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Nathan Goodyear

http://journals.sagepub.com/doi/pdf/10.1177/1534735410369673 - 0 views

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    Mistletoe improves QOL in database review.
Nathan Goodyear

Preclinical and Clinical Effects of Mistletoe against Breast Cancer - 0 views

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    Review of mistletoe
Nathan Goodyear

Albumin | Professional Education - 0 views

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    albumin
Nathan Goodyear

Cancers | Free Full-Text | A Second WNT for Old Drugs: Drug Repositioning against WNT-D... - 0 views

  • To date nearly half of known human tumors show a dysregulation of the WNT signaling pathway
  • It should be also noted that the WNT pathway is not exclusively employed during development or overactivated in cancer. In adults many healthy tissues rely on it for renewal and homeostasis maintenance, most notably the intestine, haematopoietic system, hair, bones and skin. Therefore one might expect adverse reactions in all these organ systems, which has indeed been observed for many WNT-targeting compounds upon attempts to push them into the clinics
  • The intestine seems to be the most vulnerable in this regard
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  • Ivermectin inhibits proliferation of human colon cancer and lung cancer cells both in vitro and in vivo
  • The anti-proliferative action, affecting both the bulk tumor cells and CSCs, was linked in this study to inhibition of WNT signaling
  • the anti-WNT IC50 of ivermectin is 5–10 times (~1–2 µM vs. 10 µM) lower than that of its toxic effect against chloride channels
  • oral bioavailability of the drug, as for other antiparasitic drugs discussed in this section, is very low
  • Toxicity studies in vivo have also demonstrated a wide therapeutic index for ivermectin
  • Its anti-proliferative activity has been demonstrated in a wide array of cancer cell lines representative of WNT-dependent cancers: non-small lung carcinoma [96], multiple myeloma [97], hepatoma [98], adrenocortical carcinoma [99], ovarian cancer [100] and glioblastoma
  • Niclosamide inhibits the canonical WNT pathway
  • In addition to inhibiting the canonical WNT pathway, niclosamide may mediate its anticancer activities through several other signaling pathways such as NOTCH [107], MTOR [108], NF-κB [97] and STAT3 [96]
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    review article highlights older medications that have anti-Wnt pathway effects in cancer.  Roughly, 50% of cancer involve upregulated Wnt pathway activity. Other drugs of note: metformin
Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 0 views

  • administration of low‐dose IL‐2 results in expansion of a CD3 / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
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  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
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    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

A phase II trial of trastuzumab in combination with low-dose interleukin-2 (IL-2) in pa... - 0 views

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    phase II study of herceptin and IL-2 found no benefit of NK cell expansion
Nathan Goodyear

Trastuzumab and Interleukin-2 in HER2-positive Metastatic Breast Cancer | Clinical Canc... - 0 views

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    Herceptin and IL-2 increase NK cell expansion when used in conjunction.  The IL-2 was the low dose protocol for 7 weeks.
Nathan Goodyear

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

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    EBV gastric cancer found to be associated with the best prognosis.
Nathan Goodyear

Adjuvant Analgesics in Cancer Pain Management - 0 views

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    older, yet still relevant therapy in the treatment of pain.
Nathan Goodyear

Overall survival of cancer patients with serum lactate dehydrogenase greater ... - 0 views

  • catalyzes the interconversion of pyruvate and lactate during glycolysis and gluconeogenesis
  • It has long been known that many human cancers have higher LDH levels than normal tissues
  • It has long been appreciated that LDH is a prognostic factor for survival
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  • The serum level of LDH correlated with tumor burden and was thought to reflect the tumor’s growth and invasive potential
  • the majority of patients with advanced or metastatic disease could be detected to have extremely high serum level of LDH
  • strong evidence to support effective chemotherapy of full dose even in patients with high LDH level
  • LDH is a key enzyme in the process of energy production in cancer cells, it catalyzes the conversion of pyruvate to lactate in hypoxic conditions
  • its function in anaerobic metabolism, cancer cells grow even after their rapid proliferation that leads to low-oxygen conditions in the tumor microenvironment
  • LDH plays an important role in tumor progression and maintenance
  • inhibition of LDH inhibits tumor progression and has been considered for the therapeutic target of cancer energy metabolism
  • LDH levels are increased in response to tissue injury or during disease states
  • LDH could be a marker of tumor burden for advanced cancer patients
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    High LDH, defined as >1,000, found to be maker for very poor overall survival in retrospective study.
Nathan Goodyear

Serum lactate dehydrogenase and survival following cancer diagnosis - 0 views

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    LDH found to correlate with overall and cancer-specific mortality.
Nathan Goodyear

Immunotherapy targets metastatic breast cancer-cell mutations - National Cancer Institute - 0 views

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    This is simply a press release from the NCI, but it highlights the move to immunotherapy as the future of cancer therapy.
Nathan Goodyear

http://cancerres.aacrjournals.org/content/canres/62/6/1588.full.pdf - 0 views

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    doxycycline to treat bone mets.
Nathan Goodyear

Wnt Signaling in Cancer - 0 views

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    Wnt signaling promotes carcinogenesis through positive and negative effects.
Nathan Goodyear

Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations - 0 views

  • Among the most encouraging mAb is trastuzumab, which targets the human epidermal growth factor receptor 2 and is indicated in the treatment of breast cancer
  • bevacizumab, which inhibits vascular endothelial growth factor and is indicated in the treatment of a range of diseases, including colorectal, lung, and ovarian cancer; and cetuximab, which blocks the epidermal growth factor receptor and is indicated in the treatment of colorectal and lung cancer
  • Viscum album L (VA or European mistletoe) preparations are widely used as additive cancer therapy in Europe, especially in German-speaking countries, and have been associated with a reduction in chemotherapy-related adverse drug reactions and increased HRQL
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  • leading to enhancement of interleukin-12 secretion and natural killer cell function
  • Helixor VA preparations
  • A multivariable GEE model indicated that the odds for patients experiencing an AE following mAb therapy were nearly 5 times higher compared with that for mAb plus VA
  • VA preparations (Iscador Ltd) did not inhibit chemotherapy-induced cytostasis or cytotoxicity and showed an additive inhibitory effect at higher concentrations of VA.
  • previous in vitro investigations have shown that VA preparations have either no or minor effects on a range of CYPs, suggesting that VA-drug interactions based on drug metabolism are unlikely
  • mAb do not undergo hepatic metabolism but undergo proteolytic catabolism throughout the body
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    VAE therapy found to reduce adverse events in those receiving monoclonal Ab therapy.
Nathan Goodyear

Somatic versus germinal mutation - An Introduction to Genetic Analysis - NCBI Bookshelf - 0 views

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    good review of somatic versus germline mutation
Nathan Goodyear

Importance of performance status for treatment outcome in advanced pancreatic cancer - 0 views

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    pancreatic cancer treatment
Nathan Goodyear

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor,... - 0 views

  • the MAF precursor activity of prostate cancer patient Gc protein is lost or reduced, because their serum Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells
  • Administration of 100 ng of GcMAF
  • 100 ng of GcMAF was administered intramuscularly once a week
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  • As GcMAF therapy progressed the MAF precursor activity of all five patients increased and their serum Nagalase activity decreased inversely
  • As GcMAF therapy progressed, the MAF precursor activity increased with a concomitant decrease in serum Nagalase activity
  • serum Nagalase is proportional to tumor burden
  • as GcMAF therapy progressed, serum Nagalase activity decreased and, concomitantly, tumor burden decreased
  • the serum Nagalase activities of all 16 patients decreased as GcMAF therapy progressed
  • annual computed tomographic scans of these patients confirmed them being tumor recurrence-free for the 7 years
  • undifferentiated cells were killed rapidly during the first few weeks, and the differentiated cells were killed slowly in the remaining GcMAF therapeutic period
  • PSA levels of prostatectomized patients decreased as serum Nagalase decreased during GcMAF therapy
  • In patients without tumor resection, however, although serum Nagalase activity decreased as GcMAF therapy progressed, their PSA values remained unchanged. The result suggests that the PSA derived from tumor-bearing prostate did not change while tumor burden decreased. Because tumor-induced inflammation in the noncancerous prostate tissues causes secretion of PSA [38], the PSA produced from these inflamed noncancerous prostate tissues cannot be changed by the decrease in tumor burden
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    GC-MAF levels exist in inverse relationship to nagalase.  In this study of men with prostate cancer, weekly GCMAF injections reduced Nagalase activity to levels found in healthy controls suggesting tumor free. The dose was 100 ng/week. Nagalase is a protein that suppresses GC-MAF production and thus is immunosuppressive.
Nathan Goodyear

Development of PD-1/PD-L1 Pathway in Tumor Immune Microenvironment and Treatment for No... - 0 views

  • the lack of immunologic control is recognized as a hallmark of cancer currently
  • Programmed death-1 (PD-1) and its ligand PD-L1 play a key role in tumor immune escape and the formation of tumor microenvironment, closely related with tumor generation and development
  • Blockading the PD-1/PD-L1 pathway could reverse the tumor microenvironment and enhance the endogenous antitumor immune responses.
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  • environmental factors, living habits, genetic mutations, dysfunction of the immune system and so on
  • special tumor immune microenvironment
  • cytotoxic T lymphocyte-associated antigen 4 (CLTA-4), Programmed death-1 (PD-1) and its ligands PD-L1 (B7H1) and PD-L2 (B7-DC)
  • CTLA-4 regulates T cell activity in the early stage predominantly, and PD-1 mainly limits the activity of T-cell in the tumor microenvironment at later stage of tumor growth
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    PD-1 to read.
Nathan Goodyear

Interleukin-2 enhances the response of natural killer cells to interleukin-12 through u... - 0 views

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    low dose IL-2 induces increase NK cell activity.
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