The ALDH Family Contributes to Immunocyte Infiltration, Proliferation and Epithelial-Mesenchymal Transformation in Glioma

Gliomas are malignant tumors that originate from the central nervous system. The aldehyde dehydrogenase family has been documented to affect cancer progression; however, its role in gliomas remains largely unexplored. Bulk RNA-seq analysis and single-cell RNA-Seq analysis were performed to explore the role of the aldehyde dehydrogenases family in gliomas. Training cohort contained The Cancer Genome Atlas data, while data from Chinese Glioma Genome Atlas and Gene Expression Omnibus were set as validation cohorts. Our scoring system based on the aldehyde dehydrogenases family suggested that high-scoring samples were associated with worse survival outcomes. The enrichment score of pathways were calculated by AUCell to substantiate the biofunction prediction results that the aldehyde dehydrogenases family affected glioma progression by modulating tumor cell proliferation, migration, and immune landscape. Tumor immune landscape was mapped from high-scoring samples. Moreover, ALDH3B1 and ALDH16A1, two main contributors of the scoring system, could affect glioblastoma cell proliferation and migration by inducing cell-cycle arrest and the epithelial-mesenchymal transition. Taken together, the aldehyde dehydrogenases family could play a significant role in the tumor immune landscape and could be used to predict patient prognosis. ALDH3B1 and ALDH16A1 could influence tumor cell proliferation and migration.

Does hysteroscopy promote tumor cell proliferation in endometrial cancer?

Peritoneal cytological investigation was carried out inpatients with endometrial cancer, who were subjected to hysteroscopy before the operation (37patients) or were operated on without hysteroscopy. Comparative analysis of the data didnt reveal the role of hysteroscopy in tumor cell dissemination.

PCAT6 May Be a Whistler and Checkpoint Target for Precision Therapy in Human Cancers

LncRNAs are involved in the occurrence and progressions of multiple cancers. Emerging evidence has shown that PCAT6, a newly discovered carcinogenic lncRNA, is abnormally elevated in various human malignant tumors. Until now, PCAT6 has been found to sponge various miRNAs to activate the signaling pathways, which further affects tumor cell proliferation, migration, invasion, cycle, apoptosis, radioresistance, and chemoresistance. Moreover, PCAT6 has been shown to exert biological functions beyond ceRNAs. In this review, we summarize the biological characteristics of PCAT6 in a variety of human malignancies and describe the biological mechanisms by which PCAT6 can facilitate tumor progression. Finally, we discuss its diagnostic and prognostic values and clinical applications in various human malignancies.

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma

Glioma is the common primary craniocerebral malignancy with unfavorable prognosis. It is currently treated by surgical resection supplemented by radiotherapy, although the resistance of glioma cells to radiation limits the therapeutic outcomes. The aim of the present study was to determine the potential radiosensitizing effects of borneol and the underlying mechanisms. We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells in vitro and in vivo. Furthermore, borneol markedly increased the number of autophagosomes in the glioma cells, which coincided with increased expression of beclin-1 and LC3. And the combination of borneol and radiation exposure significantly decreased the expression levels of HIF-1α, mTORC1 and eIF4E. In addition, silencing mTORC1 and eIF4E upregulated Beclin-1 and LC3 and decreased the expression of HIF-1α, thereby inhibiting tumor cell proliferation. Our findings suggest that borneol sensitizes glioma cells to radiation by inducing autophagy via inhibition of the mTORC1/eIF4E/HIF-1α regulatory axis.

Melphalan flufenamide is an Anticancer medication used to treat multiple Myeloma: A Review

Melphalan Flufenamide is a peptide-drug conjugate composed of a peptide conjugated, via an aminopeptidase-targeting linkage, to the alkylating agent melphalan, with potential antineoplastic and anti-angiogenic activities. Upon administration, the highly lipophilic melphalan flufenamide penetrates cell membranes and enters cells. In aminopeptidase-positive tumor cells, melphalan flufenamide is hydrolyzed by peptidases to release the hydrophilic alkylating agent melphalan. This results in the specific release and accumulation of melphalan in aminopeptidase-positive tumor cells. Melphalan alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages. This results in the inhibition of DNA and RNA synthesis and the induction of apoptosis, thereby inhibiting tumor cell proliferation. Peptidases are overexpressed by certain cancer cells. The administration of melphalan flufenamide allows for enhanced efficacy and reduced toxicity compared to melphalan.1,2,3

The Influence of Domain Permutations of an Albumin-Binding Domain-Fused HER2-Targeting Affibody-Based Drug Conjugate on Tumor Cell Proliferation and Therapy Efficacy

Human epidermal growth factor receptor 2 (HER2) is a clinically validated target for breast cancer therapy. Previously, a drug-fused HER2-targeting affinity protein construct successfully extended the survival of mice bearing HER2-expressing xenografts. The aim of this study was to evaluate the influence of the number and positioning of the protein domains in the drug conjugate. Seven HER2-targeting affibody-based constructs, including one or two affibody molecules (Z) with or without an albumin-binding domain (ABD), namely Z, Z-ABD, ABD-Z, Z-Z, Z-Z-ABD, Z-ABD-Z, and ABD-Z-Z, were evaluated on their effects on cell growth, in vivo targeting, and biodistribution. The biodistribution study demonstrated that the monomeric constructs had longer blood retention and lower hepatic uptake than the dimeric ones. A dimeric construct, specifically ABD-Z-Z, could stimulate the proliferation of HER2 expressing SKOV-3 cells in vitro and the growth of tumors in vivo, whereas the monomeric construct Z-ABD could not. These two constructs demonstrated a therapeutic effect when coupled to mcDM1; however, the effect was more pronounced for the non-stimulating Z-ABD. The median survival of the mice treated with Z-ABD-mcDM1 was 63 days compared to the 37 days for those treated with ABD-Z-Z-mcDM1 or for the control animals. Domain permutation of an ABD-fused HER2-targeting affibody-based drug conjugate significantly influences tumor cell proliferation and therapy efficacy. The monomeric conjugate Z-ABD is the most promising format for targeted delivery of the cytotoxic drug DM1.

STEM-11. HYDROGEN SULFIDE FUNCTIONS AS A TUMOR SUPPRESSION IN GLIOBLASTOMA

Glioblastoma (GBM) cancer stem cells (CSCs) respond to a variety of stimuli within their immediate surroundings. However, little is known about the lifestyle factors that alter CSC enrichment and function within the tumor microenvironment (TME). To examine the consequences of diet-induced obesity on the progression of GBM, we interrogated tumor growth using patient-derived and syngeneic GBM models implanted into the brains of mice fed either an obesogenic high-fat diet (HFD) or a low-fat, control diet. HFD consumption resulted in an accelerated disease trajectory, presenting significantly shortened overall survival. HFD reshaped the TME altering the lipid landscape, enhancing the CSC phenotype, stimulating tumor cell proliferation, and protecting from necrotic cell death. Similar results were not observed in metabolically obese, leptin-deficient (ob/ob) mice. We simultaneously identified a potent suppression of the gasotransmitter, hydrogen sulfide (H2S). H2S functions principally through protein S-sulfhydration and regulates multiple programs including bioenergetics, metabolism, and immune response. Inhibition of H2S increased tumor cell proliferation and chemotherapy resistance, whereas treatment with H2S donors reduced tumor cell fitness in vitro and attenuated GBM growth in vivo. Exogenous treatment with H2S donors also rescued the lipid-mediated increase in tumor cell proliferation. As H2S exerts its action though protein S-sulfhydration, we confirmed that HFD-fed mice, which experienced decreased H2S synthesis, presented a severely depleted S-sulfhydrated protein landscape. Loss of this post-translational modification was confirmed in GBM patient tissues compared to age- and sex-matched controls. Taken together, our findings provide evidence that H2S functions as a tumor suppressor in GBM. Our observations highlight a new mechanism for tumor growth dynamics that can be leveraged for new therapeutic strategies focused on boosting H2S. Finally, our findings indicate that lifestyle factors can have pleiotropic effects on GBM progression through concomitant mechanisms involving tumor metabolism, modifications to the TME, and regulation over the CSC phenotype.