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)

16 patients with disseminated malignant melanoma (1 with primary ocular melanoma) entered a multicentre phase II study of recombinant interleukin-2, (rIL-2) given by continuous intravenous infusion on days 1-5 at 18 x 10(6) IU/m2 per day, followed by dacarbazine 850 mg/m2 on day 8. After a 2 week rest, a second course was given. In the absence of disease progression, monthly maintenance cycles were given for up to four cycles. 16 patients received one cycle, 14 received two and 6 patients three or more. All 16 patients are evaluable for toxicity and 15 for response. 2 patients responded (13%). 1 patient with lung and pleural metastases achieved partial remission after two cycles and went off treatment after six cycles. 3 months later a complete response was noted lasting 396+ days. A second patient with lung metastases had a partial response lasting 153 days. 3 patients (20%) had stable disease. Mean rebound lymphocytosis (24-48 h after the end of rIL-2 therapy), cell count 4.9 x 10(9)/l (2.6-8.8 x 10(9)/l) was within the expected limits. Other toxicity was as expected. Thus sequential treatment with rIL-2 and dacarbazine is feasible but synergy did not occur.
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PMID:A phase II study of sequential recombinant interleukin-2 followed by dacarbazine in metastatic melanoma. 159 Oct 61

Pertussis toxin is known to elicit lymphocytosis in whooping cough patients and experimental animals, by blocking the extravasation of lymphocytes and stimulating their release from lymphoid organs such as the thymus. The mechanisms responsible for these unique effects of PT are not fully understood. The effect of pertussis toxin (PT) on the invasive behavior of human CCRF-CEM T lymphoma cells has been investigated with the use of a monolayer invasion assay (MIA). We had previously found that invasion of murine T lymphoma cells in this model system was correlated with their ability to extravasate and form metastases after i.v. injection in syngeneic animals. We now show that human CEM cells can also penetrate through a precultured confluent monolayer of murine 10T1/2 fibroblast-like cells within a few hours. In a quantitative MIA run over 24 h, PT at concentrations above 10(-14) M inhibited invasion of the CEM cells. In addition, PT stimulated the release ('evasion') of CEM cells that had invaded under the monolayer before the toxin was added. The A subunit of PT was totally inactive, the B subunit had a small residual effect, and reconstitution of the AB complex partially restored the activity. The invasion-inhibiting activity of two different holotoxin preparations and of the subunits perfectly matched their activity in the Chinese hamster ovary cell clustering assay, which is known to depend on a functional AB complex. We suggest that inhibition of monolayer invasion by PT can be used as an in vitro model system to investigate the cellular and molecular mechanisms underlying the lymphocytosis-promoting action of the toxin. Furthermore, the method is sufficiently sensitive to be used for titration of toxin activity. Our data indicate that the ADP-ribosylating activity of the A subunit is indeed required, and that the promotion of lymphocytosis is not elicited by the binding of the B subunit alone.
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PMID:The lymphocytosis promoting action of pertussis toxin can be mimicked in vitro. Holotoxin but not the B subunit inhibits invasion of human T lymphoma cells through fibroblast monolayers. 196 Apr 20

Thirty-six patients with metastatic melanoma were entered into a study of the therapeutic efficacy of adoptive immunotherapy with high-dose interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells. Thirty-two patients who received all components of the therapy are evaluable for response, and all patients are evaluable for toxicity. Sites of disease included lung, liver, subcutaneous nodules, and intra-abdominal metastases. One complete response (CR) and five partial responses (PRs) resulted from treatment (19% response rate). The median response duration was 5 months, with the durable CR continuing at 31+ months and one durable PR continuing for 13 months. Sites of response included lung, liver, subcutaneous nodules, and lymph nodes. Response, response duration, or site of response did not correlate with the total dose of IL-2 administered, rebound lymphocytosis, or the number of LAK cells infused. Toxicity included hypotension, fluid retention with a "capillary leak syndrome" in most patients, and transient multiorgan dysfunction that resolved promptly after the completion of therapy. Adverse cardiac events occurred in 16% of patients, with one myocardial infarction leading to a death. This study confirms the activity of the initial IL-2/LAK cell regimen in metastatic melanoma reported by Rosenberg et al, supporting the concept of adoptive immunotherapy as an important new treatment approach for this disease.
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PMID:A phase II study of interleukin-2 and lymphokine-activated killer cells in patients with metastatic malignant melanoma. 264 13

Eleven patients received four consecutive weekly cycles of human recombinant interleukin 2 (IL-2) by continuous infusion for 4 days/week. Two dose levels were tested, 1 and 3 X 10(6) units/m2/day. Toxicities experienced by most patients included fever, rigors, fatigue, anemia, eosinophilia, and liver function abnormalities. All side effects from treatment reversed and no severe or life-threatening problems occurred. A marked lymphocytosis was seen following the 4 weeks of therapy. Fresh lymphocytes obtained during this lymphocytosis mediated enhanced destruction in vitro of a natural killer cell-resistant tumor cell line (Daudi). The increase in the absolute number of circulating lymphocytes and their enhanced ability to mediate direct lysis of Daudi targets resulted in a greater than 100-fold mean increase in cytotoxic potential by the end of IL-2 treatment. One patient, with renal carcinoma, who was treated at 3 X 10(6) units/m2/day experienced a sustained measurable response with greater than 50% regression of pulmonary and hepatic metastases. Five patients were retreated with a second course of IL-2, lasting 4 weeks. This therapy was well tolerated in four of these five patients, with similar immunological changes occurring. No further antitumor responses were seen in these patients. Thus, a relatively well tolerated immunotherapy regimen using IL-2 can induce dramatic increases in lymphocyte number and augment their in vitro antitumor reactivity.
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PMID:Clinical and immunological effects of recombinant interleukin 2 given by repetitive weekly cycles to patients with cancer. 325 45

Leukocytosis (WBC counts 10,000/mm3) was detected in 77 out of 252 patients (30%) with ten different types of nonhematological malignancy (NHM) at the time of diagnosis. A full search including serological and bacteriological screening was performed to exclude other possible causes of leukocytosis. Among the different tumors, carcinomas of the lung and colorectum were the most prevalently associated with leukocytosis. Absolute monocytosis was found in 25% of the patients and absolute eosinophilia in only 4.8%. The leukocytosis was attributed mainly to an increase in the mature polymorphonuclears, suggesting a release mechanism of WBC from storage pools by factors secreted or induced by the tumor. Neither the age nor the sex of the patients affected the incidence or magnitude of leukocytosis. However, the presence of metastases was associated with a significantly higher incidence of leukocytosis (p less than 0.05). The associated leukocytosis may be regarded as a poor prognostic sign, and was associated with a significantly (p less than 0.007) shorter survival time. In contrast, absolute lymphocytosis may have a positive effect on the survival time (p = 0.01). Tumor-associated leukocytosis may be an additional tumor-associated marker, of value in assessing and monitoring patients with NHMs.
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PMID:Leukocytosis in non hematological malignancies--a possible tumor-associated marker. 394 51

In 57 patients with Stage I cervical cancer and in 25 healthy women, a determination was made of leukocytosis, counts of lymphocytes and monocytes per 1 mm3 of blood, counts of T and B lymphocytes, and PHA-induced lymphocyte ability of in vitro blast transformation. Patients with cervical cancer, as compared with controls, exhibited a decrease in lymphocytosis and in the counts and percentages of T and B lymphocytes, as well as an increase of lymphocyte reactivity to PHA. An increase in the PHA-induced lymphocyte ability of in vitro blast transformation occurred in patients with a clinical picture characterized by the presence of a large tumor of the cervix or of metastases to the lymph nodes of the pelvis. In the group of patients in Stage I with a small cervix the mean indices of blast transformation did not differ from those observed for the healthy control group; on the other hand, in the group of patients with a large cervix and metastases to the lymph nodes of the pelvis, these indices exceeded on the average by about 88% those in the control group.
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PMID:T and B lymphocyte counts and blast transformation in patients with Stage I cervical cancer. 661 Jun 5

This chapter has reviewed the limitations of the use of chemotherapy in patients with hormone resistant prostate cancer. Although demonstrating that there is a small number of patients with very chemosensitive tumours, the age profile and intolerance to chemotherapy make it highly unlikely that this modality of treatment will be used more routinely despite the increasing evidence that the slow decline of prostate specific antigen with endocrine treatment can be used early to select patients who might respond to chemotherapy. Equally certain is that it will not be of use for chemoprevention of the early stages of this disease. Although some data suggest that tumours that respond rapidly and completely to endocrine therapy may benefit from the use of non-specific immunotherapy, there is no evidence that any form of vaccination therapy would be of value in preventing the disease in the main because all attempts to find evidence of a virus, particularly a human papillomavirus subtype, involved in its aetiology have proved negative. The discovery that standard endocrine therapy induces thymic regeneration and peripheral blood lymphocytosis, taken together with the demonstration that surgical trauma induced by a needle biopsy could accelerate tumour dissemination because of tumour activation by trauma induced release of tissue repair cytokines, has led to the proposal that short term endocrine treatment should be given to all prostate specific antigen positive patients prior to needle biopsy. New information on the slow kinetics of prostate cancer growth, with cancers detected by screening being found up to 20 years before clinical presentation and more than 80% of early tumours failing to double the prostate specific antigen level within 2 years, has led to proposals for a new strategy for endocrine chemoprevention of prostate cancer. This has in part been encouraged by greater confidence in the use of intermittent hormone therapy to treat patients with metastatic disease. These observations have led to the suggestion that it might be possible to prevent deaths by treating early cases detected from prostate specific antigen screening with short term (1-3 months) endocrine treatment every 5 to 10 years.
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PMID:Intermittent endocrine therapy and its potential for chemoprevention of prostate cancer. 762 58

Patients with malignant thymoma rarely may also have a peripheral T-cell lymphocytosis. "Lymphocyte spillover" from the thymus into the peripheral blood as well as a second, associated neoplasm (ie, T-cell chronic lymphocytic leukemia) are two hypotheses that have been proposed to explain this clinical phenomenon. We describe another patient with a lymphocyte-rich malignant thymoma associated with peripheral T-cell lymphocytosis. At the time of initial diagnosis, the patient's complete blood cell count was unremarkable. However, subsequent to the development of pulmonary metastases, the patient developed persistent lymphocytosis. The total leukocyte count ranged from 20 to 30 x 10(9)/L, 80% of these cells being lymphocytes. Immunophenotypic analysis of peripheral blood specimens from this patient proved that the circulating cells were mature, polyclonal T cells. The cells expressed the alpha/beta T-cell receptor and the pan-T-cell antigens CD2, CD3, CD5, and CD7, and were negative for both terminal deoxynucleotidyl transferase (TdT) and the CD1 antigen. A mixture of T-helper (CD4+) and T-suppressor (CD8+) cells were present in a ratio of 1:1.6. Gene rearrangement studies revealed that the T-cell receptor beta chain and the immunoglobulin heavy-chain genes were in the germline configuration. Serum samples from this patient were also analyzed for thymic hormones; the level of thymosin alpha 1 was markedly elevated, while that of thymosin beta 4 was decreased. These results effectively exclude the hypothesis that the lymphocytosis represents a second, associated neoplasm. The lymphocyte spillover hypothesis also seems unlikely (although not excluded), since the lymphocytes in lymphocyte-rich thymomas usually have an immature thymic cortical immunophenotype. Furthermore, one might expect nonspecific elevation of all thymic hormone levels with lymphocyte spillover. Thus, we suggest that the lymphocytosis results from a poorly defined immunoregulatory disorder, related to the presence of thymoma, and perhaps secondary thymic hormone imbalance.
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PMID:Malignant thymoma associated with T-cell lymphocytosis. A case report with immunophenotypic and gene rearrangement analysis. 797 8

The effect of dose and schedule of continuous i.v. rIL-2 infusions on leucocyte subset counts, activation status of CD56+CD3- natural killer (NK) and CD3+ T lymphocytes, and cytolytic activities of peripheral blood mononuclear cells (PBMC) was studied. A single 4-day course of rIL-2 in escalating doses (0.9-11.5 x 10(6) U/m2 per day) was given to 18 patients with various types of metastatic cancer. The serum IL-2 concentration during rIL-2 therapy ranged between 23 and 64 U/ml and was proportional to the administered rIL-2 dose, as was the rebound lymphocytosis following therapy. Before therapy, the CD56+CD3- NK cells expressed low levels of the p75 chain of the IL-2 receptor (IL-2R) and virtually no IL-2R(p55). Most CD3+ T cells were IL-2R(p55-,p75-). Between 2 and 4 days following therapy, i.e. at the time of lymphocytosis, the percentage of CD56+,CD3- NK cells among the lymphocytes had increased proportional to the administered rIL-2 dose. The levels of IL-2R(p75) expression by the CD56+,CD3- NK cells had increased. The percentages of CD3+ T cells expressing IL-2R(p55), HLA-DR and CD45RO had increased proportional to the administered rIL-2 dose. The level of lymphokine- activated killer (LAK) activity against Daudi cells was also positively correlated with rIL-2 dose. Subsequently, seven patients received 4-weekly cycles of rIL-2 (2.9-4.4 x 10(6) U/m2 per day) during 4 consecutive weeks. This schedule led to marked increments in lymphocyte and eosinophil counts, and to increased cytolytic activities compared with pretreatment. We conclude that CD56+,CD3- NK and CD3+ T cells are activated differentially by continuous i.v. rIL-2 proportional to dose and duration of treatment.
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PMID:Activation of the immune system of cancer patients by continuous i.v. recombinant IL-2 (rIL-2) therapy is dependent on dose and schedule of rIL-2. 848 6

Carcinomas of the breast with prominent lymphoplasmacytic background are commonly encountered in cytology. The aim of this study was to assess the prevalence of different types of carcinomas that share this common feature, identify possible distinguishing cytologic features, and evaluate the diagnostic pitfalls in this group of tumors. Eighteen fine-needle aspirations (FNAs) of breast carcinomas with heavy lymphoplasmacytic background were reviewed. Histologic follow-up was reviewed in all cases. Of 18 cases, there were 9 invasive ductal carcinomas (IDC), and 9 medullary carcinomas (6 typical and 3 atypical). FNAs from typical medullary carcinomas (TMC) showed more severe nuclear atypia and macronucleoli than the cases of IDC and atypical medullary carcinomas (AMC). Gland formation was absent in the TMC but was common in IDC and AMC. No cytologic differences were noted between IDC and AMC. Nucleoli were larger in TMC (mean 4, microm) than in AMC (mean, 2 microm) and IDC (mean, 1.5 microm). We conclude that lymphocytes and plasma cells may be seen in different types of breast carcinomas and should not be considered a diagnostic feature of TMC. Features potentially helpful in the cytologic differential diagnosis of a carcinoma with prominent lymphoplasmacytic background are nucleolar size (4 microm in MC, vs. 1.5 and 2 microm in IDC and AMC, respectively) and the degree of nuclear atypia. Lymphocytosis may be part of the carcinoma or may originate from a lymph node involved by metastases. In rare cases, a prominent neutrophilic infiltrate may also be present.
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PMID:Fine-needle aspiration of breast carcinomas with prominent lymphocytic infiltrate. 1090 31


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