zu-hua Gao

McGill University | McGill · Department of Pathology

Surgical sutures are gold‐standard wound closure devices. However, they are unable to form a tight seal with surrounding tissues, raising the risks of body fluid leakage and surgical site infection. Additionally, the use of sutures can result in cracking at suture roots, damage and micro‐trauma to soft tissues due to the slicing and compression of...

Background Metastasis is the principal cause of cancer treatment failure and an area of dire diagnostic needs. Colorectal cancer metastases to the liver (CRCLMs) are predominantly classified into desmoplastic and replacement based on their histological growth patterns (HGPs). Desmoplastic responds well to current treatments, while replacement HGP h...

252 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in North America with over 50% of CRC patients developing liver metastases (LM) and 90% will die from metastatic disease. CRCLM are categorized into two main histological growth patterns (HGP) lesions: Desmoplastic (DHGP) and Replacement (RHGP). We have prev...

We produced ten high-quality grossing videos to educate our anatomical pathology residents and pathologist assistants, which will eventually benefit our patients.Each video was followed by a quiz style discussion on the differential diagnoses and associated syndromes of the entities, including renal cell carcinoma, gastrointestinal adenocarcinoma,...

Patient-derived extracellular vesicles (EVs) that contains a complex biological cargo is a valuable source of liquid-biopsy diagnostics to aid in early detection, cancer screening, and precision nanotherapeutics. In this study, we predicted that coupling cancer patient blood-derived EVs to time-resolved spectroscopy and artificial intelligence (AI)...

Introduction Colorectal cancer liver metastasis (CRCLM) remains a lethal diagnosis with an overall 5-year survival rate of 5–10%. Two distinct histopathological growth patterns (HGPs) of CRCLM are known to have significantly differing rates of patients survival, and response to treatment. We set out to review the results of 275 patients who underwe...

Hemophilia A gene therapy targets hepatocytes to express B domain deleted-(BDD) clotting factor VIII (FVIII) to permit viral encapsidation. Since BDD is prone to misfolding in the endoplasmic reticulum (ER) and ER protein misfolding in hepatocytes followed by high fat diet (HFD) can cause hepatocellular carcinoma (HCC), we studied how FVIII misfold...

Non-compressible hemorrhage is an unmet clinical challenge that accounts for high mortality in trauma. Rapid pressurized blood flows under hemorrhage impair the function and integrity of hemostatic agents and the adhesion of bioadhesive sealants. Here, we report the design and performance of bioinspired microstructured bioadhesives, formed with a m...

Tough bioadhesion has important implications in engineering and medicine but remains challenging to form and control. We report an ultrasound (US)-mediated strategy to achieve tough bioadhesion with controllability and fatigue resistance. Without chemical reaction, the US can amplify the adhesion energy and interfacial fatigue threshold between hyd...

Acinar-to-ductal metaplasia (ADM) is a recently recognized, yet less well-studied, precursor lesion of pancreatic ductal adenocarcinoma (PDAC) developed in the setting of chronic pancreatitis. Through digital spatial mRNA profiling, we compared ADM and adjacent PDAC tissues from patient samples to unveil the bridging genes during the malignant tran...

The immune contexture of pancreatic ductal adenocarcinoma (PDAC) is generally immunosuppressive. A role for immune checkpoint inhibitors (ICIs) in PDAC has only been demonstrated for the rare and hypermutated mismatch repair (MMR) deficient (MMR-d) subtype. Homologous recombination repair (HR) deficient (HR-d) PDAC is more prevalent and may encompa...

The early detection of cancer is a challenging problem in medicine. The blood sera of cancer patients are enriched with heterogeneous secretory lipid-bound extracellular vesicles (EVs), which present a complex repertoire of information and biomarkers, representing their cell of origin, that are being currently studied in the field of liquid biopsy...

Patient-derived extracellular vesicles (EVs) that contains a complex biological cargo is a valuable source of liquid biopsy diagnostics to aid in early detection, cancer screening, and precision nanotherapeutics. In this study, we predicted that coupling cancer patient blood-derived EVs to time-resolved spectroscopy and artificial intelligence (AI)...

Background Malignant vascular tumors (MVTs) are rare and often misdiagnosed due to wide range of clinical presentations, varied histology, and exquisite imagining features. We aim to characterize two different types of MVTs of the liver: hepatic angiosarcomas (HA) and hepatic epithelioid hemangioendotheliomas (HEHE). Methods Data on HA and HEHE be...

Background Traditional medical genetics models are unable to meet the growing demand for germline genetic testing (GT) in patients with exocrine pancreatic cancer (PC). This study investigates the impact of an ambulatory oncology clinic-based GT model. Methods From 2012 to 2021, patients with PC were prospectively enrolled and considered for GT. T...

Pancreatic ductal adenocarcinomas (PDACs) with DNA mismatch repair deficiency (MMRd) respond preferentially to immune checkpoint inhibitors (ICIs). However, a subset of MMRd PDACs does not respond to these agents. This report describes a patient with PDAC who experienced rapid disease progression suggestive of hyperprogressive disease. The case inv...

p>High-grade serous ovarian cancer (HGSOC) is a lethal disease often diagnosed in grade III International Federation of Gynecology and Obstetrics (FIGO) upon colonization of the peritoneal cavity, or in grade IV FIGO when it colonizes the pleural cavity. When in the pleural cavity, the disease often manifests with accumulation of pleural effusions...

Persistent acinar to ductal metaplasia (ADM) is a recently recognized precursor of pancreatic ductal adenocarcinoma (PDAC). Here we show that the ADM area of human pancreas tissue adjacent to PDAC expresses significantly higher levels of regenerating protein 3A (REG3A). Exogenous REG3A and its mouse homolog REG3B induce ADM in the 3D culture of pri...

Background: We reported that a novel oncosuppressor-mutated cell (OMC)-based platform has the potential for early cancer detection in healthy individuals and for identification of cancer patients at risk of developing metachronous metastases. Objective: Herein, we sought to determine the diagnostic accuracy of this novel OMC-based platform in a...

Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that Claudin-2 is functionally required for colorectal cancer liver metastasis and that Claudin-2 expression in primary colorectal cancers is associated with poor overall and liver metastasis-free survival. We have examined the r...

Objective: To evaluate the diagnostic performance of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for grading hepatic inflammation. Methods: In this retrospective cross-sectional dual-center study, 91 patients with chronic liver disease were recruited between September 2014 and September 2018. Patients underwent 3.0-T MRI...

Clotting factor VIII (FVIII) is the protein deficient in the bleeding disorder hemophilia A (HA). FVIII is a 330 kDa glycoprotein with a domain structure of A1-A2-B-A3-C1-C2. The B domain is dispensable for activity but in vivo hepatocyte transfection with B domain deleted (BDD) DNA vector resulted in FVIII misfolding, endoplasmic reticulum (ER) st...

Giant cell hepatitis (GCH) is a rare entity in adults that is characterized by large multinucleated hepatocyte formation and parenchymal inflammation. We present a case of acute liver failure in a 33-year-old woman secondary to autoimmune hepatitis (AIH). A liver biopsy revealed submassive hepatocyte necrosis consistent with GCH. We conducted a lit...

Background In the USA, fibrolamellar hepatocellular carcinoma (FLC) accounts for 1–2% of all cases of hepatocellular carcinoma. FLC remains poorly understood. Aim We aim to investigate the incidence, demographics, tumor characteristics, treatment, and prognosis of patients with FLC. Methods Data on FLC between 2000 and 2016 were extracted from th...

Background: Anti-soluble liver antigen/liver pancreas (anti-SLA/LP) is a highly specific serological marker for the diagnosis of autoimmune hepatitis (AIH). The aim of the present study was to define the clinical characteristics and human leucocyte antigen (HLA) genotypes of Chinese patients with anti-SLA/LP positive AIH. Methods: Ninety-one AIH...

Insulin-like growth factor (IGF) 1 is an essential growth factor and important anabolic hormone. Targeting the pancreas, both IGF-1 and -2 regulate β-cell growth, survival, and insulin secretion. In recent years, we have characterized several target genes specifically regulated by IGF-1 within the pancreas or endocrine islets. The roles of IGF-1 on...

Purpose: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinums and poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated with heterogeneous responses. Experimental d...

Colorectal cancer liver metastases (CRCLM) that present with a replacement histopathological growth pattern (HGP) are resistant to neoadjuvant anti‐angiogenic therapy. Surrogate biomarkers are not available to preoperatively identify patients with these tumors. Here we identify differentially expressed genes between CRCLM with a replacement HGP and...

Many studies have examined the biology, genetics, and chemotherapeutic response of ovarian cancer’s solid component; its liquid facet, however, remains critically underinvestigated. Floating within peritoneal effusions known as ascites, ovarian cancer cells form multicellular structures, creating a cancer niche in suspension. This study explores th...

In the past 15 years, gut microbiota emerged as a crucial player in health and disease. Enormous progress was made in the analysis of its composition, even in the discovery of novel species. It is time to go beyond mere microbiota-disease associations and, instead, provide more causal analyses. A key mechanism of metabolic regulation by the gut mic...

Pancreatic ß cell proliferation, survival and function are key elements that need to be considered in developing novel antidiabetic therapies. We recently identified CCN5/WISP2 to have potential growth promoting properties when overexpressed in ß cells; however, further investigations are needed to validate those properties. In this study, we demon...

Background: Different histological growth patterns (HGPs) of colorectal carcinoma (CRC) liver metastasis are associated with patients' prognosis and response to antiangiogenic therapy. However, the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established. Aim...

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Three different histopathological growth patterns (HGP) have been identified in colorectal cancer liver metastases (CRCLM) resected from patients: the desmoplastic HGP, the pushing HGP, and the replacement HGP. Evidence suggests that the predominant growth pattern with which a CRCLM presents has clinically relevant prognostic implications. We have...

Three different histopathological growth patterns (HGP) have been identified in colorectal cancer liver metastases (CRCLM) resected from patients: the desmoplastic HGP, the pushing HGP, and the replacement HGP. Evidence suggests that the predominant growth pattern with which a CRCLM presents has clinically relevant prognostic implications. We have...

p>The histopathology of high-grade serous ovarian cancer (HGSOC) in orthotopic mouse models has received limited attention. Using immunosuppressed mice, we generated intraperitoneal HGSOC disease that includes formation of ascites and/or pleural effusions, together with a myriad of intra-abdominal growths. We studied 3 HGSOC cell lines evolved from...

Background: We reported that horizontal transfer of malignant traits to target cells is a potential pathway to explain cancer dissemination. Although these results were encouraging, they were never corroborated by data showing the molecular mechanisms responsible for the observed phenomenon. Methods: In the present study, we exposed BRCA1-KO fib...

Background/Purpose Occult HBV infection (OBI) could have serious clinical consequences in patients receiving immunosuppressive therapy. We aimed to investigate the prevalence of OBI in Chinese patients with autoimmune hepatitis (AIH) and to analyze its clinical and virological features. Methods 103 AIH cases were enrolled. Hepatitis B virus (HBV)...

Glucagon-like peptide-1 (GLP-1)-based therapies, including GLP-1 analogs and dipeptidyl peptidase 4 inhibitors, are important options in treating patients with type 2 diabetes (T2D). GLP-1, an incretin hormone released predominantly from intestinal L-cells in response to nutrient ingestion, has clear benefits against postprandial hyperglycemia. GLP...

Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific discovery has fuelled recent ameliorations in the outcomes of many other cancers, the rates of mortality for ovarian cancer have been stagnant since around 1980. Yet despite the grim o...

We reported on the ability of immortalized or oncosuppressor-mutated cells (OMCs) to uptake circulating cancer-factors and give tumors when transplanted into mice. This led to the first biological based liquid biopsy test, which we called MATER-D platform. In the present study, we showed for the first time that a different type of OMCs (PTEN-defici...

Both chemokine receptors (CXCRs) 7 and 4 can facilitate immune cell migration and mediate a vast array of physiological and pathological events. Herein we report, in both human and animal studies, that these two CXCRs can form heterodimers in vivo and promote colorectal tumorigenesis through histone demethylation. Compared with adjacent non-neoplas...

Pathology is a specialty that bridges basic medical science and clinical practice. In the era of personalised medicine, this specialty is facing unprecedented challenges. Some of these challenges are institution-specific, while many are shared worldwide at different magnitude. This review shares our team efforts in the past 5 years, 2012–2017, to r...

Colorectal carcinoma (CRC) remains the third leading cause of cancer death in the Western world. Over 50% of CRC patients develop liver metastases (LM) and 90% will die from metastatic disease. Angiogenic inhibitors AIs (bevacizumab, Bev) were introduced with chemotherapy as first-line therapy for CRCLMs. While some patients respond well to this th...

Figure S1. Areas selected for scoring for desmoplastic histopathological growth pattern (DHGP) and replacement histopathological growth pattern (RHGP) lesions. For each lesion we selected the following areas and annotated 3 areas in each: 1. Central tumor (CT: blue); 2. Peripheral tumor (PT: red); 3. Adjacent normal liver (AN: green); 4. Distal nor...

Figure S2. VEGF‐A staining of colorectal carcinoma liver metastases (DHGP vs RHGP lesions). Tumor sections were stained with an antibody detecting VEGF‐A (red). Representative low‐magnification images are shown from each of the groups analyzed. Two insets are shown for each image at high magnification indicating adjacent liver staining and peripher...

Table S1. Histopathological characterization of colorectal carcinoma liver metastases. Serial sections were stained with H&E to visualize tissue architecture. Viable cells, inflammation grade and necrosis are represented as percentage of total lesion. Differentiation was classified as Undifferentiated (UN) and Differentiated (D). DHGP, desmoplastic...

Background Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patien...

Background: PBC is a prototypical autoimmune liver disease characterized by portal lymphoplasmacyte infiltration. ALD is a prototypical environment-driven disease, featured by mild lymphocyte infiltration. We hypothesize B cells are more involved in the pathogenesis of PBC. By analyzing the infiltrating B cell repertoire, we aimed to unveil greate...

Approximately 9% of cancer-related deaths are caused by colorectal cancer. Liver metastasis is a major factor for the high colorectal cancer mortality rate. However, the molecular mechanism underlying colorectal cancer liver metastasis remains unclear. Using a global and multidimensional integration approach, we studied sequencing data, protein-pro...

The function of node genes in PMCT PPI network. (DOCX)

The function of node genes in LMCT PPI network. (DOCX)

Gene modules in PMCT. (DOCX)

Gene modules in LMCT. (DOCX)

Modules with significant overlap. (DOCX)

The function of modules with significant overlap. (DOCX)

Modules with significant crosstalk. (DOCX)

The function of modules with significant crosstalk. (DOCX)

The resistance mechanisms that limit the efficacy of retinoid therapy in cancer are poorly understood. Sphingosine kinase 2 (SphK2) is a highly conserved enzyme that is mainly located in the nucleus and endoplasmic reticulum. Unlike well-studied sphingosine kinase 1 (SphK1) located in the cytosol, little has yet understood the functions of SphK2. H...

AIM To investigated the feasibility of using sinusoidal endotheliitis (SE) as a histological marker for liver allograft rejection. METHODS We compared the histological features of 88 liver allograft biopsies with acute cellular rejection (ACR) and 59 cases with no evidence of ACR. SE was scored as: (1) focal linear lifting up of the endothelial ce...

Maintaining pancreatic β-cell mass and function is essential for normal insulin production and glucose homeostasis. Regenerating islet-derived 2 (Reg2, Reg II, human orthologue Reg1B) gene is normally expressed in pancreatic acinar cells and significantly induced in responses to diabetes, pancreatitis, high-fat diet and during pancreatic regenerati...

In many cancers, the establishment of a patient’s future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the ‘pathological response’ to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry im...

Background: It was reported that metastases might occur via transfer of biologically active blood circulating molecules from the primary tumor to distant organs rather than only migration of cancer cells. We showed in an earlier study that exposure of immortalized human embryonic kidney cells (HEK 293) to cancer patient sera, induce their transfor...

Background High-throughput technologies have the potential to identify non-invasive biomarkers of liver pathology and improve our understanding of basic mechanisms of liver injury and repair. A metabolite profiling approach was employed to determine associations between alterations in serum metabolites and liver histology in patients with chronic h...

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to...

In search of direct targets of IGF-I action, we discovered CCN5/WISP2 as a novel protein expressed in pancreatic β-cells. As a member of Cyr61 (connective tissue growth factor in human), CTGF (cysteine rich 61, in mouse), and Nov (nephroblastoma overexpressed, in chicken) family, IGF-I together with Wnt signaling stimulate its expression. When over...

Reg family proteins have long been implicated in islet β-cell proliferation, survival, and regeneration. In our previous study, we reported that Reg3β overexpression did not increase islet growth but prevented streptozotocin-induced islet damage by inducing specific genes. In order to explore its role in type 2 diabetes (T2D), we established high-f...

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiog...

After the publication of the article, the authors noted that the affiliation for Dr Hani Choudhry is wrong. The correct affiliation should be as follows: Bo Gao1, Qin Shao2, Hani Choudhry3, Victoria Marcus2, Kung Dong5, Jiannis Ragoussis4 and Zu-Hua Gao2, 1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Ha...

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum anti-mitochondrial Ab and lymphocyte-mediated bile duct damage. This study was designed to reveal the clonal characteristics of B lymphocyte repertoire in patients with PBC to facilitate better understanding of its pathogenesis and better management of...

Colorectal cancer (CRC) is the third leading cause of cancer-related death in North America. Approximately 50% of patients will be diagnosed with CRC liver metastasis (CRLM) during the course of their disease. Untreated, patients will survive for only a few months, but with chemotherapy, a median survival of 20 months can be achieved. At present, n...

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancer types, with a 5-year survival rate <5%. Tumor specific biomarkers that can aid in early detection and treatment monitoring are urgently needed in order to improve the outcomes. Human Reg family proteins (Reg1A, Reg1B, Reg3A, Reg3G and Reg4) are a group of calcium-dependent...

Approximately 9% of cancer-related deaths are caused by colorectal cancer (CRC). CRC patients are prone to liver metastasis, which is the most important cause for the high CRC mortality rate. Understanding the molecular mechanism of CRC liver metastasis could help us to find novel targets for the effective treatment of this deadly disease. Using we...

We have read with great interest the recent report by Loncle and colleagues (1) investigating the role of REG3β in mediating protumoral effects of IL17. We agree in principal with their conclusion that Reg3β is involved in the initiation of pancreatic ductal adenocarcinoma (PDAC) and its progression. We also found Reg gene expression in duct-like s...

Successful colonization by a cancer cell of a distant metastatic site requires immune escape in the new microenvironment. Tumor necrosis factor (TNF) signaling has been implicated broadly in the suppression of immune surveillance that prevents colonization at the metastatic site and therefore must be blocked. In this study, we explored how TNF sign...

We have reported a high expression of IGF-I in pancreatic islet β-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which is responsible for the con...

Chemokine CXCL12 is an extracellular chemokine, which binds to its cell surface receptor CXCR4. High expressions of CXCR4 and CXCL12 are associated with biological malignant potential in colon cancers. We aimed to investigate the roles of the CXCR4/CXCL12 axis in activation of the Wnt/β-catenin pathway in the development of colon cancers. Using col...

Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the g...

cAMP responsive element binding protein 1 (CREB1) has been reported to be implicated in tumor development and progression of human cancers. However, the clinical significance and regulatory mechanisms of CREB1 expression in gastric cancer remain largely unknown. In the present study, immunohistochemistry was performed to detect the expression of CR...

Sorafenib is the first multikinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC), and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor a...