Journal of Cancer Prevention最新文献

This study aimed to establish an organoid culture model using small intestine tissues from male and female C57BL/6 mice and to compare it with rat organoid cultures derived from frozen tissues. Crypts were isolated from the small intestines of eight-week-old male and female mice and cultured in 3D extracellular matrix with Wnt, R-spondin, and Noggin. In addition, small intestine tissues from sixteen-week-old F344 rats were preserved in a storage solution immediately post-sacrifice and stored at -80°C before being transferred to a nitrogen tank. Upon thawing, crypts from frozen rat tissues failed to develop into organoids due to structural damage, suggesting the need for fresh tissues or optimized preservation methods. In contrast, mouse-derived organoids showed viability for 7 days, with distinct morphological changes and clear differentiation by Day 7. Quantitative real-time PCR analysis revealed that Lgr5, a stem cell marker, showed significantly higher expression in organoids than in tissues, confirming the successful establishment of the organoid culture. Among epithelial markers, the antimicrobial enzyme Lyz1 was more highly expressed in organoids, while Muc2, a key goblet cell marker, was more highly expressed in male tissues. The enterocyte marker Alp exhibited higher expression in male organoids compared to females, with no sex differences in tissues. These findings highlight sex-specific differences in gene expression related to small intestine differentiation and demonstrate the challenges in organoid culture from frozen rat tissues. The results suggest the importance of immediate tissue processing or improved preservation methods for successful organoid cultures.

Breast cancer is the most common cancer among women worldwide, with germline mutations in high-penetrance genes like BRCA1 and BRCA2, and moderate-penetrance genes such as CHEK2 and ATM contributing majorly to the onset of the same. Universal germline genetic testing offers an avenue to improve early identification and develop appropriate management guidelines. Our retrospective cohort study analyzed data from 525 newly diagnosed breast cancer patients at Mercy Hospital Fort Smith from January 2020 to December 2023. Patients underwent germline genetic testing using next-generation sequencing panels irrespective of family history of cancer. Details on patient demographics, clinical characteristics, and genetic test results were collected and analyzed. The median age at diagnosis of patients was 66, with invasive ductal carcinoma (IDC) being the major subtype (66%). CHEK2 mutations were the most common pathogenic mutations (9 patients), followed by BRCA1 and MUTYH (6 each). Pathogenic mutations were more prevalent in patients over 60 years (63%). Germline mutations were identified more frequently in IDC than in ductal carcinoma in situ. Among patients with germline mutations, there was a significant drift toward mastectomy over breast-conserving surgery. Universal germline genetic testing identified pathogenic mutations in a significant proportion of breast cancer patients, especially among the older patient population. The findings further emphasize the importance of integrating universal genetic testing into routine care to guide surgical and risk-reduction management protocols effectively. Further research is needed to regularize genetic testing in similar patients.

Bacillus Calmette-Guérin (BCG) serves as an anticancer drug for bladder cancer by enhancing the innate immune response and facilitating the expression of beta-defensin-2/-3. BCG is significantly more effective than other treatment modalities; however, it has limitations due to the nonspecific secretion of immune proteins such as interleukin-2 (IL-2) and IFN-γ, necessitating frequent injections that result in toxicity. The newly developed BCG-cell wall skeleton (BCG-CWS) is intended to address the non-specificity and the requirement for repeated treatments associated with BCG. BCG-CWS stimulates antigen-presenting cells by secreting cytokines such as IL-12, using an adjuvant to enhance the immune response and synergize with it to provoke a potent immune reaction. Nevertheless, BCG-CWS encounters issues related to cellular uptake due to the substantial molecular weight of the drug. To meet this challenge, various strategies such as the introduction of R8 protein, the liposome evaporated via an emulsified lipid method, and nanoparticle formulation have been employed which can enhance targeted drug delivery, though issues related to particle size remain unresolved. This paper aims to discuss future perspectives by examining the mechanisms and challenges of BCG-CWS.

Chromosomal alterations are frequent events in lung cancer progression. Although gains and losses of chromosomal position have been reported, the association between copy number alteration and lung cancer patient survival has not been extensively investigated. In this study, we performed a meta-analysis of public cBioPortal datasets spanning 25 lung cancer studies to identify putative cancer driver genes with copy number alterations associated with overall patient survival. Ten copy-number altered genes enriched in deceased lung cancer patients were identified. Seven of these putative driver genes were located in the 7p11.2 chromosomal location, and two were in the 9p21.3 cytoband. Among these genes, the mitochondrial ribosomal protein S17 (MRPS17) amplification was significantly associated with a lower patient survival rate (P = 1.47e-7). To investigate the functional role of MRPS17, small interfering RNA-mediated knockdown was performed in two non-small cell lung cancer cell lines, A549 and NCI-H460. MRPS17 knockdown significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth in both cell lines. Furthermore, knockdown of MRPS17 decreased the activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, suggesting its role in driving lung cancer progression through this critical oncogenic pathway. Our findings highlight MRPS17 as a potential cancer therapy target and a prognostic biomarker that may improve the survival rates of lung cancer patients. Future studies should explore its inhibition as a therapeutic strategy as well as elucidate its molecular mechanisms in cancer progression.

[This corrects the article on p. 157 in vol. 29, PMID: 39790229.].

Melanoma is a malignant tumor originating from melanocytes, characterized by its high invasiveness and metastasis, leading to poor prognosis and high mortality. Early-stage melanoma is primarily treated with surgery; however, due to its metastatic nature, surgery becomes challenging in advanced stages. Treatment strategies for advanced or metastatic melanoma include chemotherapy, radiation therapy, and targeted therapy. However, melanoma's propensity for rapid drug resistance remains a significant clinical challenge. This review summarizes the developments in the treatment of drug-resistant melanoma over the past decade and discusses the advantages and disadvantages of various therapeutic approaches and their clinical significance implications.

Renal cancer continues to offer a great challenge for its successful therapy today, thus underscoring the need for effective chemotherapeutic agents. In the current study, we explored the anticancer effects of domperidone, a dopamine D2 receptor (DRD2) antagonist, in renal cancer Caki-2 cells. Domperidone induced dose and time-dependent cytotoxic effects in Caki-2 cells, triggering intrinsic apoptosis via the stimulation of the caspase cascade and PARP cleavage. The cytotoxic effect of domperidone was found to be partially DRD2-dependent. Domperidone treatment markedly augmented the production of intracellular reactive oxygen species which induced the cell death of Caki-2 cells. In addition, domperidone suppressed Janus kinase 2 and STAT3 phosphorylation, leading to inhibition of survival and proliferation of these cells. Hence, domperidone can be considered a promising candidate for renal cancer treatment.

Due to rapid westernization, Korean dietary habits have emerged as significant risk factors for chronic disease and cancer. Despite this transition, Korea's cancer prevention guidelines have remained consistent since their establishment about 18 years ago. This study aimed to investigate the degree of awareness and practice to global dietary guidelines among Korean adults and identify demographic and lifestyle factors associated with low practice. A cross-sectional survey conducted in 2023 included 4,000 adults and assessed their awareness and practice of four global recommendations: "Eat a diet rich in whole grains," "Limit consumption of processed meat," "Limit consumption of sugar-sweetened beverages," and "Limit consumption of fast and other processed foods." While more than half of the participants recognized the guidelines' importance for cancer prevention, implementation rates remained below 40%. Furthermore, over 80% of the respondents expressed a compelling requirement for updated and tailored dietary guidelines. Younger individuals, those who were physically inactive, individuals who had not received prior nutrition education, and participants with obesity were more likely to exhibit low practice, particularly to guidelines limiting processed foods and sugary beverages intake. These findings highlight the need to revise Korea's cancer prevention recommendations by incorporating global dietary practices and addressing the westernized eating patterns prevalent within the population. Efforts should focus on promoting these updated guidelines through targeted education and public health interventions that improve practice, especially in high-risk groups, and effectively mitigate the burden of diet-related cancers in Korea.

[This corrects the article on p. 129 in vol. 29, PMID: 39790223.].

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans. This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfonylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.