Biomedical subjects

J D Beatty

Publications and source records attributed to J D Beatty.

At least 55 records · Page 3Linked to original sources

PubMed1990

Radioimmunotherapy of human colon carcinomatosis xenograft with 90Y-ZCE025 monoclonal antibody: toxicity and tumor phenotype studies.

Monoclonal antibody ZCE025 recognizes an epitope of the carcinoembryonic molecule (CEA). We have shown that when linked to 90Y, its localization in the tumor was sufficient to result in a significant tumoricidal effect in human colon carcinomatosis grown in the peritoneum of athymic mice. Intraperitoneal tumors were present 7 days after inoculation of the CEA-producing human colon carcinoma cell line LS174T, when the mice received i.p. injections with 40 to 160 microCi of 90Y-labeled ZCE025 or 96.5c (nonspecific monoclonal antibody). The animals that were autopsied 12 days after treatment displayed a significant (P less than 0.001) inhibition of tumor growth when compared to the control animals that received no treatment or similar doses of nonspecific monoclonal antibody. Microscopically, the treated tumors showed extensive radiation effect and they became progressively necrotic until only a rim of viable tissue remained in the periphery of the nodules. CEA expression was practically absent on the newly grown nodules that began to appear 3 weeks after therapy, and remained so 6 weeks thereafter. In contrast, over 80% of the tumor cells from the untreated animals expressed CEA. There was no mortality due to treatment; however, the hematopoietic organs were markedly depleted at the higher doses. The marrow and the spleen recovery began 2 weeks after treatment, and it was completed by the 4th week. No evidence of toxicity was present in any of the other organs examined. These studies suggest that 90Y-ZCE025 therapy results in clonal selection of cells lacking or minimally expressing CEA. The inherent implications of these findings are discussed.

Animals↗

PubMed1990

Radioimmunotherapy of human colon cancer in nude mice.

Nude mice bearing subcutaneous human colon cancer xenografts (LS174T) were treated with 120 microCi of yttrium 90-labeled anti-carcinoembryonic antigen monoclonal antibodies (specific therapy), 120 microCi of 90Y-labeled anti-melanoma monoclonal antibodies (nonspecific therapy), or phosphate-buffered saline solution (no treatment control). Mean (+/- SD) tumor growth rates (percent increase per day) over the first 30 days of the study were as follows: 0.6% +/- 0.2% per day (specific therapy); 17.7% +/- 5.7% per day (nonspecific therapy); and 30.5% +/- 4.2% per day (control). In all three groups, tumors over 1 g had similar doubling times (5.74 +/- 0.71 d). Specific therapy caused a lag in tumor growth corresponding to a 3-logarithm cell kill. Estimated tumor dose of radiation obtained by tissue analysis was 34 and 14 Gy for specific and nonspecific therapy, respectively. In conclusion, 120 microCi of 90Y-labeled anti-carcinoembryonic antigen monoclonal antibodies was effective in suppressing growth of human colon cancer xenografts. Clinical studies with this preparation are recommended.

Animals↗

PubMed1990

Localization of intraperitoneal xenografts of human colon cancer by radiolabeled anti-CEA antibodies.

An intraperitoneal xenograft tumor model was developed in the nude mouse to represent advanced colorectal disease in the human patient. Intraperitoneal (ip) and subcutaneous (sc) tumor xenografts were successfully localized by indium 111-labeled anti-carcinoembryonic antigen monoclonal antibodies (Indacea) administered intravenously (IV) or intraperitoneally (IP). In the sc model, tumor uptake (% injected dose per g of tumor tissue--%ID/g) was significantly improved at 72 hours postinjection when Indacea was administered IP (44.01 +/- 1.94 vs. 33.74 +/- 0.87, P less than 0.005). In the ip model, tumor uptake at 72 hours was improved with IP Indacea (28.23 +/- 5.42 vs. 19.36 +/- 5.50, P less than 0.01) and the tumor to blood ratio was significantly improved for IP Indacea (17.83 +/- 2.95 vs. 8.45 +/- 1.38, P less than 0.01). Tumor mass was not a contributing factor in these differences. This study demonstrates that ip xenografts can be successfully imaged using radiolabeled antibodies and that the IP route of administration results in better tumor uptake of the antibody in ip lesions.

Animals↗

PubMed1990

A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver.

Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02).

Adult↗

PubMed1990

A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.

The ability of perioperative cefazolin to reduce the incidence of postoperative wound infection in patients undergoing ablative surgical treatment for carcinoma of the breast was tested in this prospective, randomized, double-blinded study. From May 1983 until December 1985, 118 women were divided into two groups at random. Group 1 consisted of 59 patients and received cefazolin and group 2 was made up of 59 patients who received a placebo. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. Three infections occurred among those in group 1 and five among those in group 2 (p = 0.72). The time to onset of infection was delayed in the patients in group 1 versus those in group 2 (17.7 days versus 9.6 days, p = 0.04). Six of eight infections occurred in patients in whom an interval between biopsy and definitive surgical treatment was present. Prophylactic antibiotics in mammary operations did not reduce postoperative wound infections in this study.

Breast Neoplasms↗

PubMed1989

Effect of yttrium-90-labeled anti-carcinoembryonic antigen monoclonal antibody on the morphology and phenotype of human tumors grown as peritoneal carcinomatosis in athymic mice.

Grossly visible peritoneal carcinomatosis resembling that seen in man was produced in athymic mice 7 days after intraperitoneal injection of 8 x 10(5) cells of the carcinoembryonic antigen (CEA)-producing human colon carcinoma cell line LS174T. The mice received intraperitoneal injections of 40 to 160 microCi of yttrium-90 (90Y)-labeled anti-CEA monoclonal antibody (MAb). When the mice were killed 12 days after injection, a significant inhibition of tumor growth, ranging from 40% to 95%, was observed in the treated animals when compared to the growth of tumors in the untreated animals (P less than 0.001). No mortality secondary to the therapy was seen. The bone marrow was depleted significantly at the higher doses of labeled MAb, but total recovery was observed 4 weeks after treatment. Histologically, the treated tumors showed extensive radiation effects early in the posttherapy period and massive necrosis at later times. Minute foci of viable tumor remained in the periphery. New tumor outgrowths with histologic features similar to those in the untreated controls began to appear 3 weeks after therapy. The CEA expression of the treated tumors was similar to that of the untreated controls during the early posttreatment period, diminishing progressively as the tumors became necrotic. Newly grown tumor nodules in the treated animals lacked significant CEA expression both initially and at later times. Our studies suggest that therapy with 90Y-anti-CEA MAb therapy results in selection of tumor clones lacking CEA, and that a single large dose of 90Y-MAb should be more effective than multiple fractions of smaller doses.

Animals↗

PubMed1989

Effect of specific antibody pretreatment on liver uptake of 111In-labeled anticarcinoembryonic antigen monoclonal antibody in nude mice bearing human colon cancer xenografts.

Administration of a large dose (0.2 mg) of unlabeled specific anticarcinoembryonic antigen (anti-CEA) monoclonal antibody (MAB) to nude mice bearing LS174T human colon cancer xenografts significantly decreased normal liver uptake of 111In-labeled anti-CEA MAB (Indacea). Mice bearing tumors of approximately 1 g showed liver accumulation of indium-111 at 48 h following injection of 2 micrograms/10 microCi Indacea of 33.8 +/- 1.5% injected dose per gram (%ID/g) (N = 25). Treatment with 0.2 mg unlabeled anti-CEA MAB reduced this to 8.9 +/- 0.5% ID/g (N = 22; P less than 0.001). The dose of pretreatment was found to be critical. Increasing the amount of unlabeled MAB to 2.0 mg did not significantly improve the liver level of indium-111, but did compromise the tumor uptake of Indacea (15.9 +/- 1.3 versus 12.4 +/- 0.4% ID/g; P less than 0.05). Lowering the dose of pretreatment 10-fold resulted in increased (P less than 0.001) liver uptake of the label (26.5 +/- 2.8% ID/g). The unlabeled anti-CEA MAB treatment given as a single dose or fractionated over several days gave the same results. The decrease in liver uptake was the same for i.v. administration of the unlabeled MAB given 1 week prior to Indacea injection or mixed together with Indacea. With i.p. administration, simultaneous injection of the unlabeled MAB with Indacea was not as effective as pretreatment (20 min to 7 days) in decreasing the liver uptake of 111In (P less than 0.05). Epitope specificity and affinity were shown to be important considerations in the choice of MAB combinations used for pretreatment and imaging. Pretreatment with nonspecific MAB was ineffective in decreasing liver uptake of Indacea.

Animals↗

PubMed1989

Prolongation of survival of nude mice bearing human colon cancer. Treatment with yttrium 90-labeled anti-carcinoembryonic antigen antibody.

Nude mice bearing diffuse intraperitoneal carcinomatosis of the human colon cancer cell line LS174T were treated with an anti-carcinoembryonic antigen monoclonal antibody (MAB) that was labeled with yttrium 90 (90Y-ZCE025). Control animals were either untreated or treated with nonspecific 90Y-MAB (90Y-96.5c). The median survival (MS) for untreated animals was 26 days. The MS for specific and nonspecific therapy that consisted of 120 microCi of 90Y-MAB was 69 and 34 days, respectively. No significant improvement in the MS was observed with a second 120-microCi administration of 90Y-MAB given two weeks later. A decreased MS was observed with 80 microCi of 90Y-MAB given every four days for three cycles. In each category, specific therapy had a significant advantage over nonspecific therapy in increased effectiveness and decreased toxicity. The 90Y-ZCE025 therapy gave an increased life span of almost 200%. The therapeutic effects with different dosing regimens have important implications for treatment planning.

Animals↗

PubMed1989

Evaluation of a short-stay program for patients undergoing mastectomy.

Two hundred twenty-eight patients were included in a retrospective study to evaluate the morbidity and feasibility of early discharge after mastectomy. Group I (early discharge, n = 75) patients were given pre- and postoperative instruction related to wound and drain care. Group II (concurrent control, n = 44) was given similar postoperative instruction, but received no preoperative teaching. Group III (historical controls, n = 109) underwent surgery during a period of more liberal hospitalization and discharge policies. The groups were similar in age, cultural background, operations performed, and pathologic diagnosis. Length of stay for groups I, II, and III was 5.5 +/- 0.4, 3.5 +/- 0.2, and 8.6 +/- 0.3 days, respectively. Groups I and II had a significantly shorter stay than group III. There was no difference among the groups for the presence of wound erythema, rate of primary healing, seroma formation, or wound infection. The practice of same-day admission and early discharge to limit length of stay for patients undergoing mastectomy is safe and effective.

Breast Neoplasms↗

PubMed1989

Impact of radiolabeled antibody imaging on management of colon cancer.

One hundred patients with known or suspected colorectal cancer were studied by radioimmunoconjugate scintigraphy prior to operation. Study subjects received murine monoclonal anticarcinoembryonic antigen labeled with indium 111 (Indacea). Sensitivity of imaging was 76 percent for primary tumors, 44 percent for hepatic metastases, 38 percent for extrahepatic abdominal metastases, and 78 percent for extraabdominal metastases. Seventeen of 46 patients (37 percent) with known or suspected hepatic metastases and no evidence of extrahepatic disease by conventional imaging methods had extrahepatic metastases at exploratory surgery. Nine of the 17 patients had disease accurately predicted by the Indacea scanning. The management of each of these nine patients was, or could have been, modified by the scan findings and unnecessary surgery eliminated. A number of patients without post-operative disease had an unexplained increase in plasma carcinoembryonic antigen level due to production of human antimouse antibody. The addition of excess mouse immunoglobulin to the plasma prior to assay blocked this artifactual increase.

Adenocarcinoma↗

PubMed1989

The effects of hyperthermia on tumor carcinoembryonic antigen expression.

The effects of hyperthermia on carcinoembryonic antigen (CEA) expression were investigated. The human colon adenocarcinoma cell line, LS174T, was heated in vitro for 42 degrees C/1 hr, 43 degrees C/1 hr, or 45 degrees C/30 min. Carcinoembryonic antigen membrane expression was assayed by live cell radioimmunoassay 0-6 days after heating. A heat exposure of 45 degrees C/30 min resulted in an initial decrease in carcinoembryonic antigen membrane expression 1 day post-heating followed by a 2-3 fold increase which peaked 3 days post-heating. Carcinoembryonic antigen expression began returning to normal by the sixth day. Heat exposures of 42 degrees C/1 hr and 43 degrees C/1 hr also resulted in increased carcinoembryonic antigen expression but this increase was of lesser magnitude and of shorter duration. Carcinoembryonic antigen shed into the medium, as measured by enzyme immunoassay, also increased after heating in a temperature-dependent fashion. Flow cytometry analysis demonstrated that cells in all phases of the cell cycle expressed this increase. We conclude that hyperthermia results in significant changes in carcinoembryonic antigen membrane expression and shedding. The implications that these findings have with regards to clinical hyperthermia and radioimmunotherapy are discussed.

Adenocarcinoma↗

PubMed1989

The effects of tumor mass, tumor age, and external beam radiation on tumor-specific antibody uptake.

The effects of external beam radiation on tumor uptake of radiolabeled monoclonal antibody were investigated. Nude mice bearing carcinoembryonic antigen (CEA)-producing subcutaneous human tumor xenografts (LS174T) were irradiated (60Co) with a single fraction of 0, 2 or 20 Gy, 6 or 11 days after tumor inoculation. An Indium-111 labeled anti-CEA monoclonal antibody (T84.66) was injected 1-2 hrs after irradiation. Biodistribution studies performed at 48 hrs showed a statistically significant (p less than 0.01) inverse correlation between tumor mass and tumor antibody uptake. Tumor age was also a significant factor with 11 day old tumors having significantly less uptake (p less than 0.0001) compared to 6 day old tumors for a given mass. Radiation increased tumor antibody uptake only in those tumors where growth inhibition also occurred. Multiple regression analysis showed that this inverse correlation between tumor mass and antibody uptake was the same for irradiated and nonirradiated tumors. We conclude that, in this model system, radiation does not act independently to enhance tumor antibody deposition. Radiation's primary effect is to reduce tumor mass, with mass reduction then resulting in an increase in antibody uptake. The clinical implications of this study are discussed.

Animals↗

PubMed1988

The external oblique myocutaneous flap for extended hemipelvectomy reconstruction.

This article documents the first case report of an extended hemipelvectomy defect closure using an ipsilateral external oblique myocutaneous flap. When a hemipelvectomy usually is performed for soft tissue tumor ablation, an anterior or posterior flap can be preserved for immediate coverage of vital structures. When these flaps are also resected to obtain clear tumor margins, closure becomes difficult. In our patient, although the rectus myocutaneous flap was a next logical choice, prior surgical scars precluded it use. The external oblique flap was successfully rotated and solved a difficult problem. This flap should be considered when the rectus abdominis myocutaneous flap is unavailable for extended hemipelvectomy closures.

Abdomen↗

PubMed1988

Artifactual CEA elevation due to human anti-mouse antibodies.

Retrospective analysis of 108 patients who received indium 111-labeled murine monoclonal antibodies for imaging of cancer was performed. Most patients had operative procedures for colorectal carcinoma following completion of scintiscanning. Eleven patients had markedly elevated carcinoembryonic antigen (CEA) levels postoperatively without evidence of residual or recurrent disease. The laboratory method of measuring CEA levels was a commercially available double mouse monoclonal antibody enzyme immunoassay. It was postulated that the unexplained elevation of CEA was a reflection of the presence of human anti-mouse antibody (HAMA) induced by the administration of radiolabeled mouse antibody. A competitive assay for HAMA was undertaken by incubation of these patients' sera with a high dose of nonspecific mouse immunoglobulin prior to CEA determinations, and subsequent CEA levels were normal. The presence of HAMA was confirmed by a noncompetitive solid-phase enzyme immunoassay in 73% of tested patients who received murine monoclonal antibodies for imaging. Identification of artifactual CEA elevations is important in the treatment of cancer patients.

Aged↗

PubMed1988

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.

A prospective randomized trial was performed in patients with advanced squamous cell carcinomas (SCC) of the oral cavity, larynx, and pharynx to examine the effect of adjuvant postoperative radiation therapy on locoregional recurrence and survival following "curative" resection. Fifty-one patients with stage III or IV SCC treated from 1981 through 1984 were randomized to receive either surgery alone (n = 27) or surgery with postoperative radiation (n = 24). Five patients were excluded from the study after randomization because of ineligibility or protocol violations. Overall recurrence rates of 55.6% and 36.8% were noted in the surgery and surgery with adjuvant radiotherapy arms, respectively (p = NS). This trend towards a higher recurrence rate in the surgery only arm was in part due to the development of lymph node metastases in the contralateral, nonoperated neck. Thus far, no significant differences in either locoregional or overall survival have been noted between the two treatment arms. In this preliminary analysis, adjuvant postoperative radiotherapy does not appear to improve disease-free or overall survival.

Adult↗

PubMed1988

Radiographic evaluation for pulmonary metastases in sarcoma patients.

The records of 130 patients with soft tissue and bone sarcomas were retrospectively analyzed to identify the subgroups of patients that would benefit from tomographic studies for pulmonary metastasis. Sixty-six of 96 patients with a normal conventional chest roentgenogram (CXR) had tomography to diagnose pulmonary metastasis. Of the 53 patients who had primary disease and a normal CXR followed by tomography, only 1 (1.9%) had metastases identified on tomograms. Of the 13 patients who had locally recurrent sarcoma and a CXR plus tomographic studies, 2 (15%) had metastases detected on tomogram only. Tomographic studies detected significantly more sarcoma patients with pulmonary metastasis in the group with locally recurrent disease than in the group with primary disease (P less than 0.05).

Adult↗

PubMed1988

Intracatheter hyperthermia and iridium-192 radiotherapy in the treatment of bile duct carcinoma.

We report a case of a patient with locally advanced bile duct carcinoma treated with 4500 cGy external beam radiotherapy, followed 3 weeks later by intracatheter 915 MHz microwave hyperthermia and radiotherapy delivered through a biliary U-tube placed at the time of surgery. Heating was to 43-45 degrees C for 1 hour followed immediately by intracatheter Iridium-192 seeds to deliver 5000 cGy over a 72 hour period. Prior to treatment, a thermal dosimetry study in phanton was conducted, using the same type of U-tube catheter tubing as in the patient. Orthogonal X rays of the patient's porta hepatis region were used to reconstruct the catheter geometry in the phantom. Proper insertion depth was determined thermographically to obtain maximum heating at the center of the tumor. The maximum SAR was 8.8 watts per kilogram per watt input. During the treatment, the average power applied was 30 W. Six months after therapy, the patient is asymptomatic. Although alkaline phosphatase, SGOT and SGPT have remained elevated, bilirubin has returned to normal and computerized tomographic scans and cholangiograms remain stable. A duodenal ulcer developed after therapy and is healing well with conservative medical management. This case demonstrates that hyperthermia applied through biliary drainage catheters is technically feasible and clinically tolerated. We believe the use of intracatheter hyperthermia in conjunction with external and/or intracatheter radiotherapy in selected patients with unresectable bile duct carcinomas warrants further study.

Alanine Transaminase↗

PubMed1988

Predicting the need for prolonged enteral supplementation in the patient with head and neck cancer.

Nutritional support is an important consideration in the management of the head and neck cancer patient. In our series, characteristics significantly associated with the need for long-term postoperative nutritional support included stage IV cancers, primary pharyngeal tumors, combined treatment utilizing surgery and radiotherapy, and preoperative weight loss of more than 10 pounds. In planning nutritional support, nasogastric tube feeding is appropriate for short-term use. In contrast, gastrostomy tube feeding is preferable for those head and neck cancer patients with a high probability of requiring long-term nutritional support postoperatively.

Body Weight↗