The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
How butterfly effect or deterministic chaos theory in theorical physics expla...banafsheh61
The document discusses how chaos theory and the butterfly effect can explain the main cause of cancer. It proposes that small increases in reactive oxygen species above normal limits can cause chaos in normal cells by damaging mitochondria. This mitochondrial damage disrupts communication between the nucleus and mitochondria, causing the nucleus to signal fermentation rather than apoptosis, similar to early single-celled organisms. Over time, this evolutionary reversion enables cancer progression by allowing cells to produce energy without intact mitochondria.
Product explanation with voice (english)whitnelson
This document summarizes a product seminar about a hydrogen supplement called excellent H. It discusses the role of hydrogen in the human body, how free radicals contribute to illness, and the benefits of hydrogen as an antioxidant. Hydrogen selectively neutralizes hydroxyl radicals and improves energy by converting to water after completing its antioxidant effects. The supplement utilizes coral calcium to absorb and release hydrogen in the body. It was invented by Dr. Taneaki Oikawa and Dr. Kokichi Hanaoka.
Autophagy the housekeeper in every cellfathi neana
Autophagy is a catabolic process involving the degradation of a cell’s own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products.
It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more-essential processes. Autophagy is an evolutionarily conserved mechanism of cellular self-digestion in which proteins and organelles are degraded through delivery to lysosomes. Defects in this process are implicated in numerous human diseases including cancer.
Evaluation of salicin isolated from salix subserrata as a radioprotectorRam Sahu
1) The study investigated the radioprotective effects of salicin, a compound found in willow trees, against gamma radiation damage in rat spleen tissue.
2) Irradiation significantly increased lipid peroxidation in spleen tissue but salicin treatment reduced this effect.
3) Ultrastructural examination found no abnormalities in control or salicin groups but irradiation caused lesions and cell loss, which salicin provided some protection against.
4) Changes to protein and enzyme patterns from irradiation were detected electrophoretically and salicin treatment prevented some of these qualitative effects.
This document provides an overview of biochemistry and its relevance to medicine. It discusses the following key points:
- Biochemistry is the study of chemical processes in living organisms, from molecules to cells. It is essential for understanding normal body functions and disease states.
- The human body is composed of biomolecules like proteins, lipids, carbohydrates, nucleic acids, and water, which are organized in a hierarchical structure from atoms to cells.
- Intermolecular forces like covalent bonds, ionic bonds, hydrogen bonds, hydrophobic interactions, and van der Waals forces contribute to molecular stability.
- Metabolic processes involve the breakdown and synthesis of biomolecules, deriving energy through oxidation
Antioxidant Activity and Cytotoxicity against Cancer Cell Lines of the Extrac...Juan Hernandez
Xylaria species associated with termite nests or soil have been considered rare species in nature and the few which have been reported upon have been found to act as a rich source of bioactive metabolites. This study evaluated 10 ethyl acetate extracts of five new Xylaria species associated with termite nests or soil for their antioxidant activity, and cytotoxicity against different cancer and normal cell lines. DPPH and ABTS radical scavenging activities of the extracts demonstrated strong capacity with low IC50 values. The highest observed activities belonged to X. vinacea SWUF18-2.3 having IC50 values of 0.194 ± 0.031 mg/mL for DPPH assay and 0.020 ± 0.004 mg/mL for ABTS assay. Total phenolic content ranged from 0.826 ± 0.123 to 3.629 ± 0.381 g GAE/g crude extract which correlated with antioxidant activities. The high total phenolic content could contribute to the high antioxidant activities. Cytotoxicity was recorded against A549, HepG2, HeLa and PNT2 and resulted in broad spectrum to specific activity depending on the cell lines. The highest activities were observed with X. subintraflava SWUF16-11.1 which resulted in 11.15 ± 0.32 to 13.17 ± 2.37% cell viability at a concentration of 100 µg/mL. Moreover, LC-MS fingerprints indicated over 61 peaks from all isolates. There were 18 identified and 43 unidentified compounds compared to mass databases. The identified compounds were from various groups of diterpenoids, diterpenes, cytochalasin, flavones, flavonoids, polyphenols, steroids and derivatives, triterpenoids and tropones. These results indicate that Xylaria spp. has abundant secondary metabolites that could be further explored for their therapeutic properties
The document provides an overview of key topics in microbial physiology and genetics covered in Chapter 7, including:
- Microbial metabolism, including catabolic and anabolic reactions, and how ATP is used to store and transport energy.
- Aerobic respiration and fermentation pathways for breaking down glucose.
- Mutations and how bacteria can acquire new genetic material through transduction, transformation, conjugation and lysogenic conversion.
- Genetic engineering and how bacteria are used to produce compounds like insulin.
Molecular mechanisms of Autophagy and its Role in Plant Immunity SystemsMonuj Gogoi
Details of Autophagy Mechanisms and its roles for plant diseases management.
Numbers of papers were selected for the preparation of this presentation. So Thanks to all authors those are published.
How butterfly effect or deterministic chaos theory in theorical physics expla...banafsheh61
The document discusses how chaos theory and the butterfly effect can explain the main cause of cancer. It proposes that small increases in reactive oxygen species above normal limits can cause chaos in normal cells by damaging mitochondria. This mitochondrial damage disrupts communication between the nucleus and mitochondria, causing the nucleus to signal fermentation rather than apoptosis, similar to early single-celled organisms. Over time, this evolutionary reversion enables cancer progression by allowing cells to produce energy without intact mitochondria.
Product explanation with voice (english)whitnelson
This document summarizes a product seminar about a hydrogen supplement called excellent H. It discusses the role of hydrogen in the human body, how free radicals contribute to illness, and the benefits of hydrogen as an antioxidant. Hydrogen selectively neutralizes hydroxyl radicals and improves energy by converting to water after completing its antioxidant effects. The supplement utilizes coral calcium to absorb and release hydrogen in the body. It was invented by Dr. Taneaki Oikawa and Dr. Kokichi Hanaoka.
Autophagy the housekeeper in every cellfathi neana
Autophagy is a catabolic process involving the degradation of a cell’s own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development, and homeostasis, helping to maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products.
It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more-essential processes. Autophagy is an evolutionarily conserved mechanism of cellular self-digestion in which proteins and organelles are degraded through delivery to lysosomes. Defects in this process are implicated in numerous human diseases including cancer.
Evaluation of salicin isolated from salix subserrata as a radioprotectorRam Sahu
1) The study investigated the radioprotective effects of salicin, a compound found in willow trees, against gamma radiation damage in rat spleen tissue.
2) Irradiation significantly increased lipid peroxidation in spleen tissue but salicin treatment reduced this effect.
3) Ultrastructural examination found no abnormalities in control or salicin groups but irradiation caused lesions and cell loss, which salicin provided some protection against.
4) Changes to protein and enzyme patterns from irradiation were detected electrophoretically and salicin treatment prevented some of these qualitative effects.
This document provides an overview of biochemistry and its relevance to medicine. It discusses the following key points:
- Biochemistry is the study of chemical processes in living organisms, from molecules to cells. It is essential for understanding normal body functions and disease states.
- The human body is composed of biomolecules like proteins, lipids, carbohydrates, nucleic acids, and water, which are organized in a hierarchical structure from atoms to cells.
- Intermolecular forces like covalent bonds, ionic bonds, hydrogen bonds, hydrophobic interactions, and van der Waals forces contribute to molecular stability.
- Metabolic processes involve the breakdown and synthesis of biomolecules, deriving energy through oxidation
Antioxidant Activity and Cytotoxicity against Cancer Cell Lines of the Extrac...Juan Hernandez
Xylaria species associated with termite nests or soil have been considered rare species in nature and the few which have been reported upon have been found to act as a rich source of bioactive metabolites. This study evaluated 10 ethyl acetate extracts of five new Xylaria species associated with termite nests or soil for their antioxidant activity, and cytotoxicity against different cancer and normal cell lines. DPPH and ABTS radical scavenging activities of the extracts demonstrated strong capacity with low IC50 values. The highest observed activities belonged to X. vinacea SWUF18-2.3 having IC50 values of 0.194 ± 0.031 mg/mL for DPPH assay and 0.020 ± 0.004 mg/mL for ABTS assay. Total phenolic content ranged from 0.826 ± 0.123 to 3.629 ± 0.381 g GAE/g crude extract which correlated with antioxidant activities. The high total phenolic content could contribute to the high antioxidant activities. Cytotoxicity was recorded against A549, HepG2, HeLa and PNT2 and resulted in broad spectrum to specific activity depending on the cell lines. The highest activities were observed with X. subintraflava SWUF16-11.1 which resulted in 11.15 ± 0.32 to 13.17 ± 2.37% cell viability at a concentration of 100 µg/mL. Moreover, LC-MS fingerprints indicated over 61 peaks from all isolates. There were 18 identified and 43 unidentified compounds compared to mass databases. The identified compounds were from various groups of diterpenoids, diterpenes, cytochalasin, flavones, flavonoids, polyphenols, steroids and derivatives, triterpenoids and tropones. These results indicate that Xylaria spp. has abundant secondary metabolites that could be further explored for their therapeutic properties
The document provides an overview of key topics in microbial physiology and genetics covered in Chapter 7, including:
- Microbial metabolism, including catabolic and anabolic reactions, and how ATP is used to store and transport energy.
- Aerobic respiration and fermentation pathways for breaking down glucose.
- Mutations and how bacteria can acquire new genetic material through transduction, transformation, conjugation and lysogenic conversion.
- Genetic engineering and how bacteria are used to produce compounds like insulin.
Molecular mechanisms of Autophagy and its Role in Plant Immunity SystemsMonuj Gogoi
Details of Autophagy Mechanisms and its roles for plant diseases management.
Numbers of papers were selected for the preparation of this presentation. So Thanks to all authors those are published.
Importance of BIO-CHEMISTRY in NURSING by Dr.KDAshishRav1
This document discusses the importance of biochemistry knowledge for nurses. It notes that biochemistry is relevant from intra-cellular to extra-cellular processes and major diseases. Nurses play an important role in patient care by supporting clinicians, understanding disease conditions, and properly collecting, transporting, and ensuring the reliability of biochemical test samples and results. A sound knowledge of biochemistry pathways and how they can alter in disease is the backbone of biological science and critical for nurses to fulfill their duties and responsibilities in quality patient care.
The document analyzes the antioxidant capacity and other bioactivities of freeze-dried acai (Euterpe oleraceae Mart.) fruit pulp/skin powder through a series of assays. It was found to have exceptionally high superoxide scavenging capacity, the highest antioxidant capacity against peroxyl radicals measured by ORACFL, and mild activity against peroxynitrite and hydroxyl radicals. Acai also demonstrated anti-inflammatory properties as a potential COX-1 and COX-2 inhibitor and an effect on LPS-induced nitric oxide production, but no effect on lymphocyte proliferation or phagocytic capacity. Total phenolic content and differentiation of antioxidants into slow-acting and fast-acting components were also
This document describes a project to develop an in vitro lipoylation reaction to screen chemicals hypothesized to trigger primary biliary cirrhosis (PBC) through molecular mimicry. The student conducted a series of optimization reactions altering amounts of lipoic acid, GTP/ATP, or lipoate activating enzyme and lipoyltransferase. Little success was achieved and time did not allow screening of chemicals, requiring further work. In conclusion, both enzymes are required for lipoylation but varying amounts did not greatly affect the reaction, prompting questions about enzyme purification for future studies.
1) The study evaluated the antioxidant effects of carotenoids from the algae Dunaliella salina in vivo using rat models.
2) Rats pretreated with 125-250 μg/kg of D. salina carotenoids before being administered carbon tetrachloride showed significant protection against oxidative stress compared to controls, as measured by restored antioxidant enzyme levels and decreased lipid peroxidation.
3) Pretreatment with D. salina carotenoids provided better protection than synthetic beta-carotene, indicating D. salina is a potential source of antioxidants for health applications.
LYCOZEN-GT A SUPER ANTI-OXIDANT MULTIVITAMINpharmaindexing
This document discusses the formulation LYCOZEN-GT, a super antioxidant multivitamin and multimineral supplement containing lycopene, green tea extract, and grape seed extract. It provides background on oxidative stress and antioxidants, describing how free radicals damage cells and the body's antioxidant defenses. The formulation aims to provide antioxidants that protect against this damage. The document details the ingredients in LYCOZEN-GT and their roles in combating oxidative stress and related diseases.
Live Longer, Stay healthy, Feel better with AstashinecapsulesSriramNagarajan19
ASTASHINE capsule contains natural astaxanthin from Haematococcus pluvialis Astaxanthin has exceptional antioxidant activity to combat singlet oxygen when compared to other antioxidants. In particular, Astaxanthin can be used to defend against singlet oxygen damage, which are especially susceptible to aging effects.
In this study, Astaxanthin extracted from Haematococcus microalgae powerfully quenched singlet oxygen. Results show that the quenching effect of Astaxanthin is 800 times greater than coenzyme Q10. Astaxanthin was also about 75 times greater than alpha lipoic acid, about 550 times greater than green tea catechins and about 6000 times greater than Vitamin C.the present Article reviews the role of ASTASHINE capsules as World’s most powerful Antioxidant and Anti-aging Nutrient.
The document discusses autotrophs and heterotrophs, their carbon sources and energy sources. It defines aerobic and anaerobic organisms, as well as facultative anaerobes. It also discusses catabolic and anabolic reactions, oxidative and reductive pathways, and questions about electron acceptors, respiration types, growth requirements, metabolic pathways and the tricarboxylic acid cycle.
Yoshinori Ohsumi's research in the 1990s using yeast cells was pivotal in advancing the understanding of autophagy. He discovered 15 genes essential for autophagy by observing the accumulation of autophagosomes when he disrupted protein degradation pathways in starved yeast cells. Ohsumi's work led to the 2016 Nobel Prize in Physiology or Medicine and demonstrated that autophagy is a normal process in cells for degrading and recycling components. Autophagy is important for many cellular functions and diseases, playing both protective and pathological roles in conditions like cancer, neurodegeneration, and infection.
1. The document discusses cellular respiration and fermentation in yeast cells. It provides background on how cells harvest energy from food sources and defines aerobic respiration, which uses oxygen to break down glucose, and anaerobic respiration, called fermentation, which occurs without oxygen.
2. The main steps of aerobic respiration and fermentation are described. Aerobic respiration breaks down glucose and oxygen to produce carbon dioxide, water, and ATP. Fermentation produces ethanol or lactic acid instead of using oxygen.
3. Yeast undergoes alcoholic fermentation, converting pyruvic acid to carbon dioxide and ethanol with some ATP also produced. The rate of carbon dioxide production during fermentation would be affected by the availability of
This document discusses nutrition and inflammation. It outlines that acute inflammation is the body's normal response to injury or infection, while chronic inflammation can be caused by persistent triggers and can lead to diseases. Certain nutrients like high-GI carbohydrates, trans fats, and saturated fats are pro-inflammatory, while omega-3s and antioxidants are anti-inflammatory. While antioxidants can reduce oxidative stress, high doses may also be pro-oxidative, and antioxidant supplements have not been found effective for disease prevention in most cases. Chronic inflammation results from ongoing injuries, persistent triggers, autoimmunity, tissue damage and oxidative stress.
The document describes a high-throughput screen that identified small molecule compounds that can enhance the pharmacological effects of oligonucleotides. Several "hit" compounds were discovered that potentiated the actions of splice-switching oligonucleotides, antisense oligonucleotides, and siRNAs in cell culture. The hit compounds preferentially caused the release of fluorescent oligonucleotides from late endosomes. Studies in transgenic mice indicated the hit compounds could enhance the in vivo effects of a splice-switching oligonucleotide without significant toxicity. The findings suggest selected small molecules may help advance oligonucleotide-based therapeutics by modulating intracellular trafficking and endosomal release.
This document discusses using metabolomics to analyze the food metabolome - all metabolites derived from digestion and metabolism of food components. It notes the complexity of nutritional exposures from foods, which contain nutrients, non-nutrients from natural and man-made sources, and contaminants. Individual metabolic capacity is also influenced by genetics, microbiota, age, and other factors. The food metabolome is defined and applications are described, including discovering new food bioactives, understanding diet-health relationships, and personalized nutrition. Challenges in analyzing the large and diverse food metabolome are also outlined. Initial studies using targeted and untargeted metabolomics are discovering new biomarkers of food intake from various foods. Larger cohort studies and controlled interventions are needed
Biological balance role of oxidative status for some bacterial speciesAlexander Decker
This study evaluated the oxidative stress of three bacterial species by analyzing culture broths. E. coli, Staphylococcus aureus, and Klebsiella pneumoniae were chosen. The results showed that Klebsiella pneumoniae had higher levels of reduced glutathione and glutathione-S-transferase activity compared to the others, indicating a stronger defense system against free radicals. Peroxynitrate levels and lipid peroxidation, as measured by malondialdehyde, generally increased in the order of Klebsiella pneumoniae > Staphylococcus aureus > E. coli, suggesting more pathogenic bacteria produce more oxidative species. This supports the hypothesis that bacteria modulate antioxidant defenses in response to oxidative stress levels to protect against
When yeast cells are exposed to anoxia (no oxygen) on a non-fermentable carbon source, they enter a state of suspended animation where all observable life processes reversibly halt until oxygen is restored. Transcriptional profiling revealed differences in gene expression between yeast exposed to carbon monoxide (CO) gas versus nitrogen (N2) gas. CO can mimic oxygen binding and led to derepression of aerobic metabolism genes compared to N2 exposure. Mutants lacking components of the mitochondrial retrograde signaling pathway recovered normally from CO but not N2 exposure, indicating its importance in the cellular response to different anoxic conditions. The study establishes yeast as a model for investigating suspended animation and oxygen-regulated gene expression.
This document provides an introduction and overview of enzymes. It can be summarized in 3 sentences:
Enzymes are protein catalysts that accelerate biochemical reactions in living organisms by lowering their activation energy. They exhibit specificity for particular substrates and reactions. Factors like temperature, pH, concentration of enzymes and substrates, and presence of inhibitors or activators can influence enzyme activity and reaction rates.
The document summarizes the identification and characterization of an antimicrobial protein from the mucus of the stingray Potamotrygon cf. henlei. Through solid-phase extraction and chromatographic purification, a 16072.8 Da protein was isolated that showed antimicrobial activity against bacteria and yeast without hemolytic activity. Mass spectrometry and Edman degradation identified the protein as similar to the beta-chain of hemoglobin. Effects of the novel antimicrobial protein on the microcirculation were also evaluated. This represents the first description of a bioactive polypeptide isolated from stingray mucus.
This document defines vocabulary terms related to cellular energy from Chapter 8. It provides definitions for 61 terms including ATP, aerobic respiration, photosynthesis, chloroplast, and metabolism. The definitions are brief explanations of each term and its relevance to cellular energy processes like cellular respiration and photosynthesis.
This document discusses antioxidants, what they are, how they work, and why they are important. It defines antioxidants as molecules that prevent oxidation and free radical damage by donating or accepting electrons from free radicals. Various categories of antioxidants are described, along with tests used to measure antioxidant capacity. The document emphasizes that antioxidants play an important role in health by reducing free radical damage linked to diseases, and recommends including antioxidant-rich foods like fruits and vegetables in the diet.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
The document discusses oxidative stress and antioxidants. It provides information on:
1. Indian Dental Academy which offers online and offline dental courses and is a leader in continuing dental education.
2. How free radicals can damage cells, proteins, lipids, DNA and cause diseases. Antioxidants help prevent this damage.
3. Various antioxidants found in foods and their roles in reducing oxidative stress and preventing diseases like cancer and cardiovascular disease. Clinical trials on antioxidants have had inconsistent results.
Importance of BIO-CHEMISTRY in NURSING by Dr.KDAshishRav1
This document discusses the importance of biochemistry knowledge for nurses. It notes that biochemistry is relevant from intra-cellular to extra-cellular processes and major diseases. Nurses play an important role in patient care by supporting clinicians, understanding disease conditions, and properly collecting, transporting, and ensuring the reliability of biochemical test samples and results. A sound knowledge of biochemistry pathways and how they can alter in disease is the backbone of biological science and critical for nurses to fulfill their duties and responsibilities in quality patient care.
The document analyzes the antioxidant capacity and other bioactivities of freeze-dried acai (Euterpe oleraceae Mart.) fruit pulp/skin powder through a series of assays. It was found to have exceptionally high superoxide scavenging capacity, the highest antioxidant capacity against peroxyl radicals measured by ORACFL, and mild activity against peroxynitrite and hydroxyl radicals. Acai also demonstrated anti-inflammatory properties as a potential COX-1 and COX-2 inhibitor and an effect on LPS-induced nitric oxide production, but no effect on lymphocyte proliferation or phagocytic capacity. Total phenolic content and differentiation of antioxidants into slow-acting and fast-acting components were also
This document describes a project to develop an in vitro lipoylation reaction to screen chemicals hypothesized to trigger primary biliary cirrhosis (PBC) through molecular mimicry. The student conducted a series of optimization reactions altering amounts of lipoic acid, GTP/ATP, or lipoate activating enzyme and lipoyltransferase. Little success was achieved and time did not allow screening of chemicals, requiring further work. In conclusion, both enzymes are required for lipoylation but varying amounts did not greatly affect the reaction, prompting questions about enzyme purification for future studies.
1) The study evaluated the antioxidant effects of carotenoids from the algae Dunaliella salina in vivo using rat models.
2) Rats pretreated with 125-250 μg/kg of D. salina carotenoids before being administered carbon tetrachloride showed significant protection against oxidative stress compared to controls, as measured by restored antioxidant enzyme levels and decreased lipid peroxidation.
3) Pretreatment with D. salina carotenoids provided better protection than synthetic beta-carotene, indicating D. salina is a potential source of antioxidants for health applications.
LYCOZEN-GT A SUPER ANTI-OXIDANT MULTIVITAMINpharmaindexing
This document discusses the formulation LYCOZEN-GT, a super antioxidant multivitamin and multimineral supplement containing lycopene, green tea extract, and grape seed extract. It provides background on oxidative stress and antioxidants, describing how free radicals damage cells and the body's antioxidant defenses. The formulation aims to provide antioxidants that protect against this damage. The document details the ingredients in LYCOZEN-GT and their roles in combating oxidative stress and related diseases.
Live Longer, Stay healthy, Feel better with AstashinecapsulesSriramNagarajan19
ASTASHINE capsule contains natural astaxanthin from Haematococcus pluvialis Astaxanthin has exceptional antioxidant activity to combat singlet oxygen when compared to other antioxidants. In particular, Astaxanthin can be used to defend against singlet oxygen damage, which are especially susceptible to aging effects.
In this study, Astaxanthin extracted from Haematococcus microalgae powerfully quenched singlet oxygen. Results show that the quenching effect of Astaxanthin is 800 times greater than coenzyme Q10. Astaxanthin was also about 75 times greater than alpha lipoic acid, about 550 times greater than green tea catechins and about 6000 times greater than Vitamin C.the present Article reviews the role of ASTASHINE capsules as World’s most powerful Antioxidant and Anti-aging Nutrient.
The document discusses autotrophs and heterotrophs, their carbon sources and energy sources. It defines aerobic and anaerobic organisms, as well as facultative anaerobes. It also discusses catabolic and anabolic reactions, oxidative and reductive pathways, and questions about electron acceptors, respiration types, growth requirements, metabolic pathways and the tricarboxylic acid cycle.
Yoshinori Ohsumi's research in the 1990s using yeast cells was pivotal in advancing the understanding of autophagy. He discovered 15 genes essential for autophagy by observing the accumulation of autophagosomes when he disrupted protein degradation pathways in starved yeast cells. Ohsumi's work led to the 2016 Nobel Prize in Physiology or Medicine and demonstrated that autophagy is a normal process in cells for degrading and recycling components. Autophagy is important for many cellular functions and diseases, playing both protective and pathological roles in conditions like cancer, neurodegeneration, and infection.
1. The document discusses cellular respiration and fermentation in yeast cells. It provides background on how cells harvest energy from food sources and defines aerobic respiration, which uses oxygen to break down glucose, and anaerobic respiration, called fermentation, which occurs without oxygen.
2. The main steps of aerobic respiration and fermentation are described. Aerobic respiration breaks down glucose and oxygen to produce carbon dioxide, water, and ATP. Fermentation produces ethanol or lactic acid instead of using oxygen.
3. Yeast undergoes alcoholic fermentation, converting pyruvic acid to carbon dioxide and ethanol with some ATP also produced. The rate of carbon dioxide production during fermentation would be affected by the availability of
This document discusses nutrition and inflammation. It outlines that acute inflammation is the body's normal response to injury or infection, while chronic inflammation can be caused by persistent triggers and can lead to diseases. Certain nutrients like high-GI carbohydrates, trans fats, and saturated fats are pro-inflammatory, while omega-3s and antioxidants are anti-inflammatory. While antioxidants can reduce oxidative stress, high doses may also be pro-oxidative, and antioxidant supplements have not been found effective for disease prevention in most cases. Chronic inflammation results from ongoing injuries, persistent triggers, autoimmunity, tissue damage and oxidative stress.
The document describes a high-throughput screen that identified small molecule compounds that can enhance the pharmacological effects of oligonucleotides. Several "hit" compounds were discovered that potentiated the actions of splice-switching oligonucleotides, antisense oligonucleotides, and siRNAs in cell culture. The hit compounds preferentially caused the release of fluorescent oligonucleotides from late endosomes. Studies in transgenic mice indicated the hit compounds could enhance the in vivo effects of a splice-switching oligonucleotide without significant toxicity. The findings suggest selected small molecules may help advance oligonucleotide-based therapeutics by modulating intracellular trafficking and endosomal release.
This document discusses using metabolomics to analyze the food metabolome - all metabolites derived from digestion and metabolism of food components. It notes the complexity of nutritional exposures from foods, which contain nutrients, non-nutrients from natural and man-made sources, and contaminants. Individual metabolic capacity is also influenced by genetics, microbiota, age, and other factors. The food metabolome is defined and applications are described, including discovering new food bioactives, understanding diet-health relationships, and personalized nutrition. Challenges in analyzing the large and diverse food metabolome are also outlined. Initial studies using targeted and untargeted metabolomics are discovering new biomarkers of food intake from various foods. Larger cohort studies and controlled interventions are needed
Biological balance role of oxidative status for some bacterial speciesAlexander Decker
This study evaluated the oxidative stress of three bacterial species by analyzing culture broths. E. coli, Staphylococcus aureus, and Klebsiella pneumoniae were chosen. The results showed that Klebsiella pneumoniae had higher levels of reduced glutathione and glutathione-S-transferase activity compared to the others, indicating a stronger defense system against free radicals. Peroxynitrate levels and lipid peroxidation, as measured by malondialdehyde, generally increased in the order of Klebsiella pneumoniae > Staphylococcus aureus > E. coli, suggesting more pathogenic bacteria produce more oxidative species. This supports the hypothesis that bacteria modulate antioxidant defenses in response to oxidative stress levels to protect against
When yeast cells are exposed to anoxia (no oxygen) on a non-fermentable carbon source, they enter a state of suspended animation where all observable life processes reversibly halt until oxygen is restored. Transcriptional profiling revealed differences in gene expression between yeast exposed to carbon monoxide (CO) gas versus nitrogen (N2) gas. CO can mimic oxygen binding and led to derepression of aerobic metabolism genes compared to N2 exposure. Mutants lacking components of the mitochondrial retrograde signaling pathway recovered normally from CO but not N2 exposure, indicating its importance in the cellular response to different anoxic conditions. The study establishes yeast as a model for investigating suspended animation and oxygen-regulated gene expression.
This document provides an introduction and overview of enzymes. It can be summarized in 3 sentences:
Enzymes are protein catalysts that accelerate biochemical reactions in living organisms by lowering their activation energy. They exhibit specificity for particular substrates and reactions. Factors like temperature, pH, concentration of enzymes and substrates, and presence of inhibitors or activators can influence enzyme activity and reaction rates.
The document summarizes the identification and characterization of an antimicrobial protein from the mucus of the stingray Potamotrygon cf. henlei. Through solid-phase extraction and chromatographic purification, a 16072.8 Da protein was isolated that showed antimicrobial activity against bacteria and yeast without hemolytic activity. Mass spectrometry and Edman degradation identified the protein as similar to the beta-chain of hemoglobin. Effects of the novel antimicrobial protein on the microcirculation were also evaluated. This represents the first description of a bioactive polypeptide isolated from stingray mucus.
This document defines vocabulary terms related to cellular energy from Chapter 8. It provides definitions for 61 terms including ATP, aerobic respiration, photosynthesis, chloroplast, and metabolism. The definitions are brief explanations of each term and its relevance to cellular energy processes like cellular respiration and photosynthesis.
This document discusses antioxidants, what they are, how they work, and why they are important. It defines antioxidants as molecules that prevent oxidation and free radical damage by donating or accepting electrons from free radicals. Various categories of antioxidants are described, along with tests used to measure antioxidant capacity. The document emphasizes that antioxidants play an important role in health by reducing free radical damage linked to diseases, and recommends including antioxidant-rich foods like fruits and vegetables in the diet.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
The document discusses oxidative stress and antioxidants. It provides information on:
1. Indian Dental Academy which offers online and offline dental courses and is a leader in continuing dental education.
2. How free radicals can damage cells, proteins, lipids, DNA and cause diseases. Antioxidants help prevent this damage.
3. Various antioxidants found in foods and their roles in reducing oxidative stress and preventing diseases like cancer and cardiovascular disease. Clinical trials on antioxidants have had inconsistent results.
Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including anaerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease and how Autophagy process is activated will impact approaches to cancer management and prevention
The mitochondrial population in cells is highly dynamic, exhibiting variable turnover rates. Mitochondria are constantly renewed through a regulated transcriptional network that replenishes mitochondria while degrading old or damaged ones. The rate of mitochondrial turnover varies between tissues and can increase in response to certain stimuli, but is normally on the order of days to weeks, with a few percent replaced each day under basal conditions. Mitochondrial turnover is important for cellular homeostasis and may be regulated by circadian rhythms.
Antioxidants/ general dentistry Courses /certified fixed orthodontic courses ...Indian dental academy
Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients
State of the art comprehensive training-Faculty of world wide repute &Very affordable.
The document discusses a 1965 study conducted by Scott and colleagues to further define the toxicity of the antibiotic chloramphenicol. The study administered various doses of chloramphenicol to men and concluded that a dose of 25-30 mg prevents detrimental side effects. However, the study methods would not be considered ethical today according to guidelines. The document also discusses how informed consent was lacking in the unethical Tuskegee syphilis study, emphasizing the need for ethical guidelines. When involving human subjects in scientific studies, understanding and implementing bioethics is important to prevent repeating past ethical issues.
1. Antioxidants like vitamin E, vitamin C, and carotenoids help neutralize harmful free radicals in the body.
2. Free radicals can damage cells, DNA, and other important molecules if left unchecked and have been linked to diseases such as cancer and heart disease.
3. Antioxidants donate an electron to free radicals without becoming unstable themselves, which stops the free radical chain reaction and prevents oxidative damage throughout the body.
Free radicals are unstable molecules that can damage cells. They are produced through normal cell processes and external factors like pollution and smoking. Reactive oxygen species (ROS) are a type of free radical involving oxygen. ROS can damage DNA and proteins, contributing to cancer development. ROS also cause oxidative stress, an imbalance that promotes carcinogenesis. Antioxidants may help prevent cancer by reducing oxidative stress, though some research indicates controlled oxidative stress through substances like vitamin C can also fight tumors. Curcumin in turmeric has shown anti-cancer effects by down-regulating inflammatory genes and enzymes linked to cancer.
Glutathione is one of the body's most important antioxidants and is found in every cell. It plays a key role in neutralizing free radicals and supporting the liver's detoxification processes. Glutathione deficiency has been linked to many chronic diseases due to increased oxidative damage. Supplementing with glutathione may help reduce oxidative stress and support overall health and wellness.
Antioxidants /certified fixed orthodontic courses by Indian dental academy Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
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The document discusses phytonutrients and how they provide health benefits. It notes that modern farming practices have reduced the phytonutrient content of many fruits and vegetables. The document then describes a product called GYV that contains concentrated phytonutrients to compensate for these reductions. It discusses several phytonutrients in GYV, including quercetin, resveratrol, and coenzyme Q10, and summarizes relevant scientific research on their health benefits such as antioxidant, anti-inflammatory, and cardiovascular effects.
The Root cause and Culprit behind Chronic Diseases, Cancer and Aging is well recognized by many authorities now. 1- A state of chronic low grade inflammation. 2- Mitochondrial dysfunction.
Mitochondria Our body’s lifeline. Mitochondria are tiny organelles in our cell, thousands of them comprising 15 to 50% of the cell volume. Red blood cells and skin cells have very little to none, while germ cells have 100,000, but most cells have one to 2,000 of them. They're the primary source of energy for our body. They supply over 90% of our body’s energy. Converting the food we eat and the air we breathe into usable energy. It have enormous potential to influence our health, specifically cancer, and optimizing mitochondrial metabolism may be at the core of effective cancer treatment.
Anti-tumor drugs PPT Dr. Shahid Rasool.pptshahidrasool65
The learning Objectives are
1. To understand tumor, its types, causes and cell cycle of normal cell.
2. To learn and comprehend the pharmacognostic features of various plant and marine derived drugs having anticancer activity.
3. To know the anti cancer mechanism of these natural drugs.
Many chronic symptoms that people live with for years can have a simple underlying cause, such as a nutritional deficiency. Or, a healing potential within the body which may require assistance to naturally remove symptoms, such as chronic pain.
And that is where ASEA fits in.
ASEA is cutting edge science.
ASEA is trillions of stable, perfectly balanced Redox Signalling molecules suspended in a pristine saline solution–the same molecules that exist in the cells of the human body. Redox Signalling Molecules are vital for the health of your cells; that’s why your body makes its own supply. But as we age, our cells make fewer and fewer of these molecules. ASEA is the world’s only source for replenishing Redox Signalling molecules.
Video - http://milleniahealth.com/atomic-medical-physicist-dr-gary-samuelson-discusses-redox-signaling/
1. Professor Cristofor I. Simionescu studied crown gall disease caused by the bacterium Agrobacterium tumefaciens and its associated free radical reactions in plants.
2. His research focused on the induction, evolution, chemistry and inhibition of crown gall tumors, investigating changes in plant cell chemistry during tumor formation and studying the effects of antioxidants on inhibiting tumor growth.
3. Electrospinning can be used to encapsulate polyphenol antioxidants like gallic acid in nanofibers of polymers like PLGA for controlled release applications, providing protection against oxidative stress.
Male infertility can be caused by structural or functional abnormalities in sperm, including low sperm count, low motility, and abnormal forms. Oxidative stress from reactive oxygen species is another leading cause, as it can damage sperm DNA and membranes. The body normally defends against oxidative stress through antioxidant enzymes and compounds in seminal plasma. However, oxidative stress overwhelms these defenses in around 25-40% of infertile men. Various antioxidants taken as supplements, either alone or in combination, have been shown to reduce oxidative stress levels, boost sperm parameters, and improve fertility rates. These include CoQ10, lycopene, mixed carotenoids, omega-3 fatty acids, vitamin C, vitamin E, selenium, zinc
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This document discusses dental occlusion concepts and philosophies for complete dentures. It introduces key terms like physiologic occlusion and defines different occlusion schemes like balanced articulation and monoplane articulation. The document discusses advantages and disadvantages of using anatomic versus non-anatomic teeth for complete dentures. It also outlines requirements for maintaining denture stability, such as balanced occlusal contacts and control of horizontal forces. The goal of occlusion for complete dentures is to re-establish the homeostasis of the masticatory system disrupted by edentulism.
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This document discusses dental casting investment materials. It describes the three main types of investments - gypsum bonded, phosphate bonded, and ethyl silicate bonded investments. For gypsum bonded investments specifically, it details their classification, composition including the roles of gypsum, silica, and modifiers, setting time, normal and hygroscopic setting expansion, and thermal expansion. It provides information on how the properties of gypsum bonded investments are affected by their composition. The document serves as a comprehensive overview of dental casting investment materials.
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Temple of Asclepius in Thrace. Excavation resultsKrassimira Luka
The temple and the sanctuary around were dedicated to Asklepios Zmidrenus. This name has been known since 1875 when an inscription dedicated to him was discovered in Rome. The inscription is dated in 227 AD and was left by soldiers originating from the city of Philippopolis (modern Plovdiv).
Chapter wise All Notes of First year Basic Civil Engineering.pptxDenish Jangid
Chapter wise All Notes of First year Basic Civil Engineering
Syllabus
Chapter-1
Introduction to objective, scope and outcome the subject
Chapter 2
Introduction: Scope and Specialization of Civil Engineering, Role of civil Engineer in Society, Impact of infrastructural development on economy of country.
Chapter 3
Surveying: Object Principles & Types of Surveying; Site Plans, Plans & Maps; Scales & Unit of different Measurements.
Linear Measurements: Instruments used. Linear Measurement by Tape, Ranging out Survey Lines and overcoming Obstructions; Measurements on sloping ground; Tape corrections, conventional symbols. Angular Measurements: Instruments used; Introduction to Compass Surveying, Bearings and Longitude & Latitude of a Line, Introduction to total station.
Levelling: Instrument used Object of levelling, Methods of levelling in brief, and Contour maps.
Chapter 4
Buildings: Selection of site for Buildings, Layout of Building Plan, Types of buildings, Plinth area, carpet area, floor space index, Introduction to building byelaws, concept of sun light & ventilation. Components of Buildings & their functions, Basic concept of R.C.C., Introduction to types of foundation
Chapter 5
Transportation: Introduction to Transportation Engineering; Traffic and Road Safety: Types and Characteristics of Various Modes of Transportation; Various Road Traffic Signs, Causes of Accidents and Road Safety Measures.
Chapter 6
Environmental Engineering: Environmental Pollution, Environmental Acts and Regulations, Functional Concepts of Ecology, Basics of Species, Biodiversity, Ecosystem, Hydrological Cycle; Chemical Cycles: Carbon, Nitrogen & Phosphorus; Energy Flow in Ecosystems.
Water Pollution: Water Quality standards, Introduction to Treatment & Disposal of Waste Water. Reuse and Saving of Water, Rain Water Harvesting. Solid Waste Management: Classification of Solid Waste, Collection, Transportation and Disposal of Solid. Recycling of Solid Waste: Energy Recovery, Sanitary Landfill, On-Site Sanitation. Air & Noise Pollution: Primary and Secondary air pollutants, Harmful effects of Air Pollution, Control of Air Pollution. . Noise Pollution Harmful Effects of noise pollution, control of noise pollution, Global warming & Climate Change, Ozone depletion, Greenhouse effect
Text Books:
1. Palancharmy, Basic Civil Engineering, McGraw Hill publishers.
2. Satheesh Gopi, Basic Civil Engineering, Pearson Publishers.
3. Ketki Rangwala Dalal, Essentials of Civil Engineering, Charotar Publishing House.
4. BCP, Surveying volume 1
BIOLOGY NATIONAL EXAMINATION COUNCIL (NECO) 2024 PRACTICAL MANUAL.pptx
Retinoids and anticancer activity/prosthodontic courses
1. Retinoids and Anticancer
activity
INDIAN DENTAL ACADEMYINDIAN DENTAL ACADEMY
Leader in continuing DentalLeader in continuing Dental
EducationEducation
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2. ContentsContents
IntroductionIntroduction
Mechanistic studies on retinoidsMechanistic studies on retinoids
Clinical studies with retinoidsClinical studies with retinoids
New strategies in retinoid chemoprevention.New strategies in retinoid chemoprevention.
Conclusions.Conclusions.
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3. Role of AntioxidantRole of Antioxidant
Oxygen molecules are stable, or unreactive, when they have an evenOxygen molecules are stable, or unreactive, when they have an even
number of electrons. However, when oxygen molecules combine withnumber of electrons. However, when oxygen molecules combine with
other molecules, the oxygen can end up with an odd number of electrons.other molecules, the oxygen can end up with an odd number of electrons.
The oxygen molecule then becomes unstable and highly reactive, and theThe oxygen molecule then becomes unstable and highly reactive, and the
odd-numbered species is known as aodd-numbered species is known as a free radicalfree radical..
This free radical starts a vicious chain reaction that attacks cells, proteins,This free radical starts a vicious chain reaction that attacks cells, proteins,
and DNA, all of which contribute to aging and at times carcinogenesis.and DNA, all of which contribute to aging and at times carcinogenesis.
The body defends against free radicals with antioxidants, which impede orThe body defends against free radicals with antioxidants, which impede or
slow the chain reaction.slow the chain reaction.
Antioxidants like beta carotene and vitamins C and E “break the chain,”Antioxidants like beta carotene and vitamins C and E “break the chain,”
stopping free radicals from ripping electrons off of other molecules.stopping free radicals from ripping electrons off of other molecules.
Other antioxidants, like superoxide dismutase, catalase and glutathioneOther antioxidants, like superoxide dismutase, catalase and glutathione
peroxidase, stabilize the unstable, reactive free radicals, and thereby slowperoxidase, stabilize the unstable, reactive free radicals, and thereby slow
the free radical chain reaction.the free radical chain reaction.
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4. Unfortunately, the bodyUnfortunately, the body
does not produce or ingestdoes not produce or ingest
enough antioxidants toenough antioxidants to
neutralize all of the freeneutralize all of the free
radicals, which come fromradicals, which come from
processes that are bothprocesses that are both
endogenous (within theendogenous (within the
body, such as humanbody, such as human
metabolism) and exogenousmetabolism) and exogenous
(outside the body, from(outside the body, from
pollution, smoking, alcohol,pollution, smoking, alcohol,
and UV radiation, amongstand UV radiation, amongst
other sources).other sources).
Over time, this means freeOver time, this means free
radicals accumulate a greatradicals accumulate a great
deal of damage within thedeal of damage within the
bodybodywww.indiandentalacademy.comwww.indiandentalacademy.com
5. Introduction: Anticancer activity ofIntroduction: Anticancer activity of
antioxidantsantioxidants
The anticancer activity of antioxidant micronutrientsThe anticancer activity of antioxidant micronutrients
has now been well established in clinical studies,has now been well established in clinical studies,
animal experimentation, cell culture studies andanimal experimentation, cell culture studies and
epidemiological studies dealing with cancer risk andepidemiological studies dealing with cancer risk and
low serum values for micronutrients.low serum values for micronutrients.
In animal studies using the hamster cheek pouchIn animal studies using the hamster cheek pouch
epidermoid carcinoma model, micronutrients haveepidermoid carcinoma model, micronutrients have
been shown to be capable of inhibiting andbeen shown to be capable of inhibiting and
preventing the development and growth of chemicallypreventing the development and growth of chemically
induced tumors and also to be able to regressinduced tumors and also to be able to regress
established cancers in the cheek pouch model.established cancers in the cheek pouch model.
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7. Major interest is now focused on the possibleMajor interest is now focused on the possible
mechanisms of this surprising anti-cancer activity ofmechanisms of this surprising anti-cancer activity of
nutrients, and recent studies have suggested severalnutrients, and recent studies have suggested several
probable pathways through which these anti-oxidantprobable pathways through which these anti-oxidant
nutrients act by:nutrients act by:
Inhibiting the development of cancer cells and toInhibiting the development of cancer cells and to
destroy them through apoptosis (programmed celldestroy them through apoptosis (programmed cell
death), by their stimulation of cytotoxic cytokines, bydeath), by their stimulation of cytotoxic cytokines, by
their action on gene expression, by preventing thetheir action on gene expression, by preventing the
development of the tumor’s necessary blood supplydevelopment of the tumor’s necessary blood supply
or by stimulating cellular differentiation.or by stimulating cellular differentiation.
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8. Mechanisms of cancer inhibition by
anti-oxidant nutrients
Human studies have also tended to indicate an inhibition ofHuman studies have also tended to indicate an inhibition of
various forms of cancer and the regression of somevarious forms of cancer and the regression of some
precancerous lesions.precancerous lesions.
The biological mechanisms for cancer inhibition andThe biological mechanisms for cancer inhibition and
regression are now gradually becoming understood, and theregression are now gradually becoming understood, and the
anti-oxidant nutrients appear to act through a number ofanti-oxidant nutrients appear to act through a number of
pathways common to most of the agents studied.pathways common to most of the agents studied.
Various anti-oxidant nutrients are :beta carotene, alphaVarious anti-oxidant nutrients are :beta carotene, alpha
tocopherol and glutathione.tocopherol and glutathione.
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9. These various micronutrients appear to act through aThese various micronutrients appear to act through a
complex group of ``common pathways'' of anticancercomplex group of ``common pathways'' of anticancer
activity based upon three major mechanisms:activity based upon three major mechanisms:
(1) tumour inhibition by immune cytokines;(1) tumour inhibition by immune cytokines;
(2) stimulation of cancer suppressor genes, such as(2) stimulation of cancer suppressor genes, such as
``wild type'' p53, and diminished expression or``wild type'' p53, and diminished expression or
dysregulation of oncogenes such as mutant p53 anddysregulation of oncogenes such as mutant p53 and
H-ras;H-ras;
(3) inhibition of tumour angiogenesis through the(3) inhibition of tumour angiogenesis through the
inhibition of angiogenesis-stimulating factors such asinhibition of angiogenesis-stimulating factors such as
TGFa.TGFa.
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10. Retinoid action differs, in some respects, from otherRetinoid action differs, in some respects, from other
micronutrient anticancer mechanisms and appears tomicronutrient anticancer mechanisms and appears to
relate to its stimulation of cellular differentiationrelate to its stimulation of cellular differentiation
and resultant apoptosis of neoplastic cells.and resultant apoptosis of neoplastic cells.
Combinations of anti-oxidant nutrients have beenCombinations of anti-oxidant nutrients have been
shown to be synergistic in their anticancer activity,shown to be synergistic in their anticancer activity,
probably due to their optimal anticancer activity atprobably due to their optimal anticancer activity at
different oxygen potentials.different oxygen potentials.
Selectivity in the action on cancer cells, as opposedSelectivity in the action on cancer cells, as opposed
to normal cells, is a major feature of the anti-oxidantto normal cells, is a major feature of the anti-oxidant
micronutrients.micronutrients.
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11. Mechanistic studies on retinoidsMechanistic studies on retinoids
GeneralGeneral
Retinoids are the natural and synthetic derivatives of Vit A.Retinoids are the natural and synthetic derivatives of Vit A.
The retinoids play a role in essential biological process,The retinoids play a role in essential biological process,
includingincluding
1.1. vision,vision,
2.2. reproduction,reproduction,
3.3. metabolism,metabolism,
4.4. growth differentiation,growth differentiation,
5.5. hematopoiesis,hematopoiesis,
6.6. immunological processes,immunological processes,
7.7. bone development andbone development and
8.8. pattern formation during embryogenesis.pattern formation during embryogenesis.
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12. Epidemiologic studies have addressed the relationshipEpidemiologic studies have addressed the relationship
between retinoids and cancer.between retinoids and cancer.
It was found that serum levels of B-caroteneIt was found that serum levels of B-carotene
(provitamin A) and Vitamin A (retinol) were(provitamin A) and Vitamin A (retinol) were
significantly higher in control subjects than in oralsignificantly higher in control subjects than in oral
cancer pts.cancer pts.
Moreover, a low intake of vitamin A is associatedMoreover, a low intake of vitamin A is associated
with an increased risk for squamous-type lung cancerwith an increased risk for squamous-type lung cancer
and hyperplasia and hyperkeratosis of the oraland hyperplasia and hyperkeratosis of the oral
mucosa.mucosa.
There is a considerable evidence that retinoids haveThere is a considerable evidence that retinoids have
potent growth inhibiting effects on cancer in vitro andpotent growth inhibiting effects on cancer in vitro and
vivo.vivo.
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13. Retinoids can suppress the proliferation ofRetinoids can suppress the proliferation of
cells by blocking cell cycle transition or bycells by blocking cell cycle transition or by
inducing apoptosis.inducing apoptosis.
Retinoids can also have a regulatory functionRetinoids can also have a regulatory function
in the immune system with relation to cancer.in the immune system with relation to cancer.
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14. Uptake, transport and metabolism ofUptake, transport and metabolism of
retinol and retinoic acid (RA)retinol and retinoic acid (RA)
All retinoids in the body originate fromAll retinoids in the body originate from
retinyl-ester, carotenoids and retinol in theretinyl-ester, carotenoids and retinol in the
diet.diet.
The dietary carotenoids and preformedThe dietary carotenoids and preformed
retinoids undergo a series of metabolicretinoids undergo a series of metabolic
conversions, extracellularly in the lumen of theconversions, extracellularly in the lumen of the
intestine and intra-cellularly in the intestinalintestine and intra-cellularly in the intestinal
mucosa.mucosa.
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15. The absorbed retinol, along with other dietaryThe absorbed retinol, along with other dietary
lipids in the intestinal mucosa, is packaged aslipids in the intestinal mucosa, is packaged as
retinyl ester in nascent chylomicrons.retinyl ester in nascent chylomicrons.
The chylomicrons are secreted into theThe chylomicrons are secreted into the
lymphatic system, and the bulk of thelymphatic system, and the bulk of the
chylomicrons retinoids are eventually taken upchylomicrons retinoids are eventually taken up
by the liver, where the majority of the body’sby the liver, where the majority of the body’s
retinoids are stored.retinoids are stored.
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16. In tissues, such as the epithelial mucosa of the upperIn tissues, such as the epithelial mucosa of the upper
aerodigestive tract, retinol is oxidized via retinal toaerodigestive tract, retinol is oxidized via retinal to
retinoic acid (RA).retinoic acid (RA).
Alcohol dehydrogenases have been proposed toAlcohol dehydrogenases have been proposed to
catalyze the reversible oxidation from retinol tocatalyze the reversible oxidation from retinol to
retinal whereas short chain dehydrogenase/reductaseretinal whereas short chain dehydrogenase/reductase
enzymes are proposed to be responsible for theenzymes are proposed to be responsible for the
reduction of retinal to retinol.reduction of retinal to retinol.
All-trans-RA is also present in the blood plasma andAll-trans-RA is also present in the blood plasma and
may be an alternative source for intra-cellular RA.may be an alternative source for intra-cellular RA.
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17. Retinoic acid receptorsRetinoic acid receptors
In contrast to retinol and beta-carotene, the variousIn contrast to retinol and beta-carotene, the various
forms of retinoic acid are thought to be active throughforms of retinoic acid are thought to be active through
direct interaction with specific nuclear receptor.direct interaction with specific nuclear receptor.
The effects of retinoids are mediated by retinoic acidThe effects of retinoids are mediated by retinoic acid
receptors (RARs) and retinoid X receptors (RXRs),receptors (RARs) and retinoid X receptors (RXRs),
which act as ligand-activated transcription factors.which act as ligand-activated transcription factors.
Retinoids not only regulate transcription factors,Retinoids not only regulate transcription factors,
such as Activator Protein-1 (AP-1).such as Activator Protein-1 (AP-1).
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18. This molecule mediates the signal from growthThis molecule mediates the signal from growth
factors, inflammatory peptides, oncogenes and tumorfactors, inflammatory peptides, oncogenes and tumor
promotors, usually with cell proliferation as the end-promotors, usually with cell proliferation as the end-
result.result.
Taken together, the action of retinoids is a fine-tunedTaken together, the action of retinoids is a fine-tuned
mechanism dependent on the level of expression ofmechanism dependent on the level of expression of
specific receptor isotypes as well as on the type andspecific receptor isotypes as well as on the type and
concentration of retinoid compound in the cellconcentration of retinoid compound in the cell
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19. Oral and pharyngeal cancerOral and pharyngeal cancer
Mechanistic studies on retinoid effects inMechanistic studies on retinoid effects in
OSCC have been studied in malignant andOSCC have been studied in malignant and
non-malignant in vitro growing cells.non-malignant in vitro growing cells.
OSCC cell lines differ with respect to retinoidOSCC cell lines differ with respect to retinoid
induced growth inhibition and were found toinduced growth inhibition and were found to
be less sensitive to growth inhibition bybe less sensitive to growth inhibition by
retinoids than normal oral keratinocytes.retinoids than normal oral keratinocytes.
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20. The hypothesis was tested that RA-resistanceThe hypothesis was tested that RA-resistance
in OSCC cells was due to an increasedin OSCC cells was due to an increased
catabolism of RA in these cells, analogous tocatabolism of RA in these cells, analogous to
the situation in acute promyelocytic leukemiathe situation in acute promyelocytic leukemia
where it was found that the emergence ofwhere it was found that the emergence of
acquired clinical resistance to retinoidsacquired clinical resistance to retinoids
coincided with the induction of oxidativecoincided with the induction of oxidative
catabolism.catabolism.
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21. It was surprising to observe that within a panelIt was surprising to observe that within a panel
of OSCC cell lines a correlation was foundof OSCC cell lines a correlation was found
between the levels of retinoid turnover andbetween the levels of retinoid turnover and
growth inhibition.growth inhibition.
Cell lines with a relatively higher sensitivityCell lines with a relatively higher sensitivity
towards the growth inhibiting activity of RAtowards the growth inhibiting activity of RA
had a relatively higher RA turnover rate.had a relatively higher RA turnover rate.
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22. Others also found this relationship in vitro whenOthers also found this relationship in vitro when
using cell lines of other tumor types.using cell lines of other tumor types.
Takatsuka etal. Described it as “ an unexpectedTakatsuka etal. Described it as “ an unexpected
liason”.liason”.
Two hypothesis can be formulated to explain theTwo hypothesis can be formulated to explain the
relation between growth inhibition and metabolism inrelation between growth inhibition and metabolism in
OSCC cell lines.OSCC cell lines.
First, it might be that, in tumor cell lines, specificFirst, it might be that, in tumor cell lines, specific
catabolites of RA are responsible for the growthcatabolites of RA are responsible for the growth
inhibiting effects of RA.inhibiting effects of RA.
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23. Second, retinoid metabolism may be secondary eventSecond, retinoid metabolism may be secondary event
and an attempt to neutarlize the growth inhibitingand an attempt to neutarlize the growth inhibiting
efefcts, the first hypothesis seems the most unlikely,efefcts, the first hypothesis seems the most unlikely,
since three lines of evidence are arguing against it.since three lines of evidence are arguing against it.
Conditioned medium, containing RA- metabolitesConditioned medium, containing RA- metabolites
from an OSCC cell line with high RA turnover wasfrom an OSCC cell line with high RA turnover was
not able to induce growth inhibition in a low-not able to induce growth inhibition in a low-
metabolizing and RA-resistant OSCC cell line.metabolizing and RA-resistant OSCC cell line.
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24. Clinical studies with retinoidsClinical studies with retinoids
GeneralGeneral
Retinoids have anticancer activity against various tumorRetinoids have anticancer activity against various tumor
types.types.
Treatment with retinoids caused regression of dysplaticTreatment with retinoids caused regression of dysplatic
nevi or complete or partial remission in 10% of thenevi or complete or partial remission in 10% of the
patients with basal cell carcinoma of skin.patients with basal cell carcinoma of skin.
SCC of skin and cervix can be effectively treated withSCC of skin and cervix can be effectively treated with
the combination of 13-cis-RA and alpha-interferon,the combination of 13-cis-RA and alpha-interferon,
resulting in remissions in 68 and 50% ptsresulting in remissions in 68 and 50% pts
respectively.respectively.
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25. In adjuvant settings, retinyl palmitate given atIn adjuvant settings, retinyl palmitate given at
high dose daily for a 12-month period couldhigh dose daily for a 12-month period could
diminish the development of recurrent lungdiminish the development of recurrent lung
cancer.cancer.
Acute promyelocytic leukaemia can beAcute promyelocytic leukaemia can be
effectively treated with a low-dose of all-trans-effectively treated with a low-dose of all-trans-
RA.RA.
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26. Oral and pharyngeal cancerOral and pharyngeal cancer
Premalignant lesionsPremalignant lesions
Retinoids have been used in the treatment ofRetinoids have been used in the treatment of
oral leukoplakia , a premalignant mucosaloral leukoplakia , a premalignant mucosal
lesion that frequenlty develops into invasivelesion that frequenlty develops into invasive
OSCC. Surgery has been considered theOSCC. Surgery has been considered the
standard therapy for this condition but is oftenstandard therapy for this condition but is often
not possible.not possible.
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27. The effects of retinoids on the epithelialThe effects of retinoids on the epithelial
differentiateion and proliferation led to investigate thedifferentiateion and proliferation led to investigate the
efficacy of retinoids in revrsing oral leukoplakia.efficacy of retinoids in revrsing oral leukoplakia.
The most effective and least toxic form of retinoidThe most effective and least toxic form of retinoid
therapy has not yet been established; among thetherapy has not yet been established; among the
studies in this area, the traiol reported bu hong et alstudies in this area, the traiol reported bu hong et al
showed promising results.showed promising results.
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28. The investigators tested the activity of 13-cis-RA in aThe investigators tested the activity of 13-cis-RA in a
randomised, placebo controlled, doubleblind trialrandomised, placebo controlled, doubleblind trial
involving 44 leukoplakia pts.involving 44 leukoplakia pts.
67% of the pts had an objective clinical response to67% of the pts had an objective clinical response to
the therapy, and 54% had a histological response. Inthe therapy, and 54% had a histological response. In
contrast, the pts receiving placebo had only a 10%contrast, the pts receiving placebo had only a 10%
objective response rate.objective response rate.
However, substantial toxicity and a high rate ofHowever, substantial toxicity and a high rate of
relapse after discontinuation of the traetmentrelapse after discontinuation of the traetment
presented major clinical limitations to this high dosepresented major clinical limitations to this high dose
trial.trial.
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29. Treatment with 13-cis-RA was associated withTreatment with 13-cis-RA was associated with
a distinct toxicity profile typical ofa distinct toxicity profile typical of
Hypervitaminosis A that includesHypervitaminosis A that includes
mucocutaneous reactions (dry eyes, cheilitis,mucocutaneous reactions (dry eyes, cheilitis,
dry and itching skin), liver toxicity anddry and itching skin), liver toxicity and
myalgia.myalgia.
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30. In subsequent study, Lippman etal investigated a low dose ofIn subsequent study, Lippman etal investigated a low dose of
13-cis-RA to address the toxicity and relapse problems of the13-cis-RA to address the toxicity and relapse problems of the
first randomized trial.first randomized trial.
90% pts showed regression of the lesion or stable disease and90% pts showed regression of the lesion or stable disease and
this low dose 13-cis-RA was well tolerated, with no ptsthis low dose 13-cis-RA was well tolerated, with no pts
dropping out because of toxicity.dropping out because of toxicity.
other retinoids, including all-trans RA and retinol also showedother retinoids, including all-trans RA and retinol also showed
activity in leukoplakia.activity in leukoplakia.
All leukoplakia trials reported thus far have used reversal ofAll leukoplakia trials reported thus far have used reversal of
the premalignant lesion as the study endpoint.the premalignant lesion as the study endpoint.
With the definition of chemoprevention in mind, it can beWith the definition of chemoprevention in mind, it can be
argued that these trials actually address chemotherapy ofargued that these trials actually address chemotherapy of
leukoplakia rather than chemoprevention of oral cancer.leukoplakia rather than chemoprevention of oral cancer.
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31. A follow-up study of Lippman et al was recently published,A follow-up study of Lippman et al was recently published,
addressing the prediction of cancer development by means ofaddressing the prediction of cancer development by means of
clinical parameters and molecular markers.clinical parameters and molecular markers.
With a median follow-up of 7 years 31.4% of the leukoplakiaWith a median follow-up of 7 years 31.4% of the leukoplakia
pts developed a upper respiratory and digestive tract tumor.pts developed a upper respiratory and digestive tract tumor.
41% of tumors had developed at sites distinct from the41% of tumors had developed at sites distinct from the
leukoplakia site.leukoplakia site.
Clinical response at 12 months but not at 3 months wasClinical response at 12 months but not at 3 months was
statistically significantly associated with a lower risk forstatistically significantly associated with a lower risk for
cancer.cancer.
Of all vaiables, the histopathology had the most predictiveOf all vaiables, the histopathology had the most predictive
value.value.
In the context of retinoid reserch, the expression of RAR-BetaIn the context of retinoid reserch, the expression of RAR-Beta
was not a predictor for long term cancer risk.was not a predictor for long term cancer risk.
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32. Second primary tumors (SPT) afterSecond primary tumors (SPT) after
HNSCCHNSCC
Every year, pts have a 2-4% risk of developing SPTsEvery year, pts have a 2-4% risk of developing SPTs
following definitive treatment of early HNSCC.following definitive treatment of early HNSCC.
To alleviate this risk, hong et al. conducted a 12-monthTo alleviate this risk, hong et al. conducted a 12-month
randomized, double blind, placebo-controlled trial of high-randomized, double blind, placebo-controlled trial of high-
dose 13-cis-RA (50-100mg/m2/day) as adjuvant therapydose 13-cis-RA (50-100mg/m2/day) as adjuvant therapy
following curative surgery and/ or radiation therapy offollowing curative surgery and/ or radiation therapy of
primary HNSCC.primary HNSCC.
Of the 103 pts studied, significantly fewer 13-cis-RA-treatedOf the 103 pts studied, significantly fewer 13-cis-RA-treated
patients 4% than placebo patients 24% developed SPTs afterpatients 4% than placebo patients 24% developed SPTs after
32 months of followup.of 14 SPTs that developed, 13(93%)32 months of followup.of 14 SPTs that developed, 13(93%)
occurred in the tobacco-smoke exposed field of the upperoccurred in the tobacco-smoke exposed field of the upper
aerodigestive tract, lungs, and oesophagus.aerodigestive tract, lungs, and oesophagus.
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33. OSCCOSCC
Retinoids show some activity in the treatment of various typesRetinoids show some activity in the treatment of various types
of solid tumors in the more advanced stages.of solid tumors in the more advanced stages.
Treatment of 13-cis-RA in combination with IFN-alpha hasTreatment of 13-cis-RA in combination with IFN-alpha has
shown positive therapeutic effects in patients with skin orshown positive therapeutic effects in patients with skin or
cervical cancer.cervical cancer.
Single agent treatment with 13-cis-RA or combination of 13-Single agent treatment with 13-cis-RA or combination of 13-
cis-RA with IFN-alpha however, was not active in advancedcis-RA with IFN-alpha however, was not active in advanced
HNSCC, including OSCC.HNSCC, including OSCC.
with respect to the increased catabolism it is worth while towith respect to the increased catabolism it is worth while to
mention that this phenotype can also be measures in normalmention that this phenotype can also be measures in normal
(non-malignant) oral keratinocytesof OSCC pts.(non-malignant) oral keratinocytesof OSCC pts.
This suggests that we are dealing with an intrinsicThis suggests that we are dealing with an intrinsic
characteristic and that individuals with a relative high retinoidcharacteristic and that individuals with a relative high retinoid
turnover have an increased risk to develop OSCC.turnover have an increased risk to develop OSCC.
A similar conclusion was drawn for the relation betweenA similar conclusion was drawn for the relation between
retinoid turnover and the risk for lung cancer.retinoid turnover and the risk for lung cancer.
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34. New strategies in retinoidNew strategies in retinoid
chemopreventionchemoprevention
GeneralGeneral
It may well be that the long term response ofIt may well be that the long term response of
leukoplakia can be improved when the treatment isleukoplakia can be improved when the treatment is
extended to a longer and even to life-long period.extended to a longer and even to life-long period.
Moreover, recent publications shed light on theMoreover, recent publications shed light on the
mechanisms underlying intrinsic or acquiredmechanisms underlying intrinsic or acquired
resistance to retinoids.resistance to retinoids.
As discussed earlier, an increased catabolism ofAs discussed earlier, an increased catabolism of
retinoids and an inactivation of nuclear receptors areretinoids and an inactivation of nuclear receptors are
proposed to be important defense mechanisms.proposed to be important defense mechanisms.
These findings open the way to novel tumor-selectiveThese findings open the way to novel tumor-selective
therapeutic approaches.therapeutic approaches.
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35. RAR- gammaRAR- gamma
The presence of RAR-gamma in premalignant tissues may predictThe presence of RAR-gamma in premalignant tissues may predict
success of treatment with retinoids in the head and neck region.success of treatment with retinoids in the head and neck region.
Furthermore, the results suggest that RA-sensitivity can beFurthermore, the results suggest that RA-sensitivity can be
enhanced by restoring RAR-g expression.enhanced by restoring RAR-g expression.
Thus, one of the approaches could be local gene therapy withThus, one of the approaches could be local gene therapy with
RAR-g in tumor cells to re-activate RA-induced growthRAR-g in tumor cells to re-activate RA-induced growth
inhibition.inhibition.
A gene therapy approach may however not be expected in the nearA gene therapy approach may however not be expected in the near
future. Another more indirect approach may be the use of RAR-future. Another more indirect approach may be the use of RAR-
g independent retinoids.g independent retinoids.
It was found that inhibition of cell growth and/or anti-tumorIt was found that inhibition of cell growth and/or anti-tumor
activity could also be achieved through other receptors.activity could also be achieved through other receptors.
LGD1069 (Targretin), for instance, is a retinoid X receptor agonistLGD1069 (Targretin), for instance, is a retinoid X receptor agonist
that modulates cell proliferation [85,86] was shown to have anthat modulates cell proliferation [85,86] was shown to have an
efficacy equivalent to that of tamoxifen in mammary carcinomaefficacy equivalent to that of tamoxifen in mammary carcinoma
with no classic signs of ‘‘retinoid-associated’’ toxicities [87].with no classic signs of ‘‘retinoid-associated’’ toxicities [87].
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36. CYP- inhibitors :CYP- inhibitors :
talarozoletalarozole liarozoleliarozole
What are they?What are they?
CYP26A1CYP26A1 cytochrome P450, family 26, subfamily A, polypeptide 1cytochrome P450, family 26, subfamily A, polypeptide 1
Cytochrome P450, family 26, subfamily A, polypeptide 1Cytochrome P450, family 26, subfamily A, polypeptide 1, also known as, also known as CYP26A1CYP26A1, is a, is a
human gene.[1]human gene.[1]
This gene encodes a member of the cytochrome P450 superfamily of enzymes. TheThis gene encodes a member of the cytochrome P450 superfamily of enzymes. The
cytochrome P450 proteins are monooxygenases which catalyze many reactions involved incytochrome P450 proteins are monooxygenases which catalyze many reactions involved in
drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmicdrug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic
reticulum protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-reticulum protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-
hydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level ofhydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level of
retinoic acid which is involved in regulation of gene expression in both embryonic and adultretinoic acid which is involved in regulation of gene expression in both embryonic and adult
tissues. Two alternatively spliced transcript variants of this gene, which encode the distincttissues. Two alternatively spliced transcript variants of this gene, which encode the distinct
isoforms, have been reported.isoforms, have been reported.
RA metabolism in HNSCC distinguishes itself from that in normal oral keratinocytes by the
formation of polar metabolites. These results suggest that CYP26A1 or analogous enzymes
determine the formation of polar metabolites in HNSCC cells. This makes CYP26A1 an
interesting target in the treatment of HNSCC. Prolonged high intracellular RA concentrations
could be achieved by the inhibition of this enzyme.
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37. The approach of blocking CYPs was already suggested
by Van Wauwe and Janssen in 1989 [88], but the
clinical application has until now been unsuccessful.
Liarozole, which was the first clinically tested RA
metabolism blocking agent (RAMBA), demonstrated
anti-tumor effects, but did not have an optimal CYP
inhibition profile [89]. A new RAMBA, called
R115866, was recently tested in rodents and was
found to inhibit CYP26-dependent RA conversion in
a nanomolar range and was about three orders of
magnitude more powerful than liarozole (IC50=3
mM) [90].
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38. There are however some potential drawbacks of blocking CYP
that should be taken into account. At first, there may be a
lackof selectivity; prolonged high RA concentrations may
have toxic effects on nonmalignant epithelial and liver cells.
Second, CYP26A1 may not be the only enzyme responsible
for RA catabolism in HNSCC cell lines, since only a certain
proportion of HNSCC cell lines show significant CYP26A1
mRNA levels [46]. Furthermore, RA can be isomerized and
consequently 13-cis-RA and 9-cis-RA can be catabolized by
other enzymes [49]. For these reasons retinoids should be
found that are not easily catabolized in HNSCC cells, and
have a better (selective) anti-tumor activity.
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39. New synthetic compoundsNew synthetic compounds
In addition to the natural retinoids ATRA, 9-cis-RA and 13-cis-
RA, several novel retinoid compounds have been synthesized,
and the hope is that these derivatives may be able to provide
similar efficacy as 13-cis-RA with fewer side effects. Among
these novel compounds, the best characterized to date is all-
trans-N-(4-hydroxy-phenyl) retinamide (4HPR or fenretinide),
which is currently under evaluation in clinical trials as a
chemopreventive agent against head and neck, and breast
cancer [91] and thus far limited effect has been observed in
has been tested in lung metaplasia [92], prostate [93], and
bladder cancer [94]. Fenretinide is a synthetic retinoid that is
reported to have less toxic side effects compared to natural
occurring retinoids such as RA and 13-cis-RA and has been
shown to induce apoptosis even in RA-resistant cell lines [95].
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40. Other novel synthetic retinoids, such as CD437 and
anhydroretinol also have potent receptor-independent
apoptosis-inducing activity [96,97]. Some of the
novel synthetic retinoids have selective retinoid
receptor activity. ALRT1550, a high-affinity ligand
for all three RARs, has shown to have potent anti-
tumor activity against human oral squamous
carcinoma xenografts in nude mice [98]. LGD1069
(Targretin) is a retinoid X receptor agonist that
modulates cell proliferation [85,86]. CD437, which
acts in a receptor (RAR-g) dependent manner,
activates and upregulates the transcription factor AP-
1, leading eventually to programmed cell death [99].
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41. Combination therapies
Combinations of retinoids with cytokines, such as interferons,
receive currently much attention. Studies in cervix cancer and
squamous carcinoma of the skin have been successful, with 50
and 68% response rates, respectively (reviewed by Eisenhauer
et al. [100]).
There is evidence to suggest that interferons may modulate the
retinoid-signaling pathways by inducing or increasing the
expression of RARs or RXRs, rendering cells more sensitive
to retinoid actions and even restoring retinoic acid sensitivity
in RA-insensitive cells [101,102].
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42. Another strategy is based on the cooperative effects with
agents acting on other steroid hormone receptors,
resulting in synergistic activation of the receptor
heterodimeric complex.
Besides dimerizing with RARs, RXRs can form dimers
with many other nuclear receptors of the steroid/thyroid
hormone receptor family.
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43. This family includes the estrogen receptor, the glucocorticoidThis family includes the estrogen receptor, the glucocorticoid
receptor, the mineralocorticoid receptor, the peroxisomereceptor, the mineralocorticoid receptor, the peroxisome
proliferator-activated receptor, the progesterone receptor, theproliferator-activated receptor, the progesterone receptor, the
thyroid hormone receptor, the vitamin D receptor, and variousthyroid hormone receptor, the vitamin D receptor, and various
orphan receptors.orphan receptors.
Thus, RXRs may participate in many different signalingThus, RXRs may participate in many different signaling
pathways and act as important factors in the cross-talkpathways and act as important factors in the cross-talk
between retinoids and other hormones.between retinoids and other hormones.
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44. Cooperative effects on growth inhibition using a combinationCooperative effects on growth inhibition using a combination
of a retinoid with a vitamin D3 analogue have been observedof a retinoid with a vitamin D3 analogue have been observed
in several experimental systems, including lung cancer cellsin several experimental systems, including lung cancer cells
[103], pancreatic cells [104] and the HL-60 leukemic cells[103], pancreatic cells [104] and the HL-60 leukemic cells
[105].[105].
Other strategies are the use of selective estrogen receptorOther strategies are the use of selective estrogen receptor
modulators, polyamine biosynthesis inhibitors (e.g.modulators, polyamine biosynthesis inhibitors (e.g.
difluoromethylornithine), cyclooxygenase-2 inhibitors anddifluoromethylornithine), cyclooxygenase-2 inhibitors and
several other agent classesseveral other agent classes
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46. ConclusionsConclusions
Retinoid research in the last decade has mainly lead to a betterRetinoid research in the last decade has mainly lead to a better
understanding of the mechanisms of retinoids in the differentunderstanding of the mechanisms of retinoids in the different
stages during HNSCC carcinogenesis.stages during HNSCC carcinogenesis.
As effective chemopreventive agents, retinoids appear,As effective chemopreventive agents, retinoids appear,
however, not immediately applicable.however, not immediately applicable.
Tumor cells are able to defend themselves against the growthTumor cells are able to defend themselves against the growth
inhibiting actions of retinoids by different strategies, such asinhibiting actions of retinoids by different strategies, such as
an increased RA turnover or inactivation of retinoid receptors,an increased RA turnover or inactivation of retinoid receptors,
both leading to resistance for retinoids.both leading to resistance for retinoids.
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47. It is too early to start with individualized therapies,It is too early to start with individualized therapies,
since the great complexity of retinoid metabolism andsince the great complexity of retinoid metabolism and
the overlap with other metabolic pathways (forthe overlap with other metabolic pathways (for
instance of vitamin D3 or nitric oxide).instance of vitamin D3 or nitric oxide).
The application of gene therapy with RAR-g will beThe application of gene therapy with RAR-g will be
an attractive approach when the advantages risean attractive approach when the advantages rise
above that of surgery and radiation therapy, but willabove that of surgery and radiation therapy, but will
not be expected to be used in the near future.not be expected to be used in the near future.
Measurement of RAR-g mRNA expression inMeasurement of RAR-g mRNA expression in
premalignant tissues will be of value to predict apremalignant tissues will be of value to predict a
successful treatment with retinoids.successful treatment with retinoids.
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48. The discovery of new, synthetic retinoid analogues will enableThe discovery of new, synthetic retinoid analogues will enable
more effective therapy with less toxicity than the naturalmore effective therapy with less toxicity than the natural
occurring retinoids.occurring retinoids.
The evaluation and characterization of their mechanism willThe evaluation and characterization of their mechanism will
also contribute to a better understanding of oralalso contribute to a better understanding of oral
carcinogenesis and is essential for a rational approach incarcinogenesis and is essential for a rational approach in
chemopreventive intervention.chemopreventive intervention.
New agents may be useful in advanced disease or in anNew agents may be useful in advanced disease or in an
adjuvant setting in combination with other steroid hormones,adjuvant setting in combination with other steroid hormones,
inhibitors of specific signal transduction pathways, or ininhibitors of specific signal transduction pathways, or in
combination with cytotoxic chemotherapy agents currently incombination with cytotoxic chemotherapy agents currently in
use in the clinic.use in the clinic.
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