Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines whether primary laser excision results in augmentation of the systemic host anti-tumor response to tumor rechallenge. Single R3230AC mammary tumor implants, (0.5 x 0.5 x 1.0 mm), were grown in 112 female Fisher 344 rats. The animals were randomized. Group S tumors were excised by scalpel. Group E was excised with a Surgistat electrocautery (Valley Labs, Boulder, CO). Group CS was excised with a Sharplan 1100 CO2 laser (Sharplan, Allendale, NJ) at 25 watts (W) continuous wave (CW) (0.2 mm spot size) and the wound was "sterilized" with a 5-mm spot size by gently heating the tissue without blanching. Group K was excised with a KTP/532 laser (Laserscope, San Jose, CA) at 17 W CW using a 400 microns fiber. Group Y was excised with a Sharplan 2100 Nd:YAG laser set at 15W CW using a 0.2 mm clear sapphire tip. A second tumor implant, (0.5 x 0.5 x 1.0 mm), was placed at a remote site 14 days postoperatively. An unoperated control group was implanted. Secondary tumor volumes were measured for 36 days and the mean tumor volumes (MTV) were statistically compared. The MTV in groups CS, K, Y, and E was less than control (P less than 0.01). The MTV in groups CS, K, Y, and E was less than group S, although this was not statistically different. Lasers and cautery appear to increase the host response against subsequent tumor challenge. This study corroborates earlier studies of other modalities. Further studies to determine whether this host sensitization is an immune response and to elucidate the mechanisms of this effect are warranted.
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PMID:Augmentation of the systemic host anti-tumor response through laser excision. 150 27

To study the effect of hepatectomy on the growth of liver tumor, Shionogi Carcinoma 42, a mammary tumor, was transplanted into the liver of mice which had undergone 40% hepatectomy. The liver tumor and the number of pulmonary metastases in hepatectomized mice were significantly larger than those in nonhepatectomized mice. Responses to lectins and IL-2, subpopulations, and cytotoxicity to YAC-1 and P815 cells of splenocytes were assessed to evaluate immunological status. At the initial phase after hepatectomy and tumor transplantation into the remaining liver, NK activity transiently increased, and function of B and T cells, especially of helper T cells, decreased, while B-cell function recovered beyond normal levels in a later phase. These results suggest that liver may play an important immunological role and that the immunological modification after hepatectomy may be responsible for the accelerated growth of liver tumor. Accordingly, some adjuvant immunotherapy may be recommended for the prevention of recurrence after hepatectomy for liver tumor.
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PMID:Hepatectomy accelerates the growth of transplanted liver tumor in mice. 160 May 23

The purpose of our study was to compare the therapeutic effects of doxorubicin in 3 different formulations: (1) in PBS, (2) in conventional liposomes composed of egg phosphatidylglycerol/egg phosphatidylcholine/cholesterol/dl-alpha tocopherol, and (3) in sterically stabilized, long-circulating "Stealth" liposomes composed of hydrogenated soy phosphatidylcholine/cholesterol/polyethylene glycol-distearoylphosphatidylethanolamine. The doxorubicin formulations were used to treat recently implanted and well-established, growing primary mouse mammary carcinomas, and to inhibit the development of spontaneous metastases from intra-mammary tumor implants. In the treatment of recently implanted primary tumors, the formulations were given in 3 i.v. injections over 15 days, starting 3 or 10 days after tumor implantation. In the treatment of well-established primary tumors, the mice received 4 i.v. injections over 22 days, starting an average 38 days after tumor implantation. In the preventive treatment against metastases, the formulations were given in 4 i.v. injections over 22 days, starting 22 days or 58 days after primary tumor implantation. The Stealth liposome formulation was significantly more effective than the conventional liposome formulation or the free drug in reducing the incidence of metastases from intra-mammary implants of tumor MC19 and tumor MC65, in curing mice with recent implants of tumor MC2A, tumor MC2B, and tumor MC65, and in increasing the 8-week survival of mice with well-established implants of tumor MC2B. It is concluded that the long circulation time of the Stealth liposome doxorubicin formulation accounts for its superior therapeutic effectiveness.
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PMID:Therapy of primary and metastatic mouse mammary carcinomas with doxorubicin encapsulated in long circulating liposomes. 163 42

Causal relationships among stress, immune suppression, and enhanced tumor development have often been suggested, but direct evidence is scant. We studied stress effects in Fischer 344 rats using a tumor model in which lung metastases of a syngeneic mammary tumor (MADB106) are controlled by natural killer (NK) cells. Animals exposed to acute stress showed a substantial decrease in NK cell cytotoxicity against this tumor in an in vitro assay and, when intravenously injected with this tumor, showed a twofold increase in surface lung metastases. The critical period during which stress increases metastases appears to be the same as that during which this tumor is known to be controlled by NK cells. These findings support the hypothesis that stress can facilitate the metastatic process via suppression of the immune system.
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PMID:Stress increases metastatic spread of a mammary tumor in rats: evidence for mediation by the immune system. 165 66

Lectin binding was assessed in a transplantable pregnancy-dependent mouse mammary tumor line (TPDMT-4), its autonomous sublines (T4-0196 and T4-01165) and their artificial metastases (lung colonies), using the avidin-biotin-peroxidase technique. Soybean agglutinin (SBA) and peanut agglitinin (PNA) bound to the luminal surfaces of TPDMT-4 tumor cells, while dolicos biflorus agglutinin (DBA) showed no binding. In T4-0196 and T4-01165 tumors as well as their lung metastases, SBA and PNA binding was mixed and both positive and negative cells were detected, indicating that these lectins were not associated with the metastatic phenotype. Although the T4-0196 and T4-01165 sublines had a mixture of DBA-positive and DBA-negative cells, all the metastatic T4-0196 subclones contained only DBA-positive cells and all the metastatic T4-01165 subclones had DBA-negative cells. Thus DBA-positive, and DBA-negative subclones had respectively metastasized to the lungs from these autonomous sublines, implying that the carbohydrate moieties detected by DBA were not associated with metastatic potential but that the lung metastases were clonal in origin.
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PMID:Lectin-binding patterns in transplantable mouse mammary tumors and their metastases. 176 42

Both clinical and experimental breast tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). We have reported previously that metastatic murine mammary tumor cells also express a high-affinity PGE2 receptor. We have now shown that the receptor plays a functional role in the metastasis of two mammary tumor cell subpopulations, lines 66 and 4526. We showed that three agents, LEO101 (LEO Pharmaceuticals), SC19220 (Searle Co.), and AH6809 (Glaxo Co.), antagonize [3H]PGE2 binding to these cells and block PGE2-mediated elevation of intracellular cyclic AMP. Pretreatment of line 66 cells with nontoxic concentrations of any of the three receptor antagonists prior to i.v. injection results in more experimental lung colonies. As shown previously, and confirmed here, pretreatment of these cells with indomethacin (which inhibits endogenous PGE synthesis and therefore increases detectable PGE receptor) inhibits metastasis. Thus, the tumor cell PGE2 receptor contributes to the ability of murine mammary tumor cells to metastasize.
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PMID:Role of the prostaglandin E2 receptor in mammary tumor metastasis. 184 40

The effect of surgical removal of "primary" tumors on the cytokinetics of local tumor remnants, secondary implants, and metastases was investigated in three different rat tumor models in the Wag/Rij rat: a slow-growing (MCR83) and a fast-growing (EMR86) hormone-dependent mammary tumor and a rapidly, but autonomously growing carcinoma (MCR86). The latter two tumors had metastatic potential. Cell kinetic studies were done using in vivo labeling with 5'-bromodeoxyuridine (BrdUrd). Thirty-three hours after removal of a subcutaneous MCR83 flank tumor, secondary implants showed a significant (P less than 0.05) but transient increase in the BrdUrd labeling index (LI). A more rapid and prolonged increase, lasting for at least 7 days, was observed in EMR86 lymph node and lung metastases. In both models, no effect was observed after sham surgery (consisting of opening and closing of the skin under anesthesia). Removal of MCR86 tumors (growing in the hind leg muscle) also resulted in a rapid, transient LI increase in metastases. Continuous BrdUrd labeling experiments in this tumor model did not favor the hypothesis that the LI increase predominantly resulted from an increase in the growth fraction. Moreover, in this model, the effect was related to operation trauma. A similar increase in LI, although smaller than after tumor removal, was seen after major surgical trauma in MCR83 flank tumors. These results indicate that in the rat, tumor removal and/or major surgical trauma may modulate the cytokinetics of distant metastases significantly. A study of the systemic, possibly endocrine, factors involved in the growth-stimulating effect of surgical trauma in these rat tumor models may help to assess the clinical relevance of these findings for patients with breast cancer.
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PMID:Surgically induced cytokinetic responses in experimental rat mammary tumor models. 185 76

The ability to establish a prognosis for patients with early breast cancer is an important clinical issue. Recent studies have shown that antibodies to haptoglobin-related protein (Hpr) may be useful in stratifying early patients with breast cancer according to their relative risks of recurrence. Nearly 30% of early breast cancers express proteins bearing Hpr epitopes. Hpr-positive breast cancers are more likely to recur after primary resection and are associated with shorter disease-free intervals. This immunohistochemical study examines temporal changes in Hpr expression during the course of disease in 48 patients with fatal breast carcinoma. Thirty-seven primary tumors (77%) were Hpr positive. Ten of the 11 initially negative tumors (91%) were Hpr positive at the time of recurrence. In contrast, only 10 of the 37 initially positive tumors (27%) were Hpr negative with relapse. Of 18 axillary nodes that were examined, 16 (89%) were Hpr positive; all four lymph nodal metastases in patients with initially negative primary tumors were Hpr positive. The authors conclude that the acquisition of Hpr expression parallels increased malignant potential and that Hpr expression, once acquired, tends to remain a permanent characteristic of any given mammary tumor.
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PMID:Expression of haptoglobin-related protein in primary and metastatic breast cancers. A longitudinal study of 48 fatal tumors. 186 79

Metastasis by mouse mammary tumor cells is usually confined to lung. This paper describes the metastatic behavior of an established mouse mammary tumor cell line, 4526, that in addition to lung and liver metastasis, shows a high rate of heart metastases. The tumor cells were inoculated into the fourth mammary fat pad of syngeneic mice and their pattern of distant colonization was analysed qualitatively as well as quantitatively. We found that the cell line produced 100, 70 and 40% metastases to the lung, liver and heart, respectively. While the lung metastases appeared primarily as nodular masses, the liver metastases occurred both as nodular and diffuse masses. In addition, we observed that the metastatic load of each of the different lung lobes of individual mice was proportional directly to its relative size, and there seemed to be an inverse relationship between the occurrence of lung and liver metastases in individual mice. As compared to lung and liver metastases, heart metastases were found to be localized internally, usually in the cavity and wall of the ventricle. Furthermore, hearts with metastases revealed destruction of cardiac tissue and blockage of the cavity space. Our results show that 4526 cells are phenotypically stable, since the metastatic behavior of several clonal derivatives of the cell line obtained from lung, liver and heart colonies were found to be identical to that of the parental cell line. Thus this cell line, because of its unparalleled metastatic characteristics, offers a model for investigations into the biology of mammary tumor cell metastasis, especially heart metastasis.
Clin Exp Metastasis
PMID:Colonization characteristics of a murine mammary tumor cell line that metastasizes frequently to the heart. 186 27

The authors report on the influence of plasminogen activators (PA) on implantation of TA3Ha mammary tumor cells in the healing hepatic wounds of syngeneic strain A mice. Intravenously injected TA3Ha cells, although they rarely metastasize to the liver, formed tumors in the hepatic wounds of a significant percent (42%, P less than 0.0001) of mice. The frequency of tumor formation declined as the interval between surgery and tumor cell inoculation was increased. Furthermore, preexposure of cells to fibrinogen, fibronectin, laminin, or peptides containing the arginine-glycine-aspartic acid-serine residues dramatically reduced the frequency of tumor formation in the hepatic wounds. These results indicate that TA3Ha cells interact with fibrinogen-related proteins in the wound to aid their attachment and growth. Because these proteins are susceptible to digestion by plasmin, PA were used in this study to examine whether administration of these drugs to the mice would modulate tumor formation in the liver wounds. Among the PA tested, human plasmin B-chain-streptokinase complex (B-SK) and recombinant tissue plasminogen activator (t-PA) inhibited tumor implantation in a dose-related manner. Administration of 900 units (U) of B-SK or 3300 U of t-PA per mouse reduced the frequency of tumor formation from 42% to 0% (P = 0.02) and 11% (P = 0.02), respectively. The B-SK was complexed with p-nitrophenyl-p-guanidinobenzoate; it did not activate the plasminogen or inhibit tumor formation in the hepatic wounds. Although urokinase activated the plasminogen, it did not inhibit tumor implantation in the hepatic wound. Heparin, an anticoagulant that prevents conversion of fibrinogen to fibrin without being fibrinolytic, had no influence on tumor formation in the hepatic wounds. The PA can generate plasmin that digests the cell attachment proteins in wounds and consequently inhibits tumor cell attachment.
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PMID:Inhibition of tumor implantation at sites of trauma by plasminogen activators. 191 15


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