American journal of cancer research最新文献

[This retracts the article on p. 114 in vol. 14, PMID: 38323281.].

Breast cancer is a leading cause of cancer morbidity and mortality among young women, who often experience more aggressive disease, which may impact their treatment responses and long-term prognoses. Understanding the effectiveness of neoadjuvant chemotherapy (NAC) versus adjuvant chemotherapy (AC) in this specific population is critical for optimizing treatment strategies and improving prognoses. This research was conducted to compare the prognoses of young women (≤35 years old) with early-stage hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, who were treated with NAC versus those treated with AC. This study retrospectively analyzed data from young women with HR+/HER2- breast cancer, with complete follow-up information, sourced from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) and the Tianjin Medical University Cancer Institute and Hospital (TJMUCH) (2014-2018). Patients from both cohorts were allocated to NAC and AC groups based on their treatment regimens. Categorical variables were compared using chi-square, whereas the Kaplan-Meier method was utilized to generate survival curves; additionally, the log-rank test was employed for survival analysis. Propensity score matching (PSM) was employed to control baseline differences. Analysis of the SEER and TJMUCH cohorts revealed that patients treated with NAC had significantly worse overall survival (OS) compared to those treated with AC, as indicated by Kaplan-Meier curves both before and after PSM. The disease-free survival analysis of the TJMUCH cohort yielded similar results, indicating that patients treated with AC experienced longer periods without disease recurrence compared to their counterparts receiving NAC. Statistically significant differences were observed across both survival metrics, reinforcing the robustness of our findings. Overall, among young women (≤35 years old) with early-stage HR+/HER2- breast cancer, patients treated with AC exhibited a more favorable prognosis and improved survival outcomes compared to those treated with NAC. These findings could potentially influence clinical decision-making and treatment guidelines, advocating for a more tailored approach in managing young women with HR+/HER2- breast cancer.

OTU Deubiquitinase 6B-Antisense Transcript 1 (OTUD6B-AS1), a novel long non-coding RNA (lncRNA), has recently emerged as a critical regulator in various tumors. Current research underscores its dual functionality, acting either as an oncogene or a tumor suppressor depending on the tumor context. In this work, we compile and discuss findings from a range of studies investigating the expression patterns of OTUD6B-AS1 in different cancers and its consequent effects on tumor behavior, both in vitro and in vivo. We delve into the mechanisms through which OTUD6B-AS1 influences cancer initiation and progression, focusing on its role in regulating essential cellular processes such as cell growth, migration, invasion, angiogenesis, ferroptosis, and treatment resistance. Operating through complex interactions with microRNAs (miRNAs), proteins, and pivotal signaling pathways - most notably Wnt/β-catenin - OTUD6B-AS1 exhibits variable roles across cancer types and cellular environments. Additionally, we assess the clinical relevance of OTUD6B-AS1 expression levels, evaluating its potential as a biomarker for cancer prognosis and diagnosis, as well as a target for therapeutic intervention. By consolidating existing knowledge, this work aims to highlight the clinical implications of OTUD6B-AS1 and encourage further research in oncology, ultimately contributing to the advancement of targeted cancer therapies.

Objective: To investigate the underlying mechanism of pertuzumab combined with pyrrolitinib in the treatment of breast cancer.

Methods: Real-time PCR and Western blot (WB) were used to detect the expression of HER-2 in breast cancer cells (MCF-10A, BT-474 and SK-BR-3). Subsequently, BT-474 cells were treated with different concentrations of pertuzumab (0, 0.1, 0.5, 1, 5, 10 μg/mL), pyrrolizinib (0, 2, 4, 6, 8, 10 nMol/L) or a synergistic mixture of pertuzumab and pyrrolizinib. The cell viability, migration, invasion and programmed cell death were detected by CCK-8, cell colony formation, wound healing, transwell migration, TUNEL apoptosis assay and WB. KEGG pathway analysis was used to identify key pathways with HER-2 involvement. String database was used to analyze the relationship between HER-2 and PI3K/AKT signaling pathway related proteins. Subsequently, the effects of HER-2 knockdown on PI3K/AKT signaling pathway and cell function were investigated.

Results: Elevated HER-2 expression was observed in breast cancer tissues and cells. The combination of pertuzumab and pyrrolitinib effectively reduced HER-2 levels, inhibited cell viability, proliferation, migration and infiltration, and promoted apoptosis. Knockdown of HER-2 inhibited the viability, proliferation, migration and invasion, downregulated the expression of PI3K and AKT, and increased the apoptosis of BT-474 cells, with these effects restored by IGF-1.

Conclusion: Pertuzumab and pyrrolizinib target HER-2 to downregulate the PI3K/AKT signaling pathway, thereby inhibiting breast cancer cells.

Capicua transcriptional repressor (CIC)-rearranged sarcoma, also known as CIC-rearranged sarcoma (CRS), is a recently recognized sarcoma subtype characterized by specific molecular features. It is associated with aggressive clinical course and a poor prognosis. Here, we present a rare case of CRS, including a detailed clinical, pathological, and molecular analysis, to enhance understanding of this disease and provide a reference for future diagnosis and treatment. A 15-year-old female adolescent initially presented with a rapidly growing mass in her left buttock, accompanied by intermittent pain. A magnetic resonance imaging (MRI) scan revealed a 12.7 × 8.6 × 11.9 cm mixed-intensity mass, suggesting a mesenchymal sarcoma. After histological and immunohistochemical analysis, a preliminary diagnosis of malignant small round cell tumor was made, which was later confirmed as CRS by Fluorescence in situ hybridization (FISH). A course of VDC/IE regimen was administered as first-line neoadjuvant chemotherapy. However, a follow-up MRI showed a 28% increase in tumor volume. Given the poor response to chemotherapy, we decided to perform a wide resection surgery. Unfortunately, lung metastases developed only one month postoperatively, and local recurrence occurred two months postoperatively. The patient then underwent concurrent chemoradiotherapy. At the time of data cutoff, the patient achieved a stable disease state and retained satisfactory walking function. In conclusion, treatment paradigms for CRS have yet to be defined. For patients with large tumor volumes, preoperative neoadjuvant chemotherapy may be ineffective and could potentially delay more effective treatment. Early surgical resection is probably a more suitable treatment option. Multidisciplinary collaboration is essential in the treatment of CRS, and large studies exploring novel therapeutic options are urgently needed to bring hope to patients with this aggressive disease.

Natural compounds are an invaluable source for bioactive small molecules. Cellular activities modulated by them are generally achieved by binding specific cellular targets. However, identification of target(s) for a natural compound is challenging and a hurdle for further development of them as drugs. Sinensetin is derived from Schisandra sphenanthera and the major component of a traditional medicine. Although Sinensetin possesses pharmacological activities, including antioxidants, anti-inflammatory, and anticancer, the molecular mechanisms for its activities remain unclear due to lack of information for its target. In addition, the anticancer effects of sinensetin against non-small cell lung cancer (NSCLC) have not been studied. Here, we described sinensetin as a specific inhibitor of MKK6 with a KD value of 66.27 μM. Sinensetin inhibited the proliferation of NSCLC cells and lung patient-derived xenograft-derived organoids (LPDXO), and induced G1 phase cell-cycle arrest. Sinensetin attenuated the MAPK signaling pathway by directly inhibiting MKK6, but not MKK3. In silico molecular docking analysis indicated that sinensetin was specifically bound near the αG-helix of MKK6, but not MKK3. High MKK6 expression levels were observed in NSCLC patients. MKK6 knockout abolished the sinensetin-mediated inhibition of NSCLC cell proliferation. Taken together, sinensetin is a novel MKK6 inhibitor with therapeutic potential for NSCLC.

Background: Cognitive impairment is a common, yet often overlooked, complication in thyroid cancer patients, potentially influenced by various demographic, clinical, biochemical, and psychological factors. This study aims to analyze the prevalence and determinants of cancer-related cognitive impairment (CRCI) in thyroid cancer patients.

Methods: A retrospective case-control study was conducted involving 246 thyroid cancer patients treated at our The First Affiliated Hospital of Soochow University from January 2021 to January 2023. Patients were categorized into high cognitive function (n = 125) and low cognitive function groups (n = 121) based on Mini Mental State Examination (MMSE) scores. Data were collected on demographic variables, Charlson Comorbidity Index (CCI), disease duration, clinical stage, blood test results, inflammatory factors (interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)), psychological status (Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Self-Esteem Scale (SES)), sleep quality (Pittsburgh Sleep Quality Index (PSQI)), and quality of life (36-item Short-Form Health Survey (SF-36)). Additionally, an external validation set was established, with patients being divided into a high cognitive level group (n = 135) and a low cognitive level group (n = 128), and the model's predictive performance was validated through the external dataset.

Results: Factors significantly associated with lower cognitive function included age (P < 0.001), education level (P < 0.001), CCI scores (P < 0.001), disease duration (P < 0.001), clinical stage (P = 0.003), IL-6 (P < 0.001), IL-8 (P = 0.005), TNF-α (P < 0.001) and CRP (P < 0.001). SDS (P < 0.001), SAS (P < 0.001) and PSQI (P < 0.001) were also associated with reduced cognitive function. The Least Absolute Shrinkage and Selection Operator (LASSO) regression model demonstrated strong predictive performance with an area under the curve (AUC) of 0.903 in the training set and an AUC of 0.835 in the validation set.

Conclusion: CRCI in thyroid cancer patients is multifactorial, with significant contributions from demographic, clinical, inflammatory, and psychological factors. The developed predictive model may serve as a valuable tool in clinical practice for identifying thyroid cancer patients at high risk of cognitive impairment.

Cervical cancer is one of the most prevalent gynecologic malignancies, posing a significant threat to women's health and survival. Despite advancements in early screening and diagnosis, which have led to cervical cancer being termed a "preventable" cancer, treatment options for advanced and recurrent cervical cancer remain limited. Consequently, identifying new therapeutic targets and treatments is crucial for advancing the research and management of cervical cancer. In recent years, targeted therapy and immunotherapy have become focal points in oncology research, offering new avenues and directions for the treatment of cancer. Preclinical studies have demonstrated that targeting BMI1 can inhibit cervical cancer progression, while immunotherapy has advanced to phase III clinical trials, showing promising results. To date, there have been no reports on the combination of BMI1-targeted therapy and immunotherapy in cervical cancer. This review, therefore, elucidates the current state of research and explores the potential and perspectives of combining targeted therapy with immunotherapy for cervical cancer.

Tumor Treating Fields (TTFields) applied with standard chemotherapy have been approved for the first-line treatment of unresectable pleural mesothelioma (PM), an aggressive malignancy with limited effective therapy options. In this study, we demonstrated that the simultaneous exposure to TTFields and doxorubicin or vinorelbine enhanced treatment efficacy in patient-derived PM cells by increasing intracellular drug concentrations. This was achieved by modulating several genes that encode transport proteins, such as the downregulation of P-glycoprotein (P-gp). Using specific, sensitive and quantitative analytical techniques, we observed a more than 70% increase in intracellular concentrations of doxorubicin and vinorelbine in samples treated with TTFields, and a greater than 50% increase in drug uptake in cells exposed to TTFields and pemetrexed. This result indicates that the increased drug concentration observed in TTFields treated cells is significant not only for drugs that are P-gp substrates but also suggests that TTFields could potentially affect other efflux pumps. However, the co-exposure to the drug and TTFields was critical to increasing intracellular drug levels, highlighting the necessity of concurrent use with drugs to enhance the antiproliferative effects of treatment. The in vitro findings were further corroborated by in vivo pharmacokinetic experiments in mice subcutaneously injected with epithelioid PM tumors. Indeed, a 30% increase in intratumor concentrations was observed when vinorelbine was administered with TTFields. Our findings suggest that TTFields could be a well-tolerated approach for enhancing intratumoral drug levels and potentially achieving a more significant therapeutic impact on PM treatment.

Gestational trophoblastic neoplasia (GTN) refers to malignant diseases originating from placental trophoblast cells. Despite high complete remission rates with standard treatments, the adverse effects of chemotherapy, variation in treatment regimens, and the psychological impact on patients significantly influence the prognosis. This study aims to identify factors influencing the time to serum human chorionic gonadotropin (hCG) negativization, thereby contributing to the optimization of patient management strategies. We conducted a retrospective analysis of 206 patients diagnosed with invasive mole and gestational choriocarcinoma treated at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to May 2022. Patients- and treatment-related risk factors were collected. We evaluated 33 variables potentially related to the duration of serum hCG negativization with statistically significant variables from univariate analyses subsequently included in multivariate Cox regression analysis. Through univariate analysis, we identified 11 significant predictors that related with hCG negativization, including body mass index (BMI), age at menarche, number of miscarriages, prior pregnancy status, time since prior pregnancy, maximum tumor diameter, maximum lung tumor diameter, alkaline phosphatase levels, pre-chemotherapy hCG levels, initial chemotherapy regimen, and whether hysterectomy was performed. Cox regression analysis highlighted that increased BMI was associated with a shorter time to hCG negativization (HR=1.730, P=0.001). In contrast, higher pre-treatment hCG levels, longer time since the last pregnancy, and undergoing hysterectomy were associated with prolonged hCG conversion times. In conclusion, this study underscores the importance of individual factors such as BMI, pre-treatment hCG levels, and surgical interventions in determining the duration of hCG negativization in GTN patients. These findings suggest that tailored treatment strategies considering these factors could enhance treatment efficacy and patient outcomes. Increased awareness and careful consideration of these factors should be integral to pre-treatment planning and patient counseling.