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1.
Eur J Clin Nutr ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898286

ABSTRACT

BACKGROUND: The South Korean government implemented a multidisciplinary nutritional support team (NST) system to focus on the proper evaluation and supply of nutritional status in hospitalized patients who are at a higher risk of malnutrition. METHODS: This nationwide population-based cohort study included patients diagnosed with sepsis who were admitted to hospitals from 2016 to 2020. The NST should consist of four professional personnel (physicians, full-time nurses, full-time pharmacists, and full-time clinical dietitians). The NST group included patients with sepsis admitted to a hospital with an NST system, whereas the non-NST group included patients with sepsis admitted to a hospital without an NST system. RESULTS: A total of 323,841 patients with sepsis were included in the final analysis, and 120,274 (37.1%) admitted to a hospital with an NST system were included in the NST group. In the multivariable Cox regression analysis, the NST group showed a 15% lower 90-day mortality than the non-NST group (hazard ratio [HR]:0.85, 95% confidence interval [CI]:0.83, 0.86; P < 0.001). The NST group shows 11% lower 1-year all-cause mortality than the non-NST group (HR:0.89, 95% CI:0.87, 0.90; P < 0.001). In subgroup analyses, a more evident association of the NST group with lower 90-day mortality was shown in the intensive care unit admission group and age ≥65 years old group. CONCLUSIONS: Multidisciplinary NST intervention is associated with improved survival outcomes in patients with sepsis. Moreover, this association was more evident in patients with sepsis aged ≥65 years old who were admitted to the ICU.

2.
NPJ Vaccines ; 9(1): 108, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879560

ABSTRACT

Alzheimer's disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.

4.
Eur J Oncol Nurs ; 70: 102581, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38749385

ABSTRACT

PURPOSE: Digital health is an indispensable tool, but its use depends on the eHealth literacy (eHL) of end-users. This study aimed to understand the need for digital health and eHL among cancer patients, caregivers, and healthcare providers and to identify differences in digital health needs related to the eHL of cancer patients. METHODS: A multicenter, descriptive correlational study was conducted and included a total of 209 patients, 150 caregivers and 150 healthcare providers. Digital health needs were identified, and eHL was measured using the Korean version of the eHealth Literacy Scale. Differences in digital health needs in relation to the eHL of patients were analyzed. RESULTS: The most necessary digital health functions among cancer patients and caregivers were 'information and education on symptom management after cancer treatment' and 'education on coping methods for each type of cancer' (87.1-94.0%). Healthcare providers reported the need for a digital health function for 'medication information' and assisting in 'medical appointments' (96.7-98.0%). The preferred types of digital health were telemonitoring, mobile services, and telemedicine by telephone (81.3-90.5%). The mean eHL score of the cancer patients was 28.84 ± 6.75. Differences existed in the need for digital health functions and preferences for digital health types between cancer patients with high and low eHL. CONCLUSIONS: Cancer patients and caregivers expressed strong needs for digital health that provide information and education about symptom management and coping with cancer. Digital health interventions for cancer care need to be developed to reflect the identified needs and preferences and eHL of end-users.


Subject(s)
Caregivers , Health Literacy , Neoplasms , Telemedicine , Humans , Female , Male , Neoplasms/therapy , Neoplasms/psychology , Caregivers/psychology , Middle Aged , Adult , Republic of Korea , Aged , Needs Assessment , Health Personnel/psychology , Surveys and Questionnaires , Digital Health
5.
Brain Tumor Res Treat ; 12(1): 80-86, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38317493

ABSTRACT

We report a patient with whole neuroaxis dissemination of a sporadic supratentorial hemangioblastoma (HB) for more than 15 years. A 68-year-old female patient presented with severe radiating pain in the right leg. Gadolinium-enhanced lumbar spine MRI showed an intradural mass (2.5 cm in diameter) at the L4 level. The patient had been severely disabled for 22 years after a previous intraventricular brain tumor resection. At that time, the diagnosis was angioblastic meningioma, which was thought to be incorrect. At 14 years after the brain surgery, gamma knife radiosurgery was performed three times for newly developed or recurred supratentorial and infratentorial tumors in the cerebrospinal fluid pathway. The patient underwent lumbar spinal surgery, and a gross total removal of the mass was performed, which confirmed the histopathological diagnosis of HB. We reexamined the old histopathological specimen of the intraventricular tumor from 20 years ago and changed the diagnosis from angioblastic meningioma to supratentorial HB. Six months after spinal surgery, the patient underwent a second spinal surgery and brain surgery, and the histopathological diagnosis was HB following both surgeries, which was the same following the first spinal surgery. Here, we report a sporadic supratentorial HB patient who showed cranial and spinal disseminations for more than two decades along with a literature review.

6.
Cancers (Basel) ; 16(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38275871

ABSTRACT

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E-stained whole-slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: -0.0094; AUPRC: -0.0225) than those of the ConViT classification model. With weighted averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.

7.
Diagn Cytopathol ; 52(4): E80-E83, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38140795

ABSTRACT

Gastric-type endocervical adenocarcinoma (GEA) is a rare type adenocarcinoma of the uterine cervix that is unrelated to human papillomavirus (HPV). GEA is difficult to diagnose due to its bland-looking morphological characteristics and is therefore often underdiagnosed. Although abnormal cells may be seen on cervical cytology specimens, they are rarely diagnosed as malignant and are often classified as atypical glandular cells. As a result, GEA may be diagnosed at advanced stages, with cytology samples from other organs after it has already invaded adjacent organs. Here, we report a case of GEA diagnosed by both cytological and histological examinations of urinary bladder and uterine cervix, after being identified as a non-urothelial malignancy on a urine cytology. We also review and summarize the differential diagnoses for non-urothelial lesions, particularly for glandular lesions observed on urinary cytology specimens, as well as the cytological and histological characteristics of GEA.


Subject(s)
Adenocarcinoma , Uterine Cervical Neoplasms , Female , Humans , Adenocarcinoma/diagnosis , Cytology , Uterine Cervical Neoplasms/diagnosis
8.
Clin Nutr ; 43(2): 315-321, 2024 02.
Article in English | MEDLINE | ID: mdl-38142476

ABSTRACT

BACKGROUND & AIMS: The South Korean government established the multidisciplinary nutritional support teams (NST) system for enhancing the evaluation and adequate supply of nutritional support to patients at high risk of malnutrition. However, the impact of the NST on clinical outcomes in critically ill patients with coronavirus disease 2019 (COVID-19) remains unclear. We aimed to investigate whether NST implementation affects survival outcomes in patients with COVID-19 requiring intensive care unit (ICU) admission. METHODS: Using data from the National Health Insurance Service and Korea Disease Control and Prevention Agency in South Korea, adult patients with COVID-19 admitted to the ICU between October 8, 2020, and December 31, 2021, were included. The NST comprised four professional personnel (physicians, full-time nurses, full-time pharmacists, and full-time clinical dietitians). Patients admitted to ICUs with and without the NST system were assigned to the NST and non-NST groups, respectively. RESULTS: A total of 13,103 critically ill adult patients were included in the final analysis; among them, 10,103 (77.1 %) and 3,000 (22.9 %) patients were included in the NST and non-NST groups, respectively. In the NST group, 2,803 (27.7 %) critically ill patients with COVID-19 were prescribed enteral or parenteral nutrition by the NST. In a covariate-adjusted multivariable model, the NST group showed a 40 % lower in-hospital mortality rate than the non-NST group (odds ratio: 0.60, 95 % confidence interval: 0.51, 0.71; P < 0.001). In subgroup analyses, compared with the non-NST group, the NST group showed significantly lower in-hospital mortality rates at 2, 3, 4, and 5 points on the World Health Organization clinical progression scale among patients with acute respiratory distress and mechanical ventilatory support. CONCLUSIONS: NST implementation was associated with improved survival outcomes in critically ill patients with COVID-19; accordingly, it may be recommended for improving adequate nutritional support and evaluation in critically ill patients.


Subject(s)
COVID-19 , Enteral Nutrition , Adult , Humans , Critical Illness/therapy , COVID-19/therapy , Nutritional Support , Parenteral Nutrition , Intensive Care Units
9.
Cytotherapy ; 26(3): 242-251, 2024 03.
Article in English | MEDLINE | ID: mdl-38142382

ABSTRACT

BACKGROUND AIMS: Natural killer (NK) cell-based cancer immunotherapy is effective when combined with other treatment modalities such as irradiation and chemotherapy. NK cell's antitumor function to treat solid tumor, including head and neck squamous cell carcinoma (HNSCC), has been targeted recently. This study assessed NK cell recruitment in response to chemoradiation therapy (CRT) in HNSCC. METHODS: Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed. RESULTS: Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2Rγnull mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity. CONCLUSIONS: Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.


Subject(s)
Head and Neck Neoplasms , Killer Cells, Natural , Humans , Animals , Mice , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/metabolism , Disease Models, Animal , Cell Line, Tumor , Mice, Inbred NOD , Mice, SCID , Killer Cells, Natural/metabolism , Chemoradiotherapy , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/metabolism
10.
In Vivo ; 37(5): 2039-2043, 2023.
Article in English | MEDLINE | ID: mdl-37652486

ABSTRACT

BACKGROUND/AIM: Urinary bladder cancer has various etiologies and tends to recur and then progress to a higher grade. When muscles are invaded, the response to conventional therapy is poor and the quality of life deteriorates rapidly. Here, we summarize and compare two representative methods used to create the syngeneic mouse models required for immunological research. MATERIALS AND METHODS: In this study, we utilized six-week-old female C3H/HeNCrl mice and the mouse bladder tumor cell line MBT-2. The first method involved transurethral catheterization with poly-L-lysine pretreatment (catheter group), while the second method involved transperitoneal incision and direct injection of tumor cells into the bladder wall (open group). Mouse postoperative status was monitored on a weekly basis using magnetic resonance imaging (MRI). RESULTS: The catheter group had a tumor development rate of 47% (7 out of 15 mice), with only 1 mouse developing an intravesical tumor. In contrast, the open group had a higher tumor formation rate of 69% (47 out of 68 mice), with 27 mice showing intravesical tumor formation. Notably, with a lower cell count, urinary obstruction events were observed 2 weeks post-inoculation, which is one week later than the higher cell count group. CONCLUSION: In this study, we conducted a comparative analysis between the transurethral catheterization method and the transperitoneal incision and direct injection method in animal bladder tumor models. Our findings provide evidence of the consistent effectiveness in constructing a stable model within the open group. Well-designed orthotopic animal models are essential.


Subject(s)
Quality of Life , Urinary Bladder Neoplasms , Female , Animals , Mice , Mice, Inbred C3H , Neoplasm Recurrence, Local , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder/pathology , Disease Models, Animal
11.
Eur J Oncol Nurs ; 66: 102404, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37517339

ABSTRACT

PURPOSE: Digital self-management (SM) interventions targeting symptom relief have demonstrated positive as well as null outcomes, whereas no study has synthesized the effect of the interventions. In this study, we aimed to evaluate the effectiveness of digital SM symptom interventions on symptom outcomes in adult cancer patients. METHODS: A systematic review and meta-analysis based on the previous scoping review was conducted. Six databases (PubMed, CINAHL, Embase, the Cochrane Library, RISS [Korean], and KoreaMed [Korean]) were searched. Population was adult cancer patients. Intervention was SM interventions applying digital health tool targeting symptom management. Comparison was usual care, waitlist controls or active controls. The primary outcome was symptom burden, and the secondary outcomes were individual symptoms. RESULTS: Our meta-analysis of 32 randomized controlled trials (RCTs) including 7888 patients demonstrated that digital SM symptom interventions had a significant effect on reducing symptom burden (effect size [ES] = -0.230) and relieving pain (ES = -0.292), fatigue (ES = -0.417), anxiety (ES = -0.320), and depression (ES = -0.261). CONCLUSIONS: Digital SM interventions can improve symptom outcomes in adult cancer patients. Oncology nurses should be aware that digital SM interventions have demonstrated promising outcomes in cancer patient care.

12.
Brain Behav ; 13(9): e3137, 2023 09.
Article in English | MEDLINE | ID: mdl-37366935

ABSTRACT

BACKGROUND: The association between programed cell death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in vestibular schwannoma (VS) has been investigated in a few studies. These published studies report a difference in the PD-L1 positivity rate in malignant peripheral nerve sheath tumors. We examined PD-L1 expression and lymphocyte infiltration in patients with VS who had undergone surgical resection and investigated the association between PD-L1 expression and clinicopathological features. METHODS: The expression of PD-L1, CD8, and Ki-67 in 40 VS tissue specimens was investigated using immunohistochemistry, and a clinical review of the patients was performed. RESULTS: Of the 40 VS samples, 23 (57.5%) were positive for PD-L1 and 22 (55%) were positive for CD8. No significant differences in age, tumor size, pure-tone audiometry, speech discrimination, or Ki-67 expression were observed between patients in the PD-L1-positive and PD-L1-negative groups. A higher level of CD8-positive cell infiltration was observed in PD-L1-positive tumors than in PD-L1-negative tumors. CONCLUSION: We demonstrated that PD-L1 was expressed in VS tissues. Although no correlation was identified between clinical characteristics and PD-L1 expression, the association between PD-L1 and CD8 was confirmed. Thus, additional research on targeting PD-L1 is necessary to improve immunotherapy for VS in the future.


Subject(s)
B7-H1 Antigen , Neuroma, Acoustic , Humans , B7-H1 Antigen/metabolism , Ki-67 Antigen , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Prognosis
13.
BMC Cancer ; 23(1): 468, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37217880

ABSTRACT

BACKGROUND: Breast cancer brain metastasis (BCBM) is a growing therapeutic challenge and clinical concern. Stromal cancer-associated fibroblasts (CAFs) are crucial factors in the modulation of tumorigeneses and metastases. Herein, we investigated the relationship between the expression of stromal CAF markers in metastatic sites, platelet-derived growth factor receptor-beta (PDGFR-ß), and alpha-smooth muscle actin (α-SMA) and the clinical and prognostic variables in BCBM patients. METHODS: Immunohistochemistry (IHC) of the stromal expression of PDGFR-ß and α-SMA was performed on 50 cases of surgically resected BCBM. The expression of the CAF markers was analyzed in the context of clinico-pathological characteristics. RESULTS: Expression of PDGFR-ß and α-SMA was lower in the triple-negative (TN) subtype than in other molecular subtypes (p = 0.073 and p = 0.016, respectively). And their expressions were related to a specific pattern of CAF distribution (PDGFR-ß, p = 0.009; α-SMA, p = 0.043) and BM solidity (p = 0.009 and p = 0.002, respectively). High PDGFR-ß expression was significantly related to longer recurrence-free survival (RFS) (p = 0.011). TN molecular subtype and PDGFR-ß expression were independent prognostic factors of recurrence-free survival (p = 0.029 and p = 0.030, respectively) and TN molecular subtype was an independent prognostic factor of overall survival (p < 0.001). CONCLUSIONS: Expression of PDGFR-ß in the stroma of BM was associated with RFS in BCBM patients, and the clinical implication was uniquely linked to the low expression of PDGFR-ß and α-SMA in the aggressive form of the TN subtype.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Female , Humans , Actins/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Clinical Relevance , Fibroblasts/metabolism , Prognosis , Receptor, Platelet-Derived Growth Factor beta/genetics , Receptor, Platelet-Derived Growth Factor beta/metabolism , Brain Neoplasms/secondary
14.
Pharmaceuticals (Basel) ; 16(3)2023 Mar 05.
Article in English | MEDLINE | ID: mdl-36986493

ABSTRACT

Protein drugs have been emerging as a class of promising therapeutics. However, their topical application has been limited by their high molecular weight and poor permeability to the cell membrane. In this study, we aimed to enhance human growth hormone (hGH) permeability for topical application by conjugation of TAT peptide, a cell-penetrating peptide, to hGH via crosslinker. After TAT was conjugated to hGH, TAT-hGH was purified by affinity chromatography. TAT-hGH significantly increased cell proliferation compared with the control. Interestingly, the effect of TAT-hGH was higher than hGH at the same concentration. Furthermore, the conjugation of TAT to hGH enhanced the permeability of TAT-hGH across the cell membrane without affecting its biological activity in vitro. In vivo, the topical application of TAT-hGH into scar tissue markedly accelerated wound healing. Histological results showed that TAT-hGH dramatically promoted the re-epithelialization of wounds in the initial stage. These results demonstrate TAT-hGH as a new therapeutic potential drug for wound healing treatment. This study also provides a new method for topical protein application via enhancement of their permeability.

15.
J Cancer ; 14(3): 464-479, 2023.
Article in English | MEDLINE | ID: mdl-36860926

ABSTRACT

Aims: This study assessed the expression and clinical relevance of cancer-asssociated fibroblast (CAF)-related biomarkers in brain metastasis (BM). Moreover, molecular characterization of patient-derived primary CAFs and normal fibroblasts (NFs) was performed. Methods: Sixty-eight patients with BM from various primary cancer types were selected. Immunohistochemistry (IHC) and immunofluorescence (IF) staining were performed to evaluate the expression of various CAF-related biomarkers. CAFs and NFs were isolated from fresh tissues. Results: Various CAF-related biomarkers were expressed in CAFs in BMs of different primary cancers. However, only PDGFR-ß, α-SMA, and collagen type I were associated with BM size. PDGFR-ß and α-SMA were associated with BM recurrence after resection. PDGFR-ß was associated with recurrence-free survival (RFS). Interestingly, high expression of PDGFR-ß and α-SMA was found in the patients with previous chemotherapy or radiotherapy for primary cancer. In primary cell culture, PDGFR-ß and α-SMA were expressed at higher levels in patient-derived CAFs than in NFs or cancer cells. The origins of CAF in BM were presumed to be pericytes of blood vessels, circulating endothelial progenitor cells, or transformed astrocytes of the peritumoral glial stroma. Conclusion: Our results suggest that high expression of CAF-related biomarkers, particularly PDGFR-ß and α-SMA, is associated with poor prognosis and recurrence in patients with BM. With the elucidation of the role and origins of CAF in the tumor microenvironment, CAF can be a new imperative target for BM immunotherapy.

16.
J Med Internet Res ; 25: e38333, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36607712

ABSTRACT

BACKGROUND: Digital care has become an essential component of health care. Interventions for patients with cancer need to be effective and safe, and digital health interventions must adhere to the same requirements. OBJECTIVE: The purpose of this study was to identify currently available digital health interventions developed and evaluated in randomized controlled trials (RCTs) targeting adult patients with cancer. METHODS: A scoping review using the JBI methodology was conducted. The participants were adult patients with cancer, and the concept was digital health interventions. The context was open, and sources were limited to RCT effectiveness studies. The PubMed, CINAHL, Embase, Cochrane Library, Research Information Sharing Service, and KoreaMed databases were searched. Data were extracted and analyzed to achieve summarized results about the participants, types, functions, and outcomes of digital health interventions. RESULTS: A total of 231 studies were reviewed. Digital health interventions were used mostly at home (187/231, 81%), and the web-based intervention was the most frequently used intervention modality (116/231, 50.2%). Interventions consisting of multiple functional components were most frequently identified (69/231, 29.9%), followed by those with the self-manage function (67/231, 29%). Web-based interventions targeting symptoms with the self-manage and multiple functions and web-based interventions to treat cognitive function and fear of cancer recurrence consistently achieved positive outcomes. More studies supported the positive effects of web-based interventions to inform decision-making and knowledge. The effectiveness of digital health interventions targeting anxiety, depression, distress, fatigue, health-related quality of life or quality of life, pain, physical activity, and sleep was subject to their type and function. A relatively small number of digital health interventions specifically targeted older adults (6/231, 2.6%) or patients with advanced or metastatic cancer (22/231, 9.5%). CONCLUSIONS: This scoping review summarized digital health interventions developed and evaluated in RCTs involving adult patients with cancer. Systematic reviews of the identified digital interventions are strongly recommended to integrate digital health interventions into clinical practice. The identified gaps in digital health interventions for cancer care need to be reflected in future digital health research.


Subject(s)
Neoplasm Recurrence, Local , Quality of Life , Humans , Aged , Randomized Controlled Trials as Topic , Anxiety/therapy , Exercise
17.
Cancer Immunol Immunother ; 72(5): 1233-1246, 2023 May.
Article in English | MEDLINE | ID: mdl-36385211

ABSTRACT

The development of new treatment agents in recent decades has significantly improved the survival of patients with multiple myeloma (MM). Nonetheless, MM remains an incurable disease; therefore, novel combination therapies are required. Natural killer (NK) cells are one of the safest immunotherapeutic options. In this study, we found that the anti-myeloma activity of expanded NK cells (eNKs) was improved by daratumumab, lenalidomide, and dexamethasone (DRd) in an MM xenograft mouse model. NK cells expanded from peripheral blood mononuclear cells collected from MM patients were highly cytotoxic against DRd pretreated tumor cells in vitro. To mimic the clinical protocol, a human MM xenograft model was developed using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull (NSG) mice. MM bearing mice were randomly divided into six groups: no treatment, eNK, Rd, Rd + eNKs, DRd, and DRd + eNKs. DRd significantly enhanced the cytotoxicity of eNKs by upregulating NK cell activation ligands and effector function. DRd in combination with eNKs significantly reduced the serum M-protein level and prolonged mouse survival. In addition, DRd significantly increased the persistence of eNK and homing to MM sites. These results show that the anti-myeloma activity of ex vivo-expanded and activated NK cells is augmented by the immunomodulatory effect of DRd in MM-bearing mice, suggesting the therapeutic potential of this combination for MM patients.


Subject(s)
Multiple Myeloma , Humans , Animals , Mice , Multiple Myeloma/therapy , Lenalidomide/pharmacology , Heterografts , Leukocytes, Mononuclear , Mice, SCID , Mice, Inbred NOD , Killer Cells, Natural , Dexamethasone/pharmacology
18.
Front Oncol ; 12: 1034944, 2022.
Article in English | MEDLINE | ID: mdl-36338688

ABSTRACT

Background: Extraneural metastasis (ENM) of glioblastoma are rare. However, as patient overall survival improves, the incidence of ENM has gradually increased. Although several risk factors have been proposed, venous sinus invasion was regarded as a very exceptional route for ENM. Case description: We report a 60-year-old man with glioblastoma in the temporal lobe, invading the transverse and sigmoid venous sinus. After gross total tumor resection, the patient received the standard chemoradiation therapy. Systemic evaluation for persistent shoulder and back pain revealed widespread metastasis to lymph nodes and multiple bones 9 months after surgery. Despite spine radiation therapy, the patient became paraplegic and died 1 year after surgery. Conclusions: Venous sinus invasion should be kept in mind by physicians, as a risk factor for glioblastoma ENM. Systemic evaluation of these patients with extracranial symptoms should be performed without hesitation.

19.
Brain Tumor Res Treat ; 10(4): 265-269, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36347641

ABSTRACT

Meningiomas are the most common benign brain tumors, and most of them originate from the dura mater. However, in some cases, they can originate from the choroid plexus, and they are rarely found in the posterior cranial fossa. A 63-year-old female patient presented with dizziness and swallowing difficulty and was found to have a homogeneously enhancing mass in the right posterior cranial fossa. Mass removal was performed through retrosigmoid suboccipital craniotomy, and the mass was confirmed to originate from the choroid plexus. The pathological diagnosis was meningothelial meningioma. The patient had temporary swallowing difficulty but recovered without any neurological sequelae. We report a rare case of a lower cerebellopontine angle meningioma without dural attachment originating from the choroid plexus of the foramen of Luschka.

20.
J Clin Med ; 11(20)2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36294373

ABSTRACT

Cognitive impairment often occurs in glioblastoma (GBM) patients due to the tumor itself and treatment side effects. Choline alphoscerate (L-alpha-glycerylphosphorylcholine, GPC) is frequently used to compensate for cognitive impairment in GBM patients. This study was conducted to determine whether GPC affects the overall survival (OS) and progression-free survival (PFS) of GBM patients. From 2011 to 2020, 187 isocitrate dehydrongenase (IDH)-wild-type GBM patients were analyzed. The patients were classified based on whether GPC was continuously used for at least 3 or 12 months (mos) after GBM diagnosis. Although GPC usage (≥3 mos) did not make significant differences in survival extension, median OS in the long-term GPC group (≥12 mos) was longer with statistical significance, compared to the control group (<12 mos) (38.3 vs. 24.0 mos, p = 0.004). In addition to younger age, supratentorial location, complete resection, and MGMT promoter methylation, long-term use of GPC (≥12 mos) was significantly associated with longer OS in multivariate analysis (p = 0.019, hazard ratio [HR] 0.532, 95% confidence interval [CI] 0.314−0.900). Despite the limitations of this study, long-term GPC use was possibly associated with prolonged survival in GBM patients. Multi-center prospective randomized studies with a large number of patients are needed to validate these findings.

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