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Nathan Goodyear

The Contribution of Cytotoxic Chemotherapy to 5-year Survival in Adult Malignancies | C... - 0 views

www.scribd.com/...Survival-in-Adult-Malignancies

chemotherapy cancer

shared by Nathan Goodyear on 15 May 18 - No Cached
  • In this group, the 5-year survivalrateduesolelytocytotoxicchemotherapywas14%
  • There is also no convincing evidence that usingregimens with newer and more expensive drugs are anymore beneficial than the regimens used in the 1970s
  • two systematic reviews of chemotherapy inrecurrent or metastatic breast cancer have not been able toshow any survival benefit
  • ...12 more annotations...
  • The five most common adult malignancies (colorectal, breast, prostate, melanoma and lung cancer)
  • n breast cancer, the optimal regimen(s) for cytotoxicchemotherapy in recurrent/metastatic disease are still notdefined, despite over 30 years of ‘research’ and a plethora of RCTs since the original Cooper regimen was published in1969
  • The five most ‘chemo-sensitive’ cancers,namely testis, Hodgkin’s disease and non-Hodgkin’s lym- phoma, cervix and ovary
  • only 13 out of the 22 malignancies evaluated showed any improvement in 5-year survival, and theimprovement was greater than 10% in only three of those13 malignancies
  • the contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults is 2.3% in Australia and 2.1% in the USA
  • a benefit of less than 2.5% is likely to be applicable in other developed countries
  •   Overview The Contribution o
  • the benefit of cytotoxic chemotherapy may have been overestimated for cancers of oesophagus, stomach,rectum and brain.
  • this reflects the presentation of results as a ‘reduction in risk’ rather than asan absolute survival benefit[89,90]and by exaggerating theresponse rates by including ‘stable disease’
  • recent studies have documented impaired cognitive function inwomen receiving adjuvant treatment for breast cancer
  • the 5-year survival rate due solely to cytotoxicchemotherapy was 1.6%
  • the value of palliative chemotherapy has beenquestioned
  • Nathan Goodyear on 15 May 18
     
    Incredibly low impact of cytotoxic chemotherapy despite its wide spread utilization.  This article referenced cost yet did not evaluate the cost of cytotoxic side effect.  The question to answer: is Cytotoxic chemotherapy a valid treatment, at all, for the majority of cancers.
Nathan Goodyear

Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer t... - 0 views

www.sciencedirect.com/...S0960977617300103

HER-2 breast cancer cancer herceptin Perjeta

shared by Nathan Goodyear on 06 Aug 18 - No Cached
  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
  • ...15 more annotations...
  • shortened survival and an increased risk of disease recurrence and metastasis
  • Currently, four HER2-directed agents are approved for the treatment of patients with HER2+ breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1)
  • biosimilars
  • trastuzumab may provide greater benefit when administered concurrently with chemotherapy rather than after, and this has become the standard approach
  • concurrent use of anthracyclines (ie, doxorubicin or epirubicin) and trastuzumab is not recommended because of an increased risk for cardiac toxicity
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      avoid herceptin in conjuction with antracyclines i.e. doxorubicin
  • Sequential doxorubicin plus cyclophosphamide followed by concomitant paclitaxel or docetaxel and trastuzumab is recommended for most patients
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      top recommended regimen combination
  • Guidelines also recommend trastuzumab in combination with paclitaxel, docetaxel and carboplatin, or docetaxel and cyclophosphamide, particularly for patients with increased risk for cardiac toxicity or those with small (≤1 cm), node-negative HER2+ tumors
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      good alternative in patients with increased risk of cardiac toxicity.
  • guidelines recommend up to 1 year of adjuvant trastuzumab
  • Neoadjuvant chemotherapy with trastuzumab is associated with higher rates of pathologic complete response (pCR) than chemotherapy alone or in combination with lapatinib
  • the combination of trastuzumab, lapatinib, and chemotherapy is not recommended because it failed to demonstrate noninferiority versus trastuzumab and chemotherapy in the adjuvant setting
  • recommend the combination of trastuzumab, pertuzumab, and chemotherapy as neoadjuvant treatment for patients with locally advanced HER2+ breast cancer and for some patients (node-positive or tumor ≥2 cm) with early-stage disease
  • neoadjuvant chemotherapy in combination with pertuzumab and trastuzumab reduced the risk of progression or death by 31% and recurrence or death by 40% versus trastuzumab alone
  • Concurrent chemotherapy and HER2-directed therapy improves survival outcomes over chemotherapy alon
  • dual inhibition of HER2 with trastuzumab and pertuzumab in combination with paclitaxel reduced the risk of death or progression by approximately 40% compared with concurrent trastuzumab and paclitaxel
  • the combination of trastuzumab, pertuzumab, and taxane chemotherapy is the preferred first-line regimen
  • Nathan Goodyear on 06 Aug 18
     
    HER-2 + breast cancer = appx 15-20% of all breast cancers and is a marker of worse prognosis and an indication for targeted immunotherapy blockade.
Nathan Goodyear

http://chrisbeatcancer.com/wp-content/uploads/2011/12/contribution-of-chemotherapy-to-5... - 0 views

chrisbeatcancer.com/...therapy-to-5-year-survival.pdf

cancer chemotherapy

shared by Nathan Goodyear on 18 Feb 14 - No Cached
  • Nathan Goodyear on 18 Feb 14
     
    This study from 2004 reveals the marketing-based medicine era that we live in.  This meta-analysis of studies conducted for 5 year survival benefit found the contribution of chemotherapy was 2.3% in Australia and 2.1% in America.  The authors conclusion: "it is clear that cytotoxic chemotherapy only makes a minor contribution to cancer survival".  Compare this to the chemotherapy harm and the balance of benefit versus harm reveals a complete lack of evidence with regards to how therapy is practiced in Cancer
Nathan Goodyear

Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mecha... - 0 views

www.ncbi.nlm.nih.gov/...PMC5592784

Chemotherapy metastasis cancer TMEMs 'tumor microenvironment of metastasis' "chemotherapy metastasis"

shared by Nathan Goodyear on 22 Jan 19 - No Cached
  • Nathan Goodyear on 22 Jan 19
     
    Study looked at tumor microenvironment of metastasis structures (TMEMs) involved in metastasis. It has also been shown that taxane-based chemotherapies promote tumor regrowth by inducing angiogenesis. In this study, the tumor growth was slowed with taxanes chemotherapies, but it increased TMEMs and thus metastatic potential.
Nathan Goodyear

Antiangiogenic Scheduling of Chemotherapy Improves Efficacy against Experimental Drug-r... - 0 views

cancerres.aacrjournals.org/...1878

cancer metronomic chemotherapy angiogenesis MTD

shared by Nathan Goodyear on 26 Aug 20 - No Cached
  • Nathan Goodyear on 26 Aug 20
     
    Though not called metronomic chemotherapy, that is exactly what this was, reduced angiogenesis in chemo resistant tumors in mouse model. In fact, the higher dose intensity chemotherapy was less effective
Nathan Goodyear

Body weight change in women receiving adjuvant chemotherapy for breast cancer: A French... - 0 views

www.sciencedirect.com/...S0261561409001678

chemotherapy weight weight gain cancer metabolism

shared by Nathan Goodyear on 14 Jun 16 - No Cached
  • Nathan Goodyear on 14 Jun 16
     
    Weight gain found in patients post-chemotherapy.  The authors of this study, abstract only, attribute the association to pre-diagnosis weight gain.  It is know that chemotherapy negatively effects metabolism.
Nathan Goodyear

A CLINICAL-STUDY OF IMMUNOTHERAPY VERSUS ENDOCRINE THERAPY VERSUS CHEMOTHERAPY IN THE T... - 0 views

www.spandidos-publications.com/...1277

cancer IL-2 melatonin pancreatic cancer

shared by Nathan Goodyear on 10 May 18 - No Cached
  • Nathan Goodyear on 10 May 18
     
    Head to head study of IL-2 + melatonin versus chemotherapy in advanced pancreatic cancer found slightly better outcomes in the immunotherapy arm versus standard chemotherapy.  This difference was statistically significant.
Nathan Goodyear

Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Amo... - 0 views

www.ncbi.nlm.nih.gov/...PMC5885262

sarcoma hyperthermia cancer chemotherapy

shared by Nathan Goodyear on 25 Jan 21 - No Cached
  • Nathan Goodyear on 25 Jan 21
     
    Hyperthermia + chemotherapy significantly improves survival over chemotherapy alone.
Nathan Goodyear

Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tu... - 0 views

rupress.org/...erapy-prevents-therapy-induced

cancer metronomic chemotherapy low-dose chemotherapy

shared by Nathan Goodyear on 20 Sep 20 - No Cached
  • Nathan Goodyear on 20 Sep 20
     
    Great broad review of anti-cancer effects of low-dose metronomic chemotherapy
Nathan Goodyear

Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mecha... - 0 views

stm.sciencemag.org/...eaan0026

chemotherapy TMEM tumor microenvironment of metastasis metastasis cancer

shared by Nathan Goodyear on 11 Jul 17 - No Cached
  • We found about a twofold increase in circulating tumor cells (CTCs) (P < 0.05) after paclitaxel treatment in all experimental models examined
  • We found an increase in both the metastatic incidence (at least one micrometastatic focus of more than five tumor cells) (Fig. 3I) and the number of cancer cell micrometastases in the lungs of paclitaxel-treated mice
  • in early-stage breast cancers, chemotherapy increases vascular permeability at TMEM sites, which is accompanied by increased cancer cell dissemination.
  • ...1 more annotation...
  • significant ~1.3-fold (P = 0.027) increase in the number of CTCs
  • Nathan Goodyear on 11 Jul 17
     
    New study suggests chemotherapy may increase metastasis  via increase in TMEM.  I wonder if this increases recurrence as well.  Could the very corner stone of Cancer therapy actually increase metastatic risk potential?
Nathan Goodyear

Chemotherapeutic Dose Scheduling Based on Tumor Growth Rates Provides a Case for Low-Do... - 0 views

cancerres.aacrjournals.org/...6717

low-dose chemotherapy cancer metronomic chemotherapy

shared by Nathan Goodyear on 03 Jul 20 - No Cached
  • Nathan Goodyear on 03 Jul 20
     
    In many ways, it can be said that low-dose metronomic chemotherapy outperforms maximum tolerated chemotherapy.
Nathan Goodyear

Genetically targeted fractionated chemotherapy - 0 views

chemotherapy cancer fractionated chemotherapy low-dose chemotherapy insulin

shared by Nathan Goodyear on 03 Jul 20 - No Cached
  • Nathan Goodyear on 03 Jul 20
     
    Good article review on low-dose or fractionated chemotherapy.
Nathan Goodyear

Maximum Tolerable Dose and Low-Dose Metronomic Chemotherapy Have Opposite Effects on th... - 0 views

maximum tolerated chemotherapy low-dose chemotherapy metronomic chemotherapy

shared by Nathan Goodyear on 04 Oct 20 - No Cached
  • Nathan Goodyear on 04 Oct 20
     
    Only pdf available here. Start difference in the MTD to metronomic dosing of chemotherapy.
Nathan Goodyear

Metronomic chemotherapy offsets HIFα induction upon maximum‐tolerated dose in... - 0 views

www.embopress.org/...emmm.201911416

chemotherapy HIF-1α low-dose chemotherapy metastasis low-dose metronomic chemotherapy maxim to tolerated

shared by Nathan Goodyear on 07 Sep 23 - No Cached
  • Nathan Goodyear on 07 Sep 23
     
    MTD chemotherapy increases metastasis versus HIF-1alpha versus LDMC does not.
Nathan Goodyear

Arch Neurol -- Abstract: Prefrontal Cortex and Executive Function Impairments in Primar... - 0 views

archneur.ama-assn.org/...1447

chemotherapy brain fog side effects breast cancer executive function

shared by Nathan Goodyear on 13 Dec 11 - No Cached
  • Nathan Goodyear on 13 Dec 11
     
    Chemotherapy patients often complain of "chemo brain".  This article confirms significant reduction in prefrontal cortical activity, thus supporting brain dysfunction, "brain fog", as a result of chemotherapy.
Nathan Goodyear

http://www.spectracell.com/media/uploaded/2/0e2938319_1393442221_2132abstract2014nzmedj... - 0 views

www.spectracell.com/...s-with-high-dose-vitamin-c.pdf

IV vitamin C IV vitamin C intravenous cancer fatigue insomnia chemotherapy

shared by Nathan Goodyear on 03 Mar 14 - No Cached
  • Nathan Goodyear on 03 Mar 14
     
    IV vitamin C at 50 grams twice weekly shown to reduce side effects associated with chemotherapy.  Granted, this is a single case study without comparison, but this is supported by other studies.
Nathan Goodyear

Blocking IL1β Pathway Following Paclitaxel Chemotherapy Slightly Inhibits Pri... - 0 views

mct.aacrjournals.org/...1385.long

Chemotherapy cancer metastasis "chemotherapy metastasis"

shared by Nathan Goodyear on 22 Jan 19 - No Cached
  • Nathan Goodyear on 22 Jan 19
     
    IL1β levels are elevated in response to paclitaxel chemotherapy which is pro-metastatic.
Nathan Goodyear

Chemotherapy Enhances Metastasis Formation via VEGFR-1-Expressing Endothelial Cells | C... - 0 views

cancerres.aacrjournals.org/...6976.long

Chemotherapy "metastasis chemotherapy" metastasis cancer

shared by Nathan Goodyear on 23 Jan 19 - No Cached
  • Nathan Goodyear on 23 Jan 19
     
    Chemotherapy again found to increase metastasis in vitro and in vivo studies through the VEGF-1 expression
fnfdoc

Cancer Chemotherapy Via Drugs | Your Health Our Priority - 0 views

www.fnfdoc.com/...cancer-chemotherapy-via-drugs

Cancer Chemotherapy Treatment

shared by fnfdoc on 29 Apr 18 - No Cached
  • fnfdoc on 29 Apr 18
     
    How chemotherapy takes place? Depending on type of cancer and period of cancer, it stops cancer cells ability of damage and more to divide. Oftenly drugs are used and different for different person. This is systematic therapy also affect your entire body.
Nathan Goodyear

Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2... - 0 views

www.nature.com/...s41698-017-0044-8

cancer cancer stem cells liver cancer vitamin C IV vitamin C oncology

shared by Nathan Goodyear on 30 Jan 18 - No Cached
  • Chen et al. have revealed that ascorbate at pharmacologic concentrations (0.3–20 mM) achieved only by intravenously (i.v.) administration selectively kills a variety of cancer cell lines in vitro, but has little cytotoxic effect on normal cells.
  • Ascorbic acid (the reduced form of vitamin C) is specifically transported into cells by sodium-dependent vitamin C transporters (SVCTs)
  • SVCT-1 is predominantly expressed in epithelial tissues
  • ...41 more annotations...
  • whereas the expression of SVCT-2 is ubiquitous
  • differential sensitivity to VC may result from variations in VC flow into cells, which is dependent on SVCT-2 expression.
  • high-dose VC significantly impaired both the tumorspheres initiation (Fig. 4d, e) and the growth of established tumorspheres derived from HCC cells (Fig. 4f, g) in a time-dependent and dose-dependent manner.
  • Hepatocellular carcinoma (HCC)
  • The antioxidant, N-acetyl-L-cysteine (NAC), preventing VC-induced ROS production (a ROS scavenger), completely restored the viability and colony formation among VC-treated cells
  • DNA double-strand damage was found following VC treatment
  • DNA damage was prevented by NAC
  • Interestingly, the combination of VC and cisplatin was even more effective in reducing tumor growth and weight
  • Consistent with the in vitro results, stemness-related genes expressions in tumor xenograft were remarkably reduced after VC or VC+cisplatin treatment, whereas conventional cisplatin therapy alone led to the increase of CSCs
  • VC is one of the numerous common hepatoprotectants.
  • Interestingly, at extracellular concentrations greater than 1 mM, VC induces strong cytotoxicity to cancer cells including liver cancer cells
  • we hypothesized that intravenous VC might reduce the risk of recurrence in HCC patients after curative liver resection.
  • Intriguingly, the 5-year disease-free survival (DFS) for patients who received intravenous VC was 24%, as opposed to 15% for no intravenous VC-treated patients
  • Median DFS time for VC users was 25.2 vs. 18 months for VC non-users
  • intravenous VC use is linked to improved DFS in HCC patients.
  • In this study, based on the elevated expression of SVCT-2, which is responsible for VC uptake, in liver CSCs, we revealed that clinically achievable concentrations of VC preferentially eradicated liver CSCs in vitro and in vivo
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      the authors here made similar mistakes to the Mayo authors i.e. under doses here in this study.  They dosed at only 2 grams IVC.  A woefully low dose of IVC.
  • Additionally, we found that intravenous VC reduced the risk of post-surgical HCC progression in a retrospective cohort study.
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      positive results despite a low dose used.
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      Their comfort zone was 1mM.  They should have targeted 20-40 mM.
  • Three hundred thirty-nine participants (55.3%) received 2 g intravenous VC for 4 or more days after initial hepatectomy
  • As the key protein responsible for VC uptake in the liver, SVCT-2 played crucial roles in regulating the sensitivity to ascorbate-induced cytotoxicity
  • we also observed that SVCT-2 was highly expressed in human HCC samples and preferentially elevated in liver CSCs
  • SVCT-2 might serve as a potential CSC marker and therapeutic target in HCC
  • CSCs play critical roles in regulating tumor initiation, relapse, and chemoresistance
  • we revealed that VC treatment dramatically reduced the self-renewal ability, expression levels of CSC-associated genes, and percentages of CSCs in HCC, indicating that CSCs were more susceptible to VC-induced cell death
  • as a drug for eradicating CSCs, VC may represent a promising strategy for treatment of HCC, alone or particularly in combination with chemotherapeutic drugs
  • In HCC, we found that VC-generated ROS caused genotoxic stress (DNA damage) and metabolic stress (ATP depletion), which further activated the cyclin-dependent kinase inhibitor p21, leading to G2/M phase cell cycle arrest and caspase-dependent apoptosis in HCC cells
  • we demonstrated a synergistic effect of VC and chemotherapeutic drug cisplatin on killing HCC both in vitro and in vivo
  • Intravenous VC has also been reported to reduce chemotherapy-associated toxicity of carboplatin and paclitaxel in patients,38 but the specific mechanism needs further investigation
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      so, exclude the benefit to patients until the exact mechanism of action, which will never be fully elicited?!?!?
  • Our retrospective cohort study also showed that intravenous VC use (2 g) was related to the improved DFS in HCC patients after initial hepatectomy
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      Terribly inadequate dose.  Target is 20-40 mM which other studies have found occur with 50-75 grams of IVC.
  • several clinical trials of high-dose intravenous VC have been conducted in patients with advanced cancer and have revealed improved quality of life and prolonged OS
  • high-dose VC was not toxic to immune cells and major immune cell subpopulations in vivo
  • high recurrence rate and heterogeneity
  • tumor progression, metastasis, and chemotherapy-resistance
  • SVCT-2 was highly expressed in HCC samples in comparison to peri-tumor tissues
  • high expression (grade 2+/3+) of SVCT-2 was in agreement with poorer overall survival (OS) of HCC patients (Fig. 1c) and more aggressive tumor behavior
  • SVCT-2 is enriched in liver CSCs
  • these data suggest that SVCT-2 is preferentially expressed in liver CSCs and is required for the maintenance of liver CSCs.
  • pharmacologic concentrations of plasma VC higher than 0.3 mM are achievable only from i.v. administration
  • The viabilities of HCC cells were dramatically decreased after exposure to VC in dose-dependent manner
  • VC and cisplatin combination further caused cell apoptosis in tumor xenograft
  • These results verify that VC inhibits tumor growth in HCC PDX models and SVCT-2 expression level is associated with VC response
  • qPCR and IHC analysis demonstrated that expression levels of CSC-associated genes and percentages of CSCs in PDXs dramatically declined after VC treatment, confirming the inhibitory role of VC in liver CSCs
  • Nathan Goodyear on 30 Jan 18
     
    IV vitamin C in vitro and in vivo found to "preferentially" eradicate cancer stem cells.  In addition, IV vitamin C was found to be adjunctive to chemotherapy, found to be hepatoprotectant.  This study also looked at SVCT-2, which is the transport protein important in liver C uptake.
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