scholarly journals Uncontrolled Intracellular Osmotic Pressure Leads to Cancer

2020 ◽  
Author(s):  
Feng Zhang ◽  
Runmin Jiang ◽  
Chao Zhang
Keyword(s):  
Osmotic Pressure ◽  
Tumor Cells ◽  
Driving Force ◽  
Synergetic Effect ◽  
Tolerance Limit ◽  
Tumor Proliferation ◽  
Normal Cells ◽  
Hypotonic Stress ◽  
The One ◽  
New Hypothesis

At present more than 9 million people die of cancer every year. Simple and broad-spectrum drugs are still an urgent need for cancer patients. Recently, we proposed a new hypothesis that intracellular osmotic pressure (IOP) is the driving force of cell division, and abnormal tumor proliferation is the result of uncontrolled IOP in cells. On the one hand, aneuploidy and abnormal function of Na+/K+ pump lead to a faster rise of IOP in tumor cell than normal cells, on the other hand, abnormality of cytoskeleton assembly leads to the decrease of tolerance limit of cell membrane (TLCM) of tumor cells for resisting IOP. This hypothesis predicts: 1)Tumor cells were more intolerant to hypotonic stress than normal cells. 2) Maligancies may be sellectively killed by a suddenn increase of IOP and combined with decrease of the TLCM of tumors. Na+/K+ pump inhibitors can promotely increase the IOP of tumor cells and cytoskeleton inhibitors can dramatically lower the TLCM of tumor cells. Therefore, Na+/K+ pump and cytoskeleton inhibitors may have a synergetic effect to kill tumor cells. 3) Molecules regulating cell osmolality may be new targets for cancer treatment.

scholarly journals Metabolic Alterations in Cancer and Their Potential as Therapeutic Targets

2017 ◽  
pp. 825-832
Author(s):  
Jamie D. Weyandt ◽  
Craig B. Thompson ◽  
Amato J. Giaccia ◽  
W. Kimryn Rathmell
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Patient Outcomes ◽  
Metabolic Changes ◽  
Tumor Proliferation ◽  
Therapeutic Targeting ◽  
Normal Cells ◽  
Metabolic Alterations ◽  
Improve Patient

Otto Warburg’s discovery in the 1920s that tumor cells took up more glucose and produced more lactate than normal cells provided the first clues that cancer cells reprogrammed their metabolism. For many years, however, it was unclear as to whether these metabolic alterations were a consequence of tumor growth or an adaptation that provided a survival advantage to these cells. In more recent years, interest in the metabolic differences in cancer cells has surged, as tumor proliferation and survival have been shown to be dependent upon these metabolic changes. In this educational review, we discuss some of the mechanisms that tumor cells use for reprogramming their metabolism to provide the energy and nutrients that they need for quick or sustained proliferation and discuss the potential for therapeutic targeting of these pathways to improve patient outcomes.

scholarly journals A new hypothesis: some metastases are the result of inflammatory processes by adapted cells, especially adapted immune cells at sites of inflammation

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 175 ◽  
Author(s):  
Leili Shahriyari
Keyword(s):  
Epithelial Cells ◽  
Tumor Cells ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Inflammatory Process ◽  
The Body ◽  
Normal Cells ◽  
Activated Platelets ◽  
Inflammatory Processes ◽  
New Hypothesis

There is an old hypothesis that metastasis is the result of migration of tumor cells from the tumor to a distant site. In this article, we propose another mechanism for metastasis, for cancers that are initiated at the site of chronic inflammation. We suggest that cells at the site of chronic inflammation might become adapted to the inflammatory process, and these adaptations may lead to the initiation of an inflammatory tumor. For example, in an inflammatory tumor immune cells might be adapted to send signals of proliferation or angiogenesis, and epithelial cells might be adapted to proliferation (like inactivation of tumor suppressor genes). Therefore, we hypothesize that metastasis could be the result of an inflammatory process by adapted cells, especially adapted immune cells at the site of inflammation, as well as the migration of tumor cells with the help of activated platelets, which travel between sites of inflammation.  If this hypothesis is correct, then any treatment causing necrotic cell death may not be a good solution. Because necrotic cells in the tumor micro-environment or anywhere in the body activate the immune system to initiate the inflammatory process, and the involvement of adapted immune cells in the inflammatory processes leads to the formation and progression of tumors. Adapted activated immune cells send more signals of proliferation and/or angiogenesis than normal cells. Moreover, if there were adapted epithelial cells, they would divide at a much higher rate in response to the proliferation signals than normal cells. Thus, not only would the tumor come back after the treatment, but it would also grow more aggressively.

The Role of Reactive Oxygen Species in Tumor Treatment and its Impact on Bone Marrow Hematopoiesis

2020 ◽  
Vol 21 (5) ◽  
pp. 477-498
Author(s):  
Yongfeng Chen ◽  
Xingjing Luo ◽  
Zhenyou Zou ◽  
Yong Liang
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Oxidative Damage ◽  
Tumor Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tumor Treatment ◽  
Normal Cells ◽  
Treatment And Prevention

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

scholarly journals THE KINETICS OF EXOSMOSIS OF WATER FROM LIVING CELLS

1927 ◽  
Vol 10 (5) ◽  
pp. 659-664 ◽  
Author(s):  
Morton McCutcheon ◽  
Baldwin Lucke
Keyword(s):  
Osmotic Pressure ◽  
Salt Concentration ◽  
Driving Force ◽  
Temperature Characteristic ◽  
Living Cells ◽  
Velocity Constant ◽  
Osmotic Equilibrium ◽  
Kinetics Of

1. The rate of exosmosis of water was studied in unfertilized Arbacia eggs, in order to bring out possible differences between the kinetics of exosmosis and endosmosis. 2. Exosmosis, like endosmosis, is found to follow the equation See PDF for Equation, in which a is the total volume of water that will leave the cell before osmotic equilibrium is attained, x is the volume that has already left the cell at time t, and k is the velocity constant. 3. The velocity constants of the two processes are equal, provided the salt concentration of the medium is the same. 4. The temperature characteristic of exosmosis, as of endomosis, is high. 5. It is concluded that the kinetics of exosmosis and endosmosis of water in these cells are identical, the only difference in the processes being in the direction of the driving force of osmotic pressure.

scholarly journals Preferential expression of double-stranded ribonucleic acid in tumor versus normal cells: biological and clinical implications

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 39-46
Author(s):  
HM Kantarjian ◽  
B Barlogie ◽  
M Pershouse ◽  
D Swartzendruber ◽  
MJ Keating ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cell Lines ◽  
Ribonucleic Acid ◽  
Flow Cytometric Analysis ◽  
Myelogenous Leukemia ◽  
Cycle Phase ◽  
Low Grade ◽  
Normal Cells ◽  
Normal Peripheral Blood ◽  
Rna Content

In an effort to develop a new tumor marker suitable for flow cytometric analysis, we examined the value of double-stranded ribonucleic acid (ds- RNA) measurements using propidium iodide after DN'ase treatment. Cellular ds-RNA content was evaluated both in experimental cell lines and in clinical specimens. Higher levels of ds-RNA were present in tumor cells as compared with normal cells. In tumor cells, fluorescence was intensely localized in the nucleolus and was more diffuse in the cytoplasm. Change of less than 10% in the ds-RNA levels was observed in cell lines as a function of cytokinetic determinants such as cycle phase, culture age, and cycle traverse rate. Tumor differentiation by dimethylsulfoxide resulted in a significant decrease in cellular ds-RNA content. For quantitative comparison of clinical material, a ds-RNA excess was defined in relationship to normal peripheral blood lymphocytes. ds-RNA excess greater than 30% was observed in only one of 34 normal tissues (3%) as compared with 124 of 201 neoplastic tissue samples (62%). This incidence was higher in patients with acute leukemia (76%), high-grade and intermediate-grade lymphoma (75%), and high tumor stage myeloma (83%), as compared with chronic leukemia (20%), low-grade lymphoma (25%), and intermediate or low tumor mass myeloma (43%). Prognostically, a high pretreatment ds-RNA excess in myeloma was associated with a lower remission rate. The persistence of ds-RNA excess in the bone marrow of patients with acute myelogenous leukemia in remission predicted for a shorter remission duration (seven v 22 months; P = .05). We conclude that ds-RNA excess, as readily measured objectively and quantitatively by flow cytometry, may have important diagnostic and prognostic implications for the management of patients with malignant disease.

scholarly journals Genes in Tumor Formation

2019 ◽  
Vol 3 (2) ◽  
pp. 18-22
Author(s):  
Isolde Riede
Keyword(s):  
Tumor Cells ◽  
Genome Instability ◽  
Tumor Formation ◽  
Normal Cells ◽  
Tumor Supressors ◽  
Somatic Pairing ◽  
Definition Of

With the definition of four gene classes, all differences between tumor cells and normal cells can be explained. Proliferative mutations induce a shortcut, forcing the cell to divide. They allow replication without control, induce somatic pairing defects of chromosomes and genome instability. Intact Tumor Supressors or mutant Switch Functions can inhibit this process. Oncogene mutations optimize the growth of the cells.

scholarly journals ANTIPROLIFERATION ACTIVITIES OF ETHANOL EXTRACT OF ROBUSTA LAMPUNG GREEN COFFEE SEEDS ON DOG TUMOR LINE CELLS

2021 ◽  
Vol 22 (1) ◽  
pp. 133-140
Author(s):  
Farra Sasmita ◽  
Ietje Wientarsih ◽  
Bayu Febram Prasetyo ◽  
Bambang Pontjo Priosoeryanto
Keyword(s):  
Tumor Cells ◽  
Ethanol Extract ◽  
Positive Control ◽  
Screening Methods ◽  
Green Coffee ◽  
Normal Cells ◽  
Green Coffee Beans ◽  
Coffee Beans ◽  
Dpph Method ◽  
Cytotoxicity Effects

This study aim at determining the activity of ethanol extract of Robusta green coffee beans as an antiproliferation agent in MCA-B1, MCM-B2, and Vero normal cell lines as a control. Ethanol extract of Robusta green coffee beans was obtained by maceration method, bioactive compounds in the extract were tested by phytochemical screening methods, testing levels of antioxidants were tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, cytotoxicity effects (LC50) were tested by the method Brine Shrimp Lethallity Test (BSLT) and antiproliferation activity were carried out by counting the number of cells after being tested with several extract concentrations namely 100, 250, 400, 550, 700 and 850 ppm and doxorubicin as a positive control with a concentration of 100 ppm. The results showed that the ethanol extract of Robusta green coffee beans contained flavonoids and tannins, had very strong antioxidant levels with IC50 values of 40.9923 ppm, cytotoxicity effects obtained LC50 values of 430.64 ppm, and the highest antiproliferation activity was achieved at a concentration of 850 ppm at 69.58 % in MCM-B2 tumor cells, 60.46% in MCA-B1 tumor cells, and 14.2% in Vero normal cells. Based on the results, the ethanol extract of Robusta Lampung green coffee beans has antiproliferation activity on the test tumor cells and is relatively non-toxic to normal cells.

scholarly journals Interferon Beta and Interferon Alpha 2a Differentially Protect Head and Neck Cancer Cells from Vesicular Stomatitis Virus-Induced Oncolysis

2015 ◽  
Vol 89 (15) ◽  
pp. 7944-7954 ◽  
Author(s):  
Marlena M. Westcott ◽  
Jingfang Liu ◽  
Karishma Rajani ◽  
Ralph D'Agostino ◽  
Douglas S. Lyles ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Vesicular Stomatitis Virus ◽  
Oncolytic Viruses ◽  
Type I ◽  
Normal Cells ◽  
Vesicular Stomatitis

ABSTRACTOncolytic viruses (OV) preferentially kill cancer cells due in part to defects in their antiviral responses upon exposure to type I interferons (IFNs). However, IFN responsiveness of some tumor cells confers resistance to OV treatment. The human type I IFNs include one IFN-β and multiple IFN-α subtypes that share the same receptor but are capable of differentially inducing biological responses. The role of individual IFN subtypes in promoting tumor cell resistance to OV is addressed here. Two human IFNs which have been produced for clinical use, IFN-α2a and IFN-β, were compared for activity in protecting human head and neck squamous cell carcinoma (HNSCC) lines from oncolysis by vesicular stomatitis virus (VSV). Susceptibility of HNSCC lines to killing by VSV varied. VSV infection induced increased production of IFN-β in resistant HNSCC cells. When added exogenously, IFN-β was significantly more effective at protecting HNSCC cells from VSV oncolysis than was IFN-α2a. In contrast, normal keratinocytes and endothelial cells were protected equivalently by both IFN subtypes. Differential responsiveness of tumor cells to IFN-α and -β was further supported by the finding that autocrine IFN-β but not IFN-α promoted survival of HNSCC cells during persistent VSV infection. Therefore, IFN-α and -β differentially affect VSV oncolysis, justifying the evaluation and comparison of IFN subtypes for use in combination with VSV therapy. Pairing VSV with IFN-α2a may enhance selectivity of oncolytic VSV therapy for HNSCC by inhibiting VSV replication in normal cells without a corresponding inhibition in cancer cells.IMPORTANCEThere has been a great deal of progress in the development of oncolytic viruses. However, a major problem is that individual cancers vary in their sensitivity to oncolytic viruses. In many cases this is due to differences in their production and response to interferons (IFNs). The experiments described here compared the responses of head and neck squamous cell carcinoma cell lines to two IFN subtypes, IFN-α2a and IFN-β, in protection from oncolytic vesicular stomatitis virus. We found that IFN-α2a was significantly less protective for cancer cells than was IFN-β, whereas normal cells were equivalently protected by both IFNs. These results suggest that from a therapeutic standpoint, selectivity for cancer versus normal cells may be enhanced by pairing VSV with IFN-α2a.

scholarly journals High Membranous Expression of Fatty Acid Transport Protein 4 Is Associated with Tumorigenesis and Tumor Progression in Clear Cell Renal Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Young-Sik Kim ◽  
Jiyoon Jung ◽  
Hoiseon Jeong ◽  
Ju-Han Lee ◽  
Hwa Eun Oh ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Renal Cell Carcinoma ◽  
Fatty Acid ◽  
Tumor Cells ◽  
Clear Cell ◽  
Female Gender ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Cell Renal Cell Carcinoma ◽  
Normal Cells

The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1) synergistically activated fatty acid uptake in experimental models. In this study, we investigated the immunohistochemical expression of CD36, FATP4, and ACSL1 in 180 cases of clear cell renal cell carcinoma (RCC) in comparison with 80 specimens of the normal kidney. We also examined the clinical implication of these three fatty acid transporters in RCC, which was validated by an open-access The Cancer Genome Atlas data analysis. Both CD36 and FATP4 revealed higher membranous expressions in RCC tumor cells than in normal cells. In contrast, ACSL1 expression was remarkably reduced in RCC tumor cells compared to normal cells. CD36, FATP4, and ACSL1 showed high expressions in 74 (41.1%), 85 (47.2%), and 72 (40.0%) out of 180 RCC cases, respectively. Clinically, high FATP4 in tumor cells was associated with female gender (p=0.05), high TNM stage (p=0.039), tumor necrosis (p=0.009), and tumor recurrence (p=0.037), while high ACSL1 was only related to female gender (p=0.023). CD36 expression revealed no correlation with the clinicopathologic parameters of RCC. Increased FATP4 expression displayed an association with short recurrence-free survival (p=0.003). In conclusion, the high FATP4 expression was clinically associated with poor prognostic factors of RCC. Overexpression of membranous FATP4 and CD36 combined with reduced cytoplasmic expression of ACSL1 might be a tumor-specific feature of RCC, contributing to the tumorigenesis and tumor progression.

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