Daxx-beta and Daxx-gamma, two novel splice variants of the transcriptional co-repressor Daxx.

Daxx is involved in transcriptional control and apoptosis. It comprises several domains, including a regulatory C terminus that is responsible for the interaction with numerous proteins such as p53, promyelocytic leukemia protein (PML), and Hsp27. Here, we describe the identification and characterization of two novel variants of Daxx termed Daxx-β and Daxx-γ, which are generated by alternative splicing.

PIDDosome expression and the role of caspase-2 activation for chemotherapy-induced apoptosis in RCCs.

Background: The importance of caspase-2 activation for mediating apoptosis in cancer is not clear and seems to differ between different tumour types. Furthermore, only few data have been obtained concerning the expression of caspase-2, which can be alternatively spliced into caspase-2L and caspase-2S, and the other PIDDosome members PIDD and RAIDD in human tumours in vivo. We, therefore, investigated their expression in renal cell carcinomas (RCCs) of the clear cell type in vivo and analysed the role of caspase-2 in chemotherapy-induced apoptosis in RCCs in vitro.

Combined esophageal injury complicated by progression to a second perforation: a case report.

Introduction: Intramural dissection of the esophagus is a rare disorder characterized by a lesion between the submucosa and mucosa dividing the esophagus into a false and true lumen. The etiology of esophageal dissection remains uncertain but it affects predominantly women in their seventies and eighties. Symptoms may include uncharacteristic ones such as retrosternal pain, odynophagia or dysphagia.

Disturbed XIAP and XAF1 expression balance is an independent prognostic factor in gastric adenocarcinomas.

Background: Dysregulation of apoptosis is a key factor in carcinogenesis and tumor progression. X-linked inhibitor of apoptosis (XIAP) is the most potent member of the inhibitor of apoptosis protein (IAP) family, which directly inhibits apoptosis by binding to caspases. Antagonists of XIAP have recently been identified: second mitochondria-derived activator of caspase/direct IAP-binding protein with low PI (Smac/DIABLO) and XIAP-associated factor 1 (XAF1).

HA14-1 is able to reconstitute the impaired mitochondrial pathway of apoptosis in renal cell carcinoma cell lines.

Renal cell carcinomas (RCCs) exhibit a marked resistance towards apoptosis. Although most apoptotic stimuli converge at the level of the mitochondria, little is known about the mitochondrial apoptosis pathway in renal cell carcinomas. The aim of the present study, therefore, was to investigate the functionality of the mitochondrial apoptosis pathway in renal cell carcinoma cell lines by exposure to TRAIL, etoposide, HA14-1 and betulinic acid activating the mitochondria by different mechanisms.

Is there a role for the Fas-/Fas-Ligand pathway in chemoresistance of human squamous cell carcinomas of the head and neck (SCCHN)?

The aim of the present investigation was to determine the expression of the Fas-receptor/ligand system in established cell lines of squamous cell carcinomas of the head and neck (SCCHN), and to study it's functional impact on chemotherapy-induced apoptosis in these SCCHN cell lines. We observed constitutive expression of Fas and FasL in 13 SCCHN cell lines by RT-PCR, Southern-blotting and immunocytochemistry, respectively. Administration of the agonistic Fas-antibody CH-11 led to a significant reduction of viable cells in the colorimetric MTT-assay in 5 out of 13 (38%) cell lines tested and preincubation with Interferon-gamma (IFN-gamma) rendered 3 (23%) primarily resistant cell lines sensitive.

Caspase-8 and its inhibitors in RCCs in vivo: the prominent role of ARC.

Activation of the initiator-caspase, caspase-8 is under tight control of multiple antiapoptotic regulators including ARC, cFlip(S), cFlip(L) and PED/PEA-15. Since there is little data regarding the expression of caspase-8 and its antiapoptotic regulators in human tumours in vivo, we analysed their expression in renal cell carcinomas (RCCs) to identify which of these genes might be crucial for the well known impaired apoptosis and--as a result--resistance towards chemotherapy and ionizing radiation of RCCs. Caspase-8, cFlip(S), cFlip(L) and PED/PEA-15 mRNA expression was significantly increased only in early stages of RCCs compared to non-neoplastic renal tissue.

An uncommon cause of gastro-duodenal ulceration.

Gastrointestinal ulcers occur frequently and are mainly caused by H. pylori infection. In this report, we present a rare case of gastro-duodenal ulcer following selective internal radiation therapy (SIRT).

Hemoglobin-glutamer 200 reduces reperfusion injury of the cold preserved rat liver by induction of heme oxygenase-1.

Microcirculatory failure after cold liver preservation and reperfusion impairs tissue oxygenation and causes additional organ damage. Hemoglobin-glutamer (HbG) 200 is a hemoglobin-based oxygen carrying solution capable to improve organ oxygenation. The aim of this study was to evaluate its potential to decrease reperfusion injury after cold liver preservation.

Paclitaxel (Taxol)-induced apoptosis in human epithelioid sarcoma cell lines is enhanced by upregulation of CD95 ligand (FasL/Apo-1L).

Purpose: Metastasizing epithelioid sarcoma (ES) is an extremely aggressive tumor, because conventional chemotherapy and irradiation are largely ineffective. Here, we analyzed the impact of the CD95-mediated drug-induced apoptosis in ES cell lines.

Methods: The effects of paclitaxel (Taxol) and 5-FU were determined by MTT assay.

Differential gene expression in anticancer drug- and TRAIL-mediated apoptosis in renal cell carcinomas.

Renal cell carcinomas (RCC) exhibit marked differences in susceptibility towards anticancer drug- and TRAIL-induced apoptosis. However, the underlying mechanisms determining apoptosis-sensitivity or -resistance are not well understood. The purpose of this study was to compare gene expression patterns induced by DNA-damage- and death receptor-induced apoptosis and to detect differentially expressed genes responsible for differences in apoptosis-susceptibility.

Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome.

Context: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families.

Bone histomorphology may be unremarkable in diabetes mellitus.

Background And Purpose: Histomorphological studies on bone in human diabetes mellitus are scarce. The aim of this study was to observe the histomorphological appearance of bone in amputation specimens from feet of patients with diabetes mellitus.

Material And Methods: Routine histopathology reports on 45 amputation specimens were evaluated, provided the osteotomy was located in unaffected bone tissue.

Disturbed expression of the apoptosis regulators XIAP, XAF1, and Smac/DIABLO in gastric adenocarcinomas.

Dysregulation of apoptosis plays an important role in carcinogenesis and tumor progression. Whereas x-linked inhibitor of apoptosis (XIAP) is a potent inhibitor of apoptosis, its antagonists second mitochondria-derived activator of caspases/direct IAP binding protein with low PI (Smac/DIABLO), and XIAP-associated factor 1 (XAF1) promote apoptosis. To explore the relevance of XIAP, Smac/DIABLO, and XAF1 for carcinogenesis and tumor progression, we analyzed 46 primary gastric adenocarcinomas and non-neoplastic gastric mucosa samples by quantitative real-time polymerase chain reaction.

TRAIL-R4-beta: a new splice variant of TRAIL-receptor 4 lacking the cysteine rich domain 1.

Transcriptional modification by alternative splicing is known to be involved in the regulation of programmed cell death. Recently, alternative splice variants of the TNF-related apoptosis inducing ligand (TRAIL/APO2L) and of the death receptor TRAIL-R2/DR5 have been identified. In this study, we report the identification of a novel alternative splice variant of the decoy receptor with a truncated death domain TRAIL-R4 lacking exon 3, which we designated TRAIL-R4-beta.

Giant fibrovascular polyp of the esophagus.

Fibrovascular polyps of the esophagus are benign, pedunculated tumors that consist mostly of connective tissue and can reach impressive sizes. They arise from the upper third of the esophagus and may produce symptoms of dysphagia, progressive weight loss and regurgitation. The most serious clinical presentation is asphyxia secondary to laryngeal obstruction.

A case of a pT3, HPV 52-positive vulvar carcinoma in an 18-year-old woman.

Background: Vulvar carcinoma in young women is rare; so far, no case of an 18-year-old woman has been described. Here, we report a case with a T3 HPV 52-induced tumor 3 years after primary HPV contamination.

Case: An 18-year-old woman without risk factors complaining of dysuria and vulvar pain was treated several months for fungal infection before referred and diagnosed with a vulvar carcinoma located between clitoris and urethra.

Expression of death-associated protein kinase during tumour progression of human renal cell carcinomas: hypermethylation-independent mechanisms of inactivation.

Death-associated protein kinase (DAPK) is a pro-apoptotic Ca(2+)/calmodulin-dependent serine/threonine kinase that is widely expressed in tissues but kept silent in growing cells. Downregulation of DAPK transcription by CpG methylation has been demonstrated in a variety of tumours, providing a selective growth advantage during tumour progression. As the in vivo expression of DAPK in human renal cell carcinomas (RCCs) has not previously been analysed, 72 RCCs were investigated using semi-quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).

XIAP expression is an independent prognostic marker in clear-cell renal carcinomas.

Deregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. XIAP is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. To explore the relevance of XIAP for progression and prognosis in renal cell carcinomas (RCCs) of the clear-cell type, we analyzed XIAP protein expression in formalin-fixed tissue from 145 clear-cell RCCs by immunohistochemistry.

Identifying superficial, muscle-invasive, and metastasizing transitional cell carcinoma of the bladder: use of cDNA array analysis of gene expression profiles.

Purpose: Expression profiling by DNA microarray technology permits the identification of genes underlying clinical heterogeneity of bladder cancer and which might contribute to disease progression, thereby improving assessment of treatment and prediction of patient outcome.

Experimental Design: Invasive (20) and superficial (22) human bladder tumors from 34 patients with known outcome regarding disease recurrence and progression were analyzed by filter-based cDNA arrays (Atlas Human Cancer 1.2; BD Biosciences Clontech) containing 1185 genes.

Prognostic implications of CD95 receptor expression in clear cell renal carcinomas.

The CD95 (Apo-1/Fas) receptor-ligand system is a key regulator of apoptosis. Down-regulation of CD95 receptor and up-regulation of CD95 ligand has been reported in a variety of human tumors and is thought to confer a selective survival advantage. To explore the relevance of the CD95 system for tumor progression and prognosis in clear cell renal cell carcinomas (RCCs), we analyzed CD95 receptor and ligand expression in formalin-fixed tissue from 149 clear cell RCCs by immunohistochemistry.