Lenalidomide, bortezomib and dexamethasone followed by tandem- autologous stem cell transplantation is an effective treatment modality for multi-hit multiple myeloma

Tang, Shaohui; Lu, Yin; Zhang, Pisheng; Chen, Dong; Liu, Xuhui; Du, Xiaohong; Cao, Junjie; Ye, Peipei; Chen, Lieguang; Li, Shuangyue; Sha, Keya; Zhuang, Xian xu; Xie, Yonghui; Wu, Xiaojin; Pei, Renzhi

doi:10.1016/j.leukres.2021.106710

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…Moreover, the multi-hit nature of carcinogenesis is often described [ 284 , 285 , 286 , 287 , 288 ]. As cannabinoids can deliver both double- and single-stranded DNA breaks and cause kinetochore disruption (hyperploidy and chromosomal mis-segregation), it becomes apparent that cannabinoids are capable of delivering the multi-point genomic hit in themselves.…”

Section: Discussionmentioning

confidence: 99%

Cannabis- and Substance-Related Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Study

Reece

Bennett

Hulse

2023

JoX

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Recent European data facilitate an epidemiological investigation of the controversial cannabis–cancer relationship. Of particular concern were prior findings associating high-dose cannabis use with reproductive problems and potential genetic impacts. Cancer incidence data age-standardised to the world population was obtained from the European Cancer Information System 2000–2020 and many European national cancer registries. Drug use data were obtained from the European Monitoring Centre for Drugs and Drug Addiction. Alcohol and tobacco consumption was sourced from the WHO. Median household income was taken from the World bank. Cancer rates in high-cannabis-use countries were significantly higher than elsewhere (β-estimate = 0.4165, p = 3.54 × 10−115). Eighteen of forty-one cancers (42,675 individual rates) were significantly associated with cannabis exposure at bivariate analysis. Twenty-five cancers were linked in inverse-probability-weighted multivariate models. Temporal lagging in panel models intensified these effects. In multivariable models, cannabis was a more powerful correlate of cancer incidence than tobacco or alcohol. Reproductive toxicity was evidenced by the involvement of testis, ovary, prostate and breast cancers and because some of the myeloid and lymphoid leukaemias implicated occur in childhood, indicating inherited intergenerational genotoxicity. Cannabis is a more important carcinogen than tobacco and alcohol and fulfills epidemiological qualitative and quantitative criteria for causality for 25/41 cancers. Reproductive and transgenerational effects are prominent. These findings confirm the clinical and epidemiological salience of cannabis as a major multigenerational community carcinogen.

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Section: Discussionmentioning

confidence: 99%

Cannabis- and Substance-Related Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Study

Reece

Bennett

Hulse

2023

JoX

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“…The multi-hit hypothesis is one of the common models of carcinogenesis and involves multiple genotoxic or epigenotoxic hits to the genome, which result in genomic instability [94,[155][156][157][158]. As cannabinoids can deliver both double-and single-stranded DNA breaks and cause the disruption of key kinetochore functions (hypoploidy [11], hyperploidy [12,99], and chromosomal mis-segregation [27,44,47,102]), it is clear that significant cannabinoid exposure can deliver multi-point genomic hits in themselves.…”

Section: Cannabinoids Deliver Multiple Carcinogenic Insultsmentioning

confidence: 99%

Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study

Reece

Hulse

2022

IJERPH

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The use of Δ8THC is increasing at present across the USA in association with widespread cannabis legalization and the common notion that it is “legal weed”. As genotoxic actions have been described for many cannabinoids, we studied the cancer epidemiology of Δ8THC. Data on 34 cancer types was from the Centers for Disease Control Atlanta Georgia, substance abuse data from the Substance Abuse and Mental Health Services Administration, ethnicity and income data from the U.S. Census Bureau, and cannabinoid concentration data from the Drug Enforcement Agency, were combined and processed in R. Eight cancers (corpus uteri, liver, gastric cardia, breast and post-menopausal breast, anorectum, pancreas, and thyroid) were related to Δ8THC exposure on bivariate testing, and 18 (additionally, stomach, Hodgkins, and Non-Hodgkins lymphomas, ovary, cervix uteri, gall bladder, oropharynx, bladder, lung, esophagus, colorectal cancer, and all cancers (excluding non-melanoma skin cancer)) demonstrated positive average marginal effects on fully adjusted inverse probability weighted interactive panel regression. Many minimum E-Values (mEVs) were infinite. p-values rose from 8.04 × 10−78. Marginal effect calculations revealed that 18 Δ8THC-related cancers are predicted to lead to a further 8.58 cases/100,000 compared to 7.93 for alcoholism and −8.48 for tobacco. Results indicate that between 8 and 20/34 cancer types were associated with Δ8THC exposure, with very high effect sizes (mEVs) and marginal effects after adjustment exceeding tobacco and alcohol, fulfilling the epidemiological criteria of causality and suggesting a cannabinoid class effect. The inclusion of pediatric leukemias and testicular cancer herein demonstrates heritable malignant teratogenesis.

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Is There Still a Role for Stem Cell Transplantation in Multiple Myeloma?

Gertz

2024

Hematology/Oncology Clinics of North America

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Lenalidomide, bortezomib and dexamethasone followed by tandem- autologous stem cell transplantation is an effective treatment modality for multi-hit multiple myeloma

Cited by 3 publications

References 23 publications

Cannabis- and Substance-Related Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Study

Cannabis- and Substance-Related Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Study

Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study

Is There Still a Role for Stem Cell Transplantation in Multiple Myeloma?

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