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

Methods for the measurement of cytoplasmic and nuclear oestrogen receptors (CER and NER) are described. CERs and NERs were found to be labile at ambient temperatures; the receptors are stable for up to 1 year when stored in liquid nitrogen. Over a period of 5 years, 51% of the breast adenocarcinomas examined in women proved to be positive for CER; four adenocarcinomas of the breast obtained from men were all positive for CER; in those tumours examined for both CER and NER, 46% proved positive for CER and 30% positive for NER; no tumour was found to be positive for NER and negative for CER. In older female patients, the percentage of patients positive for oestrogen receptors increased and they were present in higher concentrations; in younger Indian women the same tendency was observed. The percentages of receptor-positive tumours in Indians, Blacks and Whites are similar. Neither the stage of the tumour nor the presence of nodal metastases influenced receptor positivity; there was no significant difference in the time to recurrence between receptor-positive and receptor-negative patients in the small number with reliable follow-up data.
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PMID:Nuclear and cytoplasmic oestrogen receptors in human mammary carcinoma. 744 81

An experimental model was designed where the frequency of blood-borne cancer cell metastases to the lungs of animals was used as an indicator to detect adverse effects of inhaled nitrogen dioxide (NO2). Animals were exposed to air containing 0.40 +/- 0.05 ppm or 0.80 +/- 0.05 ppm of NO2. After the appropriate exposure periods, the animals were infused intravenously with B16 mouse melanoma cells. At 3 wk post-infusion the animals were killed and the lungs were examined for melanoma nodule development. The lungs of the NO2-exposed animals contained a significantly higher number of melanoma nodules than the lungs of control animals (P less than .0025). These results indicate that inhalation of ambient or near ambient levels of NO2 influences the metastasis of blood-borne cancer cells. This raises the possibility that similar events may occur in the human population.
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PMID:Inhalation of NO2 and blood borne cancer cell spread to the lungs. 746 90

We examine the origins of surgical therapy, radiotherapy, and chemotherapy as they were applied to lung cancer in the mid-portion of this century. Surgical therapy for lung cancer started in the 1930s with pneumonectomies. The prognostic significance of nodal metastases was soon recognized, and surgical staging procedures became an important part of patient workup. Radical radiotherapy for potential cure of lung cancer began in the 1950s with megavoltage linear accelerators. The first application of chemotherapy for lung cancer was the use of nitrogen mustards in the 1940s. Single modality surgical therapy has become the treatment of choice for Stages I and II non-small cell lung cancer, but 50% of clinical Stage I patients die of recurrent disease, and 70% of those recur outside the chest. Biologic markers may identify high risk subgroups of Stage I and II patients who may benefit from adjuvant chemo- or radiotherapy. Within the last decade, several single and multi-institutional Phase II trials and two single institution Phase III trials have reported improved survival in Stage IIIA patients treated with cisplatin-based neoadjuvant chemotherapy prior to surgical resection. These trials have reported high response and resectability rates, but at a substantial toxicity. A new standard of care for Stage IIIA disease has not been conclusively established.
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PMID:An historical perspective of multi-modality treatment for resectable non-small cell lung cancer. 755 46

The investigation of rather insensitive metabolic parameters (protein, fibrinogen, blood urea nitrogen (BUN), blood glucose) reveals significant differences between tumor-bearing and tumor-free patients as well as benign and malignant neoplasms. Whereas metastases and glioblastomas (GBM) show significantly elevated BUN levels (21.9 +/- 1.7; 8 +/- 2.2 mg/dl) compared to benign tumors (meningioma WHO I, astrocytoma I, II) (16 +/- 0.9 mg/dl) and tumor-free matched controls (e.g. 13.9 +/- 1.4 mg/dl) only metastases depict higher glucose (141.7 +/- 11mg/dl) counts. Fibrinogen, significantly elevated in malignancy (395 +/- 25.2; 397.2 +/- 25.9 mg/dl) is without difference between meningioma, astrocytoma (253.2 +/- 16.6; 271.5 +/- 16.5 mg/dl) and controls (e.g. 270.1 +/- 10.8 mg/dl). Correlating BUN with total protein reveals a metabolic mismatch to nearly all tumor patients, regardless of dignity, as compared to tumor-free patients. Neuroendocrinoimmunological changes are the most likely reason for these overt as well as occult findings, making investigation of more sensitive metabolic parameters a rewarding task.
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PMID:Unspecific metabolic blood parameters as used in clinical routine may differentiate malignant from benign cerebral tumors. 765 23

A series of 18 ruthenium(III) complexes, structurally related to the selective antimetastatic drug Na[trans-RuCl4(DMSO)Im], and characterized by the presence of sulfoxide and nitrogen-donor ligands were tested on TLX5 lymphoma and some of them on MCa mammary carcinoma to evaluate the dependence of the degree of cytotoxicity and of antimetastatic activity on the chemical properties. In vitro cytotoxicity is present only at high concentrations (> 10(-4) M), depends upon lipophilicity and is markedly affected by the presence of 5% serum or plasma samples in the culture medium. The comparison of the effects on in vitro cytotoxicity with in vivo antitumor and antimetastatic action points out that these compounds reduce metastasis formation by a mechanism unrelated to a direct tumor cell cytotoxicity. If on one hand Na[trans-RuCl4(TMSO)Iq], the compound that shows the most potent in vitro cytotoxic effects, is the least effective against metastases, on the other Na[trans-RuCl4(DMSO)Im], the compound that better reduces metastasis formation, is rather devoid of cytotoxic effects on tumor cells kept in vitro. In particular, Na[trans-RuCl4(DMSO)Im] seems to distinguish between artificially induced metastases and spontaneous metastases and reduces only the former by a cytotoxic mechanism. Out of all the tested compounds, with the exception of Na[trans-RuCl4(DMSO)Ox], Na[trans-RuCl4(DMSO)Im] is confirmed to be the most selective antimetastatic agent of the group.
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PMID:Effects of ruthenium complexes on experimental tumors: irrelevance of cytotoxicity for metastasis inhibition. 769 44

Recent evidence supports the critical and proximate role of IL-12 in regulating both T and NK cell function during inflammation. In these studies, we evaluated the in vivo antitumor activity of murine IL-12 in murine adenocarcinoma and sarcoma models using both systemic and peritumoral administration. Antitumor effects were consistently demonstrated both in models of microdisease, in which IL-12 treatment was initiated soon after tumor inoculation (1 to 5 days), and in animals bearing large established tumors (7 to 14 days). Treatment with IL-12 markedly prolonged survival and, in most cases, caused complete tumor regression. Significant reduction in pulmonary metastases after systemic treatment was observed when treatment was delayed for 10 days after tumor inoculation. Increases in serum IFN-gamma, TNF-alpha, and nitrogen oxides were demonstrated, exceeding those observed with IL-2 treatment. Systemic administration of anti-IFN-gamma Abs before IL-12 treatment nearly completely abrogated the antitumor effect in experiments using subcutaneous tumors or pulmonary metastases. Depletion of the individual T cell subsets CD4 and CD8 by systemic administration of mAbs diminished the effectiveness of IL-12 when administered in combination. An infiltrate composed primarily of CD8+ + cells was demonstrated by using immunohistochemical analysis of tumors after IL-12 treatment. Minimal apparent toxicity was demonstrated at effective doses (0.1 to 1.0 microgram/day) of IL-12. These results indicate that IL-12 is an effective and minimally toxic antitumor agent in murine tumor models and leads to an immune-mediated rejection involving, at least in part, IFN-gamma, CD4+, and CD8+ cells. Human clinical trials of IL-12 for the treatment of malignancy are supported by these studies.
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PMID:Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. 791 43

We used the oxygen sensitivity of the histochemical reaction to detect glucose-6-phosphate dehydrogenase (G6PDH) activity based on neotetrazolium (NT) reduction to discriminate cancer cells from normal cells. Formazan generation was strongly reduced in normal but not in malignant cells when the incubation was performed in oxygen instead of nitrogen. Competition for reductive equivalents between NT and oxygen via superoxide dismutase (SOD) has been suggested. Since SOD activity is usually decreased in cancer cells, NT reduction would not be hampered in these cells. We tested this hypothesis by demonstrating NAD-dependent lactate dehydrogenase (LDH) activity instead of NADP-dependent G6PDH activity in normal rat liver and colon, in human colon carcinoma, and in experimentally induced metastases of colon carcinoma in rat livers. Reactions for both enzymes were determined cytophotometrically in an atmosphere of pure oxygen or nitrogen. G6PDH acted as described previously, showing distinct activity in cancer cells but strongly reduced activity in normal cells after incubation in oxygen, but this was not the case with LDH because formazan was also generated in normal tissue in oxygen. It appeared that after 5 min of incubation at 37 degrees C the residual activity of G6PDH in an atmosphere of oxygen compared with nitrogen was 0% in normal liver tissue and 15% in normal colon epithelium, whereas in colon carcinoma and in colon carcinoma metastasis in liver it was 48% and 33%, respectively. The residual activity of LDH in oxygen was 30% in normal female rat liver, 75% in normal male rat liver, and 38% in normal colon epithelium, whereas the residual activity in colon carcinoma and metastases in liver was 54% and 24%, respectively. These experiments clearly indicate that the oxygen sensitivity phenomenon is not solely an effect of competition for reducing equivalents between NT and oxygen via SOD, because NADPH generated by G6PDH and NADH generated by LDH have a similar redox potential. Apparently the system is more complex. The role of specifically NADPH-converting cellular systems such as NADPH-cytochrome P450 reductase was excluded because incubations in the presence of exogenous NADPH as substrate for these systems revealed oxygen sensitivity. Involvement of NADPH-dependent lipid peroxidation in the oxygen sensitivity test is discussed.
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PMID:The histochemical G6PDH reaction but not the LDH reaction with neotetrazolium is suitable for the oxygen sensitivity test to detect cancer cells. 793 May 18

Interleukin-2 (IL-2)-based therapy induces a vascular leak syndrome (VLS), manifested by hypotension, tachycardia, and oliguria, as is also seen with septic shock. The optimal method for treating such VLS is not known. A prospective randomized trial was undertaken to compare crystalloid and colloid fluid resuscitation for patients receiving bolus IL-2-based therapy for metastatic cancer. All patients received maintenance crystalloid fluid administration and were randomized to receive crystalloid (0.9% normal saline) or colloid (5% human serum albumin) fluid boluses to maintain acceptable vital signs and urine output. Patients refractory to fluid boluses were given dopamine for oliguria and/or phenylephrine for hypotension. Of 107 patients who completed one cycle of therapy on study, 76 completed a full treatment course (two cycles) on study. The total number of saline and albumin fluid boluses given were 9.5 +/- 0.9 versus 7.7 +/- 0.7 (p = 0.36, n = 107) for the first cycle and 19.2 +/- 1.8 versus 16.1 +/- 1.6 (p = 0.33, n = 76) for a complete course, respectively. Although patients receiving saline boluses had significantly more oliguria during a course of therapy, weight gain, number of IL-2 doses, tachycardia, hypotension, vasopressor use, hospital stay, and clinical response rates did not significantly differ between arms. Changes in hematocrit, hemoglobin, protein, albumin, blood urea nitrogen (BUN), and creatinine were analyzed, and patients receiving crystalloid showed greater decreases in albumin (p < 0.0001) and total protein (p < 0.05) as expected. A 40-fold greater cost associated with albumin suggested that crystalloid resuscitation be used to treat the VLS associated with IL-2 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A prospective randomized trial evaluating colloid versus crystalloid resuscitation in the treatment of the vascular leak syndrome associated with interleukin-2 therapy. 811 Jul 27

Existing hypoxia-selective cytotoxins (HSCs) are designed to kill only the hypoxic subpopulation in tumours, and to be used in conjunction with other therapies (e.g., radiation). A new class of drugs, hypoxia-activated prodrugs of diffusible cytotoxins (HPDCs) are proposed. These are designed to exploit, rather than merely deal with, tumour hypoxia, by releasing diffusible cytotoxins on bioreduction in hypoxic regions. Such diffusible cytotoxins are required to be much more cytotoxic than the parent prodrug, to be sufficiently stable (half lives from 0.1 to 10 min) to allow them to diffuse up to 200 microns from the hypoxic regions, and to be equally effective against all major tumour cell subpopulations, including non-cycling cells. Nitrogen mustards, which show little cell cycle specificity, which kill cells by a well-understood mechanism (DNA cross-links), and which have stabilities and reactivities able to be predictably controlled by structural variations, are proposed as suitable candidates fur such diffusible cytotoxins. Design parameters for two classes of potential HPDCs are discussed; nitro-deactivated aromatic mustards, and cobalt (III) complex-deactivated aliphatic mustards. Examples of both classes show greater cell-killing activity against intact compared with dissociated multi-cellular spheroids. This suggests they may indeed function as HPDCs, by penetrating to the hypoxic core of the spheroid and there releasing potent cytotoxins which diffuse out to kill surrounding cells at lower oxygen tensions.
Cancer Metastasis Rev 1993 Jun
PMID:Bioreducible mustards: a paradigm for hypoxia-selective prodrugs of diffusible cytotoxins (HPDCs). 837 17

Hepatic cryotherapy is increasingly used in the treatment of patients with multiple hepatic metastases, particularly from colorectal cancer. The Cryotech LCS 2000 system, with insulated shaft-circulated liquid nitrogen probes, was designed for this purpose and was evaluated on the bench and in an animal model. The 9-mm probe was considerably more effective than the 5-mm probe when judged on time to create an iceball of a given diameter. The use of thawing gas reduced the time until the probe could be removed from 25 to 5 min but heated gas only produced a further reduction of 2 min. In the animal model, significant reduction in treatment times occurred with vascular inflow occlusion. The zone of necrosis as a percentage of the original iceball diameter was significantly higher following a twin freeze/thaw cycle. The relationship of the edge of the iceball to the eventual zone of hepatic necrosis was studied using different unabsorbable markers. India ink and sutures proved unreliable but a Teflon cannula was more successful and the margin was only of the order of 2 mm. The discrepancy between this observation and the percentage of the original iceball diameter which apparently becomes necrotic (64 and 82%) for single- and double-freeze lesions, respectively, suggests that the cryolesion undergoes shrinkage within 1 month and that the diameter of necrosis underestimates the true zone of destruction.
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PMID:Laboratory and animal model evaluation of the Cryotech LCS 2000 in hepatic cryotherapy. 844 Jan 30


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