Not only is high dose vitamin D3 therapy more effective in reducing IL-17 compared to low dose, but it is safe to in individuals with MS. The hot topic these days is immunotherapy: that is exactly what vitamin D therapy is.
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
Percent survival at 1 year was significantly increased in patients treated with immunotherapy than in those treated with supportive care alone (9/25 vs. 3/25, p < 0.05) in study which suggests that low-dose subcutaneous IL-2 plus melatonin may be effective as a second-line therapy to induce tumor regression and to prolong percent survival at 1 year in metastatic colorectal cancer patients progressing under 5-FU and folates
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 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
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
Advanced cancer patients have high serum Nagalase activities, resulting in no macrophage activation and severe immunosuppression that explain why cancer patients die with overwhelming infection
Prognostic utility of serum α-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients
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.
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
Small phase II pilot sutyd of advanced ovarian cancer, foud low dose IL-2 at 3 million IU/day X 6 days for 4 weeks preceded by 40 mg melatonin provides some benefit in advanced disease following at least 3 failed polychemotherapy regimens.
Study, again of advanced cancer, with previous failed chemotherapy found that melatonin plus low-dose IL-2 therapy stimulated lymphocyte production and provided a partial response and stable disease. No control group.