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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the previous paper in this series, we described a form of self-reactivity among T cells called the "syngeneic T-T lymphocyte reaction" (STTLR). The phenomenon involves responder T cells that are stimulated to proliferate by irradiated antigen or self-reactive cloned T cell lines. The proliferative STTLR occurs in cultures rigorously depleted of conventional APC and is inhibitable by anti-Ia antibodies of the appropriate specificity. We also showed that both L3T4+ Lyt2- and L3T4- Lyt2+ T cell subsets participate in the STTLR-induced by the IEk-specific Lbd T cell line. In this paper, we report our studies on the effector phase of STTLRs, in particular, the cytotoxic responses induced by Lbd cells. We demonstrate that uncloned and cloned lines (called Dbl) of anti-Lbd cytotoxic cells are L3T4- Lyt2+ effector cells that kill Lbd, antigen-reactive T cells, and syngeneic B cells stimulated with LPS. They also kill syngeneic splenic cells stimulated with Con A for 72 h or less; longer culture periods in the presence of Con A yield Dbl-resistant T cells. Resting T cells are also resistant to Dbl cells. Using LPS-induced splenic B cells from H-2 congenic mice, we map the anti-self specificity of uncloned and cloned anti-Lbd cells to the Kk + IAk regions of the MHC. Seemingly concordant results were obtained using L transformants expressing IAk molecules on their surface. However, control studies with fibroblast lines and UV-induced fibrosarcoma cells unexpectedly revealed a high susceptibility to lysis by Dbl cells among certain Ia- cell lines. These results suggested that the antigen recognized by Dbl cells is not IAk itself but either an MHC-encoded or MHC-regulated gene product expressed by activated T and B cells and certain tumor cells. The target antigen is important in immunoregulation because Dbl cells suppress both the proliferation of Lbd cells to syngeneic cells and primary T cell-dependent anti-SRC PFC responses. From an immunoregulatory viewpoint, the existence of Lbd-Dbl cells offers several appealing features. Since Lbd cells cannot activate resting B cells or replace antigen-specific helper cells, they cannot initiate immune responses nonspecifically. In the presence of the appropriate antigen-specific helper T cells, Lbd and other self-reactive cells can amplify an immune response and thus facilitate its exponential growth. Since the self-reactive cells activate the Dbl cytotoxic circuit described above, they also provide the stimulus required to terminate immune responses quickly.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The syngeneic T-T lymphocyte reaction (STTLR). II. Induction of primary T anti-T cell cytotoxic responses in vitro in T cell cultures stimulated with syngeneic self-reactive T cells. 350 19

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.
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PMID:A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer. 351 86

The antitumor effects of human recombinant TNF (PAC-4D) were examined on three human gynecological carcinomas transplanted into CD-1 nude mice (uterine cervical carcinoma: UZ-1-N; ovarian carcinoma: OCl-1-N and OS-4-N). PAC-4D was administered intratumorally at a dose of 1,000 U, 3,000 U or 10,000 U/head from day 0 to day 4. Tumor size, body weight and peripheral WBC were measured on days 0, 4, 8, 12 and 16 and histological studies were made on day 6. The results were as follows: With UZ-1-N, intratumoral administration of PAC-4D at doses of 3,000 U and 10,000 U/head caused a marked inhibition of the tumor growth. Similarly, antitumor activity of PAC-4D against OCl-1-N was remarkable at a dose of 10,000 U/head. The administration of PAC-4D at doses of 3,000 U and 10,000 U/head was not effective against OS-4-N. The histological changes of grade II A-B by Ohboshi-Shimosato criteria of response were observed in the tumor of the effective groups against PAC-4D. There were no influences on the body weight and WBC after administration of PAC-4D. Although tumor cells possessed different sensitivities to PAC-4D, PAC-4D is strongly recommended for the treatment of gynecological malignancies.
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PMID:[Antitumor effects of the tumor necrosis factor (PAC-4D) against human gynecological carcinoma transplanted into nude mice]. 360 53

Ovarian carcinoma is the fifth most common cause of death among women in western countries. It is often diagnosed in an advanced stage (FIGO Stage III and IV) and requires effective chemotherapy as first-line treatment. The advent of cis-platin combined with adriamycin and cyclophosphamide has remarkably increased the response rate in advanced disease. The authors report 31 cases of epithelial ovarian neoplasia, without prior chemotherapy, treated with cis-platin, adriamycin and cyclophosphamide (PAC I). Of the 30 evaluable patients, 15 had clinical complete remissions (cCR = 50%), 10 clinical partial remissions (cPR = 33%) and 5 no response (NR = 17%). The total response (cCR + cPR) was equal to 83%. Twelve of the 15 patients in cCR underwent second-look laparotomy; in 8 of these cases, histologic and cytologic confirmation of CR was obtained. PAC I was found to be a highly effective therapeutic regimen with moderate toxicity. The individual toxicity reported was gastroenteric (nausea and vomiting), but transitory. No chronic toxic side-effects from cisplatin or adriamycin were noted. However, more definitive results must be obtained to verify its impact on the prolongation of survival.
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PMID:Combination chemotherapy in advanced ovarian carcinoma. 379 74

Three hundred and twenty five implantable catheters (PAC) were used in the treatment of 319 patients with neoplastic disease in 21 French centers. Two hundred and sixty three were inserted in central venous position, 43 in hepatic artery and 11 were intraportal. There were no failures at the time of insertion nor any deaths imputable to the method. Whilst the mean duration of use was 182 days, 72 catheters remain patent after one year of use or more. The risk of obstruction is 3,6% : 1,5% for I.V. sites and 13,9% in intra-arterial because internal caliber are smaller. There were 2,4%, of cases of skin leakage or necrosis and sepsis rate was 2,7%, more frequent er after percutaneous insertion. These result justify the use of this device in long term chemotherapy.
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PMID:[Completely implantable catheters for anticancer chemotherapy. A French experience of 325 cases]. 399 95

A total of 114 children (age range 4 months to 18 years) underwent definitive operation for life-threatening or incessant tachydysrhythmias resulting from accessory conduction pathways (Kent bundle) (79), atrial ectopic foci (18), or ventricular ectopic foci (17). Of the patients with the accessory pathway type of supraventricular tachycardia, 63.3% (50/79) had classical Wolff-Parkinson-White syndrome whereas 36.7% (29/79) had retrograde conduction only across the pathway. Locations of the pathways were as follows: left posterior 48.1% (38/79), right anterior or lateral 27.8% (22/79), posterior septal 16.5% (13/79), anterior septal 3.8% (3/79), and both right and left 3.8% (3/79). With increasing experience, the success rate (cure of tachycardia) improved from 85% in the first 40 patients to 95% in the last 40 patients. One surgical death (1.3%) occurred secondary to a paradoxical air embolus. Atrial ectopic tachycardia was treated by cryoablation (nine), excision (one), combined excision and cryoablation (six), and atrial disconnection (two). The ectopic focus was located on the right atrial wall in 13 patients (72.2%) and cardiopulmonary bypass was required in eight (44.4%). The operation was successful in 89%; two patients with multiple ectopic foci continued to have uncontrolled tachycardia after the operation. Ventricular tachycardia presenting in the first 2 years of life was due to gross tumor in three cases (rhabdomyoma two, fibroma one) or microscopic hamartomatous change (Purkinje tumor) in five cases and was treated by excision alone or with adjuvant cryoablation. In four cases no tumor was found but the area of ectopic focus was successfully cryoablated. One child with diffuse endocardial tumor died of low cardiac output after the operation. Ventricular tachycardia in older children was localized to outflow patch aneurysms or other areas in the right ventricle following tetralogy of Fallot repair (three patients, treated by excision or cryoablation) and arrhythmogenic right ventricular dysplasia (two patients, treated by right ventricular disconnection). We conclude that mapping and operation for supraventricular tachycardia resulting from accessory pathways are predictable and curative in a high percentage of patients. Atrial ectopic tachycardias are more difficult to precisely localize but can be cured by a combination of excisional and cryoablative techniques. Ventricular tachycardia in infants is lethal and is commonly due to ectopic foci or microscopic tumors that may not be apparent on preoperative angiography or echocardiography. Electrophysiologically directed operations in these patients can be lifesaving.
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PMID:Definitive operation for refractory cardiac tachyarrhythmias in children. 405 40

In this paper we have attempted to define the role of suppressor T cells in many well-defined murine tumor systems. We have knowingly omitted a blocking antibodies, suppressor B cells as mediators of tumor immunosuppression in various murine tumor systems; these have been well reviewed elsewhere. Also, we have focused on the importance of two different types of antigen-presenting cells in the induction and suppression of cell-mediated immunity and on some of the different modalities employed to inhibit Ts function. Finally, we have discussed the acquired immunodeficiency syndrome and the possible role of a defective helper pathway and enhanced suppressor pathway in its pathogenesis. We and others believe that the suppressor pathway is preferentially activated by tumor antigen(s) in the cases of many immunogenic murine tumors--possibly due to the release of tumor antigen(s) from tumor cells, their subsequent trafficking to specific areas of the spleen and other organs, and, ultimately, their presentation by certain APC to Ts. Ts may then act directly upon helper Lyt 1+2- T cells as these cells interact with tumor antigen(s) on I-A+ APC. Alternatively, if the effector pathway were somehow impaired--e.g., by ultraviolet radiation or a virus--then the suppressor pathway may be activated in an unregulated manner, often to the detriment of the host. Biochemical characterization of the tumor antigens that stimulate Ts generation and, presumably, tumor growth and definitive documentation of a role of APC in the processing and presentation of these tumor antigens to Ts need to be done. Then selective stimulation of the effector immune response, along with inhibition of the suppressor response, to tumor antigens with drugs, monoclonal antibodies, and soluble mediators or their analogues may be possible in the near future.
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PMID:Suppressor T cells and the immune response to tumors. 623 15

The control mechanism of aldosterone in 3 patients with 17 alpha-hydroxylase deficiency was compared to that in a patient with a deoxycorticosterone-producing tumor. The basal levels of plasma renin activity (PRA) and plasma aldosterone (PAC) were decreased in 2 of the 3 patients with 17 alpha-hydroxylase deficiency and in the patient with a tumor. However, in the third patient with accelerated hypertension, those levels were normal. In the 3 patients with low PRA and PAC, PAC was stimulated by various procedures, although the responses were lower than those in control subjects. In the patient with accelerated hypertension, the responses were similar to those of the control subjects. After 6 months' treatment with dexamethasone, the low levels of PRA and PAC gradually returned to the lower limit of normal in 2 of the patients with 17 alpha-hydroxylase deficiency. These results suggest that the suppression of PAC in patients with 17 alpha-hydroxylase deficiency is probably due to a suppression of the renin-angiotensin system.
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PMID:Control of aldosterone in 17 alpha-hydroxylase deficiency. 626 7

Significant and dramatic progress has been made in the diagnosis and treatment of women with ovarian carcinoma in the last 10 years, the results of which are now just being reflected in an increase in survival and cure rates. In early staged disease (Stage I and II) significant progress has been made concerning our understanding of the sites of subclinical metastasis when at surgery the tumor is clinically limited to the ovary or pelvis. A prospective study of 100 patients with Stages IA to IIB ovarian cancer who underwent restaging within 4 weeks of initial surgery will report this. Moreover, preliminary results of the first randomized therapeutic trials (melphalan versus observation; melphalan versus chromic phosphate [P-32]) in patients surgically staged and found to be Stage IA to IIB carcinoma will be discussed. For Stages IB to III, the 5-year survival rates comparing whole abdominal radiation by the moving strip technique to open field irradiation will be discussed. For advanced (Stage III and IV) ovarian carcinoma, the new techniques in debulking surgery will be illustrated. Finally, the significant progress in response rates, median duration of survival, disease-free survival, and 5-year survival rates made during the past 10 years will be presented. This will be done by comparing a unique group of 117 patients treated with melphalan alone, all of whom have been followed for 5 years or until death, to patients who received cisplatin combination chemotherapy--cyclophosphamide, hexamethylmelamine, Adriamycin (doxorubicin), and cisplatin (CHAD) or cisplatin, Adriamycin, and cyclophosphamide (PAC)--and have now been followed 3.4+ and 4+ years, respectively. What is clearly evident is that in the last decade there has been significant increase in response rates, median duration of survival, 3.4+-, 4+-, and 5-year survival rates and cure rates with the advent of debulking surgery and platinum-containing combination chemotherapy.
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PMID:Ovarian carcinoma. A decade of progress. 638 13

Generating an immune response to T-dependent antigens requires the cooperative interaction of APC, T helper cells, and B cells. T helper cells recognize antigen, not as soluble, native antigen, but as processed antigen in association with Ia molecules on the surface of an APC. Investigators from our laboratory demonstrated previously that some B lymphoma cell lines will present antigen to antigen-reactive T cells in an MHC-restricted fashion. These tumor lines are used in this study as a model system to examine the biochemical basis of antigen processing. Five different H-2d tumor cell lines, which differ in their ability to express Ia molecules and function as APC, are all shown to biochemically degrade sperm whale Mb in a similar manner. Intact Mb and four Mb fragments (4.3 to 12.5 Kd) were reproducibly recovered from each of these Mb-pulsed cell lines. This processed Mb is shown to be nonrandomly distributed in external and internal compartments, with the two smallest Mb fragments being enriched in the intracellular compartment. The Mb and Mb fragments can be completely removed from the surface of the APC by enzymatic proteolysis without quantitatively changing the ability of these cells to present Mb to Mb-reactive T cell lines. These results suggest that the processed Mb that is located intracellularly is the primary immunoreactive antigen for antigen presentation to T helper cells.
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PMID:Biochemical characterization of B lymphoma cell antigen processing and presentation to antigen-reactive T cells. 660 87


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