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1.
Sci Rep ; 14(1): 12538, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822065

RESUMO

India experienced several unprecedented floods in the recent decades. The increase in the extreme rainfall events (EREs) is the primary cause for these floods, manifesting its societal impacts. The daily downscaled and bias corrected (DBC) Coupled Model Intercomparison Project Phase 6 (CMIP6) rainfall and sea surface temperature (SST) are prepared for the Indian region and are utilized to examine the characteristics of EREs. The DBC products capture the characteristic features of EREs for the baseline period, which inspired us to assess the EREs over India in CMIP6 future projections. Consistent with the observations, DBC product shows ~ 8% of Indian land found to experienced extremely heavy rainfall associated with the long duration EREs in the baseline period. However, area and extreme rainfall thresholds are projected to increase by about 18(13)% and 58(50)%, respectively in the far future under SSP5-8.5 (SSP2-4.5) emission scenario relative to the baseline period. A two-fold-65(62)% increase in long-duration EREs compared to the short-duration EREs and substantial warming ~ 2.4(2.9) oC of Indian Ocean SSTs in the far future under SSP5-8.5 (SSP2-4.5) emission scenario compared to baseline period are reported. These findings may provide fundamental insights to formulate national climate change adaptation policies for the EREs.

2.
Sci Rep ; 13(1): 21737, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065984

RESUMO

Decadal climate predictions have been widely used to predict the near-term climate information relevant for decision-making at multi-year timescales. In the present study, we evaluate the quality of the Coupled Model Intercomparison Project phase-6 (CMIP6) Decadal Climate Prediction Project (DCPP) hindcasts in capturing the extreme rainfall events (EREs) over the monsoon core region during Indian summer monsoon season (June-September) up to lead years 1-10. For the first time, in this study, we have used quantile mapping approach to downscale and bias correct the DCPP CMIP6 simulation/hindcast rainfall for the better representation of EREs. Detailed analysis suggests that the models in general strongly underestimate the rainfall variability over the summer monsoon region. However, after the downscaling and bias correction, the representation of rainfall variability and intensity improved multifold. The bias-corrected decadal hindcasts in fact show ~ 80% improvement in capturing the frequency, intensity, and spatial distribution of rainfall associated with the EREs. Present study brought out a downscaled DCPP product, with potential prediction skill for EREs over India. It is important to highlight that the models predict an increase in the small and medium-area EREs as compared to the large-area EREs over the monsoon core region for the decade 2019-2028.

4.
Int J Oncol ; 58(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33878845

RESUMO

Following the publication of the above paper, we were contacted by the University of Illinois at Chicago, to request the retraction of the above article. Following a formal institutional investigation, the investigation panel concluded that the images in question had falsifying elements. Regarding the above study, the specific allegations that were investigated were that of falsifying elements of Fig. 6A, row 2, columns 2 and 3. Following a review of this paper conducted independently by the Editor of International Journal of Oncology, the Editor concurred with the conclusions of the investigation panel, and therefore the above paper has been retracted from the publication. We also tried to contact the authors, but did not receive a reply. The Editor apologizes to the readership for the inconvenience caused.[the original article was published in International Journal of Oncology 40: 509­518, 2012; DOI: 10.3892/ijo.2011.1255].

6.
Int J Oncol ; 58(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33655319

RESUMO

Following the publication of the above paper, we were contacted by the University of Illinois at Chicago, to request the retraction of the above article. Following a formal institutional investigation, the investigation panel concluded that the images in question had falsifying elements. Regarding the above study, the specific allegations that were investigated were that of falsifying elements of Fig. 1B, bottom panel, columns 2 and 3; Fig. 4A, top panel, columns 4, 5 and 6, and middle panel, columns 1, 2 and 3; and Fig. 7D, row 1, column 1 and row 2, column 1.
Following a review of this paper conducted independently by the Editor of International Journal of Oncology, the Editor concurred with the conclusions of the investigation panel, and therefore the above paper has been retracted from the publication. We also tried to contact the authors, but did not receive a reply. The Editor apologizes to the readership for the inconvenience caused. [the original article was published in International Journal of Oncology 38: 973­983, 2011; DOI: 10.3892/ijo.2011.934]

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7.
Int J Oncol ; 58(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33655324

RESUMO

Following the publication of the above paper, we were contacted by the University of Illinois at Chicago, to request the retraction of the above article. Following a formal institutional investigation, the investigation panel concluded that the images in question had falsifying elements. Regarding the above study, the specific allegations that were investigated were that of falsifying elements of Fig. 2A, right panel, row 3, columns 2, 3 and 4 and Fig. 4D, left panel, row 5, columns 1, 2 and 3; Fig. 4A, row 1, columns 2, 3 and 4, and Fig. 4C, row 1, columns 5, 6 and 7; and Fig. 6C, row 1, column 3, and row 2, column 1.
Following a review of this paper conducted independently by the Editor of International Journal of Oncology, the Editor concurred with the conclusions of the investigation panel, and therefore the above paper has been retracted from the publication. We also tried to contact the authors, but did not receive a reply. The Editor apologizes to the readership for the inconvenience caused. [the original article was published in International Journal of Oncology 40: 1615-1624, 2012; DOI: 10.3892/ijo.2011.987].

13.
Reprod Sci ; 25(2): 185-197, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28481180

RESUMO

BACKGROUND: Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in the placenta across gestation, in placentas of preeclamptic (PE) pregnancies, and in purified microvesicles and exosomes. METHODS: Trophoblast glycoprotein expression was analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. Regulation of 5T4 in cytotrophoblast cells was examined under either differentiating conditions of epidermal growth factor or under varying oxygen conditions. Microvesicles and exosomes were purified from supernatant of cultured and perfused placentas. RESULTS: Trophoblast glycoprotein expression was prominent at the microvillus surface of syncytiotrophoblast and on the extravillous trophoblast cells, with minimal expression in undifferentiated cytotrophoblasts and normal tissues. Trophoblast glycoprotein expression was elevated in malignant tumors. In cytotrophoblasts, 5T4 was induced by in vitro differentiation, and its messenger RNA (mRNA) was increased under conditions of low oxygen. PE placentas expressed higher 5T4 mRNA than matched control placentas. Trophoblast glycoprotein was prominent within shed placental microvesicles and exosomes. CONCLUSION: Given the potential functional and known immunological importance of 5T4 in cancer, these studies reveal a class of proteins that may influence placental development and/or sensitize the maternal immune system. In extravillous trophoblasts, 5T4 may function in epithelial-to-mesenchymal transition during placentation. The role of syncytiotrophoblast 5T4 is unknown, but its abundance in shed syncytial vesicles may signify route of sensitization of the maternal immune system.


Assuntos
Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Glicoproteínas de Membrana/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Diferenciação Celular , Feminino , Humanos , Glicoproteínas de Membrana/genética , Placentação/fisiologia , Gravidez , Primeiro Trimestre da Gravidez/metabolismo , Segundo Trimestre da Gravidez/metabolismo
15.
Stem Cell Res ; 12(3): 716-29, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24699410

RESUMO

In the present study, we investigated the effect of simultaneous downregulation of uPAR and cathepsin B (pUC), alone or in combination with radiation, on JNK-MAPK signaling pathway in regulating the migration of non-GICs (glioma-initiating cells) and GICs. The increase in the expression of p-JNK with pUC treatment was mostly localized to nucleus whereas increase in the expression of p-JNK with radiation and overexpression of uPAR and cathepsin B was confined to cytoplasm of the cells. Depletion of cytosolic p-JNK with pUC treatment inhibited migration by downregulating the expression of the adapter proteins of the focal adhesion complex. We also observed that knockdown of uPAR and cathepsin B regulated the Ras-Pak-1 pathway to induce the translocation of p-JNK from cytosol to nucleus. In control cells, Pak-1 served as a functional inhibitor for MEKK-1, which inhibits the complex formation of MEKK-1 and p-JNK and thus inhibits the translocation of this complex into nucleus. Hence, we conclude that glioma cells utilize the availability of cytosolic p-JNK in driving the cells towards migration. Finally, treating the cells with pUC alone or in combination with radiation induced the translocation of the MEKK-1-p-JNK complex from cytosol to nucleus, thereby inhibiting the migration of glioma cells.


Assuntos
Catepsina B/metabolismo , Movimento Celular , Glioma/enzimologia , MAP Quinase Quinase 4/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Animais , Catepsina B/genética , Núcleo Celular/enzimologia , Núcleo Celular/genética , Núcleo Celular/metabolismo , Citoplasma/enzimologia , Citoplasma/genética , Citoplasma/metabolismo , Citosol/enzimologia , Citosol/metabolismo , Feminino , Glioma/genética , Glioma/metabolismo , Glioma/fisiopatologia , Humanos , MAP Quinase Quinase 4/genética , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Transporte Proteico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética
16.
Mol Cancer Ther ; 13(5): 1309-22, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24623737

RESUMO

Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in the tumor-stromal invasive microenvironment in many human cancers, including medulloblastoma. The role of uPAR in tumor progression and angiogenesis has been well characterized. Previously, in medulloblastoma cells, we showed that ionizing radiation (IR)-induced uPAR is a potent activator of cancer stem cell (CSC)-like properties and is associated with various transcription factors that are involved during embryonic development and cancer. In the present study, we show that uPAR protein acts as a cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand-1. The Hand-1 protein plays an essential role in the differentiation of trophoblast giant cells and cardiac morphogenesis, and yet its precise cellular function and its contribution to cancer remain mostly unknown. We also observed that the Hand-1 protein is upregulated in uPAR short hairpin RNA-treated medulloblastoma cells and accompanies sustained cell growth and angiogenesis. Furthermore, IR-induced uPAR overexpression negatively regulates Hand-1 activity and results in the stabilization of angiogenesis-promoting molecules, including hypoxia-inducible factor-1α. Finally, uPAR overexpression and its association with Hand-1 after IR treatment indicate that uPAR is capable of regulating Hand-1 and that uPAR has a role in the process of IR-induced tumor angiogenesis.


Assuntos
Transporte Ativo do Núcleo Celular , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Meduloblastoma/metabolismo , Tolerância a Radiação , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular Tumoral , Citoplasma/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Meduloblastoma/genética , Meduloblastoma/patologia , Camundongos , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Neovascularização Patológica/genética , Ligação Proteica , Transporte Proteico , Radiação Ionizante , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Carga Tumoral
17.
Mol Neurobiol ; 49(1): 50-65, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23813097

RESUMO

A tremendous effort has been expended to elucidate the role of apoptotic molecules in ischemia. However, many agents that target apoptosis, despite their proven efficacy in animal models, have failed to translate that efficacy and specificity in clinical settings. Therefore, comprehensive knowledge of apoptotic mechanisms involving key apoptotic regulatory molecules and the temporal expression profiles of various apoptotic molecules after cerebral ischemia may provide insight for the development of better therapeutic strategies aimed at cerebral ischemia. The present study investigates the extent of apoptosis and the regulation of apoptotic molecules both at mRNA and protein levels at various time points after focal cerebral ischemia in a rat model of middle cerebral artery occlusion. In this study, we performed various techniques, such as TTC (2,3,5-triphenyltetrazolium chloride), H&E (hematoxylin and eosin), and TUNEL (terminal deoxy nucleotidyl transferase-mediated nick-end labeling) staining, along with polymerase chain reaction (PCR) microarray, antibody microarray, reverse transcription (RT)-PCR, immunofluorescence, and immunoblot analyses. Our research provided a large list of pro-apoptotic and anti-apoptotic molecules and their temporal expression profiles both at the mRNA and protein levels. This information could be very useful for designing future stroke therapies and aid in targeting the right molecules at critical time to obtain maximum therapeutic benefit.


Assuntos
Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/biossíntese , Apoptose/fisiologia , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Reperfusão , Animais , Animais Recém-Nascidos , Proteínas Reguladoras de Apoptose/fisiologia , Infarto da Artéria Cerebral Média/genética , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reperfusão/métodos , Fatores de Tempo
18.
BMC Cancer ; 13: 590, 2013 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-24325546

RESUMO

BACKGROUND: Src tyrosine kinase activates inducible nitric oxide synthase (iNOS) and, in turn, nitric oxide production as a means to transduce cell migration. Src tyrosine kinase plays a key proximal role to control α9ß1 signaling. Our recent studies have clearly demonstrated the role of α9ß1 integrin in matrix metalloproteinase-9 (MMP-9) and/or urokinase plasminogen activator receptor (uPAR)-mediated glioma cell migration. In the present study, we evaluated the involvement of α9ß1 integrin-iNOS pathway in MMP-9- and/or uPAR-mediated glioma cell migration. METHODS: MMP-9 and uPAR shRNAs and overexpressing plasmids were used to downregulate and upregulate these molecules, respectively in U251 glioma cells and 5310 glioma xenograft cells. The effect of treatments on migration and invasion potential of these glioma cells were assessed by spheroid migration, wound healing, and Matrigel invasion assays. In order to attain the other objectives we also performed immunocytochemical, immunohistochemical, RT-PCR, Western blot and fluorescence-activated cell sorting (FACS) analysis. RESULTS: Immunohistochemical analysis revealed the prominent association of iNOS with glioblastoma multiforme (GBM). Immunofluorescence analysis showed prominent expression of iNOS in glioma cells. MMP-9 and/or uPAR knockdown by respective shRNAs reduced iNOS expression in these glioma cells. RT-PCR analysis revealed elevated iNOS mRNA expression in either MMP-9 or uPAR overexpressed glioma cells. The migration potential of MMP-9- and/or uPAR-overexpressed U251 glioma cells was significantly inhibited after treatment with L-NAME, an inhibitor of iNOS. Similarly, a significant inhibition of the invasion potential of the control or MMP-9/uPAR-overexpressed glioma cells was noticed after L-NAME treatment. A prominent reduction of iNOS expression was observed in the tumor regions of nude mice brains, which were injected with 5310 glioma cells, after MMP-9 and/or uPAR knockdown. Protein expressions of cSrc, phosphoSrc and p130Cas were reduced with simultaneous knockdown of both MMP-9 and uPAR. CONCLUSIONS: Taken together, our results from the present and earlier studies clearly demonstrate that α9ß1 integrin-mediated cell migration utilizes the iNOS pathway, and inhibition of the migratory potential of glioma cells by simultaneous knockdown of MMP-9 and uPAR could be attributed to the reduced α9ß1 integrin and iNOS levels.


Assuntos
Movimento Celular , Glioma/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Óxido Nítrico Sintase/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Expressão Gênica , Glioma/genética , Glioma/patologia , Xenoenxertos , Humanos , Integrinas/metabolismo , Metaloproteinase 9 da Matriz/genética , Camundongos , Modelos Biológicos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ligação Proteica , Interferência de RNA , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética
19.
Mol Biol Cell ; 24(17): 2620-32, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23864708

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is almost always lethal. One of the underlying reasons for this lethality is believed to be the presence of cancer stem cells (CSC), which impart chemoresistance and promote recurrence, but the mechanisms responsible are unclear. Recently the poor prognosis of PDAC has been correlated with increased expression of urokinase plasminogen activator (uPA). In the present study we examine the role of uPA in the generation of PDAC CSC. We observe a subset of cells identifiable as a side population (SP) when sorted by flow cytometry of MIA PaCa-2 and PANC-1 pancreatic cancer cells that possess the properties of CSC. A large fraction of these SP cells are CD44 and CD24 positive, are gemcitabine resistant, possess sphere-forming ability, and exhibit increased tumorigenicity, known characteristics of cancer stemness. Increased tumorigenicity and gemcitabine resistance decrease after suppression of uPA. We observe that uPA interacts directly with transcription factors LIM homeobox-2 (Lhx2), homeobox transcription factor A5 (HOXA5), and Hey to possibly promote cancer stemness. uPA regulates Lhx2 expression by suppressing expression of miR-124 and p53 expression by repressing its promoter by inactivating HOXA5. These results demonstrate that regulation of gene transcription by uPA contributes to cancer stemness and clinical lethality.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Células-Tronco Neoplásicas/fisiologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Antineoplásicos/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Proteínas de Ciclo Celular/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Proteínas com Homeodomínio LIM/metabolismo , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Células da Side Population/efeitos dos fármacos , Células da Side Population/fisiologia , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/genética , Gencitabina
20.
Biochem Biophys Res Commun ; 434(3): 627-33, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23583374

RESUMO

MicroRNAs are a novel family of small non-coding RNAs that regulate the expression of several genes involved in normal development as well as human disorders including cancer. Here we show that miR-874 plays a tumor suppressor role in non-small cell lung cancer (NSCLC) in vitro and in vivo. In silico target prediction analysis revealed numerous genes associated with tumor progression including MMP-2 and uPA as the putative target genes of miR-874. Our preliminary in situ hybridization experiments demonstrated the diminution of miR-874 expression in lung cancer tissues compared to their normal counter parts. Overexpression of miR-874 in CD133-positive cancer stem cell (CSC) population led to a significant loss in CSC-phenotype and enhanced sphere de-differentiation into epithelial-like cells. Restoration of miR-874 expression drastically reduced cell invading ability in comparison to mock and control-miR-treated cells by suppressing the protein levels of MMP-2 and uPA. In in vivo experiments, miR-874 treatment decreased orthotopic tumor growth in nude mice compared to mock and control-miR treatments. Further, the immunoreactivity of human anti-MMP-2 and anti-uPA was significantly reduced in tumor sections from mice that received miR-874 treatment. In conclusion, our study highlights the possible tumor suppressor role of miR-874 in NSCLC-initiating cells and suggests miR-874 as a potential target in the treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Divisão Celular/genética , Neoplasias Pulmonares/patologia , MicroRNAs/fisiologia , Invasividade Neoplásica/genética , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Primers do DNA , Humanos , Imuno-Histoquímica , Hibridização In Situ , Neoplasias Pulmonares/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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