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Biomedical subjects

L M Ellis

Publications and source records attributed to L M Ellis.

At least 19 recordsLinked to original sources

Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.

We studied the correlation between expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors with vascularity, metastasis, and proliferative index of human colon cancers. Immunohistochemical analyses using antibodies against VEGF, bFGF, their receptors (KDR, flt-1, bek, and flg), factor VIII, and proliferating cell nuclear antigen were carried out on archival specimens of 52 human colon carcinomas and 10 adenomas. Vessels were quantitated by light microscopy (x200), and the intensity of staining for VEGF and bFGF was assessed on a scale of 0-3+. The presence or absence of immunostaining for KDR, flt-1, bek, and flg was evaluated in endothelial cells, and proliferation was determined by counting the number of proliferating cell nuclear antigen-positive cells per 500 tumor cells. Expression of VEGF and KDR was higher in metastatic than in nonmetastatic neoplasms and directly correlated with the extent of neovascularization and the degree of proliferation, whereas expression of bFGF, flt-1, bek, and flg did not differ among tumor types. Vessel counts were greater in metastatic tumors than in nonmetastatic tumors. These findings support the hypothesis that VEGF is an important angiogenic factor in primary and metastatic human colon cancer. VEGF expression and vessel counts may aid in predicting patients at risk for metastasis from colon cancer.

Adenoma

Gastrointestinal leiomyosarcoma metastatic to the liver. Durable tumor regression by hepatic chemoembolization infusion with cisplatin and vinblastine.

BACKGROUND: Gastrointestinal leiomyosarcoma metastatic to the liver is considered most resistant to any combination of systemic chemotherapy containing doxorubicin and/or ifosphamide. METHODS: Fourteen patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated with hepatic chemoembolization infusion consisting of polyvinyl alcohol sponge particles mixed with cisplatin powder (150 mg) followed by an intrahepatic arterial infusion of vinblastine (10 mg/m2). RESULTS: Ten major (> 50% regression) tumor responses were observed (70%) in patients lasting from 8 to 31+ months (median, 12 months) after an average of two hepatic chemoembolization procedures, usually 4 weeks apart. Transient side effects included right upper quadrant pain requiring narcotics, significant hepatic enzyme elevation, particularly of lactic dehydrogenase with a minimal increase in bilirubin, paralytic ileus requiring nasogastric suction up to 72 hours, urinary electrolyte losses (potassium+, magnesium++, sodium+) requiring supplements, and occasionally mild but transient leukopenia and thrombocytopenia. CONCLUSIONS: Hepatic chemoembolization infusion appears to induce a high rate of durable tumor response in patients with notoriously chemoresistant gastrointestinal leiomyosarcoma metastatic to the liver.

Adult

In situ mRNA hybridization technique for analysis of metastasis-related genes in human colon carcinoma cells.

The purpose of this study was to determine whether the expression level of several genes that regulate different steps of the metastatic process correlates with the metastatic potential of human colon carcinoma cells. The mRNA expression level for epidermal growth factor receptor (growth), basic fibroblast growth factor and interleukin-8 (angiogenesis), type IV collagenase (invasion), E-cadherin and carcinoembryonic antigen (adhesion), and the multidrug resistance gene mdr-1 (drug resistance) in the human KM12 colon carcinoma cell lines and clones with different metastatic potential was measured by Northern blot analysis and by in situ hybridization technique. Highly metastatic KM12SM and KM1214 cells growing in culture uniformly expressed high levels of epidermal growth factor receptor, basic fibroblast growth factor, and carcinoembryonic antigen mRNA, whereas cultures of low metastatic KM12C, clone 1, clone 3, and clone 6 cells displayed heterogeneous patterns of expression. KM12C (low metastatic) and KM12SM (highly metastatic) cells were implanted into the subcutis (ectopic) or the wall of the cecum (orthotopic) of nude mice. The mRNA expression level for epidermal growth factor receptor, basic fibroblast growth factor, interleukin-8, type IV collagenase, carcinoembryonic antigen, and mdr-1 was increased in the cecal wall tumors as compared with subcutaneous tumors or in vitro cultures. These data demonstrate a direct correlation between constitutive and inducible expression of several metastasis-related genes and the metastatic potential of human colon carcinoma cells.

Adenocarcinoma

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

Laparoscopic feeding jejunostomy tube in oncology patients.

Laparoscopic-guided feeding jejunostomy tubes are being utilized in two specific groups of patients: (i) patients with resectable or locally advanced adenocarcinoma of the pancreas treated on a protocol of preoperative chemoradiation, who may require nutritional support, and (ii) patients with metastatic or obstructing foregut tumours who require a route for delivery of fluid and medication. The technique, rationale and results for our first 17 patients who underwent laparoscopic placement of a tube jejunostomy are described. Laparoscopic feeding tube placement is a safe and cost-effective method to gain enteral access and stage the oncology patient's disease. This procedure is less invasive than standard surgery for tumour staging and feeding tube placement, and facilitates formula advancement and the patient's early hospital release without morbidity or mortality.

Aged

Current strategies for the treatment of hepatocellular carcinoma.

Although hepatic resection for hepatocellular carcinoma is the only known modality that offers an opportunity for cure, the practicing oncologist must be aware of alternative modes of therapy. A multidisciplinary approach between surgeon, medical oncologist, and invasive radiologist is necessary in exploring all potential therapeutic options. The oncologist must not only consider the stage of the tumor, but must also take into account the functional reserve of the nontumor-bearing liver in selecting appropriate therapy. More recently, hepatic transplantation has been recognized as a potential curative modality for specific tumor types and stages. Percutaneous ethanol injection and chemoembolization are excellent palliative measures. However, it remains clear that new and innovative techniques are necessary in the therapeutic, adjuvant, and palliative settings in the comprehensive care of the patient with hepatocellular carcinoma.

Aneuploidy

Perioperative nutritional support.

In selected malnourished patients, perioperative nutritional support can decrease the morbidity and mortality rates associated with major surgical procedures. Preoperative nutritional support should be delivered via the gastrointestinal tract whenever feasible, generally in the form of enteral diets, which can be given via a feeding tube or as a dietary supplement. Patients with a functional gut who cannot eat because of anorexia or upper gastrointestinal tract obstruction are candidates for preoperative tube feedings. Total parenteral nutrition should be the mainstay of nutritional support when the gastrointestinal tract cannot be used adequately. An improvement in nutritional indices (e.g., serum transferrin, lymphocyte count) may be associated with decreased perioperative morbidity, although the strength of this relation is not clear. In the absence of improvement in such indices, the duration of nutritional support required to decrease operative morbidity is unknown. Postoperatively, enteral tube feedings (delivered via a nasojejunal tube or feeding jejunostomy) should be provided to all preoperatively malnourished patients with a functional gastrointestinal tract who are unable to consume adequate calories orally. Postoperative TPN should be reserved for malnourished patients with a nonfunctional gut or for patients who develop a postoperative complication that precludes enteral feeding. Current nutritional formulas have often neglected the metabolic and nutritional requirements of the intestinal tract. In the future, the combined use of specific nutrients and growth factors may improve nutritional rehabilitation in catabolic patients.

Enteral Nutrition

Differential role of prostaglandin E1 on tumor metastasis.

Previous studies from our laboratory have shown that intravenous (iv) infusion of pharmacologic doses of prostaglandin E1 (PGE1) inhibits "spontaneous" metastases in mice bearing Lewis Lung carcinoma (LLC). This study was done to determine the effect of iv PGE1 on "artificial" metastases. Male hybrid mice (20 g) underwent iv catheterization and were begun on continuous infusions of either PGE1 at 10 micrograms/kg/min or 0.9% NaCl (NS). After 2 days, each mouse received an iv injection of 10(5) viable LLC cells and was continued on the infusion regimens. Pulmonary metastatic nodules were enumerated and measured 12 days after injection. The iv infusion of PGE1 increased the metastatic rate 6-fold, the number of metastases greater than or equal to 2 mm in diameter 7-fold, and the number of metastases greater than or equal to 3 mm in diameter 14-fold. Thus, PGE1 demonstrates differential effects on tumor metastases, acting as a promotor of artificial metastases, in contrast to its antimetastatic effect on an intact primary tumor. When the promotional effect of iv PGE1 on artificial metastases is evaluated in light of our previous studies, it can be concluded that the inhibitory effect of PGE1 on spontaneous metastases from an intact tumor is secondary to the effect of PGE1 at the level of the primary tumor, and not in the circulation or at the target organ of metastases (lung).

Alprostadil

Techniques for obtaining the diagnosis of malignant breast lesions.

Although fine needle aspiration is an efficacious method for diagnosing the palpable breast cancer, a negative aspirate does not exclude the presence of a malignancy. Open breast biopsy remains the standard of care in diagnosing a malignant breast lesion. All breast biopsies should be planned as if the scar were to be excised by a definitive surgical procedure (either mastectomy or tylectomy). New lesions in the treated breast require immediate biopsy because of the high likelihood of recurrent disease. Preferably, definitive surgery for malignancy should not be delayed more than 2 weeks after biopsy.

Biopsy

Inhibition of tumor growth and metastasis by chronic intravenous infusion of prostaglandin E1.

The role of prostaglandins and their synthesis inhibitors in malignant disease is undefined. The following studies were done to determine the effects of continuous intravenous prostaglandin E1 (PGE1) or a prostaglandin synthesis inhibitor, indomethacin, on tumor growth and metastasis in mice bearing Lewis lung carcinoma. Male B6D2F1 mice underwent tumor implantation in the right axilla on day 0. After 10 days of tumor growth, mice underwent intravenous (IV) catheterization and were infused with either PGE1 at 3 micrograms/kg/minute (PG-LOW), PGE1 at 6 micrograms/kg/minute (PG-HIGH), indomethacin (INDO) at 1 microgram/kg/minute, or normal saline (NS). After 10 days of infusion, tumor volume, tumor weight, and the number of metastases greater than 2 mm in diameter were significantly decreased, and tumor doubling time was significantly prolonged in the PG-HIGH group compared to NS controls. None of the other experimental groups showed differences in these parameters. A second experiment with a similar experimental design was done infusing PGE1 at 6 micrograms/kg/minute and at 12 micrograms/kg/minute to determine the maximum dose response of IV PGE1. Again a decrease in tumor volume, tumor weight, and metastatic rates were identified when compared to saline control, but there were no significant difference between the two doses of PGE1.

Alprostadil

Lability of steroid hormone receptors following devascularization of breast tumors.

Ischemia may invalidate hormone-receptor analyses. This study determined the effects of progressive ischemia on steroid hormone-receptor analyses. Breast cancer was induced in 50- to 60-day-old female Holtzman rats by intragastric administration of 25 mg of 7,12-dimethylbenz[a]anthracene. After 90 days, rats were anesthetized and breast tumors were devascularized in vivo. At 0, 30, 60, 90 and 150 minutes, a biopsy specimen from each tumor was taken and rapidly frozen. Steroid binding capacity for estrogen (ER), progesterone (PR), and androgen (AR) receptors was determined by incubation with tracer receptor ligand. Ischemia decreased ER and AR levels by 30 minutes, whereas PR levels were unchanged through 150 minutes of ischemia. Following mastectomy, tylectomy, or breast biopsy, PR may be the most reliable of the hormone receptors for determining endocrine-responsive breast cancer. However, for accurate determination of all hormone receptors, specimens should be frozen in liquid nitrogen immediately, then preserved at -70 degrees C, or processed immediately.

9,10-Dimethyl-1,2-benzanthracene

Correlation of estrogen, progesterone, and androgen receptors in breast cancer.

Breast cancer was induced in female Holtzman rats by intragastric administration of 7,12-dimethylbenz[a]antracene (DMBA). At tumor maturity, biopsies of viable tissue were obtained, frozen, and then assayed for estrogen, progesterone, and androgen receptor content. By simple linear regression analysis, progesterone receptor levels significantly correlated with both estrogen and androgen receptor levels, whereas estrogen and androgen receptor levels did not correlate with each other. Multiple regression analyses further substantiated the predictive value of the progesterone receptor for the other two hormone receptors. Knowledge of breast tumor androgen receptor levels may further enhance the value of the estrogen receptor and progesterone receptor in hormonal responsiveness. Further, the progesterone receptor may be the most sensitive of the steroid hormone receptors for selecting patients likely to respond to hormonal therapy.

9,10-Dimethyl-1,2-benzanthracene

Central venous catheter vascular erosions. Diagnosis and clinical course.

Central venous catheter (CVC) vascular erosions are difficult to diagnose, and they cause serious complications. From 1985 to 1987, ten patients receiving the surgical services at the University of Florida suffered CVC vascular erosions. By chest roentgenogram, nine CVC tips were in the superior vena cava (SVC), although three catheter tips abutted the lateral wall of the SVC. One catheter tip was in the right atrium. All patients had sudden onset of symptoms, the most common of which was shortness of breath. Initial diagnosis was respiratory insufficiency in five patients, cardiac failure in three patients, pulmonary embolism in one, and sepsis in one. Four patients required intensive care. Two patients suffered pericardial tamponade, and pleural effusions developed in eight patients. One patient died of cardiac arrest. The average time interval from CVC placement to onset of symptoms was 60.2 hours, and from the onset of symptoms to the time of diagnosis, the interval was 16.7 hours. The mean volume obtained at thoracentesis was 1324 ml and at pericardiocentesis was 250 ml.

Adult

Inflammatory breast cancer: advances in therapy.

Inflammatory breast cancer is the most aggressive breast neoplasm and one of the most ominous solid tumors. Because of distinct clinical characteristics, diagnosis can usually be made on clinical grounds. Biopsy including the overlying skin may demonstrate dermal lymphatic invasion, although the absence of dermal lymphatic invasions should not deter aggressive therapy. Surgery or irradiation alone has little effect on the natural history of this disease since lymphatic invasion and distant metastases are often present at presentation. Inflammatory breast cancer should be considered a systemic disease. Accordingly, aggressive combined modality therapy including multi-drug chemotherapy, surgery, and irradiation have prolonged disease-free survival and overall survival.

Antineoplastic Combined Chemotherapy Protocols

Partial hepatectomy decreases pancreatic parenchymal enzyme activity.

In previous studies of liver regeneration following partial hepatectomy (PH) in rats, we noted a decrease in serum amylase activity. The present study was carried out to determine if the decrease in serum amylase following PH corresponds to a decrease in pancreatic parenchymal exocrine enzyme activity. Male Wistar rats (275 g) underwent either 60% PH or sham laparotomy (SL). A third group, serving as controls (CON), received no surgical procedure. All groups were pair-fed a nutritionally balanced diet. After 48 hr, pancreas, blood, and liver were removed for analysis. Results showed that PH decreased pancreatic parenchymal protein by 43%, lipase by 44%, and trypsin by 22% compared to controls. Serum amylase decreased by 28%, a finding similar to previous experiments. However, pancreatic parenchymal amylase activity was not affected. It remains to be determined whether the reduced pancreatic function affects digestion and absorption.

Amylases

The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome.

The purpose of this study was to determine whether basal or stimulated (or both) serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 of the cycle before administration of exogenous gonadotropins can predict stimulation response and in vitro fertilization (IVF) outcome. Eighty consecutive new patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test on the morning of cycle day 3. All patients underwent the same stimulation protocol consisting of a combination of FSH and human menopausal gonadotropin (hMG). Paired discriminant analysis of FSH0 (at 0 minutes from GnRH injection) and LH0 revealed seven distinct groups of patients with statistically significant differences among the means: groups 1, 2, and 3 (26.25%) with higher means FSH0:LH0; group 4 (40%) with mean FSH0:LH0 (both levels less than 10 mIU/ml) of 1:1, and groups 5, 6, and 7 (33.75%) with higher mean LH0:FSH0. Canonical discriminant analysis of both basal and stimulated serum FSH and LH levels confirmed the seven groups and did not add to the information from analysis of FSH0 and LH0 only. Serum estradiol (E2) response during stimulation, as well as the number of preovulatory oocytes aspirated and transferred, was highest in the groups with a higher mean LH0:FSH0, intermediate in the group with mean FSH0:LH0 of 1:1, and lowest in the group with a higher mean FSH0:LH0. No pregnancy occurred in the higher FSH:LH groups. It is concluded that basal serum gonadotropin levels can distinguish different populations of IVF patients who tend to behave differently in terms of E2 response, oocytes obtained and transferred, and pregnancy rates and outcome.

Abortion, Spontaneous