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)

Bacillus Calmette-Guerin (BCG) has been shown in randomized trials to be the most effective agent against superficial bladder tumors. BCG therapy prevents or reduces tumor recurrences, abrogates tumor progression and improves survival over surgery alone. The optimal BCG schedule varies among patients, reflecting a heterogeneous tumor population. Multifocality, high grade (G2,3) and T1 tumors are risk factors for tumor recurrence or invasion. Patients presenting with such features are most likely to benefit from BCG. An incomplete response to BCG portends a high risk of tumor progression. Non-responders have a 40-60% risk of developing muscle invasion or metastases within 10 years, compared with 10-15% for BCG responders. Further, 80% of non-responders progress in the bladder within 3-5 years. After 5 years, relapses are more common in the prostate (13-35%) and upper collecting system (15-33%); one-half of these are invasive tumors. This suggests that intense therapy directed at premalignant and early bladder lesions coupled with a chemoprevention strategy designed to protect the whole urothelium will be required to reverse a pan-urothelial tumor diathesis.
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PMID:Intravesical BCG: current results, natural history and implications for urothelial cancer prevention. 130 73

The three traditional modalities of cancer treatment: surgery, radio- and chemotherapy, even when applied in optimal fashion, leave over 50% of incurable patients, because of the metastatic disease. Hence the importance of preventive methods in cancer, by directing attention to the detection and treatment of preneoplasia. Focal preneoplastic lesions have been observed prior to the appearance of malignant epithelial tissues. The phenotypic patterns of preneoplasia seem to be as varied as those of neoplasia. In the frame of persistent multicellular hyperplasia, the appearance of enzyme-altered foci is supposed to be related to the origin of neoplasia, and in this sense these lesions can be considered pre-neoplasia. If there is any immune reaction to the non-self promoted by these lesions, their detection and their enhancement or induction by a vaccine would be a cancer immuno-prevention. Preliminary experiments and clinical pilot studies have shown a specific host-resistance to a pharmaceutical placental suspension (PS), when injected intradermally (DTHS-reactivity test) in patients with clinical conditions having, as histopathological substratum, a cellular adaptive (reactive) or neoplastic proliferation. Boosting this reaction by an adjuvant (BCG, corynebacterium parvum, etc.) would be an immunotherapeutic approach to cancer, as adjunct to standard treatments and in preneoplastic-bearing patients an immuno-preventive method in cancer. In vitro studies have shown that a glycoprotein of MW 40 kDa (P40), from an extract of placental suspension (PS) is recognized by patients' serum, (Ouchterlony's technique). The monospecific rabbit antiserum (MRA) raised to P40 glycoprotein also reacts with the serum of patients with positive DTHS reactions to PS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospects for preneoplasia immuno-detection and cancer immuno-prevention. 147 28

Osteocalcin (BCG) in an osteoblast product which reflects the bone formation rate. It could be a valuable bone metastasis marker. To investigate this, we measured serum osteocalcin levels by using radioimmunoassay method in 11 healthy subjects and in 79 cancer patients. The cancer patients consisted of 36 non-metastatic, 29 with only bone metastasis and 14 with extraosseous metastases. Significance was found only between bone metastatic patients and non-metastatic patients in both sexes (p. 0.05). There was no significance between non-metastatic patients and patients with other than bone metastases. This study shows that osteocalcin measurements reflect bone formation rates in bone metastasis and could be used as a bone metastasis marker in suspicious cases.
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PMID:Osteocalcin: a valuable bone metastasis marker. 191 66

With the three modalities of cancer treatment, surgery, radio- and chemo-therapy, even when applied in optimal conditions, over 50% of patients remain incurable because of metastatic disease. Hence the importance of preventive methods of approach to cancer. Host human tumors arise in renewing cell populations, while others, which originate in tissues with a slower rate of proliferation, are often preceded by tissue injury, which induces an adaptive proliferation (irritants, viruses, hypoxia etc.). Prospective and retrospective studies have shown that a "precancerous lesion" (intraepithelial neoplasia), meaning a certain histopathological substratum which, when not disturbed in its natural history through diagnostic or therapeutic proceedings, can evolve in a significant proportion, to invasive cancer. Our earlier studies have revealed a specific host-resistance to placental suspension (PS) when injected intradermally in patients with clinical conditions having, as histopathological substratum, an adaptive cellular proliferation. These findings suggest that a successful immunologic approach for adaptive proliferation is a boosted cell-mediated hypersensitivity reaction which, as an adjunct to other therapies, would eliminate and thus prevent the progression of adaptive proliferation towards neoplasia. A vaccine consisting of PS used as an immunogen, mixed with and adjuvant (BCG) may allow the strengthening of what is a natural but ineffective bodily response to the problem of adaptive proliferation. It is easier to eliminate immunologically an antigenic homogeneous cellular proliferation process than a neoplastic one which is antigenically heterogeneous. The induction of cell-mediated hypersensitivity reaction by a PS + BCG vaccine in healthy people would also be a primary immunoprophylaxis for some solid tumors in man.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is immunoprophylaxis of cancer possible? 191 70

The effects of BCG-activated lund and peritoneal macrophages on the development of the primary tumor and metastases of B-16 melanoma in C57B1 mice have been studied. The BCG-activated macrophages reduced significantly the incidence of metastases in all treated animals and prolonged the mean survival time only in mice with Winn type of neutralization test. The possible mechanisms implied in this biological process are discussed.
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PMID:The effect of BCG-activated macrophages on the B-16 melanoma. 214 21

For the purpose of inducing the antitumor effect in the portal vein, the intrasplenic serial biological response modifier (BRM) administration was performed by using our original subcutaneously-imbedded pediculated spleen in the rats. In a view point of endogenous tumor necrosis factor (TNF) production, lipopolysaccharide, BCG and OK-432 were chosen and injected into the spleen frequently. The study of the portal blood serum revealed that intrasplenic (i.s.) BRM administration group gained higher TNF and interferon (IFN) activity than control group. On the other hand, the study of the mononuclear cells in the portal vein and splenocyte after i.s. BRM administration showed higher cytotoxic activity against YAC-1 cells than control group significantly. Compared with intravenous and intraperitoneal administration groups, i.s. group showed more effective antitumor effects in the portal vein significantly. The experimental liver metastases by intraportal transplantation of AH60C could be cured with i.s. BRM administration, which could increase % survival significantly. According to the result of this study, it is prospective that i.s. serial BRM administration could be new process for suppression of transportal hepatic metastases.
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PMID:[Induction of endogenous antitumor activities in the portal vein by using a subcutaneously-imbedded pediculated spleen in the rat; experimental study of adjuvant immunotherapy in liver metastases]. 246 67

There have been major advances in the diagnosis and treatment of bladder cancer in the last several years. Flexible cystoscopy and DNA analysis have combined to increase both comfort for the patient and detection rates of early disease. The laser has become an established alternative to transurethral resection of superficial tumors, providing identical cure rates, but with more comfort and less expense. Intravesical installation of BCG has become not only an alternative treatment for recurrent superficial bladder cancer, but the first line of treatment for diffuse carcinoma in situ of the bladder which previously had been best treated with radical cystectomy. There are now numerous alternatives to the ileal conduit, when radical cystectomy is the preferred treatment. Herein we describe the "Providence Pouch," our own variation on the theme. Lastly, metastatic disease, once universally fatal, is now responding to a new combination of chemotherapy agents based on a combination of cisplatinum and methotrexate.
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PMID:Advances in the diagnosis and treatment of bladder cancer. 267 73

The prognosis of malignant melanoma (MM) depends on the level of invasion, vertical tumour size, location of the primary, clinical stage, and sex. Whereas MMs are potentially curable in the early stage of disease, the therapeutic possibilities are very limited in advanced and disseminated MM. Most chemotherapeutic agents lack sufficient activity in MM especially with regard to survival. Dacarbazine (DTIC) is the most effective drug in MM with response rates of 20-25% followed by other drugs such as melphalan with 15-20%, hydroxyurea and platin derivates. Multidrug regimens were not shown to be more effective than DTIC alone. Radiotherapy may be relevant in local treatment of metastases. With regard to the poor prognosis and limited therapeutic approaches in advanced and disseminated MM, new strategies are required. In this context immunotherapeutic strategies with biological response modifiers are of interest for adjuvant or palliative approaches. Earlier trials with Bacillus Calmette-Guerin (BCG) +/- DTIC as adjuvant or palliative treatment revealed no effect of BCG on the prognosis. Alpha-interferon (alpha-IFN) was shown to induce remissions in about 15% and gamma-IFN in about 10% of patients. A very interesting new approach is the induction and/or activation of autologous cytotoxic cells by systemic administration of recombinant interleukin-2 (rIL-2) with response rates of 20-25% and the in vivo propagation and transfer of so-called tumour infiltrating lymphocytes. Further trials combining rIL-2 with other cytokines, chemotherapy, tumour vaccination or monoclonals against melanoma cells are required.
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PMID:Malignant melanoma--prognosis and actual treatment strategies with chemotherapy and biological response modifiers. 269 76

Two main kinds of immune strategy are possible against neoplasia. The first potentiates a selected effector arm. In vitro culture with exogenous interleukin-2 (IL-2) increases the activity of natural killer cells and leads to the expansion of T cytotoxic lymphocytes. Systemic reinfusion of both of these cells with high doses of IL-2 mediates the regression of a variety of murine and human tumors. In an alternative strategy, a few regulatory lymphocytes turn on immune reactivity by triggering a cascade of interconnected effector functions. The efficacy of this strategy rests on the repertoire of effector mechanisms moved to action. An effective immunoregulatory maneuver is the addition of helper determinants on the surface of tumor cells. Its power can be further increased by the pre-induction of helper T lymphocytes specific to the helper determinants. This approach can be achieved in mice by coupling muramyl dipeptides to tumor cells, along with eliciting T lymphocytes specifically reactive to Bacillus Calmette-Guerin. Noncytotoxic T helper lymphocytes produce factors which recruit nonspecific (macrophages) as well as specific (cytolytic T lymphocytes) anti-tumor attacking cells. In this way protection can be afforded against primary tumors and metastases, as well as leukemia cells. As the activity of helper lymphocytes rests mostly on lymphokine release, the use of molecularly defined lymphokines mimicking T-helper functions has also been attempted. In a few experimental models, the association of low doses of IL-2 with non-reactive lymphocytes from tumor-bearing mice promotes an effective anti-tumor reaction in the host. Moreover, the combination of distinct lymphokines can also build a molecularly defined helper system able to activate in sequence non-specific and specific anti-tumor reactions in vivo. Trials intended to evaluate the clinical impact of these helper approaches in the management of human tumors are being started or are already under way.
Cancer Metastasis Rev 1988 Dec
PMID:Helper strategy in tumor immunology: expansion of helper lymphocytes and utilization of helper lymphokines for experimental and clinical immunotherapy. 297 63

Following preliminary studies suggesting that some patients with metastatic renal cell carcinoma had accelerated tumor growth after entry into chemotherapy studies, 73 patients with measurable metastatic disease referred to a tertiary referral center for consideration for experimental treatment protocol have been observed to attempt to establish the incidence of spontaneous regression. Initially, patients went off study if metastases showed greater than 25% increase in products of bidimensional measurement but with increasing confidence patients only went into therapy protocols with the development of symptomatic progression. In this selective series, on observation, three complete (histologically documented) and two partial unexplained "spontaneous" regressions were observed and a further four patients had prolonged stable disease for more than 12 months. On progression, 52 were entered into treatment protocols (BCG n = 19, Mitozantrone n = 12, and Welferon n = 21). A further two complete and five partial responses (14%) and four prolonged stable disease were observed confirming that the previously reported responses with these agents are not totally explicable on the basis of "spontaneous" response.
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PMID:A phase 2 study of surveillance in patients with metastatic renal cell carcinoma and assessment of response of such patients to therapy on progression. 326 68


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