698 research outputs found
1869, Cornell University Press Podcast, Ep. 118 with Jayita Sarkar, author of Ploughshares and Swords
No full textThis episode, we speak with Jayita Sarkar, author of the new paperback and open access ebook Ploughshares and Swords: India’s Nuclear Program in the Global Cold War. Jay Sarkar is Senior Lecturer in Economic and Social History at the University of Glasgow and the Founding Director of the Global Decolonization Initiative.
We spoke to Jay about how the history of India’s first nuclear weapons test in 1974 has been overshadowed by their 1998 nuclear tests, why the conventional wisdom that India started off its nuclear program with nuclear energy first is in fact incorrect, and the strong connections between India’s nuclear program and their space program
Abstract 5891: DCIS to invasive progression in breast cancer is delayed by restoring CCN5
No full textAbstract
Malignant progression of breast cancer from pre-invasive to invasive lesions remains a mechanistically unknown event and a major challenge in medical research. By revealing the mechanism of action, our new and substantially different approach aims to demonstrate that CCN5/WISP2 might play a role in negative regulation of progression of pre-invasive lesion ductal carcinoma in-situ (DCIS) to invasive carcinoma (IC). DCIS to IC transition results primarily from the loss of the myoepithelial cell (MEC) layer surrounding the breast ducts & lobules and basement membrane (BM) degradation followed by invasion of cancer cells into the surrounding stromal tissue and vasculature. It has been recently discovered that CCN5, a matricellular protein, is highly expressed in DCIS patient specimens and facilitates regression of aggressive phenotypes. Our in-vitro studies with myoepithelial cell lines (MECs) indicate that CCN5 may prevent the DCIS to IC transition through the protection of the MEC layer. CCN5 performs it’s protective role by regulating sonic hedgehog (SHh) expression in MECs. It has been previously shown in separate studies that Neuropilin1 (Nrp1) positively regulates expression of SHh and Nrp1 is exclusively expressed in MEC layer in breast tissues. An extension of our studies indicate that CCN5 might regulate the integrity of the mammary ductal architecture by protecting the MEC layer through a novel Nrp1-SHh signaling axis. Collectively, our studies indicate that regulating CCN5 expression level in breast cancer tissues might help us controlling the rate of progression of the disease from DCIS to an invasive stage.
Citation Format: Sandipto Sarkar, Arnab Ghosh, Gargi Maity, Snigdha Banerjee, Sushanta Banerjee. DCIS to invasive progression in breast cancer is delayed by restoring CCN5 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5891. doi:10.1158/1538-7445.AM2017-5891</jats:p
Abstract 5520: CCN5/WISP-2 is a negative regulator of epithelial to mesenchymal transition and stemness in breast cancer
No full textAbstract
Background and Objective: Breast cancer is the most common cancer in women and a leading cause of cancer mortality in western countries. CCN5 (also known as Wnt-1-induced signaling protein-2 or WISP-2) is a 29-31-kDa matricellular protein that plays as a negative regulator of breast carcinoma. Our previous studies had shown the importance of CCN5/ WISP-2 in the suppression of breast and pancreatic cancer progression through the regulation of the invasive phenotypes. Considering the previous report, our aim is to investigate whether human recombinant CCN5 inhibit pathobiological events like epithelial to mesenchymal transition (EMT), migration and stemness in triple negative breast cancer cells.
Methods: To investigate the negative impact of CCN5 on EMT and stemness of TNBC, we performed several techniques like western blot, clonoogenic assay, soft agar assay, sphere formation assay etc.
Results and Conclusions: The exposure of triple negative human breast cancer cells (TNBC), MDA-MB-231 and HCC-70, to recombinant CCN5 (hrCCN5), resulted in a dose-dependent inhibition of cell-proliferation through the induction of apoptotic cell death. The treatment of hrCCN5 regulates various pathobiological events in breast cancer cells, such as reprogramming the mesenchymal to epithelial transition (MET) followed by reduction of stemness features as confirmed by sphere formation assay and delaying in vitro migration. Finally, treatment with hrCCN5 in TNBC cells significantly inhibited anchorage-dependent and independent growth of TNBC. Collectively, CCN5’s control of cancer cell physiology indicates that hrCCN5 has the potential of being used as a major therapeutic agent against triple negative breast cancer.
Citation Format: Gargi Maity, Amlan Das, Sandipto Sarkar, Snigdha Banerjee, Sushanta K. Banerjee. CCN5/WISP-2 is a negative regulator of epithelial to mesenchymal transition and stemness in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5520. doi:10.1158/1538-7445.AM2017-5520</jats:p
Roles of CCN5 in regulating progression and therapeutic sensitivity of breast cancer
No full textBreast cancer is one of the deadliest malignancies worldwide and also in the United States. Patients with triple negative breast cancer (TNBC), where the cancer cells do not express nuclear hormone receptors and human epidermal growth factor receptor 2 (HER2), have worse survival rate compared to the patients with luminal subtypes of cancer. Here, we have shown that Cysteine-rich 61-Connective Tissue Growth Factor-nephroblastoma-overexpressed 5 (CCN5) induces growth arrest of TNBC cells in-vitro and in xenograft tumors. Our studies show that after being secreted into the extracellular matrix, CCN5 binds to the α6β1 integrins of the cells leading to inhibition of the PI3K-AKT signaling pathway. This leads to stabilization and nuclear localization of FOXO3A resulting in transcriptional activation of the cyclin-dependent kinase inhibitor P27KIP1. Also, we found that the CCN5-induced PI3K-AKT inactivation leads to stabilization and nuclear accumulation of P27KIP1 resulting in cell cycle arrest of TNBC cells. Next, we have shown that CCN5 protein can induce expression of estrogen receptor-α (ER-α) in mammary epithelial cells. We found that mammary epithelium-specific overexpression of CCN5 in transgenic mice leads to an increase in ER-α expression and that this impact of CCN5 is not restricted to the normal cells. CCN5 treatment leads to an expression of functional ER-α in the TNBC cells, both in-vitro and in xenograft models, and sensitizes these cells to tamoxifen, commonly used for endocrine therapies. Mechanistically, transcriptional activation of ER-α by CCN5 is also mediated by FOXO3A stabilization via PI3K-AKT inhibition. Lack of ER-α expression in TNBC cells or loss of ER-α activation after endocrine treatment of luminal cancers makes these breast cancer cells resistant to tamoxifen and other endocrine therapies. Evidently, CCN5-mediated restoration of ER-α and its downstream signaling cascades renders the TNBC cells sensitive to tamoxifen. As these tumors mostly lack CCN5 expression, we anticipate that restoration of CCN5 expression might be able to provide breakthroughs in the treatment of these tumors. Finally, we discuss the effects of CCN5 expression on yet another aggressive breast cancer subtype, characterized by HER2 overexpression. Mammary-specific expression of CCN5 in HER2 overexpressing mice delays tumor progression significantly and reduces the tumor burden. Initial observations indicate that CCN5 induces expression of P16INK4A and P19ARF, resulting in cell cycle arrest of the tumor cells. Collectively, these studies suggest that CCN5 restoration can be beneficial for the better management of breast cancer progression
Abstract 4915: Alcohol-induced reprogramming of tumor plasticity is mediated via suppression of CCN5 signaling in breast cancer cells
No full textAbstract
Background and Objective: The epidemiological and experimental studies suggest that alcohol consumption is associated with increased risk for breast cancer development and metastasis. However, the mechanisms of alcohol-induced breast cancer progression and metastasis remain unknown. In this study, we examined the roles of CCN5, a tumor suppressor gene in alcohol induced breast cancer cell migration/invasion, epithelial to mesenchymal transition (EMT) and stemness.
Methods: Estrogen receptor-positive (ER+) human breast cancer cell line MCF-7 and immortalized normal human epithelial breast cell line MCF-12A were treated with ethanol at various concentrations in the presence and absence of human recombinant human CCN5 protein (hrCCN5) . Invasive/migratory ability of treated and untreated cells was measured by Boyden chamber assays. The mRNA and protein expression level of CCN5 was determined by real-time qRT-PCR and Western blot. EMT and stemness markers were evaluated by Western blot. Single-cell suspensions from pre-treated cells were re-suspended at a density of 500 cells/ml mammocult media in ultralow attachment dishes. Number as well as the size of the mammosphere in specified experimental set-up was monitored and recorded alternate day for 8-10 days.
Results: The studies demonstrated that alcohol promotes significantly the invasive/migratory ability and EMT phenotypes of breast cancer cells through the suppression of CCN5. Interestingly, hrCCN5 protein treatment suppresses the effect of alcohol and reprograms MET (mesenchymal to epithelial transition). In addition, alcohol-induced mammosphere formation efficiency is also suppressed by hrCCN5 protein-treatment.
Conclusions: Our findings suggest that the CCN5 signaling plays a preventive role in alcohol-induced reprogramming of tumor plasticity in breast cancer cells.
Citation Format: Inamul Haque, Arvind Subramanian, Vijayalaxmi Gupta, Sandipto Sarkar, Snigdha Banerjee, Sushanta K. Banerjee. Alcohol-induced reprogramming of tumor plasticity is mediated via suppression of CCN5 signaling in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4915. doi:10.1158/1538-7445.AM2017-4915</jats:p
An inventory model with reliability in an imperfect production process
No full textThe paper analyzes an economic manufacturing quantity (EMQ) model with price and advertising demand pattern in an imperfect production process under the effect of inflation. If the machine goes through a long-run process, it may shift from in-control state to out-of-control state. As a result, the system produces imperfect items. The imperfect items are reworked at a cost to make it as new. The production of imperfect quality items increases with time. To reduce the production of the imperfect items, the systems have to more reliable and the produced items depend on the reliability of the machinery system. In this direction, the author considers that the development cost, production cost, material cost are dependent on reliability parameter. Considering reliability as a decision variable, the author constructs an integrated profit function which is maximized by control theory. A numerical example along with graphical representation and sensitivity analysis are provided to illustrate the model. �� 2011 Elsevier Inc. All rights reserved
Some multivariate linear regression testing problems with additional observations
No full textAbstractIn an earlier paper, the present author (Sarkar (1979), Calcutta Statist. Assoc. Bull.28, 47–56) proposed a similar test for a mean testing problem with additional observations on a set of correlated auxiliary variables. This idea has been extended here to cover some multivariate linear regression testing problems with the same type of additional observations on a set of correlated auxiliary variables
Ananda K. Coomaraswamy, Benoy Kumar Sarkar, and the Śukranīti
No full textThe English-raised Ananda K. Coomaraswamy, the twentieth century’s leading historian of Indian art, is well known for prizing tradition and anonymity and for upholding the position that visualization exercises were an essential part of the creative process. The first part of this article addresses the role of the English Arts and Crafts Movement and of such lesser-known figures as Sister Nivedita and Lionel de Fonseka in shaping Coomaraswamy’s views. The middle part consists of a discussion of the passages in the nineteenth-century Sanskrit treatise the Śukranīti that Coomaraswamy depended upon to support his opinions. The final part of the article is devoted to the writings of the sociologist Benoy Kumar Sarkar, author of the standard translation of the Śukranīti. As an opponent of the over-spiritualisation of Indian civilisation, he constructed a universal grammar of art. In this enterprise, he was heavily influenced by the American painter Max Weber
Repensando la ciencia. La reconstrucción de la ciencia y de la sociedad de P. R. Sarkar
No full textFaced with the traditional or positivist science that stands outside history, culture and language, the author presents the thinking of Sarkar, who does not argue for an anti-science, anti-technology or falls into a science that would exist outside the social and political, but one within context, arguing for a new science of society. This paper raises important questions, such as: in what direction will then move social sciences: towards empathy and interpretation or towards disinterest and distance? Are we close to losing the universal perspectives as power and knowledge are localized and relativized? Or we are dealing with a new model of the real close, that becoming dominant will reformulate the categories of "science", "local" and "universal"?Frente a la ciencia tradicional o positivista que se coloca fuera de la historia, de la cultura y del lenguaje, el autor presenta el pensamiento de Sarkar, quien no argumenta por una posición anti-ciencia, anti-tecnología ni cae en una ciencia que existe fuera de lo social y lo político, sino contextualizada, abogando por una nueva ciencia de la sociedad. El trabajo plantea relevantes preguntas como: ¿En qué dirección se moverán luego las ciencias sociales: hacia la empatía e interpretación o hacia el desinterés y distancia? ¿Estamos nosotros cerca de perder los universales ya que el poder y el conocimiento son localizados y relativizados? ¿O es un nuevo modelo de lo real cercano de llegar a ser dominante que reformula estas categorías de "ciencia", "local" y "universal"
“A legacy of troubles. Bengal Partition as long-lasting narration”
No full textThis essays analyses Indian Partition Literature, focusing on the Eastern border and the novel East/West by the Bengali author Gangopadhyay
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