Search PubMed⌕ Search

Biomedical subjects

A Ramaswamy

Publications and source records attributed to A Ramaswamy.

At least 37 records · Page 2Linked to original sources
PubMed2001

Variant expression of CD44 in preneoplastic lesions of the lung.

BACKGROUND: Specific CD44 isoforms are cell surface adhesion molecules and have been shown to be associated with tumor progression and metastasis. In lung carcinoma, CD44 expression has been reported to be a feature of nonsmall cell lung carcinoma (NSCLC) but not small cell lung carcinoma. A specific variant, CD44v6, was shown to be expressed only in a subset of NSCLC, namely the squamous cell and bronchoalveolar carcinomas, suggesting that CD44 may play a role in lung carcinoma differentiation. METHODS: To determine whether differential CD44 expression is an early event in the pathogenesis of lung carcinoma, the authors investigated the pattern of expression of the standard (CD44s) and variant (CD44v6) isoforms by immunohistochemistry in normal lung, nonneoplastic specimens, and bronchial biopsies of preneoplastic lesions. RESULTS: In normal bronchial epithelium and all nonneoplastic cases, CD44s expression was limited to the basement membrane and adjacent lower strata of the epithelium, whereas CD44v6 was expressed within the basement membrane only. However, aberrant expression of both CD44s and CD44v6 was observed in all preneoplastic lesions examined. In cases of dysplasia, squamous metaplasia, goblet cell hyperplasia, and basal cell hyperplasia, all epithelial strata showed immunoreactivity for both isoforms, in contrast to normal epithelium, in which immunoreactivity was noted to be restricted to the basal layer cells. In contrast, CD44s and CD44v6 expression was completely absent in nearly all cases of adenomatosis. CONCLUSIONS: Altered CD44s and/or CD44v6 expression appears to be a feature of all preneoplastic lesions in the lung, the precise nature of which varies according to histologic tumor type. Therefore, the authors conclude that CD44s and CD44v6 may lend themselves to be markers of preneoplastic changes in the lung.

Glycoproteins↗
PubMed2001

Current concepts in the classification, diagnosis and treatment of hemangiomas and vascular malformations of the head and neck.

There are many different classifications of vascular anomalies. As the correct classification of the vascular lesion has a direct influence on therapy it is difficult to decide which treatment should be considered as the treatment of choice. Based on an extensive review of the literature and personal experience of the treatment of more than 200 patients with hemangiomas or vascular malformations of the head and neck, a clinical classification is described that allows vascular lesions to be categorized in order to plan purposeful treatment. In general, hemangiomas represent the main group of vascular lesions in infancy and childhood. They are usually apparent a few weeks after birth and are characterized by an initially rapid growth of epithelial cells, followed by spontaneous involution. Hemangiomas should be differentiated from vascular malformations that are present at birth but may not be evident clinically. Spontaneous involution of vascular malformations has never been reported, whereas laser therapy can induce involution of hemangiomas at an early stage in a majority of cases. In certain situations steroids or surgical removal may seem to be the appropriate therapy of choice. In contrast, vascular malformations have to be treated according to their histopathology and location, as well as their hemodynamic features as shown radiographically with angiography. The accurate diagnosis of vascular anomalies is essential for further treatment, as shown by clinical experience at the University of Marburg.

Arteriovenous Malformations↗
PubMed2001

Value of sentinel lymphonodectomy in head and neck cancer patients without evidence of lymphogenic metastatic disease.

OBJECTIVE: Only few communications deal with the value of sentinel node (SN) biopsy for head and neck squamous cell carcinoma (HNSCC). Based on the results of 38 investigated patients with clinically N0-neck the feasibility of SN biopsy in HNSCC is critically discussed. PATIENTS AND METHODS: Thirty-eight previously untreated patients with clinically N0-neck were staged by intraoperative SN biopsy. After intraoperative identification of the hottest node (SN(1)) and further less tracer accumulating lymph nodes (SN(2), SN(3)), patients were treated by different types of neck dissection (ND), adjusted to the location and extent of the primary tumour. Postoperatively the histologic results of the SN(1-3) and the entire ND specimen were compared. RESULTS: The stage of cervical metastatic disease was demonstrated by a disease-free SN(1) in 32 patients. In five patients an isolated metastasis could be proven in the intraoperatively identified SN(1), while in the remaining patient an isolated metastasis was found in the SN(2). CONCLUSION: Intraoperative SN biopsy seems to be valuable for the detection of occult lymph node metastases in HNSCC. This method might help to limit the extent of ipsilateral ND, if used as an intraoperative staging procedure to investigate the first draining tracer accumulating lymph nodes (SN(1-3)).

Adult↗
PubMed2001

[Sonographic variability of lactating adenoma demonstrated by a longitudinal evaluation of 4 cases].

AIM: Lactating adenoma are circumscribed benign breast lesions developing during pregnancy or lactation due to overall enhanced proliferation of steroid hormone dependent tissue. Sonography is the method of choice for imaging mainly because of the physiologically dense breast tissue. Which is the predictive value of sonography in the diagnosis of lactating adenoma? Are sonographic characteristics dependent on age of gestation or time of lactation? Which diagnostic procedure should be recommended? METHOD: We report the long time course of four patients with histologically proven (core-needle biopsy, 16 Gauge) lactating adenoma, first diagnosed during pregnancy, which were followed up sonographically (1997-2000) with real-time B-mode, panorama-mode (Siescape) and colour-sonography. RESULTS: Demonstrating a high inter- and intraindividual variability the tumors were biggest around parturitation. Despite ongoing lactation tumors regressed in size, but did not vanish completely even after definite termination of breast feeding. Evaluation of sonographical characteristics did not allow to rule out malignancy. CONCLUSION: Three percent of all breast cancers at childbearing age coincide with pregnancy and lactation, therefore, an early histologic diagnosis is absolutely necessary. Sonographically guided core-needle biopsies allow to exclude malignancy without negative effects on breast feeding.

Adenoma↗
PubMed2001

p16(INK4a) alterations in chronic pancreatitis-indicator for high-risk lesions for pancreatic cancer.

BACKGROUND: p16(INK4a) alterations are considered to be an early event in pancreatic tumorigenesis and have been described in duct lesions adjacent to pancreatic cancers. This study evaluates whether duct lesions in chronic pancreatitis tissues of patients without pancreatic cancer also harbor genetic alterations in the p16(INK4a) tumor-suppressor gene, and thus represent high-risk precursors for pancreatic cancer. METHODS: Tissues were obtained from 20 pancreatic specimens taken from patients operated on for histologically verified chronic pancreatitis. Pancreatic intraductal neoplasias (PanIN) were identified in hematoxylin-and-eosin-stained slides. p16 protein expression was investigated immunohistochemically in all specimens. DNA from PanIN and non-PanIN tissue was analyzed genetically for p16(INK4a) mutations by single-strand conformation variation analysis and direct sequencing of the encoding region. Additionally, p16(INK4a) promoter methylation was analyzed by a methylation specific polymerase test. RESULTS: PanIN-1a lesions were identified in 10 of the 20 chronic pancreatitis specimens. Four of these 10 PanIN specimens (40%), but none of the 20 non-PanIN tissues, revealed a loss of p16 expression in immunohistochemistry. The mutational analysis of the p16(INK4a) gene showed 1 known polymorphism (c.442G > A; A148T) but no mutations. Two of the 10 specimens with PanIN revealed an inactivating hypermethylation of the p16(INK4a) promoter. CONCLUSIONS: This study shows for the first time that p16(INK4a) alterations can be observed in a considerable number of PanIN1 in chronic pancreatitis tissues not associated with pancreatic cancer. Therefore, p16(INK4a) alterations, especially promoter methylation, might indicate high-risk precursors in chronic pancreatitis that might progress to cancer.

Adult↗
PubMed2001

EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption.

Enteropathogenic Escherichia coli (EPEC) alters many functions of the host intestinal epithelia. Inflammation is initiated by activation of nuclear factor (NF)-kappaB, and paracellular permeability is enhanced via a Ca2+- and myosin light-chain kinase (MLCK)-dependent pathway. The aims of this study were to identify signaling pathways by which EPEC triggers inflammation and to determine whether these pathways parallel or diverge from those that alter permeability. EPEC-induced phosphorylation and degradation of the primary inhibitor of NF-kappaB (IkappaBalpha) were tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta independent. In contrast to Salmonella typhimurium, EPEC-stimulated IkappaBalpha degradation and IL-8 expression did not require Ca2+. Instead, extracellular signal-regulated kinase (ERK)-1/2 was significantly and rapidly activated. ERK1/2 inhibitors attenuated IkappaBalpha degradation and IL-8 expression. Although ERK1/2 can activate MLCK, its inhibition had no impact on EPEC disruption of the tight junction barrier. In conclusion, EPEC-induced inflammation 1) is TNF-alpha and IL-1beta receptor independent, 2) utilizes pathways differently from S. typhimurium, 3) requires ERK1/2, and 4) employs signals that are distinct from those that alter permeability. This is the first time that EPEC-activated signaling cascades have been linked to independent functional consequences.

Calcium↗
PubMed2001

A novel insulinoma tumor suppressor gene locus on chromosome 22q with potential prognostic implications.

The molecular mechanisms contributing to the tumorigenesis of insulinomas are still poorly understood. As moderate to high rates of LOH have been found on chromosome 22q in gastrinomas, we performed a finer deletion mapping study of chromosome 22q with 8 microsatellite markers in 15 insulinomas (4 malignant and 11 benign). Fourteen of 15 (93%) insulinomas revealed LOH on chromosome 22q, whereas the shortest region of overlap implicated a deletion of approximately 700 kb at 22q12.1-q12.2 with an LOH rate of up to 57% (8 of 14). Although the expressed sequence tag marker A006E25 that is localized in the hSNF5/INI1 gene on 22q11.2 revealed LOH in 50% of informative cases (7 of 14), no alterations in this gene could be identified by single strand conformational polymorphism analysis, direct DNA sequencing, or RNA expression analysis. Remarkably, the four malignant tumors showed a common deleted region between markers D22S345 and D22S1144 compared with none of the 11 benign insulinomas. The observed high frequency of chromosome 22q12 deletions in insulinomas is suggestive for a region compatible with harboring a tumor suppressor gene. The hSNF5/INI1 gene is most likely not the candidate gene, because no alterations could be identified. The distinct pattern of allelic loss identified in this chromosomal region appears to be an attractive candidate marker for further evaluation with regard to the discrimination between benign and malignant insulinomas.

Adult↗
PubMed2000

[Diagnosis and therapy of well-differentiated neuroendocrine lung tumors].

INTRODUCTION: Neuroendocrine tumours of the lung are uncommon malignant neoplasms. They represent a heterogeneous spectrum of disease, encompassing the well-differentiated neuroendocrine tumours through to small-cell lung cancer, which has a poor prognosis and only palliative therapeutic options for most patients. Due to the low incidence of well-differentiated lung tumours there is as yet little experience. METHODS: Clinical records of 14 patients with well-differentiated neuroendocrine tumours of the lung were assessed retrospectively for patients' initial symptomatology, diagnostic procedures, therapy and results. RESULTS: Eight lobectomies, 2 bronchoplastic lobectomies, 2 segmental resections, 1 bilobectomy and 1 wedge resection were performed; seven of them without regional lymphadenectomy. All patients were alive after a mean follow-up of 38 (2-96) months. Thirteen of 14 patients were free of complaints, twelve had no recurrences and returned to work. CONCLUSIONS: Well-differentiated NET of the lung have an excellent prognosis after curative resection. Limited resections even without lymphadenectomy can be performed in some cases.

Adult↗
PubMed2000

Management of nonfunctioning islet cell carcinomas.

Tumors arising from the pancreatic islet cells are rare and represent a heterogeneous group of benign or malignant lesions. Most tumors present with well characterized syndromes, whereas others appear to be nonfunctioning. The clinical features of 11 men and 7 women with nonfunctioning islet cell carcinomas operated on between 1983 and 1998 were reviewed. The median patient age was 53.5 years (range 26-74 years). The most frequent presenting symptoms were abdominal pain (13 patients), weight loss (7 patients), and obstructive jaundice (4 patients). Gut hormone profiles were normal in all patients. Abdominal sonography and computed tomography localized the tumor in 17 patients, and correct prediction of an endocrine tumor was achieved in 12 patients. Six of seven patients showed a hypervascular tumor upon angiography, and seven of eight patients preoperatively had positive somatostatin receptor scintigraphy. At operation, regional or distant metastases were present in 15 (83%) and 6 (33%) patients, respectively. Eleven patients underwent potentially curative resections, and the remaining seven patients were managed palliatively by resection (four patients) or bypass procedures (three patients). Three patients had up to three more resection for metastases. Eight patients received postoperative octreotide, interferon alpha therapy, or both. The overall cumulative 5- and 10-year survival rates were 65.4% and 49.1%, respectively. Of the 11 patients who underwent curative resection, 10 were alive after a median follow-up of 63 months (range 7-180 months), but only 5 are free from disease. Although surgical cure is rare in nonfunctioning islet cell carcinomas, significant long-term palliation can be achieved in a large proportion of patients with an aggressive surgical approach and, when indicated, additional medical therapy.

Adult↗
PubMed2000

Pulmonary aspergillosis in an unselected autopsy series.

The present study was performed to analyze the relationship between underlying diseases and the morphologic form of aspergillosis. This retrospective analysis of 3284 autopsies yielded 18 cases of aspergillosis. The specific diagnosis of aspergillosis was rendered by a monoclonal antibody versus Aspergillus spp. Patients with hematological disorders, such as acute leukemia and aplastic anemia, made up about 35% of all patients dying of invasive aspergillosis. Diseases of the airways and the pulmonary parenchyma constituted the second most pathogenetic factor for the development of aspergillosis. The morphologic form of aspergillosis was closely related to the underlying diseases. Non- and semi-invasive forms of aspergillosis--saprophytic infection and chronic necrotizing aspergillosis--were observed only in patients with an isolated underlying pulmonary disease devoid of any other precipitating factor. In contrast, seven patients, five of whom suffered from hematological diseases, had no underlying lung disease and developed aspergillus pneumonia. The remaining 5 patients with aspergillus pneumonia showed a combination of underlying extrapulmonary disease and pulmonary alterations that preceded aspergillosis. The local distribution of fungal infection showed a characteristic distribution pattern with a predominance of the upper lung lobes. Hematogeneous spread beyond the lungs occurred exclusively in cases with aspergillus pneumonia. We conclude that the different forms of aspergillosis are closely related to the nature of the underlying disease.

Adult↗
PubMed2000

Multiple primaries in pancreatic cancer patients: indicator of a genetic predisposition?

BACKGROUND: The genetic basis of several familial cancers including breast and colon cancers has been identified recently. The occurrence of multiple cancers in one individual is also suggestive of a genetic predisposition. To evaluate inherited predisposition in pancreatic cancer we compared the clinical data of pancreatic cancer patients with and without multiple primaries as well as the frequency of malignancies among their relatives. METHODS: Detailed data on 69 pancreatic cancer patients included survival time and TNM-classification. Index case data were separated into two groups. The first group (group 1) developed only pancreatic cancer during their lifetime, whereas the second group (group 2) developed additional primary tumours. A systematic family history was taken from 59 of these pancreatic cancer patients using a standardized questionnaire. The pancreatic cancers and the multiple primaries of the 59 patients were histologically proven. RESULTS: Of the 69 pancreatic cancer patients, 13 (18.8%) had multiple primaries. Neither the clinical data nor the survival data of the index cases revealed differences between the two groups (all nominal P-values >0.05). In the family history study blood relatives developed a malignancy in 51% (24 of 47) of the families in group 1 compared to 75% (9 of 12) in group 2. The risk of relatives in group 2 of developing a malignant tumour was significantly higher (P = 0.034) than in group 1 after adjustments for family size and age of disease onset of the index case. The cancer spectrum of the 59 families mainly included tumours of the digestive tract and the reproductive organs. CONCLUSIONS: A multiple primary cancer history is a common condition among pancreatic cancer patients. Relatives of these patients seem to have an increased risk for the development of distinct malignant solid tumours, which might be caused by an inherited predisposition. Clinical and genetic investigation of pancreatic cancer patients with multiple primaries and their families might lead to the identification of predisposing gene defects providing a new goal for the understanding of a shared genetic basis of different solid tumours.

Aged↗
PubMed2000

Multiple primary tumors as an indicator for p16INK4a germline mutations in pancreatic cancer patients?

Multiple primary tumors in pancreatic cancer patients might indicate a genetic predisposition to the development of malignancies. In this study we evaluated whether the mutation rate of the TP53 and p16INK4a genes of pancreatic cancers differs in pancreatic cancer patients with and without multiple primaries. Furthermore, we investigated whether pancreatic cancer patients with multiple primaries carry germline mutations in either p16INK4a, TP53, or BRCA2 tumor suppressor genes to detect a genetic alteration that predisposes to the development of different primaries. Fourteen (23%) of 60 pancreatic cancer patients developed histologically verified additional primaries during their lifetimes. Normal constitutional and tumor DNA of the 14 patients with a positive cancer history, but negative family history, were analyzed for p16INK4a, TP53, and BRCA2 mutations by single-strand conformational variant (SSCV) analysis and direct sequencing. Hypermethylation of the p16INK4a promoter region in pancreatic cancers was identified by methylation-specific polymerase chain reaction (PCR; MSP). Four of 14 pancreatic carcinomas carried somatic intragenic p16INK4a mutations, and another four tumors revealed hypermethylation of the p16INK4a promoter region. Somatic intragenic TP53 mutations were identified in six of 14 tumors. None of the pancreatic cancer patients carried TP53 or BRCA2 germline mutations. In contrast, one of 14 pancreatic cancer patients with multiple primaries carried the p16INK4a mutation A68V in his germline. This mutation was localized in the conserved second ankyrin repeat of p16INK4a and did not occur in 100 control patients. The frequency of somatic TP53 and p16INK4a mutations in pancreatic cancer is similar in patients with and without multiple primaries. TP53 and BRCA2 germline mutations seem not to be significantly associated with the occurrence of multiple primaries in pancreatic cancer patients. However, p16INK4a germline mutations might be causative for tumor development in some pancreatic cancer patients with multiple primaries. The genetic investigation of patients with accumulation of different cancers even without a positive family history may be a new approach for the understanding of the relation of different cancers.

Adult↗
PubMed2000

Low frequency of p16(INK4a) alterations in insulinomas.

BACKGROUND/AIMS: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16(INK4a) tumor-suppressor gene was identified in a variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16(INK4a) in the tumorigenesis of insulinomas was evaluated. METHODS: Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16(INK4a) tumor-suppressor gene by SSCP, PCR-based deletion and methylation-specific assays. p16 expression was determined by immunohistochemistry. RESULTS: One malignant insulinoma showed a homozygous deletion of p16(INK4a) and another two benign insulinomas revealed aberrant methylation of the p16(INK4a) promoter region. All three tumors lacked p16 expression according to immunohistochemistry. None of the insulinomas carried intragenic p16(INK4a) mutations. In total, 17% of insulinomas had p16(INK4a) alterations. CONCLUSIONS: The p16(INK4a) tumor-suppressor gene contributes to tumorigenesis in only a small subset of insulinomas.

Cell Cycle↗
PubMed1999

Synthesis and secretion of the anticoagulant protein S and coexpression of the Tyro3 receptor in human lung carcinoma cells.

BACKGROUND: Protein S is a plasma protein that serves as an important cofactor for activated protein C in the blood anticoagulation system. Protein S also acts as a mitogen on distinct cell types and is a ligand for Tyro3, a member of the Axl family of oncogenic receptor tyrosine kinases. This lends support to the hypothesis that protein S might also be involved in tumor cell regulation. METHODS: The expression of protein S and receptor Tyro3 was examined in 22 lung carcinoma cell lines and normal bronchial epithelial cells by reverse transcriptase-polymerase chain reaction. Secreted protein S was identified by Western blot analysis of cell supernatants and tested in a protein S-dependent clotting test for anticoagulant activity. Immunohistochemistry with anti-protein S polyvalent antiserum was also performed on 31 primary lung carcinoma specimens. RESULTS: Protein S mRNA and secreted protein were found in 11 of 12 cell lines of nonsmall cell lung carcinoma (NSCLC) origin and in normal bronchial epithelial cells, but they were found in only 4 of 10 small cell lung carcinoma (SCLC) cell lines. The majority of lung carcinoma cell lines that expressed protein S (13 of 15) also revealed expression of the cognate receptor, Tyro3. Protein S that was present in cell supernatant had anticoagulant activity comparable to that of plasma protein S, suggesting that it is gamma-carboxylated. In lung tumor tissue, protein S antigen was found in 20 of 31 cases examined, predominantly in tumors of the squamous cell and bronchioalveolar cell types. Protein S was found not only in tumor cells but also in cells of the normal bronchial epithelium, in alveolar macrophages, and in endothelium. CONCLUSIONS: To the authors' knowledge, their report is the first of the synthesis of an active anticoagulant protein in epithelial cells of human cancer. It suggests that protein S, by binding to a receptor (Tyro3), may influence local anticoagulation events or other, as yet unidentified, aspects of lung tumor development.

Antigens, Neoplasm↗
PubMed1999

Malignant fibrous histiocytoma of the pancreas: a case report with genetic analysis.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is the most common type of soft tissue sarcoma in adults; it occurs frequently in the extremities, the trunk, or retroperitoneal tissues. MFH rarely is detected in digestive organs, such as the liver or stomach. METHODS: The authors report a patient with MFH of the pancreas who was treated with surgery alone. The tumor was studied for genetic alterations in the p53, p16ink4a, and DPC4 tumor suppressor genes as well as the K-ras oncogene by immunohistochemistry, single strand conformation variant (SSCV) analysis, and direct DNA sequencing. RESULTS: The authors believe that this is the 13th report of primary pancreatic MFH in the world literature and the first genetic analysis of this rare tumor. The patient is alive with no evidence of recurrence 34 months after surgery. Immunohistochemistry revealed no abnormal accumulation of the p53 protein and normal nuclear p16 expression. Mutation analysis of the p53, p16, DPC4, and K-ras genes showed only a polymorphism at codon 72 of the p53 gene and no mutations in any of the genes. CONCLUSIONS: Genotypically, MFH of the pancreas is clearly different from other malignant pancreatic tumors, which further supports the hypothesis that this tumor is a rare but distinct entity.

Aged↗
PubMed1999

Elevated expression of endoglin, a component of the TGF-beta-receptor complex, correlates with proliferation of tumor endothelial cells.

Endoglin/CD105 is a membrane protein involved in the TGF-beta receptor signalling pathway. Endoglin expression has been reported to be selective for a few cell types, in particular endothelial cells, although a number of conflicting reports have been published. In this study, we performed a detailed analysis of endoglin expression in human lung tumors and different tumor and endothelial cell lines, employing reverse-transcriptase-polymerase-chain reaction as well as immunoblotting and immunohistochemistry using verified antibodies to endoglin. Our data show a clearly preferential expression of both endoglin mRNA and protein in endothelial cells. In tumors, endoglin expression was strongly elevated in the angiogenic endothelium at the tumor edges. In agreement with this observation, we find a clear correlation between endoglin expression and markers of proliferation, such as cyclin A and Ki-67, suggesting that endoglin expression is linked to cell-cycle regulation. These findings not only resolve some of the discrepancies in the literature, but also provide the basis for further applications making use of its selective localization and expression in the tumor vasculature.

Antigens, CD↗