantification of apoptotic cells by 7-aminoactinomycin D staining and of senescent cells by X-gal staining showed that both processes were significantly increased in H460 cells treated with MDM2-specific ASODN and radiation. H460 xenografts that were treated with MDM2 ASODN plus radiotherapy also showed significant growth delay (P < 0.001) and increased apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. HUVECs transfected with MDM2-specific ASODN showed impaired viability and migration with decreased tube formation. Doppler studies showed that tumor blood flow was compromised when H460 xenografts were treated with MDM2-specific ASODN and radiation. A combination of radiotherapy and inhibition of MDM2 through the antisense approach results in improved tumor control in the H460 lung cancer model. This implies that a similar strategy should be investigated among patients with locally advanced lung cancer, receiving thoracic radiotherapy.

Animals↗
PubMed2005

The use of tyrosine kinase inhibitors in modifying the response of tumor microvasculature to radiotherapy.

The response of the tumor microvasculature to ionizing radiation can be modified to improve tumor control in preclinical mouse models of cancer. Recent studies have shown that a variety of cancer drugs can improve the response of cancers to radiotherapy. Protein tyrosine kinase inhibitors (TKIs) have been shown to enhance radiation-induced destruction of tumor blood vessels. Among these compounds are inhibitors of a broad spectrum of receptor tyrosine kinases (RTKs). Inhibition of RTKs attenuates downstream signaling from various angiogenic growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). RTK inhibitors with various specificities against the receptors for VEGF, PDGF, and FGF manifest significant antiangiogenic activities as well. We have shown using tumor vascular window model and tumor growth delay assays that these compounds can enhance tumor radiation response by attacking tumor microvasculature. Furthermore, we have shown that radiation and RTK inhibitors exert their antiangiogenic effect through inhibition of the PI3K/Akt signaling pathway, which results in induction of apoptosis. Our studies have provided a basis for future clinical investigations of combining radiotherapy and RTK inhibitors.

Angiogenesis Inhibitors↗
PubMed2005

Octyl-a-cyanoacrylate adhesive in the treatment of tibial transverse fracture in rabbits.

OBJECTIVE: To observe the effect of octyl-a-cyanoacrylate upon bone healing and its degradation in vitro after middle tibial transverse fracture in rabbitsì and to establish treatment of higher efficacy with the application of octyl-a-cyanoacrylate. METHODS: Middle tibial transverse fracture model of New Zealand rabbits was established. In the experimental group, internal fixation with 2 mm Kirschner wires was performed and the broken ends were fixed with octyl-a-cyanoacrylate. In the control group, only internal fixation with 2 mm Kirschner wires was conducted. Animals were killed at preset time intervals of 2, 4, 6, 8, 10 and 12 weeks postoperatively and samples were harvested. RESULTS: Two weeks after operation, clear fracture lines were observed in both the experimental and the control groups. Fibrous soft tissue connection was noted between the broken ends and there was soft tissue adhesion around the fracture site. There was no callus formation and the broken ends were surrounded by adhesive soft tissues. Obvious external callus formation was confirmed at 8 weeks after operation in both groups with partial disappearance of fracture lines. Ten and twelve weeks after the operation, fracture lines disappeared completely and there was obvious external callus formation and bone union. In the fourth week, fibrous cells and chondrocytes were found to grow into the colloid and surround it at the 6th week. The adhesive material was degraded and gradually absorbed at the 8th week. Chondrification was observed. CONCLUSIONS: Two weeks after fixation for tibial fracture in rabbits, octyl-a-cyanoacrylate begins in vivo degradation. Chondrocytes and fibrocytes gradually grow into the degradation area and surround the adhesive material, which broke into pieces at 8 weeks. Complete degradation and disappearance of the adhesive material is present between 10 and 12 weeks. No barrier effect hampering fracture healing is noted.

Adhesives↗
PubMed2005

[Analysis on the incidence and relevant risk factors of campus violence among college students].

OBJECTIVE: To study the incidence and risk factors of campus violence and to provide evidence for preventing campus violence among college students. METHODS: 5300 college students in two universities in a province of China were selected to participate in the study and were interviewed with questionnaires. Logistic regression was used for data analysis. RESULTS: (1) In total, 3910 useable questionnaires were gathered to show a response rate of 73.77%. 17.98% of the college students reported they had ever experienced campus violence in the last one year. 29.60% of the male students experienced campus violence so as 7.27% of the female students. The incidence of violence among male students was significantly higher than those of female students (chi2 = 329.89, P = 0.000). (2) Among male students who were victims of campus violence, the incidence rates of threat or blackmail, emotional abuse, physical assault, verbal sexual harassment, sexual assault were 18.03%, 13.97%, 10.77%, 0.85%, 0.48% respectively. Among female students who were victims of campus violence, the incidence rates were 3.64%, 5.84%, 1.38%, 1.33%, 1.13% respectively. The main source of the violence was from their schoolmates. (3) 10.40% of the male students reported they were perpetrators of campus violence in the last year, while 1.47% of the female students reported so. Schoolmates were the main subjects of their aggressive behaviors. (4) Among the college students who were victims of campus violence, logistic regression analysis revealed that smoking, drinking alcohol, frequently getting computer online were important risk factors. The OR values were 1.48, 2.96, 1.66 respectively. Among college students who were perpetrators of campus violence, the OR values were 2.92, 1.88, 2.09 respectively. CONCLUSION: Campus violence among college students was serious, suggesting that intervention measures should be taken.

China↗
PubMed2004

The Use of Antisense Oligonucleotides in Evaluating Survivin as a Therapeutic Target for Radiation Sensitization in Lung Cancer.

Elucidating the mechanism of over and under expression of proteins is critical in developing a better understanding of cancer. Multiple techniques are used to examine differential expression of proteins in cells and assess changes in protein expression in response to therapies such as radiation. Reduced expression can be caused by protein inactivation, mRNA instability, or reduced transcription. The following protocol was used to determine the mechanism for the reduced expression of an antiapoptotic factor, survivin, in normal tissues in response to radiation and the defect in cancer cells that prevents this reduction. We also examined ways to overcome survivin over expression in cancer cells in order to sensitize them to radiation. We will focus on the use of antisense oligonucleotides, cell cycle analysis, and luciferase reporter genes.

Journal Article↗
PubMed2004

XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer.

Survivin and XIAP are members of inhibitors of apoptosis (IAPs) family. They are upregulated in various malignancies. Inactivation of these molecules has resulted in chemosensitization. The purpose of this study was to determine whether inhibition of survivin, XIAP, or both enhances radiotherapy in a lung cancer model. Transient transfection of H460 cells with antisense oligonucleotides (ASOs) against either molecule has specifically reduced their expression, by Western analysis. Results from 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and clonogenic assays suggest that inhibition of survivin or XIAP greatly decreased cell survival following irradiation. A significantly increased number of apoptotic cells were detected when H460 cells were treated with either antisurvivin, anti-XIAP or both ASOs (P=0.03, 0.0003 and 0.01, respectively) plus irradiation. H460 xenografts that were treated with ASOs plus radiotherapy demonstrated growth delay beyond 15 days. Growth delay in the groups of combined treatment was greater than that in other groups. However, treatment with ASOs alone did not affect tumor growth delay in mice, but decreased the survival of H460 cells in culture. Antisense treatment did not cause any mortality or weight loss during the 32 days of study. These data suggest that inhibition of survivin or XIAP radiosensitizes H460 lung cancer cells by upregulating apoptosis and downregulating cell survival. Combination of radiotherapy and inhibition of survivin and XIAP through the antisense approach results in improved tumor control by radiotherapy in a mouse model of lung cancer.

Animals↗
PubMed2004

Survivin as a therapeutic target for radiation sensitization in lung cancer.

Expression of survivin is elevated in most malignancies, especially in radiation-resistant cell lines. In this study, we investigated how radiation affects survivin expression in primary endothelial cells as well as in malignant cell lines. We found that 3 Gy significantly reduced survivin protein level in human umbilical vein endothelial cells (HUVECs) but not in tumor cell lines. Flow cytometry studies suggest that the down-regulation of survivin is independent of cell cycle. In addition, survivin mRNA level was also down-regulatable by irradiation. However, it was abrogated by actinomycin D-mediated inhibition of gene transcription. Luciferase reporter gene assays suggest that irradiation suppressed the survivin promoter. p53 overexpression reduced survivin expression, but overexpression of a p53 mutant failed to abolish the radiation-induced down-regulation in HUVECs. Alteration of p53 status in Val138 lung cancer cell line also failed to restore the radiation-inducible down-regulation. Overexpression of survivin in 293 cells prevented apoptosis induced by irradiation and increased cell viability after irradiation. The inhibition of survivin using antisense oligonucleotides caused a significant decrease in cell viability of irradiated H460 lung cancer cells. These data suggest that radiation transcriptionally down-regulates survivin in HUVECs. This regulatory mechanism is defective in malignancies and is not mediated by p53. Survivin overexpression may lead to resistance to radiotherapy by inhibiting apoptosis and enhancing cell viability. The inhibition of survivin results in sensitization of H460 lung cancer cells to radiation. These studies suggest that survivin may be a target for cancer therapy.

DNA Damage↗
PubMed2004

Broad spectrum receptor tyrosine kinase inhibitor, SU6668, sensitizes radiation via targeting survival pathway of vascular endothelium.

PURPOSE: Recent studies have demonstrated radiosensitization by inhibiting receptor tyrosine kinases (RTKs). Irradiation activates RTKs and their downstream prosurvival molecule, Akt. In this study, we investigated the mechanism by which SU6668, an inhibitor of RTKs involved in angiogenic pathways, enhances effects of irradiation. METHODS AND MATERIALS: Western blots were used to determine Akt phosphorylation. Clonogenic assays were performed to determine endothelial survival after combination of SU6668 and irradiation. This combination therapy was also tested in mouse models with Lewis lung carcinoma or glioblastoma multiforme (GL261) for inhibition of tumor growth and tumor vasculature by examining tumor volume, tumor vascular window, and blood flow. RESULTS: We found that SU6668 inhibited the Akt activation inducible by irradiation. Clonogenic survival of endothelial cells was decreased after the combined therapy compared with radiotherapy alone. In vivo studies demonstrated reduction of tumor vasculature and blood flow. In addition, 21 Gy in 7 fractions given concurrently with SU6668 resulted in tumor growth delay compared to either treatment alone. CONCLUSION: These data suggest that the combination therapy was more effective in destroying tumor vasculature than either treatment alone. SU6668 augments tumor-suppressive effects of radiotherapy in Lewis lung carcinoma and GL261 xenographs, possibly through reducing the survival of tumor endothelium.

Animals↗
PubMed2004

Optimal multivariate matching before randomization.

Although blocking or pairing before randomization is a basic principle of experimental design, the principle is almost invariably applied to at most one or two blocking variables. Here, we discuss the use of optimal multivariate matching prior to randomization to improve covariate balance for many variables at the same time, presenting an algorithm and a case-study of its performance. The method is useful when all subjects, or large groups of subjects, are randomized at the same time. Optimal matching divides a single group of 2n subjects into n pairs to minimize covariate differences within pairs-the so-called nonbipartite matching problem-then one subject in each pair is picked at random for treatment, the other being assigned to control. Using the baseline covariate data for 132 patients from an actual, unmatched, randomized experiment, we construct 66 pairs matching for 14 covariates. We then create 10000 unmatched and 10000 matched randomized experiments by repeatedly randomizing the 132 patients, and compare the covariate balance with and without matching. By every measure, every one of the 14 covariates was substantially better balanced when randomization was performed within matched pairs. Even after covariance adjustment for chance imbalances in the 14 covariates, matched randomizations provided more accurate estimates than unmatched randomizations, the increase in accuracy being equivalent to, on average, a 7% increase in sample size. In randomization tests of no treatment effect, matched randomizations using the signed rank test had substantially higher power than unmatched randomizations using the rank sum test, even when only 2 of 14 covariates were relevant to a simulated response. Unmatched randomizations experienced rare disasters which were consistently avoided by matched randomizations.

Adult↗
PubMed2004

Radiation-guided drug delivery systems.

A primary limiting factor for cancer treatment is normal tissue toxicity. Targeted cancer treatment can potentially maximize cancer cure and minimize normal tissue toxicity. Physical energy can be used to activate inert oncologic drugs. X-rays have an advantage over other forms of physical energy because tissue penetration and precise localization can be achieved. Radiation can be used to control drug delivery through radiation-inducible gene therapy. Radiation-guided drug delivery systems involve the targeting of immunoconjugates to radiation-inducible neoantigens induced by irradiation of neoplasms. Magnetic fields can compliment these technologies by drawing magnetic particles containing oncologic drugs toward an externally applied magnetic field. The field of targeted drug delivery by use of external radiation fields will ultimately bring new delivery systems into clinical trials. This review highlights radiation-guided cancer drug delivery systems, at preclinical and clinical stages of development, to tumors and tumor blood vessels.

Animals↗
PubMed2004

Receptor tyrosine kinase inhibitors as anti-angiogenic agents.

Receptor tyrosine kinases (RTKs) and their ligands have been implicated in angiogenesis and current data suggest that they are potential cancer therapeutic targets. Split-kinase domain RTKs, including receptors for vascular endothelial growth factor receptor, platelet-derived growth factor and fibroblast growth factor, have important roles in tumor angiogenesis. RTK inhibitors targeting tumor microvasculature have shown promising results in preclinical studies, and use of these compounds as single agents, or in combination with other cytotoxic therapies, including radiation, is an area of active clinical investigation. Preclinical and clinical data from representative anti-angiogenic RTK inhibitors will be discussed in this review.

Angiogenesis Inhibitors↗
PubMed2004

[Biomechanical study of medical hard tissue adhesive bonding butterfly fracture fragment in middle part of fresh human tibia].

A medical hard tissue adhesive, octyl-a-cyanoacrylate, was tested in 6 fresh human tibiae. A 90 degrees butter-fly fracture fragment was made in the middle part of tibia by bandsaw. The compressive stress, torsional stress and angular deflection were assessed before and after osteoectomy respectively. After adhesive bonding, the compressive stress, torsional stress and angular deflection were tested again. The butterfly fracture fagment decreased the bending strength, torsion strength, yielding strength of tibia bone. In torsion test, the torque of tibia before osteoectomy is greater than bonded tibia, the bonded tibia is greater than that of the unbonded tibia. In compression test, before adhesive bonding broken, the compressive curve slope of tibia before osteoectomy is greater than that of bonded tibia, the bonded tibia is greater than that of the unbonded tibia. In angular deflection test before adhesive bonding of broken,the curve slope of tibia before osteoectomy is not different from that of bonded tibia (P>0.05), the slope the bonded tibia is greater than the slope of unbonded tibia(P<0.05). The elastic modulus, rigidity coefficient and moment of area inertia show no statistical difference between the bonded tibia and intact tibia. The used of medical hard tissue adhesive to bond the fracture fragment could improve the bending strength, torsion strength, yielding strength of tibia bone. In operation, it can reduce the soft tissue injury when the fracture fragment is being fixed, and this will benefit bone healing.

Biomechanical Phenomena↗
PubMed2003

[Reconstruction of large genomic segment coding for human immunoglobulin kappa chain by meiotic homologous recombination of yeast artificial chromosome].

Meiotic homologous recombination between overlapping yeast artificial chromosome (YAC) can be used to reconstruct larger genomic segment in vivo. We have screened CEPH and Olson human genomic YAC libraries and obtained two YAC clones containing the large genomic segments coding for partial human Ig kappa. In order to reconstruct whole gene cluster of human Ig kappa, two yeast cells containing the different YAC described over were mated and induced to undergo meiotic division and sporulation. Analyzing the results of PCR and Southern blotting, we obtained a clone containing a single recombinant YAC with 400 kb in length, which spans almost the entire gene cluster of human Ig kappa, including 32 V kappa, 5 J kappa, constant domain genes. Besides, we have improved and simplified the traditional method of meiotic recombination between overlapping YACs, and the results indicate the feasibility of this method to reconstruct any larger intact genomic segments.

Chromosomes, Artificial, Yeast↗
PubMedDate not supplied

E-cadherin promoter polymorphisms are not associated with the aggressiveness of prostate cancer in Caucasian patients.

BACKGROUND: -160C-->A and -347G-->GA polymorphisms in the promoter region decrease E-cadherin gene transcription. Decreased E-cadherin expression predicts poor outcome among patients with cancer. We sought to investigate whether -160C-->A and/or -347G-->GA polymorphisms were associated with the aggressiveness of prostate cancer. METHODS: TaqMan single nucleotide polymorphism genotyping assay (Applied Biosystems, Foster City, CA) was used to detect -160C-->A and -347G-->GA polymorphisms in deoxyribonucleic acid from the paraffin-embedded prostate tissues of 98 Caucasian patients. RESULTS: The genotype frequencies were -160C/C: 48% (47 of 98); -160C/A: 44% (43 of 98); -160A/A: 8% (8 of 98); -347G/G: 68% (67 of 98); -347G/GA: 28% (27 of 98); and -347GA/GA: 4% (4 of 98). Using the chi-square test, we found that the polymorphisms -160C-->A and -347G-->GA were not related to other clinical and pathologic parameters (i.e., age, prostate-specific antigen level, Gleason grade, and clinical stage) (P > 0.05). In combination analysis, there was no significant relationship between patients with both -160C/C and -347G/G, and these same parameters (P > 0.05). Using the log-rank test, we found no significant difference in relapse-free survival and overall survival between patients with -160C/C and those with -160A/C or -160A/A (P = 0.0764 and 0.2746, respectively), and also no significant difference between patients with -347G/G and those with -347GA/G or -347GA/GA (P = 0.9416 and 0.7367, respectively). There was also no significant difference in relapse-free survival and overall survival between patients with homozygosities of -160C/-347G and patients with other genotypes (P = 0.1418 and 0.2434, respectively). CONCLUSION: We conclude that E-cadherin -160C-->A and/or -347G-->GA polymorphisms are not associated with the aggressiveness of prostate cancer in Caucasian patients.

Adenocarcinoma↗