Category Archives: Cancer

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Cannabidiol: State of the art and new challenges for therapeutic applications.

Category : Cancer

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Cannabidiol: State of the art and new challenges for therapeutic applications.

Pharmacol Ther. 2017 Feb 20;:

Authors: Pisanti S, Malfitano AM, Ciaglia E, Lamberti A, Ranieri R, Cuomo G, Abate M, Faggiana G, Proto MC, Fiore D, Laezza C, Bifulco M

Abstract
Over the past years, several lines of evidence support a therapeutic potential of Cannabis derivatives and in particular phytocannabinoids. Δ(9)-THC and cannabidiol (CBD) are the most abundant phytocannabinoids in Cannabis plants and therapeutic application for both compounds have been suggested. However, CBD is recently emerging as a therapeutic agent in numerous pathological conditions since devoid of the psychoactive side effects exhibited instead by Δ(9)-THC. In this review, we highlight the pharmacological activities of CBD, its cannabinoid receptor-dependent and -independent action, its biological effects focusing on immunomodulation, angiogenetic properties, and modulation of neuronal and cardiovascular function. Furthermore, the therapeutic potential of cannabidiol is also highlighted, in particular in nuerological diseases and cancer.

PMID: 28232276 [PubMed – as supplied by publisher]

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Ultra-high performance liquid chromatography tandem mass-spectrometry for simple and simultaneous quantification of cannabinoids.

Category : Cancer

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Ultra-high performance liquid chromatography tandem mass-spectrometry for simple and simultaneous quantification of cannabinoids.

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 06;1048:10-18

Authors: Jamwal R, Topletz AR, Ramratnam B, Akhlaghi F

Abstract
Cannabis is used widely in the United States, both recreationally and for medical purposes. Current methods for analysis of cannabinoids in human biological specimens rely on complex extraction process and lengthy analysis time. We established a rapid and simple assay for quantification of Δ(9)-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-hydroxy Δ(9)-tetrahydrocannabinol (11-OH THC) and 11-nor-9-carboxy-Δ(9)-tetrahydrocannbinol (THCCOOH) in human plasma by U-HPLC-MS/MS usingΔ9-tetrahydrocannabinol-D3 (THC-D3) as the internal standard. Chromatographic separation was achieved on an Acquity BEH C18 column using a gradient comprising of water (0.1% formic acid) and methanol (0.1% formic acid) over a 6 min run-time. Analytes from 200μL plasma were extracted using acetonitrile (containing 1% formic acid and THC-D3). Mass spectrometry was performed in positive ionization mode, and total ion chromatogram was used for quantification of analytes. The assay was validated according to guidelines set forth by Food and Drug Administration of the United States. An eight-point calibration curve was fitted with quadratic regression (r(2)>0.99) from 1.56 to 100ngmL(-1) and a lower limit of quantification (LLOQ) of 1.56ngmL(-1) was achieved. Accuracy and precision calculated from six calibration curves was between 85-115% while the mean extraction recovery was >90% for all the analytes. Several plasma phospholipids eluted after the analytes thus did not interfere with the assay. Bench-top, freeze-thaw, auto-sampler and short-term stability ranged from 92.7 to 106.8% of nominal values. Application of the method was evaluated by quantification of analytes in human plasma from six subjects.

PMID: 28192758 [PubMed – as supplied by publisher]

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Cannabidiol: an alternative therapeutic agent for oral mucositis?

Category : Cancer

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Cannabidiol: an alternative therapeutic agent for oral mucositis?

J Clin Pharm Ther. 2017 Feb 12;:

Authors: Cuba LF, Salum FG, Cherubini K, Figueiredo MA

Abstract
WHAT IS KNOWN AND OBJECTIVE: Chemo- and radiotherapy are therapeutic modalities often used in patients with malignant neoplasms. They kill tumour cells but act on healthy tissues as well, resulting in adverse effects. Oral mucositis is especially of concern, due to the morbidity that it causes. We reviewed the literature on the etiopathogenesis of oral mucositis and the activity of cannabidiol, to consider the possibility of its use for the prevention and treatment of oral mucositis.
METHODS: We searched the PubMed database and selected complete articles published in English that met the inclusion criteria for the period 1998-2016. The search terms ‘cannabinoids’, ‘cannabidiol’, ‘oxidative stress’, ‘antioxidants’ and ‘oral mucositis’ were used.
RESULTS AND DISCUSSION: The control of oxidative stress may prevent and alleviate oral mucositis. Studies have demonstrated that cannabidiol is safe to use and possesses antioxidant, anti-inflammatory and analgesic properties.
WHAT IS NEW AND CONCLUSIONS: The literature on the use of cannabidiol in dentistry is still scarce. Studies investigating the use of cannabidiol in oral mucositis and other oxidative stress-mediated side effects of chemotherapy and radiotherapy on the oral mucosa should be encouraged.

PMID: 28191662 [PubMed – as supplied by publisher]

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Phytochemistry of Cannabis sativa L.

Category : Cancer

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Phytochemistry of Cannabis sativa L.

Prog Chem Org Nat Prod. 2017;103:1-36

Authors: ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A

Abstract
Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The plant’s behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ(9)-THC, which is produced mainly in the leaves and flower buds of the plant. Besides Δ(9)-THC, there are also non-psychoactive cannabinoids with several medicinal functions, such as cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG), along with other non-cannabinoid constituents belonging to diverse classes of natural products. Today, more than 560 constituents have been identified in cannabis. The recent discoveries of the medicinal properties of cannabis and the cannabinoids in addition to their potential applications in the treatment of a number of serious illnesses, such as glaucoma, depression, neuralgia, multiple sclerosis, Alzheimer’s, and alleviation of symptoms of HIV/AIDS and cancer, have given momentum to the quest for further understanding the chemistry, biology, and medicinal properties of this plant.This contribution presents an overview of the botany, cultivation aspects, and the phytochemistry of cannabis and its chemical constituents. Particular emphasis is placed on the newly-identified/isolated compounds. In addition, techniques for isolation of cannabis constituents and analytical methods used for qualitative and quantitative analysis of cannabis and its products are also reviewed.

PMID: 28120229 [PubMed – in process]

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Targeting calcium signaling in cancer therapy.

Category : Cancer

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Targeting calcium signaling in cancer therapy.

Acta Pharm Sin B. 2017 Jan;7(1):3-17

Authors: Cui C, Merritt R, Fu L, Pan Z

Abstract
The intracellular calcium ions (Ca(2+)) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca(2+) homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca(2+) signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca(2+) channels, transporters and Ca(2+)-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca(2+) channels/transporters or Ca(2+)-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca(2+) signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca(2+) channels or transporters.

PMID: 28119804 [PubMed]

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Inhibition of cervical cancer cell proliferation by cannabidiol.

Category : Cancer

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Inhibition of cervical cancer cell proliferation by cannabidiol.

Planta Med. 2016 Dec;81(S 01):S1-S381

Authors: Bagavandoss P, Crawford B, Kramer C

PMID: 27976061 [PubMed – in process]

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Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

Category : Cancer

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Quantitative analyses of synergistic responses between cannabidiol and DNA-damaging agents on the proliferation and viability of glioblastoma and neural progenitor cells in culture.

J Pharmacol Exp Ther. 2016 Nov 7;:

Authors: Deng L, Ng L, Ozawa T, Stella N

Abstract
Evidence suggests that the non-psychotropic cannabis-derived compound, cannabidiol (CBD), has anti-neoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the anti-proliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system (CNS) toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Co-treatment regiments combining CBD and DNA-damaging agents produced synergistic anti-proliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little-to-no therapeutic window when considering NPCs.

PMID: 27821713 [PubMed – as supplied by publisher]

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Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

Category : Cancer

Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

Oncotarget. 2016 Oct 18;:

Authors: Nabissi M, Morelli MB, Offidani M, Amantini C, Gentili S, Soriani A, Cardinali C, Leoni P, Santoni G

Abstract
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy. In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines. We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis. Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein. Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ. Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration. In summary, these results proved that this combination exerts strong anti-myeloma activities.

PMID: 27769052 [PubMed – as supplied by publisher]

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TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer.

Category : Cancer

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TRPV2 is a novel biomarker and therapeutic target in triple negative breast cancer.

Oncotarget. 2016 May 27;

Authors: Elbaz M, Ahirwar D, Xiaoli Z, Zhou X, Lustberg M, Nasser MW, Shilo K, Ganju RK

Abstract
Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs. In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERα-) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy. In addition, we showed that TRPV2 overexpression or activation by CBD significantly increased doxorubicin (DOX) uptake and apoptosis in TNBC cells. The induction of DOX uptake was abrogated by TRPV2 blocking or downregulation. In vivo mouse model studies showed that the TNBC tumors derived from CBD+DOX treated mice have significantly reduced weight and increased apoptosis compared to those treated with CBD or DOX alone. Overall, our studies for the first time revealed that TRPV2 might be a good prognostic marker for TNBC and ERα- breast cancer patient especially for those who are treated with chemotherapy. In addition, TRPV2 activation could be a novel therapeutic strategy to enhance the uptake and efficacy of chemotherapy in TNBC patients.

PMID: 27248470 [PubMed – as supplied by publisher]

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The Use of Medical Marijuana in Cancer.

Category : Cancer

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The Use of Medical Marijuana in Cancer.

Curr Oncol Rep. 2016 Jul;18(7):40

Authors: Birdsall SM, Birdsall TC, Tims LA

Abstract
The use of medical marijuana in cancer care presents a dilemma for both patients and physicians. The scientific evidence is evolving, yet much of the known information is still insufficient to adequately inform patients as to risks and benefits. In addition, evidence-based dosing and administration information on medical marijuana is lacking. Medical marijuana is now legal, on some level, in 24 states plus the District of Columbia, yet is not legal on the federal level. This review addresses the current state of the research, including potential indications, risks and adverse effects, preliminary data on anticancer effects, as well as legal and quality issues. A summary of the clinical trials underway on medical marijuana in the oncology setting is discussed.

PMID: 27215434 [PubMed – in process]

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