Prostatakrebs: Hoffnung durch schonende Therapie
Prostate cancer is a global public health problem, These Prostatakrebs it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects. To review currently relevant findings related to effects of cannabinoid receptors in prostate cancer.
Articles identified were screened for their relevance to the field These Prostatakrebs prostate cancer and interest to These Prostatakrebs urologist and pain specialists.
Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results in decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It would be These Prostatakrebs interest to conduct clinical studies These Prostatakrebs cannabinoids for patients with These Prostatakrebs prostate cancer, taking advantage not only of its These Prostatakrebs effects on prostate cancer but also of their analgesic properties for bone metastatic cancer pain.
Prostate cancer is These Prostatakrebs established public These Prostatakrebs concern in modern society and has been for decades. It is the most common cancer in men asides from non-melanoma skin cancer and the second most common cause of These Prostatakrebs death in the United States.
Cannabis and cannabinoids have often been an issue of much polemics in the realm of science, but since the discovery of cannabinoid receptors in rat brain in the late s,[ 3 ] there has been a growing interest in the research of these compounds and our knowledge continues to expand. There has been experimental evidence that cannabinoids possess anti-androgenic proprieties; the purpose of this review is to describe in detail the effects, characteristics, and possible role of cannabis and cannabinoids in the subject of prostate cancer.
Articles identified were screened for their relevance to the field of prostate cancer and likely interest to both urologist and pain specialists. This review These Prostatakrebs focuses on the effects of cannabinoids in the realm of prostate cancer pathophysiology and their potential uses. Prostate cancer is the most These Prostatakrebs cancer in American men except for non-melanoma skin cancer.
In the United States, an estimatedcases will be diagnosed in and 32, deaths will occur. Despite the fact that a higher percentage of men have localized disease at presentation, metastatic prostate cancer These Prostatakrebs an important clinical problem, both These Prostatakrebs terms of the number of affected men and its impact on their quality of life. Hematogenous spread of prostate cancer cells is a common event.
For these malignant cells, tumor These Prostatakrebs preferentially occurs in bones of the axial skeleton. The most common site of metastasis is bone and frequently is symptomatic, causing pain, debility, and functional impairment. Numerous treatment options have been established to treat bone metastatic prostate cancer; These Prostatakrebs focus on treating the underlying pathophysiology, while others These Prostatakrebs on pain management and palliative care.
More local modalities also considered in today's medical world are focal external beam radiation therapy, an excellent treatment choice for men with castrate-resistant prostate cancer and bone pain that is limited to one These Prostatakrebs a few sites, bone-targeted radioisotopes strontium 89Sr and samarium Sm for multiple blastic bone lesions, and radiofrequency ablation.
Cannabis is a bushy plant with palmate leaves and clusters of small green flowers, and it grows wild in regions of tropical weather and can attain up to 3 m height. The genus These Prostatakrebs is complemented by sativa which translates to useful.
Cannabis has indeed been used throughout history for a variety of purposes, including the production of fiber for These Prostatakrebs and textile manufacture. However, its current popularity These Prostatakrebs in its use as a recreational drug with psychoactive properties. These Prostatakrebs plant contains many chemical compounds that have different pharmacological properties, varying in quantity and quality depending on the strain, culture, and storage conditions. InMechoulam and colleagues[ 14 ] found that deltatetrahydrocannabinol THC was the major psychoactive ingredient of cannabis.
However, the endocannabinoid signaling system has only been These Prostatakrebs focus of medical research and considered a potential therapeutic target in recent times. The frequently held view of cannabis and its related products as drugs of abuse have slowed progress in the development of studies designed to take advantage of the properties of cannabinoid derivatives for therapeutic purposes.
The antagonizing effect of cannabinoids in the male reproductive system These Prostatakrebs physiology can be dated to where experimental models in male rats showed depression of spermatogenesis[ 21 ] and decrease in circulating testosterone levels.
In recent years, cannabinoids and their derivatives have drawn renewed attention due to the discovery of diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression. When the same cells were pretreated with cannabinoid receptor antagonists SR CB1 antagonist or SR CB2 antagonistthe coadministration of WIN, had no effect on cell viability, exhibiting a significant protective effect.
Androgens are involved in the maintenance and progression of prostate cancer, where the androgen receptor is assumed to These Prostatakrebs the essential mediator for androgen action. Curiously enough it was determined that high cannabinoid CB1 receptor immunoreactivity is associated with greater disease severity and poorer outcome in These Prostatakrebs cancer patients.
Patients with high CB1 receptor immunoreactivity showed a significantly worse survival rate than those with low CB1 receptor immunoreactivity hazard ratio 2. A possible explanation for these results that is in synch with the cell line data is that the expression of CB1 receptors These Prostatakrebs regulated by the local endocannabinoid release. The author's conclusion in this scenario was that a low endocannabinoid tone would allow These Prostatakrebs an increased rate of proliferation, resulting in a compensatory increase in surface expression of CB1 receptors.
Cannabinoid CB1 receptors are found mainly in the central nervous system and, in less abundance, in certain peripheral tissues. Activation of presynaptic CB1 receptors in different brain regions or on primary afferents inhibits the release of neurotransmitters by decreasing calcium conductance and by increasing the conductance of potassium. DeltaTHC is the substance with the greatest psychoactive potency of the natural cannabinoids and exhibits the greatest analgesic activity.
Studies with CBD derivatives developed to These Prostatakrebs peripheral pain responses and inflammation after binding to cannabinoid receptors have been described. Interestingly, some of these CBD derivatives did not have central nervous system effects, but maintained their antinociceptive and anti-inflammatory properties. This means that centrally inactive synthetic CBD analogues may be candidates for the development of analgesic and anti-inflammatory drugs for peripheral conditions[ 53 ] without major central nervous system alterations of the sensorium.
In animal models of cancer bone pain, synthetic cannabinoids reduced hyperalgesia by a CB1 receptor-mediated effect and possibly at the peripheral CB2 receptor. In some These Prostatakrebs, cannabinoids were superiorly effective in cancer pain when compared with These Prostatakrebs pain types.
Clinical trials have shown that nonselective cannabinoid receptor agonists are relatively safe and therapeutically efficacious, however, inducing also psychotropic side effects. Cannabinoid efficacy has also been studied clinically in cancer pain. Initial studies quantified the modest efficacy of oral 20 mg D9-THC equivalent to mg codeine with some sedation, dizziness, and confusion. Nabilone did not significantly increase adverse effects compared with the control group, and this fact could be attributed to the concurrent decrease in opioid dose.
Uncontrolled These Prostatakrebs can cause unnecessary suffering, decreased ability to cope with illness, interference with daily activities and extended hospital admissions, and decreasing overall quality These Prostatakrebs life.
Step 1 of the ladder is for patients with mild to moderate cancer-related pain. These should first be treated with acetaminophen or a nonsteroidal antiinflammatory agent NSAIDpossibly combined with an adjuvant drug that provides additional analgesia i.
Step 2 describes patients with moderate or severe pain, including those who do not achieve adequate relief after a trial of an NSAID alone; these should be treated with an opioid. The analgesic ladder promoted the doctrine of using an opioid These Prostatakrebs inferior analgesic properties i.
On both steps 2 and 3, combination therapy that includes an NSAID or other drugs to enhance analgesia or treat side effects is advocated. The combination of two antinociceptive drugs acting through different specific receptor systems provides major benefits. When These Prostatakrebs substances are given in combination, the These Prostatakrebs dose of each agent can be reduced to less than would be explained by mere addition of individual effects.
The clinical benefit of this property is fundamental in analgesic treatments because effective pain relief can be achieved with minor, fewer, or no side effects.
Chronic pain is a difficult subject to approach both for the patient and the treating These Prostatakrebs and, not uncommonly, leads to chronic opiate consumption These Prostatakrebs dependence. Cannabis has been documented to be one of such measures.
As with any therapeutic These Prostatakrebs, adverse effects must be taken into account. A number of patients will suffer from these, although most of them will be present within the first days of treatment and attenuate as they adjust to the drug. Chronic cannabis use does not produce serious cognitive disorders, as These Prostatakrebs with other substances such as alcohol, but it can aggravate preexisting mental disease. Therefore, treatment with cannabinoid receptor agonist with central actions may be contraindicated, in individuals predisposed to or with current psychiatric disorders.
No human deaths associated to cannabis use have been reported. Prostate cancer is a grave public health problem worldwide. For these reasons, it is fundamental to invest time and intellectual resources into finding new and novel targets for the treatment of prostate cancer. It seems that the studies of Sarfaraz and colleagues lead to the direction that cannabinoids should be considered as agents for the management of prostate cancer, pending support from in vivo experiments.
This would not only make sense from an anti-androgenic point of view but also for men with bone metastatic prostate cancer, perhaps from a pain These Prostatakrebs or palliative point of view. Among the patients suffering with chronic pain and receiving opioids, one in five abuse prescription controlled substances,[ These Prostatakrebs70 ] and it These Prostatakrebs not difficult to see that opioid dependence and abuse is becoming a public health problem.
Different methods of managing pain should be addressed to avoid these scenarios. The presence of pain in men with advanced prostate cancer is an immediate indication for aggressive management with analgesics, while adequate treatments that address directly the cause of the pain are pursued. These compounds harbor analgesic These Prostatakrebs that aid bone cancer pain, reduce opioid consumption, side effects, and dependence, as well as exhibiting anti-androgenic effects These Prostatakrebs experimental prostate cancer cells.
Cannabis sativa and its main active component deltaTHC have long been used for numerous purposes throughout history including medicinal, textile, and recreational. Since its legal banning in the United States init These Prostatakrebs become an issue of taboo and controversy, frowned upon for its recreational uses and psychotropic effects.
Nonetheless, the endocannabinoid signaling system has recently been the focus of medical research and considered a potential therapeutic These Prostatakrebs 15 — 17 ] since the late s when Howlett and These Prostatakrebs 3 ] identified and characterized the distinct cannabinoid receptor in rat brain.
If the hypothesis is supported by in vivo experiments. It is our conclusion that it would be of interest to conduct clinical trials involving medicinal cannabis or These Prostatakrebs cannabinoid agonists, These Prostatakrebs clinical markers such as PSA with controls, especially in men with These Prostatakrebs metastatic prostate cancer, whom would not only benefit from the possible anti-androgenic effects of cannabinoids but also from analgesia of bone pain, improving quality of life, while reducing narcotic consumption and preventing opioid dependence.
Source of Support: Nil. Conflict of Interest: None declared. National Center for Biotechnology InformationU. Journal List Indian J Urol v. Indian J Urol.
Juan A. Ramos and Fernando J. Bianco 1. Fernando J. Author information Copyright and License information Disclaimer. For correspondence: Dr. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3. This article has been cited by other articles in PMC. Abstract Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death.
Keywords: Androgen antagonists, cannabis, cannabinoids, investigational therapies, prostatic neoplasms. Overview: Prostate cancer Prostate cancer is the most common cancer in American men except for non-melanoma skin cancer.
Role of cannabinoids in male physiology Cannabis is a bushy plant with palmate leaves and clusters of small green flowers, and it grows wild in regions of tropical weather and can attain up to 3 m height. Current basic science research In recent years, cannabinoids and their derivatives have drawn renewed attention due to the discovery of diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory effects, and tumor regression.
Cannabinoids in cancer pain management Cannabinoid CB1 receptors are found mainly in the central nervous system and, in less abundance, in certain These Prostatakrebs tissues.
Cancer statistics, CA Cancer J Clin. Determination and characterization of a cannabinoid receptor in rat brain.