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1.
Sci Rep ; 13(1): 9256, 2023 06 07.
Article in English | MEDLINE | ID: mdl-37286786

ABSTRACT

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Neoadjuvant Therapy , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Receptor, ErbB-2
2.
Breast Cancer Res Treat ; 196(1): 45-56, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36056297

ABSTRACT

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.


Subject(s)
Triple Negative Breast Neoplasms , Ataxia Telangiectasia Mutated Proteins/genetics , Ataxia Telangiectasia Mutated Proteins/metabolism , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Humans , Immune Checkpoint Inhibitors , Ligands , Lymphocytes, Tumor-Infiltrating , Mutation , Prognosis , Programmed Cell Death 1 Receptor/metabolism , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/therapy , Tyrosine/metabolism
3.
Medicine (Baltimore) ; 99(40): e22583, 2020 Oct 02.
Article in English | MEDLINE | ID: mdl-33019474

ABSTRACT

INTRODUCTION: Henoch-Schönlein purpura (HSP) is an extremely rare condition in patients with pulmonary tuberculosis, with only a few reported cases. Compared to patients with typical clinical symptoms, it is difficult to make a definitive diagnosis when HSP presents as an initial manifestation in pulmonary tuberculosis patients. Herein, a case of pulmonary tuberculosis that showed HSP at first was reported, and the related literatures were reviewed. PATIENT CONCERNS: A 24-year-old man presented with palpable purpura on the extremities, accompanied by abdominal pain, bloody stools, and knee pain. DIAGNOSES: The patient was diagnosed with pulmonary tuberculosis based on the results of interferon gamma release assays, purified protein derivative test, and computed tomography. INTERVENTIONS: The patient was treated with vitamin C and chlorpheniramine for 2 weeks, and the above-mentioned symptoms were relieved. However, 3 weeks later, the purpura recurred with high-grade fever and chest pain during the inspiratory phase. The patient was then treated with anti-tuberculosis drugs, and the purpura as well as the high fever disappeared. OUTCOMES: The patient recovered well and remained free of symptoms during the follow-up examination. CONCLUSION: Pulmonary tuberculosis presenting with HSP as an initial manifestation is not common. Therefore, it is difficult to clinically diagnose and treat this disease. When an adult patient shows HSP, it is important to consider the possibility of tuberculosis to avoid misdiagnosis and delayed treatment.


Subject(s)
Antitubercular Agents/therapeutic use , IgA Vasculitis/etiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/drug therapy , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Aftercare , Ascorbic Acid/therapeutic use , Chlorpheniramine/therapeutic use , Diagnosis, Differential , Fever/diagnosis , Fever/etiology , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Histamine H1 Antagonists/therapeutic use , Humans , IgA Vasculitis/drug therapy , Interferon-gamma Release Tests/methods , Male , Treatment Outcome , Tuberculin , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/diagnostic imaging , Vitamins/therapeutic use , Young Adult
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