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)

The question of increased tumor cell dissemination after surgical stress was addressed in the model system of the spontaneously metastasizing rat adenocarcinoma BSp73ASML, wherein amputation of the hind leg 7 days after intrafootpad implantation of tumor cells cured the animals, while surgical stress by laparotomy 2 days prior to amputation resulted in lung metastases in 80% of rats. A detailed in vitro analysis of natural killer (NK) and macrophage (Mo) activity in different lymphatic compartments revealed the following impacts of surgery: splenic NK cells displayed unaltered activity. Yet, there was a considerable decrease in the number of lymphoid cells during the first 4 days after surgery, being followed by an overshooting repopulation. In the peripheral blood, activity levels of NK cells dropped significantly during the first 24 h after surgery; later on, NK cells appeared activated with an over 2-fold increase in lytic units (LU), 4 days after surgery, NK activity had returned towards normal levels. Most dramatic changes were observed in the peritoneal cavity, being directly involved in the surgical intervention. Six hours after surgery the peritoneal cavity was nearly depleted of NK cells and Mo, the few remaining cells being highly activated. Within 2 days the peritoneal cavity was repopulated with a 3-4 fold excess of lymphoid cells and Mo, but the repopulating cells were extremely low in lytic activity. It is concluded that depression of nonadaptive immunity after surgical stress is mainly due to traffic and repopulation with immature cells, i.e. there was no indication of suppressor cell activity. This was confirmed by a combined treatment consisting in a systemic application of Corynebacterium parvum 2 days before surgery and a local application of C. parvum after surgery, which counter-balanced the stress-induced depression of NK and Mo activity. Accelerated and increased metastatic spread could be prevented concomitantly.
Invasion Metastasis 1989
PMID:Depression of nonadaptive immunity after surgical stress: influence on metastatic spread. 270

A series of 252 patients with terminal cancer (mostly with bony metastases) were treated with epidural morphine. Results were good to excellent pain relief in 85% of patients, but those with malignant growths above the neck showed relatively poor response. For those who survived more than 3 months, the daily morphine requirement increased progressively from 3.5 +/- 0.6 mg to 19.5 +/- 5.3 mg. Drug tolerance developed but no signs of addiction were noted. Respiratory depression was detected in 2 cases due to negligence but resolved uneventfully. No infection of the central nervous system was seen. Systemic reactions were mild and transient. The major drawbacks were catheter failure which required reinsertion, and sharp pain during injection in the later stages of therapy. Despite the side-effects, percutaneous epidural morphine is a useful treatment modality of pain control in cancer patients because it is readily available, safe and not too expensive.
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PMID:A preliminary study of long-term epidural morphine for cancer pain via a subcutaneously implanted reservoir. 272 85

Serum melatonin was determined over 24 hours in 35 patients with breast cancer with either a fresh primary tumor (n = 23) or a secondary tumor (n = 12) and in 28 patients with untreated benign breast disease (controls) having a fibroadenoma (n = 10), fibrocystic mastopathy (n = 14), or other breast diseases (n = 4). Circadian rhythms existed in all groups with acrophases at 2 a.m. A 50% depression of peak and amplitude occurred in the group of patients with primary breast cancer compared with age-matched controls (P less than 0.001, P less than 0.01). The peak declined with increasing tumor size: 27% at Stage T1, 53% at T2 (P less than 0.001), and 73% at T3 (P less than 0.05). In contrast, patients with secondary breast cancer, particularly those receiving antiestrogen therapy, had a melatonin peak similar to controls. These results demonstrated a transient depression of pineal melatonin secretion in primary breast cancer and indicated a dynamic role of the pineal gland in malignancy. To investigate some endocrine effects of a depressed melatonin peak, the 24-hour rhythms of prolactin (PRL) and thyroid stimulating hormone (TSH) were determined in patients with primary breast cancer and compared with patients with secondary breast cancer. The PRL had significant circadian rhythms in both groups; but acrophases occurred at midnight in patients with secondary breast cancer, and there were unusually high concentrations at noon in patients with primary breast cancer. Circadian rhythms were not seen for TSH, but the 24-hour average secretion was depressed by 45% (P less than 0.01) in patients with primary breast cancer. The abnormal concentrations of PRL and TSH in these patients could be due to a depressed melatonin peak normally serving as a central circadian synchronizer and modulator of the secretion of adenohypophysial hormones. Additionally, a positive correlation existed between the nocturnal melatonin peak and progesterone and androgen receptor concentrations in primary tumors indicating a direct involvement of melatonin in the growth control of breast cancer.
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PMID:Stage-dependent depression of melatonin in patients with primary breast cancer. Correlation with prolactin, thyroid stimulating hormone, and steroid receptors. 273 89

This is a review of the current knowledge of feline leukemia virus (FeLV) associated with immune depression observed in cats. It will focus on the clinical and experimental observations associated with feline retroviral infection and presence in vivo and in vitro. We will briefly describe retroviral-associated acquired immune deficiency syndrome associated with FeLV infection in the cat and specific cellular pathology associated with FeLV latency. In addition, we will focus on the action of FeLV-p15E in vitro and describe possible mechanisms of the FeLV-associated immunosuppression observed both in vivo and in vitro. Lastly, we will evaluate the current status of immunoprevention of FeLV. We will not attempt an in-depth analysis of the current literature; our focus is to review current findings as they relate to feline AIDS and immunotherapy.
Cancer Metastasis Rev 1987
PMID:Feline leukemia virus: current status of the feline induced immune depression and immunoprevention. 282 30

Several animal studies have demonstrated that pain is modulated by spinal mechanisms involving prostaglandins and that acetylsalicylic acid (ASA) administered intrathecally has an analgesic effect. We report our experience of this treatment in 60 patients with proven and advanced cancer. An isobaric solution of lysine acetylsalicylate was administered by lumbar puncture in doses ranging from 120 to 720 mg of ASA. The results were evaluated using the habitual criteria: scoring system, behaviour, consumption of analgesic drugs. In this trial the method proved astonishingly effective (78% of the cases). Analgesia was strong, almost immediate and without influence on motricity. No thermic or neurovegetative changes were noted. The effect of one injection lasted from 3 weeks to 1 month on average; it was reproduced and often more prolonged after a repeat injection. Pain associated with bone metastases seems to constitute the best indication, notably in breast and lung cancer and in myeloma. Visceral (pancreas) or neural pain requires higher doses to respond. Failures (22%) were due to such factors as insufficient dosage at the very beginning of our experience or severe depressive syndrome. The perineal and sphincteral pain of rectal cancer often resists treatment. This simple, inexpensive and very effective method with no other complication than a frequent tendency to fatigue should rank among other analgesic measures in cancer. The lack of respiratory depression is a major advantage over catheter spinal opiate analgesia. We consider that its main indications are pain associated with osteolytic metastases of adenocarcinomas, and myelomas. Owing to the absence of formal toxicological data, its use must be limited to cancer pain and to patients with a life expectancy of less than 2 years.
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PMID:[Chronic refractory pain in cancer patients. Value of the spinal injection of lysine acetylsalicylate. 60 cases]. 295 75

Tumour cells from a squamous carcinoma (approximately 2.5 X 10(5)) were injected intraportally into a syngeneic strain of rats to produce liver metastases 14 days later. Kupffer cells were stimulated by Corynebacterium parvum (7 mg or 1 mg i.v.) and zymosan (10 mg intraportally). Kupffer cell activity was depressed by the administration of silica, gadolinium chloride or human red cells. The animals in each group were sacrificed at 14 days, the livers removed and the number of visible surface metastases counted and compared. (Mann-Whitney U-test). Kupffer cell stimulation significantly reduced the number of surface liver metastases in all animals (P 0.0048). In contrast depression of Kupffer cell activity significantly increased the number of metastases in all animals (P 0.0045), suggesting that the activity of these cells has an important effect on the development of liver metastases.
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PMID:The effect of Kupffer cell stimulation or depression on the development of liver metastases in the rat. 302 33

Lymphocyte subset phenotypes in peripheral blood and axillary lymph node cell isolated from 28 patients undergoing surgery for breast cancer were determined by two-color immunofluorescence with monoclonal antibodies and flow cytometric analysis. Lymphocyte subpopulation proportions were determined with combinations of monoclonal antibodies directed against the Leu 2, Leu 3, Leu 7, Leu 8, Leu 11, Leu 12, Leu 15, Leu M3, and HLA-DR surface markers. Patients were staged according to the postsurgical-pathological modification of the Tumor-Node-Metastases staging system, for analysis of tissue source (lymph node versus peripheral blood) and stage of disease as factors influencing lymphocyte subset size. Activated Leu 2+DR+ and Leu 3+DR+T-cells were elevated in stage 2 carcinoma compared to Stage 1. Elevation of Leu 2+8+ circulating T-cells and a reciprocal depression of Leu 2+8- T-cells were also seen in Stage 2 patients when compared to Stage 1. Total T-cells, B-cells, Leu 2+, and Leu 3+ T-cell subsets and natural killer phenotypes defined by Leu 7 and Leu 11 were unchanged in the peripheral blood of Stages 1 and 2 breast cancer. Regional lymph nodes from Stage 1 were found to contain a high frequency of Leu 3+ cells which dropped significantly in Stage 2 patients; this was found to be numerically due to a sharp decrease in the Leu 3+8- subpopulation in Stage 2 patients. Elevated B-cells (Leu 12+), activated T-cells (Leu 2+DR+ and Leu 3+DR+), total Leu 2+ cells, and Leu 7-11+ natural killer cells were demonstrated in Stage 2 lymph nodes when compared to Stage 1. Generally, no differences in subpopulations were seen when level 1 (low axillary) lymph node cells were compared to level 3 (high axillary) lymph node cells at each stage of the disease. These findings demonstrate substantial differences in the profile of lymphocyte phenotypes between Stage 1 and Stage 2 breast carcinoma, especially in the ipsilateral regional nodes. The findings presented in this study suggest that changes in local-regional immunocompetent cell subsets may be related to metastasis of tumor to the regional nodes and progression of disease without being fully reflected in the systemic circulation.
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PMID:Monoclonal antibody-defined phenotypes of regional lymph node and peripheral blood lymphocyte subpopulations in early breast cancer. 308 Dec 62

Cancer chemotherapeutic agents modify the human immune system in diverse ways including both immunosuppression and immunostimulation. We evaluated the effects of mitomycin-C on rat Kupffer cell phagocytosis, C3b receptor binding, and lysosomal enzyme activity. Kupffer cell cultures were greater than 95% pure. Phagocytosis of IgG-coated sheep red blood cells was demonstrated by 84% of control cells but by only 25% of cells isolated two weeks following mitomycin-C administration (p less than 0.0005). This depression in phagocytic ability had returned to control levels by four weeks posttreatment. Similarly, C3b receptor binding of IgM and complement coated sheep red blood cells was observed in 88% of control Kupffer cells, but declined to 47% at two weeks after drug administration (p less than 0.005) and returned to normal after four weeks. Lysosomal enzyme activity was not impaired by mitomycin-C. Histologically severe ulceration of the colon of treated animals was seen one and two weeks after drug administration, but healed by four weeks post-mitomycin-C treatment. Depression of macrophage function as a consequence of cancer chemotherapy may have important clinical consequences in host defense against bacteria and tumor metastases.
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PMID:Alteration of rat Kupffer cell function following mitomycin-C administration. 312 96

Methotrexate, Cisplatin, and Vinblastine (MCV) was followed by Cisplatin plus radiation therapy in 19 patients with muscle-invading clinical Stage T2-4NXM0 transitional cell carcinoma of the urinary bladder (including cystectomy candidates), to achieve local control and prevent distant metastases. Radical cystectomy was recommended for all patients who failed to reach a complete response (CR = biopsy negative and cytology not positive) following MCV and Cisplatin X 2 plus 4000 cGy. Completely responding patients, and those partially responding patients unsuited for cystectomy, were selected for bladder conservation treated with additional irradiation to the bladder tumor volume (total 6,480 cGy) plus one additional Cisplatin treatment. Dose reductions were required for stomatitis in 26%, mild bone marrow depression in 58%, and renal toxicity in 5% of the patients. During the Cisplatin/4000 cGy, mild dysuria occurred in 68% of patients and 36% had mild bowel hyperactivity. Serious complications have occurred in two patients to date. One patient had recurrent pulmonary emboli, marked reduction in bladder capacity, and diarrhea. A second had bladder perforation during cystoscopic evaluation after MCV and a small bowel obstruction after Cisplatin and 4000 cGy. There was no treatment-related sepsis. Three patients had initial complete transurethral resection of their tumors and therefore 16 patients are evaluable for tumor responsiveness to this protocol. Four patients (25%) were biopsy negative and cytology negative, whereas three additional patients (19%) were biopsy negative but cytology positive following initial MCV. Six patients (38%) were biopsy negative and cytology negative whereas three additional patients (19%) were biopsy negative and cytology positive following MCV and Cisplatin X 2 plus 4000 cGy pelvic radiation. Of the entire group, 9 patients were treated with full-dose radiotherapy. All of these patients are alive without evidence of tumor on rebiopsy of the original tumor site, but one has a persistent positive cytology. Seven patients had a radical cystectomy and 6 are disease free. The treatment of 3 patients deviated from the protocol. Overall, only one patient has developed distant metastases and currently 84% of the patients are disease-free, although follow-up is short. To date, this feasibility study has been clinically practical and well tolerated. The proportion of CR's suggests that this program may prove to be an organ-sparing and curative approach for a significant number of patients, but more experience and follow-up are required.
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PMID:Invasive bladder carcinoma: preliminary report of selective bladder conservation by transurethral surgery, upfront MCV (methotrexate, cisplatin, and vinblastine) chemotherapy and pelvic irradiation plus cisplatin. 318 28

Twenty patients with disseminated melanoma were treated with interferon alfa-2a, given by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 X 10(6) U/m2. Of 18 patients considered evaluable, two had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa-2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa-2a on days 3, 10, and 31) consisted of neutropenia, thrombocytopenia, and a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatment, returning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen-stimulated interleukin-2 (IL2) production, and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune system, such as depression of IL2 and immunoglobulin production in vitro, and the differences noted in clinical responses during the present study compared with those observed with interferon alfa-2b given by intravenous (IV) injection in 5-day cycles. These results suggest that interferon alfa-2a has antitumor activity in certain melanoma patients, in particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa-2a and help to optimize treatment regimens.
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PMID:Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma. 348 11


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