Assessing objective cognitive impairments in cancer survivors: Features and validity of measures for research and clinical applications.

Objective: This narrative review aims to (1) identify neuropsychological tests for assessing cognitive function impairment in patients with cancer, specifically in the domains of attention and memory, (2) summarize the characteristics of these tests, including cognitive function domains, test content, readability, and psychometric quality, and (3) evaluate the feasibility of each test in cancer care. Methods: Data sources include published test manuals, documents from official web pages, and published journal articles. Results: Our study identified eight neuropsychological tests that are most frequently used to assess the attention and memory domains of objective cognitive function in patients with breast cancer. These tests include the California Verbal Learning Test, Hopkins Verbal Learning Test, Rey Auditory Verbal Learning Test, Rey-Osterrieth Complex Figure, CNS Vital Signs, Wechsler Adult Intelligence Scale, Wechsler Memory Scale, and Trail Making Test. They demonstrate acceptable evidence of psychometric quality and varying degrees of feasibility. Test feasibility is influenced by factors such as short testing time, brevity and comprehensiveness, clear cognitive domain distinctions, availability of normative data, minimal practice effects, ease of administration, and limited attention-span requirements. These attributes determine a test's feasibility for use in cancer care. Among the evaluated measures, the California Verbal Learning Test for memory, the Trail Making Test for attention, and the CNS Vital Signs for comprehensive assessment emerge as the most practical choices for cancer care. Conclusions: The assessment and management of cognitive function impairment are crucial for enhancing the quality of life in cancer survivors. Nurses should possess knowledge of assessment tools for early detection and the ongoing monitoring of this symptom's progression.

Neuropsychological Effects of Chemotherapy: Systematic Review of Longitudinal Studies on Objective Cognitive Impairment in Breast Cancer Patients.

BACKGROUND: Findings from longitudinal studies can provide more conclusive evidence as to the impact of chemotherapy on cognitive functioning. OBJECTIVES: This study aimed to ( a ) synthesize the evidence from longitudinal studies of the neuropsychological effects associated with chemotherapy in breast cancer patients, ( b ) identify associated factors, and ( c ) evaluate methodological issues. METHODS: Data were extracted from PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Library. Inclusion criteria included the original study with the breast cancer sample, validated measure, and at least 1 baseline data point before and after chemotherapy began. Data accrued for sample characteristics, data-collection time points, statistical methods for longitudinal data analysis, outcome measures, and major findings (eg, longitudinal changes in cognitive function). RESULTS: We selected 42 articles for this review. The sample sizes ranged from 20 to 610, and most recruited were younger than 70 years. We found a trend across studies-statistically significant objective cognitive function deteriorations in severity and prevalence after initiating chemotherapy compared with a control group or relative to their baseline observations. A subsample, as high as 65%, experienced marked declines in cognitive function after initiating chemotherapy. The memory domain was most affected. The consistently associated factors were education, IQ, and regimen. Major methodological concerns were the measurement-the wide range of neuropsychological tests and a test's unclear domains. CONCLUSION: Chemotherapy affects objective cognitive function in some subsets. The highest-impact time point, mechanisms, and clinical significance of chemotherapy-associated cognitive impairment need additional evidence. IMPLICATION FOR PRACTICE: Clinicians must assess and manage cognitive impairment during and after chemotherapy.

Association of chemotherapy and subjective cognitive impairment in breast cancer patients: Meta-analysis of longitudinal prospective cohort studies.

PURPOSE: This meta-analysis with longitudinal prospective cohort studies aimed to (a) determine whether chemotherapy is associated with time-dependent subjective cognitive impairment outcomes in breast cancer patients, and (b) identify the time point with the highest impact of chemotherapy on subjective cognitive impairment. METHODS: Data were gathered from PubMed, EMBASE, CINAHL, PsycInfo, and the Cochrane Library. The mean differences of the subjective cognitive impairment level between the chemotherapy-treated patients and controls (patients not treated by chemotherapy and healthy subjects) were calculated using effect sizes (Hedges' g) by clinical time periods. The five clinical time periods were (a) baseline, (b) during chemotherapy, (c) within 1 month postchemotherapy, (d) within 1 year postchemotherapy, and (e) 1 year or longer postchemotherapy. RESULTS: Longitudinal data from nine data sets from 13 studies were pooled and analyzed. At baseline, chemotherapy-treated patients showed slightly better subjective cognitive impairment compared to patients not treated by chemotherapy and did not differ from healthy controls. Yet, the chemotherapy-treated patients had significantly worse subjective cognitive impairment compared to both type of controls after initiating chemotherapy. The effect sizes for the group differences were larger for the group comparison with healthy controls than the nonchemotherapy control (-0.50 vs. -0.19). The largest effects were found within 1 month postchemotherapy (-0.85), suggesting the acute impact of chemotherapy. CONCLUSIONS: Chemotherapy is associated with subjective cognitive impairment. The impact of chemotherapy appears to be an acute rather than a chronic side effect. Clinicians must consider including the assessment and management of subjective cognitive impairment in their routine practice.

Comparative evaluations of single-item pain-intensity measures in cancer patients: Numeric rating scale vs. verbal rating scale.

AIMS AND OBJECTIVES: To evaluate the psychometric quality of two single-item pain-intensity measures: the Numeric Rating Scale (NRS) and the Verbal Rating Scale (VRS). BACKGROUND: Measuring pain intensity is a vital step in initiating symptom management and evaluating the effectiveness of interventions with cancer patients. Single-item pain-intensity measures of the NRS and VRS format have been evaluated to be acceptable for use in clinical practice and research; however, evidence to choose one over the other, as a standardised pain-assessment format, is insufficient. DESIGN: Descriptive correlational study. The study was guided and reported following the STROBE guideline. METHODS: Data accrued at two time points during cancer treatment with a total of 249 patients treated in a Korean University Hospital. Two single-item measures were constructed to assess pain intensity over 1 week. The Brief Pain Inventory (BPI; pain intensity subscale and interference subscale) and the functional assessment of chronic illness therapy-fatigue were the criterion. Convergent and concurrent validity were tested with Pearson's correlations. RESULTS: In the convergent-validity evaluation of the cross-sectional association with the BPI, the NRS showed a much higher level of association than the VRS (0.81 versus 0.61). In convergent validity with a longitudinal association with the BPI, the NRS score change had a much higher level of association (0.61 versus 0.37). In concurrent-validity evaluation, the NRS and VRS showed similar levels of associations with fatigue (-0.48 versus -0.49). Yet, the NRS showed statistically higher levels of correlation with functional limitations than the VRS (0.55 versus 0.42), comparable to the concurrent validity of the BPI. CONCLUSION: The NRS showed higher validity than VRS when assessing overall pain intensity over the past week. RELEVANCE TO CLINICAL NURSING: Pain assessment is a vital role of nurses in caring for patients with cancer. Current study findings support the use of the single-item NRS pain measure to assess global pain intensity over the past week.

Systematic review of longitudinal studies on chemotherapy-associated subjective cognitive impairment in cancer patients.

OBJECTIVES: This systematic review of longitudinal studies, assessing subjective cognitive impairment (SCI) reported by adult cancer patients, aimed to summarize evidence on the impact of chemotherapy on SCI, identify moderators of SCI, and evaluate methodological issues. METHODS: Data accrued from Pubmed, EMBASE, CINAHL, PsychInfo, and the Cochrane library. Inclusion criteria were original studies, an exclusively adult sample, valid and reliable subjective cognitive measures, and at least one baseline data point prior to and another after the initiation of chemotherapy. Data were collected on the sample composition, data-collection time points, outcome measures, statistical analysis, and major findings (ie, longitudinal changes in prevalence, severity, and associated factors). RESULTS: Forty articles published between 2004 and 2019 were retained: 21 examined chemotherapy-treated patients only, and 19 employed control groups. Findings were mixed, with slightly more studies supporting the impact of chemotherapy on SCI. SCI tended to be more prevalent and severe after initiating chemotherapy, compared with patients' own baseline and controls not treated with chemotherapy. Impact appeared to be acute and more likely limited to subsamples. Most studies examining non-breast-cancer samples reported the lack or limited impact of chemotherapy on SCI. The most consistent moderators were depression and fatigue. Methodological issues regarding sampling design, measurement, and statistical analysis were discussed. CONCLUSION: More rigorously designed longitudinal studies would clarify direct and indirect effects of chemotherapy on SCI.

Controlled antibody immobilization onto immunoanalytical platforms by synthetic peptide.

Antibody immobilization on a solid surface is inevitable in the preparation of immunochips/sensors. Antibody-binding proteins such as proteins A and G have been extensively employed to capture antibodies on sensor surfaces with right orientations, maintaining their full functionality. Because of their synthetic versatility and stability, in general, small molecules have more advantages than proteins. Nevertheless, no small molecule has been used for oriented and specific antibody immobilization. Here is described a novel strategy to immobilize an antibody on various sensor surfaces by using a small antibody-binding peptide. The peptide binds specifically to the Fc domain of immunoglobulin G (IgG) and, therefore, affords a properly oriented antibody surface. Surface plasmon resonance analysis indicated that a peptide linked to a gold chip surface through a hydrophilic linker efficiently captured human and rabbit IgGs. Moreover, antibodies captured by the peptide exhibited higher antigen binding capacity compared with randomly immobilized antibodies. Peptide-mediated antibody immobilization was successfully applied on the surfaces of biosensor substrates such as magnetic particles and glass slides. The antibody-binding peptide conjugate introduced in this work is the first small molecule linker that offers a highly stable and specific surface platform for antibody immobilization in immunoassays.

Direct immobilization of protein g variants with various numbers of cysteine residues on a gold surface.

Protein G is an antibody binding protein, which specifically targets the Fc region of an antibody. It therefore has been widely used to immobilize different types of antibodies in numerous immunoassays. Here, we have engineered Streptococcus protein G to contain various numbers of cysteine residues at the N-terminus and therefore to form well-oriented protein G films on bare gold. SPR and SPR imaging analyses indicated that a gold surface treated with cysteine-tagged protein G possesses a superior antibody binding ability compared to one treated with tag-free protein G. AFM images indicated a higher surface coverage by antibody binding on the cysteine-tagged protein G surface than the intact protein G surface. The proper orientation of cysteine-tagged protein G on a gold surface also afforded better orientation of immobilized antibodies, resulting in enhanced antigen detection. Moreover, the protein G surfaces maintained their high antibody binding ability during multiple rounds of antibody interaction tests. The cysteine-tagged protein G constructed in this study can be a valuable link for oriented antibody immobilization in a variety of immunosensors.

Surface plasmon resonance imaging protein arrays for analysis of triple protein interactions of HPV, E6, E6AP, and p53.

We have developed a surface plasmon resonance (SPR)-based protein microarray to study protein-protein interactions in a high-throughput mode. As a model system, triple protein interactions have been explored with human papillomaviral E6 protein, tumor suppressor p53, and ubiquitin ligase E6AP. Human papillomavirus (HPV) is known to be a causative agent of cervical cancer. Upon infection, the viral E6 protein forms a heterotrimeric protein complex with p53 and E6AP. The formation of the complex eventually results in the degradation of p53. In the present study, a GST-fused E6AP protein was layered onto a glutathione (GSH)-modified gold chip surface. The specific binding of GST-E6AP protein onto the gold chip surface was facilitated through the affinity of GST to its specific ligand GSH. The interacting proteins (E6 and/or p53) were then spotted. Detection of the interaction was performed using a SPR imaging (SPRI) technique. The resulting SPRI intensity data showed that the protein-protein interactions of E6AP, E6, and p53 were detected in a concentration-dependent manner, suggesting that the SPRI-based microarray system can be an effective tool to study protein-protein interactions where multiple proteins are involved.

Detection of Bax protein conformational change using a surface plasmon resonance imaging-based antibody chip.

We describe an antibody chip technology that uses a surface plasmon resonance (SPR) imaging system to examine the conformational change of a protein. In this study, we used Bax protein, a pro-apoptotic member of the Bcl-2 family of proteins, as a model protein to investigate the conformational alteration triggered by a TNF-related apoptosis-inducing ligand (TRAIL), a potent inducer of apoptosis. To develop the antibody chip for detecting the Bax conformational change, we immobilized Bax monoclonal antibody 6A7, which recognizes only a conformationally changed Bax protein on a gold surface. The resultant immobilized Bax antibodies provided specific and accurate measurements of the active conformation-specific epitope in the apoptotic cancer cells treated with the TRAIL; these measurements corresponded to the data obtained by immunoprecipitation analysis using an active conformation-specific Bax antibody (6A7). The results of our study indicated that TRAIL-induced Bax structural change could be monitored quickly and simply using an SPR imaging system, thus demonstrating the potential for using such a system for the analysis of conformational properties of target proteins.

Surface plasmon resonance imaging-based protein arrays for high-throughput screening of protein-protein interaction inhibitors.

The E7 protein produced by high-risk human papillomavirus (HPV) induces a degradation of the retinoblastoma tumor suppressor RB through direct interaction, which suggests that an inhibitor for the interaction can be a potential anticancer drug. A surface plasmon resonance (SPR) imaging-based protein array chip was developed for the high-throughput screening of inhibitor molecules targeting RB-E7 interaction. The glutathione S-transferase-fused E7 protein (GST-E7) was first layered onto a glutathionylated gold chip surface that had been designed to specifically bind to GST-fused proteins. Subsequently, a microarrayer was used to spot the hexa-histidine-tagged RB proteins (His(6)-RB) onto the GST-E7-layered gold chip surface, and the resulting SPR image was analyzed. Upon increased His(6)-RB concentration in the spotting solution, the SPR signal intensity increased proportionally, indicating that His(6)-RB bound to GST-E7 in a concentration-dependent manner. The His(6)-RB/GST-E7 interaction was challenged by spotting the His(6)-RB solution in the presence of a RB binding peptide (PepC) derived from a motif on E7. The SPR imaging data showed that PepC inhibited the His(6)-RB/GST-E7 interaction in a concentration-dependent manner. Our results show that the SPR imaging-based protein array chip can be applied to screen small molecule inhibitors that target protein-protein interaction.