Rock, scissors, paper: How RNA structure informs function.

RNA can fold back on itself to adopt a wide range of structures. These range from relatively simple hairpins to intricate 3D folds and can be accompanied by regulatory interactions with both metabolites and macromolecules. The last 50 yr have witnessed elucidation of an astonishing array of RNA structures including transfer RNAs, ribozymes, riboswitches, the ribosome, the spliceosome, and most recently entire RNA structuromes. These advances in RNA structural biology have deepened insight into fundamental biological processes including gene editing, transcription, translation, and structure-based detection and response to temperature and other environmental signals. These discoveries reveal that RNA can be relatively static, like a rock; that it can have catalytic functions of cutting bonds, like scissors; and that it can adopt myriad functional shapes, like paper. We relate these extraordinary discoveries in the biology of RNA structure to the plant way of life. We trace plant-specific discovery of ribozymes and riboswitches, alternative splicing, organellar ribosomes, thermometers, whole-transcriptome structuromes and pan-structuromes, and conclude that plants have a special set of RNA structures that confer unique types of gene regulation. We finish with a consideration of future directions for the RNA structure-function field.

RNA multimerization as an organizing force for liquid-liquid phase separation.

RNA interactions are exceptionally strong and highly redundant. As such, nearly any two RNAs have the potential to interact with one another over relatively short stretches, especially at high RNA concentrations. This is especially true for pairs of RNAs that do not form strong self-structure. Such phenomena can drive liquid-liquid phase separation, either solely from RNA-RNA interactions in the presence of divalent or organic cations, or in concert with proteins. RNA interactions can drive multimerization of RNA strands via both base-pairing and tertiary interactions. In this article, we explore the tendency of RNA to form stable monomers, dimers, and higher order structures as a function of RNA length and sequence through a focus on the intrinsic thermodynamic, kinetic, and structural properties of RNA. The principles we discuss are independent of any specific type of biomolecular condensate, and thus widely applicable. We also speculate how external conditions experienced by living organisms can influence the formation of nonmembranous compartments, again focusing on the physical and structural properties of RNA. Plants, in particular, are subject to diverse abiotic stresses including extreme temperatures, drought, and salinity. These stresses and the cellular responses to them, including changes in the concentrations of small molecules such as polyamines, salts, and compatible solutes, have the potential to regulate condensate formation by melting or strengthening base-pairing. Reversible condensate formation, perhaps including regulation by circadian rhythms, could impact biological processes in plants, and other organisms.

Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume.

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

The revealing of a novel lipid transfer protein lineage in green algae.

BACKGROUND: Non-specific lipid transfer proteins (nsLTPs) are a group of small and basic proteins that can bind and transfer various lipid molecules to the apoplastic space. A typical nsLTP carries a conserved architecture termed eight-cysteine motif (8CM), a scaffold of loop-linked helices folding into a hydrophobic cavity for lipids binding. Encoded by a multigene family, nsLTPs are widely distributed in terrestrial plants from bryophytes to angiosperms with dozens of gene members in a single species. Although the nsLTPs in the most primitive plants such as Marchantia already reach 14 members and are divergent enough to form separate groups, so far none have been identified in any species of green algae. RESULTS: By using a refined searching strategy, we identified putative nsLTP genes in more than ten species of green algae as one or two genes per haploid genome but not in red and brown algae. The analyses show that the algal nsLTPs carry unique characteristics, including the extended 8CM spacing, larger molecular mass, lower pI value and multiple introns in a gene, which suggests that they could be a novel nsLTP lineage. Moreover, the results of further investigation on the two Chlamydomonas nsLTPs using transcript and protein assays demonstrated their late zygotic stage expression patterns and the canonical nsLTP properties were also verified, such as the fatty acids binding and proteinase resistance activities. CONCLUSIONS: In conclusion, a novel nsLTP lineage is identified in green algae, which carries some unique sequences and molecular features that are distinguishable from those in land plants. Combined with the results of further examinations of the Chlamydomonas nsLTPs in vitro, possible roles of the algal nsLTPs are also suggested. This study not only reveals the existence of the nsLTPs in green algae but also contributes to facilitating future studies on this enigmatic protein family.

Quick preparation of ABO-incompatible living donor liver transplantation for acute liver failure.

Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5 mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375 mg/m2 ) on post-operative day 1 to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60 years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure.

mRNA Localization in Plant Cells.

Localization of mRNAs at the subcellular level is an essential mechanism for specific protein targeting and local control of protein synthesis in both eukaryotes and bacteria. While mRNA localization is well documented in metazoans, somatic cells, and microorganisms, only a handful of well-defined mRNA localization examples have been reported in vascular plants and algae. This review summarizes the function and mechanism of mRNA localization and highlights recent studies of mRNA localization in vascular plants. While the emphasis focuses on storage protein mRNA localization in rice endosperm cells, information on targeting of RNAs to organelles (chloroplasts and mitochondria) and plasmodesmata is also discussed.

RNA-Binding Protein RBP-P Is Required for Glutelin and Prolamine mRNA Localization in Rice Endosperm Cells.

In developing rice (Oryza sativa) endosperm, mRNAs of the major storage proteins, glutelin and prolamine, are transported and anchored to distinct subdomains of the cortical endoplasmic reticulum. RNA binding protein RBP-P binds to both glutelin and prolamine mRNAs, suggesting a role in some aspect of their RNA metabolism. Here, we show that rice lines expressing mutant RBP-P mislocalize both glutelin and prolamine mRNAs. Different mutant RBP-P proteins exhibited varying degrees of reduced RNA binding and/or protein-protein interaction properties, which may account for the mislocalization of storage protein RNAs. In addition, partial loss of RBP-P function conferred a broad phenotypic variation ranging from dwarfism, chlorophyll deficiency, and sterility to late flowering and low spikelet fertility. Transcriptome analysis highlighted the essential role of RBP-P in regulating storage protein genes and several essential biological processes during grain development. Overall, our data demonstrate the significant roles of RBP-P in glutelin and prolamine mRNA localization and in the regulation of genes important for plant growth and development through its RNA binding activity and cooperative regulation with interacting proteins.

Improving outcomes of liver resection for hepatocellular carcinoma associated with portal vein tumor thrombosis over the evolving eras of treatment.

BACKGROUND: The outcomes and management of hepatocellular carcinoma (HCC) have undergone several evolutionary changes. This study aimed to analyze the outcomes of patients who had undergone liver resection for HCC with portal vein tumor thrombosis (PVTT) in terms of the evolving era of treatment. MATERIALS AND METHODS: A retrospective analysis of 157 patients who had undergone liver resection for HCC associated with PVTT was performed. The outcomes and prognostic factors related to different eras were further examined. RESULTS: Overall, 129 (82.1%) patients encountered HCC recurrence after liver resection, and the median time of recurrence was 4.1 months. Maximum tumor size ≥ 5 cm and PVTT in the main portal trunk were identified as the major prognostic factors influencing HCC recurrence after liver resection. Although the recurrence-free survival had no statistical difference between the two eras, the overall survival of patients in the second era was significantly better than that of the patients in the first era (p = 0.004). The 1-, 2-, and 3-year overall survival rates of patients in the second era were 60.0%, 45.7%, and 35.8%, respectively, with a median survival time of 19.6 months. CONCLUSION: The outcomes of HCC associated with PVTT remain unsatisfactory because of a high incidence of tumor recurrence even after curative resection. Although the management and outcomes of patients with HCC and PVTT have greatly improved over the years, surgical resection remains an option to achieve a potential cure of HCC in well-selected patients.

Re-programming of gene expression in the CS8 rice line over-expressing ADPglucose pyrophosphorylase induces a suppressor of starch biosynthesis.

The CS8 transgenic rice (Oryza sativa L.) lines expressing an up-regulated glgC gene produced higher levels of ADPglucose (ADPglc), the substrate for starch synthases. However, the increase in grain weight was much less than the increase in ADPglc levels suggesting one or more downstream rate-limiting steps. Endosperm starch levels were not further enhanced in double transgenic plants expressing both glgC and the maize brittle-1 gene, the latter responsible for transport of ADPglc into the amyloplast. These studies demonstrate that critical processes within the amyloplast stroma restrict maximum carbon flow into starch. RNA-seq analysis showed extensive re-programming of gene expression in the CS8 with 2073 genes up-regulated and 140 down-regulated. One conspicuous gene, up-regulated ~15-fold, coded for a biochemically uncharacterized starch binding domain-containing protein (SBDCP1) possessing a plastid transit peptide. Confocal microscopy and transmission electron microscopy analysis confirmed that SBDCP1 was located in the amyloplasts. Reciprocal immunoprecipitation and pull-down assays indicated an interaction between SBDCP1 and starch synthase IIIa (SSIIIa), which was down-regulated at the protein level in the CS8 line. Furthermore, binding by SBDCP1 inhibited SSIIIa starch polymerization activity in a non-competitive manner. Surprisingly, artificial microRNA gene suppression of SBDCP1 restored protein expression levels of SSIIIa in the CS8 line resulting in starch with lower amylose content and increased amylopectin chains with a higher degree of polymerization. Collectively, our results support the involvement of additional non-enzymatic factors such as SBDCP in starch biosynthesis.

Targeted Endoplasmic Reticulum Localization of Storage Protein mRNAs Requires the RNA-Binding Protein RBP-L.

The transport and targeting of glutelin and prolamine mRNAs to distinct subdomains of the cortical endoplasmic reticulum is a model for mRNA localization in plants. This process requires a number of RNA-binding proteins (RBPs) that recognize and bind to mRNA cis-localization (zipcode) elements to form messenger ribonucleoprotein complexes, which then transport the RNAs to their destination sites at the cortical endoplasmic reticulum. Here, we present evidence that the rice (Oryza sativa) RNA-binding protein, RBP-L, like its interacting RBP-P partner, specifically binds to glutelin and prolamine zipcode RNA sequences and is required for proper mRNA localization in rice endosperm cells. A transfer DNA insertion in the 3' untranslated region resulted in reduced expression of the RBP-L gene to 10% to 25% of that in the wild-type. Reduced amounts of RBP-L caused partial mislocalization of glutelin and prolamine RNAs and conferred other general growth defects, including dwarfism, late flowering, and smaller seeds. Transcriptome analysis showed that RBP-L knockdown greatly affected the expression of prolamine family genes and several classes of transcription factors. Collectively, these results indicate that RBP-L, like RBP-P, is a key RBP involved in mRNA localization in rice endosperm cells. Moreover, distinct from RBP-P, RBP-L exhibits additional regulatory roles in development, either directly through its binding to corresponding RNAs or indirectly through its effect on transcription factors.

Models to predict disease-free survival for hepatocellular carcinoma patients with surgical resections.

BACKGROUND AND OBJECTIVES: Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients. METHODS: Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated. RESULTS: Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P < .0001). In model 2, the patients were divided into five groups with 5-year DFS of 58.0%, 43.7%, 24.0%, 15.4%, and 0.0%, respectively (P < .0001). CONCLUSION: Based on nomogram models, DFS for the patients who had liver resection for HCC can be predicted before liver resection and re-assessed after liver resection.

Acute exacerbation of hepatitis B with hepatic failure during the first trimester of pregnancy: Delivery of a healthy term baby after liver transplantation.

The severe form of acute exacerbation of hepatitis B during pregnancy is a rare but life-threatening condition for both the mother and the fetus. A 32-year-old pregnant woman at 10 weeks of gestation was diagnosed with acute decompensated liver failure due to acute exacerbation of hepatitis B. The Model for End-stage Liver Disease score was up to 37. The patient was managed carefully with antiviral treatment, fluid resuscitation, correction of coagulopathy, close monitoring of hepatic function, and regular assessment of the fetus. She was transplanted with a deceased liver at 14 weeks and 1 day of gestation. With careful post-transplant care and avoidance of medication with risk of miscarriage and teratogenicity, a healthy baby was delivered at 39 weeks and 1 day of gestation. Herein, we report this critical condition of pregnancy that was complicated with liver failure due to acute exacerbation of hepatitis B, but had favorable outcomes for both the mother and the baby after liver transplantation.

The Role of RNA-Binding Protein OsTudor-SN in Post-Transcriptional Regulation of Seed Storage Proteins and Endosperm Development.

Tudor-SN is involved in a myriad of transcriptional and post-transcriptional processes due to its modular structure consisting of 4 tandem SN domains (4SN module) and C-terminal Tsn module consisting of Tudor-partial SN domains. We had previously demonstrated that OsTudor-SN is a key player for transporting storage protein mRNAs to specific ER subdomains in developing rice endosperm. Here, we provide genetic evidence that this multifunctional RBP is required for storage protein expression, seed development and protein body formation. The rice EM1084 line, possessing a nonsynonymous mutation in the 4SN module (SN3 domain), exhibited a strong reduction in grain weight and storage protein accumulation, while a mutation in the Tudor domain (47M) or the loss of the Tsn module (43M) had much smaller effects. Immunoelectron microscopic analysis showed the presence of a new protein body type containing glutelin and prolamine inclusions in EM1084, while 43M and 47M exhibited structurally modified prolamine and glutelin protein bodies. Transcriptome analysis indicates that OsTudor-SN also functions in regulating gene expression of transcriptional factors and genes involved in developmental processes and stress responses as well as for storage proteins. Normal protein body formation, grain weight and expression of many genes were partially restored in EM1084 transgenic line complemented with wild-type OsTudor-SN gene. Overall, our study showed that OsTudor-SN possesses multiple functional properties in rice storage protein expression and seed development and that the 4SN and Tsn modules have unique roles in these processes.

Low-dose anti-hepatitis B immunoglobulin regimen as prophylaxis for hepatitis B recurrence after liver transplantation.

BACKGROUND: Combination of anti-hepatitis B immunoglobulin (HBIg) and antiviral nucleotide/nucleoside is the most common regimen for prophylaxis against hepatitis B virus (HBV) recurrence. However, what the optimal regimen is for HBIg administration remains subject to debate. METHODS: Two hundred and thirty-two HBV patients who had liver transplantation were included in this study. According to the decline rate of HBIg, the patients were divided into quick (group Q, n = 95) and slow decline groups (group S, n = 137). Quick HBIg decline was defined as anti-HBs titer <200 IU/mL at postoperative month (POM) 1, when 24 000 IU of HBIg was given perioperatively. HBV recurrence was defined as reappearance of hepatitis B surface antigen (HBsAg). RESULTS: After a mean (range) follow-up of 42.2 (24.1-76.8) months, the HBV recurrence rate was 12.1% for all 232 patients. The median (interquartile) HBIg titer was 96.2 (41.0-158.0) IU in group Q patients, compared to 418.0 (298.8-692.8) IU in group S patients at POM 1 (P < .001). For the patients in group Q, 18 patients (18.9%) had HBV recurrence; this was higher than the 10 (7.3%) patients in group S (P = .013). Multivariate analysis showed that quick HBIg decline and hepatocellular carcinoma recurrence were the risk factors for HBV recurrence. CONCLUSION: Perioperative low-dose HBIg and antiviral nucleotide/nucleoside can effectively prevent HBV recurrence in patients with slow HBIg decline. For patients with quick HBIg decline, the idealized HBIg and antiviral agent regimen should be adjusted to establish an effective regimen as prophylaxis against HBV recurrence.

Multifunctional RNA Binding Protein OsTudor-SN in Storage Protein mRNA Transport and Localization.

The multifunctional RNA-binding protein Tudor-SN plays multiple roles in transcriptional and posttranscriptional processes due to its modular domain structure, consisting of four tandem Staphylococcus nuclease (SN)-like domains (4SN), followed by a carboxyl-terminal Tudor domain, followed by a fifth partial SN sequence (Tsn). In plants, it confers stress tolerance, is a component of stress granules and P-bodies, and may participate in stabilizing and localizing RNAs to specific subdomains of the cortical-endoplasmic reticulum in developing rice (Oryza sativa) endosperm. Here, we show that, in addition to the intact rice OsTudor-SN protein, the 4SN and Tsn modules exist as independent polypeptides, which collectively may coassemble to form a complex population of homodimer and heteroduplex species. The 4SN and Tsn modules exhibit different roles in RNA binding and as a protein scaffold for stress-associated proteins and RNA-binding proteins. Despite their distinct individual properties, mutations in both the 4SN and Tsn modules mislocalize storage protein mRNAs to the cortical endoplasmic reticulum. These results indicate that the two modular peptide regions of OsTudor-SN confer different cellular properties but cooperate in mRNA localization, a process linking its multiple functions in the nucleus and cytoplasm.

Selective sets of mRNAs localize to extracellular paramural bodies in a rice glup6 mutant.

The transport of rice glutelin storage proteins to the storage vacuoles requires the Rab5 GTPase and its related guanine nucleotide exchange factor (Rab5-GEF). Loss of function of these membrane vesicular trafficking factors results in the initial secretion of storage proteins and later their partial engulfment by the plasma membrane to form an extracellular paramural body (PMB), an aborted endosome complex. Here, we show that in the rice Rab5-GEF mutant glup6, glutelin RNAs are specifically mislocalized from their normal location on the cisternal endoplasmic reticulum (ER) to the protein body-ER, and are also apparently translocated to the PMBs. We substantiated the association of mRNAs with this aborted endosome complex by RNA-seq of PMBs purified by flow cytometry. Two PMB-associated groups of RNA were readily resolved: those that were specifically enriched in this aborted complex and those that were highly expressed in the cytoplasm. Examination of the PMB-enriched RNAs indicated that they were not a random sampling of the glup6 transcriptome but, instead, encompassed only a few functional mRNA classes. Although specific autophagy is also an alternative mechanism, our results support the view that RNA localization may co-opt membrane vesicular trafficking, and that many RNAs that share function or intracellular location are co-transported in developing rice seeds.

Clinical relevance of oncologic prognostic factors in the decision-making of pre-hepatectomy chemotherapy for colorectal cancer hepatic metastasis: the priority of hepatectomy.

BACKGROUND: Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved. METHODS: A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed. RESULTS: Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07-2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99-1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors. CONCLUSION: The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.

Magnetic Resonance Imaging of Cysts, Cystlike Lesions, and Their Mimickers Around the Knee Joint.

While interpreting routine magnetic resonance imaging (MRI) of the knee joint, a radiologist may encounter various cystic lesions such as ganglion, synovial, and meniscal cysts, among others. In some cases, MRI may demonstrate cystlike lesions around the knee due to fluid distention of normal bursa and recesses, the diagnosis of which should not be difficult if a radiologist is familiar with their characteristic location and MRI appearance. In addition, there are cyst mimickers such as hematomas, abscesses, vascular lesions, and neoplasms around knee joint that may pose a diagnostic challenge on routine MRI. Due to their atypical location and variable morphology, contrast administration is helpful as the enhancement pattern aids to differentiate them from cysts and cystlike lesions. This pictorial essay aims to classify cysts, cystlike lesions, and cyst mimickers in and around the knee joint based on their anatomic location and highlight their characteristic MRI features.

Down-regulation of metabolic proteins in hepatocellular carcinoma with portal vein thrombosis.

BACKGROUND: Hepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery. Portal vascular invasion is one of the major factors contributing to tumor recurrence and poor prognosis. However, why hepatocellular carcinoma is easy to grow into vessels is unclear. METHODS: Surgical specimens from seven hepatocellular carcinoma patients with portal vein thrombosis and seven patients without vascular invasion were utilized to analyze protein expression by proteomic technique. The proteins in the tumors were separated by 2-dimensional electrophoresis. Protein patterns in the gels were recorded as digitalized images. The differences of expression in hepatocellular carcinoma with or without portal vein thrombosis were identified by mass spectrometry. RESULTS: Clinically, the tumors with portal vein thrombosis were larger than those without portal vein thrombosis. The median survival time for the patients with portal vein thrombosis was much shorter [4 (ranged 2.5-47) vs. 53 (ranged 33-85) months, p = 0.002]. By analyzing the protein expression in cancer tissues with or without portal vein thrombosis, the differences of protein expression were mainly metabolic enzymes. Carbonic anhydrase I, betaine-homocysteine S-methyltransferase 1, fumarate hydratase, isovaleryl-CoA dehydrogenase, short-chain specific acyl-CoA dehydrogenase and arginase-1 were all down-regulated in the tumors with portal vein thrombosis. CONCLUSION: Metabolic enzymes and cytosol carbonic anhydrases were downregulated in hepatocellular carcinoma with portal vein thrombus. The deficiency of metabolic enzymes and cytosol carbonic anhydrases may alter cellular metabolisms and acid-base balance in hepatocellular carcinoma, which may facilitate to invade portal vein.