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P L Triozzi

Publications and source records attributed to P L Triozzi.

53 records · Page 3Linked to original sources
PubMed1991

Treatment strategies for AIDS-related malignancies.

We have made progress in the therapy of AIDS-related malignancies, although it is obvious that our treatment strategies, at present, are not--by any measure--satisfactory. Effective treatment should take into account the pathogenesis and etiology of the malignancy; immune and performance status of the patient; the rate of progress of the tumor; the presence or risk of developing life-threatening opportunistic infections; associated hematologic, neurologic, pulmonary, and gastrointestinal abnormalities; the toxicities of treatment; and, most importantly, the patient's desire for treatment. Aggressive supportive measures must be used. With optimal management, it should be increasingly possible to improve the outcome of patients with AIDS-related malignancies.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Human monocytes inhibit lymphokine-activated killer cell expansion in vitro.

Depleting monocytes from human peripheral blood mononuclear cells (PBMC) enhances the in vitro activation of lymphokine-activated killer (LAK) cells. To determine if monocytes also altered LAK-cell expansion, we evaluated two methods of depleting monocytes from PBMC: nylon wool adherence (NWA) and phenylalanine methyl ester (PME) treatment. Both methods of depleting monocytes enhanced interleukin-2 (IL-2) driven, LAK-cell expansion; LAK expansion, however, was significantly greater after depletion with NWA than after PME. LAK cytotoxicity after NWA and PME depletion was equivalent. The degree of monocyte depletion, determined by evaluating morphology and the number of Leu-M3 (CD14) positive cells, and the proliferation of Leu 19 (CD56), OKT-3 (CD3), Leu2 (CD8), and Leu 3a (CD4) positive cells was also equivalent. Exposure of IL-2 activated cells to PME did not alter their cytotoxic activity. However, sequential treatment of PBMC with NWA, then PME, or with PME and then NWA, resulted in reduced expansion. This reduction in expansion was similar to PBMC treated with PME alone. Exposure of PME-depleted cells to nylon wool or to supernatants obtained from cells adherent to nylon wool further decreased LAK expansion relative to cells treated with NWA alone. We conclude that even at relatively low cell density, human monocytes markedly inhibit LAK-cell expansion in IL-2 driven PBMC cultures. Further, depletion of monocytes by NWA adherence is more effective than by treatment with PME, possibly due to subtle cellular damage induced by this latter treatment. These findings have implication for the in vitro and in vivo generation of LAK-cells by IL-2.

Cell Separation↗
PubMed1990

Immunological effects of flavone acetic acid.

Flavone acetic acid (FAA) enhances natural killer and lymphokine-activated killer (LAK) cell activity in mice. We examined the immunological effects of FAA on human blood cells both in vivo and in vitro. Peripheral blood natural killer and LAK activity and lymphocyte subsets were evaluated in cancer patients after receiving 3-h infusion of FAA at either 8.5 or 10 g/m2 with alkalinization. Natural killer cell activity and the number of Leu-19 (CD56) positive cells decreased at 24 h after infusion; significant changes in LAK activity and the number of Leu-1 (CD5), Leu-3 (CD4), Leu-2 (CD8) cells were not observed. Peripheral blood mononuclear cells and peripheral blood lymphocytes collected from healthy volunteers were exposed in vitro to FAA, interleukin 2, and FAA plus interleukin 2. FAA, alone or in combination, failed to enhance LAK activity at any time point or concentration from peripheral blood mononuclear cells and peripheral blood lymphocytes. Concentrations of greater than or equal to 100 micrograms/ml antagonized the generation of LAK activity from interleukin 2 treated peripheral blood lymphocytes. These data suggest that FAA may not be useful in enhancing immunological responses in humans.

Adult↗
PubMed1990

Effects of 2'-deoxycoformycin on HL-60 cell differentiation, adenosine deaminase, and oligoadenylate synthetase.

There is evidence that 2'-deoxycoformycin (DCF) functions as a differentiating agent. We examined the effects of DCF on the differentiation of HL-60 cells, a standard model of leukemic cell differentiation. DCF did not induce morphologic or histochemical evidence of differentiation, nor did it interact with retinoic acid, 1,25-dihydroxyvitamin D3, or interferon-gamma in inducing differentiation. Furthermore, DCF and agents that differentiated HL-60 cells had opposing effects on adenosine deaminase and 2',5'-oligoadenylate synthetase activity.

2',5'-Oligoadenylate Synthetase↗
PubMed1990

Combined effects of interferon and 2'-deoxycoformycin on 2',5'-oligoadenylate synthetase and adenosine deaminase in hairy cell and chronic lymphocytic leukemia cells.

The combined effects of interferon (IFN) and 2'-deoxycoformycin (DCF) on 2',5'-oligoadenylate (2-5A) synthetase and adenosine deaminase (ADA) activity were examined in vitro in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL). In HCL cells, the effects of IFN and DCF on both OAS and ADA activity were strictly antagonistic. Antagonism in inducing OAS activity was also observed in CLL cells, although, in general, little interaction between DCF and IFN occurred in these cells. If OAS and ADA are important in the antitumor effects of IFN and DCF, our results suggest that combination therapy with IFN and DCF could be counterproductive.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Combined effects of interferon and steroid hormones on 2',5'-oligoadenylate synthetase activity in chronic lymphocytic leukemia cells.

2',5'-oligoadenylate synthetase (OAS) has been implicated in the effects of interferons (INF) and steroid hormones on cell growth and differentiation. We studied the combined effects in vitro of hormones and INF on OAS activity in cells from 10 patients with chronic lymphocytic leukemia. IFN enhanced OAS activity in all cells studied and also induced morphologic transformation. Diethylstilbestrol was also found to induce OAS activity, but not morphologic transformation. Progesterone, tamoxifen and dihydrotestosterone had no effect on enzyme activity nor on morphology. In five samples, all with estrogen receptor activity, DES and INF were synergistic in inducing OAS activity. TAM-INF synergism was observed in one sample. DES and TAM did not, however, significantly enhance IFN-induced morphologic transformations. Hydrocortisone reduced OAS activity, and antagonized INF-induced enzyme activity and morphologic transformations. We conclude that hormones can modulate OAS activity in CLL cells. These findings may be of importance in the design of INF-based therapies of CLL.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

Contributions of benzodiazepines to cancer therapy.

We have reviewed the therapeutic effects of benzodiazepines employed as adjuncts to cancer treatment. These agents have been used primarily for alleviating or attenuating situational anxiety, insomnia, chemotherapy-induced nausea and vomiting, and anticipatory nausea and vomiting. Situational anxiety not corrected by psychosocial support, symptom control, or time may be successfully treated with benzodiazepines. Procedure-related anxiety, for example, that related to bone marrow biopsy, venipuncture, intrathecal therapy, and the insertion of subclavian and femoral catheters, is a serious problem that may be alleviated by the use of benzodiazepines. Insomnia not caused by a depression serious enough to warrant treatment with a tricyclic antidepressant also may be successfully treated with benzodiazepines. Many clinicians have found benzodiazepines to be useful adjuncts to a cancer chemotherapy regimen because of their anxiolytic, sedative, and amnesic properties and also because of their suspected antiemetic properties when these drugs are used in conjunction with known antiemetic agents. The ability of lorazepam to induce antegrade amnesia has proved particularly useful in alleviating anticipatory nausea and vomiting connected with repeated courses of cytotoxic chemotherapy. Furthermore, since benzodiazepines are relatively safe drugs, their continued and probably expanded uses as cancer therapy adjuncts can be anticipated.

Anti-Anxiety Agents↗
PubMed1987

5-Fluorouracil, cyclophosphamide, and vincristine for adenoid cystic carcinoma of the head and neck.

Twenty-one patients with adenoid cystic carcinoma of the head and neck were treated with intravenous boluses of cyclophosphamide and vincristine and 5-day continuous intravenous infusions of 5-fluorouracil (CVF) every 4 weeks. Eight patients received CVF as palliation for recurrent or metastatic disease. A sustained complete response (107+ months) was observed in one patient; one partial response and one mixed response each also were observed. In four patients disease stabilized, and in one disease progressed. Thirteen patients received six courses of CVF in the adjuvant setting after surgery and radiation for either primary or locoregional recurrent disease. Recurrences developed in two of seven patients with primary disease and three of six patients with recurrent disease with a median follow-up 45 months (range, 20-108+). Recurrence rate and time interval to recurrence were comparable to those of well-matched historical controls. Distant metastases have not developed in patients treated with CVF in the adjuvant setting, whereas distant metastases had developed in historical controls within comparable periods of follow-up. Serious toxicities were not encountered in any patient. The authors conclude that CVF is a well-tolerated combination chemotherapy program with activity in adenoid cystic carcinoma of the head and neck. This regimen, however, has not had a major impact in the adjuvant setting in preventing recurrent disease.

Adult↗
PubMed1987

Optimum management of nausea and vomiting in cancer chemotherapy.

Nausea and vomiting continue to be critical problems in cancer chemotherapy, although considerable progress has been made toward understanding the neuropharmacological mechanisms of vomiting and how chemotherapeutic agents and antiemetics affect these mechanisms. The principles of behavioural psychology have also been applied in an effort to understand and effectively manage these complications which have potentially serious consequences. For example, there is now some degree of rationality to our use of metoclopramide for cisplatin-induced nausea and vomiting, the use of combination antiemetic regimens, and use of lorazepam for the prevention (albeit unproven) of anticipatory nausea and vomiting. It must be admitted, however, that our approach is for the most part still empirical. Selecting an antiemetic programme is not a simple task. The emetogenic potential of the chemotherapy being used, the presence of coexisting diseases, the potential toxicity of the antiemetic drug and whether antiemetic therapy is to take place in the hospital or in an outpatient setting, the familiarity of the clinician with the various antiemetic therapies, and cost are all factors which need to be considered. Although phenothiazines remain the standard treatment, they are of little value against chemotherapy programmes that produce moderate or severe problems. Newer pharmacological approaches including butyrophenones, cannabinoids, metoclopramide, high-dose corticosteroids, and benzodiazepines have shown increased antiemetic efficacy, as have combinations of these agents which are directed against multiple sites of emetogenic activity. The role of behavioural therapies, which have been shown to be effective particularly in children and in anticipatory nausea and vomiting, needs to be more firmly established. Rather than recommending a given antiemetic programme for any particular chemotherapy, it is preferable to think in terms of initial approaches and how they can be modified. No one antiemetic programme is effective or safe in all situations.

Antineoplastic Agents↗
PubMed1987

Supportive care of the patient with cancer.

In assessing the needs of the elderly patient with cancer, we need first to determine the extent of cancer, its complications, and the type of comorbid physical and psychologic conditions. The next step is to determine the goals of our care and specifically the extent to which supportive care is needed to deal with problems. For supportive care to be truly effective, the specific underlying condition producing a complaint must be investigated. It is also important not to underestimate the significance of a symptom such as constipation. Furthermore, nutritional support requires as much planning as, for example, the control of pain. Some problems (eg, nausea, vomiting, pain, and constipation) are best managed with preventive measures; others (eg, anemia, granulocytopenia, and coagulopathies) have very specific indications for intervention. Considerable progress has been made toward understanding the mechanisms of clinical problems such as nausea and vomiting, and a more rational approach to supportive therapy is now possible. However, it is usually not possible to recommend any one intervention for a particular problem: no one intervention is uniformly effective or safe. Aggressive supportive care in elderly cancer patients can improve their ability to tolerate anti-cancer therapies and, more importantly, provide palliation of distressing symptoms.

Aged↗
PubMed1986

Gastrointestinal involvement and multiple lymphomatous polyposis in mantle-zone lymphoma.

The clinical, histologic, and immunologic features of three cases of lymphoma presenting with gastrointestinal symptoms and involving the gastrointestinal tract were studied. Two of the cases had involvement of long segments of the bowel with polypoid lesions, a rare presentation of gastrointestinal lymphoma referred to as multiple lymphomatous polyposis (MLP). All cases were classified as mantle-zone lymphoma (MZL), a follicular variant of intermediate lymphocytic lymphoma (ILL) characterized by the proliferation of small atypical lymphoid cells as wide mantles surrounding benign-appearing germinal centers. The patients were typical of other patients with MZL in that they were male, middle age or older, and their clinical courses were not aggressive despite the presence of disease at an advanced stage. Our review of the literature suggests that there is an inordinate number of cases of MZL with gastrointestinal involvement. We also note that most reports of cases of MLP have described histologic lesions remarkably similar to what we have observed. We conclude that MZL may have predilection for involvement of the gastrointestinal tract, that this involvement is often in the manner of MLP, and that most cases of MLP probably have MZL or ILL.

Aged↗
PubMed1986

Induction of 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells by gamma interferon.

Activity of the interferon-induced enzyme 2',5'-oligoadenylate (2-5A) synthetase was measured in peripheral blood mononuclear cells (PBMC) of 32 cancer patients treated with recombinant human gamma-interferon (rHGIF). Pretreatment activities varied widely but remained constant for each individual. The minimum dose of rHGIF that consistently stimulated activity was 12 MU/m2, although in some patients as little as 0.004 MU/m2 was stimulatory. Enzyme activity in responding patients increased threefold at 24 h after the initial infusion and remained elevated nearly twofold at 72 h independent of dose. This increase is less than that observed after infusions of alpha-interferon and parallels results observed in vitro. Pretreatment enzyme activity did not correlate with response. Twenty-minute infusions of a fixed dose were as effective as four- and 24-h infusions in raising enzyme levels. The level of activity achieved after the initial infusion could not be sustained with twice-weekly infusions. We conclude that rHGIF does induce 2-5A synthetase activity in PBMC but not to the levels induced by alpha-interferon. The observation that brief infusions of low doses can be maximally stimulatory in vivo suggests that the response of PBMC in vivo is being confounded by factors yet to be determined. Furthermore, it appears that the capacity of PBMC to maximally respond to rHGIF in vivo, with increases in enzyme activity, is transient.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

Biologic effects of the adoptive transfer of cells depleted of monocytes with L-phenylalanine methyl ester.

Monocytes macrophages have negative regulatory effects on many immunologic responses. Depletion of monocytes from peripheral blood using the lysosomotropic agent, L-phenylalanine methyl ester (PME), has been shown to improve lymphokine activated killer (LAK) cell expansion in vitro. A pilot study of the adoptive transfer of LAK cells expanded with PME was performed in patients with metastatic renal cell carcinoma. Patients received interleukin-2 (IL-2) by continuous infusion for 5 days. Leukopheresis was performed daily for 4 days during the second week. Cells obtained from 8 patients were depleted of monocytes using PME in an one-step procedure; < or = 3% of the remaining cells were monocytes. All cells were expanded for 10 days in air-porous plastic bags with IL-2. Cells expanded 2.7-fold when depleted with PME and 1.7-fold when not depleted (P = 0.02). Expanded cells were administered together with IL-2. Patients received up to 60 x 10(10) PME-depleted cells (mean = 26 x 10(10)) with LAK activity (% lysis) of 60 +/- 12%. Lymphocyte phenotype and cytolytic activity were not modulated by PME-depletion, and clinical toxicities and systemic immunologic effects observed in patients receiving PME-depleted cells were similar to that of 5 patients receiving cells not expanded with PME. Thus, the use of PME to deplete monocytes ex vivo can result in the yield of large number of effectors that retain immunologic activity for potential clinical use. The process is convenient, efficient, and does not add clinical toxicity.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Human chorionic gonadotropin as a target for cancer vaccines.

Human chorionic gonadotropin (hCG) is expressed by common cancers and may play a role in cell transformation as well as angiogenic, metastatic, and immune escape phenomena that are central to cancer progression. Clinical trials with a vaccine targeting the carboxy-terminal peptide of -hCG have indicated that tolerance to this oncofetal antigen can be broken. Humoral responses that may modulate the biologic activity of tumor-associated hCG as well as cellular responses to hCG have been generated. Studies are in progress to further define the biologic significance of hCG in cancer and to develop a vaccine approach that will best target this expression.

Alleles↗