scholarly journals Unique Roles of Sphingolipids in Selected Malignant and Nonmalignant Lesions of Female Reproductive System

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Paweł Knapp ◽  
Karolina Chomicz ◽  
Magdalena Świderska ◽  
Adrian Chabowski ◽  
Robert Jach
Keyword(s):  
Cancer Biology ◽  
Membrane Lipids ◽  
Malignant Tumors ◽  
Chemotherapeutic Agents ◽  
Self Control ◽  
Cancer Tissue ◽  
Control Mechanisms ◽  
Ceramide Content ◽  
A Cell ◽  
Prevention Of Cancer

Cancer develops as a result of the loss of self-control mechanisms by a cell; it gains the ability to induce angiogenesis, becomes immortal and resistant to cell death, stops responding to growth suppressor signals, and becomes capable of invasion and metastasis. Sphingolipids—a family of membrane lipids—are known to play important roles in the regulation of cell proliferation, the response to chemotherapeutic agents, and/or prevention of cancer. Despite the underlying functions of sphingolipids in cancer biology, their metabolism in different malignant tumors is poorly investigated. Some studies showed marked differences in ceramide content between the tumor and the respective healthy tissue. Interestingly, the level of this sphingolipid could be either low or elevated, suggesting that the alterations in ceramide metabolism in cancer tissue may depend on the biology of the tumor. These processes are indeed related to the type of cancer, its stage, and histology status. In this paper we present the unique roles of bioactive sphingolipid derivative in selected gynecologic malignant and nonmalignant lesions.

scholarly journals Smart Nanoparticles for Chemo-Based Combinational Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 853
Author(s):  
Binita Shrestha ◽  
Lijun Wang ◽  
Eric M. Brey ◽  
Gabriela Romero Uribe ◽  
Liang Tang
Keyword(s):  
Cancer Treatment ◽  
Cancer Biology ◽  
Complex Disease ◽  
Rapid Development ◽  
Acquired Resistance ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Combinational Therapy ◽  
Precision Therapy ◽  
External Stimuli

Cancer is a heterogeneous and complex disease. Traditional cancer therapy is associated with low therapeutic index, acquired resistance, and various adverse effects. With the increasing understanding of cancer biology and technology advancements, more strategies have been exploited to optimize the therapeutic outcomes. The rapid development and application of nanomedicine have motivated this progress. Combinational regimen, for instance, has become an indispensable approach for effective cancer treatment, including the combination of chemotherapeutic agents, chemo-energy, chemo-gene, chemo-small molecules, and chemo-immunology. Additionally, smart nanoplatforms that respond to external stimuli (such as light, temperature, ultrasound, and magnetic field), and/or to internal stimuli (such as changes in pH, enzymes, hypoxia, and redox) have been extensively investigated to improve precision therapy. Smart nanoplatforms for combinational therapy have demonstrated the potential to be the next generation cancer treatment regimen. This review aims to highlight the recent advances in smart combinational therapy.

scholarly journals Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefania Nobili ◽  
Antonella Mannini ◽  
Astrid Parenti ◽  
Chiara Raggi ◽  
Andrea Lapucci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Cancer Biology ◽  
Cancer Cell Line ◽  
Cancer Tissue ◽  
Endoplasmic Reticulum Membrane ◽  
Mcf 7

AbstractInvasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER−/PR−/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24−/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.

scholarly journals Mitochondria and Pharmacologic Cardiac Conditioning—At the Heart of Ischemic Injury

2021 ◽  
Vol 22 (6) ◽  
pp. 3224
Author(s):  
Christopher Lotz ◽  
Johannes Herrmann ◽  
Quirin Notz ◽  
Patrick Meybohm ◽  
Franz Kehl
Keyword(s):  
Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Research Field ◽  
Calcium Handling ◽  
Control Mechanisms ◽  
Intrinsic Resistance ◽  
Atp Production ◽  
Cardiac Conditioning ◽  
A Cell

Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.

Application of Immunohistochemistry to Liver and Gastrointestinal Neoplasms: Liver, Stomach, Colon, and Pancreas

2008 ◽  
Vol 132 (3) ◽  
pp. 490-499 ◽  
Author(s):  
Stephen A. Geller ◽  
Deepti Dhall ◽  
Randa Alsabeh
Keyword(s):  
Gastrointestinal Tract ◽  
Personal Experience ◽  
Recent Literature ◽  
Malignant Tumors ◽  
Chemotherapeutic Agents ◽  
Gastrointestinal System ◽  
Data Sources ◽  
Gastrointestinal Neoplasms ◽  
Metastatic Neoplasm ◽  
Selection Of

Abstract Context.—Immunohistochemistry has become an integral component of the practice of pathology. Newer antibodies allow for increasingly precise diagnoses for tumors that previously could not be easily identified. Recently, immunohistochemical evaluations have begun to allow pathologists to actively assist in determining prognosis and even in selecting therapies. Objective.—To summarize the usefulness of currently available immunostains for the study of liver and gastrointestinal system neoplasms and to make recommendations for panels of immunostains that can be particularly helpful. Data Sources.—Information has been collected from recent literature as well as from personal experience and practice. Conclusions.—Many immunostains are now available for the practicing pathologist that allow for increasing accuracy in diagnosis of liver and gastrointestinal tract neoplasms. Panels of immunostains can be used to differentiate between various tumors and also to identify site of origin in the case of a metastatic neoplasm. Immunostains that allow for prognostic determinations and for guidance in the selection of chemotherapeutic agents can also be used by pathologists to assist in the management of patients with malignant tumors affecting the liver and gastrointestinal tract.

scholarly journals Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Liu ◽  
Xiang Ao ◽  
Guoqiang Ji ◽  
Yuan Zhang ◽  
Wanpeng Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Life Quality ◽  
Therapeutic Targets ◽  
Chemotherapeutic Agents ◽  
Response To Chemotherapy ◽  
Novel Biomarkers ◽  
Related Proteins

Gastric cancer (GC) is one of the most common malignant tumors of digestive systems worldwide, with high recurrence and mortality. Chemotherapy is still the standard treatment option for GC and can effectively improve the survival and life quality of GC patients. However, with the emergence of drug resistance, the clinical application of chemotherapeutic agents has been seriously restricted in GC patients. Although the mechanisms of drug resistance have been broadly investigated, they are still largely unknown. MicroRNAs (miRNAs) are a large group of small non-coding RNAs (ncRNAs) widely involved in the occurrence and progression of many cancer types, including GC. An increasing amount of evidence suggests that miRNAs may play crucial roles in the development of drug resistance by regulating some drug resistance-related proteins as well as gene expression. Some also exhibit great potential as novel biomarkers for predicting drug response to chemotherapy and therapeutic targets for GC patients. In this review, we systematically summarize recent advances in miRNAs and focus on their molecular mechanisms in the development of drug resistance in GC progression. We also highlight the potential of drug resistance-related miRNAs as biomarkers and therapeutic targets for GC patients.

scholarly journals THE ROLE OF ALPHA-FETOPROTEIN RECEPTOR IN THE DELIVERY OF TARGETED PREPARATIONS IN ONCOLOGY

2017 ◽  
Vol 22 (1) ◽  
pp. 4-14
Author(s):  
H. M Treshalina ◽  
G. B Smirnova ◽  
S. A Tsurkan ◽  
J. R Tcherkassova ◽  
N. A Lesnaya
Keyword(s):  
Tumor Cells ◽  
Malignant Tumors ◽  
Human Tumor ◽  
Tumor Model ◽  
Mitochondrial Pathway ◽  
Alpha Fetoprotein ◽  
Malignant Cells ◽  
Tumor Models ◽  
A Cell ◽  
Afp Production

There was executed the analysis of thematic literature during from 1956 to 2015 devoted to receptors to fetal proteins, including to alpha-fetoprotein (AFP) known in medicine as oncomarker and used by malignant cells for the organization of tumoral homeostasis. As protein carrier, AFP similar to albumin takes of vitally important molecules in a space «hydrophobic pocket» and moves inside a cell, but as the cancer-embryonal antigen (CEA) - determines the existence of a malignant tumor, but not the type of a neoplasm. On the bounding of AFP with teratogen and their internalization and delivery in an embryo there is based the development of ways of «address» delivery of substances into a cell. This is realized by means of receptor mediated endocytosis via specific membranous receptors to AFP (ReCAF) with high selectivity concerning malignant cells of various genesis. Up to 90% of all malignant cells of the human and tumor models for human and mammalians express AFP receptors, including rather recently opened stem tumor cells - the most probable source of metastasing. AFP production and expression of receptors is selectively raised in malignant tumors of patients and human tumor models. The hyperproduction of AFP and hyperexpression of ReCAF are related to the histologic type of tumor model and are characteristic for embrional cell tumors and hepatoblastomas with initially low drug sensitivity or with the resistance. When choosing the model it is necessary to consider that in different types of tumor cells ReCAF have specific features in cultivation which are not pronounced in conditions of an animal organism. More differentiated tumors are characterized by the larger level of the AFP production and a hyperexpression of ReCAF. The use of subcutaneous tumor xenografts signal for AFP localizations with the hyperexpression of receptors, allows to reveal mostly evidentially the effectiveness of the therapeutic system at the preclinical level. Address delivery of therapeutic systems created on the basis of AFP or its fragments is capable of causing the change of their pharmacological properties. The therapeutic prize is possible due to the induction of process of apoptosis via the mitochondrial pathway, but at the same time the fall in the cytotoxic capacity of system is possible.

The Life Course of Baby Boomers

Hurt ◽  
2017 ◽  
Author(s):  
Miriam Boeri
Keyword(s):  
Drug Use ◽  
Life Course ◽  
Social Control ◽  
Informal Social Control ◽  
Self Control ◽  
Life Course Theory ◽  
Control Mechanisms ◽  
Problematic Drug ◽  
Social Controls ◽  
The Life Course

Life course theory focuses attention on the impact of history, timing, and important transitions in life trajectories. In this chapter, the life course analysis of boomer drug users reveals that drug trajectories were not developmental. Instead, they were discontinuous, interrupted phases dependent on social context and situations that changed over time. The chapter provides a closer inspection of the turning points into and out of drug use phases to better understand the causes of problematic drug use and what resources are needed to control it. In contrast to law enforcement and treatment professionals, who view problematic drug use as a lack of self-control, research finds that informal social control mechanisms are more important for maintaining or regaining control over drug use. Life course theory predicts that missing critical transitions in life, such as graduating from high school, leads to fewer informal social controls. The stories in this chapter reveal the negative impact of juvenile incarceration, which did not help anyone become drug free, but instead plunged youths into a criminal culture and broke their social bonds to mainstream social networks and access to informal social control mechanisms.

Treatment of Malignant Tumors of the Extremities by Perfusion with Chemotherapeutic Agents

1959 ◽  
Vol 41 (6) ◽  
pp. 977-987 ◽  
Author(s):  
Edward T. Krementz ◽  
Oscar Creech ◽  
Robert F. Ryan ◽  
Jack Wickstrom
Keyword(s):  
Malignant Tumors ◽  
Chemotherapeutic Agents

scholarly journals Mitochondrial Quality Control Mechanisms and the PHB (Prohibitin) Complex

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 238 ◽  
Author(s):  
Blanca Hernando-Rodríguez ◽  
Marta Artal-Sanz
Keyword(s):  
Quality Control ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Stress Responses ◽  
Membrane Lipids ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Gene ◽  
Control Mechanisms ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Functions

Mitochondrial functions are essential for life, critical for development, maintenance of stem cells, adaptation to physiological changes, responses to stress, and aging. The complexity of mitochondrial biogenesis requires coordinated nuclear and mitochondrial gene expression, owing to the need of stoichiometrically assemble the oxidative phosphorylation (OXPHOS) system for ATP production. It requires, in addition, the import of a large number of proteins from the cytosol to keep optimal mitochondrial function and metabolism. Moreover, mitochondria require lipid supply for membrane biogenesis, while it is itself essential for the synthesis of membrane lipids. To achieve mitochondrial homeostasis, multiple mechanisms of quality control have evolved to ensure that mitochondrial function meets cell, tissue, and organismal demands. Herein, we give an overview of mitochondrial mechanisms that are activated in response to stress, including mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response (UPRmt). We then discuss the role of these stress responses in aging, with particular focus on Caenorhabditis elegans. Finally, we review observations that point to the mitochondrial prohibitin (PHB) complex as a key player in mitochondrial homeostasis, being essential for mitochondrial biogenesis and degradation, and responding to mitochondrial stress. Understanding how mitochondria responds to stress and how such responses are regulated is pivotal to combat aging and disease.

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