Activation of the Raf/MEK/ERK (MAPK) signal transduction cascade by RAS mutations has been found in a variety of human cancers. Mutations of BRAF provide an alternative route for activation of this signalling pathway. To determine the role of mutations in BRAF and KRAS2 in the neoplastic progression of Barrett's adenocarcinoma, we analysed both genes for common mutations.
View Article and Find Full Text PDFThe v-raf murine sarcoma viral homolog B1 (BRAF) gene, one of the human isoforms of RAF, is activated by Ras, leading to cooperative effects in cells responsive to growth factor signals. Recently, somatic missense mutations of the BRAF gene have been detected in more than 66% of malignant melanomas of the skin. We analyzed 42 malignant melanomas of the uvea, 3 corresponding liver metastases, and 10 cutaneous melanomas for possible BRAF mutations: after microdissection, mutation analysis of BRAF and KRAS was performed.
View Article and Find Full Text PDFTransplant Proc
September 2003
Characterization of the protein profiles expressed by hepatocellular carcinomas (HCCs) may identify the genes involved in hepatocellular carcinogenesis and offers the possibility of elucidating clinical biomarkers. In an effort to discover such proteins and pathways that are deregulated in hepatocellular carcinogenesis, cellular proteomes of matched normal liver cells and carcinoma were analysed by tissue microdissection and protein microarrays. Using protein microarrays made up of 83 different antibodies, it was possible to monitor alterations of the protein levels in HCC and non-neoplastic liver tissue.
View Article and Find Full Text PDFAim: The standard treatment for patients with clinically resectable rectal cancer is surgery. Postoperative radiochemotherapy (RCT) is recommended for advanced disease (pT3/4 or pN+). In recent years, encouraging results of pre-operative radiotherapy have been reported.
View Article and Find Full Text PDFThe multistep process of tumorigenesis has not been decoded to date, although numerous investigations into probable molecular changes have meanwhile been conducted. However, not only DNA changes or loss of alleles cause deregulation of gene function, but also epigenetic alterations (e.g.
View Article and Find Full Text PDFThe RAF/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates including growth, proliferation and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. This study was performed to elucidate a possible function of BRAF in squamous cell carcinoma of the head and neck (HNSCC).
View Article and Find Full Text PDFObjective: Anastomotic leakage is a serious complication after anterior resection for rectal carcinoma. It is controversial whether anastomotic leakage influences the rate of locoregional recurrence and therefore survival.
Patients And Methods: The data of 940 patients with invasive rectal carcinoma stage I-III treated by curative anterior resection from 1978 to 1996 at the Department of Surgery of the University of Erlangen were analysed.
Background: Only 20-30% of patients with hilar cholangiocarcinomas (CC) are candidates for potentially curative resection. However, even after curative (R0) resection, these patients have a disease recurrence rate of up to 76%. The current prospective Phase II study investigated photodynamic therapy (PDT) as a neoadjuvant treatment for CC.
View Article and Find Full Text PDFPurpose: To prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT).
Patients And Methods: From September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.
Background: The Raf/MEK/ERK (mitogen activated protein kinase-MAPK) signal transduction cascade is an important mediator of a number of cellular fates, including growth, proliferation, and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals.
Aims: The aim of this study was to elucidate a possible function of BRAF in liver tumours.
Background: Arterialisation of the portal vein has been propagated as a technical variant in liver transplantation. However, the consequences of this unphysiological vascular supply are insufficiently known.
Methods: Twenty-seven healthy pigs were subjected to a left hemihepatectomy and divided into three groups.
Background: Our aim here was interpret data on the perioperative course, oncological quality, and preliminary long-term results of laparoscopic colorectal surgery carried out with a curative intent.
Methods: The data were collected within the framework of a prospective multicenter observational study that has been ongoing since 1 Aug 1995 and includes 46 hospitals. Of a total of 3133 patients, 826 (26.
Objective: To examine the role of hemochromatosis (HFE) gene mutations, which are associated with porphyria cutanea tarda (PCT), in the therapeutic response to chloroquine.
Design: We retrospectively analyzed a database (Excel version 2001 [Microsoft Excel, Redmond, Wash]; date range of search, 1985-1999) of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities, and serum iron markers. Serum samples and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine.
The treatment of patients with colorectal cancer has changed over the last decades. More and more patients receive combined modality treatments including (preoperative) radiotherapy and chemotherapy. To assess the colorectal cancer specimen after neoadjuvant therapy, the pathologist has to be familiar with the histological features induced by radiochemotherapy.
View Article and Find Full Text PDFClinical Presentation: A 55-year-old woman required emergency medical care because of sudden weakness. On arrival of the emergency physician the patient presented with bradycardia with a normal rhythm. The blood pressure was not measurable.
View Article and Find Full Text PDFPurpose: Despite reservations about compliance with oncologic radical criteria, laparoscopic resection of the sigmoid colon is increasingly being used with curative intent in oncologic surgery of the colorectum. The aim of the present study was to obtain further information on the perioperative course, the oncologic radicalness of the procedure, and medium-term outcome.
Methods: The data presented here were obtained from a prospective, multicenter study conducted in Germany and Austria.
The tumor-suppressor protein p53 has recently been shown to belong to a family that includes two structurally related proteins, p63 and p73. In contrast to p53, p63 and p73 play an essential role in epithelial development, stem cell identity and cellular differentiation. Salivary gland tumors carry a wide spectrum of histopathological forms, which may share a common single-cell origin from the epithelial progenitor basal duct cells and have a different tendency of malignant progression.
View Article and Find Full Text PDFThe INK4a-ARF locus, located on chromosome 9p21, encodes 2 cell cycle-regulatory proteins, p16(INKa) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and p53 in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing.
View Article and Find Full Text PDFPleomorphic adenomas of the parotid gland are benign tumours composed of epithelial and mesenchymal cells. The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), which act as upstream regulators of the Rb-CDK4 and p53 pathways. To study the contribution of each pathway in pleomorphic adenomas, this study analysed alterations of p14(ARF), p16(INK4a), p53, and pRb in these tumours.
View Article and Find Full Text PDFMatrix metalloproteinases (MMPs) play a key role in cancer progression. Interstitial collagenase (MMP-1) and type IV collagenases (MMP-2, MMP-9) are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. Besides tumor cells, fibroblasts are especially involved in MMP production.
View Article and Find Full Text PDFVinyl chloride (VC) is a potent liver carcinogen that induces angiosarcomas in humans and animals. Recent evidence shows that liver tumors from patients with VC exposure may have a specific K-ras mutation pattern. This study was performed to determine the status of K-ras-2 in liver angiosarcomas (LAS) from workers occupationally exposed to VC.
View Article and Find Full Text PDFThe INK4a-ARF locus, located on chromosome 9p21, encodes two cell-cycle regulatory proteins, p16(INK4a) and p14(ARF), acting through the Rb-CDK4 and p53 pathways. To study the contribution of each pathway in the tumourigenesis of cholangiocarcinoma, the alterations of p14(ARF), p16(INK4a), p53, and pRb were analysed. After microdissection, DNAs from 51 cholangiocarcinomas were analysed by methylation-specific PCR (MSP), restriction-enzyme related polymerase chain reaction (RE-PCR), microsatellite analysis, mRNA expression, and DNA sequencing.
View Article and Find Full Text PDFWe present a 26 year old patient with a primary malignant synovial sarcoma of the lung that was observed for more than one year by a general practitioner and a pulmologist. Finally, because of recurrent hemoptysis a central tumor of mesenchymal origin of the left lower lobe was diagnosed by bronchoscopy. The invasion of the left atrium as far as to the mitral valve was diagnosed by MRT.
View Article and Find Full Text PDFBackground: The INK4a-ARF (CDKN2A) locus, located on chromosome 9p21, encodes two functionally distinct tumor suppressor genes, p14(ARF) and p16(INK4a), that play active roles in the p53 and Rb tumor suppressive pathways, respectively. We analyzed the alterations of p14(ARF), p16(INK4a) and p53 to study the contribution of each pathway in tumorigenesis of 29 patients with primary and consecutive (second primary) squamous cell carcinoma of the head and neck (HNSCC), with a total of 68 carcinomas.
Methods: After microdissection, the DNA of 29 primary and 39 consecutive squamous cell carcinomas was analyzed for INK4a-ARF inactivation and p53 mutation by means of DNA sequence analysis, methylation-specific polymerase chain reaction (MSP), restriction-enzyme-related polymerase chain reaction (RE-PCR), multiplex RT-PCR and immunohistochemistry.