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Nathan Goodyear

Substantial contribution of extrinsic risk factors to cancer development - 0 views

  • Here we provide evidence that intrinsic risk factors contribute only modestly (<10~30%) to cancer development
  • we conclude that cancer risk is heavily influenced by extrinsic factors. These results carry immense consequences for strategizing cancer prevention
  • cancers are proposed to originate from the malignant transformation of normal tissue progenitor and stem cells
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  • “Intrinsic processes” include those that result in mutations due to random errors in DNA replication whereas “extrinsic factors” are environmental factors that affect mutagenesis rates (such as UV radiation, ionizing radiation, and carcinogens
  • intrinsic factors do not play a major causal role.
  • intrinsic cancer risk should be determined by the cancer incidence for those cancers with the least risk in the entire group controlling for total stem cell divisions
  • if one or more cancers would feature a much higher cancer incidence, for example, lung cancer among smokers vs. non-smokers, then this most likely reflects additional (and probably extrinsic) risk factors (smoking in this case)
  • Particularly, for breast and prostate cancers, it has long been observed that large international geographical variations exist in their incidences (5-fold for breast cancer, 25-fold for prostate cancer)14, and immigrants moving from countries with lower cancer incidence to countries with higher cancer rates soon acquire the higher risk of their new country
  • Colorectal cancer is another high-incidence cancer that is widely considered to be an environmental disease17, with an estimated 75% or more colorectal cancer risk attributable to diet
  • melanoma, its risk ascribed to sun exposure is around 65–86%
  • non-melanoma basal and squamous skin cancers, ~90% is attributable to UV
  • 75% of esophageal cancer, or head and neck cancer are caused by tobacco and alcohol
  • HPV may cause ~90% cases in cervical cancer23, ~90% cases in anal cancer24, and ~70% in oropharyngeal cancer
  • HBV and HCV may account for ~80% cases of hepatocellular carcinoma
  • H pylori may be responsible for 65–80% of gastric cancer
  • While a few cancers have relatively large proportions of intrinsic mutations (>50%), the majority of cancers have large proportions of extrinsic mutations, for example, ~100% for Myeloma, Lung and Thyroid cancers and ~80–90% for Bladder, Colorectal and Uterine cancers, indicating substantial contributions of carcinogen exposures in the development of most cancers
  • onsistent estimate of contribution of extrinsic factors of >70–90% in most common cancer types. This concordance lends significant credibility to the overall conclusion on the role of extrinsic factors in cancer development
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    Really great read.  Cancer is a majority lifestyle disease.
Nathan Goodyear

Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside - 0 views

  • MAF precursor activity has also been lost or reduced after Gc-globulin treatment in some cancer cell lines
  • This appears to result from the deglycosylated ɑ-N-acetylgalactosaminidase (nagalase) secreted from cancerous cells
  • Nagalase has been detected in many cancer patients, but not in healthy individuals
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  • Studies have shown that the production of nagalase has a mutual relationship with Gc-MAF level and immunosuppression
  • It has been demonstrated that serum levels of nagalase are good prognosticators of some types of cancer
  • The nagalase level in serum correlates with tumor burden and it has been shown that Gc-MAF therapy progresses, nagalase activity decreases
  • It has been shown that Gc-MAF can inhibit the angiogenesis induced by pro-inflammatory prostaglandin E1
  • The effect of Gc-MAF on chemotaxis or activation of tumoricidal macrophages is likely the main mechanism against angiogenesis.
  • Administration of Gc-MAF stimulates immune-cell progenitors for extensive mitogenesis, activates macrophages and produces antibodies. “This indicates that Gc-MAF is a powerful adjuvant for immunization.”
  • Cancer cell lines do not develop into tumor genes in mouse models after Gc-MAF-primed immunization (29-31) and the effect of Gc-MAF has been approved for macrophage stimulation for angiogenesis, proliferation, migration and metastatic inhibition on tumors induced by MCF-7 human breast cancer cell line
  • The protocol included: "a high dose of second-generation Gc-MAF (0.5 ml) administered twice a week intramuscularly for a total of 21 injections.”
  • Yamamoto et al. showed that the administration of Gc-MAF to 16 patients with prostate cancer led to improvements in all patients without recurrence
  • Inui et al. reported that a 74-year-old man diagnosed with prostate cancer with multiple bone metastases was in complete remission nine months after initiation of GcMAF therapy simultaneously with hyper T/NK cell, high-dose vitamin C and alpha lipoic acid therapy
  • It has also been approved for non-neoplastic diseases such as autism (41), multiple sclerosis (42, 43), chronic fatigue syndrome (CFS) (40), juvenile osteoporosis (44) and systemic lupus erythematous (45).
  • Gc-MAF has been verified for use in colon, thyroid (38), lung (39), liver, thymus (36), pancreatic (40), bladder and ovarian cancer and tongue squamous carcinoma
  • Prostate, breast, colon, liver, stomach, lung (including mesothelioma), kidney, bladder, uterus, ovarian, head/neck and brain cancers, fibrosarcomas and melanomas are the types of cancer tested thus far
  • weekly administration of 100 ng Gc-MAF to cancer at different stages and types showed curative effects at different follow-up times
  • this treatment has been suggested for non-anemic patients
  • Studies have shown that weekly administration of 100 ng Gc-MAF to cancer patients had curative effects on a variety of cancers
  • Because the half-life of the activated macrophages is approximately one week, it must be administered weekly
  • In vivo weekly intramuscular administration of Gc-MAF (100 ng) for 16-22 weeks was used to treat patients with breast cancer
  • individuals harboring different VDR genotypes had different responses to Gc-MAF and that some genotypes were more responsive than others
  • Administration of Gc-MAF for cancer patients exclusively activates macrophages as an important cell in adaptive immunity
  • Gc-MAF supports humoral immunity by producing, developing and releasing large quantities of antibodies against cancer. Clinical evidence from a human model of breast cancer patients supports this hypothesis
  • There is also evidence that confirms the tumoricidal role of Gc-MAF via Fc-receptor mediation
  • It is likely that the best therapeutic responses will be observed when the nutritional and inflammatory aspects are taken together with stimulation of the immune system
  • it should be noted that no harmful side effects of Gc-MAF treatment have been reported, even when it was successfully administered to autistic children
  • The natural activation mechanism of macrophages by Gc-MAF is so natural and it should not have any side effects on humans or animal models even in cell culture
  • Besides the Gc-MAF efficacy on macrophage activity, it can be a potential anti-angiogenic agent (28) and an inhibitor of the migration of cancerous cells in the absence of macrophages (47).
  • Activating or modifying natural killer cells, dendritic cells, DC, CTL, INF and IL-2 have all been recommended for cancer immunotherapy
  • It has been reported that nagalase cannot deglycosylate Gc-MAF as it has specificity for Gc globulin alone
  • inflammation-derived macrophage activation with the participation of B and T lymphocytes is the main mechanism
  • macrophages highly-activated by the addition of Gc-MAF can show tumoricidal activity
  • Previous clinical investigations have confirmed the efficacy of Gc-MAF. In addition to activating existing macrophages, Gc-MAF is a potent mitogenic factor that can stimulate the myeloid progenitor cells to increase systemic macrophage cell counts by 40-fold in four days
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    great review on Gc-MAF in cancer.  An increase in nagalase blocks Gc-protein to Gc-MAF activity leaving the host immune system compromised.
Nathan Goodyear

Sex hormones in head and neck cancer: Current knowledge and perspectives Singh HP, Kuma... - 0 views

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    Sex hormones in head and neck cancer.  The jury is still out and probably follows other hormone sensitive cancers.  
Nathan Goodyear

Early Detection of Head and Neck Cancer: Development of a Novel Screening Tool Using Mu... - 0 views

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    Article looks at proposed 25 biomarkers to screen for Head and Neck squamous cancer.  Most of these could be used for all cancers as they are inflammatory cytokines.
Nathan Goodyear

Sleep-Related Breathing Disorders in Patients With Tumors in the Head and Neck Region - 0 views

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    Head and neck cancer patients often struggle with sleep apnea.
Nathan Goodyear

Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cel... - 0 views

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    Nrf2 inhibition decreased chemoresistance to artesunate in Patients with head and neck cancer resistant to cisplatin.
Nathan Goodyear

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multi... - 0 views

  • Patients received a median of six doses of nivolumab
  • four of the first 12 patients had partial responses
  • Nine (24% [95% CI 15–33]) of 37 patients achieved a response (seven partial responses and two complete responses
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  • no treatment-related deaths
  • the most common adverse events were anaemia (26 [70%]), fatigue (25 [68%]), and rash
  • hypothyroidism
  • hypothyroidism
  • nivolumab-related autoimmune hypothyroidism, which resolved after a short course of corticosteroids
  • No grade 3 or 4 adverse events occurred
  • Nivolumab resulted in objective responses in 24% of patients with metastatic SCCA
  • Historically, doublet chemotherapy with cisplatin and fluorouracil has been the most common treatment for patients with metastatic SCCA
  • our results suggest that immune checkpoint blockade agents might extend overall survival beyond currently available therapies, especially if provided early in the disease treatment course
  • the dose of nivolumab we used differs from the 2016 recommendation of a fixed 240 mg every 2 weeks
  • 25% of patients develop distant metastases
  • most patients with localised SCCA are cured by chemoradiation
  • More than 90% of cases of SCCA are linked to prior infection with human papillomavirus (HPV)
  • Within tumour cells, HPV oncoproteins are immunogenic and can trigger an anti-tumour host immune response by recruitment of tumour-infiltrating lymphocytes
  • Tumour cells express PD-L1 and, on binding its inhibitory receptor PD-1 on the surface of T cells, downregulate T-cell activation and thwart the local anti-tumour immune response
  • Nivolumab is a humanised monoclonal antibody against PD-1 that disrupts this interaction, enabling T-cell cytotoxicity. It has activity as a monotherapy in advanced solid cancers, such as head and neck cancer, melanoma, non-small-cell lung cancer, and renal cell carcinoma
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    study finds nivolumab helpful in some patients with surgically unresectable or metastatic anal cancer.  The dose used was 3 mg/kg every 2 weeks. 
Nathan Goodyear

FDG-PET/CT imaging biomarkers in head and neck squamous cell carcinoma - 0 views

  • F-fluoro-2-deoxyglucose (FDG) PET/CT is sensitive for the diagnosis and initial staging of several types of malignancies
  • SUV is a semiquantitative measure of the normalized concentration of radioactivity in a tumor or lesion
  • As FDG is the most common radiotracer used clinically and reflects tumor glucose metabolism, SUV is used as a surrogate marker for tumor metabolism.
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  • primary tumor SUVmax >10 predicted survival, independent of the tumor stage and diameter
  • advanced tumors tend to have higher FDG uptake (and thus higher SUV values)
  • the impact of the SUV on treatment outcome has been observed even within a given tumor stage
  • The association between FDG uptake and tumor burden or stage has been well documented
  • FDG uptake not only reflects tumor burden/stage but also expresses, at least in part, some intrinsic biologic characteristic(s) of the tumor
  • SUVmax reflects the highest voxel value within the ROI or VOI. It is the most widely used parameter to measure metabolic tumor activity in oncologic FDG-PET/CT imaging
  • Several studies suggest that primary tumor baseline SUVmax also has predictive value in assessing the tumor burden, lymph node involvement and local extension
  • According to EORTC, a drop (delta between baseline and post-therapy) of 15–25% in SUVmax may represent a good treatment response
  • PERCIST criteria was proposed by the investigators at the Johns Hopkins Medical Institutions and suggested that a decrease in SUV normalized to lean body mass of at least 30% should be achieved before considering partial tumor response
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    Good review of PET/CT scan and MaxSUV in head and neck cancers.
Nathan Goodyear

Intraperitoneal Oxidative Stress in Rabbits with Papillomavirus-Associated Head and Nec... - 0 views

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    O2-O3 triggers tumoricidal immune response after application of a repetitive highly oxidative stimulus by insufflation of a medical O3/O2 gas mixture into the peritoneal cavity in animal model. O3/O2-PP treatment, indicates an enhanced activation of the innate and adaptive arms of the immune system, implicating a role of activated TILs In the anti cancer effects of the O3. Interestingly, COX2 expression was decreased.
Nathan Goodyear

Decline of lactate in tumor tissue after ketogen... [Nutr Cancer. 2013] - PubMed - NCBI - 0 views

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    Small study specifically looked at Head and Neck Cancer.  The study found a reduction in lactate in tumor tissue after just 3 days of ketogenic diet.
Nathan Goodyear

http://ar.iiarjournals.org/content/25/3A/1539.full.pdf - 0 views

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    No correlation between SCC, CEA and CYFRA 21-1 found in metastatic head and neck cancer.
Nathan Goodyear

Cannabinoids Promote Progression of HPV-Positive Head and Neck Squamous Cell Carcinoma ... - 0 views

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    THC stimulates p38/MAPK signaling to inhibit apoptosis via CB agonism; good thing CBD is a reverse agonist on CB receptors.
Nathan Goodyear

Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell car... - 1 views

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    To be read
Nathan Goodyear

Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell car... - 1 views

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    Nice review of the tumor microenvironment in the treatment of cancer.
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