Search PubMed⌕ Search

Biomedical subjects

Liang Wang

Publications and source records attributed to Liang Wang.

At least 73 records · Page 4Linked to original sources
PubMed2005

[The development of auditory capability for infants after cochlear implantation].

OBJECTIVE: The purpose of this study is to analyze the auditory capability of infants before and after cochlear implantation by using IT-MAIS questionnaire. METHOD: Eighty-six prelingually deaf patients participated in this study. They received a cochlear implant at the age of 1 to 3 yr. The audiologists who were trained for the research used the IT-MAIS questionnaire. Audiologists asked for the parents' answers face to face and recorded all the information about the patient's spontaneous auditory behavioural responses including vocalization, behaviour, spontaneous alerting to sound and deriving meaning from sound. The evaluation was performed before operation and 1 month, 3 months, 6 months, 1 year after switch-on. RESULT: The scores of question 1 were significantly different between pre-operation and 1, 3, 6, 12 months after switch-on (P = 0.000, 0.000, 0.000, 0.000). The scores of question 2 were significantly different between pre-operation and 6, 12 months after switch-on (P = 0.000, 0.000). The scores of question 3 were significantly different between pre-operation and 3, 6, 12 months after switch-on (P = 0.001, 0.000, 0.000). The scores of question 4 were significantly different between pre-operation and 3, 6, 12 months after switch-on (P = 0.002, 0.000, 0.000). The scores of question 5 were significantly different between pre-operation and 1, 3, 6, 12 months after switch-on (P = 0.046, 0.00, 0.000, 0.000, 0.000). The scores of question 6 were significantly different between pre-operation and 3, 6, 12 months after switch-on (P = 0.037, 0.000, 0.000). The scores of question 7 were significantly different between pre-operation and 3, 6, 12 months after switch-on ( P = 0.000, 0.000, 0.000). The scores of question 8 were significantly different between pre-operation and 6, 12 months after switch-on (P = 0.001, 0.001). The scores of question 9 were significantly different between pre-operation and 3, 6, 12 months after switch-on ( P = 0.023, 0.000, 0.000). The scores of question 10 were significantly different between pre-operation and 12 months after switch-on (P = 0.048). CONCLUSION: Most of the patients showed no consistent response to sound in everyday life before implantation. After cochlear implantation, a significant increase in auditory capability occurred. The children demonstrated faster development of vocalization behaviour and spontaneous alerting to sound than deriving meaning from sound.

Audiometry, Speech↗
PubMed2005

[Study on solid phase extraction and spectrophotometric determination of uranium in water with 2-(2-quinolylazo)-5-dimthylaminophenol].

A new chromogenic reagent 2-(2-quinolylazo)-5-Dimthylaminophenol (QADMAP) was synthesized, and its structure was verified by elemental analysis, infrared spectrum, 1H nuclear magnetic resonance spectrum, mass spectrumand UV-spectrum. The color reaction of QADMAP with uranium was studied. In the presence of pH 7.8 buffer solution, when fluorin ion and TritonX-100 medium exist, QADMAP can react with uranium and fluorin to form a stable 1 : 1 : 1 stable complex [F- :QADMAP : U(VI)]. The molar absorptivity is 1.05 x 10(5) L x mol(-1) x cm(-1) at 590 nm. Beer's law is obeyed in range of 0-20 microg/10 mL. The uranium in samples can be enriched and separated by solid phase extraction with TBP resin cartridge. This method is applied to the determination of uranium in water sample. The relative standard deviations are 2.2%-3.6%, and the recoveries are 94%-105%.

Aza Compounds↗
PubMed2005

[Expressions of Axin and beta-catenin in non-small cell lung cancer].

OBJECTIVE: To investigate the protein expression of Axin and beta-catenin, the exon 3 mutation status of beta-catenin and their clinicopathological correlations in non-small cell lung cancer (NSCLC). METHODS: A total of 100 NSCLC samples and their corresponding normal lung tissues were obtained from the patients undergoing surgery in the First Affiliated Hospital of China Medical University between 2001 and 2003. Protein expressions of Axin and beta-catenin were detected by immunohistochemistry. DNA sequence alterations of exon 3 of beta-catenin were investigated by polymerase chain reaction (PCR) and direct sequencing. RESULTS: A reduced membranous expression rate of beta-catenin was observed in 80.0% of the cases (80/100) along with a nuclear expression rate of 26.0% (26/100). There was a significant difference in beta-catenin expression between well and poorly differentiated NSCLCs. Well to moderately differentiated NSCLCs showed a reduced expression rate of 70.0% (35/50), in contrast to 90.0% (45/ 50) in poorly differentiated tumors (P = 0.012). Reduced beta-catenin expression rate was 87.3% (48/55) in cases with lymph node metastasis, in contrast to 71.1% (32/45) in cases without lymph node metastasis (P = 0.044). The positive expression rate of Axin was 48.0% (48/100). Well to moderately differentiated NSCLCs demonstrated a 60.0% positive expression rate of Axin (30/50), much higher than poorly differentiated tumors [36.0% (18/50), P = 0.016]. The positive expression rate of Axin in beta-catenin nuclear expressed NSCLCs was 15.4% (4/26), much lower than cases without beta-catenin nuclear expression [59.5% (44/74), P < 0.001]. Axin nuclear expression was found in two cases in this study, suggesting that it may function as a nuclear-cytoplasmic shuttling protein. PCR and direct sequencing failed to reveal any exon 3 mutation of beta-catenin gene. CONCLUSIONS: The reduced membranous expression of beta-catenin is associated with poorly differentiated and lymph node positive NSCLCs. The expression of Axin is inversely correlated with the degree of tumor differentiation and nuclear expression of beta-catenin. The exon 3 mutations do not contribute to the abnormal protein expression of beta-catenin in NSCLCs.

Adult↗
PubMed2005

[Edit and evaluation of Mandarin sentence materials for Chinese speech audiometry].

OBJECTIVE: To edit the sentence list for mandarin speech test materials (MSTM) and to test their equivalence in order to use the list as routine clinical speech tests for evaluation of cochlear implants and hearing aids in different stages of the intervention and rehabilitation. METHODS: Firstly, two groups of professionals were set up: one for establishing the principles of the edit, another for experiments. The criteria to guide the selection of spoken sentences were as following: (1) suitable for everyday speech audiometry, esp. clinically usage; (2) a normal sampling of everyday spoken sentences in mandarin. Totally, 300 sentences were selected in 30 lists for the experiment. The record cassette was used by a male speaker. The college students (54 persons,54 ears) with normal hearing participated in the equivalence test. Two statistic methods were used for equivalence analysis. RESULTS Through speech tests and statistic analysis, 2 sets with 29 lists (290 sentences) were selected as our equivalent lists for further evaluation and clinical trial. CONCLUSIONS: By setting up the strict criteria of selecting sentences, speech test method and statistic analysis, 2 sets of 29 lists (290) sentences were chosen as our speech evaluation materials, but it was necessary for further analysis in different laboratories and clinics. The sentence lists should also get used for hearing impaired subjects, hearing aid users and cochlear implant recipients.

Adult↗
PubMed2005

[Re-operation for thyroid carcinoma].

OBJECTIVE: To evaluate the results of re-operation of thyroidectomy for patients of thyroid carcinoma. METHODS: 268 patients of thyroid carcinoma received completion thyroidectomy were retrospectively reviewed from 1984 to 2000. There were 59 males and 209 female cases. 256 cases had received nodule enucleating or partial thyroidectomy in other hospitals and 12 cases had unilateral subtotal thyroidectomy in this hospital. The types of reoperation were: Total thyroidectomy for bilateral thyroid carcinoma (6 cases); expand isthmectomy for isthmus carcinoma (1 case). Lobectomy plus isthmectomy for unilateral disease (261) Simultaneous neck dissections were performed in 196 cases. Among them, 94 cases had classical neck dissection, 102 cases had modified neck dissection. RESULTS: Pathological results confirmed that there were 78 cases with residual thyroid carcinoma. The rate of residual carcinoma was 29. 1% (78/268). There were 95 cases with lymphnode metastasis. The rate of lymphnode metastasis was 48.5% (95/196). The rate of recurrent laryngeal nerve injury was 1.1% (3/268). The 5-year and 10-year survival rates of patients were 94. 0% (251/267) and 85. 2% (127/149) respectively. CONCLUSIONS: The residual carcinoma of completing thyroidectomy was high. Therefore re-operations of thyroid in selected cases were necessary.

Adolescent↗
PubMed2004

A novel pH-dependent gradient-release delivery system for nitrendipine II. Investigations of the factors affecting the release behaviors of the system.

Nitrendipine, a dihydropyridine calcium antagonist, was used as a poorly water-soluble model drug. To improve its dissolution rate and extend the therapeutic period in vivo as well, a novel pH-dependent gradient-release drug delivery system for nitrendipine having a solid dispersed matrix structure was developed. Four factors, i.e. the amount of excipients, the pH of the dissolution medium, the rotating speed of the paddle of the dissolution apparatus and the particle size of the microspheres, all of which affect the drug-release behavior of the pH-dependent microspheres of the system were investigated in detail. The release profiles of the pH-dependent drug delivery system under simulated gastrointestinal tract pH conditions were also investigated. The results showed that the release rate of drug from the microspheres increased on increasing the amount of respective pH-dependent polymers formulated. Due to the fact that the active drug was incorporated in pH-dependent polymers and was present in a solid dispersion state in the microspheres, the release rate of the drug from the microspheres depended on the dissolution rate of the polymers, which was mainly influenced by the pH of dissolution medium, whereas the rotating speed of the paddle and the particle size of the microspheres had only a relatively minor effect. The release behavior of the system under simulated gastrointestinal tract conditions exhibited obvious gradient-release characteristics, showing that the release rate of the active drug could be controlled efficiently before the microspheres reached the appropriate region of the gut for absorption. These findings suggest that the pH-dependent drug delivery system could be fabricated by using present microspheres.

Chemistry, Pharmaceutical↗
PubMed2004

Androgen receptor (AR) NH2- and COOH-terminal interactions result in the differential influences on the AR-mediated transactivation and cell growth.

Early reports showed that androgen receptor (AR) NH2- and COOH-terminal (N-C) interaction was important for full AR function. However, the influence of these interactions on the AR in vivo effects remains unclear. Here we tested some AR-associated peptides and coregulators to determine their influences on AR N-C interaction, AR transactivation, and AR coregulator function. The results showed that AR coactivators such as ARA70N, gelsolin, ARA54, and SRC-1 can enhance AR transactivation but showed differential influences on the N-C interaction. In contrast, AR corepressors ARA67 and Rad9 can suppress AR transactivation, with ARA67 enhancing and Rad9 suppressing AR N-C interaction. Furthermore, liganded AR C terminus-associated peptides can block AR N-C interaction, but only selective peptides can block AR transactivation and coregulator function. We found all the tested peptides can suppress prostate cancer LNCaP cell growth at different levels in the presence of 5alpha-dihydrotestosterone, but only the tested FXXLF-containing peptides, not FXXMF-containing peptides, can suppress prostate cancer CWR22R cell growth. Together, these results suggest that the effects of AR N-C interactions may not always correlate with similar effects on AR-mediated transactivation and/or AR-mediated cell growth. Therefore, drugs designed by targeting AR N-C interaction as a therapeutic intervention for prostate cancer treatment may face unpredictable in vivo effects.

Amino Acid Motifs↗
PubMed2004

A novel pH-dependent gradient-release delivery system for nitrendipine: I. Manufacturing, evaluation in vitro and bioavailability in healthy dogs.

A novel pH-dependent gradient-release delivery system was developed by mixing three kinds of pH-dependent microspheres. Nitrendipine, a dihydropyridine calcium antagonist, was selected as the poorly water-soluble model drug. To obtain gradient-release of the active drug in the stomach, duodenum and lower segment of the small intestine, respectively, three kinds of pH-dependent polymers, i.e. Acrylic resins Eudragit E-100, Hydroxypropylmethylcellulose phthalate and Hydroxypropylmethylcellulose acetate succinate, were formulated to produce the microspheres, which dissolve at an acid condition, the pH of > or = 5.5 and > or = 6.5, respectively. The quasi-emulsion solvent diffusion method was employed in the manufacturing process for the microspheres. All three kinds of microspheres had a highly spherical shape and high incorporation efficiency (>91.0%). The particle sizes were mainly affected by the agitation speed and temperature of the manufacturing process. The results of X-ray diffraction suggested that nitrendipine in the microspheres was molecularly dispersed in an amorphous state. The drug dissolution behavior of the system under the simulated gastrointestinal pH conditions revealed obvious gradient-release characteristics. The dissolution profiles and content of the systems stored at a temperature of 40 degrees C and a relative humidity of 75% were unchanged during a 3-month period of accelerating storage conditions. The results of the bioavailability testing in six healthy dogs suggested that the pH-dependent gradient-release delivery system could improve efficiently the uptake of the poorly water-soluble drug and prolong the Tmax value in vivo.

Acrylates↗
PubMed2004

BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells.

BACKGROUND: BAK (Bcl-2 homologous antagonist/killer) is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. METHODS: Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. RESULTS: BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45), or in p53 mutant-type (MKN-28) gastric cancer cells. CONCLUSIONS: The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies.

Apoptosis↗
PubMed2004

The role of preoperative endorectal magnetic resonance imaging in the decision regarding whether to preserve or resect neurovascular bundles during radical retropubic prostatectomy.

BACKGROUND: Because the recovery of erectile function and the avoidance of positive surgical margins are important but competing outcomes, the decision to preserve or resect a neurovascular bundle (NVB) during radical prostatectomy (RP) should be based on the most accurate information concerning the location and extent of the tumor. In the current study, the authors determined the incremental value of endorectal magnetic resonance imaging (eMRI) in making this decision. METHODS: eMRI was performed in 135 patients preoperatively. For each NVB, tumor extension to the NVB and the need for NVB resection was judged by a surgeon on a scale from 1 (definite preservation) to 5 (definite resection) before and after reviewing eMRI with a radiologist. Histopathologic findings were used as the standard of reference. The value of eMRI was assessed using binormal receiver operating characteristic (ROC) analysis adjusted for multiple observations per patient, and a mixed effects ordinal regression model was used for risk stratification. RESULTS: Histopathologic examination determined that NVB resection was warranted in 44 of 270 NVBs (16%) because of posterolateral extracapsular extension (n = 29), positive surgical margins (n = 7), or both (n = 8). The areas under the ROC curves (AUC) were 0.741 for pre-MRI and 0.832 for post-MRI surgical planning (P < 0.01). MRI findings suggested altering the surgical plan in 39% of NVBs (106 of 270 NVBs). When the surgeon judged that the NVB resection was definitely not necessary (165 NVBs), MRI confirmed that decision in 138 NVBs (84%); the concordant decision was correct in 96% of the cases (133 of 138 NVBs). In 36 high-risk patients (> or = 75% probability of extracapsular extension), MRI findings changed the surgical plan for 28 NVBs (78%); the change was found to be appropriate in 26 cases (93%). CONCLUSIONS: MRI was found to significantly improve the surgeon's decision to preserve or resect the NVB during radical prostatectomy.

Adult↗
PubMed2004

Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells.

BACKGROUND: Neuroendocrine (NE) differentiation in prostate cancer has been suggested to be one of the early events in the development of androgen independence. In the human prostate cancer LNCaP cell line, treatment with interleukin-6 (IL-6) induces NE-like differentiation, which is similar to the phenomena observed in advanced stages of prostate cancer progression. In this study, we investigate how androgen plays a role in IL-6-mediated NE differentiation in LNCaP cell line. METHODS: Western blot, co-immunoprecipitation (co-IP), and GST pull-down assays were performed to detect the protein expression and protein-protein interaction. PI3K kinase assay was used to measure PI3K activity. RESULTS: Addition of androgen blocks IL-6-mediated PI3K activation and NE differentiation in LNCaP cells. In vivo and in vitro protein interaction assays suggested that androgen receptor (AR) can directly interact with IL-6 transducer gp130. In addition, androgen treatment enhances the interaction between AR and gp130, interrupts the IL-6-induced gp130-mediated PI3K activation, which may lead to inhibition of IL-6-mediated NE differentiation in LNCaP cells. CONCLUSIONS: Our results suggest androgen and AR can regulate IL-6-mediated LNCaP cell NE differentiation via directly modulating the IL-6-PI3K pathway.

Blotting, Western↗
PubMed2004

Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells.

Androgens play important roles in the growth of normal prostate and prostate cancer via binding to the androgen receptor (AR). In addition to androgens, AR activity can also be modulated by selective growth factors and/or kinases. Here we report a new kinase signaling pathway by showing that AR transactivation was repressed by wild type glycogen synthase kinase 3beta (GSK3 beta) or constitutively active S9A-GSK3 beta in a dose-dependent manner. In contrast, the catalytically inactive kinase mutant GSK3 beta showed little effect on the AR transactivation. The suppression of AR transactivation by GSK3 beta was abolished by the GSK3 beta inhibitor lithium chloride. The in vitro kinase assay showed that GSK3 beta prefers to phosphorylate the amino terminus of AR that may lead to the suppression of activation function 1 activity located in the NH(2)-terminal region of AR. GSK3 beta interrupted the interaction between the NH(2) and COOH termini of AR, and overexpression of the constitutively active form of GSK3 beta, S9A-GSK3 beta, reduced the androgen-induced prostate cancer cell growth in stably transfected CWR22R cells. Together, our data demonstrated that GSK3 beta may function as a repressor to suppress AR-mediated transactivation and cell growth, which may provide a new strategy to modulate the AR-mediated prostate cancer growth.

Animals↗
PubMed2004

Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer.

Androgen receptor (AR)-associated coregulator 70 (ARA70) was the first identified AR coregulator. However, its molecular mechanism and biological relevance to prostate cancer remain unclear. Here we show that ARA70 interacts with and promotes AR activity via the consensus FXXLF motif within the ARA70-N2 domain (amino acids 176-401). However, it does not promote AR activity via the classic LXXLL motif located at amino acids 92-96, although this classic LXXLL motif is important for ARA70 to interact with other receptors, such as PPARgamma. The molecular mechanisms by which ARA70 enhances AR transactivation involve the increase of AR expression, protein stability, and nuclear translocation. Furthermore, ARA70 protein is more frequently detected in prostate cancer specimens (91.74%) than in benign tissues (64.64%, p < 0.0001). ARA70 expression is also increased in high-grade prostate cancer tissues as well as the hormone-refractory LNCaP xenografts and prostate cancer cell lines. Because ARA70 can promote the antiandrogen hydroxyflutamide (HF)-enhanced AR transactivation, the increased ARA70 expression in hormone-refractory prostate tumors may confer the development of HF withdrawal syndrome, commonly diagnosed in patients with the later stages of prostate cancer. Because ARA70-N2 containing the AR-interacting FXXLF motif without coactivation function can suppress HF-enhanced AR transactivation in the hormone-refractory LNCaP cells, using the ARA70-N2 inhibitory peptide at the hormone refractory stage to battle the HF withdrawal syndrome may become an alternative strategy to treat prostate cancer.

Amino Acid Sequence↗
PubMed2004

Prostate cancer: incremental value of endorectal MR imaging findings for prediction of extracapsular extension.

PURPOSE: To assess the incremental value of endorectal magnetic resonance (MR) imaging findings in addition to clinical variables for prediction of extracapsular extension (ECE) in patients with prostate cancer. MATERIALS AND METHODS: In this cohort study, 344 consecutive patients with biopsy-proved prostate cancer underwent endorectal MR imaging prior to surgery; 216 of these patients also underwent MR spectroscopic imaging. MR images were interpreted by 10 attending radiologists. The likelihood of ECE was scored retrospectively on the basis of MR imaging reports. Clinical variables included serum prostate-specific antigen (PSA) level, Gleason score, clinical stage of tumor, greatest percentage of cancer in all core biopsy specimens, percentage of cancer-positive core specimens in all core biopsy specimens, and presence of perineural invasion. For data analysis, receiver operating characteristic (ROC) curves and univariate and multivariate logistic regression analyses were used. Jackknife analysis was used for prediction of probability from a model that included clinical variables as tested comparatively with a model that included the clinical variables plus endorectal MR imaging findings. A difference with P <.05 was considered significant. RESULTS: At univariate analysis, all variables were associated with ECE. At ROC univariate analysis, endorectal MR imaging findings had the largest area under the ROC curve. At multivariate analysis, serum PSA level, percentage of cancer in all core biopsy specimens, and endorectal MR imaging findings (P =.001, P =.001, and P <.001, respectively) were predictors of ECE. Areas under ROC curve for two models, with and without endorectal MR imaging findings, were 0.838 and 0.772, respectively (P =.022). CONCLUSION: A model containing endorectal MR imaging findings has a significantly larger area under the ROC curve than a model containing only clinical variables; thus, endorectal MR imaging findings add incremental value in the prediction of ECE.

Adult↗
PubMed2004

Prostate cancer: detection of extracapsular extension by genitourinary and general body radiologists at MR imaging.

PURPOSE: To determine whether predictive value of endorectal magnetic resonance (MR) imaging findings in detection of prostate cancer extracapsular extension (ECE) is significantly affected by the reader's subspecialty experience. MATERIALS AND METHODS: In this cohort study, 344 consecutive patients with biopsy-proved prostate cancer underwent endorectal MR imaging followed by surgery. Likelihood of ECE described in MR imaging reports was compared with clinical predictor variables. ECE was determined from the final pathologic report on specimens resected at surgery. Readers of MR images were classified into genitourinary MR imaging radiologists (n = 4) and general body MR imaging radiologists (n = 6). For data analysis, Wilcoxon rank sum and chi(2) tests, as well as receiver operating characteristic (ROC) curves and univariate and multivariate logistic regression analyses, were used. A difference with P <.05 was considered significant. RESULTS: Univariate analysis results demonstrated that all predictors except clinical stage were significantly associated with detection of ECE in both groups of readers (P <.05). In the genitourinary MR imaging radiologist group of patients, area under the ROC curve for endorectal MR imaging findings (0.833) was larger than areas under the curves for all other predictors (0.566-0.701). In the general body MR imaging radiologist group of patients, area under the ROC curve for endorectal MR imaging findings (0.646) was not larger than areas under the curves for all other predictors (0.582-0.793). Results of multivariate analysis of two models, one with all predictors and another with all predictors except endorectal MR imaging findings, demonstrated a significant increase in area under the ROC curve with endorectal MR images interpreted by genitourinary MR imaging radiologists (P =.019 and.31, respectively). CONCLUSION: Endorectal MR imaging findings are significant predictors for detection of ECE when MR images are interpreted by genitourinary radiologists experienced with MR imaging of the prostate.

Adult↗
PubMed2004

MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps.

BACKGROUND & AIMS: MYH-associated polyposis is a recently described disease that is characterized by multiple colorectal adenomas and a recessive pattern of inheritance. Individuals with MYH-associated polyposis have biallelic mutations in MYH, a base excision repair gene, and are negative for germline mutations in the APC gene. In this study, the 2 most prevalent MYH mutations in white persons, Y165C and G382D, were analyzed for their presence in 984 subjects selected from 3 groups: 400 undergoing screening colonoscopy and found to have 0-3 polyps, 444 with colorectal cancer (CRC), and 140 referred for APC mutation analysis in which a germline mutation was not identified. METHODS: Genotyping for Y165C and G382D was performed by Pyrosequencing. RESULTS: Biallelic mutations for Y165C and/or G382D were not found in any of those undergoing screening colonoscopy with 0-3 polyps (n = 400), in those APC-negative patients with <20 adenomatous polyps (n = 26), or in those with CRC who were older than 50 years (n = 328). Furthermore, these 2 MYH mutations were not found among patients whose tumors showed the presence of defective DNA mismatch repair (n = 62). However, the presence of biallelic germline MYH mutations correlated with the presence of >or=20 adenomatous polyps. Interestingly, 2 of the 116 individuals with CRC diagnosed at 50 years of age or younger also presented with biallelic germline mutations in MYH. CONCLUSIONS: These data suggest that screening of MYH should be considered not only in patients with multiple polyps but also in patients with early-onset CRC.

Adenomatous Polyposis Coli↗
PubMed2004

Human checkpoint protein hRad9 functions as a negative coregulator to repress androgen receptor transactivation in prostate cancer cells.

Positive responses to combined androgen elimination therapy and radiation therapy have been well documented in the treatment of prostate cancer patients. The detailed mechanisms how androgen-androgen receptor (AR) cross talks to the radiation-related signal pathways, however, remain largely unknown. Here we report the identification of hRad9, a key member of the checkpoint Rad protein family, as a coregulator to suppress androgen-AR transactivation in prostate cancer cells. In vivo and in vitro interaction assays using Saccharomyces cerevisiae two-hybrid, mammalian two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation methods prove that AR can interact with the C terminus of hRad9 via its ligand binding domain. The FXXLF motif within the C terminus of hRad9 interrupts the androgen-induced interaction between the N terminus and C terminus of AR. This interaction between AR and hRad9 may result in the suppression of AR transactivation, demonstrated by the repressed AR transactivation in androgen-induced luciferase reporter assay and the reduced endogenous prostate-specific antigen expression in Western blot assay. Addition of small interfering RNA of hRad9 can reverse hRad9 suppression effects, which suggests that hRad9 functions as a repressor of AR transactivation in vivo. Together, our data provide the first linkage between androgen-AR signals and radiation-induced responses. Further studies of the influence of hRad9 on prostate cancer growth may provide potential new therapeutic approaches.

Amino Acid Motifs↗