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1.
Cancer Res Treat ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38665055

ABSTRACT

Purpose: This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions. Materials and Methods: The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality. Results: Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (HR=5.32, 95% CI 3.208‒8.82, p<0.001) and NPC (HR=7.116, 95% CI 1.617‒31.314, p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR=2.225, 95% CI 1.858‒2.663, p<0.001). Conclusion: This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures.

2.
Adv Sci (Weinh) ; : e2308662, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38666427

ABSTRACT

Cancer vaccines offer a promising avenue in cancer immunotherapy by inducing systemic, tumor-specific immune responses. Tumor extracellular vesicles (TEVs) are nanoparticles naturally laden with tumor antigens, making them appealing for vaccine development. However, their inherent malignant properties from the original tumor cells limit their direct therapeutic use. This study introduces a novel approach to repurpose TEVs as potent personalized cancer vaccines. The study shows that inhibition of both YAP and autophagy not only diminishes the malignancy-associated traits of TEVs but also enhances their immunogenic attributes by enriching their load of tumor antigens and adjuvants. These revamped TEVs, termed attenuated yet immunogenically potentiated TEVs (AI-TEVs), showcase potential in inhibiting tumor growth, both as a preventive measure and a possible treatment for recurrent cancers. They prompt a tumor-specific and enduring immune memory. In addition, by showing that AI-TEVs can counteract cancer growth in a personalized vaccine approach, a potential strategy is presented for developing postoperative cancer immunotherapy that's enduring and tailored to individual patients.

3.
BMC Surg ; 24(1): 124, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658868

ABSTRACT

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.


Subject(s)
Carcinoma, Hepatocellular , Fluorodeoxyglucose F18 , Incidental Findings , Liver Neoplasms , Neoplasms, Second Primary , Parotid Neoplasms , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Humans , Positron Emission Tomography Computed Tomography/methods , Male , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/secondary , Female , Middle Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/diagnosis , Retrospective Studies , Aged , Parotid Neoplasms/diagnostic imaging , Parotid Neoplasms/pathology , Parotid Neoplasms/diagnosis , Neoplasms, Second Primary/diagnostic imaging , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/diagnosis , Adult , Neoplasm Staging , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/diagnostic imaging , Incidence
4.
Infect Chemother ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38527778

ABSTRACT

BACKGROUND: The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the endemic phase may vary from that during the previous pandemic phase. We evaluated the risk of infection in a general population with laboratory-confirmed coronavirus disease 2019 (COVID-19) in a community setting in Korea. MATERIALS AND METHODS: This study included 1,286 individuals who had been in contact with an index COVID-19 case between January 24, 2020, and June 30, 2022. Variables such as age, sex, nationality, place of contact, level of contact, the status of exposed cases, period, and level of mask-wearing were assessed. RESULTS: Among 1,286 participants, 132 (10.30%) were confirmed to have COVID-19. With increasing age, the risk of the exposed persons contracting COVID-19 from index cases tended to increase (P <0.001), especially for people in their 70s (odds ratio = 1.24, 95% confidence interval: 1.11 - 1.40, P <0.001). We found an increasing trend in the risk of a COVID-19 exposed case becoming a secondary infection case (P <0.001) in long-term care facilities where the attack rate was high. CONCLUSION: The risk of COVID-19 transmission is high in long-term care facilities where many older adults reside. Intensive management of facilities at risk of infection and strict mask-wearing of confirmed COVID-19 cases are necessary to prevent the risk of COVID-19 infection.

5.
Acta Otolaryngol ; 144(2): 153-157, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38491920

ABSTRACT

BACKGROUND: Cervical lymph node metastasis (CLNM) from remote primary sites is rare in head and neck cancer. The efficacy of neck dissection is still being investigated for therapeutic benefits of local management in oligometastasis from non-head and neck cancer. OBJECTIVES: To evaluate the clinical efficacy of neck dissection (ND) in CLNM from distant primary cancers and identify factors contributing to improved survival. MATERIALS AND METHODS: This retrospective case-control study enrolled patients who underwent ND for CLNM from distant primary cancer at Asan Medical Centre between January 2010 and December 2020. We analysed overall survival and association between clinical covariate and survival. RESULTS: The study included 31 (14 males, 17 females) among 114 patients. Ovarian cancer was the most common primary malignancy (32.3%). Patients with fewer than three metastatic lymph nodes, without extranodal extension and with adjuvant therapy after surgery had better survival rates. CONCLUSION AND SIGNIFICANCE: In patients with CLNM from a distant primary cancer, ND is beneficial as local treatment. And adequate selection of patients for ND is pivotal to improve prognosis.


Subject(s)
Lymphatic Metastasis , Neck Dissection , Humans , Female , Male , Retrospective Studies , Lymphatic Metastasis/pathology , Middle Aged , Aged , Case-Control Studies , Adult , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/secondary , Aged, 80 and over , Lymph Nodes/pathology , Survival Rate
6.
Clin Exp Otorhinolaryngol ; 16(4): 291-307, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37905325

ABSTRACT

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey's syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

7.
Leuk Lymphoma ; 64(12): 1949-1955, 2023 12.
Article in English | MEDLINE | ID: mdl-37572015

ABSTRACT

Vitamin D insufficiency has been linked to unfavourable outcomes in diverse malignancies. However, the prognostic significance of vitamin D levels in peripheral T-cell lymphoma (PTCL) remains unclear. In this study, we thus aimed to assess the prognostic relevance of 25-hydroxyvitamin D [25(OH)D] levels in patients newly diagnosed with PTCL. The analysis included 144 patients with PTCL treated from March 2015 to May 2020. The median 25(OH)D level was 12.2 (1.7-48.8) ng/mL, and 59 (41%) patients had vitamin D deficiency. Patients with vitamin D deficiency demonstrated significantly worse event-free survival (EFS) and overall survival (OS). In the multivariate analysis, vitamin D was independently associated with OS, with a hazard ratio of 1.66 (95% confidence interval, 1.05-2.63, p = 0.030). These findings suggest that vitamin D deficiency significantly correlates with poor survival outcomes in patients with PTCL.


Subject(s)
Lymphoma, T-Cell, Peripheral , Vitamin D Deficiency , Humans , Prognosis , Vitamin D , Vitamin D Deficiency/complications
8.
Pharmaceutics ; 15(2)2023 Jan 18.
Article in English | MEDLINE | ID: mdl-36839647

ABSTRACT

Extracellular vesicles (EVs) are nanovesicles that are naturally released from cells in a lipid bilayer-bound form. A subset population with a size of 200 nm, small EVs (sEVs), is enticing in many ways. Initially perceived as mere waste receptacles, sEVs have revealed other biological functions, such as cell-to-cell signal transduction and communication. Besides their notable biological functions, sEVs have profound advantages as future drug modalities: (i) excellent biocompatibility, (ii) high stability, and (iii) the potential to carry undruggable macromolecules as cargo. Indeed, many biopharmaceutical companies are utilizing sEVs, not only as diagnostic biomarkers but as therapeutic drugs. However, as all inchoate fields are challenging, there are limitations and hindrances in the clinical translation of sEV therapeutics. In this review, we summarize different types of sEV therapeutics, future improvements, and current strategies in large-scale production.

9.
Clin Exp Otorhinolaryngol ; 15(4): 297-298, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36455879
10.
J Control Release ; 351: 727-738, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36162554

ABSTRACT

The cluster of differentiation 47 (CD47) protein is abundantly expressed on various malignant cells and suppresses the phagocytic function of macrophages and dendritic cells. High CD47 expression levels are correlated with poor cancer survival. Antagonizing CD47 antibodies with potent antitumor effects have been developed in clinical trials, but have critical side effects, inducing anemia and thrombocytopenia. To develop a safe and potent CD47 blockade, we designed extracellular vesicles (EVs) harboring signal regulatory protein alpha (SIPRα)-EV-SIRPα (EVs that express SIPRα). EV-SIRPα showed minimal toxic effects on hematologic parameters and utilized RBCs as delivery vehicles to tumors rather than inducing anemia. EV-SIRPα inhibited ligation of residual CD47 molecules, which attribute to the EV-endocytosis-mediated CD47 depletion and steric hindrance of EV. In an immunologically cold tumor model, EV-SIRPα induced tumor-specific T-cell-mediated antitumor effects. When directly administered to the accessible lesions, EV-SIRPα monotherapy elicited an abscopal effect in the B16F10 tumor model by increasing immune cell infiltration and CD8+-mediated immunity against non-treated tumors. The combinational approach by loading doxorubicin into the EV-SIRPα dramatically reduced the tumor burden and led to 80% complete remission rate. Thus, a potent EV-based CD47 blockade that is hematologically safe, has efficient signaling blocking efficacy, and has systemic antitumor immunity against cancer is recommended.


Subject(s)
Extracellular Vesicles , Neoplasms , Humans , CD47 Antigen , Immunotherapy , Antigens, Differentiation/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Macrophages , Extracellular Vesicles/metabolism , Phagocytosis
11.
J Voice ; 36(6): 877.e9-877.e14, 2022 Nov.
Article in English | MEDLINE | ID: mdl-33067119

ABSTRACT

OBJECTIVE: To identify the coprevalence of presbycusis and presbycusis and analyze the effect of presbycusis on compliance and result of voice therapy in presbycusis patients. METHODS: This cross-sectional, prospective cohort study initially screened patients aged ≥65 years who visited our hospital from February 2019 to January 2020. Unaided pure tone audiometry was performed in these subjects to determine the presence of presbycusis. Perceptual voice assessment by an examiner was conducted for screening of presbycusis, and its diagnosis was confirmed through the voice handicap index-10 (VHI-10) questionnaire and a laryngoscopic exam. Patients with presbycusis underwent voice therapy and were assessed for their compliance and outcomes of the treatment according to the coexistence of presbycusis. RESULTS: Among the 221 patients, presbycusis and presbycusis were diagnosed in 125 (56.6%) and 110 (49.8%) patients, respectively. The copresence of these two disorders were identified in 87 (39.4%) patients, and there was a significant correlation between presbycusis and presbycusis. The effects of voice therapy were examined in the consecutive 40 patients who were diagnosed with presbycusis. There were 21 patients without presbycusis and 19 patients with presbycusis. The average pretreatment voice handicap index-10 score was significantly higher in presbycusis patients; there was no significant difference in the incidence of dropout from voice therapy between the groups. The patients without presbycusis showed a significant improvement in the functional communication measurement (FCM) level and maximum phonation time (MPT) compared with those of patients with presbycusis after voice therapy. CONCLUSIONS: Presbyphonia and presbycusis coexisted in many elderly people. The improvement in the FCM level and MPT after voice therapy was relatively low if patients with presbycusis accompanied by presbycusis. The copresence of presbycusis did not significantly affect compliance with voice therapy in the patients.


Subject(s)
Dysphonia , Presbycusis , Humans , Aged , Presbycusis/diagnosis , Presbycusis/epidemiology , Presbycusis/therapy , Cross-Sectional Studies , Prospective Studies , Voice Quality
12.
Oral Dis ; 28(8): 2277-2284, 2022 Nov.
Article in English | MEDLINE | ID: mdl-33930233

ABSTRACT

OBJECTIVES: In this study, we aimed to determine the relationship between oral health status and thyroid dysfunction. METHODS: A population-based cross-sectional analysis using data from the Korean National Health and Nutrition Examination Survey (KNHNES) was performed. We investigated the association between oral health-related parameters and the prevalence of thyroid diseases. In addition, the relationship between oral health status and thyroid function test (TFT) results was analyzed. One-way analysis of variances or chi-square test was used for comparisons between oral health-related parameters and presence of thyroid diseases. Univariable and multivariable logistic regression analyses were conducted to evaluate the associations between participants' characteristics including oral health-related parameters and the abnormal results of TFTs. RESULTS: A total of 18,034 adults were surveyed. Histories of thyroid diseases were found to be more common in people who brushed their teeth frequently or used oral hygiene products. However, histories of periodontitis and community periodontal index (CPI) did not show significant associations with histories of thyroid diseases. Among 14,860 participants without history of thyroid disorders, people having higher CPI values demonstrated higher probabilities of abnormal TFTs (OR 1.381, 95% CI 1.241-1.537, p < .0001); however, statistical significance was not found after adjusting for the other variables. CONCLUSIONS: Our study demonstrated that good oral health-related behavior was associated with more frequent thyroid disease history. High CPI showed a significant association with TFT abnormalities; however, the significance of this association became lower when other variables such as age and sex were adjusted. Further studies will be needed to determine how the control of oral health-related conditions actually has a causal relationship with thyroid disease/dysfunction through prospective cohort studies.


Subject(s)
Periodontal Diseases , Thyroid Diseases , Adult , Humans , Cross-Sectional Studies , Nutrition Surveys , Oral Health , Periodontal Diseases/complications , Periodontal Diseases/epidemiology , Prospective Studies , Thyroid Diseases/complications , Thyroid Diseases/epidemiology
13.
Cancer Lett ; 522: 198-210, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34571082

ABSTRACT

The purpose of this study was to determine whether statins can enhance anticancer effects in head and neck squamous cell carcinoma (HNSCC) when used with cisplatin and act as immunogenic cell death (ICD) inducers that can be used in cancer immunotherapy. Statins alone showed both in vitro and in vivo inhibitory effects against HNSCC, and synergistic antitumor effects were observed when combined with cisplatin in a syngeneic murine HNSCC model. Statins increased calreticulin exposure and endoplasmic reticulum stress-related signals in HNSCC cells. In addition, it was confirmed that statins could activate antigen-presenting cells and tumor-specific CD8+ T cells with an increase in their numbers in the tumor tissues and draining lymph nodes, with this effect showing significant improvement following the combination therapy with cisplatin. Moreover, in triple combination with both cisplatin and anti-programmed cell death 1 receptor (anti-PD-1) antibody, statins dramatically induced further tumor eradication and improved the survival of tumor-bearing mice. Taken together, these results demonstrate that statins, administered in combination with anti-PD-1 antibody, could enhance the anticancer effect of cisplatin and potentiate the efficacy of immunotherapy for HNSCC and present a rationale for repurposing statins as an adjuvant immunotherapeutic option for HNSCC.


Subject(s)
Cisplatin/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Squamous Cell Carcinoma of Head and Neck/drug therapy , Tumor Microenvironment/drug effects , Animals , Antibodies, Anti-Idiotypic/pharmacology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Drug Synergism , Humans , Immunotherapy , Mice , Programmed Cell Death 1 Receptor/immunology , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/pathology , Tumor Microenvironment/immunology , Xenograft Model Antitumor Assays
14.
J Immunother Cancer ; 9(7)2021 07.
Article in English | MEDLINE | ID: mdl-34330763

ABSTRACT

BACKGROUND: Statins preferentially promote tumor-specific apoptosis by depleting isoprenoid such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate. However, statins have not yet been approved for clinical cancer treatment due, in part, to poor understanding of molecular determinants on statin sensitivity. Here, we investigated the potential of statins to elicit enhanced immunogenicity of KRAS-mutant (KRASmut) tumors. METHODS: The immunogenicity of treated cancer cells was determined by western blot, flow cytometry and confocal microscopy. The immunotherapeutic efficacy of mono or combination therapy using statin was assessed in KRASmut tumor models, including syngeneic colorectal cancer and genetically engineered lung and pancreatic tumors. Using NanoString analysis, we analyzed how statin influenced the gene signatures associated with the antigen presentation of dendritic cells in vivo and evaluated whether statin could induce CD8+ T-cell immunity. Multiplex immunohistochemistry was performed to better understand the complicated tumor-immune microenvironment. RESULTS: Statin-mediated inhibition of KRAS prenylation provoked severe endoplasmic reticulum (ER) stress by attenuating the anti-ER stress effect of KRAS mutation, thereby resulting in the immunogenic cell death (ICD) of KRASmut cancer cells. Moreover, statin-mediated ICD enhanced the cross-priming ability of dendritic cells, thereby provoking CD8+ T-cell immune responses against KRASmut tumors. Combination therapy using statin and oxaliplatin, an ICD inducer, significantly enhanced the immunogenicity of KRASmut tumors and promoted tumor-specific immunity in syngeneic and genetically engineered KRASmut tumor models. Along with immune-checkpoint inhibitors, the abovementioned combination therapy overcame resistance to PD-1 blockade therapies, improving the survival rate of KRASmut tumor models. CONCLUSIONS: Our findings suggest that KRAS mutation could be a molecular target for statins to elicit potent tumor-specific immunity.


Subject(s)
Endoplasmic Reticulum Stress/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Proto-Oncogene Proteins p21(ras)/drug effects , Animals , Humans , Male , Mice , Mutation , Transfection
15.
Medicine (Baltimore) ; 100(5): e23871, 2021 Feb 05.
Article in English | MEDLINE | ID: mdl-33592842

ABSTRACT

ABSTRACT: Although the incidence of oral cavity cancer (OCC) in young never smoker females is increasing worldwide, there has been little research on the etiologies and characteristics of these patients to date. In this study, we sought to evaluate the annual increase in OCC incidence in young never smoker females (YNSF) in our hospital as well as to investigate their clinicopathological characteristics and different disease courses compared with those of other OCC patients. We retrospectively reviewed the medical records of patients who were diagnosed and treated at our tertiary referral hospital from 2006 to 2016. The annual incidence of OCC and proportion of YNSF (never smoker females aged 45 years or younger at the time of diagnosis) among the enrolled OCC patients were evaluated. The characteristics and prognosis of the YNSF group were analyzed using their clinicopathological and survival data. Among the OCC patients primarily enrolled in this study, the proportion of YNSF did not show significant annual increase. There were 32 YNSF among 354 OCC patients (9%), who were ultimately included for the analyses of clinicopathological characteristics and survival. However, YNSF showed no significant differences compared with other OCC patients, even in subgroup analyses for overall survival. Our study did not demonstrate significant changes in the annual proportion of YNSF among OCC patients. In addition, differences in neither clinicopathological characteristics nor survival were noted between YNSF and other OCC patients.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/epidemiology , Mouth Neoplasms/pathology , Non-Smokers/statistics & numerical data , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/etiology , Female , Humans , Incidence , Middle Aged , Mouth Neoplasms/etiology , Retrospective Studies , Young Adult
16.
J Control Release ; 331: 321-334, 2021 03 10.
Article in English | MEDLINE | ID: mdl-33434599

ABSTRACT

Cancer immunotherapy (CI) represented by immune checkpoint inhibitors (ICIs) presents a new paradigm for cancer treatment. However, the types of cancer that attain a therapeutic benefit from ICIs are limited, and the efficacy of these treatments does not meet expectations. To date, research on ICIs has mainly focused on identifying biomarkers and patient characteristics that can enhance the therapeutic effect on tumors. However, studies on combinational strategies for CI are being actively conducted to overcome the resistance to ICI treatment. Moreover, it has been confirmed that dramatic anticancer effects are achieved through "neoadjuvant" immunotherapy with ICIs in treatment-naïve cancer patients; consequently, it has become necessary to consider how to best apply cancer immunotherapies for patients, even with respect to their tumor stages. In this review, we sought to discuss the right timing of ICI treatment in consideration of the progression of cancer with a changing tumor-immune microenvironment. Furthermore, we investigated which types of combinational treatments and their corresponding sequences of administration could optimize the therapeutic effect of ICIs to expand the applicable target of ICIs and increase their therapeutic efficacy. Finally, we discussed several delivery pathways and methods that can maximize the effect of ICIs.


Subject(s)
Immunotherapy , Neoplasms , Humans , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , Neoplasms/drug therapy , Tumor Microenvironment
17.
J Immunother Cancer ; 9(1)2021 01.
Article in English | MEDLINE | ID: mdl-33479026

ABSTRACT

BACKGROUND: Uveal melanoma (UM) is the most frequent intraocular malignancy and is resistant to immunotherapy. Nearly 50% of patients with UM develop metastatic disease, and the overall survival outcome remains very poor. Therefore, a treatment regimen that simultaneously targets primary UM and prevents metastasis is needed. Here, we suggest an immunotherapeutic strategy for UM involving a combination of local photodynamic therapy (PDT), rho-kinase (ROCK) inhibitor, and PD-1/PD-L1 immune checkpoint blockade. METHODS: The antitumor efficacy and immune response of monotreatment or combinational treatment were evaluated in B16F10-bearing syngeneic mouse models. Abscopal antitumor immune responses induced by triple-combinational treatment were validated in syngeneic bilateral B16F10 models. After each treatment, the immune profiles and functional examinations were assessed in tumors and tumor draining lymph nodes by flow cytometry, ELISA, and immunofluorescence assays. In orthotopic intraocular melanoma models, the location of the immune infiltrate in the tumor microenvironment (TME) was evaluated after each treatment by multiplex immunohistochemistry and metastatic nodules were monitored. RESULTS: PDT with Ce6-embedded nanophotosensitizer (FIC-PDT) elicited immunogenic cell death and stimulated antigen-presenting cells. In situ immunogenic clearance induced by a combination of FIC-PDT with ripasudil, a clinically approved ROCK inhibitor, stimulated antigen-presenting cells, which in turn primed tumor-specific cytotoxic T cells. Moreover, local immunogenic clearance sensitized PD-1/PD-L1 immune checkpoint blockade responses to reconstruct the TME immune phenotypes of cold tumors into hot tumors, resulting in recruitment of robust cytotoxic CD8+ T cells in the TME, propagation of systemic antitumor immunity to mediate abscopal effects, and prolonged survival. In an immune-privileged orthotopic intraocular melanoma model, even low-dose FIC-PDT and ripasudil combined with anti-PD-L1 antibody reduced the primary tumor burden and prevented metastasis. CONCLUSIONS: A combination of localized FIC-PDT and a ROCK inhibitor exerted a cancer vaccine-like function. Immunogenic clearance led to the trafficking of CD8+ T cells into the primary tumor site and sensitized the immune checkpoint blockade response to evoke systemic antitumor immunity to inhibit metastasis, one of the major challenges in UM therapy. Thus, immunogenic clearance induced by FIC-PDT and ROCK inhibitor combined with anti-PD-L1 antibody could be a potent immunotherapeutic strategy for UM.


Subject(s)
Immune Checkpoint Inhibitors/administration & dosage , Isoquinolines/administration & dosage , Melanoma, Experimental/drug therapy , Melanoma/drug therapy , Photochemotherapy/methods , Sulfonamides/administration & dosage , Uveal Neoplasms/drug therapy , Animals , Antigen-Presenting Cells/metabolism , Cell Line, Tumor , Drug Synergism , Humans , Immune Checkpoint Inhibitors/pharmacology , Isoquinolines/pharmacology , Male , Melanoma/immunology , Melanoma, Experimental/immunology , Mice , Neoplasm Metastasis , Sulfonamides/pharmacology , Transplantation, Isogeneic , Treatment Outcome , Tumor Microenvironment , Uveal Neoplasms/immunology , Xenograft Model Antitumor Assays
18.
Ann Otol Rhinol Laryngol ; 129(8): 781-787, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32186395

ABSTRACT

OBJECTIVES: To identify whether combination therapy with mucolytics and proton pump inhibitors (PPIs) leads to faster and more effective symptomatic relief in patients with laryngopharyngeal reflux (LPR). METHODS: Patients diagnosed as LPR with a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7 were enrolled in this prospective study. Patients were randomly allocated to control (PPI only) or experimental (PPI + mucolytics) groups and changes in RSI and RFS values were assessed at 1- and 3-month follow-up. RESULTS: One hundred sixteen patients were randomly allocated into either the control group (n = 59) or the experimental group (n = 57). The RSI and RFS scores significantly decreased in both groups (all P < .001) after 1 month of treatment; however, there was no significant difference in RSI change between groups (P = .223). After 3 months of treatment, there remained no significant difference in RSI change between groups (P = .592). CONCLUSIONS: Combination therapy with mucolytics and PPI compared to PPI alone did not lead to faster or more effective symptomatic relief in LPR patients.


Subject(s)
Expectorants/therapeutic use , Laryngopharyngeal Reflux/drug therapy , Proton Pump Inhibitors/therapeutic use , Female , Follow-Up Studies , Humans , Laryngopharyngeal Reflux/diagnosis , Laryngoscopy , Male , Middle Aged , Prospective Studies , Treatment Outcome
19.
Clin Exp Otorhinolaryngol ; 12(2): 107-144, 2019 May.
Article in English | MEDLINE | ID: mdl-30703871

ABSTRACT

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to "surgical management of oral cancer" published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.

20.
Head Neck ; 41(7): 2058-2064, 2019 07.
Article in English | MEDLINE | ID: mdl-30652402

ABSTRACT

BACKGROUND: This study's aim was to identify CD68 and stabilin-1 expressions and their prognostic implications in patients with oral cavity cancer (OCC). METHODS: Stabilin-1 and CD68 immunochemical staining was conducted in samples from patients with OCC who underwent curative surgery in our institute. We retrospectively analyzed patients' clinical information. We investigated the relationship between CD68 and stabilin-1 expression levels and their effect on prognostic factors and survival. RESULTS: Fifty-four patients' data were analyzed. CD68 and stabilin-1 expressions were positively correlated (P = .008). CD68 and stabilin-1 expressions were not correlated with other prognostic factors (eg, T classification or lymph node metastasis). Stabilin-1 expression and tumor recurrence risk were positively correlated (P = .015). CD68 expression was neither associated with recurrence-free nor OCC-specific survival. CONCLUSION: CD68 and stabilin-1 expressions in OCC were positively correlated. Stabilin-1 expression was significantly associated with OCC recurrence risk, but the prognostic value of CD68 was not confirmed.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Cell Adhesion Molecules, Neuronal/metabolism , Mouth Neoplasms/metabolism , Neoplasm Recurrence, Local/metabolism , Receptors, Lymphocyte Homing/metabolism , Adult , Aged , Aged, 80 and over , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Multivariate Analysis , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies
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