Publications by authors named "Puja Singh"

36 Publications

Evaluation of Inflammatory Acute Phase Protein Level and Different Leukocyte Counts in Chronic Periodontitis Normolipidemic Patients after Nonsurgical Periodontal Therapy.

J Contemp Dent Pract 2021 Apr 1;22(4):373-377. Epub 2021 Apr 1.

Department of Pediatrics and Preventive Dentistry, Nalanda Medical College and Hospital, Patna, Bihar, India, Phone: +91 9472373307, e-mail:

Aim And Objective: To evaluate the effect of nonsurgical periodontal therapy on periodontal parameters, serum C-reactive protein (CRP) level, total leukocyte count (TLC), and differential leukocyte count (DLC) in normolipidemic patients with generalized chronic periodontitis.

Materials And Methods: A total of 60 subjects (38 males and 22 females) between 20 and 55 years of age were included in this study. Twenty subjects with generalized chronic gingivitis were assigned group I. Forty subjects with generalized chronic periodontitis were randomly divided into test groups, i.e., group II ( = 20) and control group, i.e., group III ( = 20). At baseline, clinical parameters (plaque and gingival indices, clinical attachment loss) were recorded and blood collected for lipid profile test, TLC, DLC, and CRP estimation. Patients with lipid values in the normal range continued the study. Groups I and II were provided nonsurgical periodontal therapy. Follow-up clinical examination and blood examination were done for CRP level, TLC, and DLC after 1 and 2 months.

Results: A significant improvement in the clinical parameters was evident following scaling and root planning in group II as compared to group III. A decrease in serum CRP and TLC count was also observed, but the difference was not significant. Moreover, a reduction was observed in neutrophils, monocytes, eosinophils post therapeutically in group II but the decrease was significant only for monocyte count.

Conclusion: Based on the findings of the study, it can be concluded that nonsurgical periodontal therapy can reduce the inflammatory component.

Clinical Significance: Periodontal diseases comprise a wide range of inflammatory conditions affecting the supporting structures of teeth. Effect of nonsurgical periodontal therapy on chronic periodontitis can be evaluated by measuring the CRP and leukocyte concentration.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2021

miRNAs play critical roles in response to abiotic stress by modulating cross-talk of phytohormone signaling.

Plant Cell Rep 2021 Jun 22. Epub 2021 Jun 22.

Molecular Biology and Biotechnology Division, CSIR-National Botanical Research Institute, Lucknow, India.

One of the most interesting signaling molecules that regulates a wide array of adaptive stress responses in plants are the micro RNAs (miRNAs) that are a unique class of non-coding RNAs constituting novel mechanisms of post-transcriptional gene regulation. Recent studies revealed the role of miRNAs in several biotic and abiotic stresses by regulating various phytohormone signaling pathways as well as by targeting a number of transcription factors (TFs) and defense related genes. Phytohormones are signal molecules modulating the plant growth and developmental processes by regulating gene expression. Studies concerning miRNAs in abiotic stress response also show their vital roles in abiotic stress signaling. Current research indicates that miRNAs may act as possible candidates to create abiotic stress tolerant crop plants by genetic engineering. Yet, the detailed mechanism governing the dynamic expression networks of miRNAs in response to stress tolerance remains unclear. In this review, we provide recent updates on miRNA-mediated regulation of phytohormones combating various stress and its role in adaptive stress response in crop plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00299-021-02736-yDOI Listing
June 2021

Comparison and Evaluation of Linear Dimensional Accuracy of Three Elastomeric Impression Materials at Different Time Intervals Using Vision Inspection System: An Study.

J Int Soc Prev Community Dent 2020 Nov-Dec;10(6):736-742. Epub 2020 Nov 24.

Department of Prosthodontics & Crown and Bridge, Buddha Institute of Dental Sciences & Hospital, Patna, Bihar, India.

Background: Making an impression represents a crucial step in fabrication of a prosthesis. Elastomers are the most commonly used materials for precise and accurate recording and reproduction of tooth morphology and surrounding soft tissue.

Aims And Objective: The aim of this study was to compare and evaluate the linear dimensional accuracy of three elastomeric impression materials: addition silicone, condensation silicone, and polyether at different time intervals up to 15 days using a vision inspection system.

Materials And Methods: Dimensional accuracy of impression materials was measured at certain designated time periods using stainless steel die. The impressions of die were made using one representative material of each type of elastomeric impression material. The die along with the impression material in the mold was held using a clamp and put in a water bath maintained at mouth temperature. The linear dimensional changes taking place in each material with time were measured using the vision inspection system.

Results: On comparison with master die impression at 30min, 1h, and 1½ h time interval, a significant decreased mean dimension of condensation silicone was observed, whereas addition silicone and polyether showed statistically nonsignificant difference. At 2, 3, 4, and 12h time span, a significant difference in mean dimension of addition and condensation silicone was noted, whereas polyether showed a nonsignificant difference. At 24h, 1 week, and 15 days duration, on comparison with the master die, a significant reduction in mean dimension of condensation silicone was discovered, whereas addition silicone and polyether showed nonsignificant difference.

Conclusion: Polyether showed significantly lesser dimensional changes among all three materials, though the differences were small enough to be considered clinically acceptable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jispcd.JISPCD_282_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791581PMC
November 2020

Effect of Intracanal Medicaments (Modified Triple Antibiotic Paste, Calcium Hydroxide, and Aloe Vera) on Microhardness of Root Dentine: An Study.

J Contemp Dent Pract 2020 Jun 1;21(6):632-635. Epub 2020 Jun 1.

Department of Oral Medicine and Radiology, Buddha Institute of Dental Sciences and Hospital Patna, Bihar, India.

Aim: To compare the effect of three different intracanal medicaments, namely, modified triple antibiotic paste (MTAP), calcium hydroxide (Ca(OH)), and aloe vera, on the root dentine microhardness.

Materials And Methods: A total of 50 extracted mandibular bicuspids were prepared using ProTaper Next rotary files. The roots of the bicuspids were alienated to three groups ( = 10 each) and one control group (untreated; = 20). In three groups, the root canals were filled with MTAP, Ca(OH), and aloe vera medicaments. After 21 days, medicaments were removed by Endo activator. Mean Knoop hardness numbers were calculated after treatment and compared with the untreated control group. Data were evaluated using the Student's test (paired), ANOVA (one-way) followed, and the test.

Results: All treated groups except the aloe vera group had shown significant reduction ( < 0.05) in microhardness of the root dentin as compared with the untreated control group. The aloe vera group showed least reduction of microhardness and was statistically insignificant ( > 0.05).

Conclusion: Aloe vera shows promising results in terms of fewer effects on microhardness of the root dentin compared to MTAP and Ca(OH).

Clinical Significance: Elimination of most of the bacterial infection from the root canal and very minimum to no effect on the microhardness of the dentin in the root part are the basics of success in any endodontic treatment. Further studies are required to compare the efficacy of these intracanal medicaments.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2020

Correlation of dental caries and dermatoglyphic patterns: A study in pediatric population.

J Family Med Prim Care 2020 Jun 30;9(6):2980-2984. Epub 2020 Jun 30.

Department of Oral Medicine and Radiology, Private Practitioner, Patna, Bihar, India.

Introduction: Dental caries is the most prevalent chronic disease among children worldwide irrespective of the advancements in oral healthcare. The basis of considering dermatoglyphic patterns as marker for dental caries is that the epithelium of finger buds and enamel are both ectodermal in origin and develop during the same period of intrauterine life.

Aim And Objective: To record and evaluate the dermatoglyphic patterns, its correlation with early childhood caries (ECC) and to predict its efficacy in assessing the caries risk.

Method: The study was carried out on 100 school going children within the age group of 36-71 months. Study population was divided into two groups comprising of 50 individuals each on the basis of def score, experimental group (def ≥ 1) and control group (def score 0). Dermatoglyphic patterns of all ten palmar digits were recorded using Cummins and Midlo method and assessed using a magnifying glass (2×).

Results: Statistically significant increase in number of whorls was found in ECC group, whereas higher number of loops was seen in control group. In ECC group, value of both, the mean axial t triradius angle and mean total ridge count was low as compared to the caries-free group.

Conclusion: There is definite variation in dermatoglyphics between the ECC and caries-free group, indicating that dermatoglyphic patterns can be used as a non-invasive predictive tool for children with ECC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jfmpc.jfmpc_208_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491820PMC
June 2020

Auxin-salicylic acid cross-talk ameliorates OsMYB-R1 mediated defense towards heavy metal, drought and fungal stress.

J Hazard Mater 2020 11 20;399:122811. Epub 2020 May 20.

Molecular Biology and Biotechnology Division, CSIR-National Botanical Research Institute, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. Electronic address:

The MYB TF family is an immensely large and functionally diverse class of proteins involved in the regulation of cell cycle, cell morphogenesis to stress signaling mechanism. The present study deciphered the hormonal cross-talk of wound inducible and stress-responsive OsMYB-R1 transcription factor in combating abiotic [Cr(VI) and drought/PEG] as well as biotic (Rhizoctonia solani) stress. OsMYB-R1 over-expressing rice transgenics exhibit a significant increase in lateral roots, which may be associated with increased tolerance under Cr(VI) and drought exposure. In contrast, its loss-of-function reduces stress tolerance. Higher auxin accumulation in the OsMYB-R1 over-expressed lines further strengthens the protective role of lateral roots under stress conditions. RNA-seq. data reveals over-representation of salicylic acid signaling molecule calcium-dependent protein kinases, which probably activate the stress-responsive downstream genes (Peroxidases, Glutathione S-transferases, Osmotins, Heat Shock Proteins, Pathogenesis Related-Proteins). Enzymatic studies further confirm OsMYB-R1 mediated robust antioxidant system as catalase, guaiacol peroxidase and superoxide dismutase activities were found to be increased in the over-expressed lines. Our results suggest that OsMYB-R1 is part of a complex network of transcription factors controlling the cross-talk of auxin and salicylic acid signaling and other genes in response to multiple stresses by modifying molecular signaling, internal cellular homeostasis and root morphology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2020.122811DOI Listing
November 2020

Inguinal Lymph Node Dissection Does Not Improve Overall Survival in Anal Cancer Nodal Disease.

J Surg Res 2020 11 12;255:13-22. Epub 2020 Jun 12.

Department of Surgery, Cooper University Hospital, Camden, New Jersey. Electronic address:

Background: Anal SCC is a rare disease mainly treated with chemoradiation. Abdominoperineal resection (APR), once the mainstay of treatment for anal cancer, now serves a role as salvage therapy for persistent or recurrent disease after chemoradiation. In addition, clinically positive nodes are currently treated by extending the radiation field to the groin. The role of inguinal lymph node dissection in recurrent or persistent anal SCC is unclear. The aim of the study is to determine the role of inguinal lymph node dissection in the management of inguinal lymph node metastasis for anal squamous cell carcinoma (SCC).

Methods: Retrospective analysis of patients with anal SCC in the National Cancer Database with positive inguinal nodes undergoing salvage APR between 2004 and 2014 was performed. A comparison of overall survival between patients who underwent APR with lymph node dissection versus APR only was analyzed using Kaplan-Meier plot.

Results: A total of 3424 patients underwent salvage APR, with 274 (8%) having clinically positive nodes. Within the subgroup that had clinically positive nodes, 195 (71%) underwent APR, whereas 79 (29%) underwent both APR and node dissection. Kaplan-Meier analysis demonstrates no difference in overall survival in the two groups (P = 0.99). Five-year survival for both groups was similar (36% versus 42%; P = 0.987). No significant difference was found when adjusted for age, gender, and Tumor Node Metastasis staging.

Conclusions: Inguinal lymph node dissection does not appear to improve overall survival in patients with advanced-stage anal cancer requiring salvage APR. Proper patient selection for node dissection is essential to spare patients from additional morbid procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2020.05.034DOI Listing
November 2020

Aurora A site specific TACC3 phosphorylation regulates astral microtubule assembly by stabilizing γ-tubulin ring complex.

BMC Mol Cell Biol 2019 12 10;20(1):58. Epub 2019 Dec 10.

School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Vithura, Thiruvananthapuram, 695551, India.

Background: Astral microtubules emanating from the mitotic centrosomes play pivotal roles in defining cell division axis and tissue morphogenesis. Previous studies have demonstrated that human transforming acidic coiled-coil 3 (TACC3), the most conserved TACC family protein, regulates formation of astral microtubules at centrosomes in vertebrate cells by affecting γ-tubulin ring complex (γ-TuRC) assembly. However, the molecular mechanisms underlying such function were not completely understood.

Results: Here, we show that Aurora A site-specific phosphorylation in TACC3 regulates formation of astral microtubules by stabilizing γ-TuRC assembly in human cells. Mutation of the most conserved Aurora A targeting site, Ser 558 to alanine (S558A) in TACC3 results in robust loss of astral microtubules and disrupts localization of the γ-tubulin ring complex (γ-TuRC) proteins at the spindle poles. Under similar condition, phospho-mimicking S558D mutation retains astral microtubules and the γ-TuRC proteins in a manner similar to control cells expressed with wild type TACC3. Time-lapse imaging reveals that S558A mutation leads to defects in positioning of the spindle-poles and thereby causes delay in metaphase to anaphase transition. Biochemical results determine that the Ser 558- phosphorylated TACC3 interacts with the γ-TuRC proteins and further, S558A mutation impairs the interaction. We further reveal that the mutation affects the assembly of γ-TuRC from the small complex components.

Conclusions: The results demonstrate that TACC3 phosphorylation stabilizes γ- tubulin ring complex assembly and thereby regulates formation of centrosomal asters. They also implicate a potential role of TACC3 phosphorylation in the functional integrity of centrosomes/spindle poles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12860-019-0242-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902513PMC
December 2019

Perception, awareness, and practice among patients seeking orthodontic treatment toward maintenance of periodontal health and factors affecting the same among patients visiting dental clinics in Patna.

J Family Med Prim Care 2019 Nov 15;8(11):3695-3699. Epub 2019 Nov 15.

Private Practitioner, Patna, Bihar, India.

Background: During the orthodontic treatment, maintenance of periodontal health is of utmost importance; hence, this study was conducted to explore the perception and awareness of patients seeking orthodontic treatment toward maintenance of periodontal health and factors affecting the same.

Materials And Methods: It was a cross-sectional descriptive questionnaire study conducted among134 patients seeking orthodontic treatment from 16 private clinics in Patna. The study was conducted in the month of June 2019. The city was divided into four directions east, west, north, and south and four clinics were selected from each directions randomly. A close-ended questionnaire was prepared consists of demographic details and questions regarding their perception, awareness, and practice to maintain periodontal health from the start of orthodontic treatment.

Results: Majority of study participants {74 (55.22%)} were between the age group of 11 and 15 years. Among all study participants, females {81 (60.45%)} were more than males. It was determined that 112 (83.58%) of patients were using tooth brush and tooth paste/powder for cleaning teeth. There was moderate awareness, negative perception, and fair practice of majority of study participants seeking orthodontic treatment toward maintenance of periodontal health. Awareness of study participants was significantly (-value ≤ 0.05*) associated with practice.

Conclusion: There was moderate awareness, negative perception, and fair practice of majority of study participants seeking orthodontic treatment toward maintenance of periodontal health. Education of study participants was significantly associated with awareness and practice regarding maintenance of periodontal health. There is further need to educate the orthodontic patients toward maintenance of periodontal health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jfmpc.jfmpc_773_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881928PMC
November 2019

Protein lysine 43 methylation by EZH1 promotes AML1-ETO transcriptional repression in leukemia.

Nat Commun 2019 11 7;10(1):5051. Epub 2019 Nov 7.

Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, 1098 Xueyuan Ave, 518060, Shenzhen, China.

The oncogenic fusion protein AML1-ETO retains the ability of AML1 to interact with the enhancer core DNA sequences, but blocks AML1-dependent transcription. Previous studies have shown that post-translational modification of AML1-ETO may play a role in its regulation. Here we report that AML1-ETO-positive patients, with high histone lysine methyltransferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. We find that EZH1 WD domain binds to the AML1-ETO NHR1 domain and methylates AML1-ETO at lysine 43 (Lys43). This requires the EZH1 SET domain, which augments AML1-ETO-dependent repression of tumor suppressor genes. Loss of Lys43 methylation by point mutation or domain deletion impairs AML1-ETO-repressive activity. These findings highlight the role of EZH1 in non-histone lysine methylation, indicating that cooperation between AML1-ETO and EZH1 and AML1-ETO site-specific lysine methylation promote AML1-ETO transcriptional repression in leukemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12960-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838331PMC
November 2019

ErbB3-binding protein 1 (EBP1) represses HNF4α-mediated transcription and insulin secretion in pancreatic β-cells.

J Biol Chem 2019 09 30;294(38):13983-13994. Epub 2019 Jul 30.

Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, Minnesota 55912

HNF4α (hepatocyte nuclear factor 4α) is one of the master regulators of pancreatic β-cell development and function, and mutations in the α gene are well-known monogenic causes of diabetes. As a member of the nuclear receptor family, HNF4α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge of the different functional complexes in which HNF4α participates. Here, to find HNF4α-binding proteins in pancreatic β-cells, we used yeast two-hybrid screening, a mammalian two-hybrid assay, and glutathione -transferase pulldown approaches, which identified EBP1 (ErbB3-binding protein 1) as a factor that binds HNF4α in a LLL motif-mediated manner. In the β-cells, EBP1 suppressed the expression of HNF4α target genes that are implicated in insulin secretion, which is impaired in HNF4α mutation-driven diabetes. The crystal structure of the HNF4α ligand-binding domain in complex with a peptide harboring the EBP1 LLL motif at 3.15Å resolution hinted at the molecular basis of the repression. The details of the structure suggested that EBP1's LLL motif competes with HNF4α coactivators for the same binding pocket and thereby prevents recruitment of additional transcriptional coactivators. These findings provide further evidence that EBP1 plays multiple cellular roles and is involved in nuclear receptor-mediated gene regulation. Selective disruption of the HNF4α-EBP1 interaction or tissue-specific EBP1 inactivation can enhance HNF4α activities and thereby improve insulin secretion in β-cells, potentially representing a new strategy for managing diabetes and related metabolic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA119.009558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755798PMC
September 2019

Dimerization defective MODY mutations of hepatocyte nuclear factor 4α.

Mutat Res 2019 03 9;814:1-6. Epub 2019 Jan 9.

Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN, United States. Electronic address:

HNF4α is a culprit gene product for a monogenic and dominantly-inherited form of diabetes, referred to as MODY1 (Maturity Onset Diabetes of the Young type 1). Reduced HNF4α activities have been linked to impaired insulin secretion and β-cell function. Numerous mutations have been identified from the patients and they have been instructive as to the individual residue's role in protein structure-function and dysfunction. As a member of the nuclear receptor (NR) superfamily, HNF4α is made of characteristic modular domains and it functions exclusively as a homodimer despite its sequence homology to RXR, a common heterodimer partner of non-steroidal NRs. Transcription factors commonly dimerize to enhance their molecular functions mainly by facilitating the recognition of double helix target DNAs that display an intrinsic pseudo-2-fold symmetry and the recruitment of the remainder of the main transcriptional machinery. HNF4α is no exception and its dimerization is maintained by the ligand binding domain (LBD) mainly through the leucine-zipper-like interactions at the stalk of two interacting helices. Although many MODY1 mutations have been previously characterized, including DNA binding disruptors, ligand binding disruptors, coactivator binding disruptors, and protein stability disruptors, protein dimerization disruptors have not been formally reported. In this report, we present a set of data for the two MODY1 mutations found right at the dimerization interface (L332 P and L328del mutations) which clearly exhibit the disruptive effects of directly affecting dimerization, protein stability, and transcriptional activities. These data reinforced the fact that MODY mutations are loss-of-function mutations and HNF4α dimerization is essential for its optimal function and normal physiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mrfmmm.2019.01.002DOI Listing
March 2019

SnapShot: Functions of Tubulin Posttranslational Modifications.

Cell 2018 05 31;173(6):1552-1552.e1. Epub 2018 May 31.

Institut Curie, 91405 Orsay, France.

Post-translational modification of tubulin offers a mechanism for functional diversification of microtubules and regulation in a variety of physiological contexts. This SnapShot recaps the current state of understanding of tubulin posttranslational modifications and their functions in the regulation of biological processes. To view this SnapShot, open or download the PDF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2018.05.032DOI Listing
May 2018

Tubulin Posttranslational Modifications and Emerging Links to Human Disease.

Cell 2018 05 31;173(6):1323-1327. Epub 2018 May 31.

Institut Curie, PSL Research University, CNRS UMR3348, Orsay, France; Université Paris Sud, Université Paris-Saclay, CNRS UMR3348, Orsay, France. Electronic address:

Tubulin posttranslational modifications are currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders. Here, we review the latest advances in understanding the physiological roles of tubulin modifications and their links to a variety of pathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2018.05.018DOI Listing
May 2018

Relevance of B-Lines on Lung Ultrasound in Volume Overload and Pulmonary Congestion: Clinical Correlations and Outcomes in Patients on Hemodialysis.

Cardiorenal Med 2018 29;8(2):83-91. Epub 2017 Nov 29.

Background: Volume overload in patients on hemodialysis (HD) is an independent risk factor for cardiovascular mortality. B-lines detected on lung ultrasound (BLUS) assess extravascular lung water. This raises interest in its utility for assessing volume status and cardiovascular outcomes.

Methods: End-stage renal disease patients on HD at the Island Rehab Center being older than 18 years were screened. Patients achieving their dry weight (DW) had a lung ultrasound in a supine position. Scores were classified as mild (0-14), moderate (15-30), and severe (>30) for pulmonary congestion. Patients with more than 60 were further classified as very severe. Patients were followed for cardiac events and death.

Results: 81 patients were recruited. 58 were males, with a mean age of 59.7 years. 44 had New York Heart Association (NYHA) class 1, 24 had class 2, and 13 had class 3. In univariate analysis, NYHA class was associated with B-line classes (<0.001) and diastolic dysfunction (0.002). In multivariate analysis, NYHA grade strongly correlated with B-line classification (0.01) but not with heart function (0.95). 71 subjects were followed for a mean duration of 1.19 years. 9 patients died and 20 had an incident cardiac event. A Kaplan-Meier survival analysis demonstrated an interval decrease in survival times in all-cause mortality and cardiac events with increased BLUS scores (p = 0.0049). Multivariate Cox regression analysis showed the independent predictive value of BLUS class for mortality and cardiac events with a heart rate of 2.98 and 7.98 in severe and very severe classes, respectively, compared to patients in the mild class (p = 0.025 and 0.013).

Conclusion: At DW, BLUS is an independent risk factor for death and cardiovascular events in patients on HD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000476000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968278PMC
March 2019

Crystal structures reveal a new and novel FoxO1 binding site within the human glucose-6-phosphatase catalytic subunit 1 gene promoter.

J Struct Biol 2017 04 20;198(1):54-64. Epub 2017 Feb 20.

Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912, United States. Electronic address:

Human glucose-6-phosphatase plays a vital role in blood glucose homeostasis and holds promise as a therapeutic target for diabetes. Expression of its catalytic subunit gene 1 (G6PC1) is tightly regulated by metabolic-response transcription factors such as FoxO1 and CREB. Although at least three potential FoxO1 binding sites (insulin response elements, IREs) and one CREB binding site (cAMP response element, CRE) within the proximal region of the G6PC1 promoter have been identified, the interplay between FoxO1 and CREB and between FoxO1 bound at multiple IREs has not been well characterized. Here we present the crystal structures of the FoxO1 DNA binding domain in complex with the G6PC1 promoter. These complexes reveal the presence of a new non-consensus FoxO1 binding site that overlaps the CRE, suggesting a mutual exclusion mechanism for FoxO1 and CREB binding at the G6PC1 promoter. Additional findings include (i) non-canonical FoxO1 recognition sites, (ii) incomplete FoxO1 occupancies at the available IRE sites, and (iii) FoxO1 dimeric interactions that may play a role in stabilizing DNA looping. These findings provide insight into the regulation of G6PC1 gene transcription by FoxO1, and demonstrate a high versatility of target gene recognition by FoxO1 that correlates with its diverse roles in biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsb.2017.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443350PMC
April 2017

Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation.

Nat Commun 2017 02 15;8:14228. Epub 2017 Feb 15.

Markey Cancer Center, The University of Kentucky, College of Medicine, Lexington, Kentucky 40506, USA.

Snail1, a key transcription factor of epithelial-mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitro and in vivo. Our study reveals a critical Dub3-Snail1 signalling axis in EMT and metastasis, and provides an effective therapeutic approach against breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms14228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316870PMC
February 2017

EB1 regulates attachment of Ska1 with microtubules by forming extended structures on the microtubule lattice.

Nat Commun 2016 05 26;7:11665. Epub 2016 May 26.

School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, CET Campus, Thiruvananthapuram 695016, India.

Kinetochore couples chromosome movement to dynamic microtubules, a process that is fundamental to mitosis in all eukaryotes but poorly understood. In vertebrates, spindle-kinetochore-associated (Ska1-3) protein complex plays an important role in this process. However, the proteins that stabilize Ska-mediated kinetochore-microtubule attachment remain unknown. Here we show that microtubule plus-end tracking protein EB1 facilitates Ska localization on microtubules in vertebrate cells. EB1 depletion results in a significant reduction of Ska1 recruitment onto microtubules and defects in mitotic chromosome alignment, which is also reflected in computational modelling. Biochemical experiments reveal that EB1 interacts with Ska1, facilitates Ska1-microtubule attachment and together stabilizes microtubules. Structural studies reveal that EB1 either with Ska1 or Ska complex forms extended structures on microtubule lattice. Results indicate that EB1 promotes Ska association with K-fibres and facilitates kinetochore-microtubule attachment. They also implicate that in vertebrates, chromosome coupling to dynamic microtubules could be mediated through EB1-Ska extended structures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms11665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894954PMC
May 2016

Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES).

Biochem Biophys Res Commun 2015 Dec 4-11;468(1-2):14-20. Epub 2015 Nov 6.

Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912, USA. Electronic address:

HNF1α (Hepatocyte Nuclear Factor 1α) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1α are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1α-specific physical binding partner and functional repressor of HNF1α-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1α mutation-driven diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2015.11.007DOI Listing
March 2016

New Caledonian crows rapidly solve a collaborative problem without cooperative cognition.

PLoS One 2015 12;10(8):e0133253. Epub 2015 Aug 12.

School of Psychology, University of Auckland, Private Bag 92019, Auckland, New Zealand.

There is growing comparative evidence that the cognitive bases of cooperation are not unique to humans. However, the selective pressures that lead to the evolution of these mechanisms remain unclear. Here we show that while tool-making New Caledonian crows can produce collaborative behavior, they do not understand the causality of cooperation nor show sensitivity to inequity. Instead, the collaborative behavior produced appears to have been underpinned by the transfer of prior experience. These results suggest that a number of possible selective pressures, including tool manufacture and mobbing behaviours, have not led to the evolution of cooperative cognition in this species. They show that causal cognition can evolve in a domain specific manner-understanding the properties and flexible uses of physical tools does not necessarily enable animals to grasp that a conspecific can be used as a social tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133253PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534463PMC
May 2016

Targeting epidermal fatty acid binding protein for treatment of experimental autoimmune encephalomyelitis.

BMC Immunol 2015 May 12;16:28. Epub 2015 May 12.

The Hormel Institute, University of Minnesota, 801 16th Avenue, NE, Austin, MN, 55912, USA.

Background: Multiple sclerosis (MS) is an autoimmune disease in which dysregulated immune cells attack myelin in the central nervous system (CNS), leading to irreversible neuronal degeneration. Our previous studies have demonstrated that epidermal fatty acid binding protein (E-FABP), widely expressed in immune cells, in particular in dendritic cells (DCs) and T lymphocytes, fuels the overactive immune responses in the mouse model of experimental autoimmune encephalomyelitis (EAE).

Methods: In the present study, we conducted an intensive computational docking analysis to identify novel E-FABP inhibitors for regulation of immune cell functions and for treatment of EAE.

Results: We demonstrate that compound [2-(4-acetylphenoxy)-9,10-dimethoxy-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one; designated as EI-03] bound to the lipid binding pocket of E-FABP and enhanced the expression of peroxisome proliferator-activating receptor (PPAR) γ. Further in vitro experiments showed that EI-03 regulated DC functions by inhibition of TNFα production while promoting IL-10 secretion. Moreover, EI-03 treatment counterregulated T cell balance by decreasing effector T cell differentiation (e.g. Th17, Th1) while increasing regulatory T cell development. Most importantly, mice treated with this newly identified compound exhibited reduced clinical symptoms of EAE in mouse models.

Conclusions: Taken together, we have identified a new compound which displays a potential therapeutic benefit for treatment of MS by targeting E-FABP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12865-015-0091-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427938PMC
May 2015

Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein.

Oncotarget 2015 Apr;6(10):7815-27

The Hormel Institute, University of Minnesota, Austin, MN, USA.

Our previous studies have demonstrated that expression of epidermal fatty acid binding protein (E-FABP) in tumor associated macrophages (TAMs) promotes macrophage anti-tumor activity by enhancing IFNβ responses in tumor models. Thus, E-FABP represents a new protective factor in enhancing tumor immune surveillance against tumor development. Herein, we report the compound 5-(benzylamino)-2-(3-methylphenyl)-1,3-oxazole-4-carbonitrile (designated EI-05) as a novel E-FABP activator for inhibition of mammary tumor growth. EI-05 was selected from the ZINC compound library using molecular docking analysis based on the crystal structure of E-FABP. Although EI-05 is unable to bind E-FABP directly, it significantly increases E-FABP expression in macrophages during inflammation. Stimulation of macrophages with EI-05 remarkably enhances lipid droplet formation and IFNβ production, which further promotes the anti-tumor activity of macrophages. Importantly, administering EI-05 in vivo significantly inhibits mammary tumor growth in a syngeneic mouse model. Altogether, these results suggest that EI-05 may represent a promising drug candidate for anti-tumor treatment through enhancing E-FABP activity and IFNβ responses in macrophages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480718PMC
http://dx.doi.org/10.18632/oncotarget.3485DOI Listing
April 2015

Suppression of centrosome protein TACC3 induces G1 arrest and cell death through activation of p38-p53-p21 stress signaling pathway.

Eur J Cell Biol 2015 Feb 5;94(2):90-100. Epub 2015 Jan 5.

School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, CET Campus, Trivandrum 695016, Kerala, India. Electronic address:

The centrosome regulates diverse cellular processes, including cell proliferation and differentiation. TACC3, a member of the human transforming acidic coiled-coil protein family, is a key centrosomal protein that is up-regulated in many cancers. Previous studies have demonstrated that TACC3 is essential for the survival of vertebrates and is involved in cell cycle regulation in human cells. However, the details of the underlying mechanisms in its cell cycle regulatory activity remain poorly understood. In this study, we showed that suppression of TACC3 expression induced G1 cell cycle arrest and triggered cell death in human cells. TACC3 depletion-induced G1 arrest and cell death were significantly reduced in cells either lacking p53 or with pharmacologically-inhibited p38, indicating that G1 arrest and cell death induction both require p53 and p38. TACC3 depletion up-regulated the levels of p53 and p21 and induced the accumulation of p53 both in the nucleus and at the centrosome. Interestingly, TACC3 depletion led to the activation of p38 and stimulated the recruitment of activated p38 to the centrosome. Depletion of TACC3 up-regulated the phosphorylation of p53 at Serine 33, a site known to be phosphorylated by p38 under cellular stress and further induced the accumulation of phosphorylated p53 to the centrosome. Loss of TACC3 affected centrosome integrity by disrupting the localization of components of the γ-tubulin ring complex at the centrosome. The results demonstrate that TACC3 depletion induces G1 arrest and cell death by activating p38-p53-p21 signaling and triggering a centrosome-mediated cellular stress response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejcb.2014.12.001DOI Listing
February 2015

Isoliquiritigenin induces apoptosis and inhibits xenograft tumor growth of human lung cancer cells by targeting both wild type and L858R/T790M mutant EGFR.

J Biol Chem 2014 Dec 3;289(52):35839-48. Epub 2014 Nov 3.

From The Hormel Institute, University of Minnesota, Minnesota 55912,

Non-small-cell lung cancer (NSCLC) is associated with diverse genetic alterations including mutation of epidermal growth factor receptor (EGFR). Isoliquiritigenin (ILQ), a chalcone derivative, possesses anticancer activities. In the present study, we investigated the effects of ILQ on the growth of tyrosine kinase inhibitor (TKI)-sensitive and -resistant NSCLC cells and elucidated its underlying mechanisms. Treatment with ILQ inhibited growth and induced apoptosis in both TKI-sensitive and -resistant NSCLC cells. ILQ-induced apoptosis was associated with the cleavage of caspase-3 and poly-(ADP-ribose)-polymerase, increased expression of Bim, and reduced expression of Bcl-2. In vitro kinase assay results revealed that ILQ inhibited the catalytic activity of both wild type and double mutant (L858R/T790M) EGFR. Treatment with ILQ inhibited the anchorage-independent growth of NIH3T3 cells stably transfected with either wild type or double-mutant EGFR with or without EGF stimulation. ILQ also reduced the phosphorylation of Akt and ERK1/2 in both TKI-sensitive and -resistant NSCLC cells, and attenuated the kinase activity of Akt1 and ERK2 in vitro. ILQ directly interacted with both wild type and double-mutant EGFR in an ATP-competitive manner. A docking model study showed that ILQ formed two hydrogen bonds (Glu-762 and Met-793) with wild type EGFR and three hydrogen bonds (Lys-745, Met-793, and Asp-855) with mutant EGFR. ILQ attenuated the xenograft tumor growth of H1975 cells, which was associated with decreased expression of Ki-67 and diminished phosphorylation of Akt and ERK1/2. Taken together, ILQ suppresses NSCLC cell growth by directly targeting wild type or mutant EGFR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M114.585513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276852PMC
December 2014

TACC3 protein regulates microtubule nucleation by affecting γ-tubulin ring complexes.

J Biol Chem 2014 Nov 22;289(46):31719-31735. Epub 2014 Sep 22.

School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, CET Campus, Thiruvananthapuram 695016, Kerala, India. Electronic address:

Centrosome-mediated microtubule nucleation is essential for spindle assembly during mitosis. Although γ-tubulin complexes have primarily been implicated in the nucleation process, details of the underlying mechanisms remain poorly understood. Here, we demonstrated that a member of the human transforming acidic coiled-coil (TACC) protein family, TACC3, plays a critical role in microtubule nucleation at the centrosome. In mitotic cells, TACC3 knockdown substantially affected the assembly of microtubules in the astral region and impaired microtubule nucleation at the centrosomes. The TACC3 depletion-induced mitotic phenotype was rescued by expression of the TACC3 C terminus predominantly consisting of the TACC domain, suggesting that the TACC domain plays an important role in microtubule assembly. Consistently, experiments with the recombinant TACC domain of TACC3 demonstrated that this domain possesses intrinsic microtubule nucleating activity. Co-immunoprecipitation and sedimentation experiments revealed that TACC3 mediates interactions with proteins of both the γ-tubulin ring complex (γ-TuRC) and the γ-tubulin small complex (γ-TuSC). Interestingly, TACC3 depletion resulted in reduced levels of γ-TuRC and increased levels of γ-TuSC, indicating that the assembly of γ-TuRC from γ-TuSC requires TACC3. Detailed analyses suggested that TACC3 facilitates the association of γ-TuSC-specific proteins with the proteins known to be involved in the assembly of γ-TuRC. Consistent with such a role for TACC3, the suppression of TACC3 disrupted localization of γ-TuRC proteins to the centrosome. Our findings reveal that TACC3 is involved in the regulation of microtubule nucleation at the centrosome and functions in the stabilization of the γ-tubulin ring complex assembly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M114.575100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231652PMC
November 2014

Microtubule +TIP protein EB1 binds to GTP and undergoes dissociation from dimer to monomer on binding GTP.

Biochemistry 2014 Sep 21;53(34):5551-7. Epub 2014 Aug 21.

School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram , CET Campus, Thiruvananthapuram, Kerala 695016, India.

The +TIP protein EB1 autonomously tracks the growing plus end of microtubules and regulates plus-end dynamics. Previous studies have indicated that EB1 can recognize GTP-bound tubulin structures at the plus end, and it localizes on the microtubule surface at a site close to the exchangeable GTP-binding site of tubulin. Although the GTP-dependent structural change in tubulin has been demonstrated to be a critical determinant for recognition of plus ends by EB1, the effect of GTP on the structure of EB1 has remained unclear. Here, we have used spectroscopic, calorimetric, and biochemical methods to analyze the effect of GTP on EB1 in vitro. Isothermal titration calorimetry and tryptophan fluorescence quenching experiments demonstrated that EB1 binds to GTP with a dissociation constant ~30 μM. Circular dichroism measurements showed that EB1 undergoes changes in its secondary structure on binding GTP. Size-exclusion chromatography and urea-induced unfolding analyses revealed that GTP binding induces dissociation of the EB1 dimer to monomers. Size-exclusion chromatography followed by biochemical analysis further determined that EB1-GTP binding involves association of approximately one molecule of GTP per EB1 monomer. The results reveal a hitherto unknown GTP-dependent mechanism of dimer-to-monomer transition in EB1 and further implicate its possible role in regulating the stability of the EB1 dimer vs monomer as well as plus-end regulation in cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/bi5007942DOI Listing
September 2014

Structural and functional analysis of g protein-coupled receptor kinase inhibition by paroxetine and a rationally designed analog.

Mol Pharmacol 2014 Feb 12;85(2):237-48. Epub 2013 Nov 12.

Life Sciences Institute and the Departments of Pharmacology and Biological Sciences (K.T.H., E.W., P.S., J.J.G.T.), and Vahlteich Medicinal Chemistry Core and the Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan (M.W.W., S.D.L.).

Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. A better understanding of the molecular basis of this selectivity is important for the development of even more selective and potent small molecule therapeutics and chemical genetic probes. We first sought to understand the molecular mechanisms underlying paroxetine selectivity among GRKs. We directly measured the K(D) for paroxetine and assessed its mechanism of inhibition for each of the GRK subfamilies and then determined the atomic structure of its complex with GRK1, the most weakly inhibited GRK tested. Our results suggest that the selectivity of paroxetine for GRK2 largely reflects its lower affinity for adenine nucleotides. Thus, stabilization of off-pathway conformational states unique to GRK2 will likely be key for the development of even more selective inhibitors. Next, we designed a benzolactam derivative of paroxetine that has optimized interactions with the hinge of the GRK2 kinase domain. The crystal structure of this compound in complex with GRK2 confirmed the predicted interactions. Although the benzolactam derivative did not significantly alter potency of inhibition among GRKs, it exhibited 20-fold lower inhibition of serotonin reuptake. However, there was an associated increase in the potency for inhibition of other AGC kinases, suggesting that the unconventional hydrogen bond formed by the benzodioxole ring of paroxetine is better accommodated by GRKs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/mol.113.089631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913355PMC
February 2014

A eukaryotic specific transmembrane segment is required for tetramerization in AMPA receptors.

J Neurosci 2013 Jun;33(23):9840-5

Graduate Program in Neuroscience, and Center for Nervous System Disorders, Stony Brook University, Stony Brook, New York 11794-5230, USA.

Most fast excitatory synaptic transmission in the nervous system is mediated by glutamate acting through ionotropic glutamate receptors (iGluRs). iGluRs (AMPA, kainate, and NMDA receptor subtypes) are tetrameric assemblies, formed as a dimer of dimers. Still, the mechanism underlying tetramerization--the necessary step for the formation of functional receptors that can be inserted into the plasma membrane--is unknown. All eukaryotic compared to prokaryotic iGluR subunits have an additional transmembrane segment, the M4 segment, which positions the physiologically critical C-terminal domain on the cytoplasmic side of the membrane. AMPA receptor (AMPAR) subunits lacking M4 do not express on the plasma membrane. Here, we show that these constructs are retained in the endoplasmic reticulum, the major cellular compartment mediating protein oligomerization. Using approaches to assay the native oligomeric state of AMPAR subunits, we find that subunits lacking M4 or containing single amino acid substitutions along an "interacting" face of the M4 helix that block surface expression no longer tetramerize in either homomeric or heteromeric assemblies. In contrast, subunit dimerization appears to be largely intact. These experiments define the M4 segment as a unique functional unit in AMPARs that is required for the critical dimer-to-tetramer transition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.2626-12.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714855PMC
June 2013

Structure of a monomeric variant of rhodopsin kinase at 2.5 Å resolution.

Acta Crystallogr Sect F Struct Biol Cryst Commun 2012 Jun 22;68(Pt 6):622-5. Epub 2012 May 22.

Life Sciences Institute and the Department of Pharmacology, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA.

G protein-coupled receptor kinase 1 (GRK1 or rhodopsin kinase) phosphorylates activated rhodopsin and initiates a cascade of events that results in the termination of phototransduction by the receptor. Although GRK1 seems to be a monomer in solution, seven prior crystal structures of GRK1 revealed a similar domain-swapped dimer interface involving the C-terminus of the enzyme. The influence of this interface on the overall conformation of GRK1 is not known. To address this question, the crystalline dimer interface was disrupted with a L166K mutation and the structure of GRK1-L166K was determined in complex with Mg(2+) · ATP to 2.5 Å resolution. GRK1-L166K crystallized in a novel space group as a monomer and exhibited little overall conformational difference from prior structures of GRK1, although the C-terminal domain-swapped region had reorganized owing to loss of the dimer interface.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S1744309112017435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370896PMC
June 2012

Metaplastic carcinoma of the breast: cytological diagnosis and diagnostic pitfalls.

Acta Cytol 2011 22;55(4):313-8. Epub 2011 Jul 22.

Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, India.

Objective: Metaplastic carcinoma of the breast is a rare malignant neoplasm comprised of ductal, squamous and/or mesenchymal elements in various proportions. Fine needle aspiration diagnosis of this entity is problematic because of its pathological heterogeneity. In this study, we have described the cytomorphological features of histologically confirmed metaplastic carcinomas and also discussed the diagnostic limitations along with a brief review of the literature.

Study Design: In this observational study, the histology and cytology files of all cases identified as metaplastic carcinomas during the study period (2004-2009) were retrieved. The slides were reviewed for the presence of various elements.

Results: Ten cases were identified as metaplastic carcinomas during the study period. All cases were diagnosed as malignant on cytology. Three cases showed presence of squamous carcinoma cells, 4 showed presence of atypical spindle cells, 2 showed presence of mesenchymal fragments and 1 showed presence of osteoclastic giant cells.

Conclusion: The presence of biphasic tumor cells, atypical spindle cells admixed with poorly differentiated carcinoma cells, squamous carcinoma cells, osteoclastic giant cells and matrix may provide clues for the fine needle aspiration diagnosis of metaplastic carcinomas. However, cytological diagnosis may not be possible in all the cases because of selective sampling of various pathological elements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000326932DOI Listing
September 2011
-->