CANNABINOIDS AND CANCER OCTUBRE 2018

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1. Anticancer Res. 2018 Oct

Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade
Synthetic Cannabidiol.

Kenyon J(1), Liu W(2), Dalgleish A(2).

Author information: 
(1)The Old Brewery, Winchester Hants, U.K. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(2)St George's University of London, London, U.K.

BACKGROUND/AIM: Cannabinoids are widely used in the management of pain, nausea
and cachexia in cancer patients. However, there has been no objective clinical
evidence of any anticancer activity yet. The aim of this study was to assess the 
effects of pharmaceutical-grade synthetic cannabidiol on a range of cancer
patients.
PATIENTS AND METHODS: We analysed the data routinely collected, as part of our
treatment program, in 119 cancer patients over a four-year period.
RESULTS: Clinical responses were seen in 92% of the 119 cases with solid tumours 
including a reduction in circulating tumour cells in many cases and in other
cases, a reduction in tumour size, as shown by repeat scans. No side-effects of
any kind were observed when using pharmaceutical grade synthetic cannabidiol.
CONCLUSION: Pharmaceutical-grade synthetic cannabidiol is a candidate for
treating breast cancer and glioma patients.

Copyright© 2018, International Institute of Anticancer Research (Dr. George J.
Delinasios), All rights reserved.


2. Pharmacol Res. 2018 Sep

Bortezomib and endocannabinoid/endovanilloid system: a synergism in osteosarcoma.

Punzo F(1), Tortora C(2), Di Pinto D(2), Pota E(2), Argenziano M(3), Di Paola
A(2), Casale F(2), Rossi F(4).

Author information: 
(1)Department of Women, Child and General and Specialist Surgery, Università
degli Studi della Campania "Luigi Vanvitelli", Via De Crecchio 4, 80138, Naples, 
Italy; Department of Experimental Medicine, Division of Pharmacology "Leonardo
Donatelli", Università degli Studi della Campania "Luigi Vanvitelli", Via S.
Maria di Costantinopoli 14, 80138, Naples, Italy.
(2)Department of Women, Child and General and Specialist Surgery, Università
degli Studi della Campania "Luigi Vanvitelli", Via De Crecchio 4, 80138, Naples, 
Italy.
(3)Department of Experimental Medicine, Division of Pharmacology "Leonardo
Donatelli", Università degli Studi della Campania "Luigi Vanvitelli", Via S.
Maria di Costantinopoli 14, 80138, Naples, Italy.
(4)Department of Women, Child and General and Specialist Surgery, Università
degli Studi della Campania "Luigi Vanvitelli", Via De Crecchio 4, 80138, Naples, 
Italy. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..

Osteosarcoma is the most common primary malignant tumor of bone in children and
adolescents. Bortezomib (BTZ) is an approved anticancer drug, classified as a
selective reversible inhibitor of the ubiquitin-dependent proteasome system, that
leads to cancer cell cycle arrest and apoptosis reducing the invasion ability of 
Osteosarcoma cells in vitro. It also regulates the RANK/RANKL/OPG system,
involved in the pathogenesis of bone tumors and in cell migration. A side effect 
of BTZ is to induce painful sensory peripheral neuropathy which lead to cessation
of therapy or dose reduction. Recently BTZ has been evaluated in combination with
Cannabinoids targeting CB1 receptor, demonstrating a promising synergic effect.
The Endocannabinoid/Endovanilloid (EC/EV) system includes two G protein-coupled
receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel and 
their endogenous ligands and enzymes. CB1 and CB2 are expressed mainly in Central
Nervous System and Immune Peripheral cells respectively. TRPV1 is also expressed 
in primary sensory neurons and is involved in pain modulation. EC/EV system
induces apoptosis, reduces invasion and cell proliferation in Osteosarcoma cell
lines and is involved in bone metabolism. We analyzed the effects of BTZ, alone
and in combination with selective agonists at CB2 (JWH-133) and TRPV1 (RTX)
receptors, in the Osteosarcoma cell line (HOS) on Apoptosis, Cell Cycle
progression, migration and bone balance. We observed that the stimulation of CB2 
and TRPV1 receptors increase the efficacy of BTZ in inducing apoptosis and
reducing invasion, cell cycle progression and by modulating bone balance. These
data suggest the possibility to use BTZ, in combination with EC/EV agonists, in
Osteosarcoma therapy reducing its dose and its side effects.

Copyright © 2018 Elsevier Ltd. All rights reserved.



3. N Engl J Med. 2018 Sep

Hemorrhagic Highs from Synthetic Cannabinoids - A New Epidemic.

Connors JM(1).

Author information: 
(1)From the Hematology Division, Brigham and Women's Hospital, Dana-Farber Cancer
Institute, and Harvard Medical School - all in Boston.



4. Prostate. 2018 Sep

Cannabinoid WIN 55,212-2 induces cell cycle arrest and apoptosis, and inhibits
proliferation, migration, invasion, and tumor growth in prostate cancer in a
cannabinoid-receptor 2 dependent manner.

Roberto D(1)(2), Klotz LH(1)(2), Venkateswaran V(1)(2).

Author information: 
(1)Department of Surgery (Urology), Sunnybrook Health Sciences Centre, Toronto,
Ontario, Canada.
(2)Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

BACKGROUND: Cannabinoids have demonstrated anticarcinogenic properties in a
variety of malignancies, including in prostate cancer. In the present study, we
explored the anti-cancer effects of the synthetic cannabinoid WIN 55,212-2 (WIN) 
in prostate cancer.
METHODS: Established prostate cancer cells (PC3, DU145, LNCaP) were treated with 
varying concentrations of WIN. Cell proliferation was determined by the MTS
assay. The anti-migration and anti-invasive potential of WIN was examined by the 
wound healing assay and the matrigel invasion assay. Cell cycle analysis was
performed by flow cytometry, and mechanistic studies were performed by Western
blot. Athymic mice (n = 10) were inoculated with human PC3 cells. Once tumors
reached 100 mm3 , animals were randomized into two groups: saline control and WIN
(5 mg/kg), delivered by intraperitoneal injection three times per week for 3
weeks.
RESULTS: WIN significantly reduced prostate cancer cell proliferation, migration,
invasion, induced apoptosis, and arrested cells in Go/G1 phase in a
dose-dependent manner. Mechanistic studies revealed these effects were mediated
through a pathway involving cell cycle regulators p27, Cdk4, and pRb.
Pre-treatment with a CB2 antagonist, AM630, followed by treatment with WIN
resulted in a reversal of the anti-proliferation and cell cycle arrest previously
seen with WIN alone. In vivo, administration of WIN resulted in a reduction in
the tumor growth rate compared to control (P < 0.05).
CONCLUSIONS: The following study provides evidence supporting the use of WIN as a
novel therapeutic for prostate cancer.

© 2018 Wiley Periodicals, Inc.


5. Am Soc Clin Oncol Educ Book. 2018 May

Care After Chemotherapy: Peripheral Neuropathy, Cannabis for Symptom Control, and
Mindfulness.

Teoh D(1), Smith TJ(1), Song M(1), Spirtos NM(1).

Author information: 
(1)From the Division of Gynecologic Oncology, University of Minnesota,
Minneapolis, MN; Division of Palliative Medicine, Johns Hopkins University,
Baltimore, MD; Division of Oncology, Johns Hopkins University, Baltimore, MD;
Division of Gynecologic Oncology, Women's Cancer Center of Nevada, Las Vegas, NV;
The Apothecary Shoppe, Las Vegas, NV.

As cancer therapies improve, patients are living longer. With these improvements 
in therapy comes a responsibility to optimize patients' quality of life during
cancer therapy and beyond. This report reviews three timely and important topics.
The first section reviews the mechanism underlying chemotherapy-induced
peripheral neuropathy and evaluates the evidence for interventions to prevent and
treat peripheral neuropathy. It also provides a framework for approaching the
diagnosis and management of this common and bothersome side effect. The second
section addresses the controversial but effective use of cannabinoids for cancer 
and chemotherapy symptoms. Although clinical trials are difficult to conduct
because of the political and social stigma of this class of drugs, this review
provides evidence of the efficacy of cannabinoids for treatment of pain and
nausea. The last section addresses the mind-body connection, with a focus on the 
negative emotions patients with cancer often experience. This section assesses
the literature regarding mindfulness-based programs to improve cancer-related
stress. These three topics may appear unrelated, but all address one common goal:
treating the body and the mind to optimize quality of life during and after
cancer therapy.