@article {332, title = {Prospective Study Reveals Host Microbial Determinants of Clinical Response to Fecal Microbiota Transplant Therapy in Type 2 Diabetes Patients.}, journal = {Front Cell Infect Microbiol}, volume = {12}, year = {2022}, month = {2022}, pages = {820367}, abstract = {

Background: Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.

Methods: We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c\% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.

Results: We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c\% (from 7.565 {\textpm} 0.148 to 7.190 {\textpm} 0.210, p\<0.01), blood glucose (from 8.483 {\textpm} 0.497 to 7.286 {\textpm} 0.454 mmol/L, p\<0.01), and uric acid (from 309.4 {\textpm} 21.5 to 259.1 {\textpm} 15.8 {\textmu}mol/L, p\<0.01) while a significant increase in postprandial C-peptide (from 4.503 {\textpm} 0.600 to 5.471 {\textpm} 0.728 ng/ml, p\<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family and the genus (family ) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.

Conclusion: Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of and in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.

}, keywords = {Diabetes Mellitus, Type 2, Fecal Microbiota Transplantation, Feces, Glycated Hemoglobin A, Humans, Prospective Studies, RNA, Ribosomal, 16S, Treatment Outcome}, issn = {2235-2988}, doi = {10.3389/fcimb.2022.820367}, author = {Ding, Dafa and Yong, Huijuan and You, Na and Lu, Wei and Yang, Xu and Ye, Xiaolong and Wang, Yayun and Cai, Tingting and Zheng, Xiaoling and Chen, Hui and Cui, Bota and Zhang, Faming and Liu, Xingyin and Mao, Jian-Hua and Lu, Yibing and Chang, Hang} } @article {102, title = {Phenotypic Characterization of Breast Invasive Carcinoma via Transferable Tissue Morphometric Patterns learned from Glioblastoma Multiforme.}, journal = {Proc IEEE Int Symp Biomed Imaging}, volume = {2016}, year = {2016}, month = {2016 Apr}, pages = {1025-1028}, abstract = {

Quantitative analysis of whole slide images (WSIs) in a large cohort may provide predictive models of clinical outcome. However, the performance of the existing techniques is hindered as a result of large technical variations (e.g., fixation, staining) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. Although unsupervised feature learning provides a promising way in learning pertinent features without human intervention, its capability can be greatly limited due to the lack of well-curated examples. In this paper, we explored the transferability of knowledge acquired from a well-curated Glioblastoma Multiforme (GBM) dataset through its application to the representation and characterization of tissue histology from the Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Our experimental results reveals two major phenotypic subtypes with statistically significantly different survival curves. Further differential expression analysis of these two subtypes indicates enrichment of genes regulated by NF-kB in response to TNF and genes up-regulated in response to IFNG.

}, issn = {1945-7928}, doi = {10.1109/ISBI.2016.7493440}, author = {Han, Ju and Fontenay, Gerald V and Wang, Yunfu and Jiang-Hua Mao and Hang Chang} } @conference {23, title = {Predictive sparse morphometric context for classification of histology sections}, booktitle = {12th {IEEE} International Symposium on Biomedical Imaging, {ISBI} 2015, Brooklyn, NY, USA, April 16-19, 2015}, year = {2015}, doi = {10.1109/ISBI.2015.7164040}, url = {http://dx.doi.org/10.1109/ISBI.2015.7164040}, author = {Hang Chang and Paul T. Spellman and Bahram Parvin} } @article {84, title = {Persistence of γ-H2AX and 53BP1 foci in proliferating and non-proliferating human mammary epithelial cells after exposure to γ-rays or iron ions}, journal = {Int J Radiat Biol}, volume = {87}, year = {2011}, month = {2011 Jul}, pages = {696-710}, abstract = {

PURPOSE: To investigate γ-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionising radiation under different cell culture conditions.

MATERIAL AND METHODS: HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure.

RESULTS: Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced γ-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both γ-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after γ-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition.

CONCLUSIONS: The disappearance of radiation-induced γ-H2AX and 53BP1 foci in HMEC has different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent γ-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double-strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodelling.

}, keywords = {Cell Line, Cell Proliferation, Gamma Rays, Heavy Ions, Histones, Human, Humans, Iron, Mammary Glands, Tumor Suppressor Protein p53}, issn = {1362-3095}, doi = {10.3109/09553002.2010.549535}, author = {Groesser, Torsten and Hang Chang and Gerald Fontenay and Chen, James and Costes, Sylvain V and Helen Barcellos-Hoff, Mary and Parvin, Bahram and Rydberg, Bjorn} } @article {179, title = {Progressive genomic instability in the FVB/Kras(LA2) mouse model of lung cancer.}, journal = {Mol Cancer Res}, volume = {9}, year = {2011}, month = {2011 Oct}, pages = {1339-45}, abstract = {

Alterations in DNA copy number contribute to the development and progression of cancers and are common in epithelial tumors. We have used array Comparative Genomic Hybridization (aCGH) to visualize DNA copy number alterations across the genomes of lung tumors in the Kras(LA2) model of lung cancer. Copy number gain involving the Kras locus, as focal amplification or whole chromosome gain, is the most common alteration in these tumors and with a prevalence that increased significantly with increasing tumor size. Furthermore, Kras amplification was the only major genomic event among the smallest lung tumors, suggesting that this alteration occurs early during the development of mutant Kras-driven lung cancers. Recurring gains and deletions of other chromosomes occur progressively more frequently among larger tumors. These results are in contrast to a previous aCGH analysis of lung tumors from Kras(LA2) mice on a mixed genetic background, in which relatively few DNA copy number alterations were observed regardless of tumor size. Our model features the Kras(LA2) allele on the inbred FVB/N mouse strain, and in this genetic background, there is a highly statistically significant increase in level of genomic instability with increasing tumor size. These data suggest that recurring DNA copy alterations are important for tumor progression in the Kras(LA2) model of lung cancer and that the requirement for these alterations may be dependent on the genetic background of the mouse strain.

}, keywords = {Animal, Animals, Cell Line, Chromosome Aberrations, Disease Models, Disease Progression, DNA, DNA Copy Number Variations, Gene Dosage, Gene Expression Regulation, Genes, Genomic Instability, Inbred C57BL, Lung Neoplasms, Mice, Neoplasm, Neoplastic, Proto-Oncogene Proteins p21(ras), ras, Tumor}, issn = {1557-3125}, doi = {10.1158/1541-7786.MCR-11-0219}, author = {To, Minh D and Quigley, David A and Jiang-Hua Mao and Del Rosario, Reyno and Hsu, Jeff and Hodgson, Graeme and Jacks, Tyler and Balmain, Allan} } @conference {53, title = {Perceptual Grouping of Membrane Signals in Cell-Based Assays}, booktitle = {Proceedings of the 2007 {IEEE} International Symposium on Biomedical Imaging: From Nano to Macro, Washington, DC, USA, April 12-16, 2007}, year = {2007}, doi = {10.1109/ISBI.2007.356906}, url = {http://dx.doi.org/10.1109/ISBI.2007.356906}, author = {Hang Chang and Kumari L. Andarawewa and Ju Han and Mary Helen Barcellos-Hoff and Bahram Parvin} }