Juan Yakisich

Juan Yakisich
--

MD, PhD

About

97
Publications
11,134
Reads
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1,355
Citations
Citations since 2016
45 Research Items
902 Citations
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2016201720182019202020212022050100150
2016201720182019202020212022050100150

Publications

Publications (97)
Article
Full-text available
The classical cancer stem cell (CSCs) theory proposed the existence of a rare but constant subpopulation of CSCs. In this model cancer cells are organized hierarchically and are responsible for tumor resistance and tumor relapse. Thus, eliminating CSCs will eventually lead to cure of cancer. This simplistic model has been challenged by experimental...
Article
Full-text available
At present there is no effective specific antiviral drug to treat the ongoing COVID-19 pandemic that has already infected millions of individual and caused hundreds of thousand deaths worldwide. There is strong indication that a cytokine storm is responsible for the severity of COVID-19 patients. Pilot studies using IL-6 receptor inhibitors such as...
Article
Full-text available
Antibodies are the most used technological tool in histochemistry. However, even with monoclonal antibodies, their standardization is difficult due to variation of biological systems as well as to variability due to the affinity and amplification of the signal arising from secondary peroxidase detection systems. In this article we combined two synt...
Article
Despite the recent announcement of promising drug candidates to treat COVID-19, there is currently no effective antiviral drug or vaccine. There is strong evidence that acute lung injury/acute respiratory distress syndrome (ALI/ARDS), likely triggered by a cytokine storm, is responsible for the severity of disease seen in COVID-19 patients. In supp...
Article
Full-text available
Electrical impedance spectroscopy (EIS) is an electrokinetic method that allows for the characterization of intrinsic dielectric properties of cells. EIS has emerged in the last decade as a promising method for the characterization of cancerous cells, providing information on inductance, capacitance, and impedance of cells. The individual cell beha...
Article
Full-text available
Air particulate matter has been associated with adverse effects in the cardiorespiratory system leading to cytotoxic and pro-inflammatory effects. Particulate matter-associated cardiac effects may be direct or indirect. While direct interactions may occur when inhaled ultrafine particles and/or particle components cross the air–blood barrier reachi...
Article
Full-text available
The biguanides metformin (MET) and to a lesser extent buformin (BUF) have recently been shown to exert anticancer effects. In particular, MET targets cancer stem cells (CSCs) in a variety of cancer types but these compounds have not been extensively tested for combination therapy. In this study, we investigated in vitro the anticancer activity of M...
Chapter
The classical cancer stem cell theory (CCSCT) proposes that tumors contain a subpopulation of rare cancer cells with stem-like properties (cancer stem cells, CSCs) that are organized hierarchically and are responsible for chemoresistance and tumor relapse. In this model, CSCs can generate non-CSCs, but this process is irreversible (unidirectional m...
Article
Full-text available
Ion homeostasis is extremely important for the survival of both normal as well as neoplastic cells. The altered ion homeostasis found in cancer cells prompted the investigation of several ionophores as potential anticancer agents. Few ionophores, such as Salinomycin, Nigericin and Obatoclax, have demonstrated potent anticancer activities against ca...
Article
Three‐dimensional (3D) culture systems such as floating spheroids (FSs) and floating tumorspheres (FTs) are widely used as tumor models of chemoresistance. FTs are considered to be enriched in cancer stem‐like cells (CS‐LCs). In this study, we used cancer cell lines (lung H460, prostate LnCAP, and breast MCF‐7) able to form FSs under anchorage‐inde...
Article
Full-text available
The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil...
Article
Despite the vast amounts of information gathered about gliomas, the overall survival of glioma patients has not improved in the last four decades. This could partially be due to an apparent failure to include basic concepts of glioma biology into clinical trials. Specifically, attempts to overcome the limitations of the blood brain barrier (BBB) an...
Article
Full-text available
While there are targeted treatments for triple positive breast cancers, lack of specific biomarkers for triple-negative breast cancers (TNBC) has hindered the development of therapies for this subset of cancers. In this study, we evaluated the anticancer properties of cardiac glycoside Digitoxin (Dtx) and its synthetic analog MonoD on breast cancer...
Article
Background: Resveratrol has been shown to have antioxidant and anti-proliferative properties in multiple cancer types. Here we demonstrate that H460 lung cancer cells are more susceptible to resveratrol treatment in comparison to human bronchial epithelial Beas-2B cells. Resveratrol decreases cell viability and proliferation, and induces significa...
Article
Full-text available
Multiple factors including tumor heterogeneity and intrinsic or acquired resistance have been associated with drug resistance in lung cancer. Increased stemness and the plasticity of cancer cells have been identified as important mechanisms of resistance; therefore, treatments targeting cancer cells independent of stemness phenotype would be much m...
Article
Full-text available
Breast cancer is second most prevalent cancer in women, and the second only to lung cancer in cancer-related deaths. It is a heterogeneous disease and has several subtypes based on the presence or absence of hormone receptors and/or human epidermal growth factor receptor 2 (HER2). Hormone receptor-positive and HER2-enriched cancers can be targeted...
Data
Figure S1. Representative images of LTs treated for 24 h with DMSO alone (control) or VP (100 µM) + SF (5 µM). Magnification: 20X (Bar = 200 µM). The inset shows an example of cell that reattach to the plate when treated with DMSO alone. In contrast, in the drug-treated plate, cells fail to reattach and clearly shows loss of cellular integrity. Fig...
Article
In cancer cells, the reversible nature of the stemness status in terms of chemoresistance has been poorly characterized. In this study, we have simulated on cycle of environmental conditions to study such reversibility by first generating floating tumorspheres (FTs) from lung and breast cancer cells by culturing them in serum-free media without the...
Article
Cellular oxidative stress is implicated not only in lung injury but also in contributing to the development of pulmonary fibrosis. We demonstrate that a cell permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger, Manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) significantly inhibited bleomycin-induced fibrog...
Article
Lung cancer is a leading cause of cancer-related death in the United States. While several drugs have been developed that target individual biomarkers, their success has been limited due to intrinsic or acquired resistance for the specific targets of such drugs. A more effective approach is to target multiple pathways that dictate cancer progressio...
Article
The efficacy of chemotherapy is hindered by both tumor heterogeneity and acquired or intrinsic multi- drug resistance caused by the contribution of multidrug resistance proteins and stemness-associated prosurvival markers. Therefore, targeting multi-drug resistant cells would be much more effective against cancer. In this study, we characterized th...
Article
Background: Digitoxin, a cardiac glycoside had shown considerable promise as an anti-cancer therapeutic. However, doses of digitoxin required to inhibit cancer cell proliferation lead to cardiotoxic side effects. We have previously shown that a novel analog of digitoxin, MonoD, activates apoptosis in human lung cancer cells at much lower concentrat...
Article
Purpose: Resistance to anticancer drugs is a common cause of failure in chemotherapy. We recently found that adherent cells growing under prolonged periods (7-12 days) of serum starvation become highly resistant to conventional anticancer drugs such as Paclitaxel, Hydroxyurea and Colchicine but retain sensitivity to therapeutic levels of the cardia...
Article
Purpose: The biguanides Metformin (MET) and to a lesser extent Buformin (BUF) have recently been shown to exert anticancer effects. In particular MET targets cancer stem cells (CSCs) in a variety of cancer types. These compounds have not been extensively tested for combination therapy. Objectives: In this study we investigated in vitro the anticanc...
Article
Titanium dioxide (TiO2) is a ubiquitous whitening compound widely used in topical products such as sunscreens, lotions and facial creams. The damaging health effects of TiO2 inhalation has been widely studied in rats, mice and humans showing oxidative stress increase, DNA damage, cell death and inflammatory gene upregulation in lung and throat cell...
Article
Full-text available
Breast cancer is the most frequently diagnosed cancer in women, and one of the leading causes of cancer-related deaths worldwide. Recent evidences indicate that dietary agents such as resveratrol may inhibit cancer progression through modulation of microRNAs (miRNAs). We demonstrate that resveratrol regulates apoptotic and cell cycle machinery in b...
Article
Full-text available
Like with most solid tumors, the presence of a subpopulation of cancer stem cells (CSCs) or cancer stem-like cells (CS-LCs) has been associated with chemoresistance and tumor relapse in lung cancer cells. In the absence of serum, CSCs/CS-LCs have the ability to grow as lung tumorspheres (LTSs), and this system is routinely used for isolation and ch...
Article
Despite significant advances in the understanding of lung cancer biology, the prognosis of cancer patients remains poor. Part of the failure of anticancer therapy is due to intratumoral heterogeneity in these patients that limits the efficacy of single agents. Therefore, there is an urgent need for new anticancer drugs or drug combination regimens...
Article
Full-text available
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a life expectancy of less than five years post diagnosis for most patients. Poor molecular characterization of IPF has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies. In this study, we have integrated a label free L...
Article
Purpose: Breast cancer is the second most common type of cancer in women and several drugs are currently being used against this disease. In spite of the availability of promising chemotherapeutic drugs, it is often observed that tumor cells develop resistance to these drugs rendering them ineffective after prolonged use. Identifying alternative an...
Article
Digitoxin, a cardiac glycoside well appreciated in the treatment of congestive heart failure, has been poorly understood and appreciated as an anti-cancer therapeutic due to its narrow therapeutic potential. Using a patented palladium-catalyzed de novo synthesis method, we have developed a library of digitoxin analogs, which alleviate the toxic sid...
Article
During the last five decades, enormous advances in treatment modalities for cancer and a better understanding of cancer cell biology have been accomplished but the prognosis of patients carrying malignant gliomas still remains poor despite hundreds of clinical trials have been carried out. In this article we review phase II clinical trials that hav...
Article
Full-text available
Lung cancer is a devastating disease that is responsible for around 160,000 deaths each year in United States. The discovery that lung cancer, like most other solid tumors, contains a subpopulation of cancer stem cells or cancer stem-like cells (CSCs/CS-LCs) that if eliminated could lead to a cure has brought new hope. However, the exact nature of...
Article
Glioblastoma is the most common primary brain tumor and one of the most devastating cancers. High-grade glioma patients’ prognoses are very poor, usually with a median survival of less than one year. Maximal neurosurgical resection followed by external adjuvant radiation therapy and chemotherapy is the conventional treatment for newly diagnosed hig...
Article
The effectiveness of anticancer therapies relies on the ability of these substances to eliminate selectively the malignant cells with little or no toxicity to normal cells. The isolation in most human tumors of a rare subpopulation of cancer stem cells (CSCs) associated with chemo resistance lead to the "stem cell theory" (SCT). The SCT proposed th...
Article
The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a key regulator of authophagy. Natural products show anticancer activity and often induce apoptosis or autophagy. The crosstalk between these two types of cell death makes autophagy an interesting target since drugs targeting this process not only can ind...
Article
Treatment of brain tumors with chemotherapy is limited mostly because of delivery impediments related to the blood-brain barrier (BBB). For gliomas, the most common and aggressive primary brain tumor, treatment includes surgery, radiotherapy, and chemotherapy usually administered orally or intravenously. These routes do not deliver effective concen...
Article
Full-text available
Exposure of cancer cells to anticancer agents in cultures induces detachment of cells that are usually considered dead. These drug-induced detached cells (D-IDCs) may represent a clinical problem for chemotherapy since they may survive anoikis, enter the circulation, invade other tissues and resume proliferation, creating a metastasis, especially i...
Data
Full-text available
Fate of detached A549 lung cancer induced by aphidicolin, etoposide, paclitaxel or hydroxyurea. Figure S1 shows that these drugs are all able to induce cell detachment and, except for etoposide, they are able to re-attach and proliferate when re-incubated in drug-free media.
Article
Full-text available
The identification of a fraction of cancer stem cells (CSCs) associated with resistance to chemotherapy in most solid tumors leads to the dogma that eliminating this fraction will cure cancer. Experimental data has challenged this simplistic and optimistic model. Opposite to the classical cancer stem cell model, we introduced the stemness phenotype...
Article
Full-text available
The anticancer drugs screening program is a long and expensive process. It is estimated that only 5% of drugs entering clinical trials are approved by the FDA. Moreover, many of the drugs that enter clinical trials are often of limited use in clinical practice, and most cancers remain untreatable. Brain tumors are particularly difficult to treat du...
Article
Full-text available
The existence of cancer cells with stem cell properties (Cancer Stem Cells, CSCs) and their association with tumor resistance and relapse has led to the search for active compounds to eliminate these cells or modulate their stemness in the hope of curing cancer. So far, three classes of drugs that target cancer stemness (Stemness Modulator Drugs) h...
Article
Full-text available
The identification of a fraction of cancer stem cells (CSCs) associated with resistance to chemotherapy in most solid tumors leads to the dogma that eliminating this fraction will cure cancer. Experimental data has challenged this simplistic and optimistic model. Opposite to the classical cancer stem cell model, we introduced the stemness phenotype...
Article
Cell cycle checkpoints are essential mechanisms safeguarding genome stability. Defects in checkpoints predispose cells to genome instability and neoplastic transformation. When cells are treated with DNA damaging agents or inhibitors that interfere with ongoing DNA replication, the intra-S checkpoint is activated to delay progression through S phas...
Article
Full-text available
Standard treatment for glioma includes surgery, radiotherapy and chemotherapy but the outcome of patients is very poor. Antineoplastic drugs are usually administered alone or in combination for variable times (continuously or in cycles) in a single phase schedule. In this study we explored in vitro the antiproliferative effect of a 2 phases treatme...