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Articles 1531 - 1560 of 2186
Full-Text Articles in Medicine and Health Sciences
Abstracts From The 23rd Annual Health Care Systems Research Network Conference, March 21–23, 2017, San Diego, California
Journal of Patient-Centered Research and Reviews
This proceedings supplement includes selected abstracts presented at the 23rd annual conference of the Health Care Systems Research Network (HCSRN), held March 21–23, 2017, in San Diego, California. Formerly called the HMO Research Network, HCSRN aims to improve individual and population health through research that connects the resources and capabilities of its member health care systems.
Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein
Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein
The Summer Undergraduate Research Fellowship (SURF) Symposium
Cancer treatment resistance and their invasive and expensive nature is propelling research towards developing alternate approaches to eradicate cancer in patients. Non-thermal, i.e., cold atmospheric plasma (CAP) and electroporation (EP) applied to the surface of cancerous tissue are new methods that are minimally invasive, safe, and selective. These approaches, both independently and synergistically, have been shown to deplete cancer cell populations, but the signaling mechanisms of death and their timelines of action are still widely unknown. To better understand the timeframe of signaling events occurring upon treatment, human cancer cell lines were treated with CAP, EP, and combined CAP with …
Three-Dimensional Microfluidic Tumor Vascular Model For Investigating Breast Cancer Metastasis, Anastasiia Vasiukhina, Brian H. Jun, Luis Solorio, Pavlos P. Vlachos
Three-Dimensional Microfluidic Tumor Vascular Model For Investigating Breast Cancer Metastasis, Anastasiia Vasiukhina, Brian H. Jun, Luis Solorio, Pavlos P. Vlachos
The Summer Undergraduate Research Fellowship (SURF) Symposium
Metastasis is one of the primary reasons for the high mortality rates in female patients diagnosed with breast cancer. It involves the migration of cancer cells into the circulatory system allowing for the dissemination of cancer cells in distal tissues. Understanding the major processes that occur in cells and tissues during metastasis can help improve currently existing therapeutic methods. In order to understand such mechanisms, developing physiologically relevant tissue models is crucial. Advancements in microfluidics have led to the fabrication of 3D culture models with shear stress gradients and flow control that can recapitulate aspects of the tumor microenvironment in …
Clinical And Therapeutic Significance Of Obesity In Melanoma, Jennifer L. Mcquade
Clinical And Therapeutic Significance Of Obesity In Melanoma, Jennifer L. Mcquade
Dissertations and Theses (Open Access)
While the FDA approval of targeted and immune therapies in metastatic melanoma (MM) have dramatically improved outcomes in this disease, de novo and/or acquired resistance can limit the clinical benefit of these agents. The IGF-1/PI3K/AKT pathway has been implicated in resistance to both targeted and immune therapy. The IGF-1/PI3K/AKT pathway has also been shown to play a key role in the pathogenesis of obesity in other malignancies. To date, the impact of energy balance on clinical outcomes and therapeutic response in MM has not been studied. I hypothesized that energy balance would impact the molecular biology, behavior, and drug sensitivity …
Metabolic Regulation Of Cellular Signaling, Rashid John Darbandi
Metabolic Regulation Of Cellular Signaling, Rashid John Darbandi
Theses and Dissertations (ETD)
Using the biochemically tractable Xenopus oocyte model system, we have previously characterized a novel metabolic regulation of cell death. We found that glucose-6-phosphate (G6P) via the pentose phosphate pathway leads to increased nicotinamide adenine dinucleotide phosphate (NADPH) levels, a subsequent increase in cytosolic acetyl-coenzyme A and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). We recently identified coenzyme A (CoA), derived from the breakdown of acetyl-CoA, as the key metabolic signal that mediates a novel mechanism of calmodulindependent activation of CaMKII. CoA binds directly to the calmodulin (CaM) binding domain (CaMBD) of CaMKII resulting in its activation and downstream inhibitory phosphorylation …
Rna Sequencing In The Development Of Cancer-Cachexia, Thomas Allen Blackwell
Rna Sequencing In The Development Of Cancer-Cachexia, Thomas Allen Blackwell
Graduate Theses and Dissertations
Introduction: Cancer is a major public health problem in the U.S. and the world. In 2013 there were an estimated 1,660,290 new cases of cancer in the U.S. Cancer-Cachexia (CC) is a common effect of many cancers, and is directly responsible for 20-40% of cancer-related deaths. The mechanisms that control the development of CC are not well understood. Most investigations of CC focus on the post-cachectic state and do not examine the progression of the condition. The purpose of this study was to utilize RNA sequencing to analyze transcriptomic alterations throughout the progression of CC. Methods: Lewis Lung Carcinoma cells …
Prostate Cancer In African American Men, Chinwe Egwudo
Prostate Cancer In African American Men, Chinwe Egwudo
Nursing Student Class Projects (Formerly MSN)
Prostate cancer, a malignancy with racial disparity, affects African American men more than Caucasians or any other race.
Cervical Cancer, Mary Jedlicka
Cervical Cancer, Mary Jedlicka
Nursing Student Class Projects (Formerly MSN)
No abstract provided.
Mk2 Promotes Colorectal Cancer Development, Invasion, And Growth Through Mk2-Induced Cytokines, Anita Lynne Ray
Mk2 Promotes Colorectal Cancer Development, Invasion, And Growth Through Mk2-Induced Cytokines, Anita Lynne Ray
Biomedical Sciences ETDs
Colorectal cancer (CRC) is the third most common malignancy in the United States for men and women. A major risk factor for CRC development and progression is inflammation, in particular the inflammatory cytokines IL-1, IL-6, and TNF-α. These proteins promote critical cancer functions, such as proliferation, invasion, survival, and migration. Control of inflammation is one potential area of therapeutic intervention for some cancers. Because signaling of these cytokines overlaps in many of the same pathways, targets upstream of protein production could prove an effective strategy to reduce inflammation. MAPK-activated protein kinase 2 (MK2) pathway controls production of these cytokines within …
Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie
Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie
Mahurin Honors College Capstone Experience/Thesis Projects
With the invention of advanced technology, focus has been put on understanding and looking for potential cures for many diseases, one of which is cancer. The difference in the leaving and non-leaving ligands of the FDA approved cancer drugs contributes to the differential cell specific cytotoxic effects. These drugs such as oxaliplatin approved for colorectal cancer, cisplatin approved for testicular cancer, and their analogs were used to treat different cancer cell lines in an MTT assay. This project aims to determine how changing the molecular shape of these compounds affects their uptake and toxicity into different cell lines. The assay …
Investigating The Synergistic Effects Of Cisplatin And Two Curcuminoid Compounds On Cancer, Denis Hodzic
Investigating The Synergistic Effects Of Cisplatin And Two Curcuminoid Compounds On Cancer, Denis Hodzic
Mahurin Honors College Capstone Experience/Thesis Projects
Cisplatin is an anti-cancer drug effective against several cancers which can produce the serious side-effect of hearing loss. Curcumin, a natural plant compound, can increase the activity of cisplatin against cancer and counteract cisplatin’s effect against hearing. Because curcumin exhibits poor bioavailability, there is considerable interest in developing synthetic curcumin analogs (curcuminoids) that are more soluble and which retain anti-cancer activity and otoprotective function. This study investigated whether two curcuminoids, EF-24 and CLEFMA, increase the cytotoxic and ototoxic effects of cisplatin against the lung cancer cell line, A549, and the colorectal cancer cell line, Caco2. Cytotoxicity was measured by using …
African American Men's Prostate Cancer Knowledge And Self-Efficacy For Informed Decision-Making: A Mixed Methods Study, Dionne J. Jones-Dendy Phd
African American Men's Prostate Cancer Knowledge And Self-Efficacy For Informed Decision-Making: A Mixed Methods Study, Dionne J. Jones-Dendy Phd
Nursing Theses and Dissertations
A mixed methods study was conducted whereby, the quantitative portion has a randomized control design, in an urban Delaware community to examine the effectiveness of an educational intervention, which included the testimony of an African American (AA) prostate cancer survivor on AA men’s (n=98) prostate cancer knowledge and self-efficacy for informed decision making. Guided by Bandura’s Social Cognitive theory, participants’ prostate cancer knowledge measured by PROCASE and for self-efficacy measured by the Prostate Cancer Screening Self-efficacy scale, were evaluated before and following viewing of the American Cancer Society’s prostate cancer video. Participants randomized to the intervention completed evaluations after the …
Impact Of Hpv Education On Knowledge, Perception, And Cultural Influence Among African American Parents, Christina Lattner
Impact Of Hpv Education On Knowledge, Perception, And Cultural Influence Among African American Parents, Christina Lattner
College of Science and Health Theses and Dissertations
Background: Infection with human papillomavirus (HPV), the sexually transmitted virus that causes cervical and penial cancer can be prevented. An effective vaccine has been approved for both boys and girls since 2006. Despite recommendation from the Center of Disease Control, vaccination initiation and completion rates among African American adolescents in the United States are lower than average in the nation.
Objectives: The purpose of this descriptive survey study was to identify African-American parents’ knowledge and perceptions of sexually transmitted HPV infection and the HPV vaccination. The secondary objective was to use a single-group pre-test post-test research design to examine …
Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan
Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan
Center for Environmental and Systems Biochemistry Faculty Publications
Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival, and eventually metastasis in a harsh environment. Stable isotope-resolved metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems, including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.
Breast Cancer Patient Preparedness For Transition To Survivorship: Individualized Survivorship Care Plans, Kimberly Beringer
Breast Cancer Patient Preparedness For Transition To Survivorship: Individualized Survivorship Care Plans, Kimberly Beringer
Master's Projects and Capstones
Purpose. For breast cancer survivors, after-effects of surgery, radiation and chemotherapy can be substantial, and recurrence is a concern requiring constant surveillance. National healthcare organizations have promulgated guidelines that include providing individualized survivorship care plans (SCP’s). At a northern California oncology department, SCP’s will be prepared for breast cancer patients and delivered in-person by the oncology nurse navigator (ONN).
Method. The author worked with the ONN to develop the format and content requirements for the SCP’s. The ONN prepared individualized plans for patients and scheduled in-person appointments to deliver the SCP’s. A feedback survey to assess preliminary impact was then …
B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips
B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips
Seton Hall University Dissertations and Theses (ETDs)
Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …
The Healing Power Of A Whole Foods, Plant-Based Diet: A Nutrition Prescription For Cancer, Meghan Adelman Mrs.
The Healing Power Of A Whole Foods, Plant-Based Diet: A Nutrition Prescription For Cancer, Meghan Adelman Mrs.
Master's Projects and Capstones
Chronic disease is quickly overtaking infectious diseases as one of the biggest threats to population health worldwide (Egger, 2012). Studies have shown that plant based diets are effective at reducing prevalence but are also a viable complimentary treatment approach to healing. Further investigation is needed into how plant based diets can reduce risk of recurrence, specifically as it relates to a cancer diagnosis. The Ceres Project is an organization that provides a healing foods philosophy to the care of cancer patients through meal delivery programs at low to no cost. The aim of this research study was to implement the …
One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii
One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii
Electronic Theses & Dissertations
In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer …
Dietary Alkylresorcinols And Cancer Prevention: A Systematic Review, Joanna Kruk, Basil Aboul‑Enein, Joshua Bernstein, Mariola Marchlewicz
Dietary Alkylresorcinols And Cancer Prevention: A Systematic Review, Joanna Kruk, Basil Aboul‑Enein, Joshua Bernstein, Mariola Marchlewicz
Health & Wellness Department Faculty Publications and Research
The potential role of alkylresorcinol compound from whole grains for prevention and inhibition of human cancer cell lines has been reported in observational and in vitro studies. The objective of this study was to present an updated review on the association between alkylresorcinols and cancer risk and aspects of their bioactivity with implications for carcinogenesis. Relevant studies were identifed by searching PubMed, Scopus, ProQuest, EBSCOhost, SpringerLink, ArticleFirst, Taylor & Francis, Wiley Online, and ScienceDirect electronic databases using these search terms and key words: alkylresorcinols, cancer, carcinoma, risk. Furthermore, references from retrieved articles were also reviewed. Four observational and 10 in …
The Clinical Impact Of Copy Number Variants In Inherited Bone Marrow Failure Syndromes, Nicolas Waespe, Santhosh Dhanraj, Manju Wahala, Elena Tsangaris, Tom Enbar, Bozana Zlateska, Hongbing Li, Robert J Klaassen, Conrad V Fernandez, Geoff D E Cuvelier, John K Wu, Yves D Pastore, Mariana Silva, Jeffrey H Lipton, Joseé Brossard, Bruno Michon, Sharon Abish, Macgregor Steele, Roona Sinha, Mark J Belletrutti, Vicky R Breakey, Lawrence Jardine, Lisa Goodyear, Liat Kofler, Michaela Cada, Lillian Sung, Mary Shago, Stephen W Scherer, Yigal Dror
The Clinical Impact Of Copy Number Variants In Inherited Bone Marrow Failure Syndromes, Nicolas Waespe, Santhosh Dhanraj, Manju Wahala, Elena Tsangaris, Tom Enbar, Bozana Zlateska, Hongbing Li, Robert J Klaassen, Conrad V Fernandez, Geoff D E Cuvelier, John K Wu, Yves D Pastore, Mariana Silva, Jeffrey H Lipton, Joseé Brossard, Bruno Michon, Sharon Abish, Macgregor Steele, Roona Sinha, Mark J Belletrutti, Vicky R Breakey, Lawrence Jardine, Lisa Goodyear, Liat Kofler, Michaela Cada, Lillian Sung, Mary Shago, Stephen W Scherer, Yigal Dror
Paediatrics Publications
Inherited bone marrow failure syndromes (IBMFSs) comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants (CNVs) were reported in some IBMFSs. It is unclear what impact CNVs play in patients evaluated for a suspected diagnosis of IBMFS. Clinical and genetic data of 323 patients from the Canadian Inherited Marrow Failure Registry from 2001 to 2014, who had a documented genetic work-up, were analyzed. Cases with pathogenic CNVs (at least 1 kilobasepairs) were compared to cases with other mutations. Genotype-phenotype correlations were performed to assess the impact of CNVs. Pathogenic …
College Of Public Health News, Georgia Southern University
College Of Public Health News, Georgia Southern University
College of Public Health: News & Publications
- Georgia Southern Examines Physical Activity Levels and Counseling in Cancer Survivors
Epidemiology News, Georgia Southern University
Epidemiology News, Georgia Southern University
Biostatistics, Epidemiology & Environmental Health Sciences: News & Publications (2011-2018)
- Georgia Southern Examines Physical Activity Levels and Counseling in Cancer Survivors
The Effects Of Lipocalin 2 On Lung Metastasis Of Colorectal And Other Cancers, Lauren Strzyzewski
The Effects Of Lipocalin 2 On Lung Metastasis Of Colorectal And Other Cancers, Lauren Strzyzewski
Senior Theses
Lipocalin 2 (Lcn2) is a member of the lipocalin family of siderophore-binding molecules that can mediate iron trafficking. It acts during the innate immune response and has been implicated in conflicting roles in metastasis, leaving its role undefined. In breast cancer LCN2 was shown in previous studies to both inhibit or promote metastasis. Previous studies the Pena laboratory showed that increasing the serum levels of LCN2 caused a significantly increase in liver metastasis of the poorly metastatic MC-38 colon cancer cell line. In this study, we examined the ability of LCN2 to promote metastasis of colon and other cancers to …
Health Policy & Management News, Georgia Southern University
Health Policy & Management News, Georgia Southern University
Health Policy & Community Health: News & Publications (2011-2018)
- Georgia Southern Examines Physical Activity Levels and Counseling in Cancer Survivors
High-Content Screen Using Zebrafish (Danio Rerio) Embryos Identifies A Novel Kinase Activator And Inhibitor, Werner J. Geldenhuys, Sadie A. Bergeron, Jackie E. Mullins, Rowaa Aljammal, Briah L. Gaasch, Wei-Chi Chen, June Yun, Lori A. Hazlehurst
High-Content Screen Using Zebrafish (Danio Rerio) Embryos Identifies A Novel Kinase Activator And Inhibitor, Werner J. Geldenhuys, Sadie A. Bergeron, Jackie E. Mullins, Rowaa Aljammal, Briah L. Gaasch, Wei-Chi Chen, June Yun, Lori A. Hazlehurst
Clinical and Translational Science Institute
In this report we utilized zebrafish (Danio rerio) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum (ER) enzyme, endoplasmic reticulum oxidoreductase (ERO1) inhibitor EN460. EN460 showed a dose response effect on the embryos with a dose of 10 μM being significantly lethal during early embryonic development. The HCS campaign which employed a small library identified a promising lead compound, a naphthyl-benzoic acid derivative coined compound 1 which had significant dosage and temporally dependent effects on notochord …
Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett
Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett
Undergraduate Honors Theses
Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no …
An In Vitro Study On The Detection Of Ovarian Cancer Using A Novel Ph-Specific Targeting Polypyrrole Nanocontrasting Agent., Phillip Chuong
An In Vitro Study On The Detection Of Ovarian Cancer Using A Novel Ph-Specific Targeting Polypyrrole Nanocontrasting Agent., Phillip Chuong
College of Arts & Sciences Senior Theses
Longitudinal tracking and accumulation of polymeric nanoparticles in the context of cancer has largely occurred through identification of a fluorescent cargo. In this study, we created a dual extracellular acidic pH targeted polypyrrole-based hollow nanoparticle as a theranostic (maintain both therapeutic and diagnostic capabilities) agent for improved detection and treatment of ovarian cancer. Polypyrrole-hollow nanospheres (PPy-CS) were fabricated through the removal of a silver chloride (AgCl) core, which served as a template, followed by coating with chitosan and further tumor targeted with a pH low insertion peptide, V7. We exploited the NIR-absorbing property of polypyrrole to track both the nanoparticle …
Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan
Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan
Undergraduate Research Symposium Posters
Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …
Sensitivity Of Diffuse Reflectance Spectroscopy To Dose- And Depth-Dependent Changes In Tumor Oxygenation After Radiation Therapy, Daria Semeniak
Sensitivity Of Diffuse Reflectance Spectroscopy To Dose- And Depth-Dependent Changes In Tumor Oxygenation After Radiation Therapy, Daria Semeniak
Graduate Theses and Dissertations
Along with chemotherapy, immunotherapy, and surgery, radiotherapy is one of the most common treatments used against cancer. Around 50% of all cancer patients undergo radiation therapy. While for some patients radiotherapy works efficiently and lead to a complete cancer disappearance, for others treatment outcome may be less favorable due to radioresistance processes happening within a tumor on the molecular level. Radioresistance remains a big challenge for modern oncology. The ability to identify radioresistance at the early stage of radiotherapy would help physicians to improve therapy efficiency. At the current moment, despite the rapid progress in cancer understanding and diagnostic modalities, …
The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely
The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely
Electronic Theses and Dissertations
Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Importantly, C12 induces apoptosis …