Intraperitoneal Tumor Growth Research Articles

The influence of pneumoperitoneum used in laparoscopic surgery on an intraabdominal tumor growth

Numerous clinical reports have raised the possibility that laparoscopic cancer surgery has an inherently detrimental effect on tumor growth. The aim of the current study was to examine the influence of a pneumoperitoneum on the morphology of the peritoneum and the intraperitoneal tumor cell implantation and growth in the case of intraabdominal spread of tumor cells. Black mice were stratified into 2 groups of 36 animals each. A CO(2) pneumoperitoneum was induced for 30 minutes in Group 1 and 200,000 cells of a malignant melanoma were injected intraperitoneally. In Group 2 only tumor cells were injected. After a defined period of hours, 4 animals were killed and the peritoneum was examined by scanning electron microscopy. In Group 1, starting 2 hours after release of the pneumoperitoneum, strong alterations of the peritoneum became visible and parts of the underlying basal lamina were laid bare. Tumor cells attached to the free basal lamina and formed predominantly diffuse metastases throughout the peritoneum within the next 96 hours. No diffuse changes of the peritoneal surface and no diffuse metastases were observed in the second group. Singular metastases followed gravity and involved the anterior abdominal wall. Because these findings explain the clinical findings of intraabdominal metastases after laparoscopy the authors conclude that the pneumoperitoneum provokes particular damage to the peritoneum that induces a specific intraperitoneal tumor growth. [See also editorial counterpoint on pages 747-8 and reply to counterpoint on pages 749-50, this issue.

The influence of pneumoperitoneum used in laparoscopic surgery on an intraabdominal tumor growth

BACKGROUND Numerous clinical reports have raised the possibility that laparoscopic cancer surgery has an inherently detrimental effect on tumor growth. The aim of the current study was to examine the influence of a pneumoperitoneum on the morphology of the peritoneum and the intraperitoneal tumor cell implantation and growth in the case of intraabdominal spread of tumor cells. METHODS Black mice were stratified into 2 groups of 36 animals each. A CO2 pneumoperitoneum was induced for 30 minutes in Group 1 and 200,000 cells of a malignant melanoma were injected intraperitoneally. In Group 2 only tumor cells were injected. After a defined period of hours, 4 animals were killed and the peritoneum was examined by scanning electron microscopy. RESULTS In Group 1, starting 2 hours after release of the pneumoperitoneum, strong alterations of the peritoneum became visible and parts of the underlying basal lamina were laid bare. Tumor cells attached to the free basal lamina and formed predominantly diffuse metastases throughout the peritoneum within the next 96 hours. No diffuse changes of the peritoneal surface and no diffuse metastases were observed in the second group. Singular metastases followed gravity and involved the anterior abdominal wall. CONCLUSIONS Because these findings explain the clinical findings of intraabdominal metastases after laparoscopy the authors conclude that the pneumoperitoneum provokes particular damage to the peritoneum that induces a specific intraperitoneal tumor growth. [See also editorial counterpoint on pages 747–8 and reply to counterpoint on pages 749–50, this issue. Cancer 1999;86:770–4. © 1999 American Cancer Society.

Impact of laparoscopic colonic resection on tumour growth and spread in an experimental model.

The influence of surgical manipulation and carbon dioxide pneumoperitoneum on intraperitoneal tumour growth and port-site metastasis during laparoscopic colon resection is still unknown. Some 33 male WAG/Rij rats were randomized into three experimental groups: a laparoscopy group with carbon dioxide pneumoperitoneum (n = 11), a gasless laparoscopy group (n = 11) and a laparotomy group (n = 11). After transanal injection of a tumour cell suspension (1 x 106 CC 531 cells) into the distal colon, a colon segment resection and an end-to-end anastomosis (laparoscopy; intra-abdominal technique) were performed. Tumour growth was scored semiquantitatively 24 days after the operation. Data were analysed by the Kruskal-Wallis test. The tumour indices from the four locations with the greatest tumour growth were significantly decreased in the laparoscopy group with carbon dioxide pneumoperitoneum compared with the gasless laparoscopy and laparotomy groups (P < 0.01). Port-site metastases were significantly decreased in the carbon dioxide pneumoperitoneum group compared with the gasless laparoscopy group (P = 0.05). A full laparotomy incision promotes greater tumour growth than does carbon dioxide pneumoperitoneum. Surgical manipulation stimulates local tumour spread more than the establishment of a carbon dioxide pneumoperitoneum.

Effects of laparoscopy on intraperitoneal tumor growth and distant metastases in an animal model

Background and aims: Laparoscopic surgery for colorectal cancer is currently being evaluated in humans. The aim of this study was to examine the effect of laparoscopy on intraperitoneal tumor growth and distant metastases in an animal model. We also examined the effect of combining laparotomy with laparoscopy and on infusing the peritoneal cavity with normal saline solution (NaCl), water, and sodium hypochlorite after laparoscopy on intraperitoneal tumor growth. Material and methods: Female Fischer rats were given MtLn3 adenocarcinoma cells by intraperitoneal injection to produce intraperitoneal tumor growth and by tail vein injection to produce lung metastases. A pneumoperitoneum was then induced to a pressure of 8 mm Hg with carbon dioxide (CO2), helium, or room air. After this, animals were allowed to either recover or underwent laparotomy or infusion of NaCl, water, or sodium hypochlorite before recovery, depending on the experiment. At 21 days all animals were killed and intraperitoneal tumor growth was assessed by counting the number of peritoneal and serosal nodules and by weighing the omental pad of tumor. Lung metastases were assessed by counting the number of metastases after fixation. Results: Laparoscopy caused a marked intraperitoneal dissemination of tumor with a median of 17 (10 to 20) peritoneal and serosal nodules for CO2, 19.5 (12.5 to 25) for helium, and 15.0 (9.5 to 17.7) for room air compared with 0 (0 to 1) for controls (P <.0001). The weight of omental tumor was also significantly increased (P <.02) in the CO2, helium, and room air groups. Infusion with NaCl, water, or sodium hypochlorite had no effect on tumor dissemination after laparoscopy. The combination of laparoscopy and laparotomy caused a significant reduction (P <.05) in the number of peritoneal nodules but had no significant effect on omental tumor growth. Laparoscopy also had no effect on the number of pulmonary metastases induced compared with controls. Conclusions: This study shows that laparoscopy promotes intraperitoneal dissemination of tumor. This effect is independent of the insufflating gas used and is not affected by use of a cytotoxic agent. The use of gasless laparoscopy should be encouraged by those undertaking curative laparoscopic surgery for colorectal cancer. (Surgery 1999;126:35-40.)

Role of Vascular Endothelial Growth Factor in Ovarian Cancer: Inhibition of Ascites Formation by Immunoneutralization

Ovarian cancer is characterized by the rapid growth of solid intraperitoneal tumors and large volumes of ascitic fluid. Vascular endothelial growth factor (VEGF) augments tumor growth by inducing neovascularization and may stimulate ascites formation by increasing vascular permeability. We examined the role of VEGF in ovarian carcinoma using in vivo models in which intraperitoneal or subcutaneous tumors were induced in immunodeficient mice using the human ovarian carcinoma cell line SKOV-3. After tumor engraftment (7 to 10 days), some mice were treated with a function-blocking VEGF antibody (A4.6.1) specific for human VEGF. A4.6.1 significantly (P < 0.05) inhibited subcutaneous SKOV-3 tumor growth compared with controls. However, tumor growth resumed when A4.6.1 treatment was discontinued. In mice bearing intraperitoneal tumors (IP mice), ascites production and intraperitoneal carcinomatosis were detected 3 to 7 weeks after SKOV-3 inoculation. Importantly, A4.6.1 completely inhibited ascites production in IP mice, although it only partially inhibited intraperitoneal tumor growth. Tumor burden was variable in A4.6.1-treated IP mice; some had minimal tumor, whereas in others tumor burden was similar to that of controls. When A4.6.1 treatment was stopped, IP mice rapidly (within 2 weeks) developed ascites and became cachectic. These data suggest that in ovarian cancer, tumor-derived VEGF is obligatory for ascites formation but not for intraperitoneal tumor growth. Neutralization of VEGF activity may have clinical application in inhibiting malignant ascites formation in ovarian cancer.

Tumor Growth and Dissemination After Laparotomy and CO 2 Pneumoperitoneum: A Rat Ovarian Cancer Model

Objective: To compare tumor growth, intraperitoneal implantation, and abdominal wall metastasis after laparotomy and CO 2 pneumoperitoneum in a rat ovarian cancer model. Methods: To mimic intraoperative rupture of an ovarian tumor in a syngenic rat ovarian carcinoma model, 10 5 malignant cells were injected intraperitoneally after a 5-cm vertical midline laparotomy or after the insufflation of a CO 2 pneumoperitoneum achieved with 4 mmHg or 10 mmHg intra-abdominal pressure. Two weeks later, the intraperitoneal tumor growth and the tumor dissemination were evaluated semiquantitatively with a scoring system. The scores attributed to each organ were added to calculate the dissemination score of each animal. Results: The mean (± SD) dissemination score was 83.4 ± 12 in the laparotomy group and 67.3 ± 16 and 71.9 ± 17 in the 4 and 10 mmHg CO 2 pneumoperitoneum groups, respectively ( P < .01). The scores for the peritoneum were 21.8 ± 3.8 in the 10 mmHg pneumoperitoneum group and 18 ± 2.4 in the laparotomy group ( P < .01). In the laparotomy group, the implant found along the midline scar accounted for a mean of 62.6 ± 15% of the peritoneal score, whereas the trocar site metastases did not influence the peritoneal score in the pneumoperitoneum groups. The incidence of wound metastasis was 96% in the laparotomy group and 55% and 54% in the 4 mmHg and 10 mmHg pneumoperitoneum groups, respectively. Conclusion: In this model, tumor growth was greater after laparotomy than after laparoscopy, but peritoneal tumor dissemination was more severe after CO 2 pneumoperitoneum.

A prospective randomized scanning electron microscopy study on the effect of a pneumoperitoneum on tumour cell implantation in nude mice

ObjectiveThe aim of the study was to examine the influence of a CO2 pneumoperitoneum on intraperitoneal tumour cell implantation and on survival in the event of intra‐abdominal spread of tumour cells during laparoscopy in nude mice.Design6‐week‐old nude mice were stratified into three groups of 47 animals each. A CO2 pneumoperitoneum was induced by a microhysteroflator with an intraperitoneal pressure of 8 mmHg for 60 min in group 1 and 100 000 cells of a malignant mesothelioma, suspended in 2 ml of Ringer solution were injected intraperitoneally. Group 2 received an identical tumour cell load after laparotomy by midline incision. In the control group 3 tumour cells were injected only. After 1, 2, 6, 12, 24, 48, 72 and 96 h respectively four animals were killed and the entire peritoneum in all animals was examined by scanning electron microscopy. The survival time of the remaining 15 animals served as controlling arm.ResultsIn group 1, scanning electron microscopy showed that within 1 h mesothelial cells had become cuboidal, detached and condensed. The basement membrane was partly denuded. After 2 h this initial reaction reached its peak; tumour cells attached to the free basement membrane. None of those changes was seen in groups 2 and 3. It appears, that in group 1 intraperitoneal metastases were promoted by the CO2 pneumoperitoneum. The survival rate of group 1 was significantly reduced compared with that of group 2 and 3.ConclusionWe conclude that the technique of CO2 pneumoperitoneum promotes intraperitoneal tumour cell implantation and growth in nude mice.

Effective of pneumoperitoneum induced by carbon dioxide and air on tumor load in a rat model.

Laparoscopic surgery for malignant disease is highly controversial mainly due to the large number of abdominal wall metastases being reported. Previous experimental studies have particularly studied CO2 pneumoperitoneum and its effect on tumor development. The purpose of this study was to compare CO2- and air-induced pneumoperitoneum with regard to intraperitoneal tumor growth. Altogether 39 rats were injected intraperitoneally with 10(5) colonic tumor cells and randomly allocated into three groups: 13 rats had a pneumoperitoneum created with CO2, 13 with air, and 13 served as controls. Tumor development was determined semiquantitatively by a peritoneal cancer index scale after 12 days. CO2 and air pneumoperitoneum equally increased intraperitoneal tumor growth compared to controls. Pneumoperitoneum induced by CO2 and air seems to increase tumor load, but the mechanisms are not established. This finding supports the hypothesis that insufflation not only by causing tumor cell movements but in fact pneumoperitoneum per se and the used gas are involved in the development of abdominal wall metastases after laparoscopic surgery.

Inhibition of peritoneal tumor cell growth and implantation in laparoscopic surgery in a rat model

Background The pathogenesis of portsite recurrences after laparoscopic surgery is still unknown, and a generally accepted approach to prevent tumor implantation does not exist. Methods The effect of taurolidine and heparin on growth of colon adenocarcinoma DHD/K12/ TRb was measured in vitro and in vivo. After incubation of the cells with heparin or taurolidine or both substances, cell kinetics were determined. In a rat model (n = 60), tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 minutes. Rats received tumor cells, tumor cells + heparin, tumor cells + taurolidine, or tumor cells + taurolidine + heparin. Results In vitro, tumor cell growth decreased after incubation with taurolidine and taurolidine/ heparin. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (298 ±155 mg) and taurolidine (149 ± 247 mg) compared with the control group (596 ± 278 mg) but even less when both substances were combined (21.5 ± 36 mg). Conclusion Heparin inhibits intraperitoneal tumor growth in vivo slightly, while taurolidine causes significant decrease of tumor cell growth in vitro as well as tumor take and intraperitoneal tumor growth in vivo.

The effects of pneumoperitoneum on intraperitoneal tumour implantation in nude mice

Objective The aim of the study was to examine the effect of a CO2 pneumoperitoneum on the intraperitoneal growth of tumour cells. Design 6‐week‐old nude mice were stratified into four groups of 15 animals each. A CO2 pneumoperitoneum was induced by a micro‐hysteroflator with an intraperitoneal pressure of 8 mm Hg for 90 min in groups 2 and 4. Two different tumour cell lines, suspended in 2 ml of Ringer solution for homogeneous spread of the cells, were injected i.p.. The control groups 1 and 3 received the tumour cells without pneumoperitoneum. Results The induction of a CO2 pneumoperitoneum resulted in an increased seeding rate of tumour cells and provoked a significant increase in the number and size of intra‐abdominal metastases. Conclusion We conclude that present laparoscopic techniques should be evaluated with regard to the potential risk of intraperitoneal tumour growth in the case of malignant tumours.

Tumor necrosis factor effects on ascites formation in an experimental tumor model.

In humans, treatment of malignant ascites with bolus TNF leads to resolution of the ascites. In an experimental model NMRI nude mice were inoculated intraperitoneally with human NIH-OVCAR3 adenocarcinoma cells, resulting in production of ascites and intraperitoneal tumor growth. Ascites formation and tumor growth after IP injection of recombinant human TNF was determined. Depending on the treatment schedule, a dual effect of TNF on the development of ascites was seen. Doses of TNF (1-10 micrograms/g) given once per week completely prevented ascites production, whereas the same doses of TNF given on a daily schedule induced enhanced ascites formation in an inverse TNF dose relationship. The area of tumor cell-covered peritoneal lining corresponded to these findings, indicating a correlation of tumor mass with ascites production. In an attempt to prevent renewal of ascites after drainage, neither inhibition nor enhancement in ascites production was seen when TNF was given five times per week. However, doses of 10 micrograms/g of TNF once per week led to almost complete inhibition of ascites reappearance. Histological examination of animals that received repeated TNF treatment demonstrated chronic peritonitis with strong stromal proliferation, angiogenesis, and increased adhesion of tumor cells to the peritoneum.

Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases.

A tumor model in the rat was used to study peritoneal tumor growth and abdominal wall metastases after carbon dioxide (CO2) pneumoperitoneum, gasless laparoscopy, and laparotomy. The role of laparoscopic resection of cancer is under debate. Insufflation of the peritoneal cavity with CO2 is believed to be a causative factor in the development of abdominal wall metastases after laparoscopic resection of malignant tumors. In the solid tumor model, a lump of 350-mg CC-531 tumor cells was placed intraperitoneally in rats having CO2 pneumoperitoneum (n = 8), gasless laparoscopy (n = 8), or conventional laparotomy (n = 8). After 20 minutes, the solid tumor was removed through a laparoscopic port or through the laparotomy. In the cell seeding model, 5 x 10(5) CC-531 cells were injected intraperitoneally before CO2 pneumoperitoneum (n = 12), gasless laparoscopy (n = 12), or laparotomy (n = 12). All operative procedures lasted 20 minutes. After 6 weeks, in the solid tumor model and after 4 weeks in the cell seeding model, tumor growth was scored semiquantitatively. All results were analyzed using the analysis of variance. In the solid tumor model, peritoneal tumor growth in the laparotomy group was greater than in the CO2 pneumoperitoneum group (p < 0.01). Peritoneal tumor growth in the CO2 group was greater than in the gasless group (p < 0.01). The size of abdominal wall metastases was greater at the port site of extraction of the tumor than at the other port sites (p < 0.001). In the cell seeding model, peritoneal tumor growth was greater after laparotomy in comparison to CO2 pneumoperitoneum (p < 0.02). Peritoneal tumor growth in the CO2 group was greater than in the gasless group (p < 0.01). The port site metastases in the CO2 group were greater than in the gasless group (p < 0.01). The following conclusions can be made: 1) that direct contact between solid tumor and the port site enhances local tumor growth, 2) that laparoscopy is associated with less intraperitoneal tumor growth than laparotomy, and 3) that insufflation of CO2 promotes tumor growth at the peritoneum and is associated with greater abdominal wall metastases than gasless laparoscopy.

Apoptosis of stomach carcinoma cells induced by a human monoclonal antibody

Although stomach carcinoma is estimated to be one of the most frequent cancers worldwide, still little is known about the immunity of patients with stomach cancer. Humoral tumor immunity has been studied by isolating B cells of patients with cancer to characterize the activity of such antibodies on tumor cells. Apoptosis, programmed cell death, explains the suicide of cells by fragmentation of DNA, cell shrinkage and dilation of endoplasmatic reticulum, followed by cell fragmentation and formation of membrane vesicles called apoptotic bodies. Apoptosis serves to remove unwanted, damaged, or dangerous, e.g., precancerous cells. The human monoclonal antibody SC-1 was isolated from a patient with a signet ring cell carcinoma of the stomach by fusion of spleen lymphocytes to the heteromyeloma SPM4-0. The antibody was tested for growth-inhibiting effects in vitro in soft agar assays, in 3-H thymidine uptake experiments, and in a mitochondrial enzymatic activity assay. In vivo intraperitoneal tumor growth was investigated in nu-nu mice. The immunoglobulin M (lambda) antibody identifies a molecule with a molecular weight of approximately 49 kilodaltons in stomach carcinoma cells. No reactivity was observed with carcinomas of other origins, melanomas, lymphomas, or normal tissue. When tested in vitro, the antibody inhibited tumor cell growth in cell culture and soft agar. In vivo growth of stomach carcinoma cells in nu-nu mice was reduced when the antibody was injected after the tumor cells. Ultrastructural and functional studies revealed that the SC-1 antibody induced apoptosis of tumor cells. The human monoclonal antibody SC-1 described here inhibited growth of stomach carcinoma cells in vitro and in vivo by inducing apoptosis, and may, therefore, be valuable for treating patients with stomach carcinoma.

Characterization of a human endometrial carcinoma cell line producing intraperitoneal tumor growth in immunodeficient mice

Establishment of laboratory models of gynecologic neoplasms provides an important means of studying the biologic characteristics of these tumors. We report a previously uncharacterized human endometrial adenocarcinoma cell line that produces both intraperitoneal and subcutaneous growth in nude mice. The line was derived from a poorly differentiated endometrial cancer and has been carried in continuous tissue culture for greater than 100 passages. Doubting time in culture is approximately 48 hr. Antigenic phenotyping against a panel of murine monoclonal antibodies by resetting cell surface assay on live cells or peroxidase assay on fixed cells has shown reactivity with a number of determinants, including MH99, MT334, MQ49, and the blood group antigens F3, 118, and 41–83. Cytogenetically, the line displays an aneuploid human karyotype with several chromosomal rearrangements and deletions. When injected intraperitoneally into nude mice, animals develop intraperitoneal nodules and ascites and succumb with wasting in 30–40 days. The intraperitoneal tumor has been passaged multiple times in nude mice by direct transfer of ascites. Subcutaneous injection of tumor cells produces nodules that grow at a reproducible rate. By light and electron microscopy, the nude mouse tumor is a poorly differentiated adenocarcinoma, similar to the original patient's tumor. It expresses both estrogen and progesterone receptors. CA 125 is not elevated in the serum of animals with tumor implants. The line appears to be cisplatin sensitive as determined by rates of growth of subcutaneous nodules. This cell line may be useful in studying the in vitro and in vivo properties of human endometrial carcinoma.

Intraperitoneal tumor growth and chemotherapy in a rat model

Animal models are important to evaluate new treatment modalities. In the present paper a new animal model is described, in which the effects of intraperitoneal (i.p.) administration of cytostatic drugs on cancers restricted to the peritoneal cavity can be studied. The tumor cell line used is a chemically induced carcinoma (CC531), sensitive in vitro to cisplatin (cDDP), carboplatin (CBDCA), 5-fluorouracil (5-FU), doxorubicin and mitoxantrone. Three to 5 weeks after i.p. inoculation of 2 × 106 CC531 cells, 80% of Wag/Rij rats develop small tumor nodules on peritoneal surfaces. Both tumor size and localization at this time are comparable to the human situation, especially to cases of minimal residual disease ovarian carcinoma. The model has been used to determine the usefulness of i.p. treatment in comparison to i.v. Changing the route of administration of cDDP from i.v. to i.p. increases tumor platinum concentrations and prolongs survival. The model offers the possibility to study drug pharmacokinetics and tumor drug penetration related to i.p. drug administration.

Characterization of a human endometrial carcinoma cell line producing intraperitoneal (IP) tumor growth in nude mice

Characterization of a human endometrial carcinoma cell line producing intraperitoneal (IP) tumor growth in nude mice

Mechanisms of organ selective tumour growth by bloodborne cancer cells.

The sites of tumour development for 6 rat tumours injected into syngeneic rats via different vascular routes was determined. Xenografts of human tumours were also injected intra-arterially (i.a.) into immunosuppressed rats. Following intravenous (i.v.) and intraportal (i.ptl.) injection of cells tumour colonies localized in lung and liver respectively due to tumour cell arrest. Arterially injected radiolabelled cells disseminated and arrested in a similar distribution to cardiac output and did not 'home' to any organs. Following arterial injection of unlabelled tumour cells colonies grew in many organs. While the pattern of growth for a particular tumour varied with the cell dose, the 'arterial patterns' for all of the tumours studied followed a similar pattern. Some organs (eg adrenals, ovaries and periodontal ligament) were consistently preferred, others (eg skin and skeletal muscle) only supported tumour growth following the delivery of large numbers of cells, while in some tissues (eg spleen and intestines) tumour never grew. Viable tumour cells could be demonstrated by bioassay in many organs for up to 24h after i.a. injection. However tumour growth only occurred in certain organs and the pattern of this growth was not related to the number of tumour cells arrested or their rate of autolysis. This site preference could be expressed quantitatively as the probability of an arrested cell developing into a tumour and was considered a 'soil effect'. Site preference was not directly related to organ vascularity. Organ colonisation was promoted by steroid treatment but the mechanism was unclear and was not secondary to T-cell immunosuppression or prostaglandin synthesis suppression. The adrenal glands were preferred sites of tumour growth but pharmacological manipulation of adrenal function did not alter tumour growth to this organ. Sites of injury and healing were preferred sites of tumour colonisation and this could not be accounted for by increased delivery of tumour cells to these regions. The possibility that the macrophage component of the inflammatory response promoted tumour growth was suggested from studies in which the interval between trauma and inoculation of tumour cells was varied as well as by promotion of intraperitoneal (i.p.) tumour growth by a macrophage infiltrate.

Relationship between tumour resistance and the in vitro and in vivo cytotoxicity elicited by Salmonella antigens in immunized mice.

Immunization of mice with the attenuated 11RX strain of Salmonella enteritidis (11RX) induces resistance to intraperitoneal (i.p.) tumour growth. Tumour resistance is much greater and lasts for a longer time following i.p. immunization than following intravenous (i.v.) immunization. This paper extends our previous observations that, after this resistance is lost, it can be recalled by a T cell-mediated reaction to an antigenic extract of the bacteria (11RX antigen) which is not protective in unimmunized mice. The duration of this sensitization to 11RX antigen was determined in mice immunized i.p. or i.v. with live 11RX by challenging them at various times after immunization with 131I (or 125I)-labelled Ehrlich ascites tumour (EAT) cells alone or mixed with 11RX antigen. In vivo killing of EAT cells was assayed by monitoring whole-body retention of radioactivity and this was correlated in the same mice with suppression of tumour growth and survival of the mice. The resistance recalled by 11RX antigen was short-lived and in vivo cytotoxic activity had subsided by 6 days after antigen injection. 11RX antigen also recalled the ability of the peritoneal cells to lyse 51Cr-labelled EAT cells in vitro and a close correlation was found between this activity and the cytotoxicity measured in vivo. The adherence properties of the cytotoxic cells and their inhibition by trypan blue indicated that they were macrophages.

Monitoring the Therapy of Human Tumor Xenografts in Nude Mice by the Use of Lactate Dehydrogenase&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;

With the use of circulating human lactate dehydrogenase (LDH) as a tumor marker, growth and remission of human tumor lines SW480, HEp-2, and Clouser, implanted into female BALB/c athymic nude mice, were followed during therapy. Three types of therapy were used: X-radiation, cyclophosphamide, and diphtheria toxin. After therapy tumor sizes were measured with calipers and compared to changes in the levels of circulating human LDH. Changes in LDH levels paralleled changes in tumor size, but the enzyme fluctuations were more pronounced. Mice bearing intraperitoneally growing SW480 and HEp-2 tumors were effectively treated with diphtheria toxin, and the measurement of circulating LDH was examined as a parameter for gauging the effectiveness of chemotherapy on tumors that could not be visualized. Circulating human LDH can be used to detect intraperitoneal tumor growth and/or remission and to predict death of the animal due to the tumor.

VIABLE TUMOR CELLS IN BLOOD AND LUNGS OF MICE WITH METASTASIZING AND NON-METASTASIZING TRANSPLANTABLE TUMORS.

SummaryExperiments were conducted to study blood-borne tumor emboli for non-metastasizing, transplantable mouse tumors. Susceptible mice were inoculated with blood and lung brei from non-metastasizing, transplantable tumor-bearing animals. Intraperitoneal tumor growth resulting from viable tumor cells in the inocula was obtained from lung tissue in the 3 non-metastasizing tumors Sa, Sb, and GL/46; and from blood in the case of Sa and GL/46. The same procedure was followed with blood and lung brei from metastasizing, transplantable tumor-bearing mice. Here, viable tumor cells were demonstrated in the blood and lung tissue of hosts for all tumors used. That metastases did not appear in hosts of Sa, Sb and GL/46 is therefore not due to absence of embolism, but to other factors which are discussed.