Long-term Impact of Psychological Rehabilitation on Isolated Hospitalization Patients with COVID-19: A Longitudinal Study.

OBJECTIVE: This study aimed to investigate the long-term effects of a psychological rehabilitation program that was effective on anxiety, depression, and quality of sleep in hospitalized COVID-19 patients. DESIGN: This is longitudinal study. 13 patients in the experimental group who received a psychological rehabilitation program during hospitalization and 16 patients in the control group who received conservative treatment completed the questionnaire 6 months after discharge. Questionnaires are the Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), Patient Health Questionnaire-9 (PHQ-9), Visual Analysis Scale (VAS), and the Korean version of the Insomnia Severity Index (ISI-K). RESULTS: The VAS for depression significantly improved in the experimental group compared with control group at discharge (E = -2.40, p < 0.001) and follow-up (E = -3.36, p < 0.001). The SDS and PHQ-9 scores significantly improved at discharge (E = -4.05, p = 0.01 and E = -2.29, p = 0.01) but not at follow-up (E = -4.64, p = 0.12 and E = -1.81, p = 0.22). There are no significant interactions for VAS for anxiety (E = -0.27, p = 0.79), SAS scores (E = -1.48, p = 0.51), and insomnia (E = -0.69, p = 0.63) scores during the follow-up. CONCLUSIONS: Psychological rehabilitation showed a significant long-term reduction in depression, but not in anxiety. Therefore, continuous intervention and management of mental health are required after discharge.

Low expression of CD40L in tumor-free lymph node of oral cavity cancer related with poor prognosis.

BACKGROUND: Recently, the genetic alterations associated with tumor progression and impaired host immunity against transformed cells draw increased attention. Here, we characterized the differential gene expression patterns and protein expression in tumor-free lymph node from recurrent and non-recurrent tumors to identify independent prognostic markers for oral squamous cell carcinoma (OSCC). METHODS: A cDNA microarray analysis was performed to identify the differentially expressed genes in regional tumor-free lymph nodes from OSCC patients with and without recurrence. Then, the protein expression of the selected genes was analyzed by immunohistochemistry in 60 OSCC patients to determine their association with survival. RESULTS: Widespread down-regulation of genes involved in antigen processing and recognition in lymph nodes was a distinctive feature. In univariate Kaplan-Meier analysis, lower expression of CD40L and CD80 in tumor-free lymph nodes was significantly correlated with poorer survival. In multivariate Cox regression analysis, CD40L was identified as an independent prognostic marker of disease-free survival. CONCLUSION: Our data indicate that impaired host immunity (decreased CD40L expression) along with the TNM staging might be an important factor determining the prognosis of OSCC.

Effect of perioperative treatment with a hypoxia-inducible factor-1-alpha inhibitor in an orthotopic surgical mouse model of thyroid cancer.

BACKGROUND/AIM: Despite an excellent prognosis, certain patients with thyroid cancer suffer from locally invasive disease that cannot be controlled by conventional therapy. Our previous study suggested that hypoxia inducible factor-1-alpha (HIF1α) might be an important marker for the identification of and a treatment target of intractable thyroid cancer. Therefore, in the present study, we established an orthotopic mouse surgical model of thyroid cancer that mimics the clinical setting, and evaluated the effect of perioperative treatment with a HIF1α inhibitor. MATERIALS AND METHODS: Seven thyroid cancer cell lines (SNU-790, BCPAP, KTC1, TPC1, TPC1-M, KTC2, and FRO) and four HIF1α inhibitors (echinomycin, LAQ824, temsirolimus, and vorinostat) were used in the present study. Expression of HIF1α and related proteins was evaluated in all cell lines; immunoblotting and cell proliferation assays were conducted; and echinomycin was validated in an orthotopic surgical mouse model. RESULTS: Nuclear expression of HIF1α increased in tumorigenic cell lines, while HIF1α inhibitors inhibited proliferation and colony formation. In the orthotopic surgical model, the group treated with surgery and the echinomycin-treatment group showed a highly significant survival gain (p=0.001) compared to the control group. CONCLUSION: The highly significant survival gain resulting from their use in perioperative adjuvant treatment in vivo and their anticancer effect in vitro suggest that HIF1α inhibitors might be candidates for perioperative adjuvant chemotherapy for thyroid cancer. Combining adjuvant HIF1α inhibitor chemotherapy with surgery might be an effective therapeutic strategy for thyroid cancer that is refractory to conventional treatments.

Targeting HIF1α peri-operatively increased post-surgery survival in a tongue cancer animal model.

BACKGROUND: The purpose of the present study was to evaluate the relationship between hypoxia-inducible factor 1 alpha subunit (HIF1α) and tumor initiation in squamous cell carcinoma cell lines and whether targeting HIF1α perioperatively might exert positive effects on survival or recurrence in an animal model. METHODS: The expression of HIF1α and tumorigenic potential in nude mice was compared using human head and neck squamous cell carcinoma cell lines (SNU1041, SNU1066, SNU1076, PCI01, PCI13, PCI50). A recurrent tongue cancer model was established by first injecting tumor cells in the lateral tongue and then excising the tongue masses for replanting in the neck. The effect of HIF1α inhibitors was assessed using this animal model. RESULTS: We observed good correlation between tumorigenic potential and HIF1α nuclear expression in the cell lines tested. Furthermore, knockdown of HIF1α inhibited tumor growth in the animal model. After in vitro testing of five HIF1α inhibitors, echinomycin and LAQ824 were selected for the animal study. Pre- and postoperative treatment with echinomycin showed significant improvement in postsurgery survival and recurrence. CONCLUSIONS: Our results suggested that adjuvant targeting of HIF1α before and after surgery could be a new targeted therapy strategy for squamous cell carcinoma.

CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma.

AIM: Perineural invasion and expression of CXCR4 is characteristic of adenoid cystic carcinoma (ACC). Herein, we aimed to demonstrate CXCR4 expression in ACC, identify its association with perineural invasion and investigate the impact of CXCR4 inhibitor in vitro and in a murine perineural invasion model. METHODS: Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The effects of gene knockdown using siRNA and specific blocker of CXCR4 (AMD3100) were evaluated in vitro. A preclinical perineural invasion model was developed using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo. RESULTS: CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumour in the animal model and in the tumour of human tissue. SDF-1 expression was also demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and inhibition by a CXCR4-specific inhibitor AMD3100 effectively abrogated invasion but not proliferation of ACC in vitro. The rate of perineural invasion was significantly decreased with AMD3100 treatment in the animal model. CONCLUSIONS: CXCR4 is associated with perineural invasion in ACC. AMD3100, which can effectively diminish perineural invasion of ACC, may have an adjuvant role in the management of ACC.

HIF-1α and HSP90: target molecules selected from a tumorigenic papillary thyroid carcinoma cell line.

It is important to properly identify aggressive tumors among differentiated thyroid cancers that are most often indolent. By comparison of a tumorigenic clone with an originally less tumorigenic papillary thyroid carcinoma (PTC) cell line, we looked for markers involved in the aggressive biology of thyroid cancer. Human PTC cell lines BHP10-3 and its tumorigenic subclone BHP10-3SC(mice) were compared using microarray analysis. Upregulated genes in the tumorigenic clone were selected for RT-PCR, immunoblot analysis and immunohistochemistry in human tissue. Hypoxia-inducible factor (HIF)-1α and its chaperone protein heat shock protein (HSP)90 showed significantly increased expression in BHP10-3SC(mice) and human PTC tissue. These two genes, HIF-1α and HSP90, were further validated using siRNA gene knockdown, pharmacological inhibition using 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of both HSP90 and HIF-1α and in vivo orthotopic animal model. Invasiveness of BHP10-3SC(mice) was abrogated by blockade of HIF-1αin vitro by both siRNA and 17-AAG. The same finding was demonstrated in the orthotopic animal model. These findings support that HIF-1α is important in tumorigenesis of PTC and that it may serve to be an important target for identification and treatment of aggressive tumors.