Cell Pathway And Malignancy

CD19 CAR-T cells have led to durable remissions in patients with refractory B-cell malignancies; nevertheless, most patients eventually relapse in the long term. Many interventions aimed at improving current products have been reported, with a subset of them focusing on a direct or indirect link to the metabolic state of the CAR-T cells. We assessed clinical products from an ongoing clinical trial utilizing CD19-28z CAR-T cells from patients with acute lymphoblastic leukemia. CAR-T clinical products leading to a complete response had significantly higher mitochondrial function (by oxygen consumption rate) irrespective of mitochondrial content...

IGFBP-3 is aberrantly expressed in many tumor types, and its serum and tumor tissue levels provide auxiliary information for assessing the degree of tumor malignancy and patient prognosis, making it a potential therapeutic target for human malignancies and conferring it remarkable clinical value for determining patient prognosis. In this review, we provide a comprehensive overview of the aberrant expression, diverse biological effects, and clinical implications of IGFBP-3 in tumors and its role as a potential prognostic marker and therapeutic target for tumors...

BACKGROUND: Ovarian cancer is a malignant tumor of the female reproductive system, and its mortality rate is as high as 70%. Estrogen receptor α (ERα)-positive ovarian cancer accounted for most of all ovarian cancer patients. ERα can promote the growth and proliferation of tumors. METHODS: The combined effect of All-trans retinoic acid (ATRA) and tamoxifen was obtained by the combination screening of tamoxifen and compound library by MTS. In addition, colony formation assay, flow cytometry analysis, immunofluorescence staining, quantitative real-time polymerase chain reaction (PCR), western blot, and tumor xenotransplantation models were used to further evaluate the efficacy of tamoxifen and ATRA in vitro and in vivo for ER-α-positive ovarian cancer...

The introduction of Chimeric Antigen Receptor (CAR) T-cell therapy represents a landmark advancement in treating resistant forms of cancer such as leukemia, lymphoma, and myeloma. However, concerns about long-term safety have emerged following an FDA investigation into reports of second primary malignancies (SPM) after CAR-T cell treatment. This review offers a thorough examination of how genetically modified T-cells might transform into CAR+ SPM. It explores genetic and molecular pathways leading to T-cell lymphomagenesis, the balance between CAR T-cell persistence, stemness, and oncogenic risk, and the trade-off of T-cell exhaustion, which may limit therapy efficacy but potentially reduce lymphomagenesis risk...

Inhibition of Bruton's tyrosine kinase (BTK) through covalent modifications of its active site (e.g., ibrutinib [IBT]) is a preferred treatment for multiple B cell malignancies. However, IBT-treated patients are more susceptible to invasive fungal infections, although the mechanism is poorly understood. Neutrophils are the primary line of defense against these infections; therefore, we examined the impact of IBT on primary human neutrophil effector activity against Aspergillus fumigatus. IBT significantly impaired the ability of neutrophils to kill A...

With high incidence of hepatocarcinoma and limited effective treatments, most patients suffer in pain. Antitumor drugs are single-targeted, toxicity, causing adverse side effects and resistance. Dihydroartemisinin (DHA) inhibits tumor through multiple mechanisms effectively. This study explores and evaluates safety and potential mechanism of DHA towards human hepatocarcinoma based on network pharmacology in a comprehensive way. Adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of DHA were evaluated with pkCSM, SwissADME, and ADMETlab...

PURPOSE: Multiple myeloma (MM) is an incurable hematological malignancy characterized by clonal proliferation of malignant plasma B cells in bone marrow, and its pathogenesis remains unknown. The aim of this study was to determine the role of kinesin family member 22 (KIF22) in MM and elucidate its molecular mechanism. METHODS: The expression of KIF22 was detected in MM patients based upon the public datasets and clinical samples. Then, in vitro assays were performed to investigate the biological function of KIF22 in MM cell lines, and subcutaneous xenograft models in nude mice were conducted in vivo...

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored...

Among central nervous system-associated malignancies, glioblastoma (GBM) is the most common and has the highest mortality rate. The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide. In precision medicine, research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity, as well as the refractory nature of GBM toward therapy...

Canine tumours including urothelial carcinoma, lung adenocarcinoma, mammary gland tumour, squamous cell carcinoma, and melanoma have been identified as causes of death, but effective therapies are limited due to insufficient knowledge of the molecular mechanisms involved. Within the tumour microenvironment, hypoxia activates hypoxia-inducible factor 1α (HIF1α) in tumour cells. High HIF1α expression correlates with enhanced glycolysis and poorer outcomes in human cancers. However, the molecular mechanisms underlying hypoxic tumour cells remain elusive in dogs...

BACKGROUND: Gastric cancer (GC) is one of the major malignancies threatening human lives and health. Non-SMC condensin II complex subunit D3 ( NCAPD3 ) plays a crucial role in the occurrence of many diseases. However, its role in GC remains unexplored. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) database, clinical samples, and cell lines were used to analyze NCAPD3 expression in GC. NCAPD3 was overexpressed and inhibited by lentiviral vectors and the CRISPR/Cas9 system, respectively...

Oral squamous cell carcinoma (OSCC) is a crucial public health problem, accounting for approximately 2% of all cancers globally and 90% of oral malignancies over the world. Unfortunately, despite the achievements in surgery, radiotherapy, and chemotherapy techniques over the past decades, OSCC patients still low 5-year survival rate. Cisplatin, a platinum-containing drug, serves as one of the first-line chemotherapeutic agents of OSCC. However, the resistance to cisplatin significantly limits the clinical practice and is a crucial factor in tumor recurrence and metastasis after conventional treatments...

Background: Colorectal cancer (CRC) is a malignancy with high incidence and mortality rates globally, categorized into left-sided and right-sided CRC, each exhibiting significant differences in molecular characteristics, clinical manifestations, and prognosis. Methods: This study employed single-cell transcriptomic data and various bioinformatics approaches, such as two-sample Mendelian randomization, reverse Mendelian randomization, colocalization analysis, directed filtering, pseudotime analysis, and intercellular communication analysis...

Despite past research linking HLF mutations to cancer development, no pan-cancer analyses of HLF have been published. As a result, we utilized multiple databases to illustrate the potential roles of HLF in diverse types of cancers. Several databases were used to assess HLF expression in the TCGA cancer samples. Additional assessments were undertaken to investigate the relationship between HLF and overall survival, immune cell infiltration, genetic alterations, promoter methylation, and protein-protein interaction...

BACKGROUND: Statins, frequently prescribed medications, work by inhibiting the rate-limiting enzyme HMG-CoA reductase (HMGCR) in the mevalonate pathway to reduce cholesterol levels. Due to their multifaceted benefits, statins are being adapted for use as cost-efficient, safe and effective anti-cancer treatments. Several studies have shown that specific types of cancer are responsive to statin medications since they rely on the mevalonate pathway for their growth and survival. RECENT FINDINGS: Statin are a class of drugs known for their potent inhibition of cholesterol production and are typically prescribed to treat high cholesterol levels...

BACKGROUND: Hepatocellular carcinoma (HCC) is a fatal malignancy with poor prognosis due to lack of effective clinical interference. DCAF1 plays a vital role in regulating cell growth and proliferation, and is involved in the progression of various malignancies. However, the function of DCAF1 in HCC development and the underlying mechanism are still unknown. This study aimed to explore the effect of DCAF1 in HCC and the corresponding molecular mechanism. METHODS: Quantitative real-time PCR, Western blot and immunostaining were used to determine DCAF1 expression in tumor tissues and cell lines...

OBJECTIVE: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1...

Modulation of DNA damage repair in lung squamous cell carcinoma (LUSC) can result in the generation of neoantigens and heightened immunogenicity. Therefore, understanding DNA damage repair mechanisms holds significant clinical relevance for identifying targets for immunotherapy and devising therapeutic strategies. Our research has unveiled that the tumor suppressor zinc finger protein 750 (ZNF750) in LUSC binds to the promoter region of tenascin C (TNC), leading to reduced TNC expression. This modulation may impact the malignant behavior of tumor cells and is associated with patient prognosis...

Colorectal cancer (CRC) is a highly malignant carcinoma associated with poor prognosis, and metastasis is one of the most common causes of death in CRC. Serpin Family A Member 1 (SERPINA1) is a serine protease inhibitor from the Serpin family. Till now, the function and mechanism of SERPINA1 in CRC progression have not been fully illustrated. We established highly metastatic colorectal cancer cells named as RKO-H and Caco2-H by mice liver metastasis model. By integrative bioinformatic approaches, we analyzed the prognostic value and clinical significance of SERPINA1 in CRC, and predicted potential transcription factors...

Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells...