[Comment on the article "Immunologic aspects of invasive squamous cell carcinoma of the cervix uteri"].
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Biomedical subjects
Publications and source records attributed to L C Fuith.
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On two occasions a patient suffering from acute intermittent porphyria (AIP) was anaesthetized with propofol as the sole agent. The concentrations of urinary porphobilinogen, porphyrins and porphyrin precursors did not exceed preoperative values, and no exacerbation of the disease was noted.
The serum concentrations of the tumor-associated antigen SCC were determined in 62 patients with invasive carcinoma of the uterine cervix. Antigen values above 2.0 ng/ml were considered as slightly positive, and those above 4.0 ng/ml as highly positive. Pretherapeutic levels were elevated (greater than 2.0 ng/ml) in 68% of the patients with cervical carcinoma. In 49 patients with carcinoma in situ, 18% of the SCC values were above the normal range. The greatest incidence of positive SCC titers (84%) was observed in women with recurrent cervical carcinoma. Only 6.7% of women in remission had elevated titers. Five of 24 cases (21%) with invasive endometrial carcinoma had SCC values exceeding 2.0 ng/ml. Slightly positive levels of tumor antigen were seen in 1.8% (1/56) of the control subjects. Serial SCC determinations revealed a correlation with the clinical course of disease in 84%. The determination of SCC is useful for the surveillance of patients with cervical squamous cell carcinoma.
Estrogen (ER) and progesterone (PR) receptors in ovarian tumors of 62 patients (51 carcinomas, 11 benign tumors) were estimated by the dextran-coated charcoal method using Scatchard plot analyses. 63% of carcinomas were ER-positive (greater than 10 fmol/mg cytosol), 38% were PR-positive (greater than 25 fmol/mg cytosol), whereas in benign tumors only 45% were ER-positive and 36% were PR-positive. We found no statistically significant correlation between receptor content and stage of disease, menopausal status or age of the patient. The highest concentration of ER and PR was observed in patients between 61 and 70 years of age. Life table analysis for patients with advanced ovarian carcinomas showed no significant difference in survival time in the group with higher ER and PR content. This study also reports the results obtained in a group of patients with receptor-positive ovarian carcinomas treated with a combination of chemotherapy and antiestrogen therapy. In comparison to treatment with cytotoxic chemotherapy alone, no significant difference in the time of survival or duration of remission could be found.
We investigated the outcome of disease in correlation with pretherapeutic urinary neopterin levels in 161 patients suffering from cervical carcinoma and 51 patients suffering from ovarian cancer. Neopterin is produced by human macrophages upon stimulation with interferon gamma and is therefore a measure for activated T cells. In both types of cancer, neopterin levels before therapy were of predictive significance. Patients with pretherapeutically high neopterin levels were more likely to die earlier. Even 12-18 months after the start of therapy this effect was significant. The data indicate that primary events in the immune surveillance are intact in those patients but effector mechanisms might be diminished. Persistent activation of cell-mediated immunity appears to be unfavorable in cancer patients.
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Case report of patient with four primary malignancies manifested independently (carcinoma in situ of uterine cervix, vulvar cancer, malignant lentigo on the face and rectal cancer). Immunologic and genetic changes could be demonstrated.
Neopterin, a pyrazinopyrimidine compound, is a marker of activation of cell-mediated immunity. The prognostic value of pretherapeutically and of serially measured urinary neopterin levels in patients with ovarian cancer was assessed, in a blinded manner, by analysis of 658 urine specimens from 74 women. The specimens were collected during a 5-year period (January 1981 to January 1986). Thirty-one deaths due to cancer were observed during the study period. By statistical analysis, a significant predictive value of pretherapeutic neopterin levels was found and compared with that of other possible prognostic clinical and laboratory findings. Multivariate analysis, using stratification by tumor stage, demonstrated that this predictive information was independent of other variables. A significant association was found between serial neopterin measurements and the current risk of death during follow-up (P less than 0.0001). In addition, current death risk was correlated with neopterin levels measured 6 months previously (P = 0.026). The histological outcome at surgical reexamination was correlated with the current neopterin levels (P = 0.016). Further, normal neopterin levels in women with evidence of tumor at surgical reexamination were shown to be a sign of better prognosis than elevated levels. Measurement of urinary neopterin levels during follow-up of women with ovarian cancer appears to be a valuable adjunct to conventional techniques, particularly in patients refusing explorative surgery.
Serum levels of CA 125 were determined in 239 patients suffering from gynecological malignancies. The upper limit for normal was 35 U/ml. Raised levels were found in 82% of patients with primary ovarian carcinoma, and in 29% of those with benign ovarian tumors. The values from patients with ovarian carcinomas in partial or complete remission were compared with those from patients with progressive disease. The former group had elevated levels in 19% compared to 89% in the latter group. Fifty-four percent of the values in progressive cervical carcinoma and 41% of the levels in progressive endometrial carcinoma were greater than 35 U/ml. High CA 125 levels were found in the cytosol of placenta, ovarian carcinoma, cervical carcinoma, and in ascitic fluid; correlation with serum levels was satisfactory. Even though CA 125 is of limited specificity for ovarian cancer, serum levels are important for follow up care and for the early detection of recurrences.
The case study reported here concerned an intrauterine death as a result of a Kell erythroblastosis. Allergization had been caused by the administration of Kell-positive banked blood. Irregular antibodies are on the increase as a result of the increasing number of blood transfusions. It is recommended that the Kell system be considered in the selection of banked blood for girls and women of childbearing age--a practice that has been followed at the Innsbruck University Clinics for almost four years now. The indirect Coombs' test should be performed in order to establish Kell antibodies and other clinically significant antibodies. The enzyme test is recommended as a supplementary examination, but should never be used as the sole antibody test. As with rhesus incompatibility, and insofar as the determination of the father's Kell characteristics show him to be an antigen carrier, monitoring of allergized pregnant women must be carried out with the help of antibody titer follow-ups, amniocenteses, and ultrasonographic examinations at short notice.
We report three patients, which showed plexus palsies after routine operations. Compression and stretch of the nerves despite pads leaded to nerve injury in patient A. Abduction of the arm, fixed wrist, hypotension in steep Trendelenburg position and a preexisting shoulder-arm-syndrome were the causes in patient B. Hyperreclination of the head in semisitting position caused the lesion in patient C. The anaesthetist should know the risks of positioning to prevent nerve injuries.
Concentrations of neopterin, a product of activated macrophages, in serum from 662 apparently healthy individuals (ages 1 to 97 years, median 22 years) were measured by radioimmunoassay and the results statistically analyzed. Consistent with prior investigations on the urinary excretion of neopterin, we found no significant sex dependence, but values for subjects younger than 18 or older than 75 years were significantly higher. Renal clearance of neopterin in nine healthy individuals was 218 (SD 44) mL/min, which suggests that the kidneys have an active role in neopterin excretion. Results for neopterin concentrations measured in serum by RIA and "high-performance" liquid chromatography (HPLC) are consistent, but for urinary neopterin the concordance between methods was weak. Therefore, the RIA should be used only for measuring neopterin in serum. In comparison of the clinical utility of serum neopterin and urinary neopterin/creatinine concentrations, in patients with gynecological tumors, the latter values (measured by HPLC) discriminated slightly better between patients with favorable and unfavorable prognoses.
In vitro, neopterin, a pyrazinopyrimidine compound, is excreted by human monocytes-macrophages after induction by supernatants from activated T-lymphocytes or by recombinant gamma-interferon. In vivo, it represents a noninvasive test for activation of cellular immune reactions. To evaluate the prognostic value of pretherapeutic urinary neopterin levels and of serial neopterin measurements during follow-up in women with cervical cancer, 1088 urine specimens from 186 consecutive patients were analyzed. Clinical assessments were made without knowledge of the results of neopterin assays (a "blinded" assessment). During the observation period (June 1980 to March 1984), 27 relapses, 18 metastases, and 26 deaths were seen. The prognostic significance of pretherapeutic neopterin and other possible prognostic clinical and laboratory parameters was tested by the univariate and multivariate Cox proportional hazards model using a stratification according to stage and surgical treatment. The combination of age at diagnosis, pretherapeutical hemoglobin, leukocyte count, and neopterin was found to predict survival best. On the basis of this result, risk groups were identified exhibiting markedly different survival behavior. A highly significant association was found between serial neopterin measurements and the risk for a relapse, metastasis, or death. The data suggest that urinary neopterin levels might be a useful adjuvant parameter in monitoring women with cervical cancer.
Treatment of Ehrlich ascites tumor cells with the alkylating agent triaziquone [2,3,5-tris(ethyleneimino)benzoquinone-1,4] and nitrogen mustard leads to a reduction of the posttranslational acetylation of histones. Acetylation of all core histones is affected. The reduction of labeling of acetylated sites is accompanied by a dose-dependent decrease in the extent of acetylation as indicated by the level of acetylation of H4. The depression of histone acetylation is expressed at all concentrations of the alkylating agents which cause significant inhibition of tumor cell proliferation. It could be excluded that the observed effects are caused by an impairment of acetyl coenzyme A synthesis.
The presence of the tumor marker CA 125 was studied in different compartments of the human placenta. Levels of CA 125 in the cytosol of chorionic villi ranged from 27-17100 U/g (median 560 U/g). In the placental amnion and chorion concentrations ranged from 175-29000 U/g, median 1060 U/g and were not statistically different. In the umbilical cord values were significantly lower (range 44-7600 U/g; median 180 U/g). Maternal serum probes were above the upper limit of normal in all cases (range 48-500 U/ml; median 131 U/ml). Immunohistochemistry detected CA 125 exclusively within the amniotic cells of the placenta and the umbilical cord. This might be because CA 125 fixes more to insoluble structures in the amnion or because of contamination of chorionic villi with the underlying decidua.
High neopterin excretion is closely associated with activation of cell-mediated immunity. We studied urine and serum neopterin concentrations and serum interferon-gamma concentrations in normal pregnant women. In our study population, neopterin concentrations exceeded the normal range in 663 of 840 samples (79%). Neopterin levels increased with the time of pregnancy. Serum samples drawn from women in the third trimester of pregnancy also showed high neopterin concentrations in almost all cases; however, no circulating interferon-gamma was detected. Whereas neopterin is able to penetrate into the blood stream because of its small size (M = 253 D), diffusion of interferon-gamma is limited. Raised neopterin levels provide evidence for activated cell-mediated immunity during pregnancy.
The human endometrial adenocarcinoma cells IK were found to be highly susceptible for TNF but rapidly developed a resistance to this cytokine. Inhibitors of RNA transcription or protein biosynthesis could not overcome this resistance. Moreover TNF resistance was not associated with increased resistance to hydrogen peroxide. The resistant phenotype remained stable and was not communicated to neighbouring cells in a paracrine manner. The TNF treatment did not induce a multidrug resistance on IK cells. Nude mice bearing xenotransplanted endometrial carcinoma cells did not benefit from TNF treatment.
Interferons have a mechanism of action different from chemotherapeutic agents. They modulate many physiologically important cellular functions and are a major building block in the network constructed by the biological response modifiers. Moreover, interferons are known to interact also with anticancer drugs to increase their therapeutic benefit. The aim of the present study was to evaluate the effects of interferon-gamma on cultured ovarian carcinoma cell lines. The growth of 3 out of 4 carcinoma cell lines (OVCAR-3, HTB-77, 2780 vs CRL-1572) was inhibited by interferon-gamma. The same cell lines which were growth inhibited also showed an induction of HLA-DR on their surface. CA-125 was found to be increased in 2 of them (OVCAR-3 and HTB-77) by interferon-gamma, whereas CEA was not detectable even after treatment. For HMFG-I, a shightly increased surface expression was induced on OVCAR-3 cells. HMFG-II expression was not significantly affected by interferon-gamma. The combined treatment with interferon-gamma and cisplatin, retinoic acid, or tumor necrosis factor alpha was studied on the ovarian carcinoma cells. For the combination with cisplatin we observed an additive or synergistic amplification of the antiproliferative activity, whereas tumor necrosis factor alpha resulted in a marked synergism in each case. In contrast to breast cancer cells retinoic acid and interferon-gamma acted synergistically only in one ovarian carcinoma cell line.