Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
DNA vaccination wikipedia , lookup
Psychoneuroimmunology wikipedia , lookup
Pathophysiology of multiple sclerosis wikipedia , lookup
Immunosuppressive drug wikipedia , lookup
Management of multiple sclerosis wikipedia , lookup
Adoptive cell transfer wikipedia , lookup
Sjögren syndrome wikipedia , lookup
Multiple sclerosis signs and symptoms wikipedia , lookup
Cancer immunotherapy wikipedia , lookup
Immunocontraception wikipedia , lookup
A scientific article There have been a number of clinical studies that have tested cancer vaccines. Thus far, there is only one cancer vaccine found to improve overall survival. Sipuleucel-T (Provenge®) is approved for use in some men with metastatic prostate cancer. It stimulates an immune response to prostatic acid phosphatase (PAP), an antigen present on most prostate cancers. In a clinical trial, Provenge increased the survival of men with hormone refractory metastatic prostate cancer by about 4 months. The vaccine is customized for each patient. Using leukopheresis, the patient's APCs are harvested and then cultured with a protein called PAP-GM-CSF. This protein consists of PAP linked to another protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF stimulates the immune system and enhances antigen presentation. APC cells cultured with PAP-GM-CSF are then infused into the patient with three treatments, usually two weeks apart. The exact mechanism of action of sipuleucel-T is unknown but, it is likely that the APCs that have taken up PAP-GM-CSF stimulate T cells to kill tumor cells that express PAP. Common side effects included fever, chills, fatigue, back and joint pain, nausea, and headache. These most often started during the cell infusions and resolved within one to two days. Even the studies of vaccines that did ultimately not work have taught us important lessons: 1. Cancer vaccines are well-tolerated. A number of Phase I and II trials have shown that cancer vaccines are generally well-tolerated, particularly with the viral and peptide vaccines. Phase I trials have reported very few significant toxicities with these vaccines. The most common toxicity in all of these trials has been local irritation at the site of the injection. In fact, it appears that patients that have a stronger local reaction to the injection may have a better response of the tumor to the treatment. This may be because a local reaction serves as a marker for people who have a good immune response to the vaccine. Patients with strong local reactions will likely have a strong reaction to the tumor as well. 2. Cancer vaccines induce an immune response. In both Phase I and Phase II trials, levels of immune activity have been measured in patients receiving cancer vaccines. Routinely, objective measures have shown an increase in the immune activity in a number of patients receiving cancer vaccines. In addition, patients who have a good immune response by objective measures have a better response of their tumors to the vaccine. 3. Several cancer vaccines show a good tumor response compared to historical results. Recently, the results of a non-randomized trial utilizing a melanoma vaccine were reported. Patients receiving the vaccine had a 5-year overall survival of 44%. Given the advanced disease in these patients, these results were quite good, and noticeably higher than historical surgical series of patients with similarly advanced disease showing 5-year overall survival rates of 20-25%. Another promising trial was recently reported which used a prostate cancer vaccine in patients with progressive disease (judged by rising PSA levels) after local therapy for prostate cancer. After a year and a half, 45% of patients did not have further increases in their PSA. 4. Results of Phase III, randomized trials have been disappointing. Despite the promising results in earlier trials, several large randomized trials have failed to show an overall survival advantage with the use of vaccines. A large trial by the Southwest Oncology Group for patients with melanoma who did not have spread of their disease to the lymph nodes showed no improvement in overall survival for patients who received the vaccine following surgery compared to patients who underwent surgery alone. Another trial for patients with renal cell carcinoma showed a small decrease in the percentage of patients who had progression of their cancer with the addition of a cancer vaccine. A story Inspection, palpation, percussion, auscultation – the unalterable, ever-applicable tetrad. Whatever part of the patient you examine, whatever disease you suspect, the four actions must be done in that order. You look first, then feel; when you have felt, you may tap, but not before – and last of all comes the stethoscope. I began to learn how to look at a patient so that even looking at his fingernails I could make a dozen diagnoses. They taught us to feel lumps, livers and spleens; how to percuss correctly and to understand the evasive murmurs transmitted through a stethoscope. Dr. Maxworth took his firm round the ward every Wednesday morning. He was a thin little man who always appeared in public in black coat and striped trousers. He was not really interested in students. For most of the round he forgot we were with him, but would suddenly recall our presence by throwing some instruction over his shoulder. He was a specialist in neurology, the diseases of the nervous system. As almost all the nervous diseases we saw in the ward appeared to be fatal, it seemed to me a very depressing speciality. But Maxworth drew certain pleasure from it. He was not concerned with treating his patients and making them better, but was delighted if he managed to make a diagnosis before the proof of the postmortem examination. He was, his assistant said, a typical physician. I began to see how the ward was managed by Sister, whom I avoided like a pile of radium. Every bodily function that could be measured – the pulse, the amount of urine, the quantity of vomit, the number of baths – was carefully recorded against a patient’s name in the treatment book, which reduced the twenty humans in the ward to a daily row of figures in her aggressive handwriting. There were two functions of the physiology in which Sister took special interest. One was temperature. The temperature charts shone neatly from the foot of the beds, and each showed a precise horizontal zigzag of different amplitude. The temperatures were taken by the junior nurses, who used four or five thermometers. However, the figures were looked as insignificant, because Sister substituted figures of her own, if the ones of the patient did not fit with her notion of what the temperature of the case ought to be. The other particular concern of the Sister was the patient’s bowels. A nurse was sent round the ward every evening with a special book to ask how many times each inmate had performed during the past twenty-four hours. The number of occasions was written in a separate square at the foot of the temperature chart. A nought was regarded by Sister as unpleasant, and more than two blank days she took as a personal insult. Treatment was simple. One nought was allowed to pass without punishment, but two automatically meant purgative, three – castor oil, and four – the supreme penalty of enema. We rapidly became accustomed to our position of inferiority to everyone on the ward staff. We did all the medical chores: urine testing, gruel meals in patients with duodenal ulcers, blood samples and a few simple investigations. For the first few weeks everything seemed easy. It was only at the end of the three-month’s practice that I realized how ignorant I was. A poem Escaping from drugs! Take me away; take me far Where I cannot listen to anyone Where there isn’t an alcohol bar Take me somewhere where there is no speed Where drugs do not exist Somewhere where I can’t take any weed Take me somewhere that I can call home Don’t leave me here in the middle of the street I need your help I can’t do this alone! Take me somewhere safe; just take me away Don’t leave me suffering, just set me free Give me the path to freedom and I’ll find the way!