TACE combined Lenvatinib plus Camrelizumab versus TACE alone in efficacy and safety for unresectable hepatocellular carcinoma: a propensity score-matching study.

BACKGROUNDS: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . METHODS: A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. RESULTS: After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. CONCLUSION: TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients.

Large Changes in Fluorescent Color and Intensity of Symmetrically Substituted Arylmaleimides Caused by Subtle Structure Modifications.

Herein we report on four diarylmaleimides based on 3- or 2-substituted benzothiophene (M3S or M2S) and benzofuran (M3O or M2O), which show very different emission properties: aggregation-caused quenching (ACQ), aggregation-induced emission (AIE), and dual-state strong emission (DSE) in both solution and solid states. Their emission color in the solid state can be adjusted from green-yellow into red. M2O displays strong red solid-state emission at 630 nm with a quantum yield of 46.3 %. Single-crystal X-ray diffraction analysis confirms that their large distinction in solid-state emission originates from their different packing structures: hydrogen-bonded organic frameworks (HOFs) for M3S, a staggered structure for M3O, J-aggregation for M2S, and weak H-aggregation for M2O. HOF of M3S and weak H-aggregation of M2O make them produce inverse-type piezochromic fluorescence: blueshifted "turn-on" and redshifted "turn-off" emission, respectively. These results provide new insight in fluorescence manipulated by subtle structure modification.

Nomogram for predicting overall survival of metastatic pancreatic cancer patients based on HBV infection and inflammatory-nutritional biomarkers.

Purpose: To develop and validate a nomogram for predicting the overall survival of patients with metastatic pancreatic cancer. Methods: This retrospective study included 236 patients with metastatic pancreatic cancer treated at Guangxi Medical University Cancer Hospital between October 2013 and October 2022. Patients were grouped according to hepatitis B virus (HBV) infection status. Cox proportional hazard regression was used to identify the prognostic factors independently associated with overall survival. Results were used to build a nomogram, which was assessed through internal validation using bootstrap resampling. Results: Patients in the HBV-positive group (N = 37) showed significantly better overall survival than those in the HBV-negative group (N=199; P = 0.014). Overall survival was independently associated with the following factors: HBV infection status, sex, chemotherapy, metastatic sites, a combined index of hemoglobin, albumin, lymphocytes, and platelets, neutrophil-albumin ratio, as well as levels of CA125. The nomogram showed good predictive power, with an area under the curve of 0.808 for the time-dependent receiver operating characteristic. Calibration and decision curve analyses indicated good calibration and clinical usefulness of the nomogram for predicting the overall survival of patients with metastatic pancreatic cancer. Conclusion: A nomogram based on the HBV infection status and inflammatory nutritional markers may help predict the overall survival of patients with metastatic pancreatic cancer and guide personalized clinical treatment.

Microsurgical anatomy of the abducens nerve.

OBJECTIVE: To clarify the oriented classification, relationships, and variations of the abducens nerve and provide a detailed description of its microsurgical anatomic features. METHODS: A microsurgical anatomic dissection of the abducens nerve was performed in 100 specimens obtained from 50 adult cadaveric heads fixed in formalin and two adult cadaveric heads stained with hematoxylin and eosin for histological examination. Important neurovascular and structural relationships of the abducens nerve were observed. RESULTS: The abducens nerve was divided into five segments (cisternal, petroclival, internal carotid artery, fissural, and intraconal). It coursed in the petroclival venous confluence and there was a complex anatomic relationship. Two new types of abducens nerve variations were found. In one type, the duplicated nerve is split into two branches for a limited length in the cavernous sinus (CS). The other is a complex type, which has a complex course and pattern. This type of duplicated abducens nerve has a communicating branch in the cistern and numerous fasciculi in the CS. In addition, the two branches do not accompany each other for the entire course in the CS. CONCLUSION: The vulnerability of the abducens nerve results from diverse factors. The inferolateral trunk, which arises from the intracavernous segment of carotid artery (also called the artery of the inferior CS), is an important landmark for finding the abducens nerve and sympathetic nerve. Variations of the abducens nerve are not rare. Keeping variations of the nerve in mind is important during skull base operations and transvenous endovascular interventions. Understanding the relationship of the abducens nerve with adjacent structures will help us in preparing for safe surgery.

Case Report: A Case of Locally Advanced Pancreatic Cancer Which Achieved Progression Free for Over 12 Months by Subsequent Therapy with Anlotinib Hydrochloride Plus Tegafur-Gimeracil-Oteracil Potassium (TS-1).

Titled the "most destructive of all cancers", pancreatic cancer is a malignant tumor with a very poor prognosis and has a poor response to systemic therapy. At present, several studies have shown that tegafur-gimeracil-oteracil potassium (hereinafter referred to as TS-1) is no less superior to gemcitabine in the treatment of advanced pancreatic cancer. In addition, a number of current clinical studies have shown that targeted therapy combined with chemotherapy reflects therapeutic advantages in pancreatic cancer. Moreover, in vitro and in vivo experiments have also demonstrated that anlotinib can curb the proliferation of pancreatic cancer cells and induce their apoptosis. Here, we report for the first time that a patient with locally advanced pancreatic cancer achieved good efficacy after switching to TS-1 chemotherapy combined with anlotinib targeted therapy. Previously, the disease of the patient still rapidly progressed without control following the first switch to abraxane combined with gemcitabine chemotherapy (AG regimen) due to the progression after chemo-radiotherapy. In this case, the patient achieved progression-free survival (PFS) of over 14 months via the treatment with anlotinib targeted therapy combined with TS-1 chemotherapy and secondary radiotherapy (prior to secondary radiotherapy, the patient achieved a PFS of nearly 12 months via the treatment with oral anlotinib combined with TS-1). Up to now, the progress of the disease is ceased. The oral administration of targeted therapy and chemotherapy are still in progress and the general condition of the patient is good. This suggests that patients with advanced pancreatic cancer may benefit from treatment with the anlotinib targeted therapy combined with TS-1 chemotherapy.

Holliday Cross-Recognition Protein HJURP: Association With the Tumor Microenvironment in Hepatocellular Carcinoma and With Patient Prognosis.

Background: Hepatocellular carcinoma is the most common type of primary liver cancer, and it is associated with poor prognosis. It often fails to respond to immunotherapy, highlighting the need to identify genes that are associated with the tumor microenvironment and may be good therapeutic targets. We and others have shown that the Holliday cross-recognition protein HJURP can promote the proliferation, migration, and invasion by hepatocellular carcinoma cells, and that HJURP overexpression is associated with poor survival. Here we explored the potential relationship between HJURP and the tumor microenvironment in hepatocellular carcinoma. Methods: We used the Immuno-Oncology-Biological-Research (IOBR) software package to analyze the potential roles of HJURP in the tumor microenvironment. Using single-cell RNA sequencing data, we identified the cell clusters expressing abundant HJURP, then linked some of these clusters to certain bioprocesses using Gene Set Enrichment Analysis (GSEA). We validated the differential expression of HJURP in tumor-infiltrating CD8+ T cells, sorted by flow cytometry into populations based on the expression level of PD-1. We used weighted gene co-expression network analysis (WGCNA) to identify immunity-related genes whose expression strongly correlated with that of HJURP. The function of these genes was validated based on enrichment in Gene Ontology (GO) terms, and they were used to establish a prognosis prediction model. Results: IOBR analysis suggested that HJURP is significantly related to the immunosuppressive tumor microenvironment and was significantly related to T cells, dendritic cells, and B cells. Based on single-cell RNA sequencing, HJURP was strongly expressed in T cells, erythrocytes, and B cells from normal liver tissues, as well as in CD8+ T cells, dendritic cells, and one cluster of hepatocytes in hepatocellular carcinoma tissues. Malignant hepatocytes strongly expressing HJURP were associated with the downregulation of immune bioprocesses. HJURP expression was significantly higher in CD8+ T cells strongly expressing PD-1 than in those expressing no or intermediate levels of PD1. WGCNA identified two module eigengenes (comprising 397 and 84 genes) related to the tumor microenvironment. We identified 24 hub genes and confirmed that they were related to immune regulation. A prognostic risk score model based on expression of HJURP, PPT1, PML, and CLEC7A showed moderate ability to predict survival. Conclusion: HJURP is associated with tumor-infiltrating immune cells, immune checkpoints, and immune suppression in hepatocellular carcinoma. HJURP-related genes involved in immune responses may be useful for predicting patient prognosis.

Retinoic acid and dexamethasone induce differentiation and maturation of somatotroph cells at different stages in vitro.

The purpose of this study was to investigate the role of retinoic acid (RA) and/or dexamethasone and growth hormone releasing hormone (GHRH) in the induction of somatotroph cell differentiation. Immunohistochemistry, radioimmunoassay, 3-(4,5-dimethylthiazol -1,2-y1)-2,5-diphenyltetrazolium bromide assay, and immune electron microscopy were employed to determine the effect of incubation with these constituents on the differentiation into somatotrophs of cells isolated from the rat embryonic pituitary gland. RA administration increased the proportion of growth hormone (GH) positive somatotroph cells and GH secretion in embryonic pituitary cells (P<0.01). After 4 days of incubation with RA, additional administration of dexamethasone further increased the proportion of somatotroph cells and GH secretion (P<0.01), and increased the number of secretory granules in the somatotroph cells. Addition of GHRH alone had no such effect (P>0.05). However, addition of GHRH to treatment with RA plus dexamethasone significantly increased both the proportion of somatotroph cells and the secretion of GH compared to treatment with RA or dexamethasone alone or RA plus dexamethasone (P<0.01). RA promoted the early differentiation of somatotroph cells, dexamethasone promoted the differentiation and maturation of somatotroph cells and in addition, RA, dexamethasone and GHRH together exerted synergistic effects that markedly promoted somatotroph cell differentiation, maturation and GH secretion.

Microsurgical anatomy of the ocular motor nerves.

This study was designed to provide anatomic data to help surgeons avoid damage to the ocular motor nerves during intraorbital operations. The microsurgical anatomy of the ocular motor nerves was studied in 50 adult cadaveric heads (100 orbits). Dissections were performed with a microscope. The nerves were exposed and the neural and muscular relationships of each portion of the nerve were examined and measured. The superior division of the oculomotor nerve coursed between the optic nerve and the superior rectus muscle after it left the annular tendon, and its branches entered into the superior rectus muscle and levator muscle. A mean of five fibers (range 3-7) innervated the superior rectus muscle, and a mean of one fiber (range 1-2) followed a medial direction (84%) or went straight through the superior rectus muscle (16%). The inferior division of the oculomotor nerve branched into the medial rectus, inferior rectus and inferior oblique muscles. The trochlear nerve ended on the orbital side of the posterior one-third of the superior oblique muscle in 76 specimens. The abducens nerve ended on the posterior one-third of the lateral rectus muscle in 86 specimens. If the belly of the lateral rectus muscle was divided into three superior-inferior parts, the nerve commonly entered into the middle one-third in 74 specimens. Based on the observed data, microanatomical relationships of the orbital contents were revised.

Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway.

PURPOSE: Oxaliplatin (OXA)-induced liver injury is one of the main limiting factors affecting the efficacy of OXA-based chemotherapy in patients with colorectal liver metastases. In addition, oxidative stress is an important pathophysiological mechanism of OXA-induced liver injury. Therefore, dietary antioxidants may decrease or prevent hepatic toxicity in vivo and be beneficial to OXA-based chemotherapy. METHODS: An experimental OXA-induced liver injury animal model was established, and the protective effects of curcumin (CUR) against OXA-induced liver injury were investigated. ELISA was used to determine the levels of MDA, SOD, CAT, and GSH in liver tissue. The effect of CUR treatment on the expression of cytokines and the Nrf2 pathway was determined by real-time PCR and Western blotting. RESULTS: CUR treatment alleviated OXA-induced hepatic pathological damage and splenomegaly. The protective effect of CUR was demonstrated to be correlated with inhibition of oxidative stress, inflammation, and the coagulation system. Furthermore, Western blotting revealed that CUR treatment reverses the suppression of Nrf2 nuclear translocation and increases the expression of HO-1 and NOQ1 in mice with OXA-induced liver injury. Moreover, the Nrf2 activation and hepatoprotective effect of CUR were abolished by brusatol. CONCLUSION: Curcumin attenuates oxaliplatin-induced liver injury and oxidative stress by activating the Nrf2 pathway, which suggests that CUR may be potentially used in the prevention and treatment of OXA-induced liver injury.

[Effect of total knee arthroplasty under computer navigation on intraoperative blood loss and joint function recovery].

OBJECTIVE: To analyze the effect of computer navigation assisted total knee arthroplasty on intraoperative hemorrhage and postoperative joint function recovery in patients with knee osteoarthritis. METHODS: From February 2015 to December 2017, 65 patients with knee osteoarthritis treated by traditional total knee arthroplasty were retrospectively analyzed as the control group and 65 patients with knee osteoarthritis treated by total knee arthroplasty under computer navigation as the experimental group. Before operation, all patients showed red swelling pain of knee, pain of going up and down stairs, and pain and discomfort of waist when sitting up and standing up. All patients were treated with total knee arthroplasty. The control group was treated with traditional total knee arthroplasty, and the experimental group was treated with total knee arthroplasty under the computer navigation system. The operation related conditions of the two groups were recorded and compared including the operation time and hospitalization time; the changes of hemoglobin and hematocrit of the two groups were detected and compared before and 5 days after the operation; the blood loss of the two groups and the induced flow at each time point calculated and compared after the operation, and the perioperative allogeneic blood transfusion rate and average blood transfusion volume of the patients were recorded; The joint function scale (KSS) was used to evaluate the recovery of knee joint function before the operation, 6 and 18 months after the operation respectively and to record the incidence of postoperative infection, lower extremity venous thrombosis and other complications. RESULTS: All the patients were successfully operated and the prognosis of the wound was good. All the patients were followed up for an average of 18 months. The operation time of the experimental group was longer than that of the control group, and the hospitalization time was shorter than that of the control group (P <0.05) ; the KSS score of the two groups at each time point after operation was higher than that before operation, but the increasing range of the test group was higher than that of the control group (P<0.05) ; there was no significant difference between the two groups in the incidence of complications (P>0.05) . CONCLUSION: Under the guidance of computer navigation, total knee arthroplasty can prolong the operation time compared with single total knee arthroplasty, but it is more conducive to reduce perioperative blood loss, reduce the rate of postoperative allogeneic blood transfusion, ideal recovery of joint function, less complications, safety and reliability.

[Differentiation of hepatic oval cell into mature hepatocyte induced by hepatic stellate cells].

OBJECTIVE: To investigate the role of hepatic stellate cells in the differentiation of hepatic oval cells into adult hepatocyte. METHODS: The oval cell were cocultured with primary hepatic stellate cells (HSC) in the same well (M-coculture) or separately cultured with HSC by millIcell (S-coculture). Oval cells were cultured alone as control; the expression of adult hepatocyte marker HNF-4alpha, albumin, and oval cell marker AFP, CK-19 in each group were detected by real-time PCR and western-blot. Phenotype changes were observed by transmission electron microscope (TEM); PAS staining was used to detect the quantity of glycogen granule in oval cell. Albumin level in supernatant was detected using ELISA kit. RESULT: (1) The relative level of HNF-4alpha and albumin mRNA expression compared with pre-coculture: M-coculture: HNF-4a: 1.9+/-0.2, 10.7+/-1.2, 12.0+/-1.3; albumin: 5.7+/-1.6, 110.7+/-13.7, 173.6+/-22.3. S-coculture: 1.4+/-0.1, 3.2+/-0.6, 8.9+/-1.4 times; albumin: 2.9+/-1.4, 22.3+/-8.5, 96.3+/-16.3. The relative level of HNF-4a and albumin mRNA expression in coculture group (M- and S-coculture) were higher than control group (LSD-t: 32.98, 10.08, 13.38, 7.96; P less than 0.01); and a higher level of HNF-4a and albumin was found in M-coculture group compared to S-coculture group (LSD-t: 32.98, 25.65; P less than 0.01). The relative level of AFP and CK-19 mRNA expression compared with pre-coculture: M-coculture: 1.1+/-0.2, 0.2+/-0.0, 0.0+/-0.0; S-coculture group: AFP: 1.0+/-0.2, 0.2+/-0.1, 0.1+/-0.0; CK-19: 0.6+/-0.1, 0.1+/-0.0, 0.0+/-0.0; control group: AFP: 1.0+/-0.1, 1.0+/-0.1, 1.1+/-0.1, CK-19: 1.0+/-0.1, 1.1+/-0.1, 1.0+/-0.1. The relative level of AFP and CK-19 mRNA expression in coculture group (M- and S-coculture) were lower than that in control group (LSD-t: 37.99, 34.50, 13.59, 22.46; P less than 0.01). (2) The albumin secretion was detected in M-coculture: 14 day: (15.30+/-0.09) ng/ml, 21: (20.98+/-0.12) ng/ml; S-coculture: 14 day: (11.41+/-0.13) ng/ml, 21 day:(15.12+/-0.17) ng/ml. (3) It showed more organelles such as endoplasmic reticulum, mitochondrion and Golgi apparatus in oval cells cocultured with HSC. And cholangiole-like structure appeared between oval cells cocultured with HSC. (4) PAS staining showed glycogen granules could be observed in coculture groups. CONCLUSION: HSC can induce differentiation of oval cell into mature hepatocyte.

Oxaliplatin aggravates hepatic oxidative stress, inflammation and fibrosis in a non­alcoholic fatty liver disease mouse model.

Oxaliplatin (OXA)­based chemotherapy is widely used in the treatment of gastrointestinal tumors; however, it is associated with chemotherapy­associated liver injury. Whether OXA induces liver injury and aggravates the already existing hepatic oxidative stress, inflammation and fibrosis in non­alcoholic fatty liver disease (NAFLD), and whether these effects can be alleviated by reduced glutathione (GSH) treatment, remains unclear. In the present study, OXA induced acute liver injury in NAFLD mice. Moreover, OXA increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased the levels of superoxide dismutase and GSH peroxidase in the livers of NAFLD mice. OXA also induced the upregulation of hepatic inflammatory cytokines, such as tumor necrosis factor (TNF)­α, interferon (IFN)­Î³ and interleukin (IL)­17, in NAFLD mice. Furthermore, collagen fiber deposition in liver tissues was increased and the expression of transforming growth factor (TGF)­ß, α­smooth muscle actin (SMA) and tissue inhibitor of metallopeptidase (TIMP)­1 was upregulated in the livers of OXA­treated NAFLD mice. Treatment with exogenous GSH alleviated OXA­induced acute liver injury in NAFLD mice, and significantly reduced the levels of ROS, MDA and TNF­α. However, GSH treatment did not inhibit collagen fiber deposition, although it reduced the levels of IFN­Î³, IL­17, TGF­ß, α­SMA and TIMP­1 in the livers of OXA­treated NAFLD mice. In conclusion, OXA chemotherapy may induce acute liver injury and aggravate the existing hepatic oxidative stress, inflammation and fibrosis in NAFLD. Treatment of NAFLD mice with exogenous GSH alleviated OXA­induced liver injury, possibly by ameliorating OXA­aggravated hepatic oxidative stress and inflammation; it did not, however, attenuate OXA­aggravated liver fibrosis.

The hepatoprotective role of reduced glutathione and its underlying mechanism in oxaliplatin-induced acute liver injury.

Currently, the underlying mechanism of oxaliplatin (OXA) induced live injury is unclear. In addition, there is no standard clinical treatment for OXA-induced acute liver injury (ALI). In this study, we established an animal model of OXA-induced ALI, and studied the role of oxidative stress in OXA-induced ALI and the impacts of reduced glutathione (GSH) treatment on OXA-induced ALI. To establish an OXA-induced ALI model, KM mice received intraperitoneal injection of OXA (8 mg/kg) for 4 days. Serum alanine aminotransferase (ALT), aspartate aminotransferase levels (AST), hepatic pathology and oxidative stress indicators in liver tissues were analyzed. To study the impact of GSH treatment on OXA-induced ALI, mice were treated with GSH (400 mg/kg, i.p). In this ALI mouse model, ALT and AST levels were significantly increased (P<0.01). Liver pathological examination revealed varying degrees of liver cell turbidity and degeneration, even balloon-like changes and focal necrosis, and sinusoidal hemorrhage in some cells. Compared with control group, the malondialdehyde (MDA) and GSH levels were significantly increased in OXA-treated group (P<0.01), while the superoxide dismutase SOD and GSH-peroxidase levels were decreased after OXA withdrawal (P<0.01). When GSH was used to treat OXA-induced ALI mice, the pathological injury of liver tissues was alleviated, and serum ALT and AST were significantly decreased. In addition, GSH treatment could reduce the OXA-induced increase of MDA level (P<0.05) in liver tissues, but had no impact on SOD level (P>0.05). We have successfully established an OXA-induced ALI model. Using this model, we discover that oxidative stress plays an important role in OXA-induced ALI. GSH-based hepatoprotective therapy can partially inhibit oxidative stress and alleviate OXA-induced ALI.

JNK inhibitor SP600125 enhances TGF-ß-induced apoptosis of RBE human cholangiocarcinoma cells in a Smad-dependent manner.

Transforming growth factor ß (TGF-ß) signaling is pivotal for the progression of specific types of tumors at certain stages. However, the mechanism by which TGF-ß is regulated by other factors remains unclear. In this study, the involvement of SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), in TGF-ß-induced apoptosis of the RBE human cholangiocarcinoma cell line was investigated. Exogenous TGF-ß1 activated Smad and non­Smad signaling pathways, including the JNK pathway in RBE cells, and induced apoptosis, which was inhibited by knockdown of Smad4 expression. SP600125 increased the TGF-ß1­induced phosphorylation of Smad2 and Smad3, which enhanced the TGF-ß1­induced transcriptional response and apoptosis in RBE cells. The effect of SP600125 on the transcriptional response and apoptosis was reduced by knockdown of Smad4 expression. In addition, TGF-ß1­induced apoptosis was abrogated using the pan-caspase inhibitor Z­VAD-fmk. SP600125 promoted the TGF-ß1­induced caspase cleavage, while knockdown of Smad4 expression counteracted this effect. These results indicate that SP600125 enhances TGF-ß-induced apoptosis of RBE cells through a Smad­dependent pathway that involves Smad­dependent caspase activation. SP600125 is hypothesized to be an ideal therapeutic candidate for treating human cholangiocarcinoma.

Targeting the ERK pathway reduces liver metastasis of Smad4-inactivated colorectal cancer.

Transforming growth factor ß (TGF-ß)/Smad signaling is involved in colorectal carcinoma (CRC) development and progression. The frequent loss of SMAD4 is associated with liver metastasis and poor prognosis of CRC, but the underlying mechanism remains elusive. This study aimed to elucidate the role of Smad-independent TGF-ß signaling in CRC metastasis. Immunohistochemistry showed that Smad4 level was negatively correlated with TNM stage and phospho-ERK level in human CRCs and liver metastasis samples. Knockdown of Smad4 in CT26 and HCT116 cells activated ERK pathway, altered the expression of MMP2 and COX-2, promoted cell motility, migration, and invasion in vitro, enhanced metastasis, and shortened the survival of metastatic tumor-bearing mice. MEK inhibitor U0126 and GSK1120212 inhibited the motility, migration, and invasion of Smad4 knockdown cells, inhibited metastasis, and prolonged the survival of metastatic tumor-bearing mice. Furthermore, MEK inhibitor could reverse the changes of phospho-ERK, MMP2, and COX-2 levels. In conclusion, our results indicate that ERK pathway plays a key oncogenic role in CRC with SMAD4 inactivation mutations, and implicate ERK as a potential therapeutic target for CRC liver metastasis.

A rare case of cavernous lymphangioma in the epidural space of the cervicothoracic spine.

STUDY DESIGN: A case report. OBJECTIVES: To report and discuss a case of lymphangioma in the epidural space of the cervicothoracic spine. SUMMARY OF BACKGROUND DATA: Lymphangioma of the soft tissue is not uncommon, but lymphangiomas presenting as a spinal soft tissue tumor in the epidural space are extremely rare. METHODS: A 61-year-old woman with pain and numbness in the left arm. Magnetic resonance imaging demonstrated a half ring-shaped soft tissue mass in the left epidural space from the C6 to T1 level. The patient underwent osteoplastic laminectomy from C6 to T1. Histopathologic diagnosis of the resected tumor was cavernous lymphangioma. RESULTS: One year after the operation, the patient reported mild pain in left upper limb, but there was no evidence of local recurrence on magnetic resonance imaging. CONCLUSION: To the authors' knowledge, this is an extremely rare reported case of lymphangioma presenting as a spinal soft tissue tumor in the cervicothoracic epidural space. Further observation is recommended because of the possibility of local recurrence.