Biomedical subjects

Xiaoxian Li

Publications and source records attributed to Xiaoxian Li.

3 recordsLinked to original sources

PubMed2026

Margin Adequacy in Phyllodes Tumors Revisited: Reappraisal of the Evidence Base and Knowledge Gaps.

The optimal surgical margin for minimizing local recurrence (LR) and distant metastasis in phyllodes tumors (PTs) remains controversial. Despite multiple observational cohorts, variation among studies limits the interpretation of margin-outcome associations. We therefore performed a structured critical interpretative synthesis (CIS) to evaluate whether the current evidence supports specific margin thresholds. The CIS incorporated a systematic review, random-effects meta-analysis, an appraisal of existing meta-analyses and guidelines, and an expert interpretative analysis of 40 single-cohort studies from 2015 to 2025 evaluating surgical margin width and outcomes in PTs. Authors' recommendations regarding margin adequacy were extracted as interpretative "author conclusions." In parallel, LR and distant metastasis outcomes were pooled by tumor grade using random-effects models with prediction intervals. Final margin recommendations were derived by integrating CIS findings and multidisciplinary expert judgment. Current management guidelines do not recommend re-excision for positive or close margins in benign PTs. Contemporary guidelines are also concordant in advising negative margins for borderline and malignant PTs, although the specified margin width ranges from 1 to 10 mm. Within this range, no association has been established between increasing margin width and the risk of LR or malignant transformation upon LR. The estimated LR rates are 12.5% for borderline and 16.5% for malignant PTs. Malignant transformation on recurrence occurred in only 1% and 3% of all benign and borderline PTs, respectively. Approximately 14% of malignant PT metastasize, often without LR. Current heterogeneous evidence does not show lower recurrence with margins wider than a negative (≥1 mm) margin in PTs. For borderline and malignant PTs, a mandatory 10-mm threshold is insufficiently supported, as narrower negative margins may be adequate in selected cases. However, an optimal margin threshold cannot be defined from current data. These conclusions are practice-supporting rather than guideline-defining and reinforce the need for high-quality evidence to establish harmonized, grade-specific margin recommendations.

Humans↗

PubMed2006

Molecular heterogeneity of inflammatory breast cancer: a hyperproliferative phenotype.

PURPOSE: Inflammatory breast cancer (IBC) is associated with very poor prognosis. The aims of this study are (a) to prospectively identify differential gene expression patterns associated with IBC and (b) to confirm these pathways using tissue arrays. EXPERIMENTAL DESIGN: For gene expression analysis, IBC (n=14) was clinically defined as rapid-onset cancer associated with erythema and skin changes, whereas non-IBC patients (n=20) had stage III breast cancers, and cDNA analysis was carried out using the Affymetrix (Santa Clara, CA) HG-U133A microarrays. Tissue arrays were constructed from paraffin-embedded material, and the molecular phenotype of 75 IBC was compared with results from>2,000 non-IBC. RESULTS: Gene expression analyses indicated that IBC has higher expression of genes associated with increased metabolic rate, lipid signaling, and cell turnover relative to non-IBC tumors. Consistent with the expression analysis, IBC had statistically higher Ki-67 (93% versus 11%; P<0.001). BAX expression, reflecting increased apoptosis and cell turnover, was significantly uniformly higher in almost all IBC (98% versus 66%; P<0.05), whereas the expression of Bcl-2 was not significantly different. IBC tumors were more likely to be steroid hormone receptor negative (estrogen receptor, 49% versus 30%; P=0.002; progesterone receptor, 68% versus 42%; P=0.001). The expression of tyrosine kinases was not significantly different. E-cadherin was found to be expressed in 87% of IBC, whereas the expression p53 was not significantly different. CONCLUSION: This study is one of the largest molecular analyses of IBC. Both IBC and non-IBC are genetically heterogeneous with consistent differences in the molecular phenotype of IBC.

Breast Neoplasms↗

PubMed2005

The codon 47 polymorphism in p53 is functionally significant.

In addition to a common polymorphism at codon 72, the p53 tumor suppressor gene also contains a rare single nucleotide polymorphism at amino acid 47. Wild type p53 encodes proline at this residue, but in <5% of African Americans, this amino acid is serine. Notably, phosphorylation of the adjacent serine 46 by the proline-directed kinase p38 MAPK is known to greatly enhance the ability of p53 to induce apoptosis. Here we showed that the serine 47 polymorphic variant, which replaces the proline residue necessary for recognition by proline-directed kinases, is a markedly poorer substrate for phosphorylation on serine 46 by p38 MAPK. Consistent with this finding, we showed that the serine 47 variant has up to 5-fold decreased ability to induce apoptosis compared with wild type p53. Mechanistically, we found that this variant has decreased ability to transactivate two p53 target genes, p53AIP1 and PUMA, but not other p53 response genes; this is the first time that phosphorylation of serine 46 has been implicated in transactivation of PUMA by p53. Down-regulation of PUMA in cells with wild type p53 using short interfering RNAs reduced apoptosis in these cells to a level comparable to that in cells containing the serine 47 variant. The combined data indicated that, like the codon 72 polymorphism, the codon 47 polymorphism of p53 is functionally significant and may play a role in cancer risk, progression, and the efficacy of therapy.

Amino Acid Sequence↗