The therapeutic efficacy of HER2/c-erbB-2/neu DNA immunization on mouse tumor cells expressing exogenous human or rat p185neu but not on mouse tumor cells naturally expressing mouse p185neu has been demonstrated. We investigated the feasibility of using N-terminal rat neu DNA immunization on mouse tumor overexpressing endogenous p185neu and enhancing the therapeutic efficacy of this vaccine by fusion to various cytokine genes, including interleukin-2 (IL-2), interleukin-4 (IL-4), or granulocyte-macrophage colony-stimulating factor. In a therapeutic model, N'-neu-IL-2 DNA vaccine was significantly better than N'-neu DNA vaccine, and N'-neu DNA vaccine was significantly better than control DNA or N'-neu-IL-4 DNA vaccine. The therapeutic efficacy of DNA vaccines was correlated with tumor infiltration of CD8+ T cells. Depletion of CD8+ T cells completely abolished the therapeutic effects of N'-neu-IL-2 DNA vaccine and N'-neu DNA vaccine. Depletion of CD4+ T cells after tumor implantation had no influence on N'-neu-IL-2 DNA vaccine, but enhanced the therapeutic efficacy of N'-neu DNA vaccine. Our results demonstrate that rat N'-neu DNA vaccine has a therapeutic effect on established tumor through the CD8+ T-cell-dependent pathway. Depletion of CD4+ T cells or fusion to the IL-2 gene can thus further enhance the therapeutic effects of N'-neu DNA immunization on mouse tumor expressing endogenous p185neu.
TKIs significantly improved PFS and RR in patients with advanced or metastatic DTC or MTC. We recommend thoroughly evaluating patients' health status and cautiously using TKIs to maximize their benefits and minimize their toxicity.
Developing treatment strategies for triple-negative breast cancer (TNBC) has become an important clinical challenge. Currently, taxane-based chemotherapy is one of the standard treatments for TNBC. However, determining the key factor of taxane-resistance is urgently in need for clinical treatment for breast cancer. We used GEO data to generate paclitaxel resistance in two basal-like TNBC cell lines (SUM149 and MDA-MB-468). Seventy-one common upregulated differentially expressed genes (DEGs) and 11 downregulated DEGs were found to be related to paclitaxel resistance. By constructing protein-protein interactions, 28 hub proteins with a degree cutoff criterion of ≥1 were found. Nine hub genes (
COL4A6
,
COL4A5
,
IL6
,
PDGFA
,
LPAR1
,
FYB
,
IL20
,
IL18R1
and
INHBA
) are involved in important signaling pathways
.
We found that upregulated
PDGFA
and downregulated
COL4A6
were significantly associated with an insensitive response to neoadjuvant paclitaxel-based therapy. A Kaplan-Meier plot was created to check the prognostic values of 11 hub DEGs in terms of recurrence-free survival. High expressions of
PDGFA
and
LAMB3
were correlated with poor recurrence-free survival, while low levels of
FYB
,
IL18R1
, and
RASGRP1
indicated poorer relapse-free survival. Our results suggest that
PDGFA
,
COL4A6
,
LPAR1
,
FYB
,
COL4A5
, and
RASGRP1
might be candidate target genes for taxane-based therapy in basal-like TNBC.
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