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1.
Article in English | WPRIM | ID: wpr-915807

ABSTRACT

Background@#Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features. @*Methods@#A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays. @*Results@#PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression. @*Conclusions@#PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

2.
Article in English | WPRIM | ID: wpr-915804

ABSTRACT

Background@#Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT). @*Methods@#A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens. @*Results@#We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression. @*Conclusions@#This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

3.
Article in English | WPRIM | ID: wpr-913764

ABSTRACT

Background@#Cadherin-11, a cell-to-cell adhesion molecule, is associated with higher tumor grade and decreased patient survival. The purpose of this study was to investigate the clinical significance of cadherin-11 expression in the progression and prognosis of a newly diagnosed primary glioblastoma (GBL). @*Methods@#Between 2007 and 2016, 52 out of 178 patients diagnosed with a GBL and satisfied the following criteria: 1) a new primary GBL, 2) gross-total resection, 3) immunohistochemically-available tissue, and 4) standardized adjuvant treatment. @*Results@#In terms of staining intensity, the low-intensity cadherin-11 group showed longer progression-free survival (PFS) than the high-intensity cadherin-11 group (median PFS, 12.0 months [95% CI, 11.1-12.9] vs. median PFS, 6.0 months [95% CI, 3.7-8.3]; p<0.001). The low-intensity cadherin-11 group revealed longer overall survival (OS) than the high-intensity cadherin-11 group (median OS, 20.0 months [95% CI, 11.8-16.6] vs. median OS, 15.0 months [95% CI, 11.8-18.2]; p=0.003). The staining intensity of cadherin-11 was a statistically significant factor in PFS and OS in terms of univariate and multivariate analyses (univariate analysis: p<0.001 and p=0.005; multivariate analysis: p<0.001 and p=0.005). @*Conclusion@#Our clinical study demonstrates high cadherin-11 expression may be associated with poor PFS and OS for a newly diagnosed primary GBL.

4.
Journal of Liver Cancer ; : 177-180, 2021.
Article in English | WPRIM | ID: wpr-900277

ABSTRACT

Sorafenib is the oldest first line systemic treatment in patients with advanced hepatocellularcarcinoma (HCC) and has been used exclusively for nearly 10 years. The superiority ofadministering a combination of atezolizumab plus bevacizumab (AteBeva) compared tosorafenib as first line systemic treatment for unresectable HCC was recently proven duringthe IMbrave150 Phase III randomized trial. While clinicians can expect improved responsesand treatment outcomes due to the good results of the IMbrave 150 trial, they must alsoconsider that atezolizumab can cause various immune-related adverse events (IrAEs). Basedon the above suggestions, we herein present a case of HCC with lymph node metastasiswho achieved complete remission following treatment with AteBeva and developed an IrAE(adrenal insufficiency). Further study of real-life data regarding combination therapy withAteBeva is needed to manage patients with advanced HCC.

5.
Journal of Liver Cancer ; : 69-75, 2021.
Article in English | WPRIM | ID: wpr-900267

ABSTRACT

Hepatocellular carcinoma (HCC) primarily originates in the liver with hepatic differentiation. However, HCCs are not homogenous, and approximately 35% of HCC cases are classified as histopathological variants that present distinct pathologic characteristics. In particular, the lymphocyte-rich variant is the rarest subtype accounting for less than 1% of HCCs, which is not well known to date about molecular features and pathophysiology. Herein, we present a case of a patient who was suspected of metastatic liver cancer and confirmed as lymphocyte-rich HCC pathologically. A 78-year-old woman who underwent a right hemicolectomy for colon cancer was referred to our hospital for a newly detected liver mass. We could not make a decision because of insufficient evidence for diagnosis from imaging studies. After resection, we found that it was a lymphocyte-rich HCC. The pathologic features and prognostic trends of this subtype are also discussed.

6.
Gut and Liver ; : 410-419, 2021.
Article in English | WPRIM | ID: wpr-898455

ABSTRACT

Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.

7.
Article in English | WPRIM | ID: wpr-875515

ABSTRACT

Background/Aims@#Untreated rupture of the thoracic aorta is associated with a high mortality rate. We aimed to review the clinical results of endovascular treatment for ruptured thoracic aortic disease. @*Methods@#We retrospectively reviewed data on 37 patients (mean age, 67.0 ± 15.18 years) treated for ruptured thoracic aortic disease from January 2005 to May 2016. The median follow-up duration was 308 days (interquartile range, 61 to 1,036.5). The primary end-point of the study was the composite of death, secondary intervention, endoleak, and major stroke/paraplegia after endovascular treatment. @*Results@#The etiologies of ruptured thoracic aortic disease were aortic dissection (n = 11, 29.7%), intramural hematoma (n = 7, 18.9%), thoracic aortic aneurysm (n = 14, 37.8%), and traumatic aortic transection (n = 5, 13.5%). Three patients died within 24 hours of thoracic endovascular aortic repair, and one showed type I endoleak. The technical success rate was 89.2% (33/37). The in-hospital mortality rate was 13.5% (5/37); no deaths occurred during follow-up. The composite outcome rate during follow-up was 37.8% (14/37), comprising death (n = 5, 13.5%), secondary intervention (n = 5, 13.5%), endoleak (n = 5, 13.5%), and major stroke/paraplegia (n = 3, 8.1%). Left subclavian artery revascularization and proximal landing zone were not associated with the composite outcome. Low mean arterial pressure (MAP; ≤ 60 mmHg, [hazard ratio, 13.018; 95% confidence interval, 2.435 to 69.583, p = 0.003]) was the most significant predictor and high transfusion requirement in the first 24 hours was associated with event-free survival (log rank p = 0.018). @*Conclusions@#Endovascular treatment achieves high technical success rates and acceptable clinical outcome. High transfusion volume and low MAP were associated with poor clinical outcomes.

8.
Article in English | WPRIM | ID: wpr-874891

ABSTRACT

Background@#Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult. @*Methods@#We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003–2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis. @*Results@#When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients. @*Conclusions@#Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.

9.
Gut and Liver ; : 117-127, 2021.
Article in English | WPRIM | ID: wpr-874578

ABSTRACT

Background/Aims@#The hepatic steatosis index (HSI) is a noninvasive method to assess the severity of hepatic steatosis. Antiviral therapy (AVT) can impact aspartate aminotransferase and alanine aminotransferase levels, which are the main components of the HSI. Thus, we investigated the accuracy of the HSI in detecting hepatic steatosis in patients with chronic hepatitis B (CHB) receiving AVT, compared with those not receiving AVT and in those with nonalcoholic fatty liver disease (NAFLD). @*Methods@#Patients with CHB or NAFLD who underwent a magnetic resonance imaging proton density fat fraction (MRI-PDFF) evaluation between March 2010 and March 2019 were recruited.Hepatic steatosis was diagnosed when the PDFF exceeded 5%. Area under the receiver operating characteristic curve (AUROC) analysis was used to assess the diagnostic accuracy of the HSI in the detection of hepatic steatosis. @*Results@#The mean age of the study population (189 men and 116 women; 244 with CHB [184 with and 60 without AVT] and 61 with NAFLD) was 55.6 years. The AUROC values for detecting hepatic steatosis were similar between patients with CHB (0.727; p<0.001) and those with NAFLD (0.739; p=0.002). However, when patients with CHB were subdivided into those receiving and not receiving AVT, the AUROC value decreased slightly in patients with CHB receiving AVT compared to those without not receiving AVT (0.707; p=0.001 vs 0.779; p=0.001). @*Conclusions@#Despite a slight attenuation, the diagnostic accuracy of the HSI in patients with CHB receiving AVT in detecting hepatic steatosis was still acceptable. Further large-scale studies are required for validation.

10.
Article in English | WPRIM | ID: wpr-917548

ABSTRACT

Purpose@#This study aimed to evaluate and compare the quality of total mesorectal excision (TME) and disease-free and overall survival rates between robotic and laparoscopic surgeries for rectal cancer. @*Methods@#From January 2015 to December 2018, 234 patients underwent curative robotic or laparoscopic surgery for rectal cancer at two centers. Ultimately, 201 patients were enrolled. To control for different demographic factors in the two groups, propensity score matching was used at a 1:1 ratio. Propensity scores were generated with the baseline characteristics, including age, sex, body mass index, American Society of Anesthesiologists score, previous abdominal surgery, tumor location, preoperative chemotherapy, and preoperative radiation. Finally, 134 patients were matched with 67 patients in the robotic surgery group and 67 patients in the laparoscopic surgery group. @*Results@#There was no significant difference in the pathologic stages between the robotic and laparoscopic surgery groups. Distal margin involvement was only observed in the robotic surgery group (1/67, 1.5%). Circumferential resection margin involvement was not different between the robotic surgery and laparoscopic surgery groups (3/67 [4.5%] and 4/67 [6.0%], respectively, P = 1.000). The quality of TME (complete, nearly complete, and incomplete) was similar between the robotic surgery and laparoscopic surgery groups (88.0%, 6.0%, 6.0% and 79.1%, 9.0%, 11.9%, respectively, P = 0.358). The disease-free and overall survival rates were not significantly different between the groups. @*Conclusion@#The quality of TME and disease-free and overall survival rates between the two surgeries were similar. There was no oncologic advantage of robotic surgery for rectal cancer compared to laparoscopic surgery.

11.
Article in English | WPRIM | ID: wpr-897674

ABSTRACT

Background/Aims@#Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. @*Methods@#Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. @*Results@#180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. @*Conclusion@#A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

12.
Article in English | WPRIM | ID: wpr-897663

ABSTRACT

Background/Aims@#The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT. @*Methods@#Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of <1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch. @*Results@#The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices <1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P<0.001). @*Conclusions@#The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.

13.
Journal of Liver Cancer ; : 177-180, 2021.
Article in English | WPRIM | ID: wpr-892573

ABSTRACT

Sorafenib is the oldest first line systemic treatment in patients with advanced hepatocellularcarcinoma (HCC) and has been used exclusively for nearly 10 years. The superiority ofadministering a combination of atezolizumab plus bevacizumab (AteBeva) compared tosorafenib as first line systemic treatment for unresectable HCC was recently proven duringthe IMbrave150 Phase III randomized trial. While clinicians can expect improved responsesand treatment outcomes due to the good results of the IMbrave 150 trial, they must alsoconsider that atezolizumab can cause various immune-related adverse events (IrAEs). Basedon the above suggestions, we herein present a case of HCC with lymph node metastasiswho achieved complete remission following treatment with AteBeva and developed an IrAE(adrenal insufficiency). Further study of real-life data regarding combination therapy withAteBeva is needed to manage patients with advanced HCC.

14.
Journal of Liver Cancer ; : 69-75, 2021.
Article in English | WPRIM | ID: wpr-892563

ABSTRACT

Hepatocellular carcinoma (HCC) primarily originates in the liver with hepatic differentiation. However, HCCs are not homogenous, and approximately 35% of HCC cases are classified as histopathological variants that present distinct pathologic characteristics. In particular, the lymphocyte-rich variant is the rarest subtype accounting for less than 1% of HCCs, which is not well known to date about molecular features and pathophysiology. Herein, we present a case of a patient who was suspected of metastatic liver cancer and confirmed as lymphocyte-rich HCC pathologically. A 78-year-old woman who underwent a right hemicolectomy for colon cancer was referred to our hospital for a newly detected liver mass. We could not make a decision because of insufficient evidence for diagnosis from imaging studies. After resection, we found that it was a lymphocyte-rich HCC. The pathologic features and prognostic trends of this subtype are also discussed.

15.
Gut and Liver ; : 410-419, 2021.
Article in English | WPRIM | ID: wpr-890751

ABSTRACT

Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.

16.
Article in English | WPRIM | ID: wpr-889970

ABSTRACT

Background/Aims@#Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. @*Methods@#Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. @*Results@#180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. @*Conclusion@#A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

17.
Article in English | WPRIM | ID: wpr-889959

ABSTRACT

Background/Aims@#The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT. @*Methods@#Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of <1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch. @*Results@#The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices <1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P<0.001). @*Conclusions@#The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.

18.
Article in English | WPRIM | ID: wpr-898918

ABSTRACT

Since the first FDA approval of Lamivudine in 1998, many nucleo(t)side analogs such as Lamivudine, Adefovir, and Entecavir have been used. However, they only inhibit DNA synthesis, and if their administration is stopped a viral breakthrough can develop, making long-term administration necessary, ultimately followed by the development of resistance. Tenofovir has been developed and drug-resistant mutations have decreased significantly, but the problem of resistance due to long-term drug use still remains, along with the drug safety problem. In this review, we introduce the recent trend in the development of hepatitis B treatment agents and the Korea National Research Institute of Health (KNIH) research for the development of a novel treatment for hepatitis B (drug repositioning) without resistance and which targets the various life cycles of HBV.

19.
Article in English | WPRIM | ID: wpr-898914

ABSTRACT

Hepatitis B virus (HBV) infection is a major public health problem, with some 250 million people currently at high risk of developing chronic liver diseases. The current antiviral treatment for chronic hepatitis B (CHB) is effective in controlling viral replication but fails to achieve a complete cure. Since the identification of sodium taurocholate cotransport polypeptide (NTCP) as an HBV receptor, anti-HBV drugs targeting viral entry, capsid assembly, cccDNA, transcription, and secretion have been developed. In this paper, the potential inhibitors in various steps of the HBV life cycle are summarized.

20.
Immune Network ; : e5-2020.
Article in English | WPRIM | ID: wpr-898561

ABSTRACT

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

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