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At least 19 recordsLinked to original sources
PubMed2006

Relationships among tumor burden, tumor size, and the changing concentrations of fibrin degradation products and fibrinolytic factors in the pleural effusions of rabbits with VX2 lung tumors.

The VX2 tumor is derived from a papilloma virus-induced rabbit epithelial cell line. If VX2 tumor cells (trapped in a plasma clot) are introduced intravenously into NZW rabbits, the cells lodge in the lung capillary bed and produce tumors. Independently of the tumor burden (ie, the total tumor weight per rabbit), approximately 15% of rabbits with VX2 lung tumors accumulate an effusion in the interpleural space and this pleural effusion contains products of hemostasis. We hypothesized that these products were of intra-tumoral origin and that they changed in concentration as tumor burden increased. Interrelationships among lung-, tumor-weights, and pleural effusion volumes, and the concentrations of fibrinolytic factors, their catabolic products, and other proteins of pleural effusions were measured in rabbits with a wide range of tumor burdens. Positive correlations between tumor burden and total lung weight and between pleural effusion volume and net lung weight suggested that interstitial fluid from the stroma of tumors passed directly into the extravascular space of the lung(s) and into the interpleural space(s). Analyses of pleural effusions indicated that plasminogen-, alpha(2)-antiplasmin-, and plasminogen activator inhibitor-1-related proteins, urokinase-like- and tissue-plasminogen activator activities, and vascular endothelial growth factor increased in concentration up to a tumor burden of approximately 20-25 g. Plasmin activity and intact fibrinogen were absent. The concentration of fibrin(ogen) degradation products did not change significantly up to a tumor burden of approximately 25 g but increased substantially as tumor burdens exceeded 25 g. In conclusion, interstitial fluid from tumors enters the extravascular space of the host and may accumulate with fluid from non-tumor sources as a pleural effusion. The concentrations of fibrinolytic factors and their products in pleural effusions reflect the tumor burden of the rabbit. Conceivably, the components of a malignant effusion contain much information about the extent of tumor growth.

Animals↗
PubMed1993

Effect of tumor burden on futile glucose and lipid cycling in tumor-bearing animals.

Futile cycling of metabolic substrates may play an important role in the development of cancer cachexia. To determine the effect of tumor burden on futile glucose and lipid cycling, 64 female Lewis/Wistar rats were randomized to control (non-tumor-bearing), small tumor burden, or large tumor burden groups (MAC-33 mammary adenocarcinoma). After 5 or 25 days of tumor growth, animals received a 5-day period of parenteral nutrition (158 kcal/kg/day) followed by a 6-hr infusion of the stable isotopes glucose-2-d and glucose-6,6-d2 or [C13]palmitate. The heavy glucose isotopes glucose-2-d and glucose-6,6-d2 are labeled with deuterium at the 2-carbon position and doubly labeled with deuterium at the 6-carbon position, respectively, to obtain differential molecular weights. No increase in glucose or lipid cycling was observed in animals with small tumor burdens. In contrast, a significant increase in plasma rate of appearance (Ra) of glucose-2-d (1377 +/- 136 mg/hr vs 947 +/- 54 mg/hr), Ra of glucose-6,6-d2 (810 +/- 88 mg/hr vs 510 +/- 24 mg/hr), and total glucose cycling (548 +/- 57 mg/hr vs 416 +/- 28 mg/hr) was seen in animals with large tumor burdens compared to control animals (P < 0.05). Although a trend toward increased lipid cycling was seen in tumor-bearing versus control animals, this change was not significant. Thus, futile cycling of glucose was significantly elevated in animals with large tumor burdens and may cause significant energy wasting to contribute to the development of cachexia in the tumor-bearing host.

Adenocarcinoma↗
PubMed1994

Luciferase activity as a marker of tumor burden and as an indicator of tumor response to antineoplastic therapy in vivo.

The gene encoding firefly luciferase has been used as a reporter gene for the study of gene function. The luciferase catalyzes its substrate and subsequently produces luminescence. In addition, it is not present in mammalian cells. We have therefore explored its use in monitoring the growth of tumors in vivo. The luciferase gene was transfected into two murine tumor lines, i.e. c162 melanoma and M109 lung carcinoma, and the luciferase activity associated with the cells was determined by a rapid chemiluminescent reaction. Luciferase activity was well-correlated with the number of tumor cells in vitro. Luciferase activity also correlated with the tumor burden in vivo, as well as with the effect of an adoptive T cell transfer therapy in the syngeneic C3H/HeN mice experimental tumor model. This assay offers the advantage of being quantitative, rapid, and reliable for the detection of tumor burden and for the evaluation of the effect of antineoplastic therapy.

Animals↗
PubMed1980

Prognostic factors in Burkitt's lymphoma: importance of total tumor burden.

In 42 patients with African Burkitt's lymphoma, we have studied biochemical and clinical correlations with prognosis. Clinical stage and anti-EA titer were the best predictive factors, but lactic dehydrogenase (LDH) and uric acid (UA) concentrations also correlated with stage and prognosis, whereas lactic acid (LA), which was significantly elevated in Stage D, did not significantly correlated with prognosis or with LDH and UA levels. All of these factors with the possible exception of LA reflect the total body burden of tumor. We conclude that the tumor burden is the single most important prognostic factor in Burkitt's lymphoma, and that this is reflected directly by LDH and UA concentrations, and probably indirectly by anti-EA titer.

Adolescent↗
PubMed1987

Gluconeogenesis in the tumor-influenced rat hepatocyte: importance of tumor burden, lactate, insulin, and glucagon.

In an attempt to define the relationship between tumor burden (cachexia) and host hepatocyte gluconeogenesis, the following experiments were performed with the use of an F344 male rat bearing a transplantable sarcoma. Food intake of tumor-bearing (TB) rats was constant until day 24 following implant and a tumor burden of 18 +/- 5.2% (mean +/- SD), at which time food intake progressively declined daily. Tumor burden was arbitrarily divided at 12.8% to determine if any measured changes occurred prior to or following the approximate time when a significant decline in food intake occurred. Plasma glucose levels decreased with tumor burden. Whole-blood lactate levels increased with tumor burden. Fasting plasma alanine levels decreased with tumor burden. Plasma 3-methylhistidine levels increased with tumor burden. Plasma glucagon levels increased with tumor burden, whereas plasma insulin levels decreased. Hormone changes were noted at small tumor burdens prior to a decline in food intake. Viable hepatocytes were isolated from 4 groups: non-tumor-bearing (NTB), small tumor burden [(STB) 3.5% total body weight (TBW)], moderate tumor burden [(MTB) 14% TBW], and large tumor burden [(LTB) 23% TBW]. As expected in NTB rats, hepatocytes produced significantly more glucose with 20 mM lactate than 20 mM alanine or than Hanks' balanced salt solution (HBSS) alone. Hepatocytes from STB rats demonstrated the same basic relationship for lactate, alanine, and HBSS, but they produced significantly more glucose from lactate and HBSS alone than NTB hepatocytes. With alanine as substrate, the rates of glucose production by hepatocytes were not affected by the presence or size of tumor. However, with lactate as substrate, hepatocytes from MTB and LTB rats produced progressively less glucose as tumor burden increased (r = -0.85, p less than .001), which may partly explain the reduction in blood glucose and elevation in blood lactate levels observed. Elevated gluconeogenesis in TB rats occurred early prior to a decline in food intake. The key precursor appeared to be lactate. The balance between glucagon and insulin appeared to promote the abnormal host carbohydrate metabolism observed.

Amino Acids↗
PubMed2003

Prospective study of the ability of serial measurements of serum chromogranin A and gastrin to detect changes in tumor burden in patients with gastrinomas.

BACKGROUND: Assessment of tumor burden changes is essential for the management of patients with neuroendocrine gastrointestinal (GI) tumors. Chromogranin A (CgA) is a tumor marker for such tumors; however, to the authors' knowledge, there is little information on whether serial assessments can assess changes in tumor burden. In this prospective study of patients with gastrinomas, serial changes in serum CgA levels were compared with changes in levels of the specific tumor marker gastrin to determine whether they reflected changes in tumor burden. METHODS: In 72 consecutive patients, the mean CgA and gastrin levels from three determinations were measured on each visit. Changes in markers were correlated with changes in tumor burden determined by imaging. By assessing daily changes, significance changes in CgA and gastrin levels were determined. RESULTS: During 103 follow-up visits (mean, 9.6 months), an increased tumor size occurred in 25% of patients, no change occurred in 62% of patients, and a decrease occurred in 13% of patients. In patients who had increasing tumor size, CgA levels increased numerically in 77% of patients, gastrin levels increased in 54% of patients, and the increases were significant in 60-80% of patients. In patients who had tumor stabilization, CgA levels in 63% of patients and gastrin levels in 73% of patients did not show a significant change. Decreased tumor size postresection showed a significant decrease in CgA and gastrin levels in all patients. The sensitivity of CgA and gastrin was as follows: sensitivity for detecting an increase, 62% for CgA and 31% for gastrin; sensitivity for detecting no change, 42% for CgA and 75% for gastrin; and sensitivity for detecting a decrease in tumor size, 85% for CgA and 85% for gastrin. The specificity varied from 53% to 99% for CgA and from 49% to 93% for gastrin. CONCLUSIONS: In patients with gastrinomas, serum CgA and gastrin levels varied considerably from day to day, and this must be taken into consideration. Both markers had low sensitivity and specificity for detecting tumor increases and stabilization. For large tumor decreases postresection, both markers had high sensitivity and specificity. The current results suggest that these markers do not have sufficient sensitivity to replace serial imaging studies for detecting important smaller changes in tumor burden in patients with gastrinomas.

Adult↗
PubMed1992

Quantitation of metastatic tumor burden from human colon tumor xenografts using radiolabelled monoclonal antibody 17-A fragments.

In realistic models of human tumor xenograft metastasis, the metastatic foci arise in perivascular sites and rarely grow to sizes which are easily quantifiable by visual inspection. As an alternative approach, we have used monoclonal antibody (MAb) 17-1A F(ab')2 fragments labelled with radioiodine (125I) to study the differential accumulation of label in xenografts and metastatic tumor sites as well as in noninvolved tissues of NIH Swiss nude mice receiving HT-29 human colon tumor cells. Images of the whole-body distribution and sites of localization were determined using a pinhole-collimated Angergamma camera. Radioactivity was determined in tissue samples using a well scintillation system, and pharmacokinetics were assessed during the initial 72 h after injection of antibody fragments. The half-life of 125I-F(ab')2 fragments in the blood, 8.6 h, was similar in nontumor-bearing control and tumor-bearing mice. The half-life in subcutaneous tumor xenografts was 30.1 h. The tumor xenograft to tissue activity ratios per unit weight (radiolocalization indices) at 72 h were: blood 90, lung 65, pancreas 50, muscle 35, spleen 20, liver and mesenteric lymph node 10. All subcutaneous xenografts were successfully imaged, and images of 5 of 9 mice (55%) appeared to demonstrate the presence of metastatic tumor by differential and focal accumulation of MAb fragments after 48 or 72 h in the lung (2 cases) or abdominal cavity (3 cases). Necropsy and subsequent histological and biodistribution studies confirmed the presence of metastatic tumor in these sites and identified tumor in several additional sites. The smallest volume of metastatic tissue in liver or lung determined at necropsy which appeared to have been detected by imaging was about 20 mm3. Generally, for mice with metastatic tumors, the radioactivity per unit weight of metastatic tumor-bearing organs compared to tumor-free organs was 2- to 7-fold greater. The results indicate that a radiolocalization index of > or = 2 is generally necessary for metastatic tumor detection by imaging although this is influenced by the extent of anatomical location of the tumor. It was possible to predict the tissue distribution of the fragments from the planar image for the amounts of radioactivity (approximately 1 mCi/kg body weight) employed in this study. These results demonstrate the utility of this approach to quantitate the metastatic burden arising from human colon tumor xenografts in this experimental model.

Animals↗
PubMed2001

Local costimulation reinvigorates tumor-specific cytolytic T lymphocytes for experimental therapy in mice with large tumor burdens.

Cytotoxic T cells recognize tumor Ags and destroy cancer cells in vitro. Adoptive transfer studies with transgenic T cells specific for tumor Ags have demonstrated that CTL are effective only in mice with small tumor burdens and thus appear to have limited potential in cancer immunotherapy. Here we used transgenic mice that express the TCR specific for an unmutated tumor Ag P1A and multiple lineages of P1A-expressing tumors to address this critical issue. We found that local costimulation, either by expression of B7-1 on the tumor cells or by local administration of anti-CD28 mAb 37N, reinvigorated the function of CTL specific for the tumor Ag, as it substantially increased the efficacy of CTL therapy for mice with large tumor burdens. Our study suggests that CTL-based immunotherapy can be manipulated to deal with large tumors.

Abatacept↗
PubMedDate not supplied

The effect of lymphatic tumor burden on sentinel lymph node biopsy results.

Increasing tumor burden in the axilla, as determined by the number of positive lymph nodes, adversely affects sentinel lymph node (SLN) identification and false-negative rates. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective, multi-institutional study. All enrolled patients underwent SLN biopsy, followed by complete level I/II axillary dissection. Participating surgeons represent a variety of practice settings, mostly community-based private practice. A total of 229 surgeons enrolled 2206 patients between August 1997 and November 2000. SLN biopsy was performed using blue dye injection alone, radioactive colloid alone, or a combination of the two agents. Two key parameters used to measure SLN biopsy success are the SLN identification rate and SLN false-negative rate. The overall SLN identification and false-negative rates were 92.5% and 8.0%, respectively. With increasing numbers of positive axillary nodes, there was a decreased sentinel node identification rate. There was no difference in the false-negative rate with increasing axillary tumor burden. Increased tumor burden in the axilla (as determined by the mean number of positive nodes) is associated with failure to identify a SLN in some cases, but is not an explanation for false-negative results. Standard axillary dissection should be performed when a SLN cannot be identified.

Axilla↗
PubMed2003

[Subcutaneous transplantation of microencapsulated Chinese hamster ovary (CHO) cells/pcDNA 3.1/mIL-12 and subcutaneous transplantation of microencapsulated CHO/pcDNA3.1/mIL-12 combined with 5-fluoro-uracil in treatment of tumor-burdened mice].

OBJECTIVE: To investigate the effect of subcutaneous transplantation of microencapsulated Chinese hamster ovary cells (CHO)/pcDNA3.1/mIL-12 and subcutaneous transplantation of microencapsulated CHO/pcDNA3.1/mIL-12 combined with 5-fluoro-uracilum (5-FU) in treatment of tumor-burdened mice. METHODS: CHO/pcDNA3.1/mIL-12 and CHO/pcDNA3.1 were suspended in solution of sodium alginate and made into microcapsules. Sixty mice were divided into 6 groups of 10 mice: (1) IL-12 group, microencapsulated CHO/pcDNA3.1/mIL-12 was injected subcutaneously, (2) combined treatment group: CHO/pcDN with 5-FU, (3) 5-FU group: 5-FU was injected intraperitoneally, (4) blank vector group: CHO/pcDNA3.1 was injected subcutaneously, (5) tumor-burdened group: without any treatment, and (6) blank control group: normal mice without any treatment. Except the mice of the blank control group, all mice were injected subcutaneously into the inner side of right thigh with mice colonic adenoma cells. The volume of tumor was measured every third day. 20 days after the treatment, 5 mice in each group were killed to examine the serum Th1 type cytokines: interferon (IFN)-gamma, IL-12, and Th2 type cytokins: IL-4, IL-10 by double antibody sandwich ELISA. The spleens were made into suspension of lymphocytes to examine the activity of natural killer cell (NK) and cytolytic T lymphocyte (CTL). The survival period of the remaining 5 mice in each group was observed till the 60th day. RESULTS: The activity of NK and CTL were significantly much more in the IL-12 group than in other groups. The activity of NK was significantly much more in combined treatment group than in the tumor-burdened group. The levels of Th1 type cytokines were the lowest in the tumor-burdened group. There was no difference in the levels of Th1 type cytokine between the tumor-burdened group and 5-FU group. However, the levels of Th1 type cytokine were significantly higher in the IL-12 group than in other groups. The levels of Th2 type cytokines were rather high in the tumor-burdened group. There was no difference in the levels of Th2 type cytokine between the tumor-burdened group and 5-FU group. However, the levels of Th2 type cytokine were the lowest in the IL-12 group than in other groups. There was no significant difference in volume of tumor among the tumor-burdened group, blank vector group, and 5-FU group. The mean diameters of tumor in the IL-12 group and combined treatment group were significantly smaller than in the 5-FU, tumor-burdened, and blank vector groups (P < 0.05), however, without a difference between the IL-12 group and combined treatment group. The survival periods of the IL-12 group and combined treatment group were significantly longer than those in the blank vector, tumor-burdened and 5-FU groups (P < 0.05). CONCLUSION: Microencapsulated CHO/pcDNA3.1/mIL-12 transplanted subcutaneously significantly improves the immune function of tumor-burdened mice and partially overcomes immune suppression caused by chemotherapy, and is effective in slowing the growth of tumor and lengthening the survival period of tumor-burdened ice.

Animals↗
PubMedDate not supplied

Effect of lymphatic tumor burden on sentinel lymph node biopsy in breast cancer.

Distal obstruction of the lymphatics by tumor and extensive tumor infiltration of the draining lymph nodes may prevent migration of the tracer to the sentinel lymph node (SLN), adversely affecting SLN identification. Rerouting of lymphatic drainage may divert flow to internal mammary nodes and cause an alternative nonsentinel node to become "sentinel," increasing the risk of a false-negative result. A total of 618 breast cancer patients underwent SLN biopsy using 99mTc albumin colloid and patent blue V injected peritumorally. This was followed by standard axillary node clearance in all patients at the same operation. The overall SLN identification and false-negative rates were 96% (593/618) and 7.6% (17/223), respectively. There was no difference in the SLN identification rate and the false-negative rate with increasing axillary tumor burden (as determined by the total number of positive nodes in the axilla). Further detailed analyses are based on the 64 patients from one center (Cardiff) who had at least one positive SLN and proceeded to axillary clearance. A total of 83 positive SLNs were removed from 64 patients. Tumor burden in the positive SLN was assessed by measuring the size of the metastasis and percentage replacement of the SLN by tumor, and by documenting extranodal invasion. Increasing tumor burden in the SLN (as determined by percentage replacement of SLN by tumor and presence of extranodal invasion) was associated with decreased radioisotope uptake (p = 0.005 and p < 0.0001, respectively). There was no correlation between radioisotope uptake and the size of the metastasis in the SLN. There was no correlation between blue dye uptake, internal mammary drainage on lymphoscintiscan, and tumor burden in the positive SLN. In conclusion, increased axillary lymphatic tumor burden is not associated with failure to identify a SLN or false-negative results when both blue dye and radioisotope are used for SLN biopsy. In an individual SLN, the percentage replacement by tumor, but not the absolute size of the metastatic deposit is associated with reduced radioisotope uptake. Extranodal invasion in the SLN is a marker of lymphatic obstruction and is significantly associated with reduced radioisotope uptake. The lymphatic tumor burden does not seem to affect blue dye uptake or internal mammary drainage.

Adult↗
PubMed1990

Seasonal changes in serum gonadotropin, testosterone, 11-ketotestosterone, and estradiol-17 beta levels and their relation to tumor burden in gonadal tumor-bearing carp x goldfish hybrids in the Great Lakes.

The hybrids of carp (Cyprinus carpio) and goldfish (Carassius auratus) collected from the lower Great Lakes between 1978 and 1981 exhibited a high frequency of gonadal neoplasms and apparent sterility, conditions which were rare in the parental species. A pronounced hyperplasia of gonadotropic cells in hybrids resulted in the accumulation of large stores of biologically active gonadotropin (GtH) in the pituitary gland. Serum GtH levels were generally higher in hybrids than in carp collected from the same areas, but seasonal trends were similar for both species. Among hybrids, tumored individuals had higher serum GtH levels than nontumored individuals. Serum levels and seasonal trends for testosterone (T), 11- and ketotestosterone (11-KT), and estradiol-17 beta (E2) were, for the most part, similar when carp and nontumored hybrids of the same gender were compared. Serum levels of T and 11-KT (but not E2) were generally higher in tumored hybrids when compared to nontumored individuals. High serum steroid levels were related to a specific tumor type, possibly of Sertoli cell origin. Although the etiology of the gonadal tumors is not yet known, the serum levels of gonadal steroids in hybrids make it unlikely that a lack of steroidal feedback is responsible for the gonadotrop hyperplasia.

Animals↗
PubMed2001

Osteoprotegerin inhibits osteolysis and decreases skeletal tumor burden in syngeneic and nude mouse models of experimental bone metastasis.

Certain malignancies, including breast cancer, frequently metastasize to bone, where the tumor cells induce osteoclasts to locally destroy bone. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, is a negative regulator of osteoclast differentiation, activation, and survival. We tested the ability of recombinant OPG to inhibit tumor-induced osteoclastogenesis, osteolysis, and skeletal tumor burden in two animal models. In a syngeneic model, mouse colon adenocarcinoma (Colon-26) cells were injected into the left ventricle of mice. Treatment with OPG dose-dependently decreased the number and area of radiographically evident lytic bone lesions, which, at the highest dose, were undetectable. Histologically, OPG also decreased skeletal tumor burden and tumor-associated osteoclasts. In a nude mouse model, OPG treatment completely prevented radiographic osteolytic lesions caused by human MDA-MB-231 breast cancer cells. Histologically, OPG decreased skeletal tumor burden by 75% and completely eradicated MDA tumor-associated osteoclasts. In both models, OPG had no effect on metastatic tumor burden in a panel of soft tissue organs. These data indicate that OPG may be an effective therapy for preventing osteolysis and decreasing skeletal tumor burden in patients with bone metastasis.

Adenocarcinoma↗
PubMed2001

Rituximab as first-line monotherapy in low-grade follicular lymphoma with a low tumor burden.

Patients with follicular lymphoma and a low tumor burden have a median overall survival of more than 10 years. Toxic conventional chemotherapy regimens are inappropriate in these patients, as they do not improve overall survival and the patients do not require palliation of symptoms. However, as most of these patients will ultimately die of their lymphoma, new therapies, with curative intent, are required. Rituximab is a human-mouse chimeric monoclonal antibody that has shown efficacy in patients with non-Hodgkin's lymphoma (NHL). The benign tolerability profile of rituximab makes it a suitable candidate for first-line treatment of follicular NHL patients with a low tumor burden. In a trial of 49 patients, 73% achieved a clinical response (26% complete response) with rituximab treatment. Molecular studies showed that 57% of patients achieved molecular remission (clearance of the bcl-2 molecular translocation from the blood, evaluated by polymerase chain reaction), 62% of these remaining bcl-2- for at least 1 year. There was a good correlation between molecular and clinical responses, with patients failing to achieve a molecular response at higher risk of disease progression. Rituximab monotherapy is therefore an effective and well-tolerated treatment for patients with low-grade lymphoma and a low tumor burden.

Antibodies, Monoclonal↗
PubMedDate not supplied

Correlation between lipid-associated sialic acid and tumor burden in melanoma.

Recent studies have suggested that lipid-associated sialic acid (LSA) may be a useful tumor marker for monitoring patients with melanoma, but the relationship between LSA and tumor burden has not been previously studied. We therefore examined LSA levels in 240 patients of whom 169 had no clinical evidence of disease (NED) and 71 had metastatic disease. There was a statistically significant difference in LSA levels in patients with NED compared with metastatic disease as well as those with high tumor burden compared with low or intermediate tumor burden. There was no difference between the groups with low and intermediate tumor burden. An LSA level of 25 mg/dl provided a positive predictive value of 70% and a negative value of approximately 80%. Our data show that LSA levels correlate with tumor burden in patients with melanoma.

Biomarkers, Tumor↗
PubMed1999

Effectiveness of the angiogenesis inhibitor TNP-470 in reducing the growth of human neuroblastoma in nude mice inversely correlates with tumor burden.

Angiogenesis plays an important role in the growth and metastasis of malignant tumors. We have previously reported that in children with neuroblastoma (NB), tumor vascularity directly correlates with metastatic disease, MYCN amplification, and poor outcome. The angiogenesis inhibitor TNP-470 has been shown to reduce the rate of NB growth in rodents with macroscopic tumors without ultimately impacting survival. To investigate whether TNP-470 could more effectively inhibit NB growth in animals with a low tumor burden, we treated 30 nude mice with minimal disease with this angiogenesis inhibitor (supplied by TAP Pharmaceuticals, Inc.). Therapy was initiated before tumors were clinically evident after s.c. inoculation of 5 x 10(6) cells from the MYCN-amplified NB cell line NBL-W-N. TNP-470 was administered 3 days/week, and after 12 weeks of treatment, 53% of the treated mice remained tumor free, whereas 100% of the control mice developed tumors (P < 0.0001). To further assess the relationship between the efficacy of TNP-470 treatment and tumor burden, TNP-470 was also administered s.c., 3 days/week, to mice with clinically evident small (<400 mm3; n = 15) and large (>400 mm3; n = 11) tumors. For animals with small tumors, the mean rate of growth was significantly decreased in the treated mice compared to the controls (P = 0.02). In contrast, there was no difference in the mean rate of tumor growth between animals with large tumors treated with TNP-470 and controls (P = 0.64). Our studies demonstrate that the effectiveness of TNP-470 inversely correlates with tumor burden. We speculate that TNP-470 may most effectively inhibit NB tumor growth in children with a low tumor burden.

Angiogenesis Inhibitors↗
PubMed1996

Endogenous interleukin 6 levels in patients with metastatic malignant melanoma: correlation with tumor burden.

The involvement of interleukin (IL-) 6 in malignant disease has been investigated in a variety of different malignancies. To evaluate whether serum IL-6 is a useful disease marker in metastatic malignant melanoma (MMM), we studied the time course of endogenous IL-6 secretion in 41 patients treated with cisplatinum, IL-2, and IFN-alpha. Furthermore, the relationship of endogenous IL-6 concentrations to the tumor burden and/or the clinical response was also evaluated. The baseline serum IL-6 levels were significantly higher in patients with MMM than in the control group (P = 0.002). When tumor burden was taken into consideration, we found that IL-6 levels were higher in patients with high tumor burden than in patients with low tumor burden. During treatment in the whole patient population, a higher serum IL-6 level was observed in nonresponding as compared to responding patients at days 7 (P = 0.0005), 21 (P = 0.002), and 35 (P = 0.009). The follow-up of serum IL-6 in patients with MMM according to the tumor burden and clinical response demonstrated that: (a) IL-6 levels were significantly higher at days 7 and 21 in patients with high tumor burden as compared to those with low tumor burden; and (b) IL-6 levels remain significantly higher in nonresponding patients as compared to responding patients regardless of the tumor burden. From these results, we can conclude that endogenous IL-6 may play a role in the failure of IL-2 therapy in such patients, since the very early IL-6 increase is correlated with the tumor mass and nonresponse to biochemotherapy. Therefore, it seems that the early detection of endogenous IL-6 may represent valuable information for monitoring the response to biochemotherapy in patients with MMM.

Adult↗