Biomedical subjects

T L Moskal

Publications and source records attributed to T L Moskal.

10 recordsLinked to original sources

PubMed1999

Small cell carcinoma of the gallbladder.

BACKGROUND AND OBJECTIVES: Small cell carcinoma of the gallbladder is rare with only 36 cases reported in the literature. Early reports demonstrated an extremely poor prognosis for this histologic type. Five new cases are reported and the previous experience in the literature is reviewed to further clarify the clinical behavior of this malignancy. METHODS: A retrospective analysis is performed on 5 new cases. An extensive review of the literature is also performed. RESULTS: Twenty-eight pure small cell carcinomas and 8 combined small cell carcinomas with adenocarcinoma are reported in the literature. Conclusions from the literature review reveal that small cell carcinoma of the gallbladder affects an elderly patient population (median age 65 years), has a female preponderance (76%), is associated with cholelithiasis (72%), metastasizes to nodes (88%), liver (88%), lung (23%), and peritoneum (19%), and has a median survival of 4 months. Pure tumors had median survivals of 9 months and combined tumors had median survivals of 4.5 months. The 5 patients in the literature treated with surgery and chemotherapy had improved median survival of 13 months. The 5 newly reported cases had similar epidemiological characteristics to the literature data, however, these cases were managed aggressively with surgery and chemotherapy, demonstrating a median survival of 31 months. CONCLUSIONS: Although small cell carcinoma of the gallbladder is a distinct histologic and clinical entity, it has many clinical characteristics similar to adenocarcinoma of the gallbladder including comparable natural history and tendency for locoregional spread. Aggressive multimodality therapy, especially the combination of surgery and chemotherapy, may improve survival.

Adult↗

PubMed1999

Efficacy and specificity of antisense laminin chain-specific expression vectors in blocking laminin induction by TGFbeta1: effect of laminin blockade on TGFbeta1-mediated cellular responses.

Transforming growth factorbeta1 (TGFbeta1) elicits a multitude of cellular responses from the epithelial-derived human colon cancer Moser cells. TGFbeta1 induces the expression of laminin and fibronectin, and previous studies show that the induction of fibronectin is functionally associated with the regulation of carcinoembryonic antigen (CEA) expression by TGFbeta1 (Huang and Chakrabarty, 1994, J Biol Chem 269:28764-28768). In this study we constructed antisense laminin chain-specific expression vectors and determined their efficacy in blocking the expression and the induction of the large multichain laminin molecule by TGFbeta1. We also determined the functional role of laminin in several TGFbeta1-mediated responses: growth inhibition, downmodulation of anchorage-independent growth, and cellular invasion. Expression of either antisense laminin chain A, B1, or B2 RNA resulted in a downmodulation of endogenous laminin mRNA expression and blocked the induction of laminin protein by TGFbeta1 without affecting the induction of other adhesion molecules such as fibronectin or CEA. It is concluded that antisense RNA directed to only one of the laminin chains was sufficient to disrupt the induction of the complex laminin molecule in quite a specific manner. Expression of antisense laminin RNA downregulated cellular adhesion to extracellular matrix (ECM) laminin and blocked the ability of TGFbeta1 to upmodulate adhesion to ECM laminin. Expression of antisense laminin RNA, however, did not alter the downregulating effect of TGFbeta1 on cellular proliferation, anchorage-independent growth, or cellular invasion, suggesting that the induction of laminin did not play a significant functional role in these TGFbeta1-mediated cellular responses. It is likely that other adhesion pathways may be involved in mediating the action of TGFbeta1 in this cell line.

Carcinoembryonic Antigen↗

PubMed1999

Left mediastinal central line malposition--a case report.

Central venous line malpositioning in the left mediastinum is a rare event. A case of left superior intercostal vein central venous line placement is reported. Chest radiographs, especially lateral views and contrast studies, are useful for position evaluation. Catheter removal is prudent although the purpose of the catheter and the symptomatology can dictate further management of the malpositioned catheter.

Aged↗

PubMed1998

Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up.

BACKGROUND: Conventional therapy for pleural mesothelioma has met with disappointing results. METHODS: From 1991 to 1996, 40 patients with malignant pleural mesothelioma were treated with surgical resection followed by immediate intracavitary photodynamic therapy. RESULTS: The series included 9 women and 31 men with a mean age of 60 years. Morbidity and treatment-related mortality rates for the entire series, pleurectomy, and extrapleural pneumonectomy were 45% and 7.5%, 39% and 3.6%, and 71% and 28.6%, respectively. Median survival and the estimated 2-year survival rate for the entire series, stages I and II patients (n = 13), and stages III and IV patients (n = 24) were 15 months and 23%, 36 months and 61%, and 10 months and 0%, respectively. Multivariate analysis identified stage, length of hospital stay, photodynamic therapy dose, and nodal status as independent prognostic indicators for survival. CONCLUSIONS: Surgical intervention and photodynamic therapy offer good survival results in patients with stage I or II pleural mesothelioma. For patients in stage III or IV, better treatment modalities need to be developed. Improvements in early detection and preoperative staging are necessary for proper patient selection for treatment.

Antineoplastic Agents↗

PubMed1998

Protein kinase Calpha controls the adhesion but not the antiproliferative response of human colon carcinoma cells to transforming growth factor beta1: identification of two distinct branches of post-protein kinase Calpha adhesion signal pathway.

Transforming growth factor beta1 (TGFbeta1) inhibits cellular proliferation and induces the expression of the matrix adhesion molecules fibronectin (FN) and laminin (LM) in a concurrent manner, followed by the induction of the intercellular adhesion molecule carcinoembryonic antigen (CEA) (collectively designated as adhesion responses) in TGFbeta1-responsive human colon carcinoma cells. Exactly how TGFbeta1 controls cellular adhesion and proliferation is poorly understood. In the present report, we showed that down-regulating protein kinase Calpha (PKCalpha) expression blocked the induction of these adhesion responses by TGFbeta1, showing that PKCalpha is a postreceptor focal point controlling the induction of these molecules. Down-regulating PKCalpha expression, however, had minimal effect on the antiproliferative response to TGFbeta1 or the induction of p21/WAF1, a marker associated with the antiproliferative effect of TGFbeta1, demonstrating that the adhesion signal pathway is distinct from that of antiproliferation. Blockade of FN induction blocked the induction of CEA but not the induction of LM. Blockade of LM induction, on the other hand, had no effect on the induction of FN and CEA. These results established the existence of two distinct and parallel postPKCalpha adhesion signal pathways, one leading to the induction of LM and the other leading to the induction of FN and CEA.

Carcinoembryonic Antigen↗

PubMed1997

Subclavian artery obstruction by tube thoracostomy.

A case of subclavian artery obstruction by tube thoracostomy for penetrating trauma is presented. The obstruction was not physiologically significant; however, it did impede the assessment of the subclavian artery for potential injury using emergency center arteriography. The difficulty was easily corrected with repositioning of the chest tube. This previously undescribed complication of tube thoracostomy is presented with its clinical implications.

Adult↗

PubMed1995

Epidermal growth factor expression in human colon and colon carcinomas: anti-sense epidermal growth factor receptor RNA down-regulates the proliferation of human colon cancer cells.

Human colon cancer cell lines express epidermal growth factor (EGF) mRNA, secrete EGF and may respond to it via the cell-surface EGF receptor (EGFR). Expression of these molecules in human colon and colon tumor, however, is not clear. Reverse transcription-polymerase chain reaction (RT-PCR) analyses of RNA prepared from paired normal human colon and colon tumor samples from 12 individuals followed by Southern blotting analyses of the RT-PCR products revealed a major fragment of 527 bp and a minor fragment of 404 bp that hybridized to a human EGF cDNA probe under stringent conditions. Identical results were obtained from 8 human colon cancer cell lines. Cloning and sequencing of PCR products confirmed that both fragments were from the human EGF gene; the 527-bp fragment corresponded exactly to nucleotides 2,891 to 3,417 of the human EGF mRNA reported by others. A deletion of 123 nucleotides (nucleotides 3,172 to 3,294) was found in the 404-bp fragment. Immunohistochemical studies using cyostat sections of human colon specimens showed that EGF was expressed in the human colon and that expression was restricted to the epithelial colonic crypt cells and epithelium-derived cancer cells. Since EGF and EGF-related molecules are potent mitogens that mediated their effect through the EGFR, we also determined the efficacy of anti-sense EGFR RNA in circumventing the EGFR-related pathway of proliferation. Expression of anti-sense EGFR RNA, by transfection with an inducible anti-sense EGFR expression vector, down-regulated cell-surface EGFR expression and proliferation of these cells and their ability to grow in soft agar. Anti-sense EGFR RNA was found to be an anti-proliferative agent in both relatively non-aggressive and highly aggressive human colon cancer cells.

Adenocarcinoma↗

PubMed1995

Serum levels of transforming growth factor alpha in gastrointestinal cancer patients.

Transforming growth factor alpha (TGF alpha), a polypeptide growth-stimulating factor, has been implicated to play a role in the progression of gastrointestinal (GI) cancer. It has been suggested that TGF alpha expression in tumors or TGF alpha in the biological fluids of cancer patients may have tumor marker value. The serum levels of TGF alpha in GI cancer patients have not been reported. In this study, the serum TGF alpha levels of 100 GI cancer patients, as well as 74 healthy individuals, were determined by a TGF alpha-specific RIA kit. All of the cancer patient sera and 67% of the normal sera had detectable levels of TGF alpha. The TGF alpha concentrations in GI cancer patients ranged from 119 to 760 pg/ml, with a mean value of 269 +/- 102 pg/ml. Fifty normal individuals had detectable levels of TGF alpha, and their levels ranged from 120 to 207 pg/ml, with a mean value of 147 +/- 18 pg/ml. Differences in serum TGF alpha concentration between cancer patients and healthy individuals were found to be statistically significant, as evaluated by Mann-Whitney and Student's t tests. Serum TGF alpha levels were found to be significantly elevated in all disease stages of gastric, pancreas, colon, and rectal cancers, and only in the late stages of esophageal cancer. Serum carcinoembryonic antigen levels were significantly elevated only in the late stages of these diseases. The potential of serum TGF alpha as a tumor marker for GI malignancy, therefore, warrants further investigation.

Adult↗

PubMed1994

Elevated serum levels of transforming growth factor-alpha in breast cancer patients.

Previous studies suggest that transforming growth factor-alpha (TGF alpha) may have the potential of a tumor marker. Since the levels of serum TGF alpha in cancer patients and healthy individuals have not been reported, we determined the serum TGF alpha levels of 83 breast cancer patients and 74 healthy individuals by using a TGF alpha radioimmunoassay kit. All of the cancer patients' sera were positive for TGF alpha; their TGF alpha concentrations ranged from 210 to 740 pg/ml, with a mean of 353 +/- 98 pg/ml. Sixty-seven percent (50 cases) of normal sera were positive for TGF alpha; the levels ranged from 120 to 207 pg/ml, with a mean of 144 +/- 17 pg/ml. The difference in serum TGF alpha levels between cancer patients of different disease stages and healthy individuals was found to be statistically significant by Student t-test and the Mann-Whitney test. No correlation was found between serum carcinoembryonic antigen and TGF alpha levels. The potential of serum immunoreactive TGF alpha as a marker for breast cancer warrants further investigation.

Adult↗

PubMedDate not supplied

Malignant pleural mesothelioma: a problematic review.

Malignant pleural mesothelioma is a rare tumor that has been difficult to study. Because of disappointing treatment results, malignant pleural mesothelioma has remained an area of active research and development. A clinicopathologic review is performed in light of several problematic issues involving diagnosis, staging, natural history, and treatment. Multimodality treatment with surgery followed by adjuvant local and systemic therapy remains the most optimal therapy. Many controversial issues still exist in the treatment of malignant pleural mesothelioma. In the ensuing years newer staging systems, better preoperative staging, newer experimental therapies, and the localization of patients at expert centers will undoubtedly have an impact on disease management.

Adult↗