Journal of Cancer Prevention最新文献

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.

Cadmium (Cd) exposure primarily occurs through inhalation, either by smoking or occupational exposure to contaminated air. Upon inhalation, Cd ultimately reaches the prostate through the bloodstream. In this review, we investigate the carcinogenic potential of Cd in both respiratory organs and the prostate. Specifically, this review examines cellular metabolism, comprehensive toxicity, and carcinogenic mechanisms by exploring gene ontology, biological networks, and adverse outcome pathways. In the respiratory organs, Cd induces lung cancer by altering the expression of IL1B and FGF2, causing DNA damage, reducing cell junction integrity, and promoting apoptosis. In the prostate, Cd induces prostate cancer by modifying the expression of EDN1 and HMOX1, leading to abnormal protein activities and maturation, suppressing tumor suppressors, and inducing apoptosis. Collectively, this review provides a comprehensive understanding of the carcinogenic mechanisms of Cd in two different organs by adopting toxicogenomic approaches. These insights can serve as a foundation for further research on cadmium-induced cancer, contributing to the establishment of future cancer prevention strategies.

Helicobacter pylori infection poses significant health risks, such as gastric adenocarcinoma, necessitating accurate diagnosis and effective treatment in primary care. This study evaluated the diagnostic efficacy of the serological current infection marker (CIM) test in identifying current H. pylori infection. The CIM test samples from 159 participants undergoing gastroscopy were collected, and H. pylori-positive outpatients received triple therapy based on histology or rapid urease test results. Following treatment, 45 patients underwent a ¹³C-urea breath test and the CIM test for eradication assessment. For pre-eradication, the CIM test demonstrated 89.6% sensitivity, 95.7% specificity, 93.8% positive predictive value, 92.6% negative predictive value, and 93.1% accuracy. Following post-eradication, the CIM test exhibited sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 71.4%, 92.1%, 62.5%, 94.6%, and 88.9%, respectively, using the ¹³C-urea breath test as the reference standard. The CIM test showcased commendable diagnostic performance, emphasizing its efficacy in both pre- and post-eradication scenarios. Notably, the accuracy, non-invasiveness, user-friendliness, and cost-effectiveness of the CIM test advocate for its recommendation as a preferred diagnostic tool in primary care settings for H. pylori infection detection.

Activating nuclear factor-erythroid 2-related factor (Nrf2), a master regulator of redox homeostasis, has been shown to suppress initiation of carcinogenesis in normal cells. However, this transcription factor has recently been reported to promote proliferation of some transformed or cancerous cells. In tumor cells, Nrf2 is prone to mutations that result in stabilization and concurrent accumulation of its protein product. A hyperactivated mutant form of Nrf2 could support the cancer cells for enhanced proliferation, invasiveness, and resistance to chemotherapeutic agents and radiotherapy, which are associated with a poor clinical outcome. Hence understanding mutations in Nrf2 would have a significant impact on the prognosis and treatment of cancer in the era of precision medicine. This perspective would provide an insight into the genetic alterations in Nrf2 and suggest the application of small molecules, RNAi, and genome editing technologies, particularly CRISR-Cas9, in therapeutic intervention of cancer in the context of the involvement of Nrf2 mutations.

Cyclic GMP-AMP (cGAMP), synthesized by cGAMP synthase (cGAS), serves as a secondary messenger that modulates various cellular processes, including cell proliferation, cell death, immune response, and inflammation. cGAS is activated upon detecting cytoplasmic DNA, which may originate from damaged genomic and mitochondrial DNA or from viral and bacterial infections. The presence of DNA in the cytoplasm can trigger a substantial inflammatory reaction and cytokine production via the cGAS-STING signaling pathway. Consequently, specific inhibitors targeting this pathway hold significant potential as chemopreventive agents. In this review, we explore the potential effectiveness of modulating cGAS activity. We discuss the role of cGAMP, the mechanism of action for distinguishing between self and foreign DNA, and the possible functions of cGAS within the nucleus.

This study aimed to investigate the efficacy and safety of apatinib plus programmed cell death protein 1 (PD-1) blockades for patients with metastatic colorectal cancer (CRC) who were refractory to the standard regimens. In this retrospective study, patients with metastatic CRC who received apatinib plus PD-1 blockades in clinical practice were included. The initial dosage of apatinib was 250 mg or 500 mg, and PD-1 blockades were comprised of camrelizumab, sintilimab and pembrolizumab. Efficacy and safety data were collected through the hospital's electronic medical record system. From October 2018 to March 2022, a total of 43 patients with metastatic CRC were evaluated for efficacy and safety. The results showed an objective response rate of 25.6% (95% CI, 13.5%-41.2%) and a disease control rate of 72.1% (95% CI, 56.3%-84.7%). The median progression-free survival (PFS) of the cohort was 5.8 months (95% CI, 3.81-7.79), and the median overall survival (OS) was 10.3 months (95% CI, 5.75-14.85). The most common adverse reactions were fatigue (76.7%), hypertension (72.1%), diarrhea (62.8%), and hand-foot syndrome (51.2%). Multivariate Cox regression analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status and location of CRC (left or right-side) were independent factors to predict PFS of patients with metastatic CRC treated with the combination regimen. Consequently, the combination of apatinib and PD-1 blockades demonstrated potential efficacy and acceptable safety for patients with treatment-refractory metastatic CRC. This conclusion should be confirmed in prospective clinical trials subsequently.

There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.

A category of diseases known as cancer includes abnormal cell development and the ability to infiltrate or spread to other regions of the body, making them a major cause of mortality worldwide. Chemotherapy, radiation, the use of cytotoxic medicines, and surgery are the mainstays of cancer treatment today. Plants or products produced from them hold promise as a source of anti-cancer medications that have fewer adverse effects. Due to the presence of numerous phytochemicals that have been isolated from various parts of the Hibiscus sabdariffa (HS) plant, including anthocyanin, flavonoids, saponins, tannins, polyphenols, organic acids, caffeic acids, citric acids, protocatechuic acid, and others, extracts of this plant have been reported to have anti-cancer effects. These compounds have been shown to reduce cancer cell proliferation, induce apoptosis, and cause cell cycle arrest. They also increase the expression levels of the cell cycle inhibitors (p53, p21, and p27) and the pro-apoptotic proteins (BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9). This review highlights various intracellular signalling pathways involved in cancer preventive potential of HS.

Roseburia faecis, a butyrate-producing, gram-positive anaerobic bacterium, was evaluated for its usefulness against repeated water avoidance stress (WAS)-induced irritable bowel syndrome (IBS) in a rat model, and the underlying mechanism was explored. We divided the subjects into three groups: one without stress exposure, another subjected to daily 1-hour WAS for 10 days, and a third exposed to the same WAS regimen while also receiving two different R. faecis strains (BBH024 or R22-12-24) via oral gavage for the same 10-day duration. Fecal pellet output (FPO), a toluidine blue assay for mast cell infiltration, and fecal microbiota analyses were conducted using 16S rRNA metagenomic sequencing. Predictive functional profiling of microbial communities in metabolism was also conducted. FPO and colonic mucosal mast cell counts were significantly higher in the WAS group than in the control group (male, P = 0.004; female, P = 0.027). The administration of both BBH024 (male, P = 0.015; female, P = 0.022) and R22-12-24 (male, P = 0.003; female, P = 0.040) significantly reduced FPO. Submucosal mast cell infiltration in the colon showed a similar pattern in males. In case of fecal microbiota, the WAS with R. faecis group showed increased abundance of the Roseburia genus compared to WAS alone. Moreover, the expression of a gene encoding a D-methionine transport system substrate-binding protein was significantly elevated in the WAS with R. faecis group compared to that in the WAS (male, P = 0.028; female, P = 0.025) group. These results indicate that R. faecis is a useful probiotic for treating IBS and colonic microinflammation.

This study aimed to estimate the medical cost of cancer in the first five years of diagnosis and in the final six months before death in people who developed cancer after human immunodeficiency virus (HIV) infection in Korea. The study utilized the Korea National Health Insurance Service-National Health Information Database (NHIS-NHID). Among 16,671 patients diagnosed with HIV infection from 2004 to 2020 in Korea, we identified 757 patients newly diagnosed with cancer after HIV diagnosis. The medical costs for 60 months after diagnosis and the last six months before death were calculated from 2006 to 2020. The mean annual medical cost due to cancer in HIV-infected people with cancer was higher for acquired immunodeficiency syndrome (AIDS)-defining cancers (48,242 USD) than for non-AIDS-defining cancers (24,338 USD), particularly non-Hodgkin's lymphoma (53,007 USD), for the first year of cancer diagnosis. Approximately 25% of the cost for the first year was disbursed during the first month of cancer diagnosis. From the second year, the mean annual medical cost due to cancer was significantly reduced. The total medical cost was higher for non-AIDS-defining cancers, reflecting their higher incidence rates despite lower mean medical costs. The mean monthly total medical cost per HIV-infected person who died after cancer diagnosis increased closer to the time of death. The estimated burden of medical costs in patients with HIV in the present study may be an important index for defining healthcare policies in HIV patients in whom the cancer-related burden is expected to increase.