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Biomedical subjects

R B Bankert

Publications and source records attributed to R B Bankert.

At least 19 recordsLinked to original sources
PubMed2003

Comparison of human lung cancer/SCID mouse tumor xenografts and cell culture growth with patient clinical outcomes.

Leukemic cell growth in SCID mice has been reported as a predictor of disease relapse. However, there is a paucity of literature regarding xenograft growth and clinical outcomes in non-small cell lung cancer (NSCLC). Seventy-nine specimens from patients with NSCLC were either subcutaneously implanted into SCID mice and/or placed in tissue culture. Retrospective chart review was correlated with stage, histology, necrosis, disease-free interval, and survival. Tumor xenografts were successfully established with 17 of 37 (46%) tumor biopsy tissues. Thirteen of 59 (22%) specimens grew in cell culture. Patients whose tumors grew in SCID mice had no difference in survival compared to those with no growth ( n=20, p=0.42). Median survival was 36 months in 13 patients whose tumors grew in cell culture compared to 39 months in 46 patients without growth. Eight of 12 (67%) patients with metastasis showed SCID/human xenograft growth, whereas nine of 25 (36%) without metastases did so ( p=0.08). Growth of tumor cells in vitro occurred in 11 of 31 (35%) adenocarcinomas, one of 25 (4%) squamous cell carcinomas, and one of three (33%) large cell carcinomas ( p=0.02). Well or moderately differentiated tumors grew in cell culture in only two of 22 (9%), whereas poorly or undifferentiated tumors grew in 11 of 32 (34%) cases ( p=0.03). We conclude that neither the ability of a tumor to engraft and grow in SCID mice nor its ability to grow in vitro in cell culture is a reliable predictor of disease outcome or survival in patients with NSCLC. The ability to propagate tumors in vitro appears to be more dependent upon the histological type of tumor and its degree of differentiation.

Adenocarcinoma↗
PubMed2001

CD40-CD40 ligand (CD154) engagement is required but not sufficient for modulating MHC class I, ICAM-1 and Fas expression and proliferation of human non-small cell lung tumors.

To determine the possible functional significance of CD40 expression on human non-small cell lung carcinomas and to assess the potential of CD40 as a therapeutic target, 18 lung tumor cell lines were established from biopsy tissues and were monitored for phenotypic changes on the cell surface and alterations in tumor cell proliferation after the ligation of CD40 with a trimeric fusion protein complex of CD40 ligand (CD40Lt). CD40 cross-linking resulted in up to a 6-fold increase in the surface expression of major histocompatibility complex (MHC) class I, Fas and intracellular adhesion molecule (ICAM)-1 in a subset of tumors expressing the highest levels of CD40. Suppression of tumor proliferation was seen after the ligation of CD40 on CD40Lt-responsive cell lines. The suppression was dose dependent, reversible and resulted from a delay of the tumor cells entering S-phase. No change in the cell phenotype or in proliferation were observed in CD40-negative tumors or in tumors expressing moderate-to-low levels of CD40 after incubation with CD40Lt. CD40-negative tumors transfected with the CD40 gene expressed high levels of CD40 on their surface, but were also unresponsive to CD40Lt cross-linking of CD40. Our data establish that CD40 is required (but not sufficient) for transducing a signal that results in phenotypic changes in human lung tumors and suppression in their proliferation. We conclude that CD40 on non-small cell lung tumors may represent a potential therapeutic target, but only on a subset of the CD40+ tumors.

Apoptosis↗
PubMed2001

Human-SCID mouse chimeric models for the evaluation of anti-cancer therapies.

The ability to engraft human tumors and human immunocompetent cells successfully in severe combined immunodeficient (SCID) mice has spawned the development and use of human-mouse chimeric models to evaluate anti-cancer therapies. The lack of standardization and many other potential pitfalls have contributed to the current controversy surrounding the reliability of these different models. Five frequently used SCID mouse models and their specific applications are summarized with the specific aim of providing an objective discussion of the strengths and limitations of each model, together with suggestions for overcoming some of the variabilities and for improving the design and use of future models.

Animals↗
PubMed2001

Antitumor efficacy of a human interleukin-12 expression plasmid demonstrated in a human peripheral blood leukocyte/human lung tumor xenograft SCID mouse model.

Genes encoding the p35 and p40 subunits of human interleukin-12 (IL-12) and the bacterial aminoglycoside phosphotransferase were cloned into a mammalian expression plasmid. The resultant plasmid, pCMVIL-12neo, was used to transfect human lung tumor cell lines in vitro. Stably transfected subclones were generated and found to secrete human IL-12 for at least 10 days following a lethal dose of gamma-radiation. The ability of the IL-12--producing tumor cells to promote an antitumor response in vivo was evaluated in SCID mice co-engrafted subcutaneously with human peripheral blood lymphocytes (PBLs) and viable human lung tumor cells (SCID-Winn assay). Using this model system, it was established that IL-12 released locally into tumors by irradiated IL-12--transfected cells activated the human PBL and promoted their ability to suppress tumor development in a dose-dependent fashion. PBL subset depletion studies revealed that the antitumor effect promoted by the IL-12--modified cells was dependent on the presence of human CD8(+) T cells and, to a lesser extent, human CD56(+) natural killer cells within the xenograft. We conclude that (a) irradiated human lung tumor cells genetically modified with pCMVIL-12neo secrete bioactive human IL-12 at concentrations sufficient to promote a human lymphocyte-mediated antitumor response in the microenvironment of the xenograft, and (b) that the SCID-Winn assay provides a useful model for the preclinical evaluation of cytokine-based human immunotherapy protocols.

Animals↗
PubMed2001

Neoadjuvant therapy with interleukin-12-loaded polylactic acid microspheres reduces local recurrence and distant metastases.

BACKGROUND: We previously demonstrated that the intratumoral injection of biodegradable polylactic acid microspheres that were loaded with interleukin (IL)-12 can induce a systemic antitumor immunity. We sought to investigate the clinical potential as neoadjuvant therapy. METHODS: Mice were inoculated with 5 x 10(7) Line-1 cells subcutaneously. Six days later, a single intratumoral injection of IL-12- or BSA-loaded microspheres were given; 14 days later, autopsy was performed to document metastases. Mice were inoculated with 5 x 10(7) Line-1 cells and 10 days later either treated with IL-12- or BSA-loaded microspheres or resected. Treated tumors were resected 6 days after treatment. Mice were observed 45 days for local recurrence before autopsy. RESULTS: Intratumoral injection of IL-12 microspheres resulted in significant suppression of tumor growth compared with controls (599 +/- 255 mm(3) vs 1591 +/- 372 mm(3); P =.001) and pulmonary metastases (0.4 vs 3.8 nodules per mouse; P =.003). Given before the operation, IL-12-loaded microspheres both decreased the local recurrence rate (100% to 40%) and pulmonary metastases (5.2 vs 0.6 nodules per mouse; P =.06). Earlier resection did not improve local recurrence or distant metastases. CONCLUSIONS: Intratumoral injection of IL-12-loaded polylactic acid microspheres promotes the development of systemic antitumor immunity that can eradicate micrometastases. As a neoadjuvant therapy, this can result in decreased local and distant recurrence.

Adenocarcinoma↗
PubMed2001

Human dendritic cells pulsed with autologous Epstein-Barr virus transformed B-cell lymphoblastoid cell (BCL) lysate elicit a BCL specific MHC-class II restricted T-cell response.

Epstein Barr Virus (EBV) associated lymphoproliferative disorders (LPD) express EBV latent antigens that are also expressed on normal B-cells transformed with EBV. This could potentially be exploited to develop immunotherapeutic strategies for LPD and other EBV associated malignancies. To this end we investigated the capacity of human monocyte derived dendritic cells (DC) pulsed with lysate from autologous EBV transformed B-cell lymphoblastoid cell (BCL) lysate to elicit an in vitro antitumor response. BCL lysate pulsed DC generate BCL specific cytotoxic lymphocytes, as lymphocytes primed with such DCs induce cytolysis of autologous (>60%) but not allogeneic BCL (<5%). In addition, lymphocytes primed with BCL lysate pulsed DC secrete gamma-IFN (3176 pg/ml). Whereas gamma-IFN production was markedly reduced (>99%) when BCL specific T-cells were stimulated by BCL lysate pulsed DC in the presence of blocking antibodies to HLA-DR, DP and DQ, use of antibodies to MHC class-I resulted in only a minimal reduction in gamma-IFN production (17%). These studies demonstrate that BCL lysate pulsed DC elicit a predominantly BCL specific, MHC class-Il restricted T cell response. This suggests that vaccination with autologous BCL lysate pulsed DC may represent a viable immunotherapeutic approach for the treatment of LPD.

B-Lymphocytes↗
PubMed2000

Antibody targeting of doxorubicin-loaded liposomes suppresses the growth and metastatic spread of established human lung tumor xenografts in severe combined immunodeficient mice.

Beta1 integrins, expressed on the cell surface of human non-small cell lung carcinomas, are used here as a target for the selective delivery of anti-cancer drug-loaded liposomes. Fab' fragments of a monoclonal antibody specific for human beta1 integrins were conjugated to sterically stabilized liposomes. Confocal microscopy of beta1 integrin-positive lung tumor cells incubated with fluorescently labeled anti-beta1 Fab immunoliposomes revealed a tumor-specific binding and efficient internalization of the liposomes into the tumor cells. The ability of these liposomes to deliver cytotoxic drugs to the tumor and kill these cells was demonstrated in vitro by incubating tumor cells with doxorubicin-loaded anti-beta1 Fab' immunoliposomes. The drug-loaded immunoliposomes were >30-fold more cytotoxic to the tumor cells than drug-loaded liposomes without antibody, nonspecific Fab' control immunoliposomes with drug or immunoliposomes without drug. The therapeutic efficacy of doxorubicin-loaded immunoliposomes was also evaluated in a metastatic human lung tumor xenograft/severe combined immunodeficient (SCID) mouse model. SCID mice that received i.v. injections of human lung tumor cells developed primary tumor nodules in the lung that subsequently metastasized to the liver and adrenal gland. Treatment of SCID mice bearing established lung tumor xenografts with doxorubicin-loaded anti-beta1 Fab immunoliposomes resulted in a significant suppression of tumor growth (monitored periodically by quantifying serum levels of a tumor marker), whereas tumors grew progressively in mice treated with control formulations. In addition to suppressing the growth of the primary lung tumor nodules, the immunoliposomes prevented the metastatic spread of the tumor to the liver and adrenal glands and increased the median survival time of the tumor-bearing mice. We conclude that Fab' immunoliposomes directed to tumor-associated integrins represent a potentially viable approach clinically for the selective delivery of drugs to solid tumors and may be useful in preventing the metastatic spread of lung cancer.

Adrenal Gland Neoplasms↗
PubMed2000

In situ tumor vaccination with interleukin-12-encapsulated biodegradable microspheres: induction of tumor regression and potent antitumor immunity.

An alternative technology for the local and sustained delivery of cytokines to tumors for cancer immunotherapy was evaluated and shown here to induce tumor regression, suppression of metastasis, and development of systemic antitumor immunity. Treatment of tumor-bearing BALB/c mice with a single intratumoral injection of biodegradable polylactic acid microspheres loaded with recombinant interleukin-12 (IL-12) promoted complete regression of the primary tumor and prevented the metastatic spread to the lung. Mice that experienced tumor regression after being treated rejected a subsequent challenge with live tumor cells, which indicated the development of systemic antitumor immunity. In situ tumor vaccination, ie., injection of IL-12 microspheres into existing tumors, was superior to vaccination of mice with mixtures of tumor cells (live or irradiated) and IL-12 microspheres in inducing systemic antitumor immunity. The sustained release of IL-12 from the microspheres was superior to bolus injection of free IL-12, and intratumoral delivery of microspheres was more effective than other routes of administration. These studies establish the utility of biodegradable polymer microspheres as a clinically feasible alternative to systemic cytokine therapy and cytokine gene-modified cell vaccines for the treatment of neoplastic disease.

Absorbable Implants↗
PubMed2000

Growth of human tumor xenografts in SCID mice quantified using an immunoassay for tumor marker protein in serum.

The accurate measurement of the response of a tumor to a given treatment is critical to evaluating novel therapeutic modalities. An experimental design is reported here that can be generally applied to monitoring human tumor xenografts growing in immunodeficient mice. A human non-small cell lung tumor cell line was transfected with a mammalian expression vector containing the gene encoding human prostate specific antigen (PSA) and has been shown to grow progressively following the subcutaneous, intraperitoneal and intravenous inoculation of the tumor into severe combined immunodeficient (SCID) mice. The transfected human tumor cells produce PSA that accumulates in the sera of all tumor inoculated SCID mice. An enzyme-linked immunoassay using a rabbit polyclonal and a mouse monoclonal antibody specific for PSA was designed and tested for the detection and quantification of serum PSA in tumor-bearing mice. Over a 5-week period, the serum levels of PSA of mice inoculated subcutaneously with the tumor increased progressively, and the estimated tumor volumes correlated with the amount of PSA detected in the serum. Serum PSA levels correlated even better with total tumor mass following the intraperitoneal inoculation of tumor cells into SCID mice. Serum PSA levels fell rapidly following the surgical debulking of tumor xenograft, reaching background levels of PSA in the serum 1 week after tumor removal. Serum PSA levels were also observed in SCID mice inoculated intravenously with a PSA transfected human lung tumor cell line adapted to grow orthotopically in the lung. The transfection of human tumors with a tumor marker and the use of an immunoassay to detect this marker establish an experimental design that provides a reliable, non-invasive, accurate and simple approach to monitor and quantify the growth of human tumor xenografts in SCID mice.

Animals↗
PubMed2000

Interleukin-12 delivered by biodegradable microspheres promotes the antitumor activity of human peripheral blood lymphocytes in a human head and neck tumor xenograft/SCID mouse model.

BACKGROUND: The role of cytokines in tumor regression is now well established. The major limitation for the clinical use of cytokines is the lack of a simple and effective protocol for the local and sustained delivery of cytokines to the tumor milieu. This study reports suppression of human head and neck squamous cell carcinoma (HNSCC) by human peripheral blood lymphocytes (HuPBL) following local, sustained delivery of interleukin-12 (IL-12) to tumors with biodegradable microspheres in a human/SCID mouse chimeric model. Materials and Methods Nondisrupted biopsy pieces (120 mg) of primary HNSCC were implanted s.c. into severe combined immunodeficient (SCID) mice and were expanded by serial passage in mice. Tumors were then titrated with different doses of allogeneic HuPBL by coengraftment of tumor pieces and HuPBL into the subcutis of SCID mice to determine whether the HuPBL possessed antitumor activity (the SCID/Winn model). The lymphocyte subsets that were responsible for the suppression of tumor engraftment were identified by selective depletion of the CD4+, CD8+, and CD56+ cells from the HuPBL prior to engraftment into mice. Attempts were then made to augment the antitumor activity of the HuPBL either by repeated intralesional bolus injections of recombinant human IL-12 (0.5 microg x 10 doses) or with a single dose of IL-12-loaded microspheres ( approximately 1.65 microg IL-12/mg microspheres, 2 mg microspheres/mouse). RESULTS: Successful engraftment of HNSCC was observed in 12 of 19 different patient samples. Normal histological architecture of tumor was maintained up to four serial passages in the SCID mice. After the first tumor engraftment, but not in subsequent passages, human immunoglobulin produced by plasma cells present in the tumor infiltrating lymphocyte population was detected in the mouse sera. Allogeneic human PBL displayed antitumor cytotoxic activity in a cell dose-dependent fashion when coengrafted with the tumors passaged in SCID mice. Lymphocyte subset depletion studies established that tumor suppression was dependent on both the CD8+ T lymphocytes and the CD56+ natural killer cells. Treatment of tumors with a single intralesional injection of IL-12-loaded microspheres was highly effective, resulting in the complete suppression of tumor engraftment in 50% of the mice. In contrast, treatment of tumors with repeated bolus IL-12 injections suppressed tumor engraftment only transiently and did not result in complete tumor rejection in any of the mice. CONCLUSION: The coengraftment of HNSCC and allogeneic lymphocytes into SCID mice provides a viable model with which to evaluate immunotherapeutic strategies for human cancer. The use of biodegradable microspheres for local sustained delivery of cytokines to augment lymphocyte mediated antitumor immunity within the tumor microenvironment provides a safer and simpler alternative to current cytokine immunotherapy protocols.

Animals↗
PubMed2000

CD40 expression on human lung cancer correlates with metastatic spread.

PURPOSE: The poor prognosis associated with lung cancer is related to the high incidence of regional and distant metastasis. There is a crucial need to identify parameters that can predict a tendancy to metastatic spread to allow better prognostic evaluation and therapeutic approach. METHODS: Using flow cytometry we evaluated 18 human lung cancer cell lines for the expression of different surface markers on lung cancers suggested to be possible prognostic parameters, including epidermal growth factor receptor (EGFR), intercellular adhesion molecule 1 (ICAM-1), Fas and CD40. RESULTS: No correlation was found between tumor prognosis and EGFR, ICAM-1 or Fas. However, a statistically significant correlation was found between the surface expression of CD40 and the metastatic spread of the tumor. In this study, 14 of 18 lung cancer cell lines (78%) expressed CD40 on their surface. All of the 4 tumors that were CD40-negative, were stage I tumors, without any evidence of regional or distant metastasis. Of the 14 tumors that expressed CD40, all but 1 (93%) had either nodal or systemic metastasis at the time of diagnosis. Patients whose tumors were CD40-negative showed a significantly better N stage, overall stage at presentation and survival than those patients with CD40-positive patients. No significant differences between the two groups were observed in tumor size, gender, age, histology, differentiation or preoperative therapy. CONCLUSIONS: These results suggest that CD40 expression on lung cancer may play a role in metastatic spread, and also may serve as a prognostic marker and an indicator of advanced disease.

CD40 Antigens↗
PubMed1998

Cytokine immunotherapy of cancer with controlled release biodegradable microspheres in a human tumor xenograft/SCID mouse model.

A novel biodegradable poly(lactic acid) microsphere formulation was evaluated for in vivo cytokine immunotherapy of cancer in a human tumor xenograft/ severe combined immunodeficiency (SCID) mouse model. Co-injection of interleukin-2 (IL-2)-loaded microspheres with tumor cells into a subcutaneous site resulted in the complete suppression of tumor engraftment in 80% of animals. In contrast, bovine-serum-albumin(BSA)-loaded particles or bolus injections of poly(ethylene glycol)/IL-2 were ineffective in preventing tumor growth. The antitumor effect of IL-2 released by the microspheres was shown to be mediated by the mouse natural killer cells. This is the first evidence that the rejection of human tumor xenografts can be provoked by the sustained in vivo delivery of IL-2 from biodegradable microspheres. The use of poly(lactic acid) microspheres to deliver cytokines to the tumor environment could provide a safer and simpler alternative to gene therapy protocols in the treatment of cancer.

Animals↗
PubMed1997

Antitumor immune response of human peripheral blood lymphocytes coengrafted with tumor into severe combined immunodeficient mice.

Here, it is established that human peripheral blood lymphocytes (HuPBLs), injected s.c. with a human lung tumor into severe combined immunodeficient (SCID) mice, engraft and display antitumor cytotoxic activity. Initial studies used HuPBLs from normal donors and an allogeneic tumor cell line derived from biopsy tissue of a patient with a squamous cell carcinoma of the lung. Evidence of HuPBL antitumor activity was revealed by a cell dose-dependent suppression of the tumor xenograft. Tumor suppression was shown to be dependent upon both CD8+ T cells and CD56+ natural killer cells in the donor HuPBLs. By titrating the antitumor activity of HuPBLs in SCID mice with and without cytokines, it was established that interleukin (IL)-12 enhanced the HuPBL-mediated tumor suppression and that IL-2 had a synergistic effect upon the IL-12 enhancement of cytotoxicity. Subsequent studies revealed that a lung cancer patient's PBLs also suppress the growth of the patient's (autologous) tumor when coinjected s.c. with the tumor cells into SCID mice. The patient's antitumor immunity was shown to be mediated by CD8+ T cells and CD56+ natural killer cells. The data presented here indicate that the s.c. coengraftment of HuPBLs and tumor into SCID mice represents a viable model with which to study (and to periodically monitor) patients' immune responses to their tumors for extended periods of time and suggest that this SCID/Winn assay could be used to evaluate novel immunotherapeutic approaches, such as bolus injections of cytokines, cytokine gene therapy, or vaccination strategies for the treatment of human cancer.

Animals↗
PubMed1996

Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts.

Liposomes containing polyethylene glycol-derivatized phospholipids are able to evade the reticuloendothelial system and thereby remain in circulation for prolonged periods. We report here that doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) suppresses the growth of established human lung tumor xenografts in severe combined immunodeficient (SCID) mice and inhibits the spontaneous metastases of these tumors. The enhanced therapeutic efficacy of S-DOX compared to free doxorubicin was demonstrated in two independent human/mouse models. In the first model, S-DOX inhibited the growth of a human non-small cell lung tumor xenograft established orthotopically in the lungs of SCID mice. Treatment of these mice with S-DOX, but not with free drug, suppressed the growth of the tumor in the lung, prevented metastasis from the lung, and enhanced survival percentage. In another model, the human lung tumor is engrafted into gonadal fat pad of SCID mice. Human tumor xenografts grow floridly in this site of engraftment, and the tumor spreads from this primary site into the peritoneal cavity and subsequently reaches the liver and lung. In this model, free drug suppressed the growth of the primary tumor but had no effect upon the subsequent spread of the tumor into the peritoneal cavity, liver, and lung. In contrast, treatment of the tumor-bearing mice with S-DOX (but not with doxorubicin in conventional liposomes) suppressed the tumor spread to the peritoneal cavity, completely arrested metastasis to the liver and lung, and suppressed the growth of the primary tumor xenograft. This report provides the first evidence that antitumor drugs delivered by sterically stabilized liposomes can arrest the metastasis of human tumor xenografts.

Animals↗
PubMed1996

Evaluation and optimization of different cationic liposome formulations for in vivo gene transfer.

Five commonly used cationic liposome formulations were tested for their ability to deliver DNA to established subcutaneous human tumor xenografts in SCID mice. Liposomes were complexed with a mammalian expression plasmid containing the bacterial beta-galactosidase gene and delivered to tumors by direct injection. The optimal lipid to DNA ratios in vivo were markedly different than those observed in vitro for each liposome formulation. Tumor size at the time of inoculation also effected transfection efficiency significantly. Of the five liposome formulations tested, DC-Cholesterol was found to be superior to all others in vivo. Even under optimal conditions however, the efficiency of in vivo transfection was low in our system (approximately 0.3%). Implications of these results for in vivo gene therapy of tumors are discussed.

Animals↗
PubMed1996

Engraftment of human tumor-infiltrating lymphocytes and the production of anti-tumor antibodies in SCID mice.

We report here the placement of nondisrupted 1-mm3 pieces of fresh human lung tumor biopsy tissue into the subcutis of severe combined immunodeficient (SCID) mice results in the engraftment of tumor-infiltrating leukocytes (TIL) in all but 5 of 148 mice inoculated with 39 different biopsy tissue specimens. In mice coengrafted with tumor and TIL the normal histologic architecture of the tumor and TIL interface was maintained for up to 22 wk. The TIL in the xenograft were shown to divide and were maintained exclusively at the site of tumor inoculation. It is established here that plasma cells in the TIL population produce Abs that react in western blots with tumor cell lysates. These Abs were shown to react with high and low m.w. proteins derived from both the membrane and cytosolic fractions of tumor cell lysates. The production of human Ig was found to be T cell dependent, and immunohistochemistry and in situ hybridization of DNA, using a human-specific cDNA probe, established the human identity of the tumor and TIL. High levels of human Ig in the sera of mice inoculated with tumor biopsy tissue are associated with the growth arrest of adenocarcinoma xenografts. Our results establish the co-engraftment of human tumors and TIL into SCID mice as new animal model with which to evaluate TIL function and novel therapeutic strategies that are designed to augment TIL anti-tumor activity.

Animals↗
PubMed1996

Consistent hepatic metastasis of human colorectal cancer in severe combined immunodeficient mice.

A major stumbling block in the study of human colorectal cancer metastasis has been the lack of an effective in vivo model producing liver metastasis on a consistent basis. In this study surgical specimens of colorectal carcinoma were implanted in scid mice and studied for engraftment, growth, and the capacity to produce hepatic metastases. Human colorectal cancers would engraft and propagate in the subcutis and intraperitoneally. Sporadic metastasis to the liver occurred in 3 of 54 (6%) animals with cancer implanted subcutaneously. Liver metastasis occurred in 24 of 25 (96%) mice with cancer implanted in the gonad fat pad. Tumor growth to extremely large volumes subcutaneously did not enhance metastatic potential, and neither did longer term growth in the subcutaneous space. Tumor placed in the gonad fat required no special manipulation and in most cases a single piece of solid tumor was implanted. In situ hybridization confirmed the persistence of the human tissue in these metastasizing tumors. Our model will allow for the study of the processes involved in metastasis of solid tumors, characterization of differences between the primary tumor and the metastatic one, and evaluation of possible therapeutic modalities.

Adipose Tissue↗