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Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...PMC4836858

cancer lifestyle

shared by Nathan Goodyear on 03 Jan 18 - No Cached
  • 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
  • ...14 more annotations...
  • “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
  • Nathan Goodyear on 03 Jan 18
     
    Really great read.  Cancer is a majority lifestyle disease.
pharmacybiz

MHRA Approves Life-Saving Zolbetuximab for Gastric & Gastro-Oesophageal Cancer - New Ho... - 0 views

www.pharmacy.biz/...ro-oesophageal-junction-cancer

Zolbetuximab-approval-UK MHRA-new-cancer-treatment-gastric-cancer-treatment-UK gastro-oesophageal-cancer-therapy monoclonal-antibody-cancer-treatment

shared by pharmacybiz on 16 Aug 24 - No Cached
  • pharmacybiz on 16 Aug 24
     
    A new cancer treatment for adults with stomach (gastric) and gastro oesophageal junction cancer has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) this week. According to the MHRA, Zolbetuximab, a monoclonal antibody, is designed to target and destroy specific cancer cells, offering a new option for patients whose cancer is inoperable or has spread. The new targeted cancer treatment for gastric and gastro-oesophageal junction cancer is administered intravenously in combination with standard chemotherapy regimens and is typically given every two to three weeks under the supervision of an experienced oncologist. Zolbetuximab is indicated for patients whose tumors are positive for the Claudin18.2 (CLDN18.2) protein and negative for the Human epidermal growth factor receptor 2 (HER2) protein.
Nathan Goodyear

Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expec... - 0 views

www.nature.com/ja201711

Ivermectin cancer

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • The avermectins are known to possess pronounced antitumor activity
  • Over the past few years, there have been steadily increasing reports that ivermectin may have varying uses as an anti-cancer agent, as it has been shown to exhibit both anti-cancer and anti-cancer stem cell properties
  • In human ovarian cancer and NF2 tumor cell lines, high-dose ivermectin inactivates protein kinase PAK1 and blocks PAK1-dependent growth
  • ...13 more annotations...
  • PAK1 is essential for the growth of more than 70% of all human cancers, including breast, prostate, pancreatic, colon, gastric, lung, cervical and thyroid cancers, as well as hepatoma, glioma, melanoma, multiple myeloma and for neurofibromatosis tumors
  • Ivermectin suppresses breast cancer by activating cytostatic autophagy, disrupting cellular signaling in the process, probably by reducing PAK1 expression
  • Cancer stem cells are a key factor in cancer cells developing resistance to chemotherapies and these results indicate that a combination of chemotherapy agents plus ivermectin could potentially target and kill cancer stem cells, a paramount goal in overcoming cancer
  • Triple-negative breast cancers, which lack estrogen, progesterone and HER2 receptors, account for 10–20% of breast cancers and are associated with poor prognosis
  • Ivermectin addition led to transcriptional modulation of genes associated with epithelial–mesenchymal transition and maintenance of a cancer stem cell phenotype in triple-negative breast cancers cells, resulting in impairment of clonogenic self-renewal in vitro and inhibition of tumor growth and metastasis in vivo
  • ivermectin synergizes with the chemotherapy agents cytarabine and daunorubicin to induce cell death in leukemia cells
  • Ivermectin-induced cytostatic autophagy also leads to suppression of tumor growth in breast cancer xenografts, causing researchers to believe there is scope for using ivermectin to inhibit breast cancer cell proliferation and that the drug is a potential treatment for breast cancer
  • Ivermectin inhibits proliferation and increases apoptosis of various human cancers
  • Activation of WNT-TCF signaling is implicated in multiple diseases, including cancers of the lungs and intestine,
  • A new screening system has found that ivermectin inhibits the expression of WNT-TCF targets
  • It represses the levels of C-terminal β-catenin phosphoforms and of cyclin D1 in an okadaic acid-sensitive manner, indicating its action involves protein phosphatases
  • In vivo, ivermectin selectively inhibits TCF-dependent, but not TCF-independent, xenograft growth without side effects
  • ivermectin has an exemplary safety record, it could swiftly become a useful tool as a WNT-TCF pathway response blocker to treat WNT-TCF-dependent diseases, encompassing multiple cancers.117
  • Nathan Goodyear on 19 Mar 18
     
    Ivermectin shows promise and usefullness in several cancer types.  This is a review article.
Nathan Goodyear

Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Ca... - 0 views

clincancerres.aacrjournals.org/...4441

EBV Epstein-Barr virus gastric cancer cancer

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • Nathan Goodyear on 18 Jun 18
     
    EBV gastric cancer found to be associated with the best prognosis.
Nathan Goodyear

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epitheli... - 0 views

www.pnas.org/E7301

Ivermectin cancer ovarian cancer oncogene oncogenes

shared by Nathan Goodyear on 20 Mar 18 - No Cached
  • we functionally validated a potent EOC oncogene, KPNB1, and showed its clinical relevance to human EOC
  • a well-established antiparasitic drug, ivermectin, has antitumor effects on EOC through its inhibition of KPNB1
  • EOC has high intertumor and intratumor heterogeneity at the molecular and epigenetic levels
  • ...22 more annotations...
  • the mortality rate of EOC has not been significantly changed for several decades
  • Sequencing revealed that almost all tumors (96%) had mutations in TP53, which serves as a major driver of this cancer
  • Low-prevalence but statistically significant mutations in nine other genes including NF1, BRCA1, BRCA2, RB1, and CDK12 were also identified, but the majority of genes were mutated at low frequency, making it difficult to distinguish between driver and passenger mutations
  • KPNB1 inhibition via any of three KPNB1 siRNAs or importazole treatment induced apoptosis in human EOC cell lines (Fig. 3 A–F and Fig. S4), and was accompanied by an increase in the expression levels of the proapoptotic proteins BAX and cleaved caspase-3
  • Stable overexpression of KPNB1 in SKOV3 and OVCAR3 (Fig. S6) significantly accelerated cell proliferation/survival (Fig. 5 A–C), confirming that KPNB1 functions as an oncogene in EOC
  • KPNB1 overexpression significantly decreased caspase-3/7 activity (Fig. 5D), in addition to the expression levels of cleaved caspase-3 and BAX proteins (Fig. 5E). KPNB1 overexpression also decreased p21 and p27 protein levels (Fig. 5E), as opposed to their increase by KPNB1 inhibition
  • KPNB1 functions as an antiapoptotic and proproliferative oncogene in EOC.
  • Patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1
  • KPNB1 acts as an oncogene in human EOC and represents a promising therapeutic target.
  • ivermectin treatment suppressed cell proliferation/viability in a dose-dependent manner (Fig. 7A), indicating that it exerts an antitumor effect on EOC
  • ivermectin also induced apoptosis
  • ivermectin increased the expression levels of BAX, and cleaved PARP, as well as p21 and p27
  • KPNB1 inhibition is responsible for the antitumor effect of ivermectin
  • we found that ivermectin synergistically reduced cell proliferation/viability in combination with paclitaxel in human EOC cells
  • Single treatment of ivermectin or paclitaxel reduced tumor growth in nude mice, but, notably, combination treatment of ivermectin and paclitaxel almost completely suppressed tumor growth
  • ERBB2, is amplified and overexpressed in many cancers, including breast (31), ovary (31), colon (32), bladder (33), non-small-cell lung (34), and gastric cancer (35), and is a poor prognostic factor in certain cancer types
  • KPNB1 was the second-highest-ranked gene identified in our screen
  • Increased KPNB1 protein levels have been reported in several cancers, including cervical cancer (42), hepatocellular carcinoma (43), and glioma (44), suggesting KPNB1’s oncogenic potential in these tumor types
  • our findings suggest that KPNB1 might serve as a master regulator of cell cycle by regulating several cell cycle-related proteins, including p21, p27, and APC/C family members
  • higher and/or more-frequent doses of ivermectin than currently approved for humans are well tolerated in humans
  • none of the mice in this study treated with the effective dosage of ivermectin for in vivo anticancer therapy showed severe adverse event
  • we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC cell lines than either drug alone
  • Nathan Goodyear on 20 Mar 18
     
    Ivermectin found to be pro-apoptotic for the epithelial ovarian cancer oncogene, KPNB1 in in Vivo study.  This effective anti-parasitic drug inhibits the KPNB1 oncogene.
Nathan Goodyear

Hyperthermia as an immunotherapy strategy for cancer - 1 views

www.ncbi.nlm.nih.gov/...PMC2828267

cancer hyperthermia

shared by Nathan Goodyear on 29 Nov 18 - No Cached
  • the notion of treating human cancers with heat dates back to the writings of Hippocrates
  • enhance the efficiency of standard cancer therapies, such as chemotherapy and radiation treatment
  • After antigen uptake at tumor sites, APCs have the ability to create a robust response by entering lymphoid compartments and programming lymphocytes
  • ...36 more annotations...
  • Hyperthermia differs fundamentally from fever in that it elevates the core body temperature without changing the physiological set point
  • hyperthermia is induced by increasing the heat load and/or inactivating heat dissipation
  • mor cells [2]. Although significant cell killing could be achieved by heating cells or tissues to temperatures > 42°C for 1 or more hours, the application, measurement and consistency of this temperature range within the setting of cancer clinical trials
  • mild temperature hyperthermia (ie, within the fever-range, 39–41°C)
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      101.2 to 105.8
  • moderate hyperthermia (41°C)
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      105.8 F
  • Hsps are a family of stress-induced proteins
  • they are key regulators of cellular protein activity, turnover and trafficking
  • Hsps ensure appropriate post-translational protein folding, and are able to refold denatured proteins, or mark irreversibly damaged proteins for destruction
  • the ability of fever-range hyperthermia to induce reactive immunity against tumor antigens through DCs and NK-cells is likely mediated by Hsps
  • thermotolerance
  • Hsps support the malignant phenotype of cancer cells by not only affecting the cells’ survival, but also participating in angiogenesis, invasion, metastasis and immortalization mechanisms
  • Hsps released from stressed or dying cells activate dendritic cells (DCs), transforming them into mature APCs
  • In theory, fever-range hyperthermia may take advantage of tumor cell Hsps by inducing their release from tumor cells and augmenting DC priming against tumor antigens
  • In several models of hyperthermia, heat-treated tumors exhibited improved DC priming and generation of systemic immunity to tumor cell
  • hyperthermia alone can enhance antigen display by tumor cells, thus rendering them even more susceptible to programmed immune clearance
  • Fever-range hyperthermia may also induce Hsps
  • Hsps may exert an adjuvant effect by bolstering MHC class II and co-stimulatory molecule expression by DCs
  • thermal ablation of liver tumors in particular has demonstrated an ability to potentiate immune responses [57, 58] and elicit robust T-cell infiltrates at ablation sites
  • specific Hsp, Hsp70, directly inhibits apoptosis pathways in cancer cells, as demonstrated in human pancreatic, prostate and gastric cancer cells
  • Cross-priming is the ability of extracellular Hsps complexed to tumor peptides to be internalized and presented in the context of MHC class I molecules on APCs, thus allowing potent priming of CTLs against tumor antigens
  • It has been reported that Hsps are generated from necrotic tumor cell lysates, but not from tumor cells undergoing apoptosis
  • tumor cells exposed to hyperthermia in the heat shock range (42°C for 4h) prior to lysing, DC activation and cross-priming were significantly enhanced with the application of heat
  • Due to the ability of Hsps to activate DCs directly by chaperoning tumor antigens upon their release [28], it is possible that both local and regional immune stimulation can be achieved with hyperthermia.
  • support the use of hyperthermia as an inducer of Hsps to serve as ‘danger signals’, activating antitumor immune responses
  • whole-body hyperthermia not only augments immune responses, but also stimulates the migration of skin-derived DCs to draining lymph nodes
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      This allows for the activation of lymphocytes by the activated dendritic cells.
  • suggest a valuable role of hyperthermia in DC cancer vaccine strategies
  • In mice treated with fever-range whole-body hyperthermia, tumor growth was significantly inhibited and NK-cell infiltration increased
    • Nathan Goodyear
      Nathan Goodyear on 04 Aug 19
       
      Hyperthermia increased NK cell activation, proliferation, and infiltration, which equals increased cytotoxicity.
  • exposure to fever-range hyperthermia resulted in improved endogenous NK-cell cytotoxicity to several cancer types
  • improved activation and function of DCs and NK cells following hyperthermia
  • Hyperthermia increases the expression ICAM-1 a key adhesion molecule,
  • The combined effects of hyperthermia on lymphoid tissue endothelium and lymphocytes can promote immune surveillance and increase the probability of naive lymphocytes leaving the circulation and encountering their cognate antigen displayed by DCs in lymphoid organs.
  • In independent clinical studies, whole-body hyperthermia resulted in a transient decrease in circulating lymphocytes in patients with advanced cancer [12, 94, 99, 100], a finding which mirrored observations in animal models in which lymphocyte entry into lymph noeds was increased following hyperthermia treatment [93]. Enhanced recruitment of lymphocytes to lymphoid tissues may be exploited in the treatment of malignancies.
  • The initial tumor antigen presentation and initiation of clonal expansion of CTLs transpires in the lymph nodes and cannot take place outside this specialized compartment
  • the ability of DCs present in the lymph nodes to stimulate an anti-tumor immune response is critical
  • hyperthermia has been shown to improve immune surveillance by T-cell
  • and to increase DC trafficking to lymph nodes
  • Nathan Goodyear on 29 Nov 18
     
    Great review of hyperthermia.
Nathan Goodyear

Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by d... - 0 views

www.ncbi.nlm.nih.gov/...PMC4406257

gastric cancer COX2 artesunate

shared by Nathan Goodyear on 07 May 20 - No Cached
  • Nathan Goodyear on 07 May 20
     
    Artesunate inhibits gastric cancer cells via COX2 inhibition.
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...PMC5718030

chloroquine hydroxychloroquine cancer repurposed drugs

shared by Nathan Goodyear on 03 May 21 - No Cached
  • 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
Nathan Goodyear

Inhibitory effect of S-adenosylmethionine on the growth of human gastric cancer cells i... - 0 views

www.cjcsysu.cn/...752.pdf

SAMe cancer gastric cancer methylation

shared by Nathan Goodyear on 27 Jun 12 - No Cached
  • Nathan Goodyear on 27 Jun 12
     
    SAMe show a decrease in gastric cell growth in vitro and in vivo studies. This appears to be secondary to the resolved hypomethylation status of the c-myc and the uPA genes.
Nathan Goodyear

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with meta... - 0 views

www.ncbi.nlm.nih.gov/...PMC6524297

cancer IV vitamin C vitamin C

shared by Nathan Goodyear on 30 Jul 19 - No Cached
  • Nathan Goodyear on 30 Jul 19
     
    IV vitamin C shown to be adjunctive with the chemotherapy regimens FOLFIRI and FOLFOX in colorectal and gastric cancer despite the therapeutic dose limited to 1.5 mg/kg/day, which is a low dose likely resulting in sub-therapeutic levels.
Nathan Goodyear

Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in ... - 0 views

www.ncbi.nlm.nih.gov/...PMC4560272

RIGVIR cancer oncolytic therapy immunotherapy cancer immunotherapy

shared by Nathan Goodyear on 16 Oct 18 - No Cached
  • Rigvir is a 2 ml frozen solution
  • ECHO-7 virus strain, Picornaviridae family, Enterovirus genus, Enteric Cytopathic Human Orphan (ECHO) type 7, group IV, positive-sense single-stranded RNA virus
  • a few side effects were reported, for example subfebrile temperature (37.5°C for a couple of days), pain in the tumour area, sleepiness and diarrhoea
  • ...12 more annotations...
  • In this retrospective study, however, there was no record of any untoward side effect from Rigvir treatment or its discontinuation
  • Early observations of tumour regressions after virus infections have been published starting from the late 19th century
  • The present results show that in substage IB, IIA, IIB and IIC melanoma patients, Rigvir administration after surgery significantly (P<0.05) prolongs survival compared with patients who were managed according to current published guidelines
  • no value higher than grade 2 was recorded in Rigvir-treated patients. This is in contrast to most other cancer therapies, where grades 3 and 4 are frequently observed
  • Administration of virus induces the formation of neutralising antibodies that might potentially influence the efficiency of Rigvir
  • In 94 healthy adult participants tested, the titres were found to be low (1 : 20 to 1 : 62) 39,40. When tested in 155 adult cancer patients who had not been treated with Rigvir, neutralising antibodies against ECHO-7 were detected in ∼50% of the patients
  • the presence of ECHO-7 antibodies was shown to increase with age in children and level off to a plateau of around 75% in adults
  • Rigvir is an immunomodulator that affects both the humoral, antibody-mediated, and the cellular immune systems
  • neutralising antibodies do not affect efficacy when local or regional administration is used
  • it reduces the viability of melanoma, as well as pulmonary, gastric, pancreatic, bone, and breast cancer cell cultures
  • It is oncolytic in melanoma and rectum cancer patients
  • shown to improve the 5-year survival in rectum cancer patients
  • Nathan Goodyear on 16 Oct 18
     
    RIGVIR shown to improve survival against standard therapy in stage IB, IIA, IIB, and IIC in malignant melanoma patients in retrospective study. Side effects are minimal. Neutralizing antibodies are an area to watch that likely effects individual outcome beyond that of the type of cancer
Nathan Goodyear

Advanced Gastric Cancer Associated with Disseminated Intravascular Coagulation Successf... - 0 views

www.ncbi.nlm.nih.gov/...PMC3705133

DIC cancer

shared by Nathan Goodyear on 03 Jul 18 - No Cached
  • Nathan Goodyear on 03 Jul 18
     
    Case study of DIC in patient with gastric cancer successfully treated with 5-fu and oxaliplatin.
Nathan Goodyear

S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylati... - 0 views

www.ncbi.nlm.nih.gov/...PMC2999854

SAMe methylation oncogenes colon cancer cancer

shared by Nathan Goodyear on 27 Jun 12 - No Cached
  • Nathan Goodyear on 27 Jun 12
     
    SAMe shown to resolve the hypomethylation status of oncogenes. This allows increased genetic expression.  By improving methylation with SAMe, we can reduce oncogenic expression and thus be a useful cancer therapy adjunct.
Nathan Goodyear

How We Read Oncologic FDG PET/CT | Cancer Imaging | Full Text - 0 views

cancerimagingjournal.biomedcentral.com/...s40644-016-0091-3

PET_CT PET scan CT cancer

shared by Nathan Goodyear on 20 Feb 18 - No Cached
  • In early PET literature focusing on analysis of solitary pulmonary nodules, some researchers defined malignancy based on a SUVmax threshold of greater than 2.5
  • We contend that SUV analysis has virtually no role in this setting.
  • tumours grow as spheres, whereas inflammatory processes are typically linear
  • ...35 more annotations...
  • Far more important than the SUVmax is the pattern rather than intensity of metabolic abnormality and the correlative CT findings
  • Descriptively, we define SUV < 5 as “low intensity”, 5–10 as “moderate”, 10–15 as “intense” and >15 as “very intense”
  • Evolving literature suggests that intensity of uptake is an independent prognostic factor and in some tumour subtypes superior to histopathologic characterisation.
  • aerobic glycolysis
  • Our practice of thresholding the grey and colour scale to liver as detailed above results in similar image intensity to a fixed upper SUV threshold of 8 to 10
  • The advantage of using the liver as a reference tissue is also aided by this organ having rather low variability in metabolic activity
  • When the liver is abnormal and cannot be used as a reference organ, we use the default SUV setting of an upper SUV threshold of 8
  • One of the most challenging aspects of oncologic FDG PET/CT review, however, is to recognise all the patterns of metabolic activity that are not malignant and which consequently confound interpretation
  • Many benign and inflammatory processes are also associated with high glycolytic activity
  • Future articles in the “How I Read” series will address the specific details of reading PET/CT in various cancers
  • The intensity of uptake in metastases usually parallels that in the primary site of disease
  • For example, discordant low-grade activity in an enlarged lymph node in the setting of intense uptake in the primary tumour suggests it is unlikely malignant and more likely inflammatory or reactive
  • By CT criteria the enlarged node is ‘pathologic’ but the discordantly low metabolic signature further characterises this is as non-malignant since such a node is not subject to partial volume effects and therefore the intensity of uptake should be similar to the primary site
  • The exception is when the lymph node is centrally necrotic as a small rim of viable tumour is subject to partial volume effects with expectant lower intensity of uptake; integrating the CT morphology is therefore critical to reaching an accurate interpretation
  • Small nodes that are visualised on PET are conversely much more likely to be metastatic as such nodes are subject to partial volume effects.
  • The exception to this rule is tumours with a propensity for tumour heterogeneity at different sites
  • The combination of FDG and a more specific tracer, which visualises the well-differentiated disease can be very useful to characterise this phenomenon
  • “metabolic signature”
  • For the majority of malignant processes, the intensity of metabolic abnormality correlates with degree of aggressiveness or proliferative rate.
  • a negative PET/CT study in a patient with biopsy proven malignancy would be considered false-negative
  • Warburg effect
  • There, however, are a significant minority of tumours that utilise substrates other glucose such as glutamine or fatty acids as a source of the carbon atoms required for growth and proliferation
  • This includes a subset of diffuse gastric adenocarcinomas, signet cell colonic adenocarcinomas and some sarcomas, particularly liposarcoma
  • There may be a role for other radiotracers such as fluorothymidine (FLT) or amino acid substrates in this setting.
  • Some tumours harbour mutations that result in defective aerobic mitochondrial energy metabolism, effectively simulating the Warburg effect
  • patients with hereditary paraganglioma and pheochromocytoma highlight this phenomenon
  • These have intense uptake on FDG PET/CT despite often having low proliferative rate.
  • Uterine fibroids, hepatic adenomas, fibroadenomas of the breast and desmoid tumours are benign or relatively benign lesions that can have quite high FDG-avidity.
  • Metabolic activity switches off rapidly following initiation of therapy
  • Common examples where patients have commenced active therapy but the referrer is requesting “staging” includes hormonal therapy (eg. tamoxifen) in breast cancer, oral capecitabine in colorectal cancer or high dose steroids in Hodgkin’s lymphoma
  • It is therefore critical to perform PET staging before commencement of anti-tumour therapy
  • The potential advantage of routine diagnostic CT is improved anatomic localisation and definition
  • Without intravenous contrast, additional identification of typical oncologic complications such as pulmonary embolism or venous thrombosis cannot be identified
  • If the study is performed as an “interim” restaging study after commencement of therapy but before completion, in order to reach a valid or clinically useful conclusion findings must be interpreted in the context of known changes that occur at a specific timing and type of therapy
  • The most well studied use of interim PET is in Hodgkin’s lymphoma where repeat PET after two cycles of ABVD-chemotherapy provides powerful prognostic information and may improve outcomes by enabling early change of management
  • Nathan Goodyear on 20 Feb 18
     
    good read on the PET/CT scan reading.  They mention that tumors are spheres and inflammation is linear, yet inflammation coexists with cancer; hard to simply delineate these on simple terms. I do agree aon the metabolic signature of the PET/CT scan
Nathan Goodyear

Artesunate inhibits the growth and induces apoptosis of human gastric | OTT - 0 views

www.dovepress.com/ric--peer-reviewed-article-OTT

Caspase-3 Caspase-9 cox-2 cancer artesunate Bcl-2 Bax

shared by Nathan Goodyear on 01 May 20 - No Cached
  • Nathan Goodyear on 01 May 20
     
    Wide spectrum of anti-cancer properties of artesunate
Nathan Goodyear

Reducing Malignant Ascites and Long-Term Survival in a Patient with Recurrent Gastric C... - 0 views

www.ncbi.nlm.nih.gov/...PMC7265700

cancer ascites gastric cancer mistletoe

shared by Nathan Goodyear on 07 Apr 21 - No Cached
  • Nathan Goodyear on 07 Apr 21
     
    Mistletoe reduced ascites in case study
Nathan Goodyear

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with meta... - 0 views

bmccancer.biomedcentral.com/...s12885-019-5696-z

IV vitamin C cancer vitamin C

shared by Nathan Goodyear on 21 May 19 - No Cached
  • Nathan Goodyear on 21 May 19
     
    Phase I study of vitamin C and FOLFOX or FOLFIRI. Numerous studies have shown the extremely high safety profile of IV vitamin C in cancer. The need to show the same thing time and time again borders on the insanity. The potential adverse events listed in this study is from the FOLFOX or FOLFIRI, not the vitamin C.
Nathan Goodyear

Effect of the oncolytic ECHO-7 virus Rigvir® on the viability of cell lines o... - 0 views

www.ncbi.nlm.nih.gov/...PMC5868171

RIGVIR cancer immunotherapy immunotherapy cancer

shared by Nathan Goodyear on 19 Oct 18 - No Cached
  • Nathan Goodyear on 19 Oct 18
     
    In vitro studies confirm reduced viability of melanoma, rhabdomyoscarcoma, gastric adenocarcinoma, lun carcinoma, and pancreas adenocarcinoma cells with the use of the oncolytic RIGVIR virus
Nathan Goodyear

Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monit... - 0 views

c.na2.content.force.com/...ervlet.EmailAttachmentDownload

thymidine kinase 1 TK-1 cancer

shared by Nathan Goodyear on 26 Jan 15 - No Cached
  • Nathan Goodyear on 26 Jan 15
     
    TK-1 to screen for cancer, as well as to follow therapy and recurrence.
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