American journal of cancer research最新文献

Tumor-associated macrophages (TAMs) are important immune cells in the tumor micro-environment (TME) and play a key role in the occurrence and development of cervical cancer. Besides, targeting TAMs can significantly inhibit cervical cancer tumor growth, invasion, metastasis, and angiogenesis as well as affect immune regulation. This review summarizes the correlation between TAM and tumors, the mechanism of action of TAM in cervical cancer, and the potential application of TAM in the treatment of cervical cancer. Therefore, this study may provide new ideas and targets for the development of further treatment strategies for cervical cancer patients.

The involvement of axillary lymph nodes (ALNs) is a critical prognostic factor affecting patient management and outcomes in breast cancer (BC). This study aims to comprehensively analyze the clinical data of BC patients, evaluate ultrasonic signs of ALNs, and explore the implications of a prediction model for ALN metastasis (ALNM) in early-stage BC patients based on ultrasonic features and clinical data. This study retrospectively analyzed ultrasonic features and clinical data from 216 patients diagnosed with unilateral invasive BC. The dataset was divided into a training (n = 162) and a validation set (n = 54) in a 3:1 ratio. Patients were then assigned into metastasis and non-metastasis groups depending on ALNM determined by pathological findings. Univariate analysis of various indicators followed by multivariate Logistic regression analysis was performed on the training set. A prediction model for ALNM in BC was established using binary logistic regression analysis, with its prediction performance evaluated by receiver operating characteristic curves (ROC) and area under the curve (AUC), and its reproducibility verified by the validation set. The pathological findings identified 57 (35.2%) cases of ALNM among 162 BC patients in the training set. Risk factors for ALNM included poorly differentiated type, high Ki-67 expression, lymph node (LN) aspect ratio ≥2, LN cortical thickness ≥1/2 of lymphatic hilum diameter, and mixed or peripheral LN blood flow. Protective factors included mass location in the outer upper quadrant and LN size >1 cm. A prediction model was established based on risk factors, with the equation being Logit (P) = -4.881 - 1.285 * differentiation degree + 1.485 * Ki-67 - 1.090 * lump quadrant - 0.956 * lymph node size + 1.244 * lymph aspect ratio + 1.032 * LN cortical thickness + 1.454 * LN medullary disappearance + 1.266 * LN blood flow. ROC analysis of the model yielded an AUC of 0.866, with a sensitivity of 80.7% and a specificity of 80.0%. The prediction model was validated using the validation set, producing an AUC of 0.809. These results demonstrate that color Doppler ultrasound effectively evaluates ALN status in BC patients. The prediction model for ALNM in BC shows strong accuracy and has potential clinical application.

No established method currently exists for evaluating tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), and their clinical significance based on infiltration site in GC remains unclear. In this study, we developed a method to evaluate TILs according to their infiltration site as a prognostic marker for GC. We retrospectively analyzed 103 patients with advanced GC who underwent curative resection. TILs located at the invasive margin (TIL_IM) and the center of tumors (TIL_CT) were scored semi-quantitatively using immunohistochemical staining of CD8+ T cells. The sum of the TIL_IM and TIL_CT scores was defined as the TILs score. Based on this score, patients were classified into low and high TILs groups. Quantitative TILs were also assessed to validate the semi-quantitative scoring method. Furthermore, we confirmed a tumor suppressive effect due to CD8+ T cells co-cultured in GC cell lines in vitro. In the univariate analysis, patients with low TIL_IM were significantly more likely to be female, younger, and have undifferentiated histological types and deeper tumor invasion compared to those with high TIL_IM. Similarly, patients with low TIL_CT had significantly more positive lymph node metastases than those with high TIL_CT. In the multivariate analysis, deeper tumor invasion and positive lymph node metastasis were identified as independent risk factors for patients with low TIL_IM and low TIL_CT, respectively. According to our semi-quantitative TILs scoring method, the low TILs group had significantly poorer prognoses compared to the high TILs group. This group had significantly larger tumor diameters, deeper tumor invasion, and more positive lymph node metastases. Additionally, deeper tumor invasion was an independent risk factor for the low TILs group. Quantitative TILs analysis revealed that the low TILs group had significantly lower TIL levels compared to the high TILs group. In vitro, CD8+ T cells induced apoptosis in GC cells in a concentration-dependent manner. Furthermore, these cells significantly suppressed the proliferative, migratory, and invasive capacities of GC cells. Our simple and versatile semi-quantitative scoring method for CD8+ TILs indicates that CD8+ TILs are sensitive prognostic markers. The low TILs group accurately reflects the low quantitative TIL levels and is associated with poor oncological prognosis.

Androgen receptor (AR) signaling is a target in prostate cancer therapy and can be treated with non-steroidal anti-androgens (NSAA) including enzalutamide, and apalutamide for patients with advanced disease. Metastatic castration-resistant prostate cancer (mCPRC) develop resistance becomes refractory to therapy limiting patient overall survival. Darolutamide is a novel next-generation androgen receptor-signaling inhibitor that is FDA approved for non-metastatic castration resistant prostate cancer (nmCRPC). Imipridone ONC201/TIC10 is first-in-class small molecule imipridone that activates the integrated stress response (ISR), upregulates TNF-related apoptosis-inducing ligand (TRAIL) and has activity against CRPC alone or in combination with enzalutamide in preclinical models. We hypothesized that combination of imipridones with androgen receptor signaling blockers such as darolutamide may synergize in anti-tumor efficacy against mCRPC cells. mCRPC cell lines 22RV1, LNCaP, DU145 and PC3 were treated with imipridones ONC201, ONC206, apalutamide, darolutamide, or enzalutamide as single agents or in combinations. Combinations of ONC201 or ONC206 and androgen receptor signaling blockers demonstrated synergistic effects in mCRPC cells. Combinations of ONC201 and darolutamide or enzalutamide reduced PSA levels in LNCaP cells and induced of ATF4 in both LNCaP and 22RV1 cell lines. Darolutamide synergized with ONC201 regardless of AR status or castration sensitivity in vitro. Flow cytometric analysis showed increased intra-tumoral NK cells in mice treated with ONC201 and combination of ONC201 and darolutamide. Trends of increased TRAIL activation within NK cells were also observed in treatment groups. ONC201 and darolutamide demonstrated anti-tumor effects in vivo in the 22RV1 CRPC model. Our results prompt further translational and clinical studies with imipridones ONC201 or ONC206 in combination with enzalutamide or darolutamide for treatment of castrate resistant advanced or metastatic prostate cancer.

Anaplastic thyroid cancer (ATC) is a lethal endocrine malignancy. It has been shown that tumor-associated macrophages (TAMs) contribute to the aggressiveness of ATC. However, stimulatory factors that could facilitate the induction and infiltration of TAMs in the ATC tumor microenvironment (TME) are not fully elucidated. In this study, we used a human leukemia monocytic cell line (THP-1) to study the differentiation of THP-1 into M2-like macrophages (M2) by conditioned media (CM) derived from each of the three human ATC cells: 8505C, THJ-11T (11T), and THJ-16T (16T). The capacity of CM to induce M2 was in the order of 16T>8505C>11T cells as determined by the expression of M2 markers (CD163, CD204, and CCL13). Cytokine arrays and ELISA assays revealed five commonly enriched cytokines (IL-6, IL-8, MCP-1, TIMP-1, and TGF-β1) in the CM derived from each of the three ATC cells. These cytokines, individually, had weak activity, but together, they mimicked full CM activity in the induction of M2. Further, they collaboratively activated STAT3, ERK, and PI3K-AKT signaling to facilitate the induction of M2 as found in CM. Importantly, we found that the CM-induced M2 could secrete soluble growth factors to promote ATC cell proliferation as evidenced by the increased Ki-67, cMYC, and cyclin D1 protein levels. Our studies identified the major stimulatory cytokines which acted collaboratively to induce M2 in the TME. Importantly, the present studies indicate that when using inhibitors to target TAMs, combination therapies would be required for effective treatment of ATC.

Objective: To retrospectively analyze the incidence of infections in elderly acute myeloid leukemia (AML) patients undergoing induction therapy with venetoclax combined with hypomethylating agents and to compare these findings with those from patients receiving standard or low-dose chemotherapy.

Methods: Medical records of 169 elderly (≥60 years old) AML patients diagnosed via MICM (morphology, immunology, cytogenetics, and molecular genetics) at the First Affiliated Hospital of USTC between June 2019 and June 2022 were reviewed. Patients were divided into three groups: venetoclax combined with hypomethylating agents group (targeted therapy group), standard chemotherapy group, and low-dose chemotherapy group. Comparisons were made across groups regarding bacterial infection rates, fungal infection cases, infection sites, and severity.

Results: The median ages at diagnosis in the targeted therapy group, standard chemotherapy group, and low-dose chemotherapy group were 73, 68, and 71 years, respectively (P<0.05). Compared with the standard chemotherapy and low-dose chemotherapy groups, the targeted therapy group had a higher prevalence of comorbidities (P<0.05). Complete remission rates in targeted therapy group, standard chemotherapy group, and low-dose chemotherapy group were 68.8%, 51.2%, and 26.4%, respectively (P<0.05). The durations of neutropenia were 9.0±8.4, 15.0±15.0, and 9.3±9.1 days, respectively (P<0.05). Bacterial infection rates were 87.5%, 95.2%, and 94.3% (P<0.05), with the most common sites being the lungs, bloodstream, upper respiratory tract, and unspecified sites. The durations of fever were 2.34±3.59, 4.52±4.38, and 3.53±4.76 days, respectively (P<0.05). The proportions of patients receiving antifungal prophylaxis were 46.8%, 46.4%, and 41.5%, respectively (P>0.05), mainly involving voriconazole and posaconazole. The proportions of clinically diagnosed or confirmed fungal infections were 6.3%, 9.5%, and 9.4%, respectively (P>0.05). The proportions of patients requiring initiation of antifungal therapy were 34.4%, 48.8%, and 43.4%, respectively (P<0.05). Among the 169 elderly AML patients, three (1.8%) developed infection-induced multiple organ dysfunction syndrome (i-MODSE), all in the standard chemotherapy group.

Conclusion: Venetoclax combined with hypomethylating agents shows a favorable safety profile and reduced infection risk in the treatment of AML in the elderly patients. Meanwhile, nontargeted therapies, a prolonged duration of neutropenia, and a prolonged duration of fever were found to be independent risk factors for fungal infections and the need for antifungal intervention.

Breast cancer is the most common malignant tumour in women, with more than 685,000 women dying of breast cancer each year. The heterogeneity of breast cancer complicates both treatment and diagnosis. Traditional methods based on histopathology and hormone receptor status are now no longer sufficient. Recently, advances in multi-omics techniques, including genomic, proteomic, and transcriptomic analyses, have deepened our understanding of breast cancer. Combining these approaches allows for precise molecular subtyping, which is essential for the detection of key mutations, protein interactions and gene expression patterns that are highly relevant to different therapeutic strategies. Genomic analyses have been effectively identifying key mutations in cancer. Meanwhile, proteomics and transcriptomics complement by identifying new therapeutic targets and elucidating gene expression dynamics. Integrating multi-omics and conventional diagnostics improves tumour characterisation and enables prognostic accuracy comparable to established standards and treatment response. Existing and emerging technologies enable real-time enhanced tumour follow-up and data analysis through liquid biopsy and artificial intelligence, respectively. Despite these clinical implementation challenges, multi-omics including clinical phenotyping offers significant potential for precision breast cancer treatment. This article describes recent advances in molecular subtyping and multi-omics technologies that are driving key innovations to optimise patient outcomes and further develop personalised medicine in the context of breast cancer care.

This study aims to identify factors influencing aesthetic outcomes following facial basal cell carcinoma (BCC) plastic surgery to enhance post-operative satisfaction and cosmetic results. A retrospective cohort study was conducted on 303 patients who underwent facial BCC plastic surgery between June 2021 and June 2023. Data on demographics, blood tests, SF-12, and Skindex-16 scores were analyzed. Patients were categorized into satisfactory and unsatisfactory outcome groups based on post-operative assessments. The training set of patients was sourced from the Third Affiliated Hospital of Soochow University, while the testing set of patients was sourced from the First Affiliated Hospital of Soochow University. Of 209 patients, 116 were in the satisfactory group, 93 in the unsatisfactory. Factors enhancing positive outcomes included reconstruction methods (P < 0.001) and smaller tumor diameters (P = 0.006). Higher pre-op 12-item Short Form Survey (SF-12) scores correlated with better outcomes (P = 0.005). Lower Skindex-16 scores were noted in the satisfactory group (P < 0.001). Logistic regression highlighted reconstruction method, aging signs, SF-12 scores, and Skindex-16 as key predictors. A random forest model achieved an area under the curve (AUC) of 0.984. External validation confirmed similar associations with satisfactory outcomes (AUC = 0.870). Aesthetic outcomes in facial BCC plastic surgery are influenced by reconstruction method and tumor diameter, patient health status (SF-12), and skin-related quality of life (Skindex-16). Personalized surgical planning and comprehensive care are essential for optimizing outcomes.

Radioactive brain injury, a severe complication ensuing from radiotherapy for head and neck malignancies, frequently manifests as cognitive impairment and substantially diminishes patients' quality of life. Despite its profound impact, the pathogenesis of this condition remains inadequately elucidated, and efficacious treatments are notably absent in clinical practice. Consequently, contemporary interventions predominantly focus on symptom alleviation rather than achieving a radical cure or reversing the injury process. This article provides a comprehensive review of the various pathogenic mechanisms and therapeutic strategies associated with radioactive brain injury, offering insights that may guide the development of novel therapeutic strategies.

Betel nut chewing, common in several Asian populations, is linked to increased cancer risk, including oral, esophageal, gastric, and hepatocellular carcinoma. Aspirin shows potential as a chemopreventive agent. This study investigates the association between aspirin use and cancer risk among betel nut chewers. Betel nut chewers aged 18 and older were included, with aspirin use defined as at least 28 cumulative defined daily doses (cDDDs). Propensity score matching and Cox proportional hazards models, adjusted for time-varying covariates, were used to assess cancer risk. The study included 46,302 betel nut chewers, equally divided between aspirin users and non-users. Aspirin use was associated with a 31% reduction in overall cancer risk (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.66 to 0.73; P<0.0001). A dose-response relationship was observed, with higher cDDDs of aspirin corresponding to greater reductions in cancer risk. The highest quartile of aspirin use (Quartile 4) showed a 62% reduction in cancer risk (aHR, 0.38; 95% CI, 0.34 to 0.41; P<0.0001). Daily aspirin intensity was also associated with a significant reduction in cancer risk, with doses greater than 1 DDD showing an aHR of 0.54 (95% CI, 0.47 to 0.61; P<0.0001) compared to 1 DDD or less. Aspirin use significantly reduces cancer risk among betel nut chewers in a dose-dependent manner. These findings suggest aspirin as a potential chemopreventive agent in high-risk populations, warranting further investigation.