Claudio Scafoglio

Claudio Scafoglio
University of California, Los Angeles | UCLA

About

48
Publications
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Introduction

Publications

Publications (48)
Article
Full-text available
Increased utilization of glucose is a hallmark of cancer. Sodium-glucose transporter 2 (SGLT2) is a critical player in glucose uptake in early-stage and well-differentiated lung adenocarcinoma (LUAD). SGLT2 inhibitors, which are FDA approved for diabetes, heart failure, and kidney disease, have been shown to significantly delay LUAD development and...
Preprint
Full-text available
Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction by glucose transporter blockade or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are unknown. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) in...
Article
Lung cancer is the most frequent cancer-related cause of death, and adenocarcinoma (LUAD) is the most frequent type. Despite the recent success of immunotherapies, survival of lung cancer patients has not significantly improved in the last decades. New therapies are necessary. We have previously identified sodium-glucose transporter 2 (SGLT2) as th...
Preprint
Full-text available
To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern in vitro and in vivo . Mito-MES had nanomolar in vitro anti...
Article
Full-text available
Recent advances in immunotherapy have reshaped the clinical management of lung cancer, and immune checkpoint inhibitors (ICIs) are now first-line treatment for advanced lung cancer. However, the majority of patients do not respond to ICIs as single agents, and many develop resistance after initial responses. Therefore, there is urgent need to impro...
Article
Full-text available
Metabolic reprogramming is a well described hallmark of cancer. Oncogenic stimuli and the microenvironment shape the metabolic phenotype of cancer cells, causing pathological modifications of carbohydrate, amino acid and lipid metabolism that support the uncontrolled growth and proliferation of cancer cells. Conversely, metabolic alterations in can...
Article
Full-text available
Simple Summary Cancer cells change their metabolism to support a chaotic and uncontrolled growth. In addition to meeting the metabolic needs of the cell, these changes in metabolism also affect the patterns of gene activation, changing the identity of cancer cells. As a consequence, cancer cells become more aggressive and more resistant to treatmen...
Article
Full-text available
Increased glucose uptake is a known hallmark of cancer. Cancer cells need glucose for energy production via glycolysis and the tricarboxylic acid cycle, and also to fuel the pentose phosphate pathway, the serine biosynthetic pathway, lipogenesis, and the hexosamine pathway. For this reason, glucose transport inhibition is an emerging new treatment...
Conference Paper
Background: Lung cancer is the number one cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent type. Lung screening with computed tomography has allowed detection of early nodules that need diagnostic definition. We have identified the sodium-dependent glucose transporter 2 (SGLT2) as a novel diagnostic and therapeutic...
Article
2-Deoxy-2-[18F]fluoro-D-glucose (2-FDG) with positron emission tomography (2-FDG-PET) is undeniably useful in the clinic, among other uses, to monitor change over time using the 2-FDG standardized uptake values (SUV) metric. This report suggests some potentially serious caveats for this and related roles for 2-FDG PET. Most critical is the assumpti...
Article
Full-text available
Squamous cell carcinoma (SCC), a malignancy arising across multiple anatomical sites, is responsible for significant cancer mortality due to insufficient therapeutic options. Here, we identify exceptional glucose reliance among SCCs dictated by hyperactive GLUT1-mediated glucose influx. Mechanistically, squamous lineage transcription factors p63 an...
Conference Paper
Lung cancer is the leading cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis and treatment are essential; however, there are no targeted diagnostic and therapeutic approaches for early LUAD. An important hallmark of cancer is the increased glucose uptake via GLUT transporters. GLUT activit...
Conference Paper
Lung cancer is the leading cause of cancer-related death, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis and treatment are essential; however, there are no targeted diagnostic and therapeutic approaches for early LUAD. An important hallmark of cancer is the increased glucose uptake via GLUT transporters. GLUT activit...
Article
Full-text available
The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed ea...
Conference Paper
Lung cancer claims approximately 160,000 lives in the United States every year, and lung adenocarcinoma (LADC) is the most frequent type. Early diagnosis is crucial; the National Lung Screening Trial showed a 20% reduction in mortality in high-risk individuals screened by computed tomography (CT). However, CT has low specificity in early-stage LADC...
Article
Full-text available
A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-d-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was ex...
Article
Full-text available
OBJECTIVES/SPECIFIC AIMS: Lung cancer claims 160,000 lives in the United States every year, and lung adenocarcinoma (LADC) is the most frequent type. Early diagnosis is crucial. Computed tomography (CT) is very sensitive in identifying early-stage lung nodules, but has low specificity. Increased glucose uptake is a hallmark of cancer measurable in...
Article
Full-text available
Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unans...
Article
Glucose homeostasis is a complex mechanism that requires the interplay between different organs. The kidney plays a central role in this process by re‐absorbing 99.5% of the filtered glucose in the proximal tubules, where SGLT1 and SGLT2 use the energy provided by the electrochemical gradient of sodium to drive glucose transport. In recent years SG...
Article
Full-text available
Significance Cancers require high amounts of glucose to grow and survive, and dogma is that uptake is facilitated by passive glucose transporters (GLUTs). We have identified a new mechanism to import glucose into pancreatic and prostate cancer cells, namely active glucose transport mediated by sodium-dependent glucose transporters (SGLTs). This mea...
Article
Full-text available
Background Estrogens play an important role in breast cancer (BC) development and progression; when the two isoforms of the estrogen receptor (ERα and ERβ) are co-expressed each of them mediate specific effects of these hormones in BC cells. ERβ has been suggested to exert an antagonist role toward the oncogenic activities of ERα, and for this reas...
Article
Full-text available
Checkpoint kinase 2 (Chk2) is a major regulator of DNA damage response and can induce alternative cellular responses: cell cycle arrest and DNA repair or programmed cell death. Here, we report the identification of a new role of Chk2 in transcriptional regulation that also contributes to modulating the balance between survival and apoptosis followi...
Data
Purification of proteins interacting with the FHA of Chk2. A) A PATH-tagged FHA domain of Chk2 was purified from bacteria and incubated with cellular extracts from HeLa cells. As a control, a mutant lacking the ability to bind target phosphopeptides was used. Purified proteins were run on polyacrylamide gels and visualized with silver stain. B) Pro...
Data
Genes whose regulation by cisplatin is affected by NCoR. The table reports the total list of genes whose regulation by CDDP in the microarray experiments was different in the cells transfected with NCoR siRNA compared to the cells transfected with scramble control siRNA. (XLS)
Data
Genes regulated by cisplatin. The table reports the total number of genes resulting regulated by CDDP in the microarrays experiment, ranked by significance as described in Methods S1. (XLS)
Data
Genes whose regulation by cisplatin is affected by SMRT. The table reports the total list of genes whose regulation by CDDP in the microarray experiments was different in the cells transfected with SMRT siRNA compared to the cells transfected with scramble control siRNA. (XLS)
Data
Time-course of cisplatin (CDDP) treatment. U2OS cells were treated with 100 µM CDDP for the indicated time points and the whole cell extracts were used for Western blot with specific antibodies against phospho-Chk2 (T68), cleaved PARP (Asp214), or β-tubulin. (TIF)
Data
Methods for the data included in Supporting Figures and detailed descriptions of microarray data analysis, plasmids and qPCR primers are included. (DOC)
Article
A key strategy to achieve regulated gene expression in higher eukaryotes is to prevent illegitimate signal-independent activation by imposing robust control on the dismissal of corepressors. Here, we report that many signaling pathways, including Notch, NF-kappaB, and nuclear receptor ligands, are subjected to a dual-repression "checkpoint" based o...
Article
Estrogen exerts a primary regulatory role on a wide variety of physiological processes in different tissues and organs. Agonistic ad antagonistic compounds are widely used in human health and, therefore, a deep understanding of their mechanisms of action at the molecular level is mandatory. The effect of 17beta-estradiol and three antiestrogenic dr...
Article
Antiestrogens used for breast cancer (BC) treatment differ among each other for the ability to affect estrogen receptor (ER) activity and thereby inhibit hormone-responsive cell functions and viability. We used high-density cDNA microarrays for a comprehensive definition of the gene pathways affected by 17beta-estradiol (E2), ICI 182,780 (ICI), 4OH...
Article
While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-...
Article
Full-text available
p38 MAPKs (mitogen-activated protein kinases) play important roles in the regulation of cellular responses to environmental stress. Recently, this signalling pathway has also been implicated in the regulation of processes unrelated to stress, for example, in T lymphocytes and cardiomyocytes. In order to identify molecular targets responsible for th...
Article
Full-text available
Review of: The inhibitor of cyclin-dependent kinase 4a/alternative reading frame (INK4a/ARF) locus encoded proteins p16INK4a and p19ARF repress cyclin D1 transcription through distinct cis elements - Volume 8 Issue 2 - C. Scafoglio, A. Weisz
Article
Full-text available
Transcriptional activation of the cyclin D1 gene (CCND1) plays a pivotal role in G1-phase progression, which is thereby controlled by multiple regulatory factors, including nuclear receptors (NRs). Appropriate CCND1 gene activity is essential for normal development and physiology of the mammary gland, where it is regulated by ovarian steroids throu...
Article
Estrogens exert a key biological role in mammary gland epithelial cells and promote breast carcinogenesis and tumor progression. We recently identified a new large set of estrogen responsive genes from breast cancer (BC) cells by DNA microarray analysis of the gene expression profiles induced by 17beta-estradiol in ZR-75.1 and MCF-7 cells. The purp...
Article
Full-text available
Estrogen controls key cellular functions of responsive cells including the ability to survive, replicate, communicate and adapt to the extracellular milieu. Changes in the expression of 8400 genes were monitored here by cDNA microarray analysis during the first 32 h of human breast cancer (BC) ZR-75.1 cell stimulation with a mitogenic dose of 17bet...
Article
Full-text available
Background Biological markers capable of predicting the risk of recurrence and the response to treatment in breast cancer are eagerly awaited. Estrogen and progesterone receptors (ER, PgR) in tumor cells mark cancers that are more likely to respond to endocrine treatment, but up to 40% of such patients do not respond. Here, the expression of a grou...
Article
Full-text available
Biological markers capable of predicting the risk of recurrence and the response to treatment in breast cancer are eagerly awaited. Estrogen and progesterone receptors (ER, PgR) in tumor cells mark cancers that are more likely to respond to endocrine treatment, but up to 40% of such patients do not respond. Here, the expression of a group of estrog...
Article
(3) Dipartimento di Patologia generale, Seconda Università degli Studi di Napoli. alessandro.weisz@unina2.it

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