Essential cysteine-alkylation strategies to monitor structurally altered estrogen receptor as found in oxidant-stressed breast cancers.

Oxidant-induced structural modifications within the cysteine-rich DNA-binding domain (DBD) of the overexpressed estrogen receptor (ER) likely contribute to its loss of DNA-binding function and altered transcriptional activity during human breast cancer development. Using recombinant ER protein as a model, procedures to detect such endogenously produced structural changes in the two Cys(4)-type zinc fingers within the DBD of ER extracted from breast cancer cells are being developed. Unfortunately, ex vivo oxidation of these ER-DBD cysteine residues can occur during routine ER purification and preparation procedures.

Prospective, randomized, single-center trial comparing 3 different 10F plastic stents in malignant mid and distal bile duct strictures.

Background: The aim of this study was to determine whether patency rates differ with respect to the material, design, and surface texture of 3 different plastic stents.

Methods: A total of 120 patients (median age 70.5 years; interquartile range 62-78 years) with malignant mid or distal bile duct strictures, seen between March 1996 and May 1999, were prospectively randomized to receive a 10F polyurethane stent, a Teflon Tannenbaum stent, or a hydrophilic hydromer-coated polyurethane stent.

Underestimation of nodules while staging hepatocellular carcinoma prior to neoadjuvant treatment on waiting list for transplantation.

Neoadjuvant therapy of hepatocellular carcinoma (HCC) has increasing importance for patients awaiting liver transplantation, as waiting time increases. The therapeutic options (ethanol injection, radiofrequency ablation, chemoembolization) are only effective locally. Therefore, occult carcinomas can overcome the efficacy of these therapies.

Understanding the age dependency of breast cancer biomarkers.

This review and study of nearly 4,000 primary breast cancers evaluates the hypothesis that human aging not only increases breast cancer incidence but also alters breast cancer biology. Clinically validated biomarkers were chosen as surrogate measures of genetic instability and tumor growth, invasiveness and metastatic potential. Our results support the premise that breast cancer clinical behavior and biology are significantly affected by patient age, but call into question key aspects of the current cancer-aging paradigm.

Endoscopic stenting for postoperative biliary strictures due to hepatic hydatid disease: effectiveness and long-term outcome.

Background: Postoperative strictures due to hepatic hydatid disease caused by Echinococcus surgery is considered to be a rare cause of benign bile duct strictures, especially in the Western world.

Goals: The aim of this retrospective study is to demonstrate possible characteristics of the strictures as well as the effectiveness of long-term endoscopic stenting.

Study: Between 1994 and 2001, we treated 10 of these cases in our clinic.

Viral escape and T-cell immunity during ganciclovir treatment of cytomegalovirus infection: case report of a pancreatico-renal transplant recipient.

Background: Pancreas-kidney transplant recipients are at high risk for cytomegalovirus (CMV) disease despite prophylactic ganciclovir therapy. Because the impact of antiviral therapy on anti-CMV immune reactions is unknown, CMV-specific T-cell subsets in primary and recurrent CMV infection were analyzed in a pancreas-kidney transplant case study.

Methods: Major histocompatibility complex class I tetramers were used to detect peripheral CMV pp65-specific CD8 T cells.

Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines.

The clinical observation of the multidrug resistance (MDR) phenotype is often associated with overexpression of the mdrl gene, in particular with respect to ovarian cancer. However, until now the mdrl-inducing potential of commonly used antineoplastics has been only incompletely explored. We performed short-term cultures of six ovarian cancer cell lines (MZOV4, EF027, SKOV3, OAW42, OTN14, MZOV20) exposed to either blank medium or cisplatin, doxorubicin or paclitaxel at concentrations related to the clinically achievable plasma peak concentration.

Transcriptional repression of ErbB2 by histone deacetylase inhibitors detected by a genomically integrated ErbB2 promoter-reporting cell screen.

The antitumor activity of histone deacetylase (HDAC) inhibitors has been linked to gene expression induced by acetylation of histone and nonhistone proteins; but the molecular basis for their antitumor selectivity remains largely unknown. With development of a genomically integrated, ErbB2 promoter-reporting breast cancer cell screen, ErbB2 promoter inhibiting activity was observed by the HDAC inhibitors trichostatin A (TSA) and sodium butyrate. Paradoxically, these agents stimulated the episomal form of this ErbB2 promoter-reporter introduced by transient transfection.

Age-dependent changes in breast cancer hormone receptors and oxidant stress markers.

Breast cancer incidence increases with age but this relationship has not been fully explored with regard to expression of estrogen receptor (ER) and ER-inducible genes (PR, pS2, Bcl2, cathepsin D), or the age-dependence of oxidant stress markers that also affect ER-inducible gene expression. In this three-part study, we first correlated age at diagnosis with expression of breast cancer markers ER, PR, pS2, Bcl2, and cathepsin D, quantitated by enzyme immunoassays from a European collective of approximately 3000 cryobanked primary breast cancers and approximately 300 adjacent non-malignant breast tissues. Results were then compared with ER and PR data reported to the SEER registry for 83,541 US cancers diagnosed during 1992-1997.

Age-associated biomarker profiles of human breast cancer.

To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii).

Therapeutic efficacy of anti-ErbB2 immunoliposomes targeted by a phage antibody selected for cellular endocytosis.

Many targeted cancer therapies require endocytosis of the targeting molecule and delivery of the therapeutic agent to the interior of the tumor cell. To generate single chain Fv (scFv) antibodies capable of triggering receptor-mediated endocytosis, we previously developed a method to directly select phage antibodies for internalization by recovering infectious phage from the cytoplasm of the target cell. Using this methodology, we reported the selection of a panel of scFv that were internalized into breast cancer cells from a nonimmune phage library.

Induction of MDR1-gene expression by antineoplastic agents in ovarian cancer cell lines.

Background: Development of resistance to anticancer drugs is a major concern in clinical oncology and might be particularly involved in the secondary treatment failure frequently seen in ovarian cancer. Clinical observation of the multidrug resistance (MDR) phenotype is often associated with overexpression of the mdr1-gene. However, until now the mdr1-inducing potential of commonly used antineoplastics has been only incompletely explored.

Pancreatic endoscopic sphincterotomy in patients with chronic pancreatitis: a single-center experience in 171 consecutive patients.

Background And Study Aims: In recent years, interest in endoscopic therapy techniques for pancreatic diseases has been constantly increasing. The aim of the present study was to assess the technical success, technique, and complications of endoscopic pancreatic sphincterotomy (EPS) in patients with chronic pancreatitis.

Patients And Methods: A total of 171 patients with chronic pancreatitis and abdominal complaints were identified in whom at least one attempt at EPS was carried out.

Does the insertion depth in push enteroscopy depend on the working length of the enteroscope?

Background And Study Aims: Using push enteroscopy, the small bowel can only be investigated in part. This preliminary prospective randomized study examined whether increasing the length of the enteroscope can have a beneficial effect on the insertion depth.

Patients And Methods: Between August 1999 and December 1999, 28 consecutive patients were investigated using push enteroscopy and were randomly assigned to two groups.

Identification and expression of human cytomegalovirus transcription units coding for two distinct Fcgamma receptor homologs.

Cellular receptors for the Fc domain of immunoglobulin G (IgG) (FcgammaRs) comprise a family of surface receptors on immune cells connecting humoral and cellular immune responses. Several herpesviruses induce FcgammaR activities in infected cells. Here we identify two distinct human cytomegalovirus (HCMV)-encoded vFcgammaR glycoproteins of 34 and 68 kDa.

ErbB2 activation of ESX gene expression.

Various members of the Ets multigene family exhibit diverse roles in development, cell differentiation, tissue-specific gene expression and human malignancy. In the search for Ets factors involved in mammary gland development and malignancy, ESX was found to be upregulated in a subset of breast tumours and cell lines. We report the transcriptional regulation of ESX in epithelial breast cancer cells.

Activated virus-specific T cells are early indicators of anti-CMV immune reactions in liver transplant patients.

Background & Aims: Cytomegalovirus (CMV) infection represents the most common infectious complication after liver transplantation. Because CMV-associated complications in liver transplantation patients are often liver-restricted and clinically unrecognized, diagnosis of early infection or reactivation is still very difficult. Because cytotoxic T cells (CTLs) are crucial for the immune control of CMV, analysis of virus-specific CTLs could contribute to diagnosis and management of CMV infection.

Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery.

Purpose: Anti-HER2 immunoliposomes combine the tumor-targeting of certain anti-HER2 monoclonal antibodies (MAbs) with the pharmacokinetic and drug delivery capabilities of sterically stabilized liposomes. We previously showed that anti-HER2 immunoliposomes bind efficiently to and internalize in HER2-overexpressing cells in vitro, resulting in intracellular drug delivery.

Experimental Design: Here we describe the pharmacokinetics and therapeutic efficacy of anti-HER2 immunoliposomes containing doxorubicin (dox) in a series of animal models.

Expression of apoptosis and apoptosis-related peptides in various stages of rejection in the human transplanted liver.

Background/aims: In the transplanted liver, the role of apoptosis and apoptosis-related proteins are largely unknown. This study addresses the question whether hepatocyte or leukocyte apoptosis plays an important role in acute rejection of the transplanted human liver and which pathways are involved.

Methodology: Cryosections from liver biopsies with acute rejection were stained with the TUNEL technique for detection of apoptosis and labeled immunohistochemically with antibodies against CD95, bcl-2, TGF-beta and iNOS.

Acute and nonacute complications associated with interscalene block and shoulder surgery: a prospective study.

Background: The incidence, etiology, and evolution of complications after interscalene brachial plexus block (ISB) are not well-known. The authors prospectively monitored 521 patients for complications during the first 9 months after ISB.

Methods: A total of 521 adults scheduled for elective shoulder surgery performed with an ISB were included in this prospective study.

Endoscopic therapy of adenomas of the papilla of Vater. A retrospective analysis with long-term follow-up.

Aims: To compare the efficacy and the complication rate between endoscopic snare resection of adenomas of Vater's papilla and endoscopic palliation.

Methods: In a retrospective, non randomized manner, we compared long-term results of our endoscopic strategies in 36 patients with histologically confirmed adenoma of Vater's papilla submitted either to local endoscopic snare resection (n=18) or to simple endoscopic palliation (n= 18), respectively.

Results: Between 1985 and 1998 results were reviewed.