Malaria and Cancer: a critical review on the established associations and new perspectives

Ellis, Toby; Eze, Elvis; Raimi-Abraham, Bahijja Tolulope

doi:10.1186/s13027-021-00370-7

Cited by 11 publications

(13 citation statements)

References 92 publications

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“…Studies show that malaria and cancer can mutually influence some of their pathophysiological manifestations [ 30 ]. Our results show for the first time that the nociceptive response or the local inflammatory induced by the Ehrlich solid tumor changes during malaria infection and persists after treatment and heals the malaria infection.…”

Section: Discussionmentioning

confidence: 99%

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The Nociceptive and Inflammatory Responses Induced by the Ehrlich Solid Tumor Are Changed in Mice Healed of Plasmodium berghei Strain ANKA Infection after Chloroquine Treatment

Rodrigues Aguiar,

Guterres,

Benarrosh

et al. 2024

Journal of Parasitology Research

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Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive and inflammatory responses through similar pathophysiological mechanisms. However, it is unclear whether malaria and antimalarial treatment can change the inflammatory and nociceptive responses induced by solid cancer. Therefore, the present study experimentally evaluated the effect of infection by Plasmodium berghei strain ANKA and chloroquine treatment on the nociceptive and inflammatory responses induced by the solid Ehrlich tumor in male BALB/c mice. On the 1st experimental day, mice were infected with Plasmodium berghei and injected with tumor cells in the left hind paw. From the 7th to the 9th experimental day, mice were treated daily with chloroquine. The parasitemia was evaluated on the 7th and 10th days after infection. On the 11th experimental day, mice were evaluated on the von Frey filament test, the hot plate test, and the paw volume test. At the end of the experimental tests on the 11th day, the peripheral blood of all mice was collected for dosing of IL-1β and TNF-α. The blood parasitemia significantly increased from the 7th to the 10th day. The chloroquine treatment significantly decreased the parasitemia on the 10th day. The presence of the tumor did not significantly change the parasitemia on the 7th and 10th days in mice treated and nontreated with chloroquine. On the 11th day, the mechanical and thermal nociceptive responses significantly increased in mice with tumors. The treatment with antimalarial significantly reduced the mechanical nociceptive response induced by tumors. The hyperalgesia induced by tumors did not change with malaria. The mechanical and thermal hyperalgesia induced by the tumor was significantly reduced in mice treated and healed from malaria. On the 11th day, the volume of the paw injected by the tumor was significantly increased. The mice treated with chloroquine, infected with malaria, or healed of malaria showed reduced paw edema induced by the tumor. Mice with tumors did not show a change in IL-β and TNF-α serum levels. Mice with tumors showed a significant increase in serum levels of IL-1β but not TNF-α when treated with chloroquine, infected with malaria, or healed of malaria. In conclusion, the results show that malaria infection and chloroquine treatment can influence, in synergic form, the nociceptive and inflammatory responses induced by the solid tumor. Moreover, the mechanical antinociception, the thermal hyperalgesia, and the antiedema effect observed in mice treated with chloroquine and healed from malaria can be related to the increase in the serum level of IL-1β.

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Section: Discussionmentioning

confidence: 99%

“…On the other hand, evidence also suggests that malaria can favor the development of several types of cancer [ 27 , 30 – 32 ]. Cases of Burkitt lymphoma, an aggressive non-Hodgkin lymphoma, have a high prevalence in areas with stable malaria transmission [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

The Nociceptive and Inflammatory Responses Induced by the Ehrlich Solid Tumor Are Changed in Mice Healed of Plasmodium berghei Strain ANKA Infection after Chloroquine Treatment

Rodrigues Aguiar,

Guterres,

Benarrosh

et al. 2024

Journal of Parasitology Research

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“…An unexpected discovery was that the EV lncRNAs uniquely expressed in stage III patients were involved in the malaria pathway. Although there is no evidence of a direct association between malaria pathway-related lncRNA targets and CC progression, previous data suggest a potential link between malaria infection and an individual’s risk of cancer development and progression [34]. In Uganda, malaria is reported as a risk factor for CC.…”

Section: Discussionmentioning

confidence: 99%

Exploration of Extracellular Vesicle Long Non-Coding RNAs in Serum of Patients with Cervical Cancer

Molika¹,

Bissanum²,

Surachat³

et al. 2023

Oncology

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Cervical cancer (CC) is the fourth most common cancer type and a leading cause of cancer-related deaths in women worldwide. Its underlying molecular mechanisms are unclear. Cancer cell-derived extracellular vesicles (EVs) are involved in cancer development and progression by delivering regulatory factors, including microRNAs and long non-coding RNAs (lncRNAs). Here, we identified the EV lncRNA expression profiles associated with different developmental stages of CC using next-generation sequencing. EVs from the serum of patients with stages I–III CC and healthy donors were characterized using EV marker immunoblotting and transmission electron microscopy. The EV concentration increases with progression of the disease. Most particles had a 100–250 nm diameter, and their sizes were similar in all groups. We identified many lncRNAs that were uniquely and differentially expressed (DE) in patients with different stages of CC. The pathway analysis results indicated that the upregulated DE EV lncRNAs abundant in stages I and II were associated with cell proliferation and inflammatory and cancer progression pathways, respectively. LINC00941, LINC01910, LINC02454, and DSG2-AS1 were highly expressed, suggesting poor overall survival of CC patients. Interestingly, DSG2-AS1 was associated with human papillomavirus infection pathway through AKT3, DLG1, and COL6A2 genes. This is the first study that reports the levels of EVs and their lncRNA contents change during cancer development, demonstrating the existence of a unique vesicle-mediated cell-to-cell communication network underlying cancer progression.

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“…In bladder cancer, ranking by the lower bound of the difference in weight leads to the gene set associated with malaria, one of the smaller gene sets, being ranked in sixth place, whereas when ranked by p-value it is ranked fifteenth. Given the potential use of anti-malarial drugs to treat different types of cancer [15] and bladder cancer more specifically [16] this may be of interest. The increased importance placed on the smaller vitamin digestion and absorption gene set in colon cancer is consistent with previous results that found perturbation of gene expression in this set to be closely linked to colon cancer progression [17].…”

Section: Our 1df Methods Found Many More Significantly Enriched Gene ...mentioning

confidence: 99%

Random-effects meta-analysis of effect sizes as a unified framework for gene set analysis

Makrooni

O’Shea

Geeleher

et al. 2022

Preprint

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Gene set analysis (GSA) remains a common step in genome-scale studies because it can reveal insights that are not apparent from results obtained for individual genes. Many different computational tools are applied for GSA, which may be sensitive to different types of signals; however, most methods test whether there are differences in the distribution of the effect of some experimental condition between genes in gene sets of interest. We have developed a unifying framework for GSA that first fits effect size distributions, and then tests for differences in these distributions between gene sets. These differences can be in the proportions of genes that are perturbed or in the sign or size of the effects. Inspired by statistical meta-analysis, we take into account the uncertainty in effect size estimates to reduce the influence of genes with greater uncertainty in effect size estimate on distribution parameters. We demonstrate, using simulation and by application to real data, that this approach provides significant gains in performance over existing methods. Furthermore, the statistical tests carried out are defined in terms of effect sizes, rather than the results of prior statistical tests measuring these changes, which leads to improved interpretability and greater robustness to variation in sample sizes. We also show that the approach naturally suggests alternative test types that are not usually considered in GSA; it can, for example, be applied to identify differences in effect size distributions between sample subgroups in a gene set of interest. Applying this approach to an analysis of gene expression changes between matched colon tumour and normal samples, we found several gene sets that showed distinct behaviour in patient subgroups with different prognoses. These may help to explain the clinical differences that have been reported between these patient groups.

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Malaria and Cancer: a critical review on the established associations and new perspectives

Cited by 11 publications

References 92 publications

The Nociceptive and Inflammatory Responses Induced by the Ehrlich Solid Tumor Are Changed in Mice Healed of Plasmodium berghei Strain ANKA Infection after Chloroquine Treatment

The Nociceptive and Inflammatory Responses Induced by the Ehrlich Solid Tumor Are Changed in Mice Healed of Plasmodium berghei Strain ANKA Infection after Chloroquine Treatment

Exploration of Extracellular Vesicle Long Non-Coding RNAs in Serum of Patients with Cervical Cancer

Random-effects meta-analysis of effect sizes as a unified framework for gene set analysis

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