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Biomedical subjects

W D Holder

Publications and source records attributed to W D Holder.

33 records · Page 2Linked to original sources
PubMed1989

The in vivo distribution of human peripheral blood lymphocytes and lymphokine-activated killer cells adoptively transferred in human pancreatic cancer-bearing nude mice.

In this study we evaluated human pancreatic cancer xenotransplanted into nude mice as a model suitable for adoptive immunotherapy studies. A pancreatic cancer cell line (MIA PaCa-2) was chosen and its growth in nude mice and sensitivity to lysis by human lymphokine-activated killer (LAK) cells were characterized. This line grew in 96% of the cases when young (4- to 6-week-old) Swiss/NIH nude mice were used. The line was highly sensitive to lysis by LAK cells in a standard chromium-51 release assay (67.8%), similarly to other cell lines known to be highly sensitive, such as K562 (75.6%) and the melanoma cell line SU.102 (53.1%). To assess their in vivo distribution, human peripheral blood lymphocytes (PBLs) and LAK cells were adoptively transferred into nude mice after labeling with indium-111 oxine. The results of this study show that adoptively transferred PBLs and LAK cells localize in this heterologous system as they do in autologous systems. PBLs are taken up mostly by the liver and spleen. The percentage of the administered dose of radioactivity taken up corrected by weight (percent dose per gram tissue) is 64.3 +/- 15.6%d/gm (liver) and 43.5 +/- 9.5%d/gm (spleen). LAK cells are taken up by liver (43.2 +/- 5.3%d/gm) and spleen (28.0 +/- 4.9%d/gm) but also localize significantly more than PBLs in other organs such as lungs (12.9 +/- 3.5%d/gm vs 1.4 +/- 0.3%d/gm, p less than 0.01), kidneys (19.1 +/- 2.1%d/gm vs 6.3 +/- 1.5%d/gm, p less than 0.001), and pancreatic tumors growing in orthotopic position (1.93 +/- 0.36%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.05). When the nude mice are pretreated with human recombinant tumor necrosis factor, localization of LAK cells compared with PBLs is even further enhanced both in tumors implanted in the pancreas (3.1 +/- 0.5%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.01) and in the subcutis (12.5 +/- 8.3%d/gm vs 0.95 +/- 0.29%d/gm, p less than 0.001).

Animals↗
PubMed1988

A new human pancreatic carcinoma cell line developed for adoptive immunotherapy studies with lymphokine-activated killer cells in nude mice.

A human tumor cell line designated SU.86 has been established from a moderate-to-poorly differentiated pancreatic carcinoma of ductal origin specifically for adoptive immunotherapy studies. This line was characterized as to its ability to be lysed in vitro by autologous and allogeneic lymphokine-activated killer (LAK) and natural killer cells and to grow in nude mice. SU.86 has been growing continuously in cell culture for more than 100 passages since 22 September 1986. Transplantation orthotopically and heterotopically into athymic Swiss nude mice showed that tumor take was 100% in the orthotopic position when young (4 to 6 wk old) mice were used and 0% when adult (8 wk old) mice were used (P = 0.004). In the heterotopic position (subcutaneous), tumor take was 100% in neonate (2 to 3 wk old) and young mice and 50% in adults. The rate of tumor growth was inversely correlated with age (P less than 0.001). The histologic pattern is similar to that observed in most human pancreatic carcinomas with pseudoglandular structures and frequent mitotic figures. SU.86 has a doubling time of 77 h in vitro and produces carcinoembryonic antigen, 594 ng/10(6) cells in 3 d. Chromosomal analysis shows heterogeneity with two notable cell subpopulations. The cell line is moderately sensitive to lysis by LAK cells in a standard, 4-h chromium-51 release assay (35.4 +/- 4.0%). When grown together with LAK cells in vitro, it is lysed completely in culture in 8 to 15 d, depending on the serum concentration.

Adenocarcinoma↗
PubMed1988

Site-directed metastasis: a model to study site variations in treatment response.

A model for the site-directed metastasis of a transplantable rat mammary carcinoma is described. The R3230AC tumor is a moderately well differentiated, phenotypically stable tumor which arose in a Fischer 344 rat and resembles human breast carcinoma in being hormonally sensitive, poorly immunogenic, and sensitive to radiation and chemotherapeutic agents. Metastases with this tumor can be consistently produced at specific sites (lung, liver, or subcutaneous) in a reproducible manner by the methods described in this paper. This model appears ideal for the evaluation of site-specific variation in response to treatment modalities.

Adenocarcinoma↗
PubMed1988

Intestinal obstruction.

Acute intestinal obstruction is an emergency that frequently requires operative intervention, either immediately or within several days. Because of the difficulty in distinguishing strangulation obstruction from simple obstruction, a philosophy of operating on all patients with intestinal obstruction has been advocated by many physicians. On the other hand, the approach of attempting tube decompression on most patients rather than immediate operation has also been advocated. Both of these approaches are extreme and somewhat simplistic in dealing with a problem that often is complex. Fluid and electrolyte replacement, intestinal tube decompression, and appropriate surgical management are crucial to the successful management of these patients. This text presents a summary of the pathogenesis and various etiologies of intestinal obstruction and offers some diagnostic and treatment guidelines that will assist the clinician in the management of his patients.

Acute Disease↗
PubMed1983

Antibody reacting with the murine mammary tumor virus in the serum of patients with breast carcinoma: a possible serological detection method for breast carcinoma.

Sera from patients with Stages A and B infiltrating ductal carcinoma of the breast, benign breast disease, cancers other than breast carcinoma, and normal female controls were examined by indirect immunoelectron microscopy (IEM) and a viral agglutination test for evidence of antibodies directed against murine mammary tumor virus (MMTV). Sera from 41 (79%) of 52 patients with breast carcinoma and eight (19%) of 42 normal subjects or patients with benign breast disease (noncancer subjects) showed evidence of MMTV labeling by IEM. In the MMTV agglutination test, significant virus agglutination (2+ to 4+) was present in eight (13%) of 61 noncancer sera, 58 (86%) of 68 breast carcinoma sera, and two (11%) of 18 other cancer sera. The results of the more rapid MMTV agglutination test correlated well with IEM. Analysis of reacting antibody by IEM revealed no immunoglobulin A and significant immunoglobulin M and immunoglobulin G antibody. Serum reactivity against MMTV was completely absorbed by MMTV but not by the glycoprotein with a molecular weight of 52,000 of MMTV, Friend murine leukemia virus, avian myeloblastosis virus, or sheep erythrocytes. It is concluded that reactivity of human antibodies to MMTV is strongly associated with, but is not entirely specific for, breast carcinoma. It remains to be determined if normal persons with these antibodies will ultimately develop breast cancer and should therefore be considered at high risk. These tests may have potential usefulness as a diagnostic screen for breast cancer.

Agglutination↗
PubMed1979

Morphological and biochemical properties of a new human breast cancer cell line.

DU4475 is a new human breast cell line derived from a cutaneous metastatic nodule from a patient with advanced breast cancer. It has been in continuous culture for more than 1 year and has survived 140 subcultivations. The cells grow in suspension, displaying clusters and free-floating aggregates with serpentine-like outgrowths. The cell line is hypotetraploid with modal chromosome numbers between 86 and 93 and possesses five to six distinctive marker chromosomes. The cells grow readily in athymic nude mice and produce tumors from which cells can be reintroduced to culture in vitro.

Breast Neoplasms↗
PubMed1977

Evaluation of a breast cyst fluid protein detectable in the plasma of breast carcinoma patients.

A radioimmunoassay has been developed for one of the major proteins isolated from human breast cyst fluid. Immunologically this protein is identical to a protein present in both human milk and saliva. Ninety-two normal women had plasma levels of this protein below 100 ng/ml (range 7-81 ng/ml; mean 31 ng/ml), and 85% had plasma levels below 50 ng/ml. More than one-half of the women with active gross cystic disease of the breast had plasma levels above 50 ng/ml. None of these women, however, had plasma levels above 150 ng/ml. A significant percentage of women with advanced breast carcinoma have been found to have plasma concentrations of this protein greater than 150 ng/ml.

Adult↗
PubMed1976

Detection of the major glycoproteins of Friend leukemia virus (gp71) and the murine mammary tumor virus (gp52) on the surface of mouse cells.

Specific rabbit antisera to the major glycoproteins of Friend leukemia virus (gp71) and the mouse mammary tumor virus (gp52) were utilized to study the surfaces of C3H-, DBA-, BALB/c-, and C57BL-transformed and normal cells by immunoelectron microscopy. Antiserum to gp71 showed reactivity with all of the mouse cells tested regardless of strain, virus production, or state of transformation. In cells producing murine leukemia virus, budding viruses and other areas of the cell surface were consistently labeled with gp71 antiserum. A gp52-like antigen was likewise detected on both cell surfaces and virions of C3H and DBA cells producing the mammary tumor virus. Budding virions with surface spikes but with crescent-shaped nucleoids in C3H/HeJ cells were labeled specifically with gp52 antiserum. The antigen localized with anti-gp52 serum was detected in low concentration on the surface of nonvirus-producing cultures of a C57BL/6 sarcoma induced by the Schmidt-Ruppin D strain of Rous avian sarcoma virus (SRD-2), a BALB/c bone marrow culture (JLS-V9), and a normal BALB/c fibroblast culture (BALB/cF). Other cell cultures transformed by either C-type virus or methylcholanthrene failed to demonstrate gp52 antigen. Both gp52- and gp71-like antigens were found to be expressed simultaneously in C3H/HeJ, C3H-MT, DBA-MT, SRD-2 (transformed) and BALB/cF, JLS-V9, and C3H-1 (normal) cultures. Expression of gp52 antigen in the absence of gp71 was not detected in any of the cultures examined. These findings demonstrate the ubiquitous expression of gp71 in a wide variety of normal and transformed mouse cells while gp52 tends to be expressed predominantly in cells from mice with high mammary tumor incidence (C3H) and DBA), but only to a minor extent in cells from low mammary tumor incidence strains (BALB/c and C57BL).

Animals↗
PubMedDate not supplied

Development of technologies aiding large-tissue engineering.

There are many clinical situations in which a large tissue mass is required to replace tissue lost to surgical resection (e.g., mastectomy). It is possible that autologous cell transplantation on biodegradable polymer matrices may provide a new therapy to engineer large tissue which can be used to treat these patients. A number of challenges must be met to engineer a large soft tissue mass. These include the design of (1) a structural framework to maintain a space for tissue development, (2) a space-filling matrix which provides for localization of transplanted cells, and (3) a strategy to enhance vascularization of the forming tissue. In this paper we provide an overview of several technologies which are under development to address these issues. Specifically, support matrices to maintain a space for tissue development have been fabricated from polymers of lactide and glycolide. The ability of these structures to resist compressive forces was regulated by the ratio of lactide to glycolide in the polymer. Smooth muscle cell seeding onto polyglycolide fiber-based matrices has been optimized to allow formation of new tissues in vitro and in vivo. Finally, polymer microsphere drug delivery technology is being developed to release vascular endothelial growth factor (VEGF), a potent angiogenic molecule, at the site of tissue formation. This strategy, which combines several different technologies, may ultimately allow for the engineering of large soft tissues.

Animals↗