been a great weekend.
My wife is looking after her dad, the kids and I went to mass and the travel expo. I called it geography study.
cars. My
. I aimed to bring geography to life. I coughed up a little blood the mucus at mass, not good!!!
.
and conventional.
my story, my approach.
Colorectal cancer is with more than 4000 new cases every year the third most common cancer in Denmark. Metastases are most often found in the liver, and 20-25% of the patients have synchronous metastases to the liver at time of primary diagnosis. Other frequent sites for metastases are lungs and lymph nodes. Without treatment the median survival for patients with metastatic colorectal cancer is 7-9 months. Patients receiving systemic or regional chemotherapy now have a median survival of approximately 20 months. Up to 40% of the patients undergoing intended curative surgery subsequently relapse with local or distant disease, and approximately 80% of the relapses appear within the first 3 years. If the cancer metastasises, and the chances of radical surgery are eliminated, the prognosis is poor. The aim of the present study was to evaluate the clinical and immunological effects of treating patients with disseminated colorectal cancer with a dendritic cell based cancer vaccine (MelCancerVac). The vaccine consisted of dendritic cells generated from autologous mononuclear cells pulsed with an allogeneic tumor cell lysate, selected for its high expression of cancer associated antigens. A clinical phase I study evaluating tolerability and toxicity of the treatment was established. Six patients with progressive disease were included and the analysis revealed that the treatment was well tolerated and not associated with toxicity. A subsequent clinical phase II study evaluating the activity of the treatment with CT-scan based measurements of tumors (RECIST), self reported quality of life (SF-36), and clinical evaluation was established. Out of twenty included patients with progressive disease, seventeen received intervention with the vaccine. Stable disease was achieved in four patients and two of these remained stable throughout the entire study period. Quality of life remained for most parameters included in the evaluation high and stable. The immunological consequences of the treatment were evaluated with plasma- and serum-levels of inflammatory and non-inflammatory markers (the following 10 cytokines: GM-CSF, INF-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-alpha, and in addition the inflammatory chemokines MIP-1beta, Eotaxin and IP-10) and biomarkers CEA and TIMP-1. These analyses showed that the vaccine induced increasing levels of Th1 cytokines such as GM-CSF, TNF-alpha, IFN-gamma, and IL-2 in patients achieving stable disease. Patients with progressive disease had increasing levels of CEA and TIMP-1, while patients achieving stable disease maintained relatively stable levels. Conclusively, treatment with this dendritic cell based cancer vaccine was non-toxic and safe, clinical response in terms of stable disease was achieved in 24% of the patients, and the patients maintained a high quality of life during treatment. The immunological analyses indicated that the treatment resulted in favourable anticancer responses in the patients' immune system in terms of polarisation towards a Th1 dominated response potentially directed against tumor cells. Since no partial or complete responses were observed and since the number of patients was relatively low these results have to be interpreted with caution. Moreover, phase II study designs do not lead to final conclusions regarding clinical efficacy, which must be validated in larger prospective, randomised and controlled studies. Pharmacokinetic and Pharmacodynamic Implications of P-glycoprotein Modulation
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858384/ this again a very interesting, and very telling story about why we continue to die, PLEASE GOD, we need to treat stage 4 metastatic with immunotherapies first. The big
tumours, the larger
tumour burden just does not succeed with immunotherapies.
FOR MY MELBOURNE FRIENDS, THIS IS WHY SOONER RATHER THAN LATER, literally doubling your tumour volume can mean either CR, PR and death!!!! read the study. For me this nice study say immuno and radiation, but its really immunotherapy and any cytotoxic therapy with efficiacy for your tumour burden.
Clinical response of advanced cancer patients to cellular immunotherapy and intensity-modulated radiation therapy
This article has been
cited by other articles in PMC.
Abstract
Patients afflicted with advanced cancers were treated with the intratumoral injection of autologous immature dendritic cells (iDCs) followed by activated T-cell infusion and intensity-modulated radiation therapy (IMRT). A second round of iDCs and activated T cells was then administered to patients after the last radiation cycle. This complete regimen was repeated for new and recurring lesions after 6 weeks of follow-up. One year post therapy, outcome analyses were performed to evaluate treatment efficacy. Patients were grouped according to both the number and size of tumors and clinical parameters at treatment initiation, including recurrent disease after standard cancer therapy, Stage IV disease, and no prior therapy. Irrespective of prior treatment status, 23/37 patients with ≤ 5 neoplastic lesions that were ≤ 3 cm in diameter achieved complete responses (CRs), and 5/37 exhibited partial responses (PRs). Among 130 individuals harboring larger and more numerous lesions, CRs were observed in 7/74 patients that had received prior SCT and in 2/56 previously untreated patients. Some patients manifested immune responses including an increase in CD8+CD56+ lymphocytes among circulating mononuclear cells in the course of treatment. To prospectively explore the therapeutic use of these cells, CD8+
nowi referenced this mtop success a few days ago, but in the light of using radiation to stimulate a continued immune response. Maybe the proton therapy is the way to go for me, I will try.
Conclusion
In this study, an in vitro assay to evaluate DC therapy efficiency was developed. Antigen presentation of DCs to CTLs, and cytotoxic effects of CTLs on target cells, can be monitored in real time by impedance analysis based on E-plates and read by the xCELLigence system. This is a simple, efficient, and real-time assay that records changes in target cell proliferation, doubling time, and proliferating or inhibiting slopes. This assay is so sensitive that small differences in ratios of DCs and CTLs, as well as antigen source and target cells, can be recorded. Thus, impedance-based analysis is a powerful tool for DC- and CTL-based immunotherapy. However, this study did not compare this assay with traditional methods, such as Cr51 releasing or flow cytometry. We hope this technique will contribute to the development and improvement of immunotherapies in the near future.
the more we learn about our immune system, and the current state of the science, makes systemic chemo look primative and barbaric. Now thats the most politically correct language in a week or so. There is a mountain of excellent science for immunotherapies and australian patients should be encouraged to go overseas and try and not die here. think of all the money we will save our fellow australians. Our politicans, and doctors can have an extra luxurious conference or meeting to discuss future directions while we all bloody well die. Well not me, and hopefully not you!!!! Dont start reading the science and the journals, you might live and become mad like me!!!!!!!!
Colorectal Cancer
Mounting evidence has suggested that CRC is an immunogenic tumor. This evidence includes: the expression of TAAs by colorectal carcinoma; the strong correlation between the infiltration of memory T cells and the recurrence and metastases of CRC; and the spontaneous humoral and cellular immune responses against tumor antigens
.17–
19 This hypothesis has been further explored in clinical trials using different cancer vaccination strategies.
http://www.ncbi.nlm.nih.gov/pubmed/18704409 do you see, paper after paper, with justifications for all that I have done, EXCEPT THE FAR OUT STUFF, but if
moga has not learned this yet, well they are staying on the
chemo gravy train just a bit longer, and the richer
moga gets, the more we die. They are what they are, and we all very very mortal.
Combinatorial treatments including vaccines, chemotherapy and monoclonal antibodies for cancer therapy.
Abstract
Accumulating evidence suggests that despite the potency of cytotoxic anticancer agents, and the great specificity that can be achieved with immunotherapy, neither of these two types of treatment by itself has been sufficient to eradicate the disease. Still, the combination of these two different modalities holds enormous potential for eliciting therapeutic results. Indeed, certain chemotherapeutic agents have shown immunomodulatory activities, and several combined approaches have already been attempted. For instance, chemotherapy has been proven to enhance the efficacy of tumor cell vaccines, and to favor the activity of adoptively transferred tumor-specific T cells. A number of mechanisms have been proposed for the chemotherapy-triggered enhancement of immunotherapy response. Thus, chemotherapy may favor tumor cell death, and by that enhance tumor-antigen cross-presentation in vivo. Drug-induced myelosuppression may induce the production of cytokines favoring homeostatic proliferation, and/or ablate immunosuppression mechanisms. Furthermore, the recently reported synergy between monoclonal antibodies and chemotherapy or peptide vaccination is based upon the induction of endogenous humoral and cellular immune responses. This would suggest that monoclonal antibodies may not only provide passive immunotherapy but can also promote tumor-specific active immunity. This article will review several strategies in which immunotherapy can be exploited in preclinical and clinical studies in combination with other agents and therapeutic modalities that are quite unique when compared with "conventional" combination therapies (ie, treatments with chemotherapeutic drugs or chemotherapy and radiotherapy based protocols). The results from these studies may have significant implications for the development of new protocols based on combinatorial treatments including vaccines, chemotherapy and monoclonal antibodies, suggesting an exciting potential for therapeutic synergy with general applicability to various cancer types. Given the complicity of immune-based therapies and cancer pharmacology, it will be necessary to bring together cancer immunologists and clinicians, so as to provide a robust stimulus for realizing the successful management of cancer in the near future.
Colorectal cancer and immunity: what we know and perspectives.
Abstract
Strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer. In particular, the density of T CD8⁺ and CD45⁺ lymphocyte infiltration was recently shown to have a better prognostic value than the classic tumor node metastasis classification factor. Other immune subsets, as macrophages, natural killer cells or unconventionnal lymphocytes, seem to play an important role. Induction of regulatory T cells (Tregs) or immunosuppressive molecules such as PD-1 or CTLA-4 and downregulation of antigen-presenting molecules are major escape mechanisms to antitumor immune response. The development of these mechanisms is a major obstacle to the establishment of an effective immune response, but also to the use of immunotherapy. Although immunotherapy is not yet routinely used in colorectal cancer, we now know that most treatments used (chemotherapy and biotherapy) have immunomodulatory effects, such as induction of immunogenic cell death by chemotherapy, inhibition of immunosuppression by antiangiogenic agents, and antibody-dependent cytotoxicity induced by cetuximab. Finally, many immunotherapy strategies are being developed and tested in phase I to III clinical trials. The most promising strategies are boosting the immune system with cytokines, inhibition of immunoregulatory checkpoints, vaccination with vectorized antigens, and adoptive cell therapy. Comprehension of antitumor immune response and combination of the different approaches of immunotherapy may allow the use of effective immunotherapy for treatment of colorectal cancer in the near future. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983433/Macrophages: Tumor infiltrating macrophages (TIM) can be divided into two different subtypes with different roles in cancer[18]. M1 TIMs are intimately involved in innate immunity, as they target altered cells, produce pro-inflammatory molecules (IL-6, IL-12, IL-23 and TNFα) and promote adaptive immunity through increased expression of MHC and costimulatory molecules. They may also target tumor cells linked to antibodies because they express a receptor for immunoglobulin constant fragments (ADCC). Activated M2 TIMs are engaged in wound healing and can promote tumor progression through immunosuppressive cytokines (IL-10 and TGFβ). While infiltration by macrophages is generally a poor prognostic factor in different types of cancer, in CRC it seems to be associated with a better prognosis[19], suggesting that antitumorigenic properties dominate in vivo.
CONTROLLING FRAUD,
WASTE, AND ABUSE
IN THE PUBLIC SECTOR
The principle that sunlight is the best disinfectant is applicable to much public sector activity.
The more visible the transaction, the less vulnerable it is to fraud and corruption (Gardiner &
Lyman 1978, p.145; p.211). Whilst it can be argued that matters of individual privacy, trade
secrecy, and national security might militate against public access to many transactions
involving public sector agencies, democratic principles imply that activity conducted on behalf
of the public should be visible to that public. For example, regulations require the gazettal of
Commonwealth government purchases. Beyond this, aggressive investigative journalists and
citizen"watchdog" groups have an important role to play in enhancing the visibility of public
sector activity (Grabosky 1990).
HOW DO I FIND AN AGGRESSIVE INVESTIGATIVE JOURNALIST
? one day!
and one last paper to dream about, if
its possible for the bugs to use the
macropgae, then maybe the
tumour cell also.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244692/http://www.hindawi.com/journals/jir/2012/948098/5. Conclusion
Heterogeneity is one of the most important characteristics of macrophages. In different diseases, macrophages can be polarized into different phenotypes. In most tumors, macrophages are considered to be polarized into the M2 phenotype. TAMs express a series of cytokines, chemokines, and proteases to promote angiogenesis, lymphangiogenesis, tumor growth, metastasis, and immunosuppression. Recently, it has also been reported that TAMs interact with CSCs, which facilitate tumorigenicity, metastasis, and drug resistance. Taken together, these findings indicate that targeting macrophages in the tumor microenvironment may provide more efficacious novel therapies for future tumor management.
Low-carbohydrate diets are a safe, effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure, diminishing resistance to insulin with an improvement in blood levels of glucose and insulin and they also have neurological and antineoplastic benefits.