The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by immunoblotting using the monoclonal antibody PAb 1801. Two hundred and five carcinomas (45%) showed positive p53 accumulation and 55% were p53 negative. When comparing p53 positivity and other clinicopathological parameters, significant differences were found with younger age (p = 0.017), premenopausal status (p = 0.003), increasing tumor size (p = 0.026), negative estrogen receptor (p = 0.003) and negative progesterone receptor (p = 0.047), but not with histologic grade, axillary lymph node status, stage or erbB-2 expression. With a median follow-up of 34 months (range 3–70), relapse has occurred in 73 patients. Disease-free survival curves showed that patients with p53-positive tumors had a significantly shorter disease-free survival than patients with p53-negative carcinomas (log-rank test, p = 0.027). A multivariate analysis of disease-free survival showed that p53, tumor size, histologic grade and progesterone receptor had significant independent prognostic value. The immunoblotting technique was controlled with p53 immunohistochemistry in 94 paired samples. We obtained a statistically significant correlation (p = 0.0004) between the two methods. Our results show that the immunoblotting technique offers an alternative approach in evaluating the p53 status of breast biopsy material using cytosolic extracts, and confirm that p53 accumulation is a significant independent indicator of a poor prognosis in operable breast carcinoma.
Background: Hispanics in the US have a lower age-adjusted mortality in NSCLC and may have a different gene expression profile than NHWs. Additional data is thus needed to validate outcomes in Hispanic patients with NSCLC treated with ICIs. Our aim was to compare clinical outcomes between Hispanic and NHW patients with advanced NSCLC treated with ICIs at 5 large institutions in the US and Latin America. Method: Retrospective clinical review on 436 Hispanic pts with advanced NSCLC that had failed at least one prior line of chemotherapy or were treated with single-agent immunotherapy as first line. Pts with actionable genetic aberrations (EGFR, ALK, and ROS-1) were excluded. Primary endpoints assessed were OS, PFS, and ORR (CR+PR) while secondary endpoint was DCR (ORR+SD). Results: Patient characteristics are summarized in table 1. Primary endpoint results are summarized in table 2. There were no statistical significant differences seen in the secondary endpoint (DCR) among Hispanics and NHW pts. Conclusion: No significant differences were found in the clinical outcomes between Hispanic and NHW patients despite expected genomic differences. As expected, higher response rates were seen in first line therapy and patients with PD-L1 (+) status. These findings validate efforts in making immunotherapy more available to Hispanic patients worldwide.
receiving more than two circles of ICIs monotherapy (anti-programmed death 1 or anti-PD-L1) in Shanghai pulmonary hospital from January 2016 to December 2018. Detailed clinical characteristics, metastasis status and progress-free survival (PFS, calculated from the first day receiving ICIs until the disease progressed) was recorded. Result: 76 patients were enrolled in this study. 10 of them received immunotherapy in the first-line and 46 of them in the second-line. The rate of extra-thoracic metastasis was 50% (38/76), including brain metastasis (10/38), liver metastasis (11/38), bone marrow metastasis (30/38), adrenal metastasis (4/38), extrathoracic lymph node metastasis (10/38) and others (5/38). Patients with extra-thoracic metastasis had a significantly shorter PFS than those without (median PFS 4.20 VS 7.10months; hazard ratio [HR] 1.939, 95% CI 1.221-3.389; p¼0.0072). In subgroup analysis, patients with brain metastasis, liver metastasis or bone marrow metastasis showed significantly shorter PFS than those without (3.35 vs 4.60m, p¼0.0499; 2.50 vs 4.60m, p¼0.0007; 3.70 vs 5.80m, p¼0.0003 respectively). The disease control rate (DCR) is numerically lower in patients with extra-thoracic metastasis (66.7% vs 80%) comparing with those without, even though not statistically significant. Conclusion: The current study suggested that advanced NSCLC patients with extra-thoracic metastasis indicated worse clinical outcomes on ICIs monotherapy and more clinical strategies should be considered to improving treatment efficacy for them.
Melanoma is a highly malignant skin cancer that is known for its resistance to treatments. In recent years, there has been significant progress in the study of non-apoptotic cell death, such as pyroptosis, ferroptosis, necroptosis, and cuproptosis. This review provides an overview of the mechanisms and signaling pathways involved in non-apoptotic cell death in melanoma. This article explores the interplay between various forms of cell death, including pyroptosis, necroptosis, ferroptosis, and cuproptosis, as well as apoptosis and autophagy. Importantly, we discuss how these non-apoptotic cell deaths could be targeted as a promising therapeutic strategy for the treatment of drug-resistant melanoma. This review provides a comprehensive overview of non-apoptotic processes and gathers recent experimental evidence that will guide future research and eventually the creation of treatment strategies to combat drug resistance in melanoma.
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