Lack Of Encapsulation Research Articles

Establishment of a hepatocellular carcinoma patient-derived xenograft platform and its application in biomarker identification.

Using a method optimized in hepatocellular carcinoma (HCC), we established patient-derived xenograft (PDX) models with an increased take rate (42.2%) and demonstrated that FBS +10% dimethyl sulfoxide exhibited the highest tumor take rate efficacy. Among 254 HCC patients, 103 stably transplantable xenograft lines that could be serially passaged, cryopreserved and revived were established. These lines maintained the diversity of HCC and the essential features of the original specimens at the histological, transcriptome, proteomic and genomic levels. Tumor engraftment was associated with lack of encapsulation, poor tumor differentiation, large size and overexpression of cancer stem cell biomarkers, and was an independent predictor for overall survival and tumor recurrence after resection. To confirm the preclinical value of the PDX model in HCC treatment, several antitumor agents were tested in 16 selected PDX models. The results revealed a high degree of pharmacologic heterogeneity in the cohort, as well as heterogeneity to different agents in the same individual. The sorafenib responses observed between HCC patients and the corresponding PDXs were also consistent. After molecular characterization of the PDX models, we explored the predictive markers for sorafenib response and found that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) might play an important role in sorafenib resistance and sorafenib response is impaired in patients with MAP3K1 downexpression. Our results indicated that PDX models could accurately reproduce patient tumors biology and could aid in the discovery of new treatments to advance in precision medicine.

Comparison of early and delayed EUS-guided drainage of pancreatic fluid collection.

Background and study aims While endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collection (PFC) is recommended to be performed ≥ 4 weeks after onset of acute pancreatitis (AP), early (< 4 weeks) interventions are needed in some symptomatic cases. Despite feasibility of early percutaneous drainage, there have been few studies about early EUS-guided drainage of PFC. Patients and methods Consecutive patients who received EUS-guided drainage (EUS-PCD) of infected or symptomatic PFC at the University of Tokyo were retrospectively studied. Contraindications for EUS-PCD are lack of encapsulation or adhesion to the gastrointestinal tract. Safety and effectiveness of early vs delayed (≥ 4 weeks) EUS-PCD were compared. Results A total of 35 patients underwent EUS-PCD (12 early and 23 delayed) using 19 large-bore fully-covered metallic stent and 16 plastic stents. The median diameter of PFC was 110 mm (40 – 180) and 122 mm (17 – 250) in the early and delayed drainage groups, respectively. Median time from onset of AP to drainage was 23 and 85 days for early and delayed drainage, respectively. The technical success rate of EUS-guided drainage was 100 %. Endoscopic necrosectomy was performed in six early and 16 cases of delayed drainage. The adverse event rate was 25 % (3 bleeding) and 13 % (2 perforations and 1 CO 2 retention) in the early and delayed drainage groups, respectively. Two patients died (1 early and 1 delayed) due to multiorgan failure. Conclusion Endoscopic drainage and subsequent necrosectomy of symptomatic PFC within 4 weeks after onset of acute pancreatitis was feasible, given that the collection was encapsulated and attached to the gastrointestinal tract.

MUC15 Inhibits Dimerization of EGFR and PI3K–AKT Signaling and Is Associated With Aggressive Hepatocellular Carcinomas in Patients

Aberrant expression of MUC15 correlates with development of colorectal adenocarcinoma, and MUC15 has been reported to prevent trophoblast invasion of human placenta. However, little is known about the role of MUC15 in pathogenesis of hepatocellular carcinoma (HCC). We analyzed HCC samples and matched nontumor liver tissues (controls) collected from 313 patients who underwent hepatectomy in Shanghai, China, from January 2006 through September 2009. Levels of messenger RNAs and proteins were determined by immunohistochemical, quantitative reverse transcription polymerase chain reaction, and immunoblot analyses. Statistical analyses were used to associate levels of MUC15 with tumor features and patient outcomes. Levels of MUC15 messenger RNA and protein were reduced in a greater percentage of HCC samples than control tissues. Tumors with reduced levels of MUC15 were more likely to have aggressive characteristics (eg, high levels of α-fetoprotein, vascular invasion, lack of encapsulation, and poor differentiation) than those with low levels. Patients whose tumors had reduced levels of MUC15 had shorter overall survival times (24 months vs 46 months for patients with tumors with high levels of MUC15) and time to disease recurrence. Stable expression of MUC15 in HCC cell lines (SMMC-7721 and HCC-LM3) reduced their proliferation and invasive features in vitro, and ability to form metastatic tumors in mice. MUC15 reduced transcription of the matrix metalloproteinases 2 and 7 increased expression of tissue inhibitor of metalloproteinase-2, which required phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Physical interaction between MUC15 and epidermal growth factor receptor led to its relocation and degradation within early endosomes and was required for inactivation of phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Reduced levels of MUC15 in HCCs are associated with shorter survival times of patients and reduced time to disease recurrence. Expression of MUC15 in HCC cells reduces their aggressive behavior in vitro and in mice by inducing dimerization of epidermal growth factor receptor and decreasing phosphoinositide 3-kinase signaling via v-akt murine thymoma viral oncogene homolog.

PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection

Phosphatidylethanolamine-binding protein 1 (PEBP1, also RKIP) plays a pivotal role in cancer by regulating multiple cellular signaling processes and suppressing metastasis in animal models. We examined whether PEBP1 expression in hepatocellular carcinoma (HCC) correlated with the risk of recurrence and survival after resection. A randomly selected cohort of 240 Chinese HCC patients, predominantly hepatitis B related, formed the basis of the study. PEBP1 expression levels were evaluated by immunohistochemistry and real-time reverse-transcriptase PCR. Survival analysis was performed by univariate and multivariate analyses. The results were further validated in an independent series of 403 patients. The relevance of PEBP1 to phospho-ERK was determined by Western blot analysis on clinical samples and hepatoma cell lines. PEBP1, prevalently down-regulated in HCC, was significantly associated with tumor invasive characteristics (such as vascular invasion, lack of encapsulation, poor differentiation and large size). Both PEBP1 protein and mRNA levels were independent predictors for tumor recurrence (hazard ratio (HR) = 1.877, p=0.001; HR = 2.633, p = 0.001; respectively), and patient survival (HR = 1.796, p = 0.004; HR = 1.730, p = 0.044; respectively). The prognostic value of PEBP1 was then confirmed in the validation cohort. In addition, Western blot suggested that loss of PEBP1 led to hyperactivity of MAPK signaling. Down-regulation of PEBP1 in HCC indicated aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify the patients at high risk of post-operative recurrence.

Macrophage-mediated Bystander Effect Triggered by Tumor Cell Apoptosis

Restoration of apoptosis is an important therapeutic strategy for cancer, but bystander effects may be crucial to treatment success. We examined the involvement of bystander effects in the outcome of pro-apoptotic treatments and investigated the role of macrophages. Using a murine N202 breast cancer chamber model and intravital microscopy, we observed bystander apoptosis in vivo in mixed spheroids consisting of bystander N202 cells plus modified N202 cells overexpressing the p14ARF N-terminal region, which promotes p53-mediated apoptosis. The effect was not observed in cocultures in vitro, and could not be transferred through conditioned medium from modified N202 cells. However, if macrophages were also included in the N202 co-cultures, bystander apoptosis was restored, and correlated with elevated surface expression of phosphatidyl serine, a macrophage recognition molecule, on the modified N202 cells. Bystander killing was not observed in cocultures of N202 cells plus macrophages plus cisplatin-treated or 5-fluorouracil-treated N202 cells, where apoptosis induction in the target cell population was inefficient, suggesting that specific activation of macrophages by apoptotic tumor cells was required. The results suggest that pro-apoptotic therapies benefit both from the intrinsic vulnerability of cancer cells to apoptosis and from an innate immune response that amplifies the therapeutic effect.

Enfermedad quística renal unilateral localizada

Unilateral and localized cystic disease of the kidney, is characterized by the substitution of either all or a portion of one of the kidneys, by no encapsulated, multiple simple cysts. We present a case - to our knowledge the first in the Spanish bibliography -, of this rare benign condition that needs to be recognized to be differentiated from more transcendent ones. Contrary to autosomal dominant polycystic kidney disease, it is unilateral, it is not familiar, and it is neither progressive nor associated with renal insufficiency or with cysts in other abdominal organs. Lack of encapsulation allows, in general, to distinguish it from multilocular cystic nephroma and cystic renal carcinoma.

Neurilemmomas of the paranasal sinuses

Within the head and neck region, neurilemmomas are rarely found in the nasal cavity or paranasal sinuses. A 70-year-old man presented with complaints of left-sided epiphora, rhinorrhea, epistaxis, and transient diplopia. Nasal endoscopy showed a large necrotic mass filling the left middle meatus. A computed tomography scan showed a large left ethmoid mass, with erosion of the medial wall of the orbit and the anterior cranial base. Multiple biopsies were nondiagnostic. Complete excision of the tumor was performed with endoscopic techniques. Small dural defects were repaired with a middle turbinate mucosal flap. Postoperatively, the patient was treated with nasal packing and a lumbar spinal drain. Final pathology showed a benign neurilemmoma. There has been no evidence of recurrence or cerebrospinal fluid leakage in follow-up. A review of the literature shows a similar presentation of patients with neurilemmomas of the paranasal sinuses. Bony destruction and intracranial extension is viewed. Lack of encapsulation and locally destructive growth in an otherwise histologically typical neurilemmoma should not suggest malignant potential. Many benign tumors of the paranasal sinuses with bone destruction may be removed by using endoscopic techniques. (Am J Otolaryngol 2001;22:215-218. Copyright © 2001 by W.B. Saunders Company)

Typechecking and modules for multi-methods

Two major obstacles hindering the wider acceptance of multi-methods are concerns over the lack of encapsulation and modularity and the absence of static typechecking in existing multi-method-based languages. This paper addresses both of these problems. We present a polynomial-time static typechecking algorithm that checks the conformance, completeness, and consistency of a group of method implementations with respect to declared message signatures. This algorithm improves on previous algorithms by handling separate type and inheritance hierarchies, abstract classes, and graph-based method lookup semantics. We also present a module system that enables independently-developed code to be fully encapsulated and statically typechecked on a per-module basis. To guarantee that potential conflicts between independently-developed modules have been resolved, a simple well-formedness condition on the modules comprising a program is checked at link-time. The typechecking algorithm and module system are applicable to a range of multi-method-based languages, but the paper uses the Cecil language as a concrete example of how they can be applied.

Lipomatous Hamartoma of the Orbit

Proliferations of mature adipose tissue, while common in retroperitoneal and subcutaneous sites, rarely occur in the orbit. We describe the clinical, radiographic, and histopathologic findings of a nonencapsulated lipomatous tissue overgrowth of the right orbit in a 35-year-old man. The mass had caused proptosis since childhood and was apparently present since birth. Due to the age at onset, the histologic similarity to normal orbital fat, and the lack of encapsulation or choristomatous elements, we propose the term lipomatous hamartoma for this entity.

High resolution B-scan ultrasonography of the orbit. II. Hemangiomas of the orbit.

Unilateral exophthalmos is often caused by lymphomas of the orbit. B-scan ultrasonographic examination demonstrates certain characteristic features of orbital lymphomas, facilitating their clinical diagnosis. These ultrasonic features include an irregular contour, a lobulated configuration, acoustic homogeneity, and definite acoustic solidity. The ultrasonic characteristics of orbital lymphomas correlate well with the pathologic characteristics of these tumors. Lack of encapsulation and diffuse spread in the orbit are typical of lymphomas and result in the irregular contour and lobulated configuration found on ultrasonic examination. Lymphomas are homogeneous, monotonously cellular tumors and are acoustically homogeneous. These tumors are solid masses and appear solid on ultrasonic examination.

Intraoral (submucosal) pseudosarcomatous nodular fasciitis: Report of a case

This report on pseudosarcomatous fasciitis reviews the historical background, histopathology, and clinical characteristics of this lesion. Because of its histologic appearance, it may be misdiagnosed as fibrosarcoma. The apparent infiltration of adjoining muscle by lesional tissue, the lack of encapsulation, the plump fibroblastic component, and the rapid growth of this lesion are probably responsible for the erroneous diagnosis rendered in the past. Careful serial study of the pathologic material will reveal “inflammatory stigmata” and should lead to the proper diagnosis and treatment of the patient.

Salivary gland adenomas of the palate.

A histological survey of 383 tumours primary in the palate revealed a salivary gland tumour in 170 cases; 95 benign and 75 malignant. The benign tumours were all adenomas, 61 of pleomorphic and 34 of monomorphic type. Three of the 75 malignant cases were denoted as carcinomas in pleomorphic adenoma. The incidence of monomorphic adenomas is higher in the palate than in the parotid and subman-dibular glands. Lack of encapsulation was found a common feature but was not considered a histological sign of malignancy. In 88 patients with adenomas followed up for 5–45 years, local recurrences arose in 7 cases, in 5 with pleomorphic and in 2 with monomorphic adenoma. None of the patients with a salivary gland adenoma had metastasis or died of the tumour disease. There was no difference in the clinical outcome between patients with pleomorphic and monomorphic adenomas. Two of the 3 patients with carcinoma in pleomorphic adenoma succumbed to metastasizing tumour and the third patient died of in-tercurrent disease. P...