scholarly journals ROS Pleiotropy in Melanoma and Local Therapy with Physical Modalities

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Sanjeev Kumar Sagwal ◽  
Sander Bekeschus
Keyword(s):  
Skin Cancer ◽  
Oxidative Damage ◽  
Cell Biology ◽  
Local Therapy ◽  
Therapy Resistance ◽  
Physical Therapy Modalities ◽  
Premature Aging ◽  
Metabolic Energy ◽  
Cancer Therapies ◽  
Targeting Therapy

Metabolic energy production naturally generates unwanted products such as reactive oxygen species (ROS), causing oxidative damage. Oxidative damage has been linked to several pathologies, including diabetes, premature aging, neurodegenerative diseases, and cancer. ROS were therefore originally anticipated as an imperative evil, a product of an imperfect system. More recently, however, the role of ROS in signaling and tumor treatment is increasingly acknowledged. This review addresses the main types, sources, and pathways of ROS in melanoma by linking their pleiotropic roles in antioxidant and oxidant regulation, hypoxia, metabolism, and cell death. In addition, the implications of ROS in various physical therapy modalities targeting melanoma, such as radiotherapy, electrochemotherapy, hyperthermia, photodynamic therapy, and medical gas plasma, are also discussed. By including ROS in the main picture of melanoma skin cancer and as an integral part of cancer therapies, a greater understanding of melanoma cell biology is presented, which ultimately may elucidate additional clues on targeting therapy resistance of this most deadly form of skin cancer.

scholarly journals PENGGUNAAN TABIR SURYA BAGI KESEHATAN KULIT

2019 ◽  
Vol 11 (1) ◽  
pp. 87
Author(s):  
Prima Minerva
Keyword(s):  
Skin Cancer ◽  
Adverse Effects ◽  
Uv Light ◽  
Light Exposure ◽  
Premature Aging ◽  
Negative Effects ◽  
Physical Protection ◽  
Skin Immunity ◽  
Long Time ◽  
The Right

Most activities are done outside the home often make the skin exposed to UV light. Exposure UV light excessively or in a long time can cause the occurrence of skin disorders such as Sunburn, premature aging, lowering skin immunity to skin cancer. In preventing the negative effects of UV light on the skin, various ways can be done such as by using a protector such as clothes, hats, glasses or umbrellas. But this physical protection is not sufficient because of the UV light penetrating power. Sunscreen is a skin care cosmetic that provides physical protection against UV light. Proper use of sunscreen and routine can protect the skin from the negative effects of UV light. This paper describes the effects of UV light on the skin, the function of sunscreen and the right use and compatible types sunscreen in maintaining skin health from the adverse effects of UV light.

scholarly journals REDUCED ER-MITOCHONDRIA CONNECTIVITY PROMOTES NEUROBLASTOMA MULTIDRUG RESISTANCE

2021 ◽  
Author(s):  
Jorida Coku ◽  
David M. Booth ◽  
Jan Skoda ◽  
Madison C. Pedrotty ◽  
Jennifer Vogel ◽  
...  
Keyword(s):  
Neuroblastoma Cell ◽  
Therapy Resistance ◽  
Cancer Therapies ◽  
Cytochrome C Release ◽  
Isolated Mitochondria ◽  
Resistant Disease ◽  
Mitochondrial Dna Content ◽  
Diagnostic Models ◽  
Stress Signals ◽  
Neuroblastoma Cell Lines

Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptotic programs. We isolated mitochondria from neuroblastoma cell lines obtained from children at diagnosis and after relapse following failed therapy, and profiled responses to tBid and Bim, death effectors activated by therapeutic stress. Mitochondria from post-relapse models had markedly attenuated cytochrome c release (surrogate for apoptotic commitment) in comparison with patient-matched diagnostic models. Mitochondrial DNA content, size, and shape did not differ consistently. However, we used electron microscopy to identify reduced endoplasmic reticulum-mitochondria contacts (ERMCs) as correlated with therapy resistance. ERMCs form microdomains for the transfer of Ca2+ to mitochondria. We confirmed reduced Ca2+ transfer in resistant cells, with restoration by re-opposing ERMCs via genetically-encoded linkers. However, reduced Ca2+ transfer was not present in all ERMC-reduced cancers with therapy resistance, supporting Ca2+-independent mechanisms. Genetically or biochemically reducing ERMCs in therapy sensitive tumors phenocopied resistance, validating these inter-organelle contacts as physiologic regulators of apoptosis. Our work confirms the importance of ERMCs in stress signaling and provides a previously unrecognized mechanism for cancer cell resistance that is not exclusive to other contributors.

scholarly journals Targeting Therapy Resistance: When Glutamine Catabolism Becomes Essential

Cancer Cell ◽  
2018 ◽  
Vol 33 (5) ◽  
pp. 795-797 ◽  
Author(s):  
Michael J. Lukey ◽  
William P. Katt ◽  
Richard A. Cerione
Keyword(s):  
Therapy Resistance ◽  
Targeting Therapy

Development of a Skin Cancer Prevention Program

2003 ◽  
Vol 19 (2) ◽  
pp. 89-92 ◽  
Author(s):  
Grace Hatmaker
Keyword(s):  
Skin Cancer ◽  
Cancer Prevention ◽  
Prevention Program ◽  
Sun Exposure ◽  
School Nurses ◽  
Premature Aging ◽  
Skin Cancer Prevention ◽  
School Age Children ◽  
Ultraviolet Rays ◽  
Cancer Prevention Program

The Centers for Disease Control and Prevention (CDC) now categorizes skin cancer as epidemic. Nearly 90% of these deadly cancers start from sun exposure during the childhood years. This makes sun exposure in school-age children a serious public health risk, also one that school nurses can address. Solar radiation is now classified as a “known human carcinogen,” with ultraviolet rays joining the ranks of other known cancer-causing elements such as tobacco, arsenic, and radon. Sun exposure to unprotected skin results in painful burns, premature aging, cataracts, and weakened immune systems. School nurses can use the new CDC guidelines along with other local and state resources to develop a specific skin cancer prevention program for their schools. They are in a pivotal position to partner with students, parents, administrators, teachers, and coaches to reduce the occurrence of skin cancer in children. The article describes one high school’s skin cancer prevention project.

scholarly journals Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4318
Author(s):  
Brittany P. Rickard ◽  
Christina Conrad ◽  
Aaron J. Sorrin ◽  
Mustafa Kemal Ruhi ◽  
Jocelyn C. Reader ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Biology ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Therapy Response ◽  
Therapy Resistance ◽  
Malignant Ascites ◽  
Molecular Characteristics ◽  
The Impact

Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.

scholarly journals Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT

2020 ◽  
Author(s):  
Wen Jia ◽  
Shubham Tripathi ◽  
Priyanka Chakraborty ◽  
Adithya Chedere ◽  
Annapoorni Rangarajan ◽  
...  
Keyword(s):  
Cell Division ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Studies ◽  
Therapy Resistance ◽  
Cancer Therapies ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Molecular Determinants ◽  
Cancer Types ◽  
Mesenchymal Epithelial Transition

AbstractEpithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are central to metastatic aggressiveness and therapy resistance in solid tumors. While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and MET inducers has come into focus recently, and has been implicated in the failure of anti-cancer therapies. Recent experimental studies have shown that some cells can undergo an irreversible EMT depending on the duration of exposure to EMT-inducing signals. While the irreversibility of MET, or equivalently, resistance to EMT, has not been studied in as much detail, evidence supporting such behavior is slowly emerging. Here, we identify two possible mechanisms that can underlie resistance of cells to undergo EMT: epigenetic feedback in ZEB1/GRHL2 feedback loop and stochastic partitioning of biomolecules during cell division. Identifying the ZEB1/GRHL2 axis as a key determinant of epithelial-mesenchymal plasticity across many cancer types, we use mechanistic mathematical models to show how GRHL2 can be involved in both the abovementioned processes, thus driving an irreversible MET. Our study highlights how an isogenic population may contain subpopulation with varying degrees of susceptibility or resistance to EMT, and proposes a next set of questions for detailed experimental studies characterizing the irreversibility of MET/resistance to EMT.

A Balancing Act: p53 Activity from Tumor Suppression to Pathology and Therapeutic Implications

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Mengxiong Wang ◽  
Laura D. Attardi
Keyword(s):  
Tumor Suppression ◽  
Human Cancer ◽  
Suppressor Gene ◽  
Premature Aging ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Therapies ◽  
Therapeutic Implications ◽  
Cycle Arrest ◽  
Stress Signals

TP53, encoding the p53 transcription factor, is the most frequently mutated tumor suppressor gene across all human cancer types. While p53 has long been appreciated to induce antiproliferative cell cycle arrest, apoptosis, and senescence programs in response to diverse stress signals, various studies in recent years have revealed additional important functions for p53 that likely also contribute to tumor suppression, including roles in regulating tumor metabolism, ferroptosis, signaling in the tumor microenvironment, and stem cell self-renewal/differentiation. Not only does p53 loss or mutation cause cancer, but hyperactive p53 also drives various pathologies, including developmental phenotypes, premature aging, neurodegeneration, and side effects of cancer therapies. These findings underscore the importance of balanced p53 activity and influence our thinking of how to best develop cancer therapies based on modulating the p53 pathway. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Crispr/Cas9 Based Kinome Screen Identifies Novel Targets That Determine Sensitivity for Asparaginase Therapy in Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2629-2629 ◽  
Author(s):  
Laurens T Van Der Meer ◽  
Jiangyan Yu ◽  
Miriam Butler ◽  
Jolien M R van der Meer ◽  
Roland P Kuiper ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Amino Acid ◽  
B Cell ◽  
Cell Biology ◽  
Rational Design ◽  
Lymphoblastic Leukemia ◽  
Therapy Resistance ◽  
Specific Gene ◽  
Loss Of Function ◽  
Amino Acid Response

Abstract Despite the high cure rate of pediatric acute lymphoblastic leukemia (ALL), relapse and associated therapy resistance remains a significant problem. Recent studies have identified genomic lesions that predict poor outcome (for example: loss of IKZF1 or P53). Because the effects on cell biology of most of these alterations are unknown, rational design of alternative therapy protocols is difficult. We used a CRISPR/Cas9 based knockout screen in the (cytogenetically normal) B cell progenitor-ALL cell line Nalm6 to identify novel genes involved in resistance towards asparaginase, a key component of current ALL treatment protocols. As a proof-of-principle experiment, we introduced loss-of-function mutations by transiently expressing the Cas9 nuclease in Nalm6 cells transduced with a guideRNA (gRNA) library that targets 507 of the human kinases, each with 10 unique gRNAs (Wang et al. Science 2014;343 (6166):80-4). We treated these cells in the absence or presence of an IC50 dose of asparaginase for two weeks. Subsequently, genomic DNA from treated and untreated control cells was isolated and subjected to the Illumina HiSeq platform for paired-end sequencing. We retrieved 84% of all gRNA sequences with a median of 997 reads per gRNA in the sample before treatment. Furthermore, 454 out of the 507 genes were targeted by 6 or more gRNAs. This indicates that the library complexity was sufficiently maintained during the transduction and culture procedure to study dynamics during treatment. The frequency of each gRNA before and after treatment was compared to determine the effect of loss of function of individual kinases on sensitivity towards asparaginase treatment. The MAGeCK algorithm (Li et al. Genome Biology 2014, 15:554) was used to the prioritize genes of which the gRNAs were selectively enriched or depleted during treatment. This algorithm ranks genes by comparing the performance of each gRNA that targets a specific gene. This analysis yielded 18 genes that were found to be associated with resistance (figure 1), as illustrated by the enrichment of multiple gRNAs targeting these genes. To the converse, 31 (out of 454 evaluable) genes were selectively depleted during treatment (figure 2), suggesting that loss of these genes enhances sensitivity to asparaginase treatment. These gRNAs frequently target pro-survival kinases, including components of B cell receptor signaling (BTK, MAPK, AKT3, and Yes1), suggesting that inhibiting these kinases may be used to enhance treatment response. The apoptosis inducing effects of Asparaginase treatment impinge on changes in cell metabolism as a result of amino acid starvation. In line with this, our dataset revealed enrichment of gRNAs targeting genes either directly involved in the amino acid response route (TRIB3) or other metabolic pathways (BCKDK). For an initial validation step, we used RNAi to suppress expression of one of these genes, Tribbles homologue 3 (TRIB3), a pseudokinase acting as a pro-apoptotic protein in the amino acid response pathway. Indeed, shRNA mediated knockdown of TRIB3 was sufficient to render these cells refractory to the apoptosis inducing effects of asparaginase. We conclude from these results that our CRISPR/Cas9 based screens can be used to (i) delineate pathways that contribute therapy resistance and (ii) identify protein (kinase) targets that can be selectively inhibited to improve therapy response. Disclosures No relevant conflicts of interest to declare.

scholarly journals Survival of the Fittest: Cancer Stem Cells in Therapeutic Resistance and Angiogenesis

2008 ◽  
Vol 26 (17) ◽  
pp. 2839-2845 ◽  
Author(s):  
Christine E. Eyler ◽  
Jeremy N. Rich
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Therapeutic Resistance ◽  
Antiangiogenic Agents ◽  
Cancer Therapies ◽  
Tumor Initiating Cells

In an increasing number of cancers, tumor populations called cancer stem cells (CSCs), or tumor-initiating cells, have been defined in functional assays of self-renewal and tumor initiation. Moreover, recent work in several different cancers has suggested the CSC population as a source of chemotherapy and radiation-therapy resistance within tumors. Work in glioblastoma and breast cancers supports the idea that CSCs may possess innate resistance mechanisms against radiation- and chemotherapy-induced cancer cell death, allowing them to survive and initiate tumor recurrence. Several resistance mechanisms have been proposed, including amplified checkpoint activation and DNA damage repair as well as increased Wnt/β-catenin and Notch signaling. Novel targeted therapies against the DNA damage checkpoint or stem-cell maintenance pathways may sensitize CSCs to radiation or other therapies. Another important category of cancer therapies are antiangiogenic and vascular targeting agents, which are also becoming integrated in the treatment paradigm of an increasing number of cancers. Recent results from our laboratory and others support a role for CSCs in the angiogenic drive as well as the mechanism of antiangiogenic agents. Identifying and targeting the molecular mechanisms responsible for CSC therapeutic resistance may improve the efficacy of current cancer therapies.

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