The Interplay between cancer biology and the endocannabinoid system - significance for cancer risk, prognosis and response to treatment

The various components of the endocannabinoid system (ECS), such as the cannabinoid receptors (CBRs), cannabinoid ligands, and the signalling network behind it, are implicated in several tumour-related states, both as favourable and unfavourable factors. This review analyses the ECS's complex involvement in the susceptibility to cancer, prognosis, and response to treatment, focusing on its relationship with cancer biology in selected solid cancers (breast, gastrointestinal, gynaecological, prostate cancer, thoracic, thyroid, CNS tumours, and melanoma). Changes in the expression and activation of CBRs, as well as their ability to form distinct functional heteromers a ect the cell's tumourigenic potential and their signalling properties, leading to pharmacologically di erent outcomes. Thus, the same ECS component can exert both protective and pathogenic e ects in di erent tumour subtypes, which are often pathologically driven by di erent biological factors. The use of endogenous and exogenous cannabinoids as anti-cancer agents, and the range of e ects they might induce (cell death, regulation of angiogenesis, and invasion or anticancer immunity), depend in great deal on the tumour type and the specific ECS component that they target. Although an attractive target, the use of ECS components in anti-cancer treatment is still interlinked with many legal and ethical issues that need to be considered

The endocannabinoid system as a target in cancer diseases: are we there yet?

The endocannabinoid system (ECS) has been placed in the anti-cancer spotlight in the last decade. The immense data load published on its dual role in both tumorigenesis and inhibition of tumor growth and metastatic spread has transformed the cannabinoid receptors CB1 (CB1R) and CB2 (CB2R), and other members of the endocannabinoid-like system, into attractive new targets for the treatment of various cancer subtypes. Although the clinical use of cannabinoids has been extensively documented in the palliative setting, clinical trials on their application as anti-cancer drugs are still ongoing. As drug repurposing is significantly faster and more economical than de novo introduction of a new drug into the clinic, there is hope that the existing pharmacokinetic and safety data on the ECS ligands will contribute to their successful translation into oncological healthcare. CB1R and CB2R are members of a large family of membrane proteins called G protein-coupled receptors (GPCR). GPCRs can form homodimers, heterodimers and higher order oligomers with other GPCRs or non-GPCRs. Currently, several CB1R and CB2R-containing heteromers have been reported and, in cancer cells, CB2R form heteromers with the G protein-coupled chemokine receptor CXCR4, the G protein-coupled receptor 55 (GPR55) and the tyrosine kinase receptor (TKR) human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2). These protein complexes possess unique pharmacological and signaling properties, and their modulation might affect the antitumoral activity of the ECS. This review will explore the potential of the endocannabinoid network in the anti-cancer setting as well as the clinical and ethical pitfalls behind it, and will develop on the value of cannabinoid receptor heteromers as potential new targets for anti-cancer therapies and as prognostic biomarkers

The Endocannabinoid System as a Target in Cancer Diseases: Are We There Yet?

The endocannabinoid system (ECS) has been placed in the anti-cancer spotlight in the last decade. The immense data load published on its dual role in both tumorigenesis and inhibition of tumor growth and metastatic spread has transformed the cannabinoid receptors CB1 (CB1R) and CB2 (CB2R), and other members of the endocannabinoid-like system, into attractive new targets for the treatment of various cancer subtypes. Although the clinical use of cannabinoids has been extensively documented in the palliative setting, clinical trials on their application as anti-cancer drugs are still ongoing. As drug repurposing is significantly faster and more economical than de novo introduction of a new drug into the clinic, there is hope that the existing pharmacokinetic and safety data on the ECS ligands will contribute to their successful translation into oncological healthcare. CB1R and CB2R are members of a large family of membrane proteins called G protein-coupled receptors (GPCR). GPCRs can form homodimers, heterodimers and higher order oligomers with other GPCRs or non-GPCRs. Currently, several CB1R and CB2R-containing heteromers have been reported and, in cancer cells, CB2R form heteromers with the G protein-coupled chemokine receptor CXCR4, the G protein-coupled receptor 55 (GPR55) and the tyrosine kinase receptor (TKR) human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2). These protein complexes possess unique pharmacological and signaling properties, and their modulation might affect the antitumoral activity of the ECS. This review will explore the potential of the endocannabinoid network in the anti-cancer setting as well as the clinical and ethical pitfalls behind it, and will develop on the value of cannabinoid receptor heteromers as potential new targets for anti-cancer therapies and as prognostic biomarkers

Detection of humoral and cellular immune response to anti-SARS-CoV-2 BNT162b2 vaccine in breastfeeding women and naïve and previously infected individuals

This study explored humoral and cellular responses to anti-SARS-CoV-2 BNT162b2 mRNA vaccine in breastfeeding women and naïve and seropositive individuals in the first six months after vaccination.Sixty-one volunteers vaccinated with two doses of the BNT162b2 mRNA vaccine were enrolled in the study. In-house developed ELISA was used for the quantification of SARS-CoV-2 RBD-specific antibodies. Cell surface marker expression and intracellular IFN-γ analysis were carried out by flow cytometry. The concentrations of IFN-γ, IL-6 and TNF were determined by ELISA. A significant rise in anti-RBD IgG antibody levels was observed 14 days after the first vaccine dose (p < 0.0001) in serum and milk. The expression of CD28 on CD4+ T cells was significantly higher compared to baseline (p < 0.05). There was a significant increase (p ≤ 0.05) in B cell lymphocyte subset after revaccination, and increased percentage of CD80+ B cells. The expression of IFN-γ in peripheral blood lymphocytes, CD3+ T cells and serum was significantly increased (p < 0.05). No significant difference in immune response was observed between breastfeeding women and other study participants. The anti-SARS-CoV-2 BNT162b2 mRNA vaccine-induced measurable and durable immune response in breastfeeding women and in naïve and previously infected individuals

Biological evaluation of transdichloridoplatinum( II) complexes with 3-and 4-acetylpyridine in comparison to cisplatin

Background. In our previous study we reported the synthesis and cytotoxicity of two trans-platinum(II) complexes: trans-[PtCl2(3-acetylpyridine)(2)] (1) and trans-[PtCl2(4-acetylpyridine)(2)] (2), revealing significant cytotoxic potential of 2. In order to evaluate the mechanism underlying biological activity of both trans-Pt(II) isomers, comparative studies versus cisplatin were performed in HeLa, MRC-5 and MS1 cells. Materials and methods. The cytotoxic activity of the investigated complexes was determined using SRB assay. The colagenolytic activity was determined using gelatin zymography, while the effect of platinum complexes on matrix metalloproteinases 2 and 9 mRNA expression was evaluated by quantitative real-time PCR. Apoptotic potential and cell cycle alterations were determined by FACS analyses. Western blot analysis was used to evaluate the effect on expression of DNA-repair enzyme ERCC1, and quantitative real-time PCR was used for the ERCC1 mRNA expression analysis. In vitro antiangiogenic potential was determined by tube formation assay. Platinum content in intracellular DNA and proteins was determined by inductively coupled plasma-optical emission spectrometry. Results. Compound 2 displayed an apparent cytoselective profile, and flow cytometry analysis in HeLa cells indicated that 2 exerted antiproliferative effect through apoptosis induction, while 1 induced both apoptosis and necrosis. Action of 1 and 2, as analyzed by quantitative real-time PCR and Western blot, was associated with down-regulation of ERCC1. Both trans-complexes inhibited MMP-9 mRNA expression in HeLa, while 2 significantly abrogated in vitro tubulogenesis in MS1 cells. Conclusions. The ability of 2 to induce multiple and selective in vitro cytotoxic effects encourages further investigations of trans-platinum(II) complexes with substituted pyridines

Pathological Diagnosis, Work-Up and Reporting of Breast Cancer 1st Central-Eastern European Professional Consensus Statement on Breast Cancer

Abstract This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.The 1st Central-Eastern European Professional Consensus Statements on Breast Cancer were initiated, organized and granted by the Central-Eastern European Academy of Oncology (CEEAO), the National Institute of Oncology, Hungary and the Bács-Kiskun County Teaching Hospital. This regional oncological project was supported by Prof. Miklós Kásler, founder of CEEAO, Minister of Human Capacities, the Government of Hungary

The endocannabinoid system as a target in cancer diseases: are we there yet?

The endocannabinoid system (ECS) has been placed in the anti-cancer spotlight in the last decade. The immense data load published on its dual role in both tumorigenesis and inhibition of tumor growth and metastatic spread has transformed the cannabinoid receptors CB1 (CB1R) and CB2 (CB2R), and other members of the endocannabinoid-like system, into attractive new targets for the treatment of various cancer subtypes. Although the clinical use of cannabinoids has been extensively documented in the palliative setting, clinical trials on their application as anti-cancer drugs are still ongoing. As drug repurposing is significantly faster and more economical than de novo introduction of a new drug into the clinic, there is hope that the existing pharmacokinetic and safety data on the ECS ligands will contribute to their successful translation into oncological healthcare. CB1R and CB2R are members of a large family of membrane proteins called G protein-coupled receptors (GPCR). GPCRs can form homodimers, heterodimers and higher order oligomers with other GPCRs or non-GPCRs. Currently, several CB1R and CB2R-containing heteromers have been reported and, in cancer cells, CB2R form heteromers with the G protein-coupled chemokine receptor CXCR4, the G protein-coupled receptor 55 (GPR55) and the tyrosine kinase receptor (TKR) human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2). These protein complexes possess unique pharmacological and signaling properties, and their modulation might affect the antitumoral activity of the ECS. This review will explore the potential of the endocannabinoid network in the anti-cancer setting as well as the clinical and ethical pitfalls behind it, and will develop on the value of cannabinoid receptor heteromers as potential new targets for anti-cancer therapies and as prognostic biomarkers

The endocannabinoid system as a target in cancer diseases: are we there yet?

The endocannabinoid system (ECS) has been placed in the anti-cancer spotlight in the last decade. The immense data load published on its dual role in both tumorigenesis and inhibition of tumor growth and metastatic spread has transformed the cannabinoid receptors CB1 (CB1R) and CB2 (CB2R), and other members of the endocannabinoid-like system, into attractive new targets for the treatment of various cancer subtypes. Although the clinical use of cannabinoids has been extensively documented in the palliative setting, clinical trials on their application as anti-cancer drugs are still ongoing. As drug repurposing is significantly faster and more economical than de novo introduction of a new drug into the clinic, there is hope that the existing pharmacokinetic and safety data on the ECS ligands will contribute to their successful translation into oncological healthcare. CB1R and CB2R are members of a large family of membrane proteins called G protein-coupled receptors (GPCR). GPCRs can form homodimers, heterodimers and higher order oligomers with other GPCRs or non-GPCRs. Currently, several CB1R and CB2R-containing heteromers have been reported and, in cancer cells, CB2R form heteromers with the G protein-coupled chemokine receptor CXCR4, the G protein-coupled receptor 55 (GPR55) and the tyrosine kinase receptor (TKR) human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2). These protein complexes possess unique pharmacological and signaling properties, and their modulation might affect the antitumoral activity of the ECS. This review will explore the potential of the endocannabinoid network in the anti-cancer setting as well as the clinical and ethical pitfalls behind it, and will develop on the value of cannabinoid receptor heteromers as potential new targets for anti-cancer therapies and as prognostic biomarkers