Cancer detection and prevention. Supplement : official publication of the International Society for Preventive Oncology, Inc最新文献

Blood transfusions are associated with phenomena attributable to immune suppression. Since perioperative blood transfusion is associated with early cancer recurrence in patients with malignancies, we prospectively studied T-cell subsets and natural killer cytotoxicity in patients undergoing potentially curative surgery for colorectal cancer. Preoperative total peripheral lymphocyte number was significantly (P = 0.0191) depressed in patients who were subsequently transfused, but returned to normal by follow-up 1 to 3 months after surgery. Natural killer cytotoxicity declined significantly (P less than 0.05) at follow-up in patients who were not transfused. These results do not explain the association of blood transfusion with cancer recurrence observed in colorectal cancer patients. Blood transfusion in this study was followed by increased numbers of peripheral lymphocytes and higher natural killer cytotoxicity.

An increased incidence of certain neoplasms occurs in immunodeficiency states. The incidence of cancer in organ transplant patients is approximately 4%. The predominant tumors are lymphomas, carcinomas of the skin and lips, carcinomas of the vulva/perineum, in situ carcinomas of the uterine cervix, and Kaposi sarcoma (KS). Tumors appear a relatively short time after transplantation. Unusual features of the lymphomas are the high incidence of non-Hodgkin lymphomas, frequent involvement of extranodal sites, and marked predilection for the brain. Skin cancers present unusual features: predominance of squamous cell carcinomas, young age of the patients, and a high incidence of multiple tumors. Cancers of the vulva/perineum occur at a younger age than in the general population and may be preceded by condyloma acuminatum or herpes genitalis. Lymphomas, leukemias, and skin cancers are increased in nontransplant patients who receive immunosuppressive therapy for nonmalignant diseases. Second tumors that develop in cancer patients, after treatment with cytotoxic therapy, are mainly leukemias, lymphomas, and bladder carcinomas.

Immunologic assays have been instrumental in implicating the Epstein-Barr virus (EBV) as an etiologic factor in nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). In this report, the importance of a variety of specific assays to detect EBV in tumor biopsies and antibodies to EBV antigens in serum from patients with NPC and BL is reviewed. In both NPC and BL, the involvement of EBV appears to differ in various geographic locations. Therefore, it is necessary to be able to interpret the available immunologic laboratory tests to know if a specific patient has "EBV-associated" or "non-EBV-associated" cancer. Such information is not only relevant to etiologic studies in different populations but to identifying individuals at high risk for NPC and BL, to monitoring their response to therapy, and to determining the most appropriate forms of therapy.

Several biological response modifiers (BRMs) were demonstrated to increase myelopoiesis and effector cell responses (M phi and natural killer cell activity) in vivo. The increased myelopoiesis was reflected by an increase in bone marrow cellularity and granulocyte-M phi colony-forming cells (GM-CFU-C). The increase in myelopoiesis appeared to be related to a concomitant increase in colony-stimulated factor (CSF) production and secretion by M phi and bone marrow cells. CSF induction by BRMs increased myelopoiesis and counteracted the myelosuppressive and immunosuppressive effects of cyclophosphamide. CSF induced in vivo by BRMs attained high titers and were maintained over a longer period than exogenously injected CSF, which was rapidly cleared from serum.

Patients with certain malignant diseases excrete in their urine elevated levels of modified nucleosides originating predominantly from the breakdown of transfer RNA (tRNA). Acquired immune deficiency syndrome (AIDS), often associated with rapidly progressing Kaposi's sarcoma (KS), is currently occurring in many countries. Male homosexuals are considered to be at highest risk of developing these disorders. We have previously reported that patients with AIDS excrete elevated levels of modified nucleosides. In this communication, we report on modified nucleoside levels measured in 77 male homosexuals without clinical manifestations of AIDS at the time of examination. A high frequency of abnormal nucleoside levels was found in this high-risk group. There was a trend towards higher levels in individuals with lymphadenomegaly, considered a prodrome of AIDS. Statistically significant correlations were found between some of the nucleosides (pseudouridine and dimethylguanosine) and degree of lymphadenomegaly. Pseudouridine, 1-methyl-adenosine and dimethylguanosine were inversely related to percentages of total T-lymphocytes (T11), suppressor T-lymphocytes (T8), and number of natural killer cells (Leu-7). These findings suggest that determination of urinary nucleoside levels may help identify individuals at high risk of developing AIDS.

LAV/HTLV-III has been found to be the etiological cause of AIDS. This new human retrovirus has a selective tropism for T lymphocytes of the OKT4/leu 3 subset, in which it induces a cytopathic effect. We have compared Southern blot patterns of integrated proviral DNAs from different individuals at risk or not using a nick-translated LAV probe. We find that LAV/HTLV-III is very similar to our Haitian isolate and close to an isolate from an early-recognized (in 1982) AIDS case in New York. More variation is apparent with Zaïrian isolates as well as an isolate from a nonhigh-risk group when we used Hind III or Bgl II Sac-digested fragments. We also looked at virus isolated from a Sicilian child who developed AIDS after allogenic bone marrow transplant and transfusion. This isolate shows two forms: One is similar to the prototype LAV, the second much different.

Immunoglobin (Ig) has been found to accumulate on P815Y (H-2d) and L5178Y (H-2d) tumor cells during progressive growth in syngeneic host DBA/2 mice. Density of the accumulated Ig per cell increases as the tumor grows while the tumor cells become resistant to lysis by ascitic syngeneic cytotoxic cells. Tumor cells grown in vivo coated with this specific Ig no longer bind significant amounts of antibodies against H-2D and H-2K antigens. The membrane-bound Ig reacts with a rabbit antimouse Fab and a rabbit antimouse IgM reagent, but it does not react with a rabbit antimouse IgG or IgA reagent. It binds specifically to tumor cell lines that are sensitive to the ascitic cytotoxic cells but not to resistant tumor cell lines. The membrane-bound Ig can be eluted from tumor cells with 3 M NaSCN or 0.2 M acetic acid. Binding studies indicate that this eluted Ig is not an anti-H-2D/K antibody, yet it immunoprecipitates H-2D/K antigens from NP40 lysates of P815Y cells. It is proposed that the Ig is directed against a tumor antigen that is physically associated with the H-2D/K antigens of the tumors.

Family histories of 189 patients with lymphomas and leukemias and 14 patients with stomach cancer were used in this study. Controls consisted of family histories of 391 patients with other tumors. In the 189 probands with lymphoproliferative disorders stomach cancer accounted for 17.3% of the total cancers in the relatives, whereas in the probands with breast and other types of cancer the corresponding figures were 8.1% and 8.3% as against an incidence of 5.9% of stomach cancers in Basel. In first-degree relatives, the incidence of stomach cancer was higher than expected in the families of probands with malignant lymphoma and stomach cancer. It is suggested that an inherited subclinical disturbance of the immune system is involved in familial association of stomach cancer with malignant lymphoproliferative disorders.

Immunological and clinical functions were studied over a 2 year period in conjunction with a placebo controlled trial of isoprinosine and chlorambucil in 21 patients with exacerbating remitting multiple sclerosis. Laboratory and clinical evaluations were performed at 3 month intervals and during relapses. In placebo-treated patients, the decrease in circulating T8+ cells was maximum during relapses, T lymphocyte function was impaired, and five of the six patients experienced clinical worsening. Chlorambucil treatment was responsible for a decrease in circulating T4+ and T8+ cells; nevertheless, T lymphocyte function was slightly improved during relapses. The alterations of delayed hypersensitivity responses were not accompanied by improvement in relapse rate or in intensity and major side effects: mainly infections with leukopenia and thrombocytopenia. During isoprinosine therapy, a regulation of circulating T lymphocytes and cell proliferation occurred. The higher level of circulating T cells was related to the increase in T4+ and T8+ cells, which did not decrease during relapses. The absence of Leu 7+ cell modifications suggest that NK were numerically unaffected by isoprinosine therapy and that in vivo regulation of circulating T suppressor cells was performed by this treatment. Four out of seven patients did not experience any relapse during the duration of the trial. In relapsing patients, the frequency and duration of the relapses were significantly different from that of other patients. A reduction of the disease progression was observed without any side effects. While no conclusion can be drawn on the long-term effectiveness, the results of this pilot study are consistent indicators of the immunological and clinical beneficial effects of isoprinosine therapy in patients with exacerbating remitting multiple sclerosis.

The immunopharmacologic effects of Isoprinosine (INPX) have been associated with clinical benefit to the patient in a number of conditions characterized by immunodeficiency of diverse etiology. Immunodepressed homosexuals at risk of developing acquired immunodeficiency syndrome (AIDS) treated with placebo or INPX experienced an increase in the function and number of immunocompetent cells associated with clinical improvement. A multicenter trial designed to confirm these results has demonstrated that INPX produced an increase in natural killer (NK)-cell activity, total T cells, and T-helper cells, with certain effects persisting for months after completion of the 28-day treatment period. INPX-treated patients also experienced clinical improvement and decreased incidence of progression to AIDS. The administration of INPX for longer periods to patients with frank AIDS under a compassionate-use protocol has also proved useful. Clinical benefit associated with INPX treatment has been demonstrated in other patients with a depressed immune response, such as aged patients, cancer patients, severely burned patients, ill patients, and surgery patients. This program of clinical trials supports the therapeutic use of INPX in the treatment of AIDS and other acquired immunodeficiencies of clinical importance.