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
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
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
The activation of each of them leads to an inhibition of adenylyl cyclase via G proteins (Gi/o), which in turn activates many metabolic pathways such as mitogen‐activated protein kinase pathway (MAPK), phosphoinositide 3‐kinase pathway (PI3K), cyclooxygenase‐2 pathway (COX‐2), accumulation of ceramide, modulation of protein kinase B (Akt), and ion channels
phytocannabinoids, endocannabinoids, and synthetic cannabinoids
Action of THC in human organism relies on mimicking endogenous agonists of CB receptors—endocannabinoids
The upregulated expression of CB receptors and the elevated levels of endocannabinoids have been observed in a variety of cancer cells (skin, prostate, and colon cancer, hepatocellular carcinoma, endometrial sarcoma, glioblastoma multiforme, meningioma and pituitary adenoma, Hodgkin lymphoma, chemically induced hepatocarcinoma, mantel cell lymphoma)
concentration of endocannabinoids, expression level of their receptors, and the enzymes involved in their metabolism frequently are associated with an aggressiveness of cancer
CB2 receptor contributes to human epidermal growth factor receptor (HER2) pro‐oncogenic signaling and an overexpression of CB2 increases susceptibility for leukemia development after leukemia viral infection
endocannabinoid‐degrading enzymes are upregulated in cancer cell lines and in human tumors
Many cannabinoids, ranging from phytocannabinoids (THC, CBD), endocannabinoids (2‐arachidonoylglycerol, anandamide), to synthetic cannabinoids (JWH‐133, WIN‐55,212‐2), have shown ability to inhibit proliferation, metastasis, and angiogenesis in a variety of models of cancer
Despite some inconsistent data, the main effect of cannabinoids in a tumor is the inhibition of cancer cells’ proliferation and induction of cancer cell death by apoptosis
CB1 and CB2 receptor agonists stimulate apoptotic cell death in glioma cells by induction of de novo synthesis of ceramide, sphingolipid with proapoptotic activity
process of autophagy is upstream of apoptosis in mechanism of cell death induced by cannabinoids
Ivermectin can inactivate the protein kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines
PAK proteins encoded by the PAK1 gene are critical for cytoskeleton reorganization and nuclear signaling.
PAK-1 kinase is required for the growth of more than 70% of human cancers such as pancreatic, colon, breast and prostate cancers, and neurofibromatosis
PAK1 has also been implicated for maintenance of glucose homeostasis in pancreatic beta cells and skeletal muscle
Ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells (Blood, November 4, 2010, vol.115). The paper states Ivermectin synergizes with chemo agents cytarabine and daunorubicin to induce cell death in leukemia cells.
Praziquantel , my other favorite parasite medication for liver flukes, synergistically enhances Paclitaxel (Taxol) efficacy to inhibit cancer cell growth
upregulation of glycolysis in cancer cells, with subsequent exhaustion of glucose in the microenvironment, leading to the death of T cells from starvation
PD‐L1 expression promotes the production of interleukin 10, a cytokine involved in the death of activated T cells
PD‐L1 expression in tumor tissue might lead to T‐cell exhaustion and unresponsiveness
ER beta and prostate cancer. More aggressive prostate cancer is found to be associated with lower ER beta expression in the prostate. this makes sense, as other studies have shown that ER beta in the prostate can induce apoptosis (cell death), which is a powerful mechanism to regulate uncontrolled growth as found in cancer.
study finds no increased risk of CHD, HF, or CV death in subclinical hypothyroidism in older adults. No insight is gained from this article, due to the use of TSH as the only tool for thyroid assessment. TSH has been shown to become unreliable as a sole thyroid assessment tool an aging population.
TA-65 administration during 4 months significantly improved the capacity to uptake glucose after a glucose pulse
liver protective action of TA-65
A disadvantage of mTERT potentiation could be associated to its capacity to favor proliferation of cancerous cells in murine models
TA-65 treated mice presented a similar incidence of malignant cancers at time of death, with a tendency to show decreased sarcomas and slightly increased lymphomas
We demonstrate here that TA-65 leads to a significant rescue of short telomeres through telomerase activation
TA-65 treatment increases proliferation and mobilization potential of mouse keratinocytes in vitro, a situation mimicking telomerase overexpression
TAT2, a similar molecule, have beneficial effects in the activation of CD8+ T lymphocytes from HIV-infected patients where they observe an increase of the proliferative potential and enhancement of cytokine/chemokine production
TA-65 resulted in a similar rescue of short telomeres in leukocytes post-treatment as observed with humans, most likely through an activation of telomerase
we observe that TA-65 lead to 10 fold increase of telomerase RNA levels in the liver of treated mice comparing to the non-treated same-age cohorts
TA-65 regulates telomerase at the transcription level, probably through the regulation of the MAPK pathway
TA-65 dependent telomerase activation results in a better organ fitness as demonstrated by the improved scores at the glucose tolerance test and insulin levels at fasting
TA-65 supplemented mice also present modest enhancement of the subcutaneous and epidermal thickness, as well as higher bone density, representative of an overall fitness status improvemen
TA-65 treated mice present higher levels of RBC and hemoglobin comparing to the control cohorts
improved health-span of TA-65 treated mice is not accompanied by increased cancer incidence, which may be related to the fact that TERT levels are very modestly increased in all tissues tested except for the liver
systemic telomerase overexpression from the germline leads to protection from aging associated pathologies
similar situation could be mimicked expressing telomerase late in life in a telomerase deficient background
we observed a higher proliferation rate and a partial protection from cell death in some tissues of TA65 treated mice
Members of the most powerful drug gang in Brazil killed 31 inmates in a penitentiary on Friday, decapitating and cutting off the hearts of most of them, to take revenge for a separate massacre that left 56 dead this week.
Finally, something that lowers the risk associated with synthetic progestins. Progestins are progesterone pretenders that increase breast cancer. Apigenin, a component of bioflavonoid, was shown to inhibit growth and intact cause cell death.
IV T3 was given to patients with chronic heart failure. What the study found may surprise you: improved heart function (ventricular), improved BNP, decrease heart rate, no side effects. T3 has been shown to be more predictive of cardiac death in those with cardiac disease, than elevated lipids or decreased ejection fraction.