Skip to main content

Home/ Dr. Goodyear/ Group items tagged BREAK

Rss Feed Group items tagged

wheelchairindia9

Karma 8020 Wheelchair - 0 views

  •  
    Heavy duty wheelchair can either be manually-operated or motorized, each with its own pros and cons. A manual heavy-duty wheelchair gives full control of motion to the user, but the added weight from the reinforcements makes pushing or propelling the wheelchair much harder than normal. A motorized heavy duty wheelchair offers a solution to this dilemma, but is often more expensive and harder to maintain than a manual wheelchair. Some designs offer a combination of both, with a small motor assisting those pushing the wheelchair. The proper choice between types of Heavy Duty wheelchair depends largely on the user's expected level of activity. Heavy duty wheelchairs typically have larger seats than conventional wheelchairs. The frames of these wheelchairs can be made from several different reinforced metals, although a titanium wheelchair is often the most popular choice. The wheels themselves are made of thicker rubber than normal, preventing any possible failure due to the greater amount of weight supported. Most makes of heavy duty wheelchairs fold like regular wheelchairs, making storage relatively easy despite the wheelchair increased size. Heavy Duty Wheelchair specialy design for disabled and handicapped persons. They are two types of Heavy Duty Wheelchair for handicapped and disability product like- Karma 8020 X Heavy Duty Wheelchair Karma 8520 Heavy Duty Wheelchair Karma 8020 X Heavy Duty Wheelchair: It comes with detachable swing away footrests. The wheel chair has flip-back armrests. It comes with centre of gravity adjustment. The wheel chair has wide profile casters. Seat Size 20'' inch & 22'' inch Total Weight 17 K.G. Designed for maximum strength & weight capacity for people over 250 lbs. These end to be heavier and wider. This heavy duty bariatric wheelchair has seat dimensions of 24 inches wide by 18 inches deep to accommodate a weight capacity of up to 400 lbs. This wheelchair is dual axle, which means that the floor to seat heigh
wheelchairindia9

Transport Chair - 0 views

  •  
    Lightweight wheelchairs provide convenience and comfort to the user and caregiver alike and are often built using materials like aluminum and titanium alloy, while foldable wheelchairs allow for easy storage and transport. Merge the two styles, and got a great mobility aid that isn't a pain to lug around. Utilizing small wheels and lighter materials, transport wheelchairs can tip the scale at as little as 19 lbs, ideal for those looking for a highly portable option. Transport chairs also tend to be more affordable and offer the benefit of increased mobility without breaking the bank. Transport wheelchairs or companion chairs are companion wheelchairs where the purpose is for a companion to push the user. Most transporters have swing-away leg rests, fixed armrests, and side panels. Instead of the usual large back - small front wheels typical of most wheelchairs, light travel chairs have four small wheels providing much easier maneuverability of the chair. Karma KM 2500 Small Wheel Wheelchair: Karma KM 2500 Small Wheel Wheelchair Specifications: Width 18" Front/Rear Wheels 6" to 14" Seat Width 47cm Seat Depth 40cm Overall Width 66cm Overall Collapsed Width 36cm Armrest Height 21cm Overall Length 90cm Seat Height 47cm Backrest Height 38cm Overall Height 86cm Weight 9.2 k.g. Karma KM 2500 Small Wheel Wheelchair Seat and Back: AEGIS Microbe Shield Approved by the FDA, EPA, EU, etc., bonded anti-microbial barrier upholstery protects from odor, staining and deterioration from bacteria, fungus and other microorganisms. It is a shield for your health. Karma KM 2500 Small Wheel Wheelchair Extended Armrest: By simulating the natural position of arms, the extended armrest design is ergonomic and creates bigger seating space. An Ultra lightweight wheelchair (9.2 kg) with a compact design for either attendant assisted or self propelling users. The use of aircraft-grade aluminium alloy and double cross brace provide this model
wheelchairindia9

Karma S-Ergo 105 Manual Wheelchair - 0 views

  •  
    Ergonomic chairs are designed to confirm to a person's physical dimensions, allowing them to sit naturally and comfortably for long periods of time, while reducing the risk of pressure ulcers. Ergonomic system (Intelligent s-shaped ergonomic seating) provides efficient pressure relief by spreading weight over a greater area, at the same time provides stabilization and reduced sliding. With their lightweight frames and seats designed to reduce or prevent pressure points, ergonomic wheelchairs provide a comfortable option for mobility impaired users who have the upper body strength to propel themselves, or a caregiver strong enough to do so. Karma Ergo Lite 2501 Wheelchair: The extremely lightweight Ergo Lite 2501 Transport Wheelchair weighs only 8.16 kg. and features an ergonomically-designed seat and backrest, making it one of the most comfortable transport chairs on the market. The folding seat and backrest make the S-Ergo ideal for storage or travel, and the built in AEGIS anti-bacterial cushion provides added comfort and support. Despite its light weight, the S-Ergo features a 115 kg. weight capacity along with large, 14" flat-free polyurethane rear tires. Karma Ergo Lite 2501 Wheelchair Features: Lightest transporter on the market! Patented S-Style Ergonomic Seat Frame 6061 T-6 Aircraft-grade Aluminum Only 18 lb . (w/ footrests) Built in Silver Aegis Anti-bacterial Cushion Fixed Armrests w/Concaved Armpads Pocket Behind Backrest & Small Carry Pouch on Each Armrest 6" x 1" Polyurethane Front Casters 16" x 17" or 18" x 17" Seat Width S-Style Ergonomic Seat 14" Rear Polyurethane, High Tread, Flat Free Wheels 3-Stage handle brake: allows light to firm grip for lock Folding Backrest/ Folding Seat for Transporting in Vehicle or Travel Fixed Footrests w/ Extra Wide Footplates Frame Color: Pearl Silver Weight Capacity of 100 kg Ergonomic Transporter w/ handle brakes Karma Ergo Lite 2501 Wheelchair Measurements: Seat Width 16 inch., 18
Syed Amjad Ali

E-Templates - A new approach in Rapid E-Learning Course Development - 0 views

  •  
    Advanced eLearning Authoring Tools have made eLearning Development Easy The rapid and extensive advances in technology have brought on incredible innovation in all fields of human interest. The impact of the same can be seen in the e-learning space, and these days, this specialized segment is breaking new ground continuously.
Nathan Goodyear

Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain an... - 0 views

  •  
    Only abstract available here, but sugar in the form of sucrose found to lower cortisol.  Increased activity in the hippocampus was evident in the sucrose arm of this study.  Both of these activities will lead to stress induced food addictions--particularly of sugar.  Sugar is highly addictive and should be especially avoided in children.  Of note, this study followed the cortisol levels through saliva.
wheelchairindia9

Karma KM 2500 Wheelchair - 0 views

  •  
    Karma KM 2500 Small Wheel Wheelchair: Karma KM 2500 Small Wheel Wheelchair Specifications: Width 18" Front/Rear Wheels 6" to 14" Seat Width 47cm Seat Depth 40cm Overall Width 66cm Overall Collapsed Width 36cm Armrest Height 21cm Overall Length 90cm Seat Height 47cm Backrest Height 38cm Overall Height 86cm Weight 9.2 k.g. Karma KM 2500 Small Wheel Wheelchair Seat and Back: AEGIS Microbe Shield Approved by the FDA, EPA, EU, etc., bonded anti-microbial barrier upholstery protects from odor, staining and deterioration from bacteria, fungus and other microorganisms. It is a shield for your health. Karma KM 2500 Small Wheel Wheelchair Extended Armrest: By simulating the natural position of arms, the extended armrest design is ergonomic and creates bigger seating space. An Ultra lightweight wheelchair (9.2 kg) with a compact design for either attendant assisted or self propelling users. The use of aircraft-grade aluminium alloy and double cross brace provide this model with outstanding strength and durability. Karma Healthcare KM-2500 Premium Wheelchair is amazingly light and compact transit wheelchair which is ideal for outings and travelers. It folds down to take up virtually no space in the boot of a car and weighs just over 9.2 kg making it easy for anyone to lift into a vehicle. Backrest folds-down for easy transportation. Maximum user weight: 100 K.g. Aluminium frame. Fixed armrest/fixed footrest. Foldable frame via double cross bars. Comfortable & durable upholstery. Swing-away foot plates. Puncture proof tyres. Attendant cable brake. 14" flat-free rear wheels. Detachable and washable cushion. One Year Warranty. It folds down to take up virtually no space in the boot of a car. This amazingly light and compact transit wheelchair is ideal for outings and travelling. It comes with detachable and washable cushion. The wheel chair has attendant cable brake. It is made from aircraft-grade aluminium alloy fra
wheelchairindia9

Transport Chairs - 0 views

  •  
    Lightweight wheelchairs provide convenience and comfort to the user and caregiver alike and are often built using materials like aluminum and titanium alloy, while foldable wheelchairs allow for easy storage and transport. Merge the two styles, and got a great mobility aid that isn't a pain to lug around. Utilizing small wheels and lighter materials, transport wheelchairs can tip the scale at as little as 19 lbs, ideal for those looking for a highly portable option. Transport chairs also tend to be more affordable and offer the benefit of increased mobility without breaking the bank. This type of lightweight wheelchair is often referred to as a "transfer chair" and is typically used for shorter trips. Since it's geared towards storability and portability, it features four smaller wheels and dispenses with the larger, rear-mounted wheels that characterize standard wheelchairs. Its construction ensures that it's always foldable and portable, but does so at the expense of self-propulsion. Instead, a transport chair is built so that a caregiver can easily push the user. Transport wheelchairs or companion chairs are companion wheelchairs where the purpose is for a companion to push the user. Most transporters have swing-away leg rests, fixed armrests, and side panels. Instead of the usual 'large back - small front' wheels typical of most wheelchairs, light travel chairs have four small wheels providing much easier maneuverability of the chair. Karma Travel Wheelchair KM TV 20.2: Karma Travel Wheelchair KM TV 20.2 - 606 T-6 aircraft-grade aluminum-alloy frame provides incredible strength. Easy-to-fold in three seconds. Karma Travel Wheelchair KM TV 20.2 Features: Type: Travel Wheelchair. T-6 aircraft-grade aluminum. Secure brake improve safety. Padded flip back armrest. PU front caster & rear wheel. Karma Travel Wheelchair KM TV 20.2 Measurements: Weight: 8.9kg. Seat width: 39.5cm. Tyre: PU front casters and rear wheels. Capacity: 100
wheelchairindia9

Karman S-Ergo 115 - 0 views

  •  
    Ergonomic wheelchairs have been tested and proven to be effective for relieving pressure throughout the body; this is confirmed by pressure chart mapping. Feeling comfortable on a wheelchair is something every user demands out of their new wheelchair, the ergonomic cushion that is included with the ergonomic series provides a level of comfort that is unparalleled. Ergonomic Transport Wheelchair provides the perfect shape to fit the human body to relieve pressure, increase stabilization, weight distribution and lower the risk of pressure sores and scoliosis. Lightweight Ergonomic Wheelchair features wide arm pads for extra support, folding back rest, detachable swing-away footrests, and a Tube-in Center foot-plate that provides extra support for the leg muscles. This wheelchair can hold up to daily use and is excellent for traveling. Ergonomic features flip-back armrest and swing away footrests. A lightweight frame that is 25 lbs. without footrests and a folding backrest allows easy travel or storage. The chair comes equipped with a padded anti-bacterial upholstery that is comfortable and washable. Karma Ergo Lite 2501 Wheelchair: The extremely lightweight Ergo Lite 2501 Transport Wheelchair weighs only 8.16 kg. and features an ergonomically-designed seat and backrest, making it one of the most comfortable transport chairs on the market. The folding seat and backrest make the S-Ergo ideal for storage or travel, and the built in AEGIS anti-bacterial cushion provides added comfort and support. Despite its light weight, the S-Ergo features a 115 kg. weight capacity along with large, 14" flat-free polyurethane rear tires. Karma Ergo Lite 2501 Wheelchair Features: Lightest transporter on the market! Patented S-Style Ergonomic Seat Frame 6061 T-6 Aircraft-grade Aluminum Only 18 lb . (w/ footrests) Built in Silver Aegis Anti-bacterial Cushion Fixed Armrests w/Concaved Armpads Pocket Behind Backrest & Small Carry Pouch on Each Armrest 6" x 1" Polyurethane
kunalkumar03

Improve your Skin tone with Laser Toning - 1 views

  •  
    Laser toning is simply using of laser light to penetrate the dermal layers of skin and break the pigment that results in ageing, dark spots even acne. Laser toning is performed using non ablative lasers thus depending on thermolysis and not causing any damage to the surface skin. This thermal injury causes triggering of collagen production in the dermis and rejuvenates the skin as a result.
Nathan Goodyear

Vitamin C increases DNA breaks and suppresses DNA damage-independent activation of ATM ... - 0 views

  •  
    Vitamin C impairs the DNA repair induced by + ATM
Nathan Goodyear

Vitamin C increases DNA breaks and suppresses DNA damage-independent activation of ATM ... - 0 views

  •  
    Vitamin C increased the efficacy of bleomycin.
Nathan Goodyear

Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer... - 0 views

  • More than half of cancer patients are treated with IR at some point during their treatment
  • fractionation schedule is the delivery of 1.8–2.0 Gy per day, five days per week
  • Nuclear DNA is the primary target of IR; it causes DNA damage (genotoxic stress) by direct DNA ionization
  • ...121 more annotations...
  • IR also indirectly induces DNA damage by stimulating reactive oxygen species (ROS) production
  • IR is known to induce EMT in vitro
  • p53 is activated in response to IR-induced DNA damage
  • IR paradoxically also promotes tumour recurrence and metastasis
  • DNA double-strand breaks (DSBs)
  • cancer cells undergoing EMT acquire invasive and metastatic properties
  • changes in the tumour microenvironment (TME)
  • IR seems to induce EMT and CSC phenotypes by regulating cellular metabolism
  • EMT, stemness, and oncogenic metabolism are known to be associated with resistance to radiotherapy and chemotherapy
  • Hanahan and Weinberg proposed ten hallmarks of cancer that alter cell physiology to enhance malignant growth: 1) sustained proliferation, 2) evasion of growth suppression, 3) cell death resistance, 4) replicative immortality, 5) evasion of immune destruction, 6) tumour-promoting inflammation, 7) activation of invasion and metastasis, 8) induction of angiogenesis, 9) genome instability, and 10) alteration of metabolism
  • EMT is a developmental process that plays critical roles in embryogenesis, wound healing, and organ fibrosis
  • IR is known to induce stemness and metabolic alterations in cancer cells
  • transforming growth factor-β [TGF-β], epidermal growth factor [EGF]) and their associated signalling proteins (Wnt, Notch, Hedgehog, nuclear-factor kappa B [NF-κB], extracellular signal-regulated kinase [ERK], and phosphatidylinositol 3-kinase [PI3K]/Akt
  • activate EMT-inducing transcription factors, including Snail/Slug, ZEB1/δEF1, ZEB2/SIP1, Twist1/2, and E12/E47
  • Loss of E-cadherin is considered a hallmark of EMT
  • IR has been shown to induce EMT to enhance the motility and invasiveness of several cancer cells, including those of breast, lung, and liver cancer, and glioma cells
  • IR may increase metastasis in both the primary tumour site and in normal tissues under some circumstance
  • sublethal doses of IR have been shown to enhance the migratory and invasive behaviours of glioma cells
  • ROS are known to play an important role in IR-induced EMT
  • High levels of ROS trigger cell death by causing irreversible damage to cellular components such as proteins, nucleic acids, and lipids, whereas low levels of ROS have been shown to promote tumour progression—including tumour growth, invasion, and metastasis
  • hypoxia-inducible factor-1 (HIF-1) is involved in IR-induced EMT
  • Treatment with the N-acetylcysteine (NAC), a general ROS scavenger, prevents IR-induced EMT, adhesive affinity, and invasion of breast cancer cells
    • Nathan Goodyear
       
      NAC for all patients receiving radiation therapy
  • Snail has been shown to play a crucial role in IR-induced EMT, migration, and invasion
  • IR activates the p38 MAPK pathway, which contributes to the induction of Snail expression to promote EMT and invasion
  • NF-κB signalling that promotes cell migration
  • ROS promote EMT to allow cancer cells to avoid hostile environments
  • HIF-1 is a heterodimer composed of an oxygen-sensitive α subunit and a constitutively expressed β subunit.
  • Under normoxia, HIF-1α is rapidly degraded, whereas hypoxia induces stabilisation and accumulation of HIF-1α
  • levels of HIF-1α mRNA are enhanced by activation of the PI3K/Akt/mammalian target of rapamycin (mTOR)
  • IR is known to increase stabilisation and nuclear accumulation of HIF-1α, since hypoxia is a major condition for HIF-1 activation
  • IR induces vascular damage that causes hypoxia
  • ROS is implicated in IR-induced HIF-1 activation
  • IR causes the reoxygenation of hypoxic cancer cells to increase ROS production, which leads to the stabilisation and nuclear accumulation of HIF-1
  • IR increases glucose availability under reoxygenated conditions that promote HIF-1α translation by activating the Akt/mTOR pathway
  • The stabilised HIF-1α then translocates to the nucleus, dimerizes with HIF-1β, and increases gene expression— including the expression of essential EMT regulators such as Snail—to induce EMT, migration, and invasion
  • TGF-β signalling has been shown to play a crucial role in IR-induced EMT
  • AP-1 transcription factor is involved in IR-induced TGF-β1 expression
  • Wnt/β-catenin signalling is also implicated in IR-induced EMT
  • Notch signalling is known to be involved in IR-induced EMT
  • IR also increases Notch-1 expression [99]. Notch-1 is known to induce EMT by upregulating Snail
  • PAI-1 signalling is also implicated in IR-induced Akt activation that increases Snail levels to induce EMT
  • EGFR activation is known to be associated with IR-induced EMT, cell migration, and invasion by activating two downstream pathways: PI3K/Akt and Raf/MEK/ERK
  • ROS and RNS are also implicated in IR-induced EGFR activation
  • IR has also been shown to activate Hedgehog (Hh) signalling to induce EMT
  • IR has been shown to induce Akt activation through several signalling pathways (EGFR, C-X-C chemokine receptor type 4 [CXCR4]/C-X-C motif chemokine 12 [CXCL12], plasminogen activator inhibitor 1 [PAI-1]) and upstream regulators (Bmi1, PTEN) that promote EMT and invasion
  • CSCs possess a capacity for self-renewal, and they can persistently proliferate to initiate tumours upon serial transplantation, thus enabling them to maintain the whole tumour
  • Conventional cancer treatments kill most cancer cells, but CSCs survive due to their resistance to therapy, eventually leading to tumour relapse and metastasis
  • identification of CSCs, three types of markers are utilised: cell surface molecules, transcription factors, and signalling pathway molecules
  • CSCs express distinct and specific surface markers; commonly used ones are CD24, CD34, CD38, CD44, CD90, CD133, and ALDH
  • Transcription factors, including Oct4, Sox2, Nanog, c-Myc, and Klf4,
  • signalling pathways, including those of TGF-β, Wnt, Hedgehog, Notch, platelet-derived growth factor receptor (PDGFR), and JAK/STAT
  • microRNAs (miRNAs), including let-7, miR-22, miR-34a, miR-128, the miR-200 family, and miR-451
  • Non-CSCs can be reprogrammed to become CSCs by epigenetic and genetic changes
  • EMT-inducing transcription factors, such as Snail, ZEB1, and Twist1, are known to confer CSC properties
  • Signalling pathways involved in EMT, including those of TGF-β, Wnt, and Notch, have been shown to play important roles in inducing the CSC phenotype
  • TGF-β1 not only increases EMT markers (Slug, Twist1, β-catenin, N-cadherin), but also upregulates CSC markers (Oct4, Sox2, Nanog, Klf4) in breast and lung cancer cells
  • some CSC subpopulations arise independently of EMT
  • IR has been shown to induce the CSC phenotype in many cancers, including breast, lung, and prostate cancers, as well as melanoma
  • Genotoxic stress due to IR or chemotherapy promotes a CSC-like phenotype by increasing ROS production
  • IR has been shown to induce reprogramming of differentiated cancer cells into CSCs
  • In prostate cancer patients, radiotherapy increases the CD44+ cell population that exhibit CSC properties
  • IR also induces the re-expression of stem cell regulators, such as Sox2, Oct4, Nanog, and Klf4, to promote stemness in cancer cells
  • EMT-inducing transcription factors and signalling pathways, including Snail, STAT3, Notch signalling, the PI3K/Akt pathway, and the MAPK cascade, have been shown to play important roles in IR-induced CSC properties
  • STAT3 directly binds to the Snail promoter and increases Snail transcription, which induces the EMT and CSC phenotypes, in cisplatin-selected resistant cells
  • Other oncogenic metabolic pathways, including glutamine metabolism, the pentose phosphate pathway (PPP), and synthesis of fatty acids and cholesterol, are also enhanced in many cancers
  • metabolic reprogramming
  • HIF-1α, p53, and c-Myc, are known to contribute to oncogenic metabolism
  • metabolic reprogramming
  • tumour cells exhibit high mitochondrial metabolism as well as aerobic glycolysis
  • occurring within the same tumour
  • CSCs can be highly glycolytic-dependent or oxidative phosphorylation (OXPHOS)-dependen
  • mitochondrial function is crucial for maintaining CSC functionality
  • cancer cells depend on mitochondrial metabolism and increase mitochondrial production of ROS that cause pseudo-hypoxia
  • HIF-1 then enhances glycolysis
  • CAFs have defective mitochondria that lead to the cells exhibiting the Warburg effect; the cells take up glucose, and then secrete lactate to 'feed' adjacent cancer cells
  • lactate transporter, monocarboxylate transporter (MCT)
  • nutrient microenvironment
  • Epithelial cancer cells express MCT1, while CAFs express MCT4. MCT4-positive, hypoxic CAFs secrete lactate by aerobic glycolysis, and MCT1-expressing epithelial cancer cells then uptake and use that lactate as a substrate for the tricarboxylic acid (TCA) cycle
  • MCT4-positive cancer cells depend on glycolysis and then efflux lactate, while MCT1-positive cells uptake lactate and rely on OXPHOS
  • metabolic heterogeneity induces a lactate shuttle between hypoxic/glycolytic cells and oxidative/aerobic tumour cells
  • bulk tumour cells exhibit a glycolytic phenotype, with increased conversion of glucose to lactate (and enhanced lactate efflux through MCT4), CSC subsets depend on oxidative phosphorylation; most of the glucose entering the cells is converted to pyruvate to fuel the TCA cycle and the electron transport chain (ETC), thereby increasing mitochondrial ROS production
  • the major fraction of glucose is directed into the pentose phosphate pathway, to produce redox power through the generation of NADPH and ROS scavengers
  • HIF-1α, p53, and c-Myc, are known to contribute to oncogenic metabolism
  • regulatory molecules involved in EMT and CSCs, including Snail, Dlx-2, HIF-1, STAT3, TGF-β, Wnt, and Akt, are implicated in the metabolic reprogramming of cancer cells
  • HIF-1 induces the expression of glycolytic enzymes, including the glucose transporter GLUT, hexokinase, lactate dehydrogenase (LDH), and MCT, resulting in the glycolytic switch
  • HIF-1 represses the expression of pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), thereby inhibiting mitochondrial activity
  • STAT3 has been implicated in EMT-induced metabolic changes as well
  • TGF-β and Wnt play important roles in the metabolic alteration of cancer cells
  • Akt is also implicated in the glycolytic switch and in promoting cancer cell invasiveness
  • EMT, invasion, metastasis, and stemness
  • pyruvate kinase M2 (PKM2), LDH, and pyruvate carboxylase (PC), are implicated in the induction of the EMT and CSC phenotypes
  • decreased activity of PKM2 is known to promote an overall shift in metabolism to aerobic glycolysis
  • LDH catalyses the bidirectional conversion of lactate to pyruvate
  • High levels of LDHA are positively correlated with the expression of EMT and CSC markers
  • IR has been shown to induce metabolic changes in cancer cells
  • IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
  • IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
  • IR also elevates MCT1 expression that exports lactate into the extracellular environment, leading to acidification of the tumour microenvironment
  • IR increases intracellular glucose, glucose 6-phosphate, fructose, and products of pyruvate (lactate and alanine), suggesting a role for IR in the upregulation of cytosolic aerobic glycolysis
  • Lactate can activate latent TGF-
  • lactate stimulates cell migration and enhances secretion of hyaluronan from CAF that promote tumour metastasis
  • promote tumour survival, growth, invasion, and metastasis; enhance the stiffness of the ECM; contribute to angiogenesis; and induce inflammation by releasing several growth factors and cytokines (TGF-β, VEGF, hepatocyte growth factor [HGF], PDGF, and stromal cell-derived factor 1 [SDF1]), as well as MMP
  • tumours recruit the host tissue’s blood vessel network to perform four mechanisms: angiogenesis (formation of new vessels), vasculogenesis (de novo formation of blood vessels from endothelial precursor cells), co-option, and modification of existing vessels within tissues.
  • immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
  • immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
  • intrinsic immunogenicity or induce tolerance
  • cancer immunoediting’
  • three phases: 1) elimination, 2) equilibrium, and 3) escape.
  • The third phase, tumour escape, is mediated by antigen loss, immunosuppressive cells (TAM, MDSCs, and regulatory T cells), and immunosuppressive cytokines (TGF-β and IL-10).
  • IR can elicit various changes in the TME, such as CAF activity-mediated ECM remodelling and fibrosis, cycling hypoxia, and an inflammatory response
  • IR activates CAFs to promote the release of growth factors and ECM modulators, including TGF-β and MMP
  • TGF-β directly influences tumour cells and CAFs, promotes tumour immune escape, and activates HIF-1 signalling
    • Nathan Goodyear
       
      And now the receipts
  • MMPs degrade ECM that facilitates angiogenesis, tumour cell invasion, and metastasis
    • Nathan Goodyear
       
      Receipts and mechanisms
  • IR also promotes MMP-2/9 activation in cancer cells to promote EMT, invasion, and metastasis
  • IR-induced Snail increases MMP-2 expression to promote EMT
  • Radiotherapy has the paradoxical side-effect of increasing tumour aggressiveness
  • IR promotes ROS production in cancer cells, which may induce the activation of oncogenes and the inactivation of tumour suppressors, which further promote oncogenic metabolism
  • Metabolic alterations
  • oncogenic metabolism
  • elicit various changes in the TME
  • Although IR activates an antitumour immune response, this signalling is frequently suppressed by tumour escape mechanisms
  •  
    Important review article.
Nathan Goodyear

Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer ... - 0 views

  • HCQ, doses for long-term use range between 200 and 400 mg per day.
  • Short-term administration of CQ or HCQ rarely causes severe side effects
  • Short-term administration of CQ or HCQ rarely causes severe side effects
  • ...24 more annotations...
  • bone marrow suppression
  • cardiomyopathy
  • irreversible retinal toxicity
  • hypoglycaemia
  • daily doses up to 400 mg of HCQ or 250 mg CQ for several years are considered to carry an acceptable risk for CQ-induced retinopathies, with the exception of individuals of short stature
  • chronic CQ or HCQ therapy be monitored through regular ophthalmic examinations (3–6 month intervals), full blood counts and blood glucose level checks
  • long-term HCQ exposure, skeletal muscle function and tendon reflexes should be monitored for weakness
  • both CQ and HCQ, specific caution is advised in patients suffering from impaired hepatic function (especially when associated with cirrhosis), porphyria, renal disease, epilepsy, psoriasis, glucose-6-phosphate dehydrogenase deficiency and known hypersensitivity to 4-aminoquinoline compounds
  • CQ and HCQ can effectively increase the efficacy of various anti-cancer drugs
  • CQ can prevent the entrapment of protonated chemotherapeutic drugs by buffering the extracellular tumour environment and intracellular acidic spaces
  • This study recommends an adjuvant HCQ dose of 600 mg, twice daily.
  • HCQ addition was shown to produce metabolic stress in the tumours
  • HCQ (400 mg/day)
  • important effects of CQ and HCQ on the tumour microenvironment
  • The main and most studied anti-cancer effect of CQ and HCQ is the inhibition of autophagy
  • the expression levels of TLR9 are higher in hepatocellular carcinoma, oesophageal, lung, breast, gastric and prostate cancer cells as compared with adjacent noncancerous cells, and high expression is often linked with poor prognosis
  • TLR9-mediated activation of the NF-κB signalling pathway and the associated enhanced expression of matrix metalloproteinase-2 (MMP-2), MMP-7 and cyclo-oxygenase 2 mRNA
  • HCQ can activate caspase-3 and modulate the Bcl-2/Bax ratio inducing apoptosis in CLL, B-cell CLL and glioblastoma cells
  • In triple-negative breast cancer, CQ was shown to eliminate cancer stem cells through reduction of the expression of Janus-activated kinase 2 and DNA methyl transferase 1 [106] or through induction of mitochondrial dysfunction, subsequently causing oxidative DNA damage and impaired repair of double-stranded DNA breaks
  • CQ or HCQ would be considered for use in combination with immunomodulation anti-cancer therapies
  • Therapies used in combination with CQ or HCQ include chemotherapeutic drugs, tyrosine kinase inhibitors, various monoclonal antibodies, hormone therapies and radiotherapy
  • Most studies hypothesise that CQ and HCQ could increase the efficacy of other anti-cancer drugs by blocking pro-survival autophagy.
  • daily doses between 400 and 1200 mg for HCQ are safe and well tolerated, but two studies identified 600-mg HCQ daily as the MTD
  • HCQ is often administered twice daily to limit plasma fluctuations and toxicity
pharmacybiz

David Webb - England New Chief Pharmaceutical Officer - 0 views

  •  
    David Webb has been appointed as the new chief pharmaceutical officer (CPO) for England. He will take over from Dr Keith Ridge who steps down next month after serving the role for sixteen year. Webb is currently chief pharmacist and clinical director for pharmacy and medicines optimisation at Guy's and Thomas's NHS Foundation Trust, London. Sharing the news of his appointment on Twitter on Friday afternoon (January 7), he said he was "really delighted and honoured" to be named the CPO for NHS England and that he was as the appointed Chief Pharmaceutical officer for "looking forward to working with pharmacy leaders, colleagues & teams across all sectors from February." He also extended his gratitude to the outgoing CPO for his "outstanding contribution" who, in turn, congratulated Webb and said it was "an honour to be handing over to him". In the same message, Dr Ridge thanked "all the great people I've worked with over the last 16 years for your support, friendship, good humour, great ideas & challenge. I wish you all well for the future."
« First ‹ Previous 41 - 55 of 55
Showing 20 items per page