المؤلفون: Susan E. Yost, Zheng Liu, Yate-Ching Yuan, Y Liang, Y Yuan, Angela Ying-Jian Li, Charles Warden, Peiguo G. Chu, Xiwei Wu, L Goldstein, Jerry Wang

المصدر: Cancer Research. 77:P1-05

مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, Primary (chemistry), business.industry, Internal medicine, medicine, Bioinformatics, business, Triple-negative breast cancer

الوصف: Background: Triple negative breast cancer (TNBC) is a heterogeneous disease with several molecular subtypes: basal-like1 (BL1), basal-like 2 (BL-2), mesenchymal(M), mesenchymal-stem-like(MSL), immune-modulatory(IM) and unclassified (UNC) Molecular evolution of TNBC through chemotherapy selection pressure is well recognized but poorly understood. This study was carried out to perform paired genomic analysis of TNBC comparing primary breast cancer with recurrent/refractory disease. Here we report the result of the first10 paired tissue analysis. Methods: 49 paired specimens were identified through an IRB-approved protocol via COH biorepository search (2002- 2015). miRNA and mRNA profiling of 22 samples were performed. The miRNA libraries were prepared and sequenced on Hiseq2500. Sequences were aligned to hg19 genome and miRNA expression levels were counted by in house built R scripts. Go and pathway annotation was performed using DAVID online tool. Affymetrix human Genechip 2.0st was used for mRNA expression profiling. Raw data were normalized and processed using Expression Console, and linear regression was performed using Limma to identify the differentially expressed genes between primary and recurrent/refractory TNBCs. Result: Through mRNA profiling, we identified several unique gene expression patterns comparing the paired TNBC. Significant mRNA expression alterations were observed in: cell cycle, DNA repair and adhesion. Using Vanderbilt TNBC sub-classification tool, we have identified “phenotype shift” between primary and recurrent TNBCs. Of the 8 paired specimen analyzed, 3 paired tissue remain in the same subclass (2 in IM, 1 in M). Phenotype shift observed in: 1 from BL1 to BL2, 1 from BL2 to BL1, 1 UNC to IM; 1 MSL to UNC; 1 from M to UNC. 15 up regulated and 13 down regulated miRNAs were identified. Most significantly differentially expressed miRNA (with more than 4 fold expression changes, P-value < 0.001) included: miR-206, miR-203, miR-144, miR-16-2, miR-15b, and miR-20b (un-regulated) and miR-10b, miR-125b and let-7c(down-regulated). These miRNA genes are involved in regulation of hormonal receptor signaling, cell cycle, proliferation and metastases. Statistically significant differentially expressed miRNAs identified from our TNBC patient cohort will be further validated using RT-PCR. Conclusion: A number of mRNA gene pathways and miRNAs showed differential expression between paired recurrent and primary TNBC tumor specimen. The underlying biology driven the phenotype shift is being studied. Further analysis to include a total of 49 paired TNBCs is currently underway. Contact information: Yuan Yuan MD PhD, Email: yuyuan@coh.org. Citation Format: Yuan Y, Li A, Yost S, Yuan Y-C, Chu P, Warden C, Wang J, Liu Z, Liang Y, Goldstein L, Wu X. Genomic analysis of molecular discordance of paired primary and recurrent triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-26.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::40c178b4f572f20d3cb43268cc9ae5c5Test
https://doi.org/10.1158/1538-7445.sabcs16-p1-05-26Test

المؤلفون: Y-C. Yuan, V. Bedell, Joseph Chao, S.J. Klempner, M.S. Li, Peiguo G. Chu, R-J. Lin

المصدر: Annals of Oncology. 28:v235

مصطلحات موضوعية: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, business.industry, 030220 oncology & carcinogenesis, Cancer research, Medicine, Hematology, business, Gastroesophageal Junction

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::adac9214734656e3832c061b995b988cTest
https://doi.org/10.1093/annonc/mdx369.075Test

المؤلفون: James H. Doroshow, Peter Danenberg, G. Somlo, Wei Ye, K. Danenberg, Peiguo G. Chu, Susan Groshen, Paul Frankel

المصدر: Annals of Oncology. 19:1853-1859

مصطلحات موضوعية: Adult, Cyclin-Dependent Kinase Inhibitor p21, Oncology, medicine.medical_specialty, Axillary lymph nodes, Receptor, ErbB-2, Gene Expression, Estrogen receptor, Breast Neoplasms, Cell Growth Processes, Inflammatory breast cancer, Disease-Free Survival, Cohort Studies, Breast cancer, Growth factor receptor, Risk Factors, Internal medicine, medicine, Humans, Epidermal growth factor receptor, Neoplasm Staging, biology, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Gene Expression Profiling, Cancer, Original Articles, Hematology, Middle Aged, medicine.disease, Immunohistochemistry, ErbB Receptors, medicine.anatomical_structure, Cancer research, biology.protein, Female, Breast disease, business

الوصف: Background: Patients with high-risk primary breast cancer remain at high risk for relapse. More precise prognostic and predictive tools are needed to improve treatment of such patients. Patients and methods: Formalin-fixed, paraffin-embedded tumors from 239 high-risk breast cancer patients were examined for expression of human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), estrogen receptor, progesterone receptor, Ki-67, p16, p21, p27, and p53 by immunohistochemistry. Gene expression of EGFR, HER2, glutathione S-transferase-Pi (GSTP1), excision repair cross complementation1 (ERCC1), p21, β-tubulin-3, multidurg resistance (MDR1), cyclooxygenase2 (COX2), and cyclin-E was measured by RT-PCR. Results: Eighty percent of patients presented with locally advanced, or ≥10 axillary nodal metastasis, and 20% with inflammatory breast cancer. The median age was 46 years (26–62 years) and the median number of involved axillary lymph nodes was 12 (0–42). At a median follow-up of 86 months, relapse-free survival (RFS) and overall survival for the entire group were 50% (95% CI 43% to 57%) and 62% (95% CI 56% to 69%). Multivariate Cox stepwise analysis resulted in a simple model for RFS consisting only of p21 expression, EGFR expression assessed by RT-PCR, and number of axillary nodal metastases. Conclusion: A prognostic model on the basis of the expression of a limited number of proteins and genes may help to guide target-specific therapies in patients with high-risk breast cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a0abf063e476fdd1df2a4e34edb9cc2Test
https://doi.org/10.1093/annonc/mdn402Test

المؤلفون: Y, Yen, Dean W, Lim, Vincent, Chung, Robert J, Morgan, Lucille A, Leong, Stephen I, Shibata, Lawrence D, Wagman, Stephen D, Wagman, Howard, Marx, Peiguo G, Chu, Jeffrey A, Longmate, Heinz-Josef, Lenz, Ramesh K, Ramanathan, Chandra P, Belani, David R, Gandara

المصدر: American Journal of Clinical Oncology. 31:317-322

مصطلحات موضوعية: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Organoplatinum Compounds, Phases of clinical research, Antineoplastic Agents, Cholangiocarcinoma, Capecitabine, Carcinoma, Non-Small-Cell Lung, Internal medicine, medicine, Humans, neoplasms, Aged, Aged, 80 and over, Salvage Therapy, Response rate (survey), business.industry, Liver Neoplasms, Cancer, Hepatitis C, Middle Aged, Prognosis, medicine.disease, digestive system diseases, Oxaliplatin, Survival Rate, Treatment Outcome, Hepatocellular carcinoma, Toxicity, Female, Neoplasm Recurrence, Local, business, medicine.drug

الوصف: Prolonged survival for patients with unresectable hepatocellular carcinoma (HCC) is consistently reported at lower than 6 months. Oxaliplatin has recently demonstrated activity in HCC. The objective of this study was to determine the response rate, survival, time to progression, and toxicity in patients with poor prognosis HCC when treated with oxaliplatin.Patients were required to have measurable recurrent, metastatic or unresectable HCC, and to have previously been exposed to no more than 2 prior chemotherapy regimens. Karnofsky performance of 70% or above and adequate organ and hematologic function were required. All patients received treatment with oxaliplatin 100 mg/m on day 1 and 15 as a 2-hour intravenous infusion and were pretreated with antiemetics. Treatment was repeated every 28 days.Thirty-six patients were enrolled and evaluated, although 6 expired before the first planned evaluation. Karnofsky performance status was 70/80/90/100% in 5/9/9/13 patients, respectively. The median time to progression was 2 months; median survival was 6 months. The 6-month overall survival was 55% (95% confidence interval 41%-74%), and the 6 month event-free survival was 11% (95% confidence interval 4%-28%).Single agent, oxaliplatin, has produced one partial response of good duration in 36 patients, but failed to meet the a priori criterion for promise in this trial. Sixteen patients were observed to have stable disease with a well tolerated toxicity profile. The combination of oxaliplatin and other agents should be considered to treat HCC in those patients with good functional status.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7efeb2f6e6903806d9a0fde2d870fe7aTest
https://doi.org/10.1097/coc.0b013e318162f57dTest

المؤلفون: Lawrence M. Weiss, Huiying He, Liang Cheng, Peiguo G. Chu

المصدر: Leukemia & Lymphoma. 48:1976-1980

مصطلحات موضوعية: Male, Oncology, Cancer Research, medicine.medical_specialty, Lymphoma, B-Cell, Time Factors, medicine.medical_treatment, Chronic lymphocytic leukemia, Antineoplastic Agents, Models, Biological, Disease-Free Survival, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Neoplasm Metastasis, B-cell lymphoma, B cell, Aged, Prostatectomy, Chemotherapy, business.industry, Prostatic Neoplasms, Neoplasms, Second Primary, Hematology, Middle Aged, Prognosis, medicine.disease, Lymphoma, Treatment Outcome, medicine.anatomical_structure, Mantle cell lymphoma, Radiology, business, Recurrent Prostate Carcinoma, Follow-Up Studies

الوصف: Incidental pelvic node malignant B-cell lymphomas diagnosed at the time of radical prostatectomy are rare. Their clinical outcome has not been studied. We studied thirteen such cases with long-term clinical follow-up. Patients were followed between 9 and 94 months after surgery. Of 13 cases, 9 were chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 3 marginal zone B-cell lymphoma (MZL) and 1 mantle cell lymphoma (MCL). All 13 patients did not receive radiation or chemotherapy; and five of 13 cases showed hematologic evidence of lymphoma progression between 1 and 5 months after radical prostatectomy. After progression, the mantle cell lymphoma patient received aggressive chemotherapy and had systemic dissemination. Two of 13 cases had recurrent prostate carcinoma. None of 13 patients had died from lymphoma or prostate carcinoma at the last follow-up. In conclusion, most incidental pelvic node lymphomas (8/13) showed no evidence of systemic dissemination to peripheral blood or bone marrow after a mean 42.8 weeks of follow-up despite the fact that no additional treatment was given. Strong consideration should be given to withholding further treatment in patients diagnosed with pelvic low-grade B-cell lymphoma at the time of radical prostatectomy until disease progression occurs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3dc5d020734fab57ecb8be9e32a791cTest
https://doi.org/10.1080/10428190701584007Test

المؤلفون: Barbara F. Banner, Zhong Jiang, Gary R Fanger, Steven G. Reed, Karen Dresser, Paul A. Algate, Bruce A. Woda, Peiguo G Chu, Jiangchun Xu, Kenneth L. Rock

المصدر: Cancer Detection and Prevention. 27:422-426

مصطلحات موضوعية: Adenoma, Male, Cancer Research, Pathology, medicine.medical_specialty, Colon, Colorectal cancer, Racemases and Epimerases, Adenocarcinoma, Biology, Gene Expression Regulation, Enzymologic, Prostate cancer, Biomarkers, Tumor, medicine, Humans, RNA, Messenger, chemistry.chemical_classification, Peroxisome, medicine.disease, digestive system diseases, Real-time polymerase chain reaction, Enzyme, Oncology, chemistry, Hyperplastic Polyp, Case-Control Studies, Colonic Neoplasms, Cancer research, Red meat, Immunohistochemistry, Female

الوصف: Epidemiological studies have shown that consumption of red meat increases the risk of developing colon cancer. An enzyme, α-methylacyl CoA racemase (AMACR), also known as P504S, plays an important role in peroxisomal β-oxidation of branched-chain fatty acids from red meat and dairy products. High expression of AMACR was recently found in prostate cancer. In this study, we investigated expression of AMACR in 242 cases of colonic tumors including 176 colorectal carcinomas, 38 colon adenomas and 28 hyperplastic (non-neoplastic) polyps by immunohistochemical analysis. The mRNA levels of AMACR expression in normal and colon cancer tissues were assessed by real-time PCR. Significant up-regulation of AMACR mRNA was found in colon carcinomas compared to normal tissue. There was very low or no expression of AMACR protein in normal colon, but AMACR was highly expressed in 76 and 75% of well and moderately differentiated colon carcinomas, respectively, and in 79% of adenomas. In contrast, only 4% of hyperplastic polyps expressed AMACR. Since this enzyme is involved in the metabolism of branched-chain fatty acids from beef, milk and dairy products, our results provide important molecular information regarding a possible link between diet and development of colon cancer. AMACR may also serve as a molecular marker for colon cancers and its precursor lesions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4d44d3b986651c7d1a4bbf20a29220cTest
https://doi.org/10.1016/j.cdp.2003.07.003Test

المؤلفون: Rebecca A. Nelson, Keqiang Zhang, Shu Zheng, Peiguo G. Chu, Shuya Hu, Yan Wang, Lily L. Lai, Mei-Ling Kuo, Xiaochen Wang, Bingsen Zhou, Lijun Xue, Suzhan Zhang, Sofia Leora, Hang Zhang, Jun Wu, Xiyong Liu, Yun Yen, Yafan Wang, Lun Zhou

مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, Pathology, Colorectal cancer, Molecular Sequence Data, Transplantation, Heterologous, Cell Cycle Proteins, Biology, Transfection, Article, Antibodies, Metastasis, Mice, Antibody Specificity, Mice, Inbred NOD, Internal medicine, Ribonucleotide Reductases, medicine, Biomarkers, Tumor, Animals, Humans, Neoplasm Invasiveness, Amino Acid Sequence, Survival rate, Lymph node, Neoplasm Staging, Cancer, medicine.disease, HCT116 Cells, Prognosis, Immunohistochemistry, Transplantation, Survival Rate, medicine.anatomical_structure, Cancer cell, Female, Colorectal Neoplasms

الوصف: Ribonucleotide reductase subunit RRM2B (p53R2) has been reported to suppress invasion and metastasis in colorectal cancer (CRC). Here, we report that high levels of RRM2B expression are correlated with markedly better survival in CRC patients. In a fluorescence-labeled orthotopic mouse xenograft model, we confirmed that overexpression of RRM2B in nonmetastatic CRC cells prevented lung and/or liver metastasis, relative to control cells that did metastasize. Clinical outcome studies were conducted on a training set with 103 CRCs and a validation set with 220 CRCs. All participants underwent surgery with periodic follow-up to determine survivability. A newly developed specific RRM2B antibody was employed to carry out immunohistochemistry for determining RRM2B expression levels on tissue arrays. In the training set, the Kaplan–Meier and multivariate Cox analysis revealed that RRM2B is associated with better survival of CRCs, especially in stage IV patients (HR = 0.40; 95% CI = 0.18–0.86, P = 0.016). In the validation set, RRM2B was negatively related to tumor invasion (OR = 0.45, 95% CI = 0.19–0.99, P = 0.040) and lymph node involvement (OR = 0.48, 95% CI = 0.25–0.92, P = 0.026). Furthermore, elevated expression of RRM2B was associated with better prognosis in this set as determined by multivariate analyses (HR = 0.48, 95% CI = 0.26–0.91, P = 0.030). Further investigations revealed that RRM2B was correlated with better survival of CRCs with advanced stage III and IV tumors rather than earlier stage I and II tumors. Taken together, our findings establish that RRM2B suppresses invasiveness of cancer cells and that its expression is associated with a better survival prognosis for CRC patients. Cancer Res; 71(9); 3202–13. ©2011 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3182a0bad669fa96f75e0ce38af323d8Test
https://europepmc.org/articles/PMC3085570Test/

المؤلفون: Wei Feng, Peiguo G. Chu, Yun Yen

المصدر: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 22(11)

مصطلحات موضوعية: Cancer Research, Pathology, medicine.medical_specialty, Parathyroid hormone-related protein, Cancer case, business.industry, Metabolic disorder, Liver Neoplasms, Parathyroid Hormone-Related Protein, Parathyroid hormone, Middle Aged, medicine.disease, Paraneoplastic Endocrine Syndromes, Cholangiocarcinoma, Oncology, medicine, Hypercalcemia, Humans, Female, business, Biliary tract disease

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::365e40534ca55eece3b31f0ff895b56dTest
https://pubmed.ncbi.nlm.nih.gov/15169815Test

المؤلفون: Yuan-Yuan Chen, Lawrence M. Weiss, Arturo Molina, Peiguo G. Chu, Daniel A. Arber

المصدر: Leukemialymphoma. 43(12)

مصطلحات موضوعية: Cancer Research, Pathology, medicine.medical_specialty, Lymphoma, B-Cell, Genotype, Gene Rearrangement, B-Lymphocyte, Heavy Chain, CD19, Immunophenotyping, Antibodies, Monoclonal, Murine-Derived, Recurrence, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Leukemia, B-Cell, Medicine, Gene Rearrangement, B-Lymphocyte, Light Chain, Humans, Treatment Failure, B cell, CD20, biology, business.industry, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, Hematology, Gene rearrangement, CD79A, Antigens, CD20, medicine.anatomical_structure, Oncology, biology.protein, Rituximab, Antibody, business, medicine.drug, Follow-Up Studies

الوصف: Rituximab has been widely used to treat relapsing or advanced stage B-cell neoplasms with an efficacy of about 50%. However, approximately 40-50% of Rituximab treated patients will recur. It is not clear whether these recurrent diseases have the same immunophenotype as that of the original tumors. At the City of Hope, we treated 91 cases of CD20-positive B-cell neoplasms with Rituximab in combination with chemotherapy and hematopoietic stem cell transplantation between August 1999 and December 2000. Thirty-five of 91 patients (38%) experienced recurrence during the time period within one year from treatment. Tumor cells from all of the recurrent patients expressed one or more B cell antigens (CD19, CD20, CD22, CD45RA, or CD79a). However, thirteen of 35 recurrent cases showed aberrant loss of CD20 expression (37%) by immunohistochemical or flow cytometric studies. Pre- and post-Rituximab treated tumor cell DNA was successfully extracted from archival paraffin sections, hematoxylin and eosin (H and E) stained slides, smears, or frozen cells in 10 of 13 CD20 negative recurrent cases. PCR studies for immunoglobulin (Ig) heavy chain gene rearrangements were performed in all these cases. Five cases showed identical Ig heavy chain gene rearrangements in the paired specimens. PCR assay for Ig kappa (kappa) gene rearrangement was performed in the five paired specimens lacking detectable Ig heavy chain gene rearrangements; 2 of them showed identical Igkappa gene rearrangements. Three pairs showed unmatched Ig heavy chain and Igkappa gene rearrangements, probably due to poor quality of recovered DNA. Aberrant loss of CD20 antigens may be a mechanism of treatment resistance and should be considered in the immunophenotyping of recurrent Rituximab-treated B-cell neoplasms; therefore, a panel of B cell markers is recommended for the immunologic diagnosis of recurrent B cell malignancies after Rituximab therapy. Seven of ten pairs of recurrent CD20-negative cases showed identical Ig heavy chain and Igkappa gene rearrangements by PCR assay, strongly suggesting that the pre- and post-Rituxan treated B cell neoplasms are clonally-related.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b7a8b2d971a77476c49183cc8ea37beTest
https://pubmed.ncbi.nlm.nih.gov/12613521Test

المؤلفون: Kimberley Ho, Helen Lin, Peiguo G Chu, David K. Ann, Yun Yen

المصدر: Head & Neck Oncology

مصطلحات موضوعية: Oncology, medicine.medical_specialty, Pathology, endosomal sorting complexes required for transport, medicine.medical_treatment, Parotid gland cancer, Review, multi-vesicular bodies, medicine.disease_cause, chemistry.chemical_compound, stomatognathic system, Internal medicine, medicine, Animals, Humans, Parotid Gland, Epidermal growth factor receptor, targeted therapeutics, salivary gland cancer, Chemotherapy, biology, vascular endothelial growth factor, business.industry, Cancer, medicine.disease, Prognosis, Parotid gland, Parotid Neoplasms, Vascular endothelial growth factor, Radiation therapy, medicine.anatomical_structure, chemistry, Otorhinolaryngology, Salivary gland cancer, biology.protein, vacuolar protein sorting-associated protein 4B, Carcinogenesis, business, epidermal growth factor receptor

الوصف: Cancer of the parotid gland is relatively rare, but carries poor prognosis owing to its prevailing distant metastases. In addition to the disease's basic epidemiology and pathology, we review some current discoveries of its tumorigenesis molecular mechanism. Based on published salivary gland cancer clinical trial data, non-surgical antitumor efficacies amongst a range of chemotherapy, radiation, and concurrent therapy regimens are compared. We also present the current development status of novel radiation therapy and targeted therapeutics, focusing on intensity-modulated radiation therapy (IMRT), and epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) blockages, which are showing promise for improving parotid gland cancer management.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b54a9d2a91307f2a601bb01dc4937c2bTest
http://europepmc.org/articles/PMC3197557Test