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1.
Front Oncol ; 14: 1399502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863620

RESUMO

Objective: This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer. Methods: The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT's effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed. Results: In the effective group, the patients' age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%. Conclusion: The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect.

2.
Int J Biol Macromol ; 267(Pt 1): 131574, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615857

RESUMO

Caulerpa lentillifera is rich in polysaccharides, and its polysaccharides show a significant effect in different biological activities including anti-cancer activity. As an edible algae-derived polysaccharide, exploring the role of colon cancer can better develop the application from a dietary therapy perspective. However, more in-depth studies of C. lentillifera polysaccharide on anti-colon cancer activity and mechanism are needed. In this study, we found that Caulerpa lentillifera polysaccharides (CLP) showed potential anti-colon cancer effect on human colon cancer cell HT29 in monolayer (IC50 = 1.954 mg/mL) and spheroid (IC50 = 0.402 mg/mL). Transcriptomics and metabolomics analyses revealed that CLP had an inhibitory effect on HT29 3D spheroid cells by activating aminoacyl-tRNA biosynthesis as well as arginine and proline metabolism pathways. Furthermore, the anti-colon cancer effects of CLP were confirmed through other human colon cancer cell HCT116 and LoVo in monolayer cells (IC50 = 1.890 mg/mL and 1.437 mg/mL, respectively) and 3D spheroid cells (IC50 = 0.344 mg/mL and 0.975 mg/mL, respectively), and three patient-derived organoids with IC50 values of 6.333-8.780 mg/mL. This study provided basic data for the potential application of CLP in adjuvant therapeutic food for colon cancer on multiple levels, while further investigation of detailed mechanism in vivo was still required.


Assuntos
Caulerpa , Neoplasias do Colo , Algas Comestíveis , Polissacarídeos , Esferoides Celulares , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Caulerpa/química , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Técnicas de Cultura de Células em Três Dimensões/métodos , Proliferação de Células/efeitos dos fármacos , Células HT29 , Linhagem Celular Tumoral , Células HCT116 , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
3.
J Clin Invest ; 134(8)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412034

RESUMO

Adoptive transfer of T cell receptor-engineered T cells (TCR-T) is a promising strategy for immunotherapy against solid tumors. However, the potential of CD4+ T cells in mediating tumor regression has been neglected. Nasopharyngeal cancer is consistently associated with EBV. Here, to evaluate the therapeutic potential of CD4 TCR-T in nasopharyngeal cancer, we screened for CD4 TCRs recognizing EBV nuclear antigen 1 (EBNA1) presented by HLA-DP5. Using mass spectrometry, we identified EBNA1567-581, a peptide naturally processed and presented by HLA-DP5. We isolated TCR135, a CD4 TCR with high functional avidity, that can function in both CD4+ and CD8+ T cells and recognizes HLA-DP5-restricted EBNA1567-581. TCR135-transduced T cells functioned in two ways: directly killing HLA-DP5+EBNA1+ tumor cells after recognizing EBNA1 presented by tumor cells and indirectly killing HLA-DP5-negative tumor cells after recognizing EBNA1 presented by antigen-presenting cells. TCR135-transduced T cells preferentially infiltrated into the tumor microenvironment and significantly inhibited tumor growth in xenograft nasopharyngeal tumor models. Additionally, we found that 62% of nasopharyngeal cancer patients showed 50%-100% expression of HLA-DP on tumor cells, indicating that nasopharyngeal cancer is well suited for CD4 TCR-T therapy. These findings suggest that TCR135 may provide a new strategy for EBV-related nasopharyngeal cancer immunotherapy in HLA-DP5+ patients.


Assuntos
Neoplasias Nasofaríngeas , Camundongos , Animais , Humanos , Neoplasias Nasofaríngeas/terapia , Herpesvirus Humano 4 , Receptores de Antígenos de Linfócitos T , Linfócitos T CD4-Positivos , Imunoterapia , Imunoterapia Adotiva/métodos , Microambiente Tumoral
4.
J Int Med Res ; 49(12): 3000605211067414, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34939432

RESUMO

OBJECTIVE: We aimed to develop a nomogram to predict cancer-specific survival (CSS) in patients with hypopharyngeal squamous cell carcinoma (HSCC) treated with primary surgery to provide more accurate risk stratification for patients. METHODS: We retrospectively collected data of 1144 eligible patients with HSCC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Patients were randomly divided into training and validation groups (ratio 6:4) and we used univariate and multivariate Cox analysis. We developed and validated a nomogram using calibration plots and time-dependent receiver operating characteristic, Kaplan-Meier, and decision curves. RESULTS: Age; marital status; T, N, and M stage; and postoperative adjuvant therapy were independent factors associated with CSS, which were included in the nomogram. The nomogram's C-index was 0.705 to 0.723 in the training group and 0.681 to 0.736 in the validation group, which were significantly higher than conventional American Joint Committee on Cancer (AJCC) staging. Calibration curves showed good agreement between prediction and observation in both groups. Kaplan-Meier and decision curves suggested the nomogram had better risk stratification and net benefit than conventional AJCC staging. CONCLUSIONS: We established a nomogram that was superior to conventional AJCC staging in predicting CSS for HSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Nomogramas , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Programa de SEER , Carcinoma de Células Escamosas de Cabeça e Pescoço
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