World journal of clinical oncology最新文献

Background: Primary vaginal cancer is rare and most vaginal tumors are metastatic, often arising from adjacent gynecologic structures. Primary vaginal cancers are also more common among postmenopausal women and most of these are squamous cell carcinomas, with adenocarcinomas being relatively rare. Vaginal bleeding is the most common clinical manifestation of vaginal adenocarcinoma. About 70% of vaginal adenocarcinomas are stage I lesions at the time of diagnosis, for which radical surgery is recommended. However, more advanced vaginal cancers are not amenable to radical surgical treatment and have poor clinical outcomes. Optimal treatments modes are still being explored. Here, we report a rare case of stage IIb primary vaginal adenocarcinoma for which an individually designed vaginal applicator for after-loading radiotherapy was used to achieve good tumor control.

Case summary: A 62-year-old woman presented to our clinic after 3 months of abnormal postmenopausal vaginal bleeding. Gynecological examination, computed tomography (CT), and positron emission tomography-CT showed a large mass (about 5 cm) on the anterior vaginal wall. Colposcopy biopsy confirmed adenocarcinoma of vaginal origin. After three cycles of carboplatin plus paclitaxel chemotherapy, the lesion partially shrunk. The patient then received external irradiation of 45 gray (gy) in 25 fractions, which further reduced the vaginal lesion, followed by after-loading radiotherapy of 30 gy in 5 fractions with an individually designed vaginal applicator. Three months later, magnetic resonance imaging showed a slight thickening of the anterior vaginal wall.

Conclusion: Primary vaginal adenocarcinoma is rare, and prognosis is poor in most vaginal cancers of locally advanced stages, which cannot be treated with radical surgery. Better tumor control can be achieved with an individualized vaginal applicator that allows administration of a higher radical dose to the tumor area while protecting normal tissues.

Cancer, the second leading global cause of death, impacts both physically and emotionally. Conventional treatments such as surgeries, chemotherapy, and radiotherapy have adverse effects, driving the need for more precise approaches. Precision medicine enables more targeted treatments. Genetic mapping, alongside other molecular biology approaches, identifies specific genes, contributing to accurate prognoses. The review addresses, in clinical use, a molecular perspective on treatment. Biomarkers like alpha-fetoprotein, beta-human chorionic gonadotropin, 5-hydroxyindoleacetic acid, programmed death-1, and cytotoxic T lymphocyte-associated protein 4 are explored, providing valuable information. Bioinformatics, with an emphasis on artificial intelligence, revolutionizes the analysis of biological data, offering more accurate diagnoses. Techniques like liquid biopsy are emphasized for early detection. Precision medicine guides therapeutic strategies based on the molecular characteristics of the tumor, as evidenced in the molecular subtypes of breast cancer. Classifications allow personalized treatments, highlighting the role of trastuzumab and endocrine therapies. Despite the benefits, challenges persist, including high costs, tumor heterogeneity, and ethical issues. Overcoming obstacles requires collaboration, ensuring that advances in molecular biology translate into accessible benefits for all.

Gastrointestinal cancer (GIC) is a common and widespread form of tumor, with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions. However, many patients are already in the late stages when first diagnosed with such cancer, resulting in a poor prognosis. Thus, it is necessary to explore new methods and research directions in order to improve the treatment of GIC. Given the specific nature of the gastrointestinal tract, research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells. Interestingly, six transmembrane epithelial antigens of the prostates (STEAPs) have been found to be significantly linked to the progression of malignant tumors, associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function. This paper explores the mechanism of STEAPs in the inflammatory response of GIC, providing a theoretical basis for the prevention and early intervention of GIC. The basic properties of the STEAP family as metal reductase are also explained. When it comes to intervention for GIC prevention, STEAPs can affect the activity of Fe³⁺, Cu²⁺ reductase and regulate metal ion uptake in vivo, participating in inflammation-related iron and copper homeostasis. Thus, the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

Background: Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. However, the underlying mechanisms remain elusive.

Aim: To detect the differential expression profiles of plasma exosomal microRNAs (miRNAs) in poor and good responders and explore the potential mechanisms of chemoresistance.

Methods: In this study, the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses (poor/good responders) and treatment courses (pre/post-nCRT) using RNA sequencing.

Results: Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT. Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, such as the MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. Further analysis indicated that MAPK3, RAX2, and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer, and the profiles of MAPK3, TSPYL5, and ZNF417 were correlated with tumor stage. In addition, the expression profiles of MAPK3, RNF165, and ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.

Conclusion: This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.

In this editorial, we comment on the article by Zhu et al published in the recent issue of the World Journal of Clinical Oncology. We focus specifically on the characteristics and mechanisms of pyroptosis and the impact of changes in the tumor immune microenvironment (TIME) on cancer prognosis. Pyroptosis is a distinct form of programmed cell death; its occurrence can change the TIME and regulate the growth and spread of tumors and therefore is significantly correlated with cancer prognosis. Previous research has demonstrated that pyroptosis-related genes can be used in prognostic models for various types of cancer. These models enhance the mechanistic understanding of tumor evolution and serve as valuable guides for clinical treatment decision-making. Nevertheless, further studies are required to thoroughly understand the function of pyroptosis within the TIME and to assess its mode of action. Such studies should reveal new tumor therapeutic targets and more successful tumor immunotherapy strategies.

Recent advancements in next generation sequencing have allowed for genetic information become more readily available in the clinical setting for those affected by cancer and by treating clinicians. Given the lack of access to geneticists, medical oncologists and other treating physicians have begun ordering and interpreting genetic tests for individuals with cancer through the process of "mainstreaming". While this process has allowed for quicker access to genetic tests, the process of "mainstreaming" has also brought several challenges including the dissemination of variants of unknown significance results, ordering of appropriate tests, and accurate interpretation of genetic results with appropriate follow-up testing and interventions. In this editorial, we seek to explore the process of informed consent of individuals before obtaining genetic testing and offer potential solutions to optimize the informed consent process including categorization of results as well as a layered consent model.

Background: Celiac disease (CeD) is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. Recent research has unveiled a heightened risk of developing specific malignant neoplasms (MN) and various malignancies, including gastrointestinal, lymphomas, skin, and others, in individuals with CeD.

Aim: To investigate the prevalence of MN in hospitalized CeD patients in the United States.

Methods: Using data from the National Inpatient Sample spanning two decades, from January 2000 to December 2019, we identified 529842 CeD patients, of which 78128 (14.75%) had MN. Propensity score matching, based on age, sex, race, and calendar year, was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio.

Results: Positive associations were observed for several malignancies, including small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis. Conversely, CeD patients exhibited a reduced risk of respiratory and secondary malignancies. Moreover, certain malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers.

Conclusion: Our study is unique in highlighting the detailed results of positive, negative, or null associations between different hematologic and solid malignancies and CeD. Furthermore, it offers insights into evolving trends in CeD hospital outcomes, shedding light on advancements in its management over the past two decades. These findings contribute valuable information to the understanding of CeD's impact on health and healthcare utilization.

Pancreatic cancer is associated with a poor prognosis, even in the early stages, mainly due to metastatic progression. New diagnostic techniques that predict unfavorable outcomes are needed in order to improve treatment strategies. Circulating tumor cells (CTCs) are showing promising results as a predictive biomarker for various tumors. In this editorial we comment on the article by Zhang et al, who published the first systematic review and meta-analysis evaluating the prognostic value of CTCs as biomarkers in early-stage pancreatic cancer patients undergoing surgery. CTCs were detected in peripheral or central venous system blood, before or during surgery. Positive CTCs showed a correlation with decreased overall survival and decreased relapse-free, disease-free and progression-free survival in this meta-analysis. However, the heterogeneity was significant. The authors suggest that this result was related to the separation methods used between studies, but other differences such as the margin status or the neoadjuvant and adjuvant treatments used are also important to consider. CTCs may be a potential prognostic biomarker in pancreatic cancer patients, but it is necessary to compare and standardize the platforms used to isolate CTCs, to compare different biomarkers from liquid biopsy and to determine the impact on prognosis when therapeutic changes are made based on CTCs levels.

Gliomas originate from glial cells in the central nervous system. Approximately 80%-85% of malignant brain tumors in adults are gliomas. The most common central nervous system tumor in children is low-grade pediatric glioma. Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral diagnosis. Molecular characterization has led to better diagnostic and prognostic staging, which in turn has increased the precision of treatment. Current efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with glioma. However, improvements in survival have been modest. Currently, clinical guidelines, as well as the article by Mohamed et al accompanying this editorial piece, are adapting treatment recommendations (surgery, chemotherapy, and radiotherapy) according to diagnosis and prognosis guided by molecular biomarkers. Furthermore, this paves the way for the design of clinical trials with new therapies, which is especially important in pediatric gliomas.

Background: Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos (PF) has significant biological activities against liver damage, tumors and inflammation. Kakkatin is an isoflavone polyphenolic compound isolated from PF flower. However, the effect of kakkatin and its derivatives on anti-tumor has not been well explored.

Aim: To design and synthesize a kakkatin derivative [6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (HK)] to explore its anti-tumor biological activity.

Methods: Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol, and the derivative of kakkatin was prepared; the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability, a clone formation assay was adopted to detect cell proliferation, apoptosis, necrosis, and cell cycles were analyzed by Annexin V/propidium iodide staining and flow cytometry. Cell migration and invasion ability were evaluated by cell scratch assay and transwell assay. The potential mechanism of HK on hepatocellular carcinoma (HCC) SMMC-7721 cells was explored through network pharmacology and molecular docking, and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of HK.

Results: Compared with kakkatin, the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells, but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times, with an IC₅₀ value of 2.5 μM, and the tumor inhibition effect was better than cisplatin, which could significantly inhibit the cloning, invasion and metastasis of HCC SMMC-7721 cells, and induce apoptosis and G2/M cycle arrest. Its mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP pathway.

Conclusion: HK have a significant inhibitory effect on HCC SMMC-7721 cells, and the targets of their action may be PDE3B and NFKB1 proteins in the cAMP pathway, making it a good lead drug for the treatment of HCC.