Suzanne Batra

Independent Researcher

Most people know the honey bees, Apis mellifera, and perhaps also the big black carpenter bees, Xylocopa spp., so conspicuous on the plains and favourite subjects for romantic poetry. As early as Vedic times, several sorts of bees were generally recognized. The “bhramara,” “bhowra” or carpenter bees (Xylocopa) were apparently used to carry messages...

MUC16/CA125 is a tumor marker currently used in clinics for the follow-up of patients with ovarian cancer. However, MUC16 expression is not entirely restricted to ovarian malignancies and has been reported in other cancers including breast cancer. Although it is well established as a biomarker, function of MUC16 in cancer remains to be elucidated....

Pancreatic cancer is one of the most deadly human malignant diseases. The median 5-year survival rate of patients is less than 5%. During the progression of precursor lesions into PDAC, somatic mutations within critical tumor susceptibility loci accumulate, including Kras, Cdkn2a, and Trp53. Also, overexpression of the c-Myc oncogene has been repor...

Pancreatic cancer (PC) harbours an activated point mutation (Kras(G12D)) in the Kras proto-oncogene that has been demonstrated to promote the development of PC. This study was designed to investigate the effect of the oncogenic Kras(G12D) allele on aggressiveness and metastatic potential of PC cells. We silenced the oncogenic Kras(G12D) allele expr...

MUC4 is a heterodimeric large transmembrane mucin expressed by several normal epithelial tissues like testis, lungs and colon and is aberrantly over expressed by most human adenocarcinomas. MUC4 has been strongly implicated to play the role of an oncogene in the progression and metastasis of pancreatic, breast and ovarian cancers. On the other hand...

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC The membrane-bound mucins belong to an ever-increasing family of O-glycoproteins. Based on their structure and localization at the cell surface they are thought to play important biological roles in cell-cell and cell-matrix interactions and cell signaling. The human muc...

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Pancreatic cancer (PC) is a highly lethal malignancy (5-year survival 90ng/ml, NGAL was 67% sensitive (95% C.I. 60%-80%) and 93% specific (95% C.I. 76%-99%) in distinguishing PC from controls. In comparison, CA19-9 at a cut-off of >37U/ml was 82% sensitive (95% C.I. 73%-...

Pancreatic cancer remains one of the most lethal cancers in the world. Currently, the existing therapies have not been optimized and the survival of pancreatic cancer patients remains under 5% after being diagnosed. The high molecular weight glycoprotein Mucin-4 (MUC4) contributes to the regulation of differentiation, proliferation, and metastasis...

Pancreatic cancer is a major problem worldwide and the fourth leading cause of cancer-related deaths in the United States. In the pancreatic malignancy, long term smoking is the most established risk factor. Cigarette smoke contains a variety of constituents of which nicotine is the major component present. Previously, we have shown that MUC4, a me...

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Pancreatic cancer (PC) has a dismal five-year survival rate of about 5%. MUC4 mucin is a large glycoprotein aberrantly expressed by PC cells. We have previously shown that MUC4 stabilizes the receptor tyrosine kinase HER-2. Fluticasone propionate (FP) is a potent glucoco...

The acquisition of invasiveness in ovarian cancer (OC) is accompanied by the process of epithelial-to-mesenchymal transition (EMT). The MUC4 mucin is overexpressed in ovarian tumors and has a role in the invasiveness of OC cells. The present study was aimed at evaluating the potential involvement of MUC4 in the metastasis of OC cells by inducing EM...

MUC17 glycoprotein is a membrane-associated mucin that is mainly expressed in the digestive tract. It has been suggested that MUC17 expression is correlated with the malignancy potential of pancreatic ductal adenocarcinomas (PDACs). In the present study, we provided the first report of the MUC17 gene expression through epigenetic regulation such as...

Accumulating lines of experimental evidence have revealed that the malignant transformation of multipotent tissue-resident adult stem/progenitor cells into cancer stem/progenitor cells endowed with a high self-renewal capacity and aberrant multilineage differentiation potential may be at origin of the most types of human aggressive and recurrent ca...

Only limited data are available regarding mucin antigen expression in adenocarcinoma of the uterine cervix. Fifty-two patients with mucinous adenocarcinoma of the endocervical type were enrolled for making clear implication of the mucin antigens. The expression of mucin antigens in hysterectomized specimens were determined immunohistochemically. Cl...

Mucins (MUC) are high molecular weight O-linked glycoproteins whose primary functions are to hydrate, protect, and lubricate the epithelial luminal surfaces of the ducts within the human body. The MUC family is comprised of large secreted gel forming and transmembrane (TM) mucins. MUC1, MUC4, and MUC16 are the well-characterized TM mucins and have...

An elevated level of macrophage inhibitory cytokine-1 (MIC-1) is reported in the sera of patients with metastatic prostate cancer compared with that of benign diseases and healthy adults. We investigated the mechanistic role of MIC-1 overexpression in the metastasis of prostate cancer cells. Our study showed a progressive increase in secretory MIC-...

A major obstacle to the successful management of pancreatic cancer is to acquire resistance to the existing chemotherapeutic agents. Resistance to gemcitabine, the standard first-line chemotherapeutic agent for advanced and metastatic pancreatic cancer, is mainly attributed to an altered apoptotic threshold in the pancreatic cancer. The MUC4 transm...

Ovarian cancer, the most aggressive gynecologic cancer, is the foremost cause of death from gynecologic malignancies in the developed world. Over 90% of ovarian cancers arise from the surface epithelium, which are classified as epithelial ovarian cancer (EOC). EOCs can be categorized as serous, mucinous, endometrioid, clear cell, and transitional c...

The transcription, which is the RNA ( ribonucleic acid ) biosynthesis, constitutes a tightly regulated multistep process involving the spatial and temporal recruitment of numerous protein complexes. The three main steps of the process are transcription initiation with the formation of the transcription preinitiation complex (PIC), elongation and te...

The fascinating discovery of tissue-resident adult stem/progenitor cells in recent years led to an explosion of interest in the development of novel stem cell-based therapies for improving the regenerative capacity of these endogenous immature cells or transplanted cells for the repair of damaged and diseased tissues. In counterbalance, a growing b...

Recent progress on pancreatic stem/progenitor cell research has revealed that the putative multipotent pancreatic stem/progenitor cells and/or more committed beta cell precursors may persist in the pancreatic gland in adult life. The presence of immature pancreatic cells with stem cell-like properties offers the possibility of stimulating their in...

The mucin MUC4 is a high molecular weight transmembrane glycoprotein. It consists of a mucin-type subunit (MUC4alpha) and a transmembrane growth factor-like subunit (MUC4beta). The mucin MUC4 is overexpressed in many epithelial malignancies including ovarian cancer, suggesting a possible role in the pathogenesis of these cancers. In this study, we...

MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas...

This review summarizes the recent knowledge obtained on the molecular mechanisms involved in the intrinsic and acquired resistance of cancer cells to current cancer therapies. We describe the cascades that are often altered in cancer cells during cancer progression that may contribute in a crucial manner to drug resistance and disease relapse. The...

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27...

The rapid progression from aggressive primary cancers into locally advanced and invasive and/or metastatic diseases remains a big obstacle for an early diagnosis and curative therapeutic intervention for cancer patients. The late-stage leukemias and disseminated and metastatic sarcomas, melanomas, brain tumors and epithelial cancers are the devasta...

Genetic instabilities are believed to be one of the major causes of developing a cancer phenotype in humans. During the progression of cancer, aberrant expression of proteins, either owing to genetic (amplification, mutation and deletion) or epigenetic modifications (DNA methylation and histone deacetylation), contributes in different ways to the d...

MUC4 is a transmembrane mucin, which is aberrantly expressed in pancreatic adenocarcinoma with no detectable expression in the normal pancreas. Here, we present a novel mechanism of IFN-gamma-induced expression of MUC4 in pancreatic cancer cells. Our studies highlight the upregulation of STAT-1 as a basis for MUC4 induction and demonstrate that its...

In this review, we describe the critical functions assumed by the interplay of epidermal growth factor, hedgehog, Wnt/β-catenin, tumor growth factor-β and integrin signaling cascades in tumorigenic and migrating cancer progenitor cells and activated stromal cells during carcinogenesis. These growth factors provide an important role for the sustaine...

Basic and clinical research accomplished during the last few years on embryonic, fetal, amniotic, umbilical cord blood, and adult stem cells has constituted a revolution in regenerative medicine and cancer therapies by providing the possibility of generating multiple therapeutically useful cell types. These new cells could be used for treating nume...

Introduction Functions of cancer progenitor cells in the cancer initiation and progression New model of carcinogenesis based on the cancer progenitor cells Isolation and ex vitro and in vivo characterization of functional properties of cancer progenitor cells Functions of cancer progenitor cells in the cancer development Influence of local tumour m...

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4alpha, and a membrane-bound growth factor-like subunit, MUC4beta. MUC4 mRNA contains unique 5' and 3' coding sequences along with a large variable number of tandem repeat (VNTR) domain...

The mortality of lung cancer remains high, despite improved diagnostic techniques that allow small lung tumors to be detected. In this study, we evaluated the prognostic significance of the tracheal mucin MUC4 by immunohistochemical investigation of the expression profiles of MUC4, ErbB2, p27 and MUC1 in lung adenocarcinoma specimens (non-bronchiol...

MUC4 mucin is a high molecular weight transmembrane glycoprotein that plays important roles in tumour biology. It is aberrantly expressed in pancreatic adenocarcinoma, while not being detectable in the normal pancreas. Previous studies have demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is...

Many of the patients with extrahepatic bile duct carcinoma (EHBDC) show a poor outcome. We have reported that MUC4 is a novel prognostic factor of pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to evaluate the prognostic significance of MUC4 expression in EHBDC. We examined the expression profile of MUC4 in...

The 19q13 amplicon in pancreatic cancer cells contains a novel pancreatic differentiation 2 (PD2) gene (accession number AJ401156), which was identified by differential screening analysis. PD2 is the human homologue of the RNA polymerase II-associated factor 1 (hPaf1). In yeast, Paf1 is part of the transcription machinery, acting as a docking prote...

Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. To investigate the prognostic significance of MUC4 expression in IDC. The express...

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specif...

Mucins are members of an expanding family of large multifunctional glycoproteins. Pancreatic mucins have important biological functions, including the protection, lubrication, and moisturisation of the surfaces of epithelial tissues lining ductal structures within the pancreas. Several lines of evidence support the notion that deregulated mucin pro...

Pleomorphic adenoma of the salivary gland (PA) is essentially a benign neoplasm. However, patients with recurrent PA are difficult to manage. There are rare reports on useful immunohistochemical markers to detect a high risk of recurrence when the primary lesions are resected. To find a new marker to predict the recurrence of PA. Primary lesions of...

Recent advances in understanding of the biological functions of the epidermal growth factor and epidermal growth factor receptor (EGF-EGFR) system and ceramide production for the maintenance of skin integrity and barrier function are reported. In particular, the opposite roles of EGFR and ceramide cascades in epithelial keratinocyte proliferation,...

Tumors with clinically recognizable mucin production arising from bile duct, "mucin-producing bile duct tumors (MPBTs)," have not been studied yet for their pathologic features and classification in details. The clinical findings of MPBT have a lot of similarities to those of pancreatic intraductal papillary-mucinous neoplasm. In the present study,...

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectop...

Complete surgical resection of the tumor is the sole approach to improve the cure rate of patients with intrahepatic cholangiocarcinoma-mass forming type (ICC-MF). Although patients are treated by curative resection, many of them show poor outcome. Mucin (MUC)4 expression has been implicated as a marker for diagnosis and progression of pancreatic a...

Mucins are important biomolecules that frequently display an altered expression under pathological conditions. In a search for a unique and reliable marker(s) specific for pancreatic adenocarcinoma, we investigated the expression of different MUC genes in pancreatic tumors and tumor cell lines, in chronic pancreatitis, and in the normal pancreas. T...

One major constraint in the clinical application of murine monoclonal antibodies (MAbs) is the development of a human antimurine antibody response. The immunogenicity of MAbs can be minimized by replacing nonhuman regions with corresponding human sequences. The studies reported in our article were undertaken to analyze the immunoreactivity and the...

Genetic mechanisms involved in prostate tumor progression from the androgen-responsive to androgen-unresponsive stage are not well understood because of the tremendous heterogeneity in the tumor as well as the lack of suitable models. Using 165 repeat microsatellite DNA markers distributed equally over all of the chromosomes, we determined an assoc...

Radioimmunopharmaceutical agents enabling rapid high-resolution imaging, high tumor-to-background ratios, and minimal immunogenicity are being sought for cancer diagnosis and imaging. Genetic engineering techniques have allowed the design of single-chain Fv's (scFv's) of monoclonal antibodies (mAbs) recognizing tumor-associated antigens. These scFv...

Studies on host-pathogen interactions have led to the discovery of various cell surface associated and secretory molecules. Mucins and mucin-like molecules have recently been described in several protozoan parasites, at different stages of the life cycle. These share many structural and compositional features with mammalian mucins, but vary in seve...

The cells of living organisms in contact with the external environment are constantly attacked by different kinds of substances such as micro-organisms, toxins, and pollutants. With evolution, defense mechanisms, such as the secretion of mucus has been developed. Mucins are the main components of mucus. They are synthesized and secreted by speciali...

Many cancer and diseased cells are distinguished from their normal counterparts by an altered expression of cell-surface epitopes. One family of molecules that show altered expression on tumor cells is mucins (MUC). Unlike normal tissue where MUC exists as heavily glycosylated form, the disease- or tumor-associated MUC molecules are underglycosylat...

Tumor-specific antigens are usually defined by monoclonal antibodies (MAbs) and can play critical roles in the diagnosis and therapy of carcinomas. Despite advances in the understanding of the molecular genetics of human prostate carcinomas, therapeutic approaches require that tumor-specific markers, preferably on the cell surface, should be define...

It has been established that ductal cells or precursor cells within the ductal tree of the pancreas can differentiate into islet cells. Although islet cells can also form exocrine cells, it is unclear whether they arise from precursor (stem) cells or from mature endocrine cells by transdifferentiation. Using a defined culture medium and technique f...

The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. To evaluate in vivo the O-glycos...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a novel member of the tumor necrosis factor superfamily of cytokines that induces cell death by apoptosis. TRAIL has been shown to be effective in almost two-thirds of solid tumors tested thus far, but its effect on pancreatic cancer cells is unknown. We tested the effect of TRAIL o...

Pancreatic cancer (PC) is a common disease that is seldom cured. Current approaches to the treatment of PC are not effective because the non-specific nature of both chemotherapy and external beam radiation results in toxicity to normal tissue. Monoclonal antibodies (MAbs) can be used as selective carriers for delivering radionuclides, toxins, or cy...

MUC4 is a membrane-bound mucin and is considered as the human homologue of the rat sialomucin complex (SMC). The deduced structural organization of the wild type-MUC4 cDNA (WT-MUC4) sequence revealed two subunits: a large amino mucin type subunit (MUC4alpha) and a transmembrane subunit (MUC4beta). MUC4beta is a membrane-bound growth factor like sub...

CD44 is an integral cell-surface glycoprotein. Overexpression of the CD44 standard (CD44st) and its variants (CD44v) has been implicated in transformation and progression of many cancer types. Here, we investigated expression of CD44st, CD44v3-7, CD44v7/8, and v10 in five human pancreatic tumor cell lines and normal human pancreatic duct cells tran...

The long-term maintenance of human islets in culture has remained a challenge. Despite advancements in culture techniques, human islets proved to have a short life span in vitro. For the first time, we have succeeded in maintaining human islets in a defined culture medium for more than 12 months. Freshly isolated islets from a 38-year-old donor wer...

The prospects of radiolabeled antibodies in cancer detection and therapy remain promising. However, efforts to achieve cures, especially of solid tumors, with the systemic administration of radiolabeled monoclonal antibodies (MAbs) have met with limited success. Using genetic engineering techniques, MAbs have been tailored to improve the therapeuti...

Failure of radiolabeled monoclonal antibodies (MAbs) in the treatment of solid tumors, for the most part, is a result of undesirable pharmacokinetics that lead to significant radiation exposure of normal tissues and an inadequate delivery of radiation doses to tumors. Using genetic engineering, antitumor MAbs can be optimized for desirable clinical...

Cultivation and preservation of human pancreatic ductal cells have remained a challenge. With a defined culture medium and refinement of culturing techniques, we have been able to maintain human pancreatic ductal cells without any genetic manipulation in culture for more than 16 months. Freshly isolated ductal fragments were placed on a rocker in M...

The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, rat Muc4) due to its similar structural organization. Like SMC, MUC4 may also exist as two subunits: a mucin type unit known as MUC4alpha and a growth factor-like transmembrane subunit, MUC4beta. The expression of MUC4 in normal human pancreas is not detectable, but it is...

The human MUC4 gene is not expressed in normal pancreas; however, its dysregulation results in high levels of expression in pancreatic tumors. To investigate the tumor-associated expression, MUC4 cDNA was cloned from a human pancreatic tumor cell line cDNA expression library using a polyclonal antibody raised against human deglycosylated mucin and...

The MUC4 mucin gene encodes a putative membrane-anchored mucin with predicted size of 930 kDa, for its 26.5-kb allele. It is composed of two regions, the 850-kDa mucin-type subunit MUC4alpha and the 80-kDa membrane-associated subunit MUC4beta. In this study, we cloned and characterized unique MUC4 cDNA sequences that differ from the originally publ...

Tumor transplants into nude mice (NM) may reveal abnormal biological behavior compared with the original tumor. Despite this, human tumor xenografts in NM have been widely used to study the biology of tumors and to establish diagnostic and therapeutic modalities. Clearly, precise differences in the biology of a given tumor in human and in NM cannot...

Our previous studies in the hamster pancreatic cancer model have shown that exocrine pancreatic cancer arises from ductal/ductular cells, as well as from within the islets, most probably from islet precursor (stem) cells. To identify and characterize these cells, we established a long-term culture from isolated hamster islets and investigated their...

Single-chain variable fragments (scFvs) are tumor-recognition units that hold enormous potential in antibody-based therapeutics. Their clinical applications, however, require the large scale production and purification of biologically active recombinant scFvs. In the present study, we engineered and expressed divalent non-covalent [(scFv)(2)-His(6)...

Giant cell carcinoma of the pancreas is a rare tumor. Its histogenesis is still controversial. In a Syrian hamster pancreatic cancer model, tumors similar to human giant cell carcinomas have been induced at an extremely low rate of incidence and after the use of high doses of pancreatic carcinogens. Thus far no tumors of giant cell type have been i...

Progress in the use of monoclonal antibodies (MAbs) for the treatment of solid tumors is limited by a number of factors, including poor penetration of the labeled IgG molecule into the tumors, their inability to reach the tumor in sufficient quantities without significant normal tissue toxicity, and the development of a human antimouse antibody res...