Pharmacokinetics and pharmacodynamics of angiogenesis inhibitors used to treat cervical cancer: current and future.

Introduction: The treatment of advanced cervical cancer is continuously developing. There is a critical need to explore new treatment options to improve cure rates and make treatment more affordable. Despite efforts in prevention, cervical cancer remains the fourth most common cancer worldwide in terms of both incidence and mortality.

-(2-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Induces Apoptosis and Cell Cycle Arrest in Breast Cancer Cells, Decreasing GPER Expression.

In this work, we performed anti-proliferative assays for the compound -(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) on breast cancer (BC) cells (MCF-7, SKBR3, and triple-negative BC (TNBC) MDA-MB-231 cells) to explore its pharmacological mechanism regarding the type of cell death associated with G protein-coupled estrogen receptor (GPER) expression. The results show that HO-AAVPA induces cell apoptosis at 5 h or 48 h in either estrogen-dependent (MCF-7) or -independent BC cells (SKBR3 and MDA-MB-231). At 5 h, the apoptosis rate for MCF-7 cells was 68.

The inhibitory and transcriptional effects of the epigenetic repurposed drugs hydralazine and valproate in lymphoma cells.

Lymphoma is a disease that affects countless lives each year. In order to combat this disease, researchers have been exploring the potential of DNMTi and HDACi drugs. These drugs target the cellular processes that contribute to lymphomagenesis and treatment resistance.

Multitargeted polypharmacotherapy for cancer treatment. theoretical concepts and proposals.

Introduction: The pharmacological treatment of cancer has evolved from cytotoxic to molecular targeted therapy. The median survival gains of 124 drugs approved by the FDA from 2003 to 2021 is 2.8 months.

Role of as a Tumor Suppressor in Cervical Cancer.

Background: The gene is silenced in various types of cancer, including cervical cancer; we recently demonstrated that the gene is also silenced in cervical cancer by hypermethylation of the CpG island in the gene promoter. This study aims to analyze whether could be a tumor suppressor in cervical cancer.

Methods: After ectopic expressing SLC5A8 in the HeLa cell line, we evaluated its effects on cell behavior both and by Confocal immunofluorescence, cell proliferation, migration assays, and xenograft transplants.

The non-vesicle cell-free DNA (cfDNA) induces cell transformation associated with horizontal DNA transfer.

Background: Cell-free DNA (cfDNA) is a source for liquid biopsy used for cancer diagnosis, therapy selection, and disease monitoring due to its non-invasive nature and ease of extraction. However, cfDNA also participates in cancer development and progression by horizontal transfer. In humans, cfDNA circulates complexed with extracellular vesicles (EV) and macromolecular complexes such as nucleosomes, lipids, and serum proteins.

Selection of clinically relevant drug concentrations for in vitro studies of candidates drugs for cancer repurposing: a proposal.

Drug repurposing of widely prescribed patent-off and cheap drugs may provide affordable drugs for cancer treatment. Nevertheless, many preclinical studies of cancer drug repurposing candidates use in vitro drug concentrations too high to have clinical relevance. Hence, preclinical studies must use clinically achievable drug concentrations.

Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer.

One of the primary diseases that cause death worldwide is cancer. Cancer cells can be intrinsically resistant or acquire resistance to therapies and drugs used for cancer treatment through multiple mechanisms of action that favor cell survival and proliferation, becoming one of the leading causes of treatment failure against cancer. A promising strategy to overcome chemoresistance and radioresistance is the co-administration of anticancer agents and natural compounds with anticancer properties, such as the polyphenolic compound resveratrol (RSV).

Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells.

The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs.

PaSTe. Blockade of the Lipid Phenotype of Prostate Cancer as Metabolic Therapy: A Theoretical Proposal.

Background: Prostate cancer is the most frequently diagnosed malignancy in 112 countries and is the leading cause of death in eighteen. In addition to continuing research on prevention and early diagnosis, improving treatments and making them more affordable is imperative. In this sense, the therapeutic repurposing of low-cost and widely available drugs could reduce global mortality from this disease.

Does Therapeutic Repurposing in Cancer Meet the Expectations of Having Drugs at a Lower Price?

Therapeutic repurposing emerged as an alternative to the traditional drug discovery and development model (DDD) of new molecular entities (NMEs). It was anticipated that by being faster, safer, and cheaper, the development would result in lower-cost drugs. As defined in this work, a repurposed cancer drug is one approved by a health regulatory authority against a non-cancer indication that then gains new approval for cancer.

Progress in Metabolic Studies of Gastric Cancer and Therapeutic Implications.

Background: Worldwide, gastric cancer is ranked the fifth malignancy in incidence and the third malignancy in mortality. Gastric cancer causes an altered metabolism that can be therapeutically exploited.

Objective: The objective of this study is to provide an overview of the significant metabolic alterations caused by gastric cancer and propose a blockade.

Regulation of miRNAs Expression by Mutant p53 Gain of Function in Cancer.

The p53 roles have been largely described; among them, cell proliferation and apoptosis control are some of the best studied and understood. Interestingly, the mutations on the six hotspot sites within the region that encodes the DNA-binding domain of p53 give rise to other very different variants. The particular behavior of these variants led to consider p53 mutants as separate oncogene entities; that is, they do not retain wild type functions but acquire new ones, namely Gain-of-function p53 mutants.

MPS1 is involved in the HPV16-E7-mediated centrosomes amplification.

Background: It has been reported that the oncoprotein E7 from human papillomavirus type 16 (HPV16-E7) can induce the excessive synthesis of centrosomes through the increase in the expression of PLK4, which is a transcriptional target of E2F1. On the other hand, it has been reported that increasing MPS1 protein stability can also generate an excessive synthesis of centrosomes. In this work, we analyzed the possible role of MPS1 in the amplification of centrosomes mediated by HPV16-E7.

Hereditary diffuse gastric cancer (HDGC). An overview.

It is estimated that up to 10% of gastric carcinomas show familial aggregation. In contrast, around 1-3 % (approximately 33,000 yearly) are genuinely hereditary. Hereditary diffuse gastric cancer (HDGC) is a rare malignancy characterized by autosomal dominant inheritance of pathological variants of the CDH1 and CTNNA1 genes encoding the adhesion molecules E-cadherin and α-catenin, respectively.

BAPST. A Combo of Common Use Drugs as Metabolic Therapy for Cancer: A Theoretical Proposal.

Cancer therapy advances have yet to impact global cancer mortality. One of the factors limiting mortality burden reduction is the high cost of cancer drugs. Cancer drug repurposing has already failed to meet expectations in terms of drug affordability.

Expression of miR-34a and miR-15b during the progression of cervical cancer in a murine model expressing the HPV16 E7 oncoprotein.

The high-risk human papillomavirus (HR-HPV) E7 oncoprotein appears to be a major determinant for cell immortalization and transformation altering critical processes such as cell proliferation, apoptosis, and immune response. This oncoprotein plays an essential role in cervical carcinogenesis, but other cofactors such as long-term use of hormonal contraceptives are necessary to modulate the risk of cervical cancer (CC). The role of HR-HPVs in the alteration of microRNA (miRNA) levels in persistent viral infections currently remains unclear.

Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy.

The malignant energetic demands are satisfied through glycolysis, glutaminolysis and de novo synthesis of fatty acids, while the host curses with a state of catabolism and systemic inflammation. The concurrent inhibition of both, tumor anabolism and host catabolism, and their effect upon tumor growth and whole animal metabolism, have not been evaluated. We aimed to evaluate in colon cancer cells a combination of six agents directed to block the tumor anabolism (orlistat + lonidamine + DON) and the host catabolism (growth hormone + insulin + indomethacin).

The combination of orlistat, lonidamine and 6-diazo-5-oxo-L-norleucine induces a quiescent energetic phenotype and limits substrate flexibility in colon cancer cells.

Cancer upregulates glycolysis, glutaminolysis and lipogenesis, and induces a catabolic state in patients. The concurrent inhibition of both tumor anabolism and host catabolism, and the energetic consequences of such an approach, have not previously been fully investigated. In the present study, CT26.

Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug.

Purpose: Ivermectin is an antiparasitic drug that exhibits antitumor effects in preclinical studies, and as such is currently being repositioned for cancer treatment. However, divergences exist regarding its employed doses in preclinical works. Therefore, the aim of this study was to determine whether the antitumor effects of ivermectin are observable at clinically feasible drug concentrations.

Erratum: A combination of inhibitors of glycolysis, glutaminolysis and fatty acid synthesis decrease the expression of chemokines in human colon cancer cells.

[This corrects the article DOI: 10.3892/ol.2019.

A combination of inhibitors of glycolysis, glutaminolysis and fatty acid synthesis decrease the expression of chemokines in human colon cancer cells.

Lonidamine, 6-Diazo-5-oxo-L-norleucine (DON) and orlistat are well known inhibitors of glycolysis, glutaminolysis and of fatty acid synthesis, respectively. Although their antitumor effects have been explored in detail, the potential inhibition of the malignant metabolic phenotype and its influence on the expression of chemokines and growth factors involved in colon cancer, have not been previously reported to the best of our knowledge. In the present study, dose-response curves with orlistat, lonidamine or DON were generated from cell viability assays conducted in SW480 colon cancer cells.

Growth inhibition and transcriptional effects of ribavirin in lymphoma.

Ribavirin exhibits inhibitory effects on the epigenetic enzyme enhancer of zeste homolog 2 (EZH2), which participates in lymphomagenesis. Additionally, preclinical and clinical studies have demonstrated the anti‑lymphoma activity of this drug. To further investigate the potential of ribavirin as an anticancer treatment for lymphoma, the tumor‑suppressive effects of ribavirin were analyzed in lymphoma cell lines.

Antimetastatic effect of epigenetic drugs, hydralazine and valproic acid, in Ras-transformed NIH 3T3 cells.

Introduction: Metastasis involves the accumulation of genetic and epigenetic alterations leading to activation of prometastatic genes and inactivation of antimetastatic genes. Among epigenetic alterations, DNA hypermethylation and histone hypoacetylation are the focus of intense translational research because their pharmacological inhibition has been shown to produce antineoplastic activity in a variety of experimental models.

Aims: This study aimed to evaluate the antimetastatic effect of the DNA-methylation inhibitor, hydralazine, and the histone deacetylase inhibitor, valproic acid.