Biomedical subjects

Rebecca C Arend

Publications and source records attributed to Rebecca C Arend.

3 recordsLinked to original sources

PubMed2026

Harnessing Id1 as a biomarker in a plasmid reporter system for cervical cancer.

Stagnancy of ten-year cervical cancer (CC) incidence in the U.S., despite screening advancements, suggests the need for new CC screening technologies. This study in preclinical CC models evaluated a diagnostic plasmid that induces expression of a reporter (secreted embryonic alkaline phosphatase, SEAP) through the control of cancer-specific promoter sequence (inhibitor of differentiation 1, Id1). The plasmid (pId1-SEAP) was used to transfect CC cells in vitro and characterize SEAP production based on Id1 expression. Western Blot and immunohistochemistry were used to establish Id1 expression in cell models and human tissues. Timed transfections in various conditions were used to correlate Id1 and SEAP expression. CC cell lines expressed increased normalized baseline Id1 (HeLa 3.0 ± 0.13, SiHa 2.9 ± 0.27, both P < 0.0001) compared to non-cancer 3T3 fibroblasts (1.0 ± 0.0). Normal cervical tissues had a mean Id1 staining value of 3E4 ± 3E4, while early- and late-stage CC tissues had increased mean Id1 staining (3E5 ± 1E5 P < 0.0001 and 2E5 ± 1E5 P = 0.0002, respectively). HeLa and SiHa lines produced increased normalized SEAP (0.63 ± 0.25 and 0.50 ± 0.10, P < 0.05) compared to 3T3 cells, both with pId1-SEAP (0.16 ± 0.058). As few as 12,500 pId1-SEAP transfected HeLa cells resulted in increased SEAP (3E4 ± 3E3 P = 0.004) compared to background (1E4 ± 4E2). SiHa xenograft ex vivo tumor transfected with 25 µg/µL pId1-SEAP produced significantly greater SEAP (21.7 ± 8.6, P = 0.0003) relative to muscle transfected in the same conditions (0.94 ± 0.24). pId1-SEAP can transfect CC cells to produce SEAP proportionally to endogenous Id1 expression, demonstrating its potential for additional studies in CC models.

Female↗

PubMed2025

HER2 alterations across solid tumors: implications for comprehensive testing.

PURPOSE: ERBB2 (HER2) alterations (eg, overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial. METHODS: HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association. RESULTS: Of the 653 cases, HER2 IHC scores were distributed as 3+ (3.1%), 2+ (13.2%), and 1+ (19.8%), with 63.9% being IHC-negative. ERBB2 CN amplification was observed in 3.1%, with 75% exhibiting IHC3+. Pathogenic mutations were found in 3.1%, with low IHC3+ rates (5%). Among samples with ERBB2 mutations, only 3 had CN amplifications (1-positive, 2-intermediate). Somers'-D analysis revealed a strong association between CNV and IHC expression (D = 0.73, P < .001). CONCLUSION: This study highlights ERBB2 alterations across diverse cancers, demonstrating their heterogeneity and clinical significance. ERBB2 mutation-carrying tumors are less likely to have HER2 protein 3+ expression or CN amplification, indicating the need for comprehensive genomic analysis to identify those patients. In the context of pan-tumor approval of T-DXd for HER2, findings support integrating genomic and phenotypic data to enhance diagnostic precision and inform therapeutic decision-making. Comprehensive ERBB2 (HER2) testing across tumor types is essential to expand access to HER2-targeted therapies.

Humans↗

PubMed2025

A randomized pilot study of HPV16 L2E7E6 fusion protein vaccination site post-treatment for HPV16+ cervical cancer.

OBJECTIVE: Since anti-tumor immunity is enhanced by vaccination of mice adjacent to human papillomavirus type 16 (HPV16+) tumors, we examined whether HPV16 L2E7E6 fusion protein (TA-CIN) vaccination in the thigh of HPV16+ cervical cancer patients would be more immunogenic than their arm. METHODS: HPV16+ cervical cancer (stage IB1-IVA) patients, who had completed standard-of-care treatment within the past year and absent evidence of disease (NED), were enrolled in a pilot study (NCT02405221). Participants were randomized 1:1 to receive three 100 μg TA-CIN monthly intramuscular immunizations either in the arm or thigh and followed for two years for safety (CTCAEv4.0), immune response, and recurrence. RESULTS: Fifteen patients were enrolled (median age 44, range 35-83 years); one patient experienced a non-vaccine-related adverse event after one vaccination and withdrew. Treatment-related adverse events (n = 8) were grade 1, primarily at the injection site, and self-resolved. No recurrence was observed. TA-CIN-specific antibody titers tended to be higher in thigh-vaccinated patients. Bulk TCRseq revealed significant increases in expanded and de novo T cell clones following thigh-vaccination compared with the arm. No correlation with prior treatment modality was observed. E6-, E7-, and L2-specific TCR clones expanded, although L2-specific T cell responses were predominant. One month post-vaccination, scRNAseq revealed significant expansion of MAIT and cytotoxic CD8+ T cells, and both expanded and novel TCR clonotypes were identified in the latter. CONCLUSIONS: Thigh or arm vaccination with TA-CIN was well tolerated, but the former elicited higher CD8 T cell and antibody responses in HPV16+ cervical cancer patients with NED after primary therapy.

Humans↗