Background Treatment for platinum-resistant ovarian cancer is challenging. Currently, platinum-resistant ovarian cancer is typically treated with non-platinum single-agent chemotherapy ± bevacizumab, but the prognosis is often extremely poor. In the treatment of platinum-resistant ovarian cancer patients, reports of triple therapy with interstitial implantation radiotherapy combined with immunotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) (PRaG for short) are relatively rare. Case description Here, we report a patient with oligometastatic platinum-resistant ovarian cancer. The patient achieved partial response (PR) of the lesion and sustained benefit for more than six months after receiving interstitial implantation radiotherapy combined with immunotherapy along with GM-CSF. Conclusion This triple therapy may provide additional options for these patients.
BACKGROUND:The aim of this study was to establish a predictive model for prognostic factors and overall survival (OS) in nasopharyngeal lymphoepithelial carcinoma (NLEC) patients. MATERIAL AND METHODS:The data of 538 NLEC patients diagnosed between 1988 and 2015 were extracted from the Surveillance, Epidemiology, and End Results database. Patients who were diagnosed from 1988 to 1999 were included in the validation cohort, and those diagnosed from 2000 to 2015 in the primary cohort. Least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed. The discrimination and calibration capabilities of the predictive models were evaluated using the receiver operating characteristic (ROC) curve and calibration plot, respectively. RESULTS:Radiotherapy (P<0.0001), early-stage cancer based on the American Joint Committee on Cancer (AJCC) staging system (P<0.0001), younger age (P=0.0005) were associated with better OS rates. In the primary cohort, the areas under the ROC curves (AUC) of the nomogram for predicting 1-, 10-, and 15-year OS were 0.749, 0.754, and 0.81, respectively. Meanwhile, in the validation cohort, the AUC of the nomogram for predicting 1-, 10-, and 15-year OS were 0.692, 0.692, and 0.682, respectively. Furthermore, the calibration plot exhibited optimal agreements between the nomogram-predicted and actual 1-, 10-, and 15-year OS in both cohorts. The 1-, 10-, and 15-year OS rates were 93.6%, 62.7%, and 49.9%, respectively. CONCLUSIONS:Age, early-stage cancer based on the AJCC staging system, radiotherapy, and gender can be used to predict OS in nasopharyngeal lymphoepithelial carcinoma patients.
Background Colorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development. Methods We analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant bacterial taxa were identified via MR analysis. Single-cell RNA sequencing and enrichment analyses elucidated underlying pathways, and drug predictions identified potential therapeutics. Results MR identified 19 bacterial taxa significantly associated with CRC. Protective effects were observed in taxa like RUG343 and Streptococcus_umgs_2425, while HOT-345_umgs_976 and W5053_sp000467935_mgs_712 increased CRC risk. Single-cell RNA sequencing revealed key pathways, including JAK-STAT signaling and tyrosine metabolism. Drug prediction highlighted potential therapeutics like Menadione Sodium Bisulfite and Raloxifene. Conclusion This study establishes the critical role of the oral microbiome in colorectal cancer development, identifying specific microbial taxa linked to CRC risk. Single-cell RNA sequencing and drug prediction analyses further elucidate key pathways and potential therapeutics, providing novel insights and personalized treatment strategies for CRC.
Breast cancer (BC) is one of the most common and fatal malignancies among women worldwide. Circadian rhythms have emerged in recent studies as being involved in the pathogenesis of breast cancer. In this paper, we reviewed the molecular mechanisms by which the dysregulation of the circadian genes impacts the development of BC, focusing on the critical clock genes, brain and muscle ARNT-like protein 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK). We discussed how the circadian rhythm disruption (CRD) changes the tumor microenvironment (TME), immune responses, inflammation, and angiogenesis. The CRD compromises immune surveillance and features and activities of immune effectors, including CD8+ T cells and tumor-associated macrophages, that are important in an effective anti-tumor response. Meanwhile, in this review, we discuss bidirectional interactions: age and circadian rhythms, aging further increases the risk of breast cancer through reduced vasoactive intestinal polypeptide (VIP), affecting suprachiasmatic nucleus (SCN) synchronization, reduced ability to repair damaged DNA, and weakened immunity. These complex interplays open new avenues toward targeted therapies by the combination of clock drugs with chronotherapy to potentiate the immune response while reducing tumor progression for better breast cancer outcomes. This review tries to cover the broad area of emerging knowledge on the tumor-immune nexus affected by the circadian rhythm in breast cancer.
Background: Breast cancer, comprising 15% of newly diagnosed malignancies, poses a formidable global oncological challenge for women. The severity of this malady stems from tumor infiltration, metastasis, and elevated mortality rates. Disulfidptosis, an emerging cellular demise mechanism, presents a promising avenue for precision tumor therapy. Our aim was to construct a prognostic framework centered on long non-coding RNAs (lncRNAs) associated with disulfidptosis, aiming to guide the strategic use of clinical drugs, enhance prognostic precision, and advance immunotherapy and clinical prognosis assessment. Methods: We systematically analyzed the TCGA-BRCA dataset to identify disulfidptosis-linked lncRNAs. Employing co-expression analysis, we discerned significant relationships between disulfidptosis-associated genes and lncRNAs. Identified lncRNAs underwent univariate Cox regression and validation through LASSO regression, culminating in the identification of eight signature lncRNAs using a multivariate Cox proportional risk regression model. Then, we utilized the selected genes to build prognostic prediction models. Results: The DAL model exhibited outstanding prognostic efficacy, establishing itself as an autonomous determinant for breast cancer prognosis. It adeptly differentiated low and high-risk patient cohorts, with high-risk individuals experiencing significantly abbreviated survival durations. Notably, these cohorts displayed marked discrepancies in clinical markers and tumor microenvironment attributes. Conclusions: The DAL model has performed well in clinical prognostic assessment by combining it with other clinical traditional indicators to construct Nomogram plots and use gene expression data to calculate patients' disease risk scores. This approach provides new ideas for clinical decision support and personalized treatment decisions for patients with different risk levels.
Purpose In recent years, traditional Chinese medicine has received widespread attention in the field of cancer pain treatment. This meta-analysis is the first to evaluate the effectiveness and safety of acupuncture point stimulation in the treatment of stomach cancer pain. Methods For this systematic review and meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Embase, WANFANG, China National Knowledge Infrastructure (CNKI), and Chinese Journal of Science and Technology (VIP) databases as well as forward and backward citations to studies published between database creation to July 27, 2023. All randomized controlled trials (RCTs) on acupuncture point stimulation for the treatment of patients with stomach cancer pain were included without language restrictions. We assessed all outcome indicators of the included trials. The evidence from the randomized controlled trials was synthesized as the standardized mean difference (SMD) of symptom change. The quality of the evidence was assessed using the Cochrane Risk of Bias tool. This study is registered on PROSPERO under the number CRD42023457341. Results Eleven RCTs were included. The study included 768 patients, split into 2 groups: acupuncture point stimulation treatment group ( n = 406), medication control group ( n = 372). The results showed that treatment was more effective in the acupuncture point stimulation treatment group than in the medication control group (efficacy rate, RR = 1.63, 95% CI 1.37 to 1.94, p < 0.00001), decreasing in NRS score was greater in acupuncture point stimulation treatment group than in the medication control group (SMD = −1.30, 95% CI −1.96 to −0.63, p < 0.001). Systematic Review Registration https://clinicaltrials.gov/ , identifier CRD42023457341.
Previous studies have reported on several genetic variants related to breast cancer, but a substantial proportion of mutation loci have not yet been identified. In the current study, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of interleukin-10 (IL-10) and susceptibility to breast cancer in Shaanxi Han women in China.Six SNPs were genotyped in 530 breast cancer patients and 628 healthy women from the First Affiliated Hospital of Xi'an Jiaotong University Hospital. Odds ratios and 95% confidence intervals were calculated by unconditional logistic regression analysis to assess the association between breast cancer risk and polymorphisms of six loci.Two SNPs, rs3024490 and rs1800871, were found to be significantly different between breast cancer patients and healthy women. These SNPs also increased the risk of breast cancer in co-dominant and dominant models. Moreover, another SNP, rs1554286, was significantly associated with an increased risk of breast cancer in the co-dominant model. Functional assessments indicated that these three variants may influence the expression and transcription factor binding of IL-10.Our findings suggest that variants of IL-10 may be likelihood risk factors for the development and progression of breast cancer. Future studies should replicate this study and evaluate functional assessments in Chinese Han women and women from other regions.
Human epidermal growth factor receptor (HER)‑2‑positive breast cancer accounts for ~25% of all breast cancer cases, has a high propensity for relapse, metastasis and drug resistance, and is associated with a poor prognosis. Therefore, it is necessary to develop more effective therapeutic targets for the treatment of HER‑2‑positive breast cancer. CD44+/CD24‑/low is currently the most commonly used marker for breast cancer stem cells (CSCs), which are considered the main cause of drug resistance, relapse and metastasis. In the present study, the ratio of CD44+/CD24‑/low cells was almost zero in SK‑BR‑3 cells; however, it was >90% in MDA‑MB‑231 cells, as determined by flow cytometry. Since SK‑BR‑3 and MDA‑MB‑231 cells both exhibit a strong propensity for invasion and migration, it was hypothesized that there may be other markers of CSCs in SK‑BR‑3 cells. Therefore, transcriptome sequencing was performed for SK‑BR‑3 and MDA‑MB‑231 cells. It was observed that several leukocyte differentiation antigens and other CSC markers were significantly more highly expressed in SK‑BR‑3 cells. Furthermore, the expression of aldehyde dehydrogenase (ALDH)1A3, CD164 and epithelial cell adhesion molecule (EpCAM) was higher in SK‑BR‑3 cells compared with in other subtypes of breast cell lines, as determined by reverse transcription‑polymerase chain reaction and western blot analysis. In addition, the expression levels of ALDH1A3, ALDH3B2 and EpCAM were higher in HER‑2‑positive breast cancer compared with in paracancerous tissues and other subtypes of breast cancer, as determined by immunohistochemistry. The expression of β‑catenin in the Wnt signaling pathway was lower in SK‑BR‑3 cells compared with in MDA‑MB‑231 cells, which may be used as a prognostic indicator for breast cancer. These findings may help identify novel CSC markers and therapeutic targets for HER‑2‑positive breast cancer.
ABSTRACT Background Immune checkpoint inhibitors have brought hope for patients with advanced lung cancer, among which PD-1/PD-L1 and CTLA-4 inhibitors have achieved considerable results. This meta-analysis aims to investigate the efficacy and safety of PD-1/PD-L1 combined with CTLA-4 antibodies in patients with advanced lung cancer. Materials and Methods Randomized controlled trials (RCTs) study of PD-1/PD-L1 combined with CTLA-4 inhibitors for advanced lung cancer was searched in the database for systematic review and meta-analysis. Results The meta-analysis finally included 4 trials (actually 3 trials), and the results showed that the overall response rate of PD-1/PD-L1 combined with CTLA-4 inhibitor was higher than that of the control group (ORR = 2.29 [95% CI 1.58 3.32], P <0.0001). PFS significantly improved compared with conventional treatment (HR = 0.69 [95% CI 0.56, 0.85], P = 0.0005), which was statistically significant. OS also improved but did not statistically significant (HR = 0.80 [95% CI 0.61, 1.05], P = 0.11). PD-1/PD-L1 combined with CTLA-4 inhibitors had a higher incidence of adverse reactions than conventional treatment (OR = 1.72 [95% CI 0.59, 5.09], P = 0.33), but the incidence of grade≥3 AEs was lower than the control group (OR = 0.96 [95% CI 0.64, 1.44], P = 0.85). Conclusion Double checkpoint inhibitor PD-1/PD-L1 combined with CTLA-4 antibody has synergistic anti-cancer activity and improved ORR and PFS in lung cancer. Adverse reactions are more common than conventional treatment, but are generally controllable. Therefore, PD-1/PD-L1 combined with CTLA-4 inhibitors provides a beacon for the treatment of advanced lung cancer, which has guiding significance for the treatment selection in the future.
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