Peiguo G Chu

City of Hope National Medical Center, Duarte, California, United States

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Publications (100)448.91 Total impact

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    ABSTRACT: Ribonucleotide reductase (RR) is an essential enzyme involved in DNA synthesis. We hypothesized that RR subunit M2 (RRM2) might be a novel prognostic and predictive biomarker for estrogen receptor (ER)-negative breast cancers.
    BMC Cancer 09/2014; 14(1):664. · 3.33 Impact Factor
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    ABSTRACT: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in patients with refractory gastrointestinal cancers.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 07/2014;
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    ABSTRACT: Cancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. miR-105 can be detected in the circulation at the premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer.
    Cancer cell 04/2014; 25(4):501-15. · 25.29 Impact Factor
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    ABSTRACT: Although breast cancer frequently metastasizes to the bones and brain, rarely breast cancer patients may develop isolated liver metastasis. There is increasing data that anti-HER2 targeted therapy in conjunction with systemic chemotherapy may lead to increased rates of pathologic complete response in the primary breast cancer. However, little is known about its effects on metastatic liver disease. We report the treatment of a 54-year-old female who was diagnosed with HER2-positive invasive ductal carcinoma and synchronous breast cancer liver metastasis (BCLM). The patient underwent eight cycles of standard docetaxel with two anti-HER2 targeted agents, trastuzumab and pertuzumab. Subsequent radiographic imaging demonstrated complete radiographic response in the primary lesion with an approximate 75% decrease in the liver metastasis. After informed consent the patient underwent modified radical mastectomy that revealed pathologic complete response. Re-staging demonstrated no new disease outside the liver and a left hepatectomy was performed for resection of BCLM. Final pathologic examination revealed no residual malignant cells in the liver specimen, indicating pathologic complete response. Herein, we discuss the anti-HER2 targeted agents trastuzumab and pertuzumab and review the data on dual HER2 antagonism for HER2-positive breast cancer and the role of surgical resection of BCLM. The role of targeted agents for metastatic HER2-positive breast cancer is under active clinical trial investigation and we await the maturation of trial results and long-term survival data. Our results suggest that these agents may also be effective for producing considerable pathologic response in patients with BCLM.
    BMC Cancer 04/2014; 14(1):242. · 3.33 Impact Factor
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    ABSTRACT: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b microRNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT. Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, RT-PCR, and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1-/-) were investigated by antisense inhibition and ectopic overexpression studies. The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = -0.34, P < 0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3% (15/18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells. Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of AT/RT patients.
    Clinical Cancer Research 01/2014; · 7.84 Impact Factor
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    ABSTRACT: Rare cases of Merkel cell carcinoma have been encountered in lymph nodes with unknown extranodal primary, which exhibit similar morphologic and immunophenotypic features to those in primary cutaneous Merkel cell carcinomas. However, it is uncertain whether the nodal Merkel cell carcinoma is a primary tumor of the lymph node or represents a metastasis from an occult or regressed extranodal lesion. To establish an accurate diagnosis of the nodal Merkel cell carcinoma can be challenging because of significant morphologic mimics, including lymphoblastic lymphoma and metastatic small cell carcinoma. Moreover, there is no consensus for a diagnostic term, and many different terms have been used, which can be confusing and may not fully reflect the nature of nodal Merkel cell carcinoma. In this study, we investigated the detailed clinicopathologic features of 22 nodal Merkel cell carcinomas, with comparison to 763 primary cutaneous cases retrieved from the literature. Overall, the nodal and cutaneous Merkel cell carcinomas shared similar clinical presentations, morphologic spectrum, and immunophenotype; both were mostly seen in elderly male with a typical neuroendocrine morphology. Most of cases expressed CK20, synaptophysin, and chromogranin A; and PAX5 and TdT were also positive in majority of cases. However, nodal Merkel cell carcinomas had a significantly lower association with Merkel cell polyomavirus than cutaneous cases (31% vs 76%, P=0.001). Therefore, these two entities may arise from overlapping but not identical biological pathways. We also recommend the use of the diagnostic term 'Merkel cell carcinoma of lymph node' to replace many other names used.Modern Pathology advance online publication, 10 January 2014; doi:10.1038/modpathol.2013.250.
    Modern Pathology 01/2014; · 5.25 Impact Factor
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    ABSTRACT: To investigate the prognostic significance of ribonucleotide reductase small subunit M2 (RRM2) in low- and intermediate-risk prostate cancer (PCa). A retrospective outcome study was conducted on 164 eligible PCa samples from the City of Hope (n = 90) and the Taipei Medical University (n = 74). The RRM2 protein levels were detected by immunohistochemistry. Biochemical recurrence was assessed using Kaplan-Meier and Cox proportional hazard analyses. Cell invasion assays, Ras/Raf, and matrix metallopeptidase 9 activities were determined to evaluate the role of RRM2 on invasiveness of PCa. Expression of RRM2 was significantly increased in patients with higher Gleason score, who had advanced T stage, and who were margin/capsule positive (P<0.05). Analysis revealed that the expression of RRM2 positively associated with biochemical recurrence of PCa in the City of Hope set (hazard ratio = 5.26; 95% CI 1.50-24.71) and the Taipei Medical University set (hazard ratio = 2.55; 95% CI 1.30-9.22). In stratification analysis, RRM2 was significantly correlated with poor outcome in patients with lower-risk PCa, including those with Gleason score 4 to 7, margin(-), capsule(-), and stage T1-T2. In patients with Gleason score 4 to 7, the risk of recurrence was proportional to RRM2 protein levels. The prognostic performance of RRM2 was superior to that of pathoclinical factors, including margin/capsule status and T stage. An in vitro study demonstrated that RRM2 could promote tumor invasion activities in PCa cell lines. Suppression of RRM2 reduced the Ras/Raf and matrix metallopeptidase 9 activities. RRM2 plays a critical role in proliferation and invasion of PCa. Adding RRM2 as a biomarker in clinical assessments may increase model precision in predicting recurrence in patients with low-risk PCa.
    Urologic Oncology 01/2014; 32(1):51.e9-51.e19. · 3.65 Impact Factor
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    ABSTRACT: Cancer radiotherapy may be immunogenic, but it is unclear why its immunogenic effects are rarely sufficient to prevent tumor recurrence. Here we report a novel Toll receptor-9 (TLR9)-dependent mechanism that initiates tumor regrowth after local radiotherapy. Systemic inhibition of TLR9, but not TLR4, delayed tumor recurrence in mouse models of B16 melanoma, MB49 bladder cancer and CT26 colon cancer after localized high-dose tumor irradiation. Soluble factors in the microenvironment of regressing tumors triggered TLR9 signaling in freshly recruited myeloid cells appearing within four days of radiotherapy. The tumorigenic effects of TLR9 depended on MyD88/NF-κB-mediated upregulation of IL-6 expression, which in turn resulted in downstream activation of Jak/STAT3 signaling in myeloid cells. By comparing global gene expression in wild-type, TLR9- or STAT3-deficient myeloid cells derived from irradiated tumors, we identified a unique set of TLR9/STAT3-regulated genes involved in tumor-promoting inflammation and re-vascularization. Blocking STAT3 function by two myeloid-specific genetic strategies corrected TLR9-mediated cancer recurrence after radiation therapy. Our results suggest that combining localized tumor irradiation with myeloid cell-specific inhibition of TLR9/STAT3 signaling may help eliminate radiation-resistant cancers.
    Cancer Research 10/2013; · 9.28 Impact Factor
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    ABSTRACT: Background Preclinical studies have demonstrated that low-dose hydroxyurea (HU) enhances the cytotoxic effects of gemcitabine on human cancer cells; however, the combination has not been well studied on patients with recurrent, locally persistent head and neck squamous cell carcinomas (HNSCC). Additionally, the potential biomarkers to predict the response of HNSCC to the regimen remain largely unknown. Methods Twenty-two HNSCC patients underwent two-day HU (500 mg/m2, day 1 and 8) and gemcitabine (500 mg/m2, day 2 and 9) infusions every 21 days for a median of two (1–12) cycles until disease progression or adverse effects prohibited further therapy. RNA from pre-therapy tissues was subjected to cDNA microarray analysis to identify differentially expressed genes between stable and progressive disease. Validation of selected genes was performed by quantitative RT-PCR and immunohistochemistry.To further investigate the impact of growth arrest and DNA-damage-inducible protein alpha (GADD45α)on cellular sensitivity to the combination of HU and gemcitabine, GADD45α was over expressed in human oropharyngeal carcinoma KB cells. Results Ten patients displayed partial remission and/or stable disease, while nine patients displayed progressive disease. The progression free survival for stable disease was 5.88 months and the median overall survival was 12.4 months, while the progression free survival and the median overall survival for all patients were 1.71 and 7.23 months, respectively. A set of 112 genes was differentially expressed between stable and progressive disease. mRNA expression of c-Fos, BCL2/adenovirus E1B 19 kDa-interacting protein 3, paired-like homeodomain 1 and phosphoglycerate kinase 1 was more highly expressed in progressive disease, while mRNA and protein expressin of GADD45α and GADD45γ were significantly decreased in progressive disease in stable disease. Moreover, over expression of GADD45α sensitized KB cells to the combination of HU and gemcitabine. Conclusions The combination of HU and gemcitabine may be useful in HNSCC control with reasonable tolerance and toxicity. Based on gene expression profiles, a subset of patients may be potentially identified to gain increased treatment benefits.
    Head & Neck Oncology 02/2013; 5(3):25. · 3.13 Impact Factor
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    ABSTRACT: Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown. Herein, we first comparatively examined the amplification and expression of FRS2 with CDK4 and MDM2 in dedifferentiated liposarcoma (DDLS) and undifferentiated high-grade pleomorphic sarcoma (UHGPS). Amplification and expression of the three genes were identified in 90% to 100% (9-11 of 11) of DDLS, whereas that of FRS2, CDK4, and MDM2 were observed in 55% (41 of 75), 48% (36 of 75), and 44% (33/75) of clinically diagnosed UHGPS, suggesting that these "UHGPS" may represent DDLS despite lacking histologic evidence of lipoblasts. Immunohistochemical analysis of phosphorylated FRS2 protein indicated that the FGFR/FRS2 signaling axis was generally activated in about 75% of FRS2-positive high-grade liposarcomas. Moreover, we found that FRS2 and FGFRs proteins are highly expressed and functional in three high-grade liposarcoma cell lines: FU-DDLS-1, LiSa-2, and SW872. Importantly, the FGFR selective inhibitor NVP-BGJ-398 significantly inhibited the growth of FU-DDLS-1 and LiSa-2 cells with a concomitant suppression of FGFR signal transduction. Attenuation of FRS2 protein in FU-DDLS-1 and LiSa-2 cell lines decreased the phosphorylated extracellular signal-regulated kinase 1/2 and AKT and repressed cell proliferation. These findings indicate that analysis of FRS2 in combination with CDK4 and MDM2 will more accurately characterize pathologic features of high-grade liposarcomas. Activated FGFR/FRS2 signaling may play a functional role in the development of high-grade liposarcomas, therefore, serve as a potential therapeutic target. Cancer Res; 73(4); 1-10. ©2012 AACR.
    Cancer Research 02/2013; · 9.28 Impact Factor
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    ABSTRACT: : The standard treatment for locally advanced rectal cancer is preoperative cheimoradiation and total mesorectal excision. After surgery, tumors are classified according to the depth of tumor invasion, nodal involvement, and tumor regression grade. However, these staging systems do not provide information about the distribution of residual cancer cells within the bowel wall. : This study aimed to determine the distribution of residual cancer cells in each layer of the bowel wall in rectal cancer specimens. : This was a secondary analysis of data from a prospective phase II study. : This study was performed in a multi-institutional setting. : Included were 153 patients with stage II or stage III rectal cancer. : Patients were treated with chemoradiation and surgery. The surgical specimen tumor tissue was analyzed, and the distribution of residual cancer cells in each layer of the bowel wall was determined. : Statistical analysis was used to examine the correlation of residual cancer cells in each layer of the bowel wall with the clinical/pathologic stage and tumor regression grade. : Forty-two of 153 (27%) patients had complete response in the bowel wall (ypT0). Of the remaining 111 patients who had residual cancer cells, 5 (3%) were ypTis, 12 (8%) were ypT1, 41 (27%) were ypT2, 50 (33%) were ypT3, and 3 (2%) were ypT4. Of the 94 patients with ypT2-4 tumors, 12 (13%) had cancer cells in the mucosa, and 53 (56%) had cancer cells in the submucosa; 92 (98%) had cancer cells in the muscularis propria. Pretreatment cT correlated with the distribution of residual cancer cells. Tumor regression grade was not associated with the distribution of residual cancer cells after chemoradiation. : Patients received different chemotherapy regimens. : Residual cancer cells in rectal cancer specimens after chemoradiation are preferentially located close to the invasive front. This should be considered when designing strategies to diagnose complete pathologic response and when investigating the mechanisms of tumor resistance to chemoradiation.
    Diseases of the Colon & Rectum 02/2013; 56(2):142-9. · 3.34 Impact Factor
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    ABSTRACT: Immunohistochemical expression of napsin A in primary pulmonary mucinous tumors is not well established. Napsin A immunoreactivity was evaluated in 43 mucin-producing adenocarcinomas of the lung consisting of 18 tumors formerly classified as mucinous bronchioloalveolar carcinoma, 15 colloid adenocarcinomas, 5 solid predominant adenocarcinomas with mucin production, and 5 adenocarcinomas with signet ring cell features, as well as in 25 extrapulmonary mucinous adenocarcinomas of different anatomic sites. Immunohistochemical expression of thyroid transcription factor 1 (TTF-1) was also compared. Thirty-three percent of mucinous lung tumors exhibited positive immunoreactivity for napsin A, whereas 42% expressed TTF-1. All 25 extrapulmonary mucinous adenocarcinomas lacked expression of napsin A and TTF-1. Mucin-producing neoplasms of the lung infrequently express napsin A, suggesting that immunohistochemical assessment of napsin A may have limited diagnostic usefulness for distinguishing primary and metastatic mucinous adenocarcinomas involving the lung.
    American Journal of Clinical Pathology 02/2013; 139(2):160-6. · 2.88 Impact Factor
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    ABSTRACT: We aimed to investigate the prognostic value of RRM1 in GC patients. A total of assessable 389 GC patients with clinicopathological and survival information were enrolled from City of Hope (COH, n = 67) and Zhejiang University (ZJU, n = 322). RRM1 protein expression was determined by immunohistochemistry on FFPE tissue samples. Kaplan-Meier and Cox analyses were used to measure survival. Ras/Raf activity and invasion assays were used to evaluate the role of RRM1 in GC cell lines. In vitro experiments demonstrated RRM1 activated Ras/Raf/MAPK signal transduction and promoted GC cell proliferation. Meanwhile, RRM1 expression was significantly associated with lymph node involvement, tumor size, Ki67 expression, histological subtype and histological grade in the GC tissue samples (p<0.05). Kaplan-Meier analysis illustrated that high RRM1 expression predicted poor survival in GC patients in the COH and ZJU cohorts (log-rank p<0.01). In multivariate Cox analysis, the hazard ratios of RRM1 for overall survival were 2.55 (95% CI 1.27-5.15) and 1.51 (95% CI 1.07-2.13) in the COH and ZJU sets, respectively. In particular, RRM1 specifically predicted the outcome of advanced GCs with poor differentiation and high proliferative ability. Furthermore, inhibition of RRM1 by siRNA significantly reduced the dNTP pool, Ras/Raf and MMP-9 activities and the levels of p-MEK, p-ERK and NF-κB, resulting in growth retardation and reduced invasion in AGS and NCI-N87 cells. RRM1 overexpression predicts poor survival in GC patients with advanced TNM stage. RRM1 could potentially serve as prognostic biomarker and therapeutic target for GCs.
    PLoS ONE 01/2013; 8(7):e70191. · 3.53 Impact Factor
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    ABSTRACT: The development of resistance against anticancer drugs has been a persistent clinical problem for the treatment of locally advanced malignancies in the head and neck mucosal derived squamous cell carcinoma (HNSCC). Recent evidence indicates that the DNA translesion synthesis (TLS) polymerase η (Pol η; hRad30a gene) reduces the effectiveness of gemcitabine/cisplatin. The goal of this study is to examine the relationship between the expression level of Pol η and the observed resistance against these chemotherapeutic agents in HNSCC, which is currently unknown. Sixty-four mucosal derived squamous cell carcinomas of head and neck (HNSCC) from 1989 and 2007 at the City of Hope National Medical Center (Duarte, CA) were retrospectively analyzed. Pretreatment samples were immunostained with anti-Pol η antibody and the correlation between the expression level of Pol η and clinical outcomes were evaluated. Forty-nine cases treated with platinum (n=40) or gemcitabine (n=9) based chemotherapy were further examined for Pol η expression level for comparison with patient response to chemotherapy. The expression of Pol η was elevated in 67% of the head and neck tumor samples. Pol η expression level was significantly higher in grade 1 to grade 2 tumors (well to moderately differentiated). The overall benefit rate (complete response+ partial response) in patients treated with platinum and gemcitabine based chemotherapy was 79.5%, where low Pol η level was significantly associated with high complete response rate (p=0.03), although not associated with overall survival. Furthermore, no significant correlation was observed between Pol η expression level with gender, age, tobacco/alcohol history, tumor stage and metastatic status. Our data suggest that Pol η expression may be a useful prediction marker for the effectiveness of platinum or gemcitabine based therapy for HNSCC.
    PLoS ONE 01/2013; 8(12):e83978. · 3.53 Impact Factor
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    ABSTRACT: Accurate tumor classification is fundamental to inform predictive biomarker testing and optimize therapy. Gene expression-based tests are proposed as diagnostic aids in cases with uncertain diagnoses. This study directly compared the diagnostic accuracy of IHC analysis versus molecular classification using a 92-gene RT-PCR assay for determination of the primary tumor site. This prospectively defined blinded study of diagnostically challenging cases included 131 high-grade, primarily metastatic tumors. Cases were reviewed and reference diagnoses established through clinical correlation. Blinded FFPE sections were evaluated by either IHC/morphology analysis or the 92-gene assay. The final analysis included 122 cases. The 92-gene assay demonstrated overall accuracy of 79% (95% CI, 71% to 85%) for tumor classification versus 69% (95% CI, 60% to 76%) for IHC/morphology analysis (P = 0.019). Mean IHC use was 7.9 stains per case (median, 8; range, 2 to 15). IHC/morphology analysis accuracy was 79%, 80%, and 46% when 1 to 6 (n = 42), 7 to 9 (n = 41), and >9 (n = 39) IHC stains were used, respectively, versus 81%, 85%, and 69%, respectively, with the 92-gene assay. Results from this blinded series of high-grade metastatic cases demonstrate superior accuracy with the 92-gene assay versus standard-of-care IHC analysis and strongly support the diagnostic utility of molecular classification in difficult-to-diagnose metastatic cancer.
    The Journal of molecular diagnostics: JMD 12/2012; · 3.48 Impact Factor
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    ABSTRACT: Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Dysregulation of miR-657 has been observed in several types of cancers, but its biological function is still largely unknown. Our results showed that miR-657 expression can be induced by hepatitis viral proteins and is significantly increased in hepatocellular carcinoma (HCC) tissues. Moreover, introduction of miR-657 dramatically increases proliferation and colony formation of HCC cells in vitro and induces tumor development in immunodeficient mice. Further studies showed that miR-657 directly targets the TLE1 3'UTR and activates NF-κB pathways that contribute to hepatocarcinogenesis. This study identified a mechanism whereby of miRNA-657 contributed to HCC through novel cancer pathways, and provides new insights into the potential molecular mechanisms of hepatic carcinogenesis. (HEPATOLOGY 2012.).
    Hepatology 11/2012; · 12.00 Impact Factor
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    ABSTRACT: Aromatase inhibitors (AIs) are important drugs for treating postmenopausal patients with hormone receptor-positive breast cancer. However, acquired resistance to AI therapies is a significant problem. Our study has revealed that the histone deacetylase inhibitor LBH589 treatment abrogated growth of AI-resistant cells in vitro and in vivo, causing cell cycle G2/M arrest and induced apoptosis. LBH589 treatment also reduced the level of NF-κB1 which is overexpressed when AI resistance develops. Analyzing paired tumor specimens from 12 patients, we found that NF-κB1 expression was increased in recurrent AI-resistant tumors as compared to the paired primary tumors before AI treatment. This finding was consistent with up-regulated NF-κB1 expression seen in a collection of well-established AI-resistant cell lines. Furthermore, knockdown of NF-κB1 expression significantly suppressed the proliferation of AI-resistant cells. Treatment of AI-resistant cell lines with LBH589 suppressed NF-κB1 mRNA and protein expression. In addition, LBH589 treatment abrogated growth of AI-resistant tumors in mice, and was associated with significantly decreased levels of NF-κB1 in tumors. In all, our findings strongly support further investigation of LBH589 as a novel therapeutic strategy for patients with AI-resistant breast cancer, in part by suppressing the NF-κB1 pathway.
    Breast Cancer Research and Treatment 11/2012; · 4.47 Impact Factor
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    ABSTRACT: The overexpression of ribonucleotide reductase small subunit M2 (RRM2) dramatically enhances the ability of the cancer cell to proliferate and to invade. To further investigate the relevance of RRM2 and colorectal cancers (CRC), we correlated the expression of RRM2 with the clinical outcome of CRCs. A retrospective outcome study was conducted on CRCs collected from City of Hope National Medical Center (COH, 217 cases) and Zhejiang University (ZJU, 220 cases). The immunohistochemistry (IHC) was employed to determine the protein expression level of RRM2, and the quantitative real-time PCR was employed to validate. Multivariate Logistic analysis indicated that the adjusted odds ratios (ORs) of RRM2-high for distant metastases were 2.06(95% CI 1.01-4.30) and 5.89(95% CI 1.51-39.13) in the COH and ZJU sets respectively. The Kaplan-Meier analysis displayed that highly expression of RRM2 negatively impacted the overall (OS) and progress-free survival (PFS) of CRC in both sets significantly. The multivariate COX analysis further demonstrated that hazard ratios (HRs) of RRM2-high for OS were 1.88(95% CI 1.03-3.36) and 2.06(95% CI 1.10-4.00) in the COH and ZJU set respectively. Stratification analysis demonstrated that the HR of RRM2-high dramatically increased to 12.22(95% CI 1.62-258.31) in MMR-deficient subgroup in COH set. Meanwhile, a real-time study demonstrated that down-regulation of RRM2 by siRNA could significantly and specifically reduce the cell growth and adhesion ability in HT-29 and HCT-8 cells. Therefore, RRM2 is an independent prognostic factor and prognoses poor survival of CRCs. It is also a potential predictor for identifying good responders to chemotherapy for CRCs.
    Clinical Science 11/2012; · 4.86 Impact Factor
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    Hannah H Wong, Peiguo Chu
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    ABSTRACT: Gastrointestinal tract tumors include a wide variety of vastly different tumors and on a whole are one of the most common malignancies in western countries. These tumors often present at late stages as distant metastases which are then biopsied and may be difficult to differentiate without the aid of immunohistochemical stains. With the exception of pancreatic and biliary tumors where there are no distinct immunohistochemical patterns, most gastrointestinal tumors can be differentiated by their unique immunohistochemical profile. As the size of biopsies decrease, the role of immunohistochemical stains will become even more important in determining the origin and differentiation of gastrointestinal tract tumors.
    Journal of gastrointestinal oncology 09/2012; 3(3):262-84.
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    ABSTRACT: Objective Bronchobiliary fistula (BBF) is abnormal between the bronchial and biliary tree. Misdiagnosis and delayed treatment may have a high mortality rate. Although some characteristics relevant to BBF have been introduced, difficulties and controversies in diagnosis and treatment need further investigation. MethodologyIn this study, we summarize the diagnostic and surgical treatment experience of a 65-year-old male patient who presented with an irritating cough and biliptysis. Since he had the history of aortic valve replacement surgery and schistosomial cirrhosis, the provisional diagnosis was BBF, which might be secondary to a foreign body reaction or liver cirrhosis and chronic cholecystitis and cholelithiasis. ResultsDuring the surgery, it was discovered that the right lobe of liver was significantly atrophied with irregular contours and the gallbladder was adjacent to the diaphragm with a fistula between the fundus of gallbladder and the right semi-diaphragm. These results confirmed that the BBF in this patient resulted from cholelithiasis associated with serious schistosomial cirrhosis. He was successfully treated with a right hepatic lobe resection and Roux-en-Y hepaticojejunostomy. The diaphragm defect was repaired by imbrication of the repaired liver and lower lobe's edges. ConclusionsA high index of clinical suspicion can be generated by patients who present with recurring irritating cough and production of bile-like sputum. The manifestations and responses to conservative treatment are crucial in clinical judgment and surgical intervention is the primary treatment choice when other approaches have failed or there are complications from the underlying disease.
    Surgical Practice 09/2012; · 0.11 Impact Factor

Publication Stats

2k Citations
448.91 Total Impact Points

Institutions

  • 2000–2014
    • City of Hope National Medical Center
      • • Department of Pathology
      • • Department of Molecular Pharmacology
      • • Division of Anatomic Pathology
      Duarte, California, United States
  • 2013
    • Sir Run Run Shaw Hospital
      Hang-hsien, Zhejiang Sheng, China
    • Taipei Medical University
      T’ai-pei, Taipei, Taiwan
  • 2012
    • Beckman Research Institute
      Duarte, California, United States
  • 2009–2012
    • Ruijin Hospital North
      Shanghai, Shanghai Shi, China
  • 2003
    • University of Massachusetts Medical School
      • Department of Pathology
      Worcester, MA, United States