Rilmenidine Phosphate

The idea of drug-induced/exogenic Nitrosogenesis is driven by the possibility of prolonged exposure of the human body to the influence of nitrosamines within the drug intake - substances or contaminants that have been proven to be carcinogenic or mutagenic one.Until recently, there was a complete lack of data in the scientific literature on the relationship between cancer, polymedication and polycontamination with nitrosamines. In the last decade, melanoma has been described repeatedly in the medical literature as a possible side-effect within the intake of possibly with nitrosamines contaminated medications such as: Valsartan, Hydrochlorothiazide, Amlodipine, Nebivolol, Bisoprolol and Perindopril. However, the contribution of the currently presented new data (5 new patients) is also due to the establishment of the possible pathogenetic role (with respect to melanoma) of several completely new drugs, previously unknown to the scientific community (potentially/actually contaminated with carcinogens/nitrosamines), such as: Ranitidine, Rosuvastatin, Lercanidipine, Rilmenidine, Trandolapril, Moxonidine and Verapamil.The leading and connecting link in shared new and old drug combinations of heterogeneous drug classes (polymedication) and melanoma development and progression remains again one and the same: the possible availability of nitroso component in the frame of exogenous nitrosogenesis according to the official FDA lists of 2023.The number of drugs shared as contaminated with nitrosamines after whose intake melanomas occur is increasing. Nitrosogenesis remains a new beginning, a new understanding and new interpretation of the carcinogenesis concerning melanoma, but probably also of cancer in general. Its further elucidation looks more than promising and is yet to come. More than worrying at the moment remains the fact that the scientific community has to clarify if: 1) peak concentrations of nitrosamines or NDSRIs within the framework of monomedication or 2) normal concentrations within the polymedication (catalogued in the list of FDA/ 2023 as potentially contaminated with hypothetical carcinogens), could hide relatively short-term risk of the development of real tumors: cutaneous melanomas and/or their precursor lesions. The validation of the concept of Nitrosogenesis and its relationship to Сarcinogenesis, is achieved in practice on the basis of the following facts: that it is the occurrence of the same monomorphic clinical pattern (melanoma/dysplastic nevi), developing after the intake of drugs with different mechanism of action, contaminated with nitrosamines/NDSRIs. The unifying link between the intake of certain drugs and the development of certain tumours remains the presence of nitrosamines. Ingredients that are present in drug preparations, identified as availability and as carcinogenic potency, but not yet reflected in packaging or prescriptions. The question remains: why?

Hepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments.

LncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by Oncomine cohorts.

LINC01116 and the PCG OLFML2B are differentially and highly expressed in tumor tissues (both P ≤ 0.050). We found that LINC01116, TMSB15A, PLAU, OLFML2B, and MRC2 have diagnostic potentials (all AUC ≥ 0.700, all P ≤ 0.050) while LINC01116 and TMSB15A have prognostic significance (both adjusted P ≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed that MRC2, OLFML2B, PLAU, and TMSB15A are negatively associated with the purity but positively associated with the specific cell types (all P < 0.050). Analysis of promoter methylation demonstrated that MRC2, OLFML2B, and PLAU have differential and high methylation levels in primary tumors (all P < 0.050). Validation results of the differential expressions and diagnostic potential of OLFML2B (Oncomine) were consistent with those obtained in the TCGA cohort (P < 0.050, AUC > 0.700).

Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates.