Judith Hugh | University of Alberta (original) (raw)

Papers by Judith Hugh

Research paper thumbnail of Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy

The British Journal of Radiology, 2000

Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echoca... more Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echocardiographic identi®cation of the disorder can be made. We believe that the ultrasound features of this disorder have not been previously reported.

Research paper thumbnail of Absence of estrogen receptors in a case of virginal hypertrophy of the breasts related to oral contraceptives

Research paper thumbnail of Abstract P2-11-10: Estrogen drives the therapeutic hormonal response in ER+ breast cancers

Cancer Research, 2020

Background: It is thought that estrogen induces proliferation in all estrogen receptor positive (... more Background: It is thought that estrogen induces proliferation in all estrogen receptor positive (ER+) breast cancer cells. However, there are paradoxical reports of a therapeutic effect of estrogen (E2) with possible E2 induced apoptosis in tumors that are chronically E2 deprived such as after the menopause. We tested whether E2 induced proliferation or apoptosis in post-menopausal women with newly diagnosed breast cancer. Method: We treated 19 women with low dose estradiol (6mg/day) in a window of opportunity trial. Changes in Ki67 and the Prosigna™ Risk of Recurrence Score (ROR) were measured. 13 patients with sufficient tissue had whole transcriptome RNA-seq analysis on pre- and post-treatment specimens to test pathway induction and to derive a gene expression profile (GEP) associated with response to E2. 13 contemporaneous untreated patients were matched for surgical ROR scores to serve as post-hoc controls. The E2-response GEP was then tested on publicly available datasets of E...

Research paper thumbnail of DREAM, a possible answer to the estrogen paradox of the Women's Health Initiative Trial

Heliyon, 2021

WHI trial found that estrogen decreases some ERþ post-menopausal breast cancers. Our prospective ... more WHI trial found that estrogen decreases some ERþ post-menopausal breast cancers. Our prospective clinical trial confirmed an anti-proliferative effect of estradiol. DREAM pathway genes were downregulated during the anti-proliferative response. This suggests that estrogen may activate DREAM quiescence of ERþ breast cancers.

Research paper thumbnail of BCIRG 001 molecular analysis: Identification of prognostic factors in patients (pts) receiving adjuvant therapy for node- positive (N+) breast cancer (BC)

Journal of Clinical Oncology, 2007

525 Background: BCIRG 001 (1,491 pts) demonstrated significant superiority of docetaxel/doxorubic... more 525 Background: BCIRG 001 (1,491 pts) demonstrated significant superiority of docetaxel/doxorubicin/cyclophosphamide (TAC) over fluorouracil/doxorubicin/cyclophosphamide (FAC) given as adjuvant therapy for N+ operable BC in terms of disease-free survival (DFS) and overall survival (OS) (Martin et al, N Eng J Med, 2005). This ancillary study was aimed to identify tumor-associated factors related to DFS and OS. Methods: Formalin-fixed primary tumors from pts in BCIRG 001 were analysed by immunohistochemistry. Protocol- specified assessment of histological grade (GR), tumor size (TS), estrogen (ER) and progesterone receptors (PR), lymph node status (LN), HER2, MUC1, Mib, p53, Bcl-2, Bax, Bcl-X, Bag-1, tubulin β isotypes II, III and IV, tau protein and detyrosinated a tubulin was performed. Parameters were scored as the percentage of positive cells and analysed as lower or greater than median values. The samples were randomly split into training (2/3) and validation (1/3) sets. Associat...

Research paper thumbnail of Sialosyl-TN (B72.3) Shows Coordinated Expression with Polymorphic Epithelial Mucin in Normal and Malignant Breast After Trypsin Pretreatment

Laboratory Investigation, 1995

Research paper thumbnail of Monocytoid B-Cell Lymphoma - a Clinicopathological Study of 35 Cases

Laboratory Investigation, 1992

Research paper thumbnail of Abstract P6-05-05: The estrogen switch: Estrogen receptor alpha levels determine the proliferative response to estrogen

Cancer Research

Background: The premise that estrogen promotes the growth of all estrogen receptor positive (ER) ... more Background: The premise that estrogen promotes the growth of all estrogen receptor positive (ER) + breast cancers has led to anti-estrogen therapies as the standard of care for all ER+ tumors. Paradoxically, estrogen (E2) has demonstrated a therapeutic effect in the adjuvant, palliative and prevention of breast cancers in some women suggesting that there is a subset of ER+ breast cancers that may be growth-suppressed by E2. Our companion window-of-opportunity trial (abstract submitted) found E2 is growth suppressive for some post-menopausal women with high ER expressing tumors. We utilized an in vitro cell model to investigate whether differential growth responses to E2 could be due to transcriptional differences mediated by the level of the ER. Method: We generated a stable MCF-7 transfectant (MCF7-ER) using a fluorescently labelled lentiviral plasmid with a doxycycline inducible ER and compared the response to E2 against an MCF-7 mock transfectant (MCF7-EM). We assessed changes in...

Research paper thumbnail of MUC1 synthetic peptide inhibition of intercellular adhesion molecule-1 and MUC1 binding requires six tandem repeats

Cancer research, 1998

We reported recently that breast cancer-associated MUC1 is a ligand for intercellular adhesion mo... more We reported recently that breast cancer-associated MUC1 is a ligand for intercellular adhesion molecule-1 (ICAM-1; L. H. Regimbald et al., Cancer Res., 56: 4244-4249, 1996). We report here the results of a competitive indirect binding assay to detect the molecular requirements for binding between ICAM-1 and MUC1. The assay involved inhibition of the binding of recombinant human ICAM-1 to a murine breast adenocarcinoma cell line transfected with human MUC1. The addition of a library of human MUC1 synthetic peptides ranging from 9 to 24 amino acids (aa) showed minimal or no inhibition. However, a 120-aa peptide that corresponds to six tandem repeats of the human mucin MUC1 was as effective an inhibitor as purified tumor MUC1 and MUC1 epitope (PDTRPAP)-specific antibody (B27.29). We conclude that the number of MUC1 tandem repeats necessary for an ordered tertiary structure (D. Fontenot et al., Cancer Res., 53: 5386-5394, 1993) is also important for ICAM-1 recognition. These findings ar...

Research paper thumbnail of A novel framework to integrate convolutional neural network with compressed sensing for cell detection

2017 IEEE International Conference on Image Processing (ICIP)

Research paper thumbnail of Developing a clinical-pathologic model to predict genomic risk of recurrence in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative, node negative breast cancer

Cancer Treatment and Research Communications

Research paper thumbnail of BIK drives an aggressive breast cancer phenotype through sublethal apoptosis and predicts poor prognosis of ER-positive breast cancer

Cell Death & Disease

Apoptosis is fundamental to normal animal development and is the target for many anticancer thera... more Apoptosis is fundamental to normal animal development and is the target for many anticancer therapies. Recent studies have explored the consequences of “failed apoptosis” where the apoptotic program is initiated but does not go to completion and does not cause cell death. Nevertheless, this failed apoptosis induces DNA double-strand breaks generating mutations that facilitate tumorigenesis. Whether failed apoptosis is relevant to clinical disease is unknown. BCL-2 interacting killer (BIK) is a stress-induced BH3-only protein that stimulates apoptosis in response to hormone and growth factor deprivation, hypoxia, and genomic stress. It was unclear whether BIK promotes or suppresses tumor survival within the context of breast cancer. We investigated this and show that BIK induces failed apoptosis with limited caspase activation and genomic damage in the absence of extensive cell death. Surviving cells acquire aggressive phenotypes characterized by enrichment of cancer stem-like cells,...

Research paper thumbnail of Utilization of the 21-gene assay for breast cancer treatment decision-making in Alberta

Journal of Clinical Oncology

Research paper thumbnail of Estrogen receptor regulates hormone-induced growth arrest in a luminal A like breast cancer model

Estrogen receptor positive (ER+) breast cancer has been divided into two subtypes, luminal A and ... more Estrogen receptor positive (ER+) breast cancer has been divided into two subtypes, luminal A and luminal B, which differ in their ER expression and response to hormone therapy. The absence of luminal A cell lines means the extensive amount of in vitro work studying the response to hormones in ER+ breast cancers is biased for the luminal B subtype. We have developed a luminal A like cell model by increasing the ER expression in the MCF-7 cell line. Our results show that increased ER expression promotes an anti-proliferative response to estrogen through regulation of genes involved in the G1/S-phase transition of the cell cycle. Furthermore, increased ER expression increases ER-DNA binding in the absence of estrogen and regulates basal gene transcription by promoting DNA looping. These results provide novel evidence that the characteristic increased ER expression of luminal A tumors may promote a novel chromatin configuration that enables growth of these tumors in the absence of estro...

Research paper thumbnail of Training Convolutional Neural Networks and Compressed Sensing End-to-End for Microscopy Cell Detection

IEEE Transactions on Medical Imaging

Automated cell detection and localization from microscopy images are significant tasks in biomedi... more Automated cell detection and localization from microscopy images are significant tasks in biomedical research and clinical practice. In this paper, we design a new cell detection and localization algorithm that combines deep convolutional neural network (CNN) and compressed sensing (CS) or sparse coding (SC) for end-to-end training. We also derive, for the first time, a backpropagation rule, which is applicable to train any algorithm that implements a sparse code recovery layer. The key observation behind our algorithm is that cell detection task is a point object detection task in computer vision, where the cell centers (i.e., point objects) occupy only a tiny fraction of the total number of pixels in an image. Thus, we can apply compressed sensing (or, equivalently sparse coding) to compactly represent a variable number of cells in a projected space. Then, CNN regresses this compressed vector from the input microscopy image. Thanks to the SC/CS recovery algorithm (L 1 optimization) that can recover sparse cell locations from the output of CNN. We train this entire processing pipeline end-to-end and demonstrate that end-to-end training provides accuracy improvements over a training paradigm that treats CNN and CS-recovery layers separately. Our algorithm design also takes into account a form of ensemble average of trained models naturally to further boost accuracy of cell detection. We have validated our algorithm on benchmark datasets and achieved excellent performances.

Research paper thumbnail of An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, Jan 24, 2018

The nuclear proliferation biomarker Ki67 has potential prognostic, predictive, and monitoring rol... more The nuclear proliferation biomarker Ki67 has potential prognostic, predictive, and monitoring roles in breast cancer. Unacceptable between-laboratory variability has limited its clinical value. The International Ki67 in Breast Cancer Working Group investigated whether Ki67 immunohistochemistry can be analytically validated and standardized across laboratories using automated machine-based scoring. Sets of pre-stained core-cut biopsy sections of 30 breast tumors were circulated to 14 laboratories for scanning and automated assessment of the average and maximum percentage of tumor cells positive for Ki67. Seven unique scanners and 10 software platforms were involved in this study. Pre-specified analyses included evaluation of reproducibility between all laboratories (primary) as well as among those using scanners from a single vendor (secondary). The primary reproducibility metric was intraclass correlation coefficient between laboratories, with success considered to be intraclass cor...

Research paper thumbnail of Combinational siRNA delivery using hyaluronic acid modified amphiphilic polyplexes against cell cycle and phosphatase proteins to inhibit growth and migration of triple-negative breast cancer cells

Acta biomaterialia, Jan 15, 2018

Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options... more Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options if it recurs after adjuvant chemotherapy. RNA interference could be an alternative therapy for metastatic breast cancer, where small interfering RNA (siRNA) can silence the expression of aberrant genes critical for growth and migration of malignant cells. Here, we formulated a siRNA delivery system using lipid-substituted polyethylenimine (PEI) and hyaluronic acid (HA), and characterized the size, ζ-potential and cellular uptake of the nanoparticulate delivery system. Higher cellular uptake of siRNA by the tailored PEI/HA formulation suggested better interaction of complexes with breast cancer cells due to improved physicochemical characteristics of carrier and HA-binding CD44 receptors. The siRNAs against specific phosphatases that inhibited migration of MDA-MB-231 cells were then identified using library screen against 267 protein-tyrosine phosphatases, and siRNAs to inhibit cell migr...

Research paper thumbnail of Calciphylaxis of the breast with associated diffuse dermal angiomatosis

Human Pathology: Case Reports

Research paper thumbnail of Radiotherapy in the Multidisciplinary Management of Adenomyoepithelioma of the Breast with an Axillary Lymph Node Metastasis: A Case Report and Review of the Literature

Cureus, Jan 21, 2017

We describe a case of aggressive adenomyoepithelioma (AME) of the breast with a lymph node metast... more We describe a case of aggressive adenomyoepithelioma (AME) of the breast with a lymph node metastasis. A 63-year-old female presented with a fluctuating breast mass and clinically palpable lymph nodes. The patient underwent excisional biopsy followed by mastectomy with lymph node dissection and adjuvant radiotherapy (RT). Clinical behavior of both benign and malignant AME is described with the review of the literature and treatment recommendations.

Research paper thumbnail of Cell Counting by Regression Using Convolutional Neural Network

Lecture Notes in Computer Science, 2016

Research paper thumbnail of Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy

The British Journal of Radiology, 2000

Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echoca... more Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echocardiographic identi®cation of the disorder can be made. We believe that the ultrasound features of this disorder have not been previously reported.

Research paper thumbnail of Absence of estrogen receptors in a case of virginal hypertrophy of the breasts related to oral contraceptives

Research paper thumbnail of Abstract P2-11-10: Estrogen drives the therapeutic hormonal response in ER+ breast cancers

Cancer Research, 2020

Background: It is thought that estrogen induces proliferation in all estrogen receptor positive (... more Background: It is thought that estrogen induces proliferation in all estrogen receptor positive (ER+) breast cancer cells. However, there are paradoxical reports of a therapeutic effect of estrogen (E2) with possible E2 induced apoptosis in tumors that are chronically E2 deprived such as after the menopause. We tested whether E2 induced proliferation or apoptosis in post-menopausal women with newly diagnosed breast cancer. Method: We treated 19 women with low dose estradiol (6mg/day) in a window of opportunity trial. Changes in Ki67 and the Prosigna™ Risk of Recurrence Score (ROR) were measured. 13 patients with sufficient tissue had whole transcriptome RNA-seq analysis on pre- and post-treatment specimens to test pathway induction and to derive a gene expression profile (GEP) associated with response to E2. 13 contemporaneous untreated patients were matched for surgical ROR scores to serve as post-hoc controls. The E2-response GEP was then tested on publicly available datasets of E...

Research paper thumbnail of DREAM, a possible answer to the estrogen paradox of the Women's Health Initiative Trial

Heliyon, 2021

WHI trial found that estrogen decreases some ERþ post-menopausal breast cancers. Our prospective ... more WHI trial found that estrogen decreases some ERþ post-menopausal breast cancers. Our prospective clinical trial confirmed an anti-proliferative effect of estradiol. DREAM pathway genes were downregulated during the anti-proliferative response. This suggests that estrogen may activate DREAM quiescence of ERþ breast cancers.

Research paper thumbnail of BCIRG 001 molecular analysis: Identification of prognostic factors in patients (pts) receiving adjuvant therapy for node- positive (N+) breast cancer (BC)

Journal of Clinical Oncology, 2007

525 Background: BCIRG 001 (1,491 pts) demonstrated significant superiority of docetaxel/doxorubic... more 525 Background: BCIRG 001 (1,491 pts) demonstrated significant superiority of docetaxel/doxorubicin/cyclophosphamide (TAC) over fluorouracil/doxorubicin/cyclophosphamide (FAC) given as adjuvant therapy for N+ operable BC in terms of disease-free survival (DFS) and overall survival (OS) (Martin et al, N Eng J Med, 2005). This ancillary study was aimed to identify tumor-associated factors related to DFS and OS. Methods: Formalin-fixed primary tumors from pts in BCIRG 001 were analysed by immunohistochemistry. Protocol- specified assessment of histological grade (GR), tumor size (TS), estrogen (ER) and progesterone receptors (PR), lymph node status (LN), HER2, MUC1, Mib, p53, Bcl-2, Bax, Bcl-X, Bag-1, tubulin β isotypes II, III and IV, tau protein and detyrosinated a tubulin was performed. Parameters were scored as the percentage of positive cells and analysed as lower or greater than median values. The samples were randomly split into training (2/3) and validation (1/3) sets. Associat...

Research paper thumbnail of Sialosyl-TN (B72.3) Shows Coordinated Expression with Polymorphic Epithelial Mucin in Normal and Malignant Breast After Trypsin Pretreatment

Laboratory Investigation, 1995

Research paper thumbnail of Monocytoid B-Cell Lymphoma - a Clinicopathological Study of 35 Cases

Laboratory Investigation, 1992

Research paper thumbnail of Abstract P6-05-05: The estrogen switch: Estrogen receptor alpha levels determine the proliferative response to estrogen

Cancer Research

Background: The premise that estrogen promotes the growth of all estrogen receptor positive (ER) ... more Background: The premise that estrogen promotes the growth of all estrogen receptor positive (ER) + breast cancers has led to anti-estrogen therapies as the standard of care for all ER+ tumors. Paradoxically, estrogen (E2) has demonstrated a therapeutic effect in the adjuvant, palliative and prevention of breast cancers in some women suggesting that there is a subset of ER+ breast cancers that may be growth-suppressed by E2. Our companion window-of-opportunity trial (abstract submitted) found E2 is growth suppressive for some post-menopausal women with high ER expressing tumors. We utilized an in vitro cell model to investigate whether differential growth responses to E2 could be due to transcriptional differences mediated by the level of the ER. Method: We generated a stable MCF-7 transfectant (MCF7-ER) using a fluorescently labelled lentiviral plasmid with a doxycycline inducible ER and compared the response to E2 against an MCF-7 mock transfectant (MCF7-EM). We assessed changes in...

Research paper thumbnail of MUC1 synthetic peptide inhibition of intercellular adhesion molecule-1 and MUC1 binding requires six tandem repeats

Cancer research, 1998

We reported recently that breast cancer-associated MUC1 is a ligand for intercellular adhesion mo... more We reported recently that breast cancer-associated MUC1 is a ligand for intercellular adhesion molecule-1 (ICAM-1; L. H. Regimbald et al., Cancer Res., 56: 4244-4249, 1996). We report here the results of a competitive indirect binding assay to detect the molecular requirements for binding between ICAM-1 and MUC1. The assay involved inhibition of the binding of recombinant human ICAM-1 to a murine breast adenocarcinoma cell line transfected with human MUC1. The addition of a library of human MUC1 synthetic peptides ranging from 9 to 24 amino acids (aa) showed minimal or no inhibition. However, a 120-aa peptide that corresponds to six tandem repeats of the human mucin MUC1 was as effective an inhibitor as purified tumor MUC1 and MUC1 epitope (PDTRPAP)-specific antibody (B27.29). We conclude that the number of MUC1 tandem repeats necessary for an ordered tertiary structure (D. Fontenot et al., Cancer Res., 53: 5386-5394, 1993) is also important for ICAM-1 recognition. These findings ar...

Research paper thumbnail of A novel framework to integrate convolutional neural network with compressed sensing for cell detection

2017 IEEE International Conference on Image Processing (ICIP)

Research paper thumbnail of Developing a clinical-pathologic model to predict genomic risk of recurrence in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative, node negative breast cancer

Cancer Treatment and Research Communications

Research paper thumbnail of BIK drives an aggressive breast cancer phenotype through sublethal apoptosis and predicts poor prognosis of ER-positive breast cancer

Cell Death & Disease

Apoptosis is fundamental to normal animal development and is the target for many anticancer thera... more Apoptosis is fundamental to normal animal development and is the target for many anticancer therapies. Recent studies have explored the consequences of “failed apoptosis” where the apoptotic program is initiated but does not go to completion and does not cause cell death. Nevertheless, this failed apoptosis induces DNA double-strand breaks generating mutations that facilitate tumorigenesis. Whether failed apoptosis is relevant to clinical disease is unknown. BCL-2 interacting killer (BIK) is a stress-induced BH3-only protein that stimulates apoptosis in response to hormone and growth factor deprivation, hypoxia, and genomic stress. It was unclear whether BIK promotes or suppresses tumor survival within the context of breast cancer. We investigated this and show that BIK induces failed apoptosis with limited caspase activation and genomic damage in the absence of extensive cell death. Surviving cells acquire aggressive phenotypes characterized by enrichment of cancer stem-like cells,...

Research paper thumbnail of Utilization of the 21-gene assay for breast cancer treatment decision-making in Alberta

Journal of Clinical Oncology

Research paper thumbnail of Estrogen receptor regulates hormone-induced growth arrest in a luminal A like breast cancer model

Estrogen receptor positive (ER+) breast cancer has been divided into two subtypes, luminal A and ... more Estrogen receptor positive (ER+) breast cancer has been divided into two subtypes, luminal A and luminal B, which differ in their ER expression and response to hormone therapy. The absence of luminal A cell lines means the extensive amount of in vitro work studying the response to hormones in ER+ breast cancers is biased for the luminal B subtype. We have developed a luminal A like cell model by increasing the ER expression in the MCF-7 cell line. Our results show that increased ER expression promotes an anti-proliferative response to estrogen through regulation of genes involved in the G1/S-phase transition of the cell cycle. Furthermore, increased ER expression increases ER-DNA binding in the absence of estrogen and regulates basal gene transcription by promoting DNA looping. These results provide novel evidence that the characteristic increased ER expression of luminal A tumors may promote a novel chromatin configuration that enables growth of these tumors in the absence of estro...

Research paper thumbnail of Training Convolutional Neural Networks and Compressed Sensing End-to-End for Microscopy Cell Detection

IEEE Transactions on Medical Imaging

Automated cell detection and localization from microscopy images are significant tasks in biomedi... more Automated cell detection and localization from microscopy images are significant tasks in biomedical research and clinical practice. In this paper, we design a new cell detection and localization algorithm that combines deep convolutional neural network (CNN) and compressed sensing (CS) or sparse coding (SC) for end-to-end training. We also derive, for the first time, a backpropagation rule, which is applicable to train any algorithm that implements a sparse code recovery layer. The key observation behind our algorithm is that cell detection task is a point object detection task in computer vision, where the cell centers (i.e., point objects) occupy only a tiny fraction of the total number of pixels in an image. Thus, we can apply compressed sensing (or, equivalently sparse coding) to compactly represent a variable number of cells in a projected space. Then, CNN regresses this compressed vector from the input microscopy image. Thanks to the SC/CS recovery algorithm (L 1 optimization) that can recover sparse cell locations from the output of CNN. We train this entire processing pipeline end-to-end and demonstrate that end-to-end training provides accuracy improvements over a training paradigm that treats CNN and CS-recovery layers separately. Our algorithm design also takes into account a form of ensemble average of trained models naturally to further boost accuracy of cell detection. We have validated our algorithm on benchmark datasets and achieved excellent performances.

Research paper thumbnail of An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, Jan 24, 2018

The nuclear proliferation biomarker Ki67 has potential prognostic, predictive, and monitoring rol... more The nuclear proliferation biomarker Ki67 has potential prognostic, predictive, and monitoring roles in breast cancer. Unacceptable between-laboratory variability has limited its clinical value. The International Ki67 in Breast Cancer Working Group investigated whether Ki67 immunohistochemistry can be analytically validated and standardized across laboratories using automated machine-based scoring. Sets of pre-stained core-cut biopsy sections of 30 breast tumors were circulated to 14 laboratories for scanning and automated assessment of the average and maximum percentage of tumor cells positive for Ki67. Seven unique scanners and 10 software platforms were involved in this study. Pre-specified analyses included evaluation of reproducibility between all laboratories (primary) as well as among those using scanners from a single vendor (secondary). The primary reproducibility metric was intraclass correlation coefficient between laboratories, with success considered to be intraclass cor...

Research paper thumbnail of Combinational siRNA delivery using hyaluronic acid modified amphiphilic polyplexes against cell cycle and phosphatase proteins to inhibit growth and migration of triple-negative breast cancer cells

Acta biomaterialia, Jan 15, 2018

Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options... more Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options if it recurs after adjuvant chemotherapy. RNA interference could be an alternative therapy for metastatic breast cancer, where small interfering RNA (siRNA) can silence the expression of aberrant genes critical for growth and migration of malignant cells. Here, we formulated a siRNA delivery system using lipid-substituted polyethylenimine (PEI) and hyaluronic acid (HA), and characterized the size, ζ-potential and cellular uptake of the nanoparticulate delivery system. Higher cellular uptake of siRNA by the tailored PEI/HA formulation suggested better interaction of complexes with breast cancer cells due to improved physicochemical characteristics of carrier and HA-binding CD44 receptors. The siRNAs against specific phosphatases that inhibited migration of MDA-MB-231 cells were then identified using library screen against 267 protein-tyrosine phosphatases, and siRNAs to inhibit cell migr...

Research paper thumbnail of Calciphylaxis of the breast with associated diffuse dermal angiomatosis

Human Pathology: Case Reports

Research paper thumbnail of Radiotherapy in the Multidisciplinary Management of Adenomyoepithelioma of the Breast with an Axillary Lymph Node Metastasis: A Case Report and Review of the Literature

Cureus, Jan 21, 2017

We describe a case of aggressive adenomyoepithelioma (AME) of the breast with a lymph node metast... more We describe a case of aggressive adenomyoepithelioma (AME) of the breast with a lymph node metastasis. A 63-year-old female presented with a fluctuating breast mass and clinically palpable lymph nodes. The patient underwent excisional biopsy followed by mastectomy with lymph node dissection and adjuvant radiotherapy (RT). Clinical behavior of both benign and malignant AME is described with the review of the literature and treatment recommendations.

Research paper thumbnail of Cell Counting by Regression Using Convolutional Neural Network

Lecture Notes in Computer Science, 2016