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Nathan Goodyear

Anti-helminth compound niclosamide downregulates Wnt Signaling and elicits antitumor re... - 0 views

  • Others have reported that niclosamide inhibits the NF-κB pathway in leukemia cell lines (26) or mTOR signaling in MCF-7 breast cancer cells
  • niclosamide enhances the anti-tumor effect of oxaliplatin
  • In the more rapidly growing tumor (HCT116), a dose of 200 mg/kg of body weight was needed to suppress the tumor growth
  • ...13 more annotations...
  • however, 100 mg/kg of niclosamide could suppress the growth of the relatively slow-growing tumor (CRC039) to the same level
  • niclosamide was confirmed to inhibit the growth of human CRCs in NOD/SCID mice
  • niclosamide can inhibit Wnt pathway activation in CRC
  • The mechanism of action of the niclosamide in our studies is thought to be through internalization of Fzd1 and downregulation of Wnt pathway intermediaries
  • Recently, Jin et al. (26) reported that niclosamide inhibited the NF-κB pathway and increased reactive oxygen species levels to induce apoptosis in AML cells. In contrast, we did not observe any inhibitory effect of niclosamide on NF-κB signaling in our CRC model
  • oral administration of niclosamide does result in sufficient distribution of the drug into tumor tissue, to prove a prolonged inhibitory effect on Wnt/ß-catenin signaling, resulting in tumor growth inhibition
  • we required higher doses (100 ~ 200 mg/kg body weight) of niclosamide in order to demonstrate significant inhibition of tumor growth in NOD/SCID mice
  • niclosamide concentrations in tumor tissue showed good correlation with those in plasma, suggesting the efficient distribution of niclosamide from blood to tumor tissue
  • we observed downregulation of Dvl2 and ß-catenin cytosolic expression in niclosamide-treated tumor cells in vivo
  • One potential concern for the use of niclosamide as an anticancer therapy is the poor absorption of this drug
  • The Wnt signaling pathway, fundamental to embryonic tissue patterning, is also activated in stem-like cells
  • The canonical Wnt pathway is activated in approximately 80% of sporadic CRC primarily due to mutations in the APC gene
  • recent observations reveal that Wnt ligands or inhibitors may affect the growth and survival of colon cancer cells in spite of the presence of APC or CTNNB1 mutations
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    Niclosamide found to inhibit Wnt/B-catenin signaling pathway, and thus promotion of apoptosis, in colorectal cancer cells in Vivo study.  It was also found to augment chemotherapeutic.
Nathan Goodyear

Estrogen Receptors in Colorectal Cancer: Goalkeepers, Strikers, or Bystanders? - 0 views

  • one can conclude that ERβ has an overall antiproliferative effect, thereby inhibiting cancer cell proliferation and antagonizing ERα function in the breast
  • HRT with estrogen alone did not increase the risk of breast cancer in the Women's Health Initiative clinical trials program
  • colorectal normal or cancer epithelium does not coexpress ERα and ERβ
  • ...7 more annotations...
  • ERβ expression resulted in the inhibition of proliferation and G1 phase cell-cycle arrest
  • ERβ expression strongly inhibited cMyc and tumor growth in a xenograft mouse model
  • induced ERβ in CRC cells has an antiproliferative, tumor-suppressive function that is independent of ERα
  • ERs also have the ability to bind many other compounds with an estrogen-like structure, including phytoestrogens and xenoestrogens (or endocrine disruptors)
  • Phytoestrogens are a diverse class of natural compounds with structural similarity to estradiol
  • Barone et al. recently found that two ERβ-selective phytoestrogens effectively counteracted CRC tumorigenesis and surprisingly increased ERβ expression in mice with mutations of the tumor-suppressor gene adenomatous polyposis coli
  • We can conclude that estrogens are important in protecting against CRC initiation and progression, and that the protective effect most likely is mediated by ERβ
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    ER beta is a new potential mode of therapy in colon cancer.  ER beta stimulation has been shown to inhibit colon cancer cell growth.
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

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    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
wheelchairindia9

Hand Driven Tricycle India - 0 views

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    Tricycle is also better and will enable the rider to make sharper turns on roads. Every time a person needs to be seated in a conventional tricycle or disembark from it, the needs help. But attached footrests to help the rider. With a bigger seat and stronger tyres, the vehicle will also help vendors. And every part of the cycle can be dismantled too, which makes it easier to transport. Although tricycles are often associated with toddlers, they are also widely ridden by adults. 'Trikes' are often ridden by older adults or people with disabilities who prefer the extra balance offered by a third wheel. Characteristics of Tricycles: Three wheels. Easily balanced. Brakes. Gears. Often have a storage basket at the rear. Can buy electric powered tricycles. In tricycles distinct types of pedal-driven motion. The tricycle was conceived and produced especially for children from the outset, however bicycles for children were derived by a simple reduction of the scale of the adult counterpart. Standard Single Hand Drive Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality Color : Black Painted Brake : Front Wheel liver System Drive : Rear Wheel Right Side Tricycle with rear wheel chain-driven transmission and a diamond shaped frame, it quickly entered into widespread use for transportation, work, and leisure purposes. Tricycles are available to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles make it possible for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider.
wheelchairindia9

Tricycle Manufacturers - 0 views

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    Tricycles make cycling accessible to all, whatever personal challenges. There are a wide range of disability cycles that suit people with a variety of learning and physical disabilities, as well as health issues. Tricycles have 3 wheels, which means that the rider does not need to be able to balance. This is particularly useful for people with learning disabilities, such as Dyspraxia, and those recovering from illnesses. Tricycles can be fitted with foot plates to make it easier for riders to rotate the pedals and they come in upright or recumbent (horizontal sitting position). For adults and children with balance issues, stabilisers can also be fitted to standard bikes, which makes them more like tricycles. Tricycles come in a variety of accessible styles for people of all abilities including many persons with spinal cord injury disabilities. Tricycles is a great upper body workout and can provide a great sense of freedom for persons with disabilities. While the high cost prevents many from enjoying Tricycles they are steadily growing in popularity. Tricycle Deluxe Double Hand Drive: Frame : Made by E.R.W. Tubes 38.0 mm-16 G. 25.4 mm & 22.22 mm- 18 G. Seat & Back: M S, C.R.C. Sheet. Seat Size 18"x 16" Wheel Size: Wheel Diameter 24"x 1 1/2" Tyre and Tube Standard Company. Parts: Standard Quality. Color: Black Painted. Brake: Front Wheel liver System Drive: Rear Wheel Right Side. Hand powered cycles work along the same principle as standard cycles. The pedals are replaced with handles that also steer, and riders use their arms to push the handles around to drive the chain and wheels. Most hand cycles have 3 wheels, although some have 4 wheels. 4-wheel cycles may have power assistance instead of the rider turning handles,or they may be built for going down hill, in which case gravity powers the bike. As with tricycles, hand cycles can have upright seats or low down recumbent seats. Specialist 'clip on' cycles are also available that can be attached
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

  •  
    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

  •  
    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
wheelchairindia9

A Friendly Tricycle For Disabled People - 0 views

  •  
    A tricycle for special needs is made so can go along for the ride in wheelchair or sitting in a special seat, both of which are attached right in front of another adult's trike. Tricycles to accommodate a vast array of special needs. Hand-pedaled recumbent tricycles are available for those without the use of their legs. Children, teens and adults with cerebral palsy and similar disorders can select tricycles specially designed to increase strength and coordination. Caregivers to autistic children can ride with their child on tandem special needs tricycles built to accommodate one adult and one child rider. Accessories are also available to convert standard trikes to suit specific needs. The objective of tricycle design is to produce wheelchairs that perform well and can provide appropriate seating and postural support without compromising strength, durability and safety. A Hand Driven Tricycle, abbreviated to trike is a three-wheeled passenger vehicle, usually carrying a single rider. The tricycle consists of a motorbike and an attached passenger sidecar and should not be confused with the tricycle. The trike is a motorized three-wheeled pedicab. Human-powered trikes are powered by pedals or hand cranks. Motorized trikes use motorcycle or scooter,or electric motors. Tricycles tend to be used for commercial purposes: such as "pedicabs" for transport passengers, and freight trikes for making deliveries. In the adult-sized tricycles are used primarily for recreation, shopping, and exercise. Tricycles are favoured by children and senior adults alike for their apparent stability versus a bicycle; but a conventional trike has poor dynamic lateral stability, and the rider must take care when cornering to avoid tipping the trike over. Standard Single Hand Driven Tricycle: Frame : Made by E.R.W. Tubes 22.22 mm- 18 G. Seat & Back : MS, CRC Sheet Seat Size 18"x 16" Wheel Size : Wheel Diameter 28"x 1 1/2" Tyre and Tube Standard Company. Parts : Standard Quality
Nathan Goodyear

Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxy... - 0 views

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    In KRAS + CRC, vitamin C downregulates PDK GLUT1, thereby increasing PD increasing Acetyl CoA production.
Nathan Goodyear

In Hyperthermia Increased ERK and WNT Signaling Suppress Colorectal Cancer Cell Growth - 0 views

shared by Nathan Goodyear on 16 Sep 20 - No Cached
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    Interesting study that hyperthermia >42C increased apoptosis in CRC cell line via increase in Wnt signaling.
Nathan Goodyear

PLOS ONE: Microbial Dysbiosis in Colorectal Cancer (CRC) Patients - 0 views

  • differences in the colon microbiota in individuals with colon cancer versus those with a normal colonoscopy
  • qPCR revealed significant elevation of the Bacteroides/Prevotella population in cancer patients that appeared to be linked with elevated IL17 producing cells in the mucosa of individuals with cancer.
  • Bacteroides genus populations and more specifically those of Bacteroides fragilis, have recently been shown to produce a metalloprotease in colon cancer patients, but not in controls [12] suggesting this species sub population might favor carcinogenesis
  • ...3 more annotations...
  • It is noteworthy that among the many mechanisms that may mediate associations between microbiota and human health [21]–[22], pro-inflammatory and immune cell activation in colon mucosa are of great importance in relation to malignancy
  • B. fragilis has been shown to induce mucosal regulatory T-cell responses in the intestine involving TH17 cell recruitment in experimental models
  • the elevations of Bacteroides in the stool and/or IL17 immunoreactive cells in the normal mucosa appear to be promising sensitive markers
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    A relationship between dysbiosis and colon cancer appears to be present.  Particularly an increase in Bacteroidetes and Prevotella species were found in those with colon cancer versus those without.  An inflammatory up regulation of IL-17 appears to be involved.  Whether this is a cause or effect is yet to be determined, but the presence of elevated Bacteroidetes species with increased IL17 could be used as sensitive biomarkers.
Nathan Goodyear

Dihydroartemisinin is potential therapeutics for treating late-stage CRC by targeting t... - 0 views

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    Ras mutation connected to abnormal expression of Myc
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