1.Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on High-Dose Methotrexate Toxicity in Pediatric Mature B-cell lymphoma Patients
Jia-Qian XU ; Juan WANG ; Su-Ying LU ; Yan-Peng WU ; Lan-Ying GUO ; Bo-Yun SHI ; Fei-Fei SUN ; Jun-Ting HUANG ; Jia ZHU ; Zi-Jun ZHEN ; Xiao-Fei SUN ; Yi-Zhuo ZHANG
Journal of Experimental Hematology 2024;32(6):1733-1737
Objective:To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients. Methods:Fifty-eight intermediate and high risk patients under 18 years of age with mature B-cell lymphoma who received 5 g/m2 MTX (24 h intravenous infusion) in Sun Yat-sen University Cancer Center from August 2014 to December 2021 were included,and their toxicity of high-dose MTX (HD-MTX) were monitored and analyzed. Results:Among the 58 pediatric patients,the number of CC,CT,and TT genotypes for MTHFR C677T was 33,19 and 6,respectively. A total of 101 courses of HD-MTX therapy were counted,of which plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion were observed in 35 courses,≤0.2 μmol/L in 66 courses. Inter-group comparison showed that plasma MTX level>0.2 μmol/L at 48 h post-MTX infusion increased the risk of developing oral mucositis (P<0.05). Compared with wild-type (CC genotype),patients in the mutant group (CT+TT genotype) were more likely to develop myelosuppression,manifested as anemia,leucopenia,neutropenia and thrombocytopenia. However,plasma MTX level at 48 h was not associated with MTHFR C677T gene polymorphism. Conclusion:The risk of developing oral mucositis in children with mature B-cell lymphoma is associated with plasma MTX concentration. Polymorphism of MTHFR C677T gene is not related to plasma MTX concentration in children with mature B-cell lymphoma,but is related to grade Ⅲ to Ⅳ hematological toxicity.
2.Clinical Analysis of High-Dose Melphalan Combined with Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma
Zhong-Ling WEI ; Lan-Xin ZHANG ; Chen HUANG ; Cai-Ting CHEN ; Guang-Xi LI ; Dong-Ping HUANG ; Lai-Quan HUANG
Journal of Experimental Hematology 2024;32(6):1752-1758
Objective:To investigate the safety,efficacy,and prognosis of high-dose melphalan in combination with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of multiple myeloma (MM). Methods:The clinical data of 17 patients with newly diagnosed MM who underwent ASCT as first-line consolidation therapy at the Yijishan Hospital of Wannan Medical College from March 2020 to October 2022 were retrospectively analyzed. The safety,efficacy,and prognosis of this treatment approach were evaluated. Results:Of the 17 patients,10 were male and 7 were female,with a median age of 56 (45-64) years. The stem cell engraftment rate was 100%,with a median neutrophil engraftment time of+10 (9-12) days and a median platelet engraftment time of+12 (10-21) days. The incidence of oral mucositis and intestinal infection after transplantation was 100%,with 2 cases of pulmonary infection,1 case of urinary tract infection,1 case of skin infection,and 11 cases of transient elevation of serum amylase. After transplantation,13 patients achieved a complete response (CR) or better,and the CR rate showed an increasing trend compared to before transplantation (13/17 vs 8/17;P=0.078). The median follow-up time was 18 (6-36) months,and 15 patients survived without progression,1 patient experienced disease progression,and 1 patient died due to clinical relapse and abandonment of treatment. The 2-year overall survival (OS) rate and progression-free survival (PFS) rate were approximately 90.0% and 83.9%,respectively. Conclusion:High-dose melphalan in combination with ASCT as first-line consolidation therapy for MM can enhance the depth of patient response,further improve therapeutic efficacy,and the transplant-related complications are controllable,making it a viable option worth promoting in clinical practice.
3.WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling.
Qingling HUANG ; Yi XIAO ; Ting LAN ; Youguang LU ; Li HUANG ; Dali ZHENG
International Journal of Oral Science 2024;16(1):7-7
Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Animals
;
Humans
;
Squamous Cell Carcinoma of Head and Neck
;
Carcinogenesis/genetics*
;
Cell Transformation, Neoplastic
;
Wnt Signaling Pathway
;
Disease Models, Animal
;
Head and Neck Neoplasms/genetics*
;
Wnt Proteins
;
Frizzled Receptors/genetics*
;
Janus Kinase 1
;
STAT3 Transcription Factor
4.Human papillomavirus infection in healthy women aged 18‒45 years in Panzhihua of Sichuan Province
Hua LI ; Ting HUANG ; Xi LAN ; Xiaomei HUANG
Shanghai Journal of Preventive Medicine 2024;36(8):721-725
ObjectiveTo determine the human papillomavirus (HPV) infection status and possible influencing factors among healthy women aged 18‒45 years, and to provide a scientific evidence for the prevention of HPV infection and cervical cancer. MethodsA total of 23 HPV types were examined by PCR-reverse dot blot hybridization in 1 210 healthy women who voluntarily participated in the study. Infection status of each HPV genotype and possible factors associated with the infection were determined, including age, ethnicity, marital history, pregnancy history, number of sexual partners, and age at first sexual intercourse. ResultsA total of 1 210 healthy women were examined, of which267 tested positive for HPV, with a prevalence of 22.07%. The prevalence did not differ significantly across age groups or ethnicities (all P>0.05). Moreover, the highest prevalence was found in the divorced/widowed participants (53.57%), compared with other marital status (χ2=35.16, P<0.05). Among the 1 207 participants with pregnancy history, the highest HPV prevalence was 30.58% in those with five or more pregnancies; however, it did not significantly associated with numbers of pregnancies (χ2=10.07, P=0.07). Number of sexual partners showed a significantly positive association with HPV infection (P<0.05). In addition, earlier age at first sexual intercourse was significantly associated with HPV infection (χ2=17.37, P<0.05). ConclusionHealthy women in Panzhihua City were mainly infected with a single HPV type, and the dominant types were HPV 52, 81, and 53. Marital history status, higher number of sexual partners, and younger age at first sexual intercourse were influencing factors associated with HPV infection. It suggested that regular sexual partners and stable marital relationship may reduce the risk of HPV infection.
5.WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling
Huang QINGLING ; Xiao YI ; Lan TING ; Lu YOUGUANG ; Huang LI ; Zheng DALI
International Journal of Oral Science 2024;16(1):85-96
Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
6.WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling
Huang QINGLING ; Xiao YI ; Lan TING ; Lu YOUGUANG ; Huang LI ; Zheng DALI
International Journal of Oral Science 2024;16(1):85-96
Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
7.WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling
Huang QINGLING ; Xiao YI ; Lan TING ; Lu YOUGUANG ; Huang LI ; Zheng DALI
International Journal of Oral Science 2024;16(1):85-96
Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
8.WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling
Huang QINGLING ; Xiao YI ; Lan TING ; Lu YOUGUANG ; Huang LI ; Zheng DALI
International Journal of Oral Science 2024;16(1):85-96
Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
9.WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling
Huang QINGLING ; Xiao YI ; Lan TING ; Lu YOUGUANG ; Huang LI ; Zheng DALI
International Journal of Oral Science 2024;16(1):85-96
Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
10.WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling
Huang QINGLING ; Xiao YI ; Lan TING ; Lu YOUGUANG ; Huang LI ; Zheng DALI
International Journal of Oral Science 2024;16(1):85-96
Wnt signaling are critical pathway involved in organ development,tumorigenesis,and cancer progression.WNT7A,a member of the Wnt family,remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma(HNSCC).According to the Cancer Genome Atlas(TCGA),transcriptome sequencing data of HNSCC,the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues,which was validated using Real-time RT-PCR and immunohistochemistry.Unexpectedly,overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC.Instead,our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway,leading to enhanced cell proliferation,self-renewal,and resistance to apoptosis.Furthermore,in a patient-derived xenograft(PDX)tumor model,high expression of WNT7A and phosphorylated STAT3 was observed,which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

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