Development of a Direct Non-Puncture Device for Measuring Portal Venous Pressure during Liver Transplantation-A Swine Model.

Portal hypertension-related complications pose a significant risk for liver failure post-transplantation. Thus, accurate monitoring of intraoperative portal venous pressure (PVP) is crucial. However, current PVP monitoring techniques requiring direct percutaneous puncture carry the risk of graft damage. In this study, we present an innovative non-puncture PVP monitoring device (PVPMD) using a 3D-printed prototype. PVPMD design is inspired by the sphygmomanometer principle, and strategically encompasses the portal vein and enables precise PVP measurement through blood flow ultrasonography after temporary occlusion. By a series of mini-pig experiments, the prototype PVPMD demonstrated a strong correlation with invasive catheter measurements in the main trunk of the portal vein (rs = 0.923, p = 0.000). There was a significant repeatability and reproducibility between the prototype PVPMD- and invasive catheter-measured PVP. This indicates that the PVPMD holds immense potential for direct application in liver transplantation and surgery. Moreover, it has the potential to replace catheter-based central venous pressure (CVP) measurements, thereby mitigating catheter-related complications during many surgeries. In conclusion, our innovative device represents a significant advancement in PVP monitoring during liver transplantation, with comprehensive validation from principle exploration to successful animal experiments. We anticipate that this groundbreaking PVPMD will attract the attention of researchers and clinicians, propelling the noninvasive measurement of PVP or other venous/arterial pressures into a new era of clinical practice.

PF-429242 exhibits anticancer activity in hepatocellular carcinoma cells via FOXO1-dependent autophagic cell death and IGFBP1-dependent anti-survival signaling.

Effective therapies for hepatocellular carcinoma (HCC) are urgently needed, as it is a type of cancer resistant to chemotherapy. Recent evidence showed that PF-429242, a membrane-bound transcription factor site-1 protease (MBTPS1) inhibitor, exhibited anticancer activities against glioblastomas, renal cell carcinoma, and pancreatic cancer. However, its anticancer activity against HCC has yet to be investigated. In this study, we found that PF-429242 induced autophagy-dependent cell death in HCC cells. RNA-sequencing analysis indicated that the primary effect of PF-429242 was inhibition of the sterol regulatory element-binding protein (SREBP) signaling pathway. However, overexpression of SREBP proteins did not efficiently rescue PF-429242-induced autophagy and cell death. Mechanistically, PF-429242 induced forkhead box protein O1 (FOXO1)-dependent autophagic cell death. Additionally, PF-429242 caused FOXO1-independent upregulation of insulin-like growth factor-binding protein 1 (IGFBP1), ultimately leading to autophagy-independent cell death. The in vivo anticancer activity of PF-429242 against HCC cells was demonstrated in a tumor xenograft mouse model. Therefore, PF-429242 is a potential anticancer agent to treat HCC by triggering FOXO1-dependent autophagic cell death and IGFBP1-mediated anti-survival signaling in parallel.

The online interactive visual learning improves learning effectiveness and satisfaction of physicians with postgraduate year during the COVID-19 pandemic in Taiwan.

BACKGROUNDS: Medical education has shifted from passive forms of teaching to more active learning strategies, particularly in response to the COVID-19 pandemic. Research has discussed the challenges and disadvantages associated with online education, but there is limited documentation on physicians' perceptions of this sudden and unexpected transformation in medical education. This study aimed to determine the effect of online interactive visual learning on physicians' perceptions of the effectiveness and their satisfaction with this online learning experience. METHODS: We routinely recruited 64 unclassified physicians in the hospital's postgraduate year (PGY) program between September 2021 and April 2022. PGY physicians received an online interactive visual learning course. Online (Google Form) testing and questionnaires before and after this course evaluated learning performance, learning attitude and satisfaction of these physicians. RESULTS: The interactive online learning tools facilitated the physicians' active learning processes by reducing their learning burden (burden vs. no burden: 4.69% vs. 68.75%) and increasing their learning interest (interest vs. no interest: 84.38% vs. 3.12%) in the online format. Post-test scores were significantly improved compared with pretest scores (post-test vs. pre-test: 5 vs. 4; p < 0.05) and their imaging recognition was markedly improved from baseline (post-test vs. pre-test: 85.19% vs. 61.11%). Levels of satisfaction correlated positively with the physicians' learning burden (rs = 0.541), learning interest (rs = 0.562), and perceived benefits of imaging recognition (post-course: rs = 0.508; future: rs = 0.563) (all p < 0.05). CONCLUSIONS: Our online course with interactive visual learning facilitated PGY physicians' learning performance, levels of satisfaction, interest, and perceived benefits of online learning. Hospitals and policymakers need to be aware that this learning approach can markedly enhance physicians' academic outcomes and levels of clinical practice.

Inhibition of CDK9 exhibits anticancer activity in hepatocellular carcinoma cells via targeting ribonucleotide reductase.

Cyclin-dependent kinase 9 (CDK9) inhibitors are a novel category of anticancer treatment for cancers. However, their effects on hepatocellular carcinoma (HCC) are rarely investigated. Human ribonucleotide reductase (RR, which consists of RRM1 and RRM2 subunits) catalyzes the conversion of ribonucleoside diphosphate into 2'-deoxyribonucleoside diphosphate to maintain the homeostasis of nucleotide pools, which play essential roles in DNA synthesis and DNA repair. In this study, we identified that CDK9 protein expression in adjacent non-tumor tissues predicted HCC patients' overall and progression-free survivals. The anticancer activity of a CDK9-selective inhibitor, LDC000067, on HCC cells was positively associated with its ability to inhibit the expression of RRM1 and RRM2. LDC000067 downregulated RRM1 and RRM2 expression through post-transcriptional pathway. Specifically, LDC000067 triggered RRM2 protein degradation via multiple pathways, including proteasome-, lysosome-, and calcium-dependent pathways. Furthermore, CDK9 positively correlates with RRM1 or RRM2 expression in HCC patients, and the expressions of these three genes were associated with the higher infiltration of immune cells in HCC. Taken together, this study identified the prognostic relevance of CDK9 in HCC and the molecular mechanism for the anticancer effect of CDK9 inhibitors on HCC.

Wasabi Component 6-(Methylsulfinyl)hexly Isothiocyanate and Derivatives Improve the Survival of Skin Allografts.

We tested the effect of 6-(Methylsulfinyl)hexyl Isothiocyanate (6-MITC) and derivatives (I7447 and I7557) on the differentiation and maturation of human myeloid dendritic cells (DCs) in vitro, and skin transplantation in vivo. Triggering of CD14+ myeloid monocyte development toward myeloid DCs with and without 6-MITC and derivatives to examine the morphology, viability, surface marker expression, and cytokine production. Stimulatory activity on allogeneic naive T cells was measured by proliferation and interferon-γ production. The skin allograft survival area model was used to translate the 6-MITC and derivatives' antirejection effect. All of the compounds had no significant effects on DC viability and reduced the formation of dendrites at concentrations higher than 10 µM. At this concentration, 6-MITC and I7557, but not I7447, inhibited the expression of CD1a and CD83. Both 6-MITC and I7557 exhibited T-cells and interferon-γ augmentation at lower concentrations and suppression at higher concentration. The 6-MITC and I7557 prolonged skin graft survival. Both the 6-MITC and I7557 treatment resulted in the accumulation of regulatory T cells in recipient rat spleens. No toxicity was evident in 6-MITC and I7557 treatment. The 6-MITC and I7557 induced human DC differentiation toward a tolerogenic phenotype and prolonged rat skin allograft survival. These compounds may be effective as immunosuppressants against transplant rejection.

Bioinformatics Analysis Identifies Precision Treatment with Paclitaxel for Hepatocellular Carcinoma Patients Harboring Mutant TP53 or Wild-Type CTNNB1 Gene.

Hepatocellular carcinoma (HCC) is an aggressive and chemoresistant cancer type. The development of novel therapeutic strategies is still urgently needed. Personalized or precision medicine is a new trend in cancer therapy, which treats cancer patients with specific genetic alterations. In this study, a gene signature was identified from the transcriptome of HCC patients, which was correlated with the patients' poorer prognoses. This gene signature is functionally related to mitotic cell cycle regulation, and its higher or lower expression is linked to the mutation in tumor protein p53 (TP53) or catenin beta 1 (CTNNB1), respectively. Gene-drug association analysis indicated that the taxanes, such as the clinically approved anticancer drug paclitaxel, are potential drugs targeting this mitotic gene signature. Accordingly, HCC cell lines harboring mutant TP53 or wild-type CTNNB1 genes are more sensitive to paclitaxel treatment. Therefore, our results imply that HCC patients with mutant TP53 or wild-type CTNNB1 genes may benefit from the paclitaxel therapy.

PERK/ATF4-Dependent ZFAS1 Upregulation Is Associated with Sorafenib Resistance in Hepatocellular Carcinoma Cells.

Sorafenib, a multi-kinase inhibitor, is the first-line treatment for advanced hepatocellular carcinoma (HCC) patients. However, this drug only provides a short improvement of patients' overall survival, and drug resistance is commonly developed. Thus, the identification of resistant factor(s) or biomarker(s) is needed to develop more efficient therapeutic strategies. Long, non-coding RNAs (lncRNAs) have recently been viewed as attractive cancer biomarkers and drive many important cancer phenotypes. A lncRNA, ZFAS1 (ZNFX1 antisense RNA 1) has been found to promote HCC metastasis. This study found that sorafenib induced ZFAS1 expression specifically in sorafenib-resistant HCC cells. Although ZFAS1 knockdown did not restore the sensitivity of HCC cells to sorafenib, its expression may act as a resistant biomarker for sorafenib therapy. Bioinformatics analysis predicted that sorafenib tended to induce pathways related to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in sorafenib-resistant HCC cells. In vitro experimental evidence suggested that sorafenib induced protein kinase RNA-like ER kinase (PERK)/activating transcription factor 4 (ATF4)-dependent ZFAS1 expression, and sorafenib resistance could be overcome by PERK/ATF inhibitors. Therefore, PERK/ATF4/ZFAS1 signaling axis might be an attractive therapeutic and prognostic biomarker for sorafenib therapy in HCC.

Trilostane, a 3ß-hydroxysteroid dehydrogenase inhibitor, suppresses growth of hepatocellular carcinoma and enhances anti-cancer effects of sorafenib.

Background Human 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) is an enzyme associated with steroidogenesis, however its' role in hepatocellular carcinoma (HCC) biology is unknown. Trilostane is an inhibitor of HSD3B1 and has been tested as a treatment for patients with breast cancer but has not been studied in patients with HCC. Methods and Results The expression of HSD3B1 in HCC tumors in 57 patients were examined. A total of 44 out of 57 tumors (77.2%) showed increased HSD3B1 expression. The increased HSD3B1 in tumors was significantly associated with advanced HCC. In vitro, the knockdown of HSD3B1 expression in Mahlavu HCC cells by a short hairpin RNA (shRNA) led to significant decreases in colony formation and cell migration. The suppression of clonogenicity in the HSD3B1-knockdown HCC cells was reversed by testosterone and 17ß-estradiol. Trilostane-mediated inhibition of HSD3B1 in different HCC cells also caused significant inhibition of clonogenicity and cell migration. In subcutaneous HCC Mahlavu xenografts, trilostane (30 or 60 mg/kg, intraperitoneal injection) significantly inhibited tumor growth in a dose-dependent manner. Furthermore, the combination of trilostane and sorafenib significantly enhanced the inhibition of clonogenicity and xenograft growth, surpassing the effects of each drug used alone, with no documented additional toxicity to animals. HSD3B1 blockade was found to suppress the phosphorylation of extracellular signal-regulated kinase (ERK). The decreased ERK phosphorylation was reversed by testosterone or 17b-estradiol. Conclusions Trilostane significantly inhibited the growth of HCC by inhibiting HSD3B1 function and augmenting the efficacy of sorafenib.

CDKN2A-Inactivated Pancreatic Ductal Adenocarcinoma Exhibits Therapeutic Sensitivity to Paclitaxel: A Bioinformatics Study.

The mutation of cyclin dependent kinase inhibitor 2A (CDKN2A) is frequently found in pancreatic ductal adenocarcinoma (PDAC). However, its prognostic and therapeutic roles in PDAC have not been extensively investigated yet. In this study, we mined and integrated the cancer genomics and chemogenomics data to investigate the roles of CDKN2A genetic alterations in PDAC patients' prognosis and treatment. We found that functional CDKN2A inactivation caused by mutations and deep deletions predicted poor prognosis in PDAC patients. CDKN2A inactivation was associated with the upregulation of genes related to estrogen response, which can be overcome by CDKN2A restoration. Chemosensitivity profiling of PDAC cell lines and patient-derived organoids found that CDKN2A inactivation was associated with the increased sensitivity to paclitaxel and SN-38 (the active metabolite of irinotecan). However, only paclitaxel can mimic the effect of CDKN2A restoration, and its drug sensitivity was correlated with genes related to estrogen response. Therefore, our study suggested that CDKN2A-inactivated PDAC patients could benefit from the precision treatment with paclitaxel, whose albumin-stabilized nanoparticle formulation (nab-paclitaxel) has been approved for treating PDAC.

Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway.

PURPOSE: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. METHODS: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. RESULTS: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. CONCLUSION: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.

Inhibition of 3ß-Hydroxysteroid Dehydrogenase Type 1 Suppresses Interleukin-6 in Breast Cancer.

BACKGROUND: Recently, we demonstrated that the expression of 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) in breast cancer is associated with shorter recurrence-free survival, and genetic or pharmacologic inhibition of HSD3B1 reduced colony formation and xenograft growth. However, the mechanisms are unclear. METHODS: Triple-negative MDA-MB-231 and BT-20 breast cancer cells underwent HSD3B1 silencing. Microarray and bioinformatic analysis were performed. The interleukin-6 (IL-6) expression and secretion were evaluated using real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Clonogenic ability and cell viability were determined in the absence or presence of recombinant IL-6. RESULTS: Functional and pathway enrichment analyses showed that HSD3B1 silencing modulates the expression of several growth factors and cytokines. Cells transfected with HSD3B1-targeting small interfering RNA or treated with an HSD3B1 inhibitor (trilostane) had decreased IL-6 expression and secretion. HSD3B1 inhibition reduced colony formation, which was partially rescued by IL-6 supplementation. The HSD3B1 knockdown enhanced paclitaxel sensitivity, and IL-6 treatment partially reversed the augmented cytotoxicity. CONCLUSIONS: Our findings suggest that the therapeutic potential of targeting HSD3B1 is in part mediated by IL-6 suppression.

Macrophage-secreted interleukin-35 regulates cancer cell plasticity to facilitate metastatic colonization.

A favorable interplay between cancer cells and the tumor microenvironment (TME) facilitates the outgrowth of metastatic tumors. Because of the distinct initiating processes between primary and metastatic tumors, we investigate the differences in tumor-associated macrophages (TAMs) from primary and metastatic cancers. Here we show that dual expression of M1 and M2 markers is noted in TAMs from primary tumors, whereas predominant expression of M2 markers is shown in metastatic TAMs. At metastatic sites, TAMs secrete interleukin-35 (IL-35) to facilitate metastatic colonization through activation of JAK2-STAT6-GATA3 signaling to reverse epithelial-mesenchymal transition (EMT) in cancer cells. In primary tumors, inflammation-induced EMT upregulates IL12Rß2, a subunit of the IL-35 receptor, in cancer cells to help them respond to IL-35 during metastasis. Neutralization of IL-35 or knockout of IL-35 in macrophages reduces metastatic colonization. These results indicate the distinct TMEs of primary and metastatic tumors and provide potential targets for intercepting metastasis.

Expression of 3ß-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status.

BACKGROUND: Human 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings. METHODS: Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo. RESULTS: The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth. CONCLUSIONS: Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.

Hepatic carcinosarcoma: clinicopathologic features and a review of the literature.

Hepatic carcinosarcoma (HCS) is defined as a malignant tumor containing an intimate mixture of carcinomatous and sarcomatous elements. Here, we report the case of a 72-year-old man who developed HCS from an otherwise normal liver. The patient had no history of alcohol abuse or hepatitis B or C infection. An enhanced abdominal CT scan revealed a 9-cm heterogeneous tumor, with enhancement during the arterial phase and delayed wash-out in the latter phases. Also, a marked elevation in alpha-fetoprotein level (15,164 ng/mL; normal range, < 10 ng/mL) was noted. He underwent resection of liver segments V and VI under a pre-operative diagnosis of atypical hepatocellular carcinoma (HCC). The diagnosis of HCS was made based on thorough pathologic examination with a panel of immunohistochemical staining. Following surgery, the patient made an uneventful recovery, and at present, 16 months post-surgery, he remains well with no evidence of tumor recurrence. In conclusion, pre-operative diagnosis of HCS is difficult and radical resection in the early stage is encouraged to improve the prognosis of these patients.

Sorafenib induces autophagy in human myeloid dendritic cells and prolongs survival of skin allografts.

BACKGROUND: Sorafenib, a multikinase inhibitor approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma, has been reported inhibitory on the function of dendritic cells. This study was aimed to determine the effects of sorafenib on inducing autophagy and immunomodulatory activity and its implication on graft rejection. METHODS: Cell viability and surface antigens were examined by 7-amino-actinomycin D and flow cytometric analysis. Autophagy was characterized using light microscopy and transmission electron microscopy for morphology, Western blotting for LC3B-I lipidation and mammalian target of rapamycin signaling molecules, and immunofluorescence staining for endogenous LC3B, GFP-LC3 transfection, and acidic component vacuoles. Skin allograft in mice was used as an experimental transplantation rejection model. Soluble factors contained in culture medium and serum were measured by enzyme-linked immunosorbent assay. RESULTS: We found that sorafenib inhibited the viability of dendritic cells accompanied by morphologic changes characteristic of autophagy and immature differentiation. This autophagic effect induced by sorafenib was validated by LC3B-I lipidation and autophagosome accumulation. Sorafenib treatment was associated with the down-regulation of phosphorylated mammalian target of rapamycin and its downstream substrate p70S6K. We next performed skin graft model to testify the role of sorafenib-induced immature and autophagic dendritic cells. Intriguingly, sorafenib prolonged the survival of skin allograft without major toxicity. Blockade of autophagic flux by chloroquine partially diminished the protective effect of sorafenib, indicating an autophagy-related mechanism in vivo. CONCLUSION: This study suggests that sorafenib, in addition to being an anticancer agent, may have potential to be developed as a new category of immunosuppressant drugs acting via autophagy induction of dendritic cells.

Sorafenib induces autophagy and suppresses activation of human macrophage.

BACKGROUND: Sorafenib, a multi-kinase inhibitor approved for treatment of advanced renal cell carcinoma and other malignancies, has been shown as a modulator for dendritic cells. This study was designed to examine the effects of sorafenib on macrophages, the major ontogeny of innate immunity. MATERIALS AND METHODS: Macrophages were derived from sorted CD14(+) monocytes of human peripheral blood mononuclear cells. Cell viability and surface antigens were examined by trypan blue analysis. Autophagy was characterized by light microscopy and transmission electron microscopy for morphology, Western blotting for microtubule associated light chain protein 3B (LC-3B) I lipidation, and acridine orange staining for acidic component vacuoles. Soluble factors contained in culture medium and serum were measured by ELISA. RESULTS: We found that sorafenib inhibited the viability of macrophages accompanied by morphological changes characteristic of autophagy. This autophagy-inducing effect was validated by LC3B-I lipidation and autophagosome accumulation. The surface antigen expression and the function of activated macrophages were inhibited by sorafenib, including the expression of co-stimulatory molecule CD80, phagocytosis, and the production of reactive oxygen species. The secretion of IL-10, but not IL-6, TNF-α nor TGF-ß, was reduced by sorafenib. CONCLUSION: Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.

Increased percentage of B cells in patients with more advanced hepatocellular carcinoma.

To compare immunologic phenotypes between (1) hepatocellular carcinoma (HCC) patients and a healthy population and (2) more advanced and early stage HCC patients, we studied 45 HCC patients and 46 healthy controls from January 2006 to January 2008. Using fluorescent activated cell sorter (FACS) analysis, HCC patients were demonstrated to exhibit stronger phagocytosis of granulocytes and monocytes and more peripheral blood mononuclear cells (PBMCs) in the G2/M phase compared with healthy volunteers. By contrast, lower percentages of B and T(h) lymphocytes were also found in the peripheral blood of HCC patients than in the healthy population. Most importantly, a higher percentage of B cells was found in patients with advanced HCC than in those with early HCC in terms of TNM stage (II and III vs I, p = 0.004), the Japanese Integrated Scoring system (2-3 vs 0-1, p = 0.0235), and tumor numbers (> or =2 vs 1, p = 0.005). In conclusion, our findings suggested that HCC patients might exhibit enhanced innate immunity and reduced adaptive immunity compared with healthy volunteers. A higher percentage of B cells was found in patients with more advanced HCC compared with patients with early stage HCC, which might serve as an indicator of the severity of HCC.

Potentiation of the immunotherapeutic effect of autologous dendritic cells by pretreating hepatocellular carcinoma with low-dose radiation.

PURPOSE: To determine whether exposing hepatocellular carcinoma (HCC) to low dose radiation increases the efficacy of dendritic cell-mediated immunotherapy for HCC. METHODS: Tumour specimens collected from 20 recruited patients with HCC were cultured in primary culture (half successfully) and then exposed to low-dose radiation (0.5 Gy). Immature DCs derived from peripheral blood monocytes of patients were pulsed with autologous HCC cell lysates and matured with a cytokine cocktail. Autologous tumour lysate-pulsed DCs (TLP-DCs) were used to stimulate mixed lymphocytes, which were then tested for inhibitory effect on the growth of HCC cells. Surface markers of immunogenicity on primary HCC cells, MHC, and Fas were investigated before and after low-dose irradiation. RESULTS: Exposing HCC cells to low-dose (0.5 Gy) radiation enhanced the immunotherapeutic effect of TLP-DC-stimulated lymphocytes. Growth inhibition increased from 50.6+/-7.5% without irradiation to 74.3+/-4.3% with radiation. The expression of MHC class ll and Fas was upregulated after irradiating HCC cells. CONCLUSION: Exposing tumour cells to a low dose of radiation can enhance the immunotherapeutic effect of the autologous tumor lysate-pulsed DC vaccine.