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Changes in tumor-antigen expression profile as human small-cell lung cancers progress.

Ge LS, Hoa NT, Lambrecht N, Dacosta-Iyer M, Ouyang Y, Abolhoda A, Jadus MR - Cancer Biol Med (2015)

Bottom Line: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection.When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

View Article: PubMed Central - PubMed

Affiliation: 1 Research Service, 2 Pathology and Laboratory Medicine Service, VA Long Beach Healthcare System, Long Beach, CA 90822, USA ; 3 Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA ; 4 Surgical Health Care Group, Veterans Affairs Medical Center, Long Beach, CA 90822, USA ; 5 Chao Family Comprehensive Cancer Center, UC, Irvine School of Medicine, University of California, Irvine, Orange, CA 92868, USA.

ABSTRACT

Objective: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein (TAPP). We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production.

Methods: SCLC samples (eight surgical resections and three autopsy samples) and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets.

Results: Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of P53-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.

Conclusion: Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

No MeSH data available.


Related in: MedlinePlus

Significant TAPP expression in both surgical and autopsy SCLC. The same RNA preparations used in Figure 1 were examined for B-cyclin and MDM2. In both experiments the mRNA levels displayed significant differences (P<0.05) between the normal lung mRNA when compared to the SCLC specimens.
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f2: Significant TAPP expression in both surgical and autopsy SCLC. The same RNA preparations used in Figure 1 were examined for B-cyclin and MDM2. In both experiments the mRNA levels displayed significant differences (P<0.05) between the normal lung mRNA when compared to the SCLC specimens.

Mentions: We found that two putative precursor antigens (B-cyclin and MDM2) were significantly elevated both in surgical samples and autopsy samples compared with normal-lung autopsy specimens (Figure 2). The surgical samples had an intermediate value, whereas the autopsy samples had higher amounts of mRNA. Thus, not all antigens displayed this all-or-none effect, suggesting that an intermediate level of TAPP can exist in SCLC surgical samples.


Changes in tumor-antigen expression profile as human small-cell lung cancers progress.

Ge LS, Hoa NT, Lambrecht N, Dacosta-Iyer M, Ouyang Y, Abolhoda A, Jadus MR - Cancer Biol Med (2015)

Significant TAPP expression in both surgical and autopsy SCLC. The same RNA preparations used in Figure 1 were examined for B-cyclin and MDM2. In both experiments the mRNA levels displayed significant differences (P<0.05) between the normal lung mRNA when compared to the SCLC specimens.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493377&req=5

f2: Significant TAPP expression in both surgical and autopsy SCLC. The same RNA preparations used in Figure 1 were examined for B-cyclin and MDM2. In both experiments the mRNA levels displayed significant differences (P<0.05) between the normal lung mRNA when compared to the SCLC specimens.
Mentions: We found that two putative precursor antigens (B-cyclin and MDM2) were significantly elevated both in surgical samples and autopsy samples compared with normal-lung autopsy specimens (Figure 2). The surgical samples had an intermediate value, whereas the autopsy samples had higher amounts of mRNA. Thus, not all antigens displayed this all-or-none effect, suggesting that an intermediate level of TAPP can exist in SCLC surgical samples.

Bottom Line: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection.When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

View Article: PubMed Central - PubMed

Affiliation: 1 Research Service, 2 Pathology and Laboratory Medicine Service, VA Long Beach Healthcare System, Long Beach, CA 90822, USA ; 3 Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA ; 4 Surgical Health Care Group, Veterans Affairs Medical Center, Long Beach, CA 90822, USA ; 5 Chao Family Comprehensive Cancer Center, UC, Irvine School of Medicine, University of California, Irvine, Orange, CA 92868, USA.

ABSTRACT

Objective: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein (TAPP). We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production.

Methods: SCLC samples (eight surgical resections and three autopsy samples) and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets.

Results: Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of P53-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.

Conclusion: Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

No MeSH data available.


Related in: MedlinePlus