Biology subjects

Mwaiselage, J.

Publications and source records attributed to Mwaiselage, J..

3 recordsLinked to original sources

bioRxiv2026

Low-intensity vibration (LIV) cellular mechanotherapy reprograms tumor transcriptomes to suppress cancer-promoting inflammation

LIV is a non-pharmacological intervention for multiple pathologies, most notably pain, yet its potential in oncology remains unexplored due to poorly understood mechanotransduction pathways. Its therapeutic efficacy depends on precise dosing parameters - frequency, amplitude, and duration; suboptimal application, whether excessive or insufficient, risks exacerbating symptoms or rendering treatment ineffective. In a breast cancer-immune cell co-culture model, a 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient metastasis-incompetent "benignant" state that retains oncogenic markers but loses invasive capacity. Our results reveal LIV as a non-drug inhibitor of IFN{gamma} and CXCL12{beta} - silencing IFN{gamma} impairs inflammatory bursts, while silencing CXCL12{beta} starves the CXCR4/CXCR7 axis, depriving tumor cells of motility cues. LIV enforces a genome-wide transcriptional brake, upregulating tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) while downregulating protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p). This work repositions LIV as a non-drug modality for coordinately targeting multiple cancer hallmarks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/716739v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@1100863org.highwire.dtl.DTLVardef@196bcf4org.highwire.dtl.DTLVardef@14f3903org.highwire.dtl.DTLVardef@2802fd_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_ST_ABSDosing PrecisionC_ST_ABSLIV mechanotherapy has an optimal therapeutic window. Too little is ineffective, while too much can exacerbate symptoms. This mirrors the pharmacokinetic language of classical pharmacology. The "Benignant" ConceptA 15-min regimen of 90-Hz, 0.43-g LIV attenuates protumorigenic crosstalk by suppressing proinflammatory cytokines and reprogramming malignant cells into a transient, metastasis-incompetent benignant state defined by mechanical constraint rather than pharmacological intervention. Dual Cytokine SilencingLIV acts as a non-pharmaco-logical inhibitor of IFN{gamma} and CXCL12{beta}. IFN{gamma} is a double-edged sword in cancer (pro-immunity vs. exhaustion), and CXCL12{beta} is the specific isoform implicated in metastasis. Targeting both simultaneously addresses immune crosstalk and chemotaxis. In briefMeena et al. demonstrate that the efficacy of LIV hinges on optimal dosing parameters. When applied correctly, it functions as a non-drug modality to target multiple oncogenic and inflammatory pathways. At the molecular level, LIV drives global transcriptional repression via miRNA regulation, increasing tumor-suppressive miRNAs (hsa-miR-141, hsa-miR-122) and decreasing protumorigenic miRNAs (hsa-miR-105-5p, hsa-miR-181a-5p).

cancer biology↗

bioRxiv2021

An international report on bacterial communities in esophageal squamous cell carcinoma

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One proposed biological pathway linking poor oral health and ESCC involves the alteration of the microbiome. Thus, we performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors and WGS of synchronous collections of saliva specimens from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella, and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed a similar tumor enrichment of the ESCC-associated bacterial community in these cancers. Because these genera are traditionally considered members of the oral microbiota, we explored if there is a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes are significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of ESCC patients. Longitudinal studies of the pre-diagnostic oral microbiome are needed to investigate whether these cross-sectional similarities reflect temporal associations.

microbiology↗

bioRxiv2018

The Relationship Between the Cervical Microbiome, HIV Status, and Pre-Cancerous Lesions

Nearly all cervical cancers are causally associated with Human Papillomavirus (HPV). The burden of HPV-associated dysplasias in Sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep-sequenced. Alpha diversity metrics; Chao1, PD whole tree, and operational taxonomic Unit (OTU) estimates, displayed significantly higher bacterial richness in HIV positive patients (P = 0.01) than in HIV negative patients. Within HIV positive patients, there was higher bacterial richness in patients with high grade squamous intraepithelial lesions (HSIL; P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepitheilal lesions (HSIL) were Mycoplasmatales, Pseudomonadales, and Staphylococcus. We suggest that a chronic mycoplasma infection of the cervix can contribute to HPV-dependent dysplasia by sustained inflammatory signals.

cancer biology↗