The ability of clostridium novyi-NT spores to induce apoptosis via the mitochondrial pathway in mice with HPV-positive cervical cancer tumors derived from the TC-1 cell line DOI Creative Commons

Behrouz Ebadi Sharafabad,

Asghar Abdoli,

Parisa Jamour

et al.

BMC Complementary Medicine and Therapies, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 28, 2024

A precise observation is that the cervix's solid tumors possess hypoxic regions where oxygen concentration drops below 1.5%. Hypoxia negatively impacts host's immune system and significantly diminishes effectiveness of several treatments, including radiotherapy chemotherapy. Utilizing oncolytic spores Clostridium novyi-NT to target has emerged as a noteworthy treatment strategy. The transplantation procedure involved injecting TC-1 cells, capable expressing HPV-16 E6/7 oncoproteins, into subcutaneous layer 6-8-week-old female C57/BL6 mice. cell line, was subcutaneously transplanted tumor-bearing mice were randomly divided 4 groups, after selecting control group, they treated with different methods. Group 1- without (0.1 ml sterile PBS intratumor) 2- received cisplatin intraperitoneally (10 mg/kg) 3- 107Clostridium systemically through tail vein 4-tumor intratumorally. 20 days start treatment, sacrificed tumor tissues isolated. In order clarify mechanism therapeutic effect spores, amount ROS ceramide measured by ELISA technique, expression level cytochrome c, cleaved caspase- 3, Bax, Bcl-2, HIF-1α, VEGF proteins western blotting. Our results clearly showed injection (either intratumorally or intravenously) causes regression mouse cervical tumors. Spore germination induces internal apoptosis in cancer cells inducing production increasing total ceramide, releasing c damaging mitochondria. Additionally, provided clear evidence significant decrease HIF-1 alpha among groups when compared both cisplatin-treated group group. study's outcomes demonstrated introduction triggered (derived from line) via mitochondrial pathway, subsequently resulting model.

Language: Английский

Carbonic anhydrase IX: An atypical target for innovative therapies in cancer DOI Creative Commons
Roberto Ronca, Claudiu T. Supuran

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(4), P. 189120 - 189120

Published: May 25, 2024

Carbonic anhydrases (CAs), are metallo-enzymes implicated in several pathophysiological processes where tissue pH regulation is required. CA IX a tumor-associated isoform induced by hypoxia and involved the adaptation of tumor cells to acidosis. Indeed, tumor-driving pathways can induce expression, this turn has been associated cancer invasion metastatic features as well induction stem-like features, drug resistance recurrence. After its functional structural characterization targeting approaches have developed inhibit activity neoplastic tissues, date field seen an incredible acceleration terms therapeutic options biological readouts. Small molecules inhibitors, hybrid/dual drugs, antibodies adoptive (CAR-T based) cell therapy at preclinical level, whereas sulfonamide inhibitor antibody entered Phase Ib/II clinical trials for treatment imaging different solid tumors. Here recent advances on biology pharmacology cancer, will be discussed.

Language: Английский

Citations

28
Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction DOI Creative Commons
Francesco Verona, Sebastiano Di Bella,

Roberto Schirano

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Cancer stem cells (CSCs) are a small subset within the tumor mass significantly contributing to cancer progression through dysregulation of various oncogenic pathways, driving growth, chemoresistance and metastasis formation. The aggressive behavior CSCs is guided by several intracellular signaling pathways such as WNT, NF-kappa-B, NOTCH, Hedgehog, JAK-STAT, PI3K/AKT1/MTOR, TGF/SMAD, PPAR MAPK kinases, well extracellular vesicles exosomes, molecules cytokines, chemokines, pro-angiogenetic growth factors, which finely regulate CSC phenotype. In this scenario, microenvironment (TME) key player in establishment permissive niche, where engage intricate communications with diverse immune cells. "oncogenic" mainly represented B T lymphocytes, NK cells, dendritic Among macrophages exhibit more plastic adaptable phenotype due their different subpopulations, characterized both immunosuppressive inflammatory phenotypes. Specifically, tumor-associated (TAMs) create an milieu production plethora paracrine factors (IL-6, IL-12, TNF-alpha, TGF-beta, CCL1, CCL18) promoting acquisition stem-like, invasive metastatic TAMs have demonstrated ability communicate via direct ligand/receptor (such CD90/CD11b, LSECtin/BTN3A3, EPHA4/Ephrin) interaction. On other hand, exhibited capacity influence creating favorable for progression. Interestingly, bidirectional TME leads epigenetic reprogramming sustains malignant transformation. Nowadays, integration biological computational data obtained cutting-edge technologies (single-cell RNA sequencing, spatial transcriptomics, trajectory analysis) has improved comprehension biunivocal multicellular dialogue, providing comprehensive view heterogeneity dynamics CSCs, uncovering alternative mechanisms evasion therapeutic resistance. Moreover, combination biology will lead development innovative target therapies dampening CSC-TME Here, we aim elucidate most recent insights on complex interactions specifically TAMs, tracing exhaustive scenario from primary

Language: Английский

Citations

2
Molecular Imaging of Cancer Stem Cells and Their Role in Therapy Resistance DOI Creative Commons
Sofia Nascimento dos Santos, Timothy H. Witney

Journal of Nuclear Medicine, Journal Year: 2025, Volume and Issue: 66(1), P. 14 - 19

Published: Jan. 1, 2025

Despite recent therapeutic breakthroughs, cancer patients continue to face high recurrence and mortality rates due treatment resistance. Cancer stem cells (CSCs), a subpopulation with self-renewal capabilities, are key drivers of refractive disease. This review explores the application molecular imaging techniques, such as PET SPECT, for noninvasive detection CSCs. By providing real-time monitoring CSCs, these methods have potential predict therapy resistance guide personalized approaches. Here, we cover biological characteristics mechanisms resistance, identification targeting CSC-specific biomarkers imaging. Additionally, address challenges opportunities clinical translation CSC imaging, highlighting strategies where can be used improve patient outcomes.

Language: Английский

Citations

1
Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer DOI Open Access

Jennifer Haynes,

Prasath Manogaran

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1988 - 1988

Published: Feb. 25, 2025

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide, with significant impact on public health. Current treatment options include surgery, chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy. Despite advancements in these therapeutic modalities, resistance remains challenge, often leading to failure, poor progression-free survival, recurrence. Mechanisms CRC are multifaceted, involving genetic mutations, epigenetic alterations, tumor heterogeneity, the microenvironment. Understanding mechanisms at molecular level crucial for identifying novel targets developing strategies overcome resistance. This review provides an overview diverse driving drug sporadic discusses currently under investigation counteract this Several promising being explored, including targeting transport, key signaling pathways, DNA damage response, cell death modifications, stem cells, The integration emerging approaches that target aims enhance efficacy current treatments improve patient outcomes.

Language: Английский

Citations

1
Morusin suppresses the stemness characteristics of gastric cancer cells induced by hypoxic microenvironment through inhibition of HIF-1α accumulation DOI
Mo Chen,

Shu-Feng Xiao,

Ping Sun

et al.

Toxicon, Journal Year: 2024, Volume and Issue: 241, P. 107675 - 107675

Published: March 1, 2024

Language: Английский

Citations

4
Exploiting the DNA Damage Response for Prostate Cancer Therapy DOI Open Access
Travis H. Stracker,

Oloruntoba I. Osagie,

Freddy E. Escorcia

et al.

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 83 - 83

Published: Dec. 23, 2023

Prostate cancers that progress despite androgen deprivation develop into castration-resistant prostate cancer, a fatal disease with few treatment options. In this review, we discuss the current understanding of cancer subtypes and alterations in DNA damage response (DDR) can predispose to development affect its progression. We identify barriers conventional treatments, such as radiotherapy, new therapies, many which target DDR or take advantage recurring genetic DDR. place context advances variation immune landscape CRPC could help guide their use future strategies. Finally, several emerging agents may advance lethal disease, highlighting selected clinical trials.

Language: Английский

Citations

6
Mitochondrial–Stem Cell Connection: Providing Additional Explanations for Understanding Cancer DOI Creative Commons
Pierrick Martinez,

Ilyes Baghli,

Géraud Gourjon

et al.

Metabolites, Journal Year: 2024, Volume and Issue: 14(4), P. 229 - 229

Published: April 17, 2024

The cancer paradigm is generally based on the somatic mutation model, asserting that a disease of genetic origin. mitochondrial–stem cell connection (MSCC) proposes tumorigenesis may result from an alteration mitochondria, specifically chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells, which forms cells (CSCs) and leads to malignancy. Reviewed evidence suggests MSCC could provide comprehensive understanding all different stages cancer. metabolism altered (OxPhos insufficiency) must be compensated by using glycolysis glutaminolysis pathways, are essential their growth. mitochondria regulate tumor microenvironment, also necessary for evolution. Therefore, help improve our tumorigenesis, metastases, efficiency standard treatments, relapses.

Language: Английский

Citations

1
Morphological Features and Clinical Significance of Tumor Microvessels in Glandular and Squamous Cell Cancers DOI
M. A. Senchukova

Interdisciplinary cancer research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

1
Novel Inhibition of Central Carbon Metabolism Pathways by Rac and CDC42 inhibitor MBQ167 and Paclitaxel DOI
Ailed Cruz‐Collazo, Olga Katsara, Nilmary Grafals-Ruíz

et al.

Molecular Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 23(11), P. 1613 - 1625

Published: Aug. 1, 2024

Abstract Triple negative breast cancer (TNBC) represents a therapeutic challenge in which standard chemotherapy is limited to paclitaxel. MBQ167, clinical stage small molecule inhibitor that targets Rac and Cdc42, inhibits tumor growth metastasis mouse models of TNBC. Herein, we investigated the efficacy MBQ167 combination with paclitaxel TNBC preclinical models, as prelude safety trials this patients advanced cancer. Individual or therapy was more effective at reducing cell viability increasing apoptosis compared alone. In orthotopic human (MDA-MB231 MDA-MB468), individual paclitaxel, reduced mammary similar efficacy, no apparent liver toxicity. However, single agent treatment significantly increased lung metastasis, whereas combined, metastasis. syngeneic 4T1/BALB/c model, combined decreased established metastases by ∼80%. To determine molecular basis for improved on 4T1 extracts from BALB/c mice treated were subjected transcriptomic analysis. Gene set enrichment identified specific downregulation central carbon metabolic pathways but not compounds. Biochemical validation, immunoblotting Seahorse analysis, shows reduces glycolysis. This study provides strong rationale testing potential identifies unique mechanism action.

Language: Английский

Citations

1
Chromosomal instability as an architect of the cancer stemness landscape DOI Creative Commons
Shahnawaz Ahmad Baba,

Aran Zakeri,

Jay S. Desgrosellier

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 13, 2024

Despite a critical role for tumor-initiating cancer stem cells (CSCs) in breast progression, major questions remain about the properties and signaling pathways essential their function. Recent discoveries highlighting mechanisms of CSC-resistance to stress caused by chromosomal instability (CIN) may provide valuable new insight into underlying forces driving stemness properties. While tolerance is well-known attribute CSCs, CIN-induced distinctive since levels appear increase during tumor initiation metastasis. These dynamic changes CIN serve as barrier constraining effects non-CSCs shaping landscape early stages disease progression. In contrast most other stresses, can also paradoxically activate pro-tumorigenic antiviral signaling. Though seemingly contradictory, this indicate that inflammatory closely collaborate define CSC state. Together, these unique features form basis relationship between

Language: Английский

Citations

1