Development of dynamic nomogram for predicting cancer-specific survival in hepatoid adenocarcinoma: A comprehensive SEER-based population analysis.

Hepatoid adenocarcinoma (HAC) is a poorly differentiated extrahepatic tumor that can produce alpha-fetoprotein (AFP). The literature does not provide a comprehensive understanding of the prognostic factors for HAC. Therefore, we present a novel nomogram to predict the cancer-specific survival (CSS) of patients with HAC. We analyzed 265 cases of HAC from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2004 to 2015. Using a Cox proportional hazard regression model, we identified several risk factors and incorporated them into our predictive nomogram. The nomogram's predictive ability was assessed by utilizing the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC). Results from a multivariate Cox regression showed that CSS was independently correlated with liver metastasis, surgery, and chemotherapy. Our nomogram had a C-index of 0.71 (95% CI 0.71-0.96). Furthermore, calibration curves demonstrated concordance between the predicted survival probability from the nomogram and the observed survival probability. The areas under the curve (AUC) for 6-month, 1-, and 3-year survival were 0.80, 0.82, and 0.88, respectively. Our study successfully formulated a prognostic nomogram that offers promising predictions for the 6-month, 1-, and 3-year CSS of patients with HAC. This nomogram holds potential for practical use in guiding treatment decisions and designing clinical trials.

Efficacy and safety analysis of a HER2-targeting antibody-drug conjugate combined with immune checkpoint inhibitors in solid tumors: a real-world study.

BACKGROUND: Disitamab Vedotin is a novel antibody-drug conjugate (ADC) drug targeting HER2, which has shown a potential synergistic effect between Disitamab Vedotin and immune checkpoint inhibitors (ICIs). Therefore, we plan to conduct a retrospective real-world study to evaluate the efficacy and safety of Disitamab Vedotin monotherapy or combined with ICIs in the treatment of advanced or metastatic solid tumors. METHODS: This retrospective study involved patients with locally advanced or metastatic solid tumors who were treated with Disitamab Vedotin monotherapy or combined with ICIs at West China Hospital of Sichuan University from July 2019 to June 2023. The observation items included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: This study included 49 patients, out of which 34 patients were treated with Disitamab Vedotin plus ICIs and 15 patients received Disitamab Vedotin alone. In all patients, the median PFS was 10 months. The 6-month and 1-year OS rates were 91.1% and 82.3%, respectively. Eighteen (36.7%) patients achieved a partial response, and sixteen (32.7%) patients had stable disease. The combination therapy of Disitamab Vedotin plus ICIs showed a higher ORR (44.1% vs. 20.0%) and a longer median PFS (14 vs. 8 months) compared to Disitamab Vedotin alone. The median PFS for patients expressed with HER2 2+/3+ was 10 months and was not reached for patients expressed with HER2 0/1+. Grade 3-4 TRAEs occurred in 14.7% of patients who received the combination treatment and in 26.7% of patients who received Disitamab Vedotin alone. CONCLUSIONS: Our study showed that Disitamab-Vedotin-based treatment, alone or in combination with ICIs, exerted considerable prognosis and good tolerance in patients with locally advanced or metastatic solid tumors, regardless of the HER2 expression levels. Whether combination therapy with ICIs provides greater therapeutic benefits compared to monotherapy needs to be further explored through randomized controlled trials.

Personalised neoantigen-based therapy in colorectal cancer.

Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer-specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti-tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen-based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen-based therapy holds great promise as an effective treatment approach for patients with CRC.

Comparison of trimodality therapy and neoadjuvant chemotherapy combined with radical cystectomy for the survival of muscle-invasive bladder cancer: a population-based analysis.

BACKGROUND: Trimodality therapy (TMT) is a mature alternative to radical cystectomy (RC) for patients with muscle-invasive bladder cancer (MIBC) who seek to preserve their primary bladder or are inoperable due to comorbidities. To date, there has been increasing evidence of the effectiveness of TMT as an alternative to RC. In contrast, no literature has stated the effectiveness of neoadjuvant chemotherapy combined with RC (NAC + RC) compared with TMT. OBJECTIVE: We aimed to compare the prognosis between patients receiving TMT and NAC + RC. METHODS: The clinicopathological characteristics of patients with T2-4aN0M0 MIBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression models and Kaplan‒Meier survival curves were used for the survival analysis. Propensity-score matching (PSM) was applied to determine the differences between the two groups. The primary outcome was cancer-specific survival (CSS), and the secondary outcome was overall survival (OS). RESULTS: In total, 1,175 patients with MIBC who underwent TMT (n = 822) or NAC + RC (n = 353) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. After 1:1 PSM, the final patient sample included 303 pairs. The prognosis of patients receiving NAC + RC was significantly better than that of patients receiving TMT in both unmatched and matched cohorts (5-year CSS: before PSM, 75.4% vs. 50.6%, P < 0.0001; after PSM, 76.3% vs. 49.5%, P < 0.0001; 5-year OS: before PSM, 71.7% vs. 37.4%, P < 0.0001; after PSM, 71.7% vs. 31.4%, P < 0.0001). The survival advantages of NAC + RC remained remarkable in the stratified analysis of most factors after PSM. Multivariate Cox regression analysis showed that being older than 68 years old, unmarried, grade III/IV, T3-4a stage, and undergoing TMT independently correlated with poor OS. CONCLUSION: Thus, in this study, patients with MIBC receiving NAC + RC presented with a better prognosis than those receiving TMT.

Super-Resolution Quantification of T2DM-Induced Mitochondrial Morphology Changes and Their Implications in Pharmacodynamics of Metformin and Sorafenib.

Mitochondria, as the powerhouse of cells, are involved in various processes of cellular homeostasis, especially energy metabolism. The morphology of mitochondria is a critical indicator for their functions, referring to mitochondrial fusion and fission. Here, we performed structured illumination microscopy (SIM) to measure the mitochondrial morphology in living cells. Benefitting from its nano-scale resolution, this SIM-based strategy can quantify the fusion and fission of mitochondria with high sensitivity. Furthermore, as type 2 diabetes mellitus (T2DM) is caused by a disorder of energy substrate utilization, this strategy has the potential to study T2DM by analyzing the mitochondrial morphology of insulin-resistant (IR) cells. With SIM, we found that mitochondrial fission was increased in IR MRC-5, LO2, FHs 74 Int, and HepG2 cells but not in IR Huh7 cells with high-invasiveness ability. Furthermore, we found that metformin could inhibit mitochondrial fission in IR cells, and sorafenib could promote mitochondrial fusion in HepG2 cancer cells, especially in those IR cells. To conclude, mitochondrial fission is involved in T2DM, and cancer cells with high-invasiveness ability may be equipped with stronger resistance to energy metabolism disorder. In addition, the pharmacodynamics of metformin and sorafenib in cancer may be related to the inhibition of mitochondrial fission, especially for patients with T2DM.

Survival outcomes in patients with parotid gland carcinoma treated with postoperative therapies using risk stratification.

BACKGROUND: To evaluate the role of postoperative treatment in parotid gland carcinoma (PGC) based on risk stratification. MATERIAL AND METHODS: A total of 301 PGC patients were retrospectively analyzed using risk stratification. The Kaplan-Meier method and Cox analysis were performed to conduct survival analysis. RESULTS: In the high-risk group, those treated with postoperative radiotherapy (RT) had a better 5-year disease-free survival (DFS) than those treated with surgery alone. In the low-risk group, both surgery + RT and surgery + chemotherapy (CT) significantly improved DFS when compared with surgery alone. Cox analysis showed that patients who underwent surgery + RT or surgery + CT had a lower risk of disease progression than those who underwent surgery alone in the low-risk group. In the high-risk group, patients who underwent surgery + RT had a lower risk of disease progression. CONCLUSIONS: Postoperative RT showed considerable benefit in improving disease control in patients with PGC, even in those without high-risk factors.

Clinical and survival analysis of nasopharyngeal carcinoma with consistently negative Epstein-Barr virus DNA.

BACKGROUND: To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level. METHODS: Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis. RESULTS: Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p < .001; p = .015). And patients with consistently negative EBV level were significantly associated with preferable 3-year DFS (95.0% vs. 84.4%, p = .004), DMFS (98.3% vs. 89.4%, p = .009), and OS (100% vs. 97.6%, p = .004). CONCLUSIONS: NPC patients with consistently negative EBV DNA level performed an earlier clinical stage and negative EBV DNA level was related to preferable survival outcomes.

Effects of lifestyle interventions on rural patients with type 2 diabetes mellitus.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is rising rapidly in rural areas, and lifestyle interventions can effectively reduce the blood glucose levels of patients with T2DM. However, current dietary and exercise guidelines are still at experimental stages and are difficult for subjects to understand and implement. The Human Metabolism Analyzer provides real life interventions for the prevention and treatment of T2DM, and our pilot research has demonstrated its effectiveness and good compliance. AIM: To investigate the effect of and compliance with lifestyle interventions in rural patients with T2DM. METHODS: A total of ten rural villages were randomly selected in Chaoshui Township, Penglai City, Shandong Province, China, to conduct health screening among residents aged 50 years or older. Each rural village represented a group, and 12 patients with T2DM were randomly selected from each group (total: 120) to participate in this study and receive real life lifestyle interventions and medication guidance. Lifestyle interventions included changing the meal order (A), postprandial activities (B), resistance exercise (C), and reverse abdominal breathing (D). Diabetes education was conducted at least once a month with a weekly phone follow-up to monitor exercise and diet. Waist circumference, blood pressure, body mass index (BMI), motor function, body composition, fasting blood glucose, and glycated hemoglobin (HbA1c) were analyzed before and 3 mo after the intervention. Moreover, patient compliance and adjustments of hypoglycemic drugs were evaluated. RESULTS: A total of 109 subjects completed the study. The compliance rates for lifestyle interventions A, B, C, and D were 57.79%, 60.55%, 64.22%, and 75.23%, respectively. Among the subjects who received hypoglycemic drugs, the dose was reduced 2 to 3 times based on blood glucose in 54 (67.50%) subjects and was tapered and discontinued in 5 (6.25%) subjects within 3 mo, with no significant fluctuations in blood glucose after dose reduction and withdrawal. After lifestyle interventions, waist circumference, BMI, fasting blood glucose, and HbA1c significantly decreased (P < 0.001); motor function and body composition also significantly improved (P < 0.001). CONCLUSION: For patients with T2DM, compliance to real-life lifestyle interventions is good, and the interventions significantly improve metabolic indicators such as waist circumference, BMI, blood pressure, HbA1c, body composition, and motor function. Some patients are able to taper or discontinue hypoglycemic drugs.

[Effect of Icaritin on K562 Cell Proliferation and Intracellular Reactive Oxygen Species].

OBJECTIVE: To investigate the effect of icaritin (ICT) on proliferation of K562 cells and reactive oxygen species (ROS) in patients with chronic myeloid leukemia (CML). METHODS: MTT assay was used to detect the effect of ICT on the proliferation of K562 cells. Flow cytometry was used to detect the apoptosis of K562 cells and intracellular ROS level. The expression of PARP protein was detected by Western blot. RESULTS: ICT obviously inhibited the proliferation of K562 cells and induced their apoptosis, the expression of PARP protein was enhanced, and the intracellular ROS increased significantly. CONCLUSION: The ICT showes the inhibitory effects on proliferation and apoptosis-inducing effects on K562 cells, and thier mechanism relats with the increase of reactive oxygen species in the cells.

High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.