CANNABINOIDS AND CANCER FEBRERO 2019

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1. J Pancreat Cancer. 2019 Jan

Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer.

Sharafi G(1), He H(1), Nikfarjam M(1).

Author information: 
(1)Department of Surgery, University of Melbourne, Austin Health, Melbourne,
Australia.

Background: Cannabinoid extracts may have anticancer properties, which can
improve cancer treatment outcomes. The aim of this review is to determine the
potentially utility of cannabinoids in the treatment of pancreatic cancer.
Methods: A literature review focused on the biological effects of cannabinoids in
cancer treatment, with a focus on pancreatic cancer, was conducted. In vitro and 
in vivo studies that investigated the effects of cannabinoids in pancreatic
cancer were identified and potential mechanisms of action were assessed. Results:
Cannabinol receptors have been identified in pancreatic cancer with several
studies showing in vitro antiproliferative and proapoptotic effects. The main
active substances found in cannabis plants are cannabidiol (CBD) and
tetrahydrocannabinol (THC). There effects are predominately mediated through, but
not limited to cannabinoid receptor-1, cannabinoid receptor-2, and
G-protein-coupled receptor 55 pathways. In vitro studies consistently
demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic
derivatives. Synergistic treatment effects have been shown in two studies with
the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in
xenograft and genetically modified spontaneous pancreatic cancer models. There
are, however, no clinical studies to date showing treatment benefits in patients 
with pancreatic cancer. Conclusions: Cannabinoids may be an effective adjunct for
the treatment of pancreatic cancer. Data on the anticancer effectiveness of
various cannabinoid formulations, treatment dosing, precise mode of action, and
clinical studies are lacking.



2. J Surg Res. 2019 Mar
30.

Cannabinoids as a Potential New and Novel Treatment for Melanoma: A Pilot Study
in a Murine Model.

Simmerman E(1), Qin X(2), Yu JC(3), Baban B(4).

Author information: 
(1)Department of Oral Biology/Dental College of Georgia, Augusta University
Medical Center, Augusta, Georgia; Division of Plastic Surgery/Medical College of 
Georgia, Department of Surgery, Augusta University Medical Center, Augusta,
Georgia. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(2)Department of Oral Biology/Dental College of Georgia, Augusta University
Medical Center, Augusta, Georgia.
(3)Division of Plastic Surgery/Medical College of Georgia, Department of Surgery,
Augusta University Medical Center, Augusta, Georgia.
(4)Department of Oral Biology/Dental College of Georgia, Augusta University
Medical Center, Augusta, Georgia; Division of Plastic Surgery/Medical College of 
Georgia, Department of Surgery, Augusta University Medical Center, Augusta,
Georgia.

BACKGROUND: Malignant melanoma is a complex malignancy with significant morbidity
and mortality. The incidence continues to rise, and despite advances in
treatment, the prognosis is poor. Thus, it is necessary to develop novel
strategies to treat this aggressive cancer. Synthetic cannabinoids have been
implicated in inhibiting cancer cell proliferation, reducing tumor growth, and
reducing metastasis. We developed a unique study focusing on the effects of
treatment with a cannabinoid derivative on malignant melanoma tumors in a murine 
model.
METHODS: Murine B16F10 melanoma tumors were established subcutaneously in C57BL/6
mice. Mice were then treated with intraperitoneal injections of vehicle twice per
week (control-group 1, n = 6), Cisplatin 5 mg/kg/wk (group 2; n = 6), and
Cannabidiol (CBD) 5 mg/kg twice per week (group 3; n = 6). Tumors were measured
and volume calculated as (4π/3) × (width/2)2 × (length/2). Tumor size and
survival curves were measured. Results were compared using a one-way ANOVA with
multiple comparison test.
RESULTS: A significant decrease in tumor size was detected in mice treated with
CBD when compared with the control group (P = 0.01). The survival curve of
melanoma tumors treated with CBD increased when compared with the control group
and was statistically significant (P = 0.04). The growth curve and survival curve
of melanoma tumors treated with Cisplatin were significantly decreased and
increased, respectively, when compared with the control and CBD-treated groups.
Mice treated with Cisplatin demonstrated the longest survival time, but the
quality of life and movement of CBD-treated mice were observed to be better.
CONCLUSIONS: We demonstrate a potential beneficial therapeutic effect of
cannabinoids, which could influence the course of melanoma in a murine model.
Increased survival and less tumorgenicity are novel findings that should guide
research to better understand the mechanisms by which cannabinoids could be
utilized as adjunctive treatment of cancer, specifically melanoma. Further
studies are necessary to evaluate this potentially new and novel treatment of
malignant melanoma.

Copyright © 2018 Elsevier Inc. All rights reserved.
3. Internist (Berl). 2019 Jan 24. doi: 10.1007/s00108-019-0556-0. [Epub ahead of print] [Cannabis and cannabinoids-easier access, hype and disappointment : What has been confirmed in therapy?] Rasche T(1), Emmert D(2), Stieber C(2), Conrad R(3), Mücke M(2). Author information: (1)Zentrum für Seltene Erkrankungen (ZSEB), Universitätsklinikum Bonn, 53127, Bonn, Deutschland. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. (2)Zentrum für Seltene Erkrankungen (ZSEB), Universitätsklinikum Bonn, 53127, Bonn, Deutschland. (3)Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Bonn, Bonn, Deutschland. BACKGROUND: Cannabis products are being increasingly liberalized all over the world and there is a huge interest in cannabis-based medicine. OBJECTIVES: Presentation of current studies on the efficacy of different cannabis-based medicine for the treatment of various diseases CURRENT DATA: In German pharmaceutical legislation, nabiximols is approved for the treatment of moderate to severe therapy-resistant spasticity in multiple sclerosis and nabilone is approved for the treatment of therapy-resistant chemotherapy-associated nausea and vomiting. In case of therapy failure cannabinoids, as part of an individual therapeutic attempt, may be considered for the treatment of chronic pain (neuropathic pain, cancer pain, non-neuropathic noncancer pain), cachexia in human immunodeficiency virus as well as for Dravet and Lennox-Gastaut syndrome. From the authors' perspective there is not enough evidence for the use in chemotherapy-associated nausea and vomiting and chronic non-neuropathic pain. CONCLUSIONS: Currently, a wide use of cannabinoids does not seem probable in the near future. Further studies involving more patients and evaluating long-term effects are necessary. 4. Cancers (Basel). 2019 Jan Prospects for the Use of Cannabinoids in Oncology and Palliative Care Practice: A Review of the Evidence. Dzierżanowski T(1). Author information: (1)Laboratory of Palliative Medicine, Department of Social Medicine and Public Health, Medical University of Warsaw, ul. Oczki 3, Warszawa 02-007, Poland. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. There is an increased interest in the use of cannabinoids in the treatment of symptoms in cancer and palliative care patients. Their multimodal action, in spite of limited efficacy, may make them an attractive alternative, particularly in patients with multiple concomitant symptoms of mild and moderate intensity. There is evidence to indicate cannabis in the treatment of pain, spasticity, seizures, sleep disorders, nausea and vomiting, and Tourette syndrome. Although the effectiveness of cannabinoids is limited, it was confirmed in neuropathic pain management and combination with opioids. A relatively favorable adverse effects profile, including no depressive effect on the respiratory system, may make cannabis complement a rather narrow armamentarium that is in the disposition of a palliative care professional. 5. Cannabis Cannabinoid Res. 2018 Dec Synthetic Cannabinoid Activity Against Colorectal Cancer Cells. Raup-Konsavage WM(1), Johnson M(1), Legare CA(1), Yochum GS(2), Morgan DJ(1)(3), Vrana KE(1). Author information: (1)Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania. (2)Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania. (3)Department of Anesthesiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new therapeutic strategies are still required. Here we screened a synthetic cannabinoid library to identify compounds that uniformly reduce the viability of seven CRC cell lines. Material and Methods: Seven distinct CRC cell lines were treated with 10 μM cannabinoid compounds (from a library of 370 molecules) for 48 h, and cell viability was subsequently measured with MTS assay. Dose-response curves were conducted for compounds that were found to reproducibly reduce cell viability of one or more cell lines. Results: We identified 10 compounds from the library that were able to reduce cell viability of CRC cell lines (with an IC50 ≤ 30 μM). Of these compounds, seven were specific for CRC cells, and six were effective in all CRC cell lines tested. Treatment with traditional phytocannabinoids (THC or CBD) was either ineffective or much less potent and only partially efficacious. Treatment with antagonists for the known cannabinoid receptors (alone or in combination) failed to block the activity of the most potent of identified compounds. Conclusion: We identified three families of cannabinoid compounds that reduce CRC cell viability through a noncanonical receptor mechanism. Future modification of these compounds may lead to the development of novel therapies to treat this disease.