Effect of radiotherapy and chemoradiotherapy on circulating antioxidant system of human uterine cervical carcinoma

Circulating lipid peroxide, antioxidant components and the activities of defense enzymes were estimated in uterine cervical carcinoma patients (before and after radiotherapy and radiotherapy combined chemotherapy) and compared with controls. Some of the antioxidant components such as glutathione, vitamin E and selenium are reduced in cervical cancer. The reduced levels of vitamin E and glutathione were normalized after treatment. Erythrocyte lipid peroxide (E-LPx) and erythrocyte membrane lipid peroxide (EM-LPx) levels were found to be increased in all the stages of uterine cervical carcinoma. The important antioxidant enzymes such as erythrocyte superoxide dismutase (E-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) were found to be decreased in uterine cervical carcinoma. These altered biochemical parameters were reversed to normal, of course with varied degree after different mode of therapy. Significant normalization was observed in Type 11 chemoradiotherapy.     

Transient form of serum albumin in gynecologic cancer

The frequency of diagnostic errors in examination of 3827 patients with gynecological cancer diseases accounted for 21.6 up to 35%. The conformation of serum albumin in these patients was studied by means of different biochemical assays. The determination of the amount of the transitory form of albumin by reprecipitation with trichloroacetic acid appeared the most valuable for practical uses. Structural injuries to albumin depended on the localization, pattern and stage of the disease, and features of tumor metastatic spreading. The amount of the transitory form in patients with benign tumors and tumor-like processes in the ovaries (4.5-23.5%), hydatidiform mole (25%), uterine myoma (2-12.6%) rose insignificantly (5 +/- 2% in control) and increased in patients with initial stages of malignant tumors of the ovaries and uterus (28.9-43.7%). In uterine cervix carcinoma and uterine body sarcoma (stage II and higher stages) as well as in ovarian carcinoma, stages III and IV, its amount reached 57-100%.     

Lysozyme, alkaline phosphatase and neutrophils in uterine secretions of mares with differing resistance to endometritis

A study was conducted to 1) determine differences in the inflammatory response following bacterial challenge between normal mares and mares with chronic endometritis and 2) to determine if enzyme activity in uterine fluid can be used to evaluate degree of inflammation in the equine uterus. Six normal mares (Group 1) and four mares with chronic endometritis (Group 2) received an intrauterine infusion of beta-hemolytic streptococci on the second day of estrus. Neutrophil concentration as well as lysozyme and alkaline phosphatase activity were determined in uterine secretions obtained by placing tampons in the uterus of mares. All mares had a similar inflammatory response following bacterial challenge of the uterus, as indicated by a neutrophil response of the same magnitude. Neutrophil numbers, lysozyme and alkaline phosphatase concentrations were all increased 12 h postinoculation and declined rapidly to normal preinoculation values by 48 h after inoculation. In spite of the similarity of the clinical signs, neutrophil concentrations and enzyme activity, mares in group 1 demonstrated a markedly higher ability to eliminate the infection than mares in group 2. It is concluded that factors other than neutrophil numbers, lysozyme and alkaline phosphatase activity account for the inability of the mare to eliminate uterine infections.     

Radiation-induced micronucleus frequency in peripheral blood lymphocytes is correlated with normal tissue damage in patients with cervical carcinoma undergoing radiotherapy

In an effort to find a test to predict the response of normal tissue to radiotherapy, the lymphocyte micronucleus assay was used on blood samples from patients with cervical carcinoma. Peripheral blood samples from 55 patients with advanced-stage (II B-IV B) cervical carcinoma were obtained before radiotherapy. The patients were treated with external-beam radiotherapy followed by high-dose-rate brachytherapy. Acute and late normal tissue reactions were scored and correlated with the micronucleus frequency in lymphocytes after irradiation with 4 Gy in vitro. Great interindividual variability was observed in the radiation-induced lymphocyte micronucleus frequency, especially at 4 Gy. The mean number of micronuclei per 100 binucleated cells in cells irradiated with 4 Gy in vitro was significantly higher in samples from patients who suffered from acute and/or late normal tissue reactions than in those from patients with no reactions (51.0 +/- 17.7 and 29.6 +/- 10.1, respectively). A significant correlation was also found between the micronucleus frequency at 4 Gy and the severity of acute reactions and late reactions. However, the overlap between the micronucleus frequencies of patients with high-grade late normal tissue reactions and low-grade reactions is too great to recommend the micronucleus assay in its present form for routine clinical application.     

Neutral metalloendopeptidase associated with the smooth muscle cells of pregnant rat uterus

The pregnant rat uterus contains a membrane-bound metalloendopeptidase that is biochemically and immunologically similar to kidney enkephalinase (E.C.3.4.24.11). The uterus enzyme readily cleaved specific neutral endopeptidase substrates and oxytocin as well as the synthetic elastase substrate, Suc(Ala)3-pNA, yet did not digest native elastin. Using specific inhibitors, the uterus endopeptidase was identified as a metallopeptidase and not a serine protease, having an absolute requirement for zinc and perhaps calcium for maximal activity. The uterus endopeptidase cross-reacted with polyclonal antiserum to kidney microvillar endopeptidase and a monoclonal antibody to common acute lymphocytic leukemia antigen. Immunohistochemical localization of the enzyme in a 17 day pregnant uterus indicated that the enzyme was localized on the smooth muscle bundles of the myometrium and the endometrial epithelium. Total enzyme activity was 25 times higher in the late-term pregnant uterus (17th day of pregnancy) than in the nonpregnant uterus. Enzyme levels dropped rapidly prior to parturition and within 4 days after delivery the enzyme activity had returned to control levels. Inhibition of NEP in uterine strips with phosphoramidon resulted in a marked potentiation of oxytocin-induced contractions. Our results suggest that the uterine endopeptidase may have an important role in regulating uterine smooth muscle cell contraction during the later stages of pregnancy through its action on oxytocin and perhaps other biologically active peptides.     

Cervical intraepithelial neoplasia and associated condylomatous lesions. A preliminary report on 4,764 women from Northern Israel

During the period spanning the years 1973 to 1981, 4,764 women visited the Gynecology Out-Patient Clinics and Colposcopy Unit of the Nahariyya Hospital to be examined colposcopically and cytologically (and histologically whenever indicated) for precancerous and cancerous lesions of the cervix. Of these women, 2,614 (55%) were referred because of symptoms of cervical pathology and 2,150 (45%) for other (prophylactic) reasons. The subdivision of all women according to their demographic backgrounds afforded a comparison of the findings in Israeli-born Jewesses with those of foreign-born Jewesses and non-Jewish females living in the same geographic area of the Western Galilee district of Israel. Despite the low prevalence of cervical cancer in Jewesses throughout the world, the preliminary report of our pilot study demonstrated that the percentage rates of all degrees of dysplasia/cervical intraepithelial neoplasia (CIN I, II and III) of the uterine cervix of Israeli-born Jewesses was 5.4% in patients with cervical pathology and 3.24% in noncervical-pathology patients. These rates were the highest recorded for any of the demographic groups: 2.06% and 0.33%, respectively, in Moslem women; 1.23% in Christian women with cervical pathology; 2.38% and 1.78%, respectively, in European/American-born Jewesses; and 1.63% and 0.48%, respectively, in Asian/African-born Jewesses. The highest proportion of CIN lesions occurred in the 15- to 30-year-old age groups. Of 100 CIN lesions found in all patients, 45 were cytohistologically associated with the cells of condylomatous lesions. Of 36 patients in whom cervical squamous-cell carcinoma lesions were detected, 18 (50%) were staged (FIGO) as carcinoma in situ (stage 0); the remainder were in stages IA, IB, IIA and IIB, with none in stages III or IV.     

Use of respiratory mixture containing 8.0-8.5% of oxygen in hypoxic radiotherapy of cervical neoplasms]

Combined radiotherapy of patients with cervical carcinoma of stages IIb and IIIb was conducted. Hypoxia (8.0-8.5% of O2 in the respiratory mixture) was used in microfractionated (2 Gy) irradiation of metastatic spreading zones. When irradiating under conditions of hypoxia, the number of fractions was brought up to 28 as compared to 20 in control. Despite a 40%-increase of the dose, seriousness of radiation reactions and remote injuries remained at the same level. It is found that patients endure well the respiratory mixture for 6 min. necessary for irradiation.     

Extracellular matrix components and proteolytic enzymes in uterine cervical carcinoma

The important components of mucopolysaccharides and collagen have been analyzed in tissues of control and carcinoma of uterine cervix. Among these components hyaluronic acid and chondroitin sulphate levels were found to be increased, whereas decreased level of collagen was observed in uterine cervical carcinoma. Serum cathepsin B, D and acid and alkaline phosphatases have also been analyzed in controls and carcinoma patients before and after treatments. The activities of these enzymes have been found to increase prominently in advanced stages. Among these enzymes cathepsin B and alkaline phosphatase have exhibited remarkable increase in activity in uterine cervical carcinoma. Different modes of treatment exerted reversion of the elevated activities of these enzymes. However, combined therapy type II (radiation combined with cisplatin and cyclophosphomide) seems to be more effective in reverting the activities of these enzymes to normal levels.     

Tumor-specific antibodies in sera from patients with squamous cell carcinoma of the uterine cervix

Summary An indirect immunofluorescence assay is described which specifically detects antibodies against cervical carcinoma-associated membrane antigens. Cells from the ME-180 cervical carcinoma cell line were used as target cells. Sera had to be absorbed with pooled tonsillar lymphocytes prior to use, to remove nonspecific antibodies. The antibody was detected in 61 of 74 patients (82%) with invasive squamous cell carcinoma of the uterine cervix and in 5 of 65 controls (8%). A group of 49 patients with early or preneoplastic stages of this tumor (microinvasive carcinoma, carcinome-in-situ, and dysplasia) did not differ from the control group in the incidence of the antibody (5 of 49 patients, 10%). It is concluded that the occurrence of this antibody is specific for cervical carcinoma (P<0.001). However, the assay cannot be used as a diagnostic marker for preneoplastic stages of this tumor.     

Postmenopausal bleeding of nonmalignant origin

A study was made of the medical records of 102 patients hospitalized because of postmenopausal bleeding. Diagnostic procedures used included vaginal examination, Papanicolaou smears, curettage and cervical biopsy. The major associated pathological conditions (possibly etiological factors) in the series were chronic cervicitis, fibromyoma of the uterus, endometrial polyps, cervical polyps and adenomyosis of the uterus. Sclerosis of the uterine vessels was suggested as another possible cause of this type of bleeding. Neither the amount and type of bleeding nor the pattern of associated symptoms were of diagnostic value.A history of hormonal therapy prior to the onset of bleeding is not sufficient evidence to establish that as the cause of the bleeding and the patient should be as completely investigated as if this history were not present. In over 61 per cent of cases in this series, uterine curettage with or without cervical biopsy, cauterization, conization or trachelorrhaphy, was the only treatment required for both diagnosis and therapy.     

Uterine adrenergic and cholinesterase-positive nerves and myometrial catecholamine concentrations during pregnancy in sheep

Uterine adrenergic and cholinesterase (AChE)-positive innervation of the sheep uterus during anestrus and at 4 stages of pregnancy were examined by histochemical methods. In addition, uterine and cervical myometrium concentrations of norepinephrine (NE) and dopamine (DA) were determined using high-performance liquid chromatography. During anestrus, adrenergic and AChE-positive nerve fibers in the uterine myometrium and endometrium were primarily associated with the vasculature. Innervation of myometrial smooth muscle was almost exclusively by adrenergic fibers. In the endometrium, fibers of both types were observed closely associated with endometrial glands, and adrenergic fibers were observed in the connective tissue beneath the luminal epithelium. Density of uterine innervation decreased by day 65 of pregnancy with an additional decrease by day 105. Myometrial NE concentrations were higher in the cervix than the uterus. Uterine NE concentrations generally were not affected by pregnancy. Although cervical NE per gram of tissue decreased during pregnancy, this effect of pregnancy was not detected when NE was expressed per microgram of DNA. Myometrial DA concentrations were higher in uterine segments than in the cervix. DA concentrations decreased during pregnancy in all tissues except the posterior uterine segment. The DA to NE ratio in the uterus was greater than that for the cervix and was not generally affected by the stage of pregnancy. These results demonstrate that cholinergic and adrenergic nerves supply the sheep uterus. Decreasing fiber density during pregnancy suggests that a majority of the innervation to the sheep uterus is supplied by 'short' nerve fibers whose activity is regulated by steroids of pregnancy. The possible role of DA as a neurotransmitter in the sheep uterus is discussed.     

Implantation-induced changes in uterine arylamidase localization in the rabbit, rat, hamster and guinea-pig

Localization of uterine arylamidase activity varied between species: arylamidase was found primarily in the apical aspect of uterine epithelial cells in the rabbit, hamster and non-pregnant rat; only moderate staining was observed in these animals in the endometrial stroma. By contrast, arylamidase localization was primarily stromal in the guinea-pig at all stages studied while the luminal epithelium was devoid of reactivity. In all species, uterine enzyme activity increased before implantation but decreased in the vicinity of the blastocyst once implantation had begun. A generalized increase over the entire length of the uterus was seen during the preimplantation phase in the uterine epithelium of the rabbit and in the endometrial stroma of the guinea-pig. Increase in stromal activity appeared to indicate predecidual transformations which were embryo-dependent (i.e. localized to the implantation site) in the rat, or embryo-independent (i.e. occurring throughout the uterus) in the guinea-pig. A subsequent decrease in enzyme activity occurred in the vicinity of the implanting embryo irrespective of the cell type involved (epithelium in the rabbit, stroma/decidua in the rat and guinea-pig). Since arylamidases of the type studied here are integrated membrane proteins, the uniformity of changes observed in different species may reflect profound changes in membrane properties of endometrial cells as an element of the implantation reaction.     

Glutathione level and its relation to radiation therapy in patients with cancer of uterine cervix

Glutathione functions as an important antioxidant in the destruction of hydrogen peroxide and lipid peroxides by providing substrate for the glutathione peroxidase and also promotes the ascorbic acid. Glutathione plays a vital role in detoxification of xenobiotics, carcinogens, free radicals and maintenance of immune functions. The study was aimed to determine plasma glutathione as well as erythrocyte glutathione and glutathione peroxidase in patients with invasive cervical carcinoma (n = 30) before initiation and after completion of radiotherapy and subsequently, at the time of first three monthly follow-up visit. The levels of plasma glutathione, erythrocyte glutathione and glutathione peroxidase activity were found to be lower in all cervical cancer patients as compared to age matched normal control women. The study indicates a change in antioxidant status in relation with the glutathione system among patients with invasive carcinoma of the uterine cervix. This study also demonstrates the effect of radiation therapy on this antioxidant system.     

Unstable chromosome aberrations in peripheral blood lymphocytes from patients with cervical uterine cancer following radiotherapy.

Scoring of unstable chromosomes aberrations (dicentrics, rings and fragments) in circulating lymphocytes is the most extensively studied biologic system for estimating individual exposure to ionizing radiation. In this work, blood samples from 5 patients, with cervical uterine cancer, were analyzed by conventional cytogenetic in order to correlate the frequency of chromosome aberrations in lymphocytes with the dose absorbed by the patient, as a result of radiotherapy with 60Co gamma. The samples were collected in three phases of the treatment: before irradiation, 24 hr after receiving 0.08 Gy and 1.8 Gy, respectively. On the basis of the frequencies of unstable aberrations observed, a good agreement was obtained between doses estimated by calibration curve and the doses previously planned to radiotherapy. This report discusses the methodology employed as an important tool for dose assessment as a result of partial-body exposure to ionizing radiation.     

Influence of sex hormones on prostaglandin dehydrogenase activity in the rat uterus

The present experiments report the effects of estradiol or of progesterone on the activity of 15-prostaglandin-dehydrogenase (PGDH) in the uterus of spayed rats. When the substrate was PGF_2α the treatment with progesterone (4 mg.day⁻¹, two days) or with estradiol-17-beta (0.5 ug + 1 ug) did not show any effect on the activity of the enzyme. On the contrary, uteri from ovariectomized rats injected with a higher dose of estradiol- 17-beta (0.5 ug + 50 ug) exhibited a significant increment. When the substrate was PGE₂, progesterone failed again to modify the enzyme activity, whereas estradiol, both at a low and at a high doses, enhanced significantly the uterine PGDH activity. The possibility of two different PGDHs for each PG and the role of estradiol in enhancing PGE₂ catabolism into 15-keto- PGE₂ as a mechanism subserving the effect of estrogens on the output of this PG in the rat uterus, are discussed.     

Optimal Extent of Prophylactic Irradiation of Paraaortic Lymph Nodes in Patients with Uterine Cervical Cancer

Purpose

The purpose of this study was to determine optimal extent of prophylactic irradiation of paraaortic lymph nodes (PALN) in patients with uterine cervical cancer who had metastatic pelvic LNs.

Methods and Materials

We retrospectively evaluated 103 patients with cervical cancer and pelvic lymph node metastasis who were treated with prophylactic semi-extended field radiotherapy (SEFRT) between 1990 and 2012. The semi-extended field included PALN below the second lumbar spine with prescribed doses of 45 to 50 Gy. Survival outcomes were calculated using the Kaplan-Meier method, and acute and late toxicities were scored using the Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer toxicity criteria.

Results

The median follow-up after SEFRT was 61 (range 5–296) months. Overall, 28 patients (27.2%) experienced treatment failures, which were classified as local in 8 patients (7.8%), regional in 8 patients (7.8%), and distant in 13 patients (12.6%). Of the regional failures, only two involved PALN failure around the renal artery or the renal hilum area at the upper margin of the semi-extended field. At 5 years, the overall survival was 82%. Grade 3 or higher acute gastrointestinal and genitourinary toxicities occurred in one and two patients, respectively. As a late toxicity, one patient developed grade 3 small bowel obstruction.

Conclusion

Prophylactic SEFRT provided favorable outcomes with little acute or late gastrointestinal toxicity. For prophylaxis of PALN recurrences, upper part of PALN might not need to be included in patients with uterine cervical cancer and metastatic pelvic LNs.     

Uterine adenylate cyclase activity during the estrous cycle and early progestation in the rat: responses to fluoride activation and decidual induction

Uterine adenylate cyclase (AC) activity of the rat was measured by radiochemical analysis during the estrous cycle and early pseudopregnancy. During the estrous cycle, AC activity increased from 4.6 to 16.9 pmol cAMP formed/min X mg protein between metestrus and proestrus. Although AC was activated 2- to 3-fold at all cycle stages by 10 mM NaF, the resulting pattern of activity was similar to that measured in the absence of fluoride. The results demonstrated that the pattern of AC activity during the cycle was similar to that of other estrogen-sensitive uterine enzymes and that the ovarian hormones probably altered enzyme biosynthesis and turnover to a greater extent than activation and kinetic properties. Following the induction of pseudopregnancy by cervical stimulation, enzymic activity increased from 3.5 to 9.4 pmol between Days 1-4 (Day 1=leukocytic vaginal smear) and declined thereafter. AC activity was increased 2- to 5-fold by NaF on all days. AC activity was similarly increased by a mechanical trauma to the uterus, but only when the trauma was applied on Day 4. Following trauma to the uterus, AC activity was not increased further by NaF. The similarities between the physicochemical characteristics of AC during the estrous cycle and early progestation suggested that the enzyme during all endocrine states had virtually identical properties. However, the transient sensitivity to activation after trauma on Day 4 was unique to progestational uteri. Because the properties of enzyme were not altered by the endocrine state of the tissue, the transient sensitivity to activation by trauma was suggested to be a result of hormone-induced alterations in the membrane in which AC is sequestered.     

Phagocytic activity of alveolar macrophages in patients with bronchogenic carcinoma

Summary Human bronchoalveolar cells were obtained by lavage during diagnostic fiberoptic bronchoscopy of 21 patients suspected of having lung malignancies. Of these patients 11 were diagnosed as having primary lung cancer (Group I) and included individuals with squamous cell carcinoma, adenocarcinoma, undifferentiated large and oat cell carcinoma at varying locations and TNM stages, 4 patients demonstrated nonprimary metastatic carcinoma (Group II), and 6 patients did not reveal detectable tumors by bronchoscopy or follow-up (Group III) and were included as study controls. We examined the ability of pulmonary alveolar macrophages (PAMs) lavaged from patients in each of the three study groups to phagocytose opsonized sheep red blood cells. Phagocytic activity varied among patients in the same and different study groups; however, no significant differences were observed in the phagocytic or tumoristatic activities of PAMs recovered from tumor-bearing and nontumor-bearing lung regions of the same patient. Moreover, lavage fluids collected from tumor-bearing regions did not suppress the phagocytic activity of PAMs collected from control lungs nor lung regions contralateral to the tumor-bearing lung. The data do not support the view that bronchial neoplasms or their secreted products suppress phagocytic functions of alveolar macrophages.     

宫颈癌患者四维能量多普勒超声血管血流参数与疾病分期的相关性分析

摘要 目的：探究宫颈癌患者四维能量多普勒超声血管血流参数与其疾病分期的相关性。方法：选择2019年8月至2022年7月于我院接受治疗的80例确诊为宫颈癌患者为研究组,另取同期入院检测的50例宫颈癌上皮内瘤变患者为CIN组,取同期确诊为子宫良性病变的50例患者为对照组,分别对其进行了四维能量多普勒超声检测,对比三组患者超声参数差异,将研究组患者按照FIGO标准区分为不同疾病分期（I期23,II期34,III期23）,对比不同分期宫颈癌患者超声参数差异,通过绘制受试者曲线（ROC）的方式评估超声参数对不同宫颈癌分期的鉴别价值。结果：研究组、CIN组和对照组之间超声血流参数PSV及RI存在显著差异,同时两两相比较同样组间差异具有统计学意义（P<0.05）;不同宫颈癌分期患者超声血流参数之间存在显著差异,以FIGO III期的PSV最高,RI最低,各组两两相比较同样差异具有统计学意义（P<0.05）;PSV对FIGO I期至FIGO II期诊断AUC为0.6829（95% CI=0.5333-0.8324,P=0.0200）,对FIGO II期至FIGO III期诊断AUC为0.7698（95% CI=0.6402-0.8995,P=0.0006）,对FIGO I期至FIGO III期诊断AUC为0.7505（95% CI=0.6072-0.8937,P=0.0036）;RI对FIGO I期至FIGO II期诊断AUC为0.9309（95% CI=0.8662-0.9957,P<0.0001）,对FIGO II期至FIGO III期诊断AUC为0.7148（95% CI=0.5804-0.8493,P=0.0063）,对FIGO I期至FIGO III期诊断AUC为0.9811（95% CI=0.9504-1.000,P<0.0001）。结论：宫颈癌患者四维能量多普勒超声血管血流参数与其疾病分期具有一定的关联,将PSV和RI指数应用于宫颈癌分期鉴别中具有较好的应用价值,具有推广应用意义。