Biomedical subjects

H Ben-Hur

Publications and source records attributed to H Ben-Hur.

At least 19 recordsLinked to original sources

PubMed2002

Response of the immune system of mammary tumor-bearing rats to cyclophosphamide and soluble low-molecular mass tumor-associated antigens: the spleen and lymph nodes.

In a previous study, we showed that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed the underlaying mechanisms. Studies were performed on the spleen and lymph nodes from the following groups of mammary tumor-bearing rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, i.v.) rats treated with CPA and sTAA. Different zones of the spleen and lymph nodes were measured and their T cell content (CD4(+) and CD8(+) cells) was analyzed immunohistochemically. CPA decreased the size and cell content of follicles, splenic areas related to the production of B cells, of the marginal zone and to a lesser extent of the periarterial lymph sheath, and decreased the number of CD4(+) and, at a lower rate, of CD8(+ )T cells in the spleen. Addition of sTAA restored activity in the splenic zones producing these cells. Similar effects of CPA and sTAA were found in lymph nodes with accumulation of B lymphocytes in the primary and secondary follicles and of T lymphocytes, including both CD4(+) and CD8(+) cells, in the paracortical zone. We suggest that inhibition of the functional activity of the immune system is one of the main reasons for the toxic effects of chemotherapeutic drugs such as CPA and that the tumor-suppressive antitoxic effects of sTAA result from their activation of B- and T-lymphocyte production in this system, particularly in the spleen and lymph nodes.

Animals↗

PubMed2002

Soluble low-molecular-mass tumor-associated antigens promote the suppression of rat mammary tumors by tamoxifen and prevent its toxic effect.

This study examined whether the soluble tumor-associated antigens (sTAA) of 66 kDa and 51 kDa could promote suppression of chemically-induced rat mammary tumorigenesis by the hormone-related anticancer drug tamoxifen and prevent the drug's toxic side-effects. Dimethylbenzanthracene (DMBA, 10 mg/rat, 3 administrations) was used to induce mammary tumors in 8-week-old Wistar rats. Then, for 13-17 more weeks, preparations of sTAA (50 microg/rat) and tamoxifen (10 mg/rat) were administered, separately or in combination, on a weekly basis. The experiment was continued for 18 weeks and was terminated when the number of dead rats reached 50% in each group. Treatment with tamoxifen inhibited tumor growth and their malignance: the number of rats without malignant tumors significantly increased compared to controls, 27.3% and 5.6%, respectively. Treatment with sTAA resulted in a significant increase in the number of regressed tumors to 10.1% compared to 0% and 1.4% in control and tamoxifen-treated rats, respectively. Moreover, the period of 50% survival increased from 13 weeks in tamoxifen-treated rats to 17 weeks, and as a result, rats treated with sTAA were involved in the experiment for an average 14.3 weeks compared to 10 and 10.4 weeks in control and tamoxifen-treated groups. In rats treated simultaneously with tamoxifen and sTAA, the time of appearance of each new tumor increased from 4.5 weeks to 6.6 weeks with a significant increase to 14.3% in the number of regressed tumors. The period to 50% survival increased to 18 weeks, and these rats were involved in the experiment for up to 16.4 weeks. The number of rats without malignant tumors increased to 22.2% and the time of appearance of malignancy increased to 9.6 weeks, as compared to 7.3 weeks in controls. The results demonstrated that sTAA have tumor-suppressive properties, and also enhance the anticancer effects of tamoxifen and prevent its toxic side-effects.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Trophoblastic peritoneal implants after laparoscopic treatment of ectopic pregnancy.

Persistent trophoblastic activity after salpingostomy for ectopic pregnancy implies the presence of intra-abdominal trophoblastic tissue, usually within the fallopian tube. We report a case of disseminated trophoblastic peritoneal implants, presenting as hemoperitoneum three weeks after laparoscopic salpingectomy. Only 23 such cases have been reported. Surgical treatment of ectopic pregnancy, especially by the laparoscopic technique, may cause intraperitoneal spread and reimplantation of trophoblastic tissue. Precautions for minimizing this complication are discussed.

Adult↗

PubMed2001

Immunoprotection of gonads and genital tracts in human embryos and fetuses: immunohistochemical study.

PROBLEM: The immune protection of genital organs in embryogenesis has not been sufficiently studied. The purpose of this study was to investigate the development of the secretory immune system (SIS) in the gonads and genital tracts of human embryos and fetuses. MATERIALS AND METHODS: Developing gonads at different stages and genital tracts from 18 embryos and 39 fetuses in the first to third trimester of gestation were analyzed for presence of different component of SIS: secretory component (SC), joining (J) chain. IgA, IgM, IgG, macrophages, and subsets of lymphocytes. The material was divided into two groups: cases not subjected to foreign antigenic effects (group I, n = 31) and those under antigenic attack (chorioamnionitis, group II, n = 26). RESULTS: In embryos and fetuses of group I, SC, J chain, and IgG were seen in the epithelium of mesonephric and paramesonephric ducts, proliferating coelomic epithelium, epithelium of the uterine tubes and uterus, epithelium of the vas deferens, epididymis, and rete testis. IgA and IgM appeared in 6-week-old embryos. J chain, IgA, IgM, and IgG, but not SC, were found in the primary oocytes and oogonia, spermatogonia. and interstitial cells. An abundance of macrophages was seen in 4-week-old embryos. T and B lymphocytes first appeared in 6-7-week-old embryos. In embryos and fetuses of group II, reactivity of immunoglobulins (Igs) decreased until they disappeared altogether. CONCLUSIONS: Components of SIS were seen in genital organs in 4-5-week-old embryos and were present during the whole intrauterine period. We suggest the presence of two forms of immune protection of fetal genital organs. One form contains SC, J chain, and Igs and is present in the genital tract epithelium. The second form contains only J chain and Igs and is present in germ cells of gonads. The loss of Igs in cases with chorioamnionitis reflects the functional participation of the SIS of genital organs in response to antigen attack.

Antigens, CD↗

PubMed2001

Effects of the soluble low-molecular-mass proteins on spleen activity and cellular composition of infiltrates in rat mammary gland tumors.

We showed previously that soluble low-molecular-mass tumor-associated antigens (TAA) could suppress chemically-induced tumorigenesis. In this study, we analyzed the mechanism of those findings. Studies were performed on the spleen and mammary gland tumors obtained from the following groups of rats: i) control rats treated with dimethyl-benz(alpha)antracene (DMBA), ii) vaccinated and carcinogen-treated rats with non regressed tumors, iii) vaccinated and carcinogen-treated rats with regressed tumors. Different zones of the spleen and tumors and their cellular content (Ki67+ and CD8+ cells, and macrophages) were analyzed morphometrically and immunohistochemically. Reaction of the spleen to vaccination was manifested in a significant increase in all areas of the white pulp and in a decrease in the size of the red pulp. The total number of cells in the white pulp (germinal center and PALS) and in the marginal zone was significantly higher in the spleen of rats with regressed tumors. The number of Ki67+ cells decreased significantly in both groups of vaccinated rats, but most prominently in the marginal zone and the red pulp in rats with regressed tumors. An increased number of CD8+ lymphocytes and macrophages was also seen in the red pulp. Different areas of the tumors (peripheral vs. inside at depth) showed different responses to vaccination and this difference was related to conditions of carcinogenesis, i.e. non-regressed vs. regressed tumors. In regressed tumors, all parameters studied were easily distinguishable in both areas of the tumors, while in non-regressed tumors, a marked distinction was seen only at their periphery. In regressed tumors, a negative correlation was seen at depth tumors between the number of Ki67+ cells and the number of CD8+ lymphocytes (r=-0.48). The findings indicated a strict antitumor effect of vaccination with the soluble low-molecular-mass TAA, which prevents the development of insufficiency of the immune system when an intensive immune reaction takes place.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Tumor-induced insufficiency in T cell activity and hyperproduction of interleukin-2 in rat giant hepatomas.

The roles of lymphoid elements and apoptosis-related proteins in the development of extremely large hepatomas were studied in rats. Hepatoma cells were inoculated subcutaneously into 6-week-old rats, and 4 months later the quantities of T and B cells, macrophages, and cells positive for Fas, Fas ligand (FasL) and interleukin-2 (IL-2) were immunochemically evaluated in tumors. Grafting of hepatoma cells caused the development of giant tumors that could reach one-third of the rat's body weight. Within the hepatomas, almost all CD8(+) T cells were destroyed as they passed from the tumoral stroma into the parenchyma and came in contact with tumor epithelial cells. This could be the consequence of IL-2 production, since about 90% of tumor cells were CD25(+). The tumoral mass increased despite the significant increase in tumor necrosis. Cells with Ki67 or in mitosis, and cells positive for Fas and FasL were found only among tumor epithelial cells that were necrotic and never among viable cells. We suggest that progress in tumorigenesis is facilitated by inhibition of T helper cells, and the extensive death of T killer cells is caused by the high levels of the tumor produced IL-2.

Animals↗

PubMed2001

Serological markers for detection of cancer (Review).

We reviewed the effectiveness of commercial serological markers for the early detection of cancer and monitoring cancer patients. Parameters, such as specificity and variability of tumor markers were compared with a new approach for cancer detection which was recently developed in our laboratory. We demonstrate that the absence of tumor specificity and the extremely high variability of tumor markers are the reason that none of them can be used for early cancer diagnosis. We developed a method for the isolation of tumor-associated antigens (TAA) and found that two soluble low-molecular mass 66 and 51 kDa proteins could be isolated from the blood of cancer patients. The first protein, albumin, belongs to a group of heat-shock proteins (HSP), while the second is connected with TAA. The progress in cancer is characterized by a relative decrease in the concentration of HSP and a high increase in blood levels of TAA. Our method was shown to be highly sensitive and specific for the early detection of different types of cancer, such as of the colon, uterus, ovary, and breast, as well as melanoma.

Biomarkers, Tumor↗

PubMed2001

The immune system, apoptosis and apoptosis-related proteins in human ovarian tumors (a review).

Our studies on the relationships among the lymphoid system, apoptosis and apoptosis-related proteins (ARP) in human ovarian benign cysts, borderline tumors, and carcinomas are reviewed and analyzed. Fas and Fas ligand are expressed in 50% to 80% of the epithelial cells in all studied tumors. Many bcl-2-positive tumor epithelial cells are seen in benign cysts and they disappear as tumorigenesis progresses, whereas p53 protein is found only in borderline tumors and in carcinomas. Many exceptions to the opinion that bcl-2 inhibits apoptosis and p53 promotes it are encountered. Bcl-2 is lacking in epithelial cells of mucoid tumors of all grades, and its absence does not stimulate their apoptosis. P53 protein is absent from most lymphocytes, macrophages and epithelial tumor cells, nevertheless, they undergo apoptosis. Indeed, in many tumors apoptosis is regulated without the participation of bcl-2 and p53. Different components of the immune system become active during different stages of tumor development. The weak reaction of T-cell killers and macrophages is typical in benign cysts. In borderline tumors, the activity of T-cell killers increases in the parenchyma, and that of T helpers and macrophages in the stroma. In carcinomas with high lymphoid infiltration, a strong reaction of macrophages and T cell killers in the tumoral parenchyma as well high reaction of T helpers and B lymphocytes in the stroma are typical. Apoptosis that should protect against tumor also stimulates apoptotic death of lymphocytes and macrophages, and this has catastrophic consequences, as seen in weakly infiltrated carcinomas. In conclusion, our studies indicate that during malignancy the major task of the immune system is curtailment and control of tumorigenesis.

Apoptosis↗

PubMed2001

Soluble low-molecular-mass tumor-associated proteins promote the suppression of mammary tumors by cyclophosphamide.

This study examined whether the soluble tumor-associated-antigens (TAA), of 66 kDa and 51 kDa, could promote suppression by anticancer drugs of chemically-induced mammary tumorigenesis. Dimethylbenzanthracene (DMBA, 10 mg/rat, twice) was used to induce mammary tumors. Then, for nine more weeks, the preparation of TAA and cyclophosphamide (CPA), alone or in combination with TAA, were administered in weekly doses. Twenty weeks after DMBA exposure, the mammary tumor yield was 2.4, 2.8 and 2.9 in the experimental groups compared to 3.5 in the controls. Seventy-five percent of the rats in the control group, but only 37% of TAA, 50% of the CPA, and 30% of the CPA and TAA treated animals had malignant tumors. In the experimental groups, 6.5%, 25% and 38%, respectively, of the tumors regressed, compared to 3% in controls. In the groups receiving CPA or TAA, regression was observed in the fifth week of treatment, and in the group receiving combined treatment, already in the first week. The size of the tumors in control rats increased during the last 10 weeks 3.6 times, in the CPA treated rats 1.15 times, but in those receiving CPA plus TAA it decreased by 0.7 times. The results of our experiment demonstrated that TAA have distinct tumor-suppressive properties, and can enhance the anticancer effects of CPA.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Lymphoid elements and apoptosis-related proteins (Fas, Fas ligand, p53 and bcl-2) in lichen sclerosus and carcinoma of the vulva.

We studied some of the morphological and immunohistochemical parameters of lichen sclerosus (LS) and carcinomas of the vulva in order to verify some characteristics in LS related to neoplasm transformation. Parameters such as proliferating index, rate of proliferation of lymphoid elements into a tumor and types of such elements were studied. In parallel, the number of cells positive to apoptosis-related proteins such as Fas, Fas ligand, p53 and bcl-2 were evaluated. Biopsy material from patients with different vulvar disorders--22 samples with LS and 23 samples with vulvar squamous cell carcinoma (VSCC)--was studied by the methods of morphometry and immunohistochemistry. In LS, the number of T cells is a few times higher than those of B cells. Among the T cells, the number of killers is significantly higher than the number of helpers. Carcinomas, especially those with lymphoid depletion, are characterized by a further significant increase in some parameters such as the rate of lymphoid proliferation and the number of T helpers and killers. The progression in to tumorigenesis was accompanied with a significant increase in the number of Fas+ and FasL+ lymphocytes. In tumor epithelial cells the proliferative index increased in carcinomas with lymphoid depletion. The number of p53+ epithelial cells increased whereas the number of bcl-2+ cells showed a distinct tendency to decrease with progression in to tumorigenesis. Development of a tumor is manifested in deep changes in relationships between different lymphoid components. Only two lymphoid markers are significantly different in VSCC compared to LS: the number of T killers and macrophages. The other parameters studied (rate of proliferative activity, the total number of T cells and T helpers, B cells, IL-2-connective cells) already showed high expression in LS as the first signs of transformation of this inflammation into neoplasia.

Apoptosis↗

PubMed2001

An immunohistochemical study of the secretory immune system in human fetal endocrine glands and their precursors.

We examined the presence and distribution of components of the secretory immune system (SIS) in fetal endocrine organs and their embryonic precursors. Specimens from 16 embryos (4 to 8 weeks of development) and 32 fetuses (9 to 38 weeks) were divided into those that had not been exposed to massive foreign antigenic effects (Group I, n=28) and those that had suffered from chorioamnionitis (Group II, n=20). An immunohistochemical study was performed using antibodies against the secretory component (SC), joining (J) chain, IgA, IgM, IgG, subsets of T and B lymphocytes, and macrophages. Positive immunostaining for SIS components in the precursors of endocrine organs was seen from 4 to 6 weeks of development, and was present thereafter in the pituitary body, thyroid, pancreatic islets and adrenals. J chain and immunoglobulins were found in all endocrine cells throughout intrauterine development, but the massive antigenic influence caused by chorioamnionitis decreased the latters immunoreactivity. The presence of SC in the precursors of adenohypophysis and pancreatic islet cells decreased significantly after their transformation into definitive endocrine organs. In the thyroidal follicular epithelium and the pars intermedia of the pituitary body cells, SC was present during the entire period of pregnancy. In adrenals, SC was not found. Maternal immunoglobulins, together with SC and J chain, are accumulated in endocrine gland cells from the early stages of intrauterine life. They are the major mechanism of endocrine cell defense during the early prenatal period when the common immune system is still structurally and functionally incompetent.

B-Lymphocytes↗

PubMed2000

beta2 microglobulin-deficient (B2m(null)) NOD/SCID mice are excellent recipients for studying human stem cell function.

Human SCID repopulating cells (SRC) are defined based on their functional ability to repopulate the bone marrow of NOD/SCID mice with both myeloid and lymphoid cell populations. The frequency of SRC in umbilical cord blood cells is 1 in 9.3 x 10(5) mononuclear cells. We report that as few as 8 x 10(4) human cord blood mononuclear cells transplanted into NOD/SCID/B2m(null )mice resulted in multilineage differentiation in the murine bone marrow, revealing a more than 11-fold higher SRC frequency than in NOD/SCID mice. Moreover, as few as 2 to 5 x 10(3) CD34(+) cells recovered from the bone marrow of primary transplanted NOD/SCID mice were sufficient for engrafting secondary NOD/SCID/B2m(null )mice with SRC, suggesting SRC self-renewal. Thus, by using NOD/SCID/B2m(null )mice as recipients, we established a functional assay for human stem cells capable of engrafting the bone marrow of primary and secondary transplanted immune-deficient mice with SRC, providing a model that better resembles autologous stem cell transplantation.

Animals↗

PubMed2000

The plant lectin FRIL supports prolonged in vitro maintenance of quiescent human cord blood CD34(+)CD38(-/low)/SCID repopulating stem cells.

Ex vivo maintenance of human stem cells is crucial for many clinical applications. Current culture methods rely on optimized combinations of cytokines. Although these conditions provide some level of stem cell support, they primarily induce proliferation and differentiation, resulting in reduced repopulation capacity. The recently identified legume lectin FRIL has been shown to preserve human cord blood progenitors up to a month in suspension culture without medium changes. To test whether FRIL also preserves human SCID repopulating stem cells (SRC), we cultured human CD34(+) cord blood cells in medium containing FRIL, with or without subsequent exposure to cytokines, and tested their repopulating potential. We report that FRIL maintains SRC between 6 and 13 days in culture. Incubation of CD34(+) cells with FRIL results in significantly lower numbers of cycling cells compared with cytokine-stimulated cells. CD34(+) cells first cultured with FRIL for 6 days and subsequently exposed to cytokines for an additional 4 days generated significantly more mononuclear and progenitor cells and higher levels of engraftment in NOD/SCID mice compared with CD34(+) cells cultured with FRIL alone. Similar results were obtained with CD34(+)CD38(-/low) cells, including expansion of SRC that were cultured in FRIL followed by cytokine stimulation. Moreover, CD34(+) cells precultured with FRIL successfully engrafted primary and more importantly secondary recipients with lymphoid and myeloid cells, providing further support that FRIL maintains SRC for prolonged periods.FRIL's ability to preserve quiescent primitive cells in a reversible manner may significantly expand the time and range of ex vivo manipulations of human stem cells for clinical applications.

Animals↗

PubMed2000

Laparoscopic hysterectomy.

STUDY OBJECTIVE: To determine the soundness of laparoscopic hysterectomy compared with vaginal and abdominal hysterectomy Design. Nonrandomized, uncontrolled, retrospective study (Canadian Task Force classification III). SETTING: Medium-size community hospitals. PATIENTS: One thousand six hundred forty-eight women undergoing laparoscopic hysterectomy, including those with uterine size 17 weeks' gestation or less. INTERVENTION: Laparoscopic hysterectomy staged as level 4, which includes laparoscopic dissection of the uterine artery. MEASUREMENTS AND MAIN RESULTS: The median duration of surgery was 36 minutes (range 24-104 min), compared with the usual 115 minutes for laparoscopic-assisted vaginal hysterectomy. Complication rate was 0.66%. No complications occurred in the last 3 years when the procedures included transillumination of the ureters. Although the costs associated with disposable equipment are high, the technique is cost effective. CONCLUSION: With proper training and ureteral transillumination, laparoscopic hysterectomy is safe and effective, and with stents, ureteral injury is avoided.

Cost-Benefit Analysis↗

PubMed2000

Small intestinal development in the young chick: crypt formation and enterocyte proliferation and migration.

1. Post-natch mucosal development was examined in the chick small intestinal epithelium using immunostaining with proliferating cell nuclear antigen (PCNA) and 5-bromo-2-deoxyuridine (BrdU). 2. On the day of hatching jejunal crypts were small and a single crypt per villus was observed. However, during the 108 h post-hatch crypts developed rapidly branching and increasing in size, cell numbers and cell size. 3. Almost all epithelial cells in the small intestine of the hatching chick were proliferating, as indicated by PCNA and BrdU, while more than 80% of proliferating cells were localised in the crypts after 108 h post hatch. 4. Estimate of villus cell transit time using BrdU was only possible from 48 h post-hatch when villus transit time was 72 h in the jejunum, whereas at 336 h transit time was 96 h. 5. In the 108 h post hatch a rapid transition occurs from total jejunal epithelial cell proliferation and immature crypts to a defined proliferative zone in the crypts, with constant division and migration.

Animals↗

PubMed2000

Transplacental effects of maternal feeding with high fat diets on lipid exchange and response of the splenic lymphoid system in mice offspring exposed to low doses of carcinogen.

We studied whether feeding pregnant female mice with different fats affects lipid exchange and activity of the splenic lymphoid system in offspring exposed to low doses of carcinogen. Female mice were fed diets with either 7% or 15% corn oil or olive oil. The 4-week-old offspring of these mice were transferred to a chow diet, and exposed to a low dose of the carcinogen, dimethylbenz(a)antracene (2 mg/kg). Results of experiments were studied 5 months later. Concentrations of polyunsaturated linoleic and oleic acids were determined in the blood and liver of mothers and offspring. The activity of the splenic immune system in offspring was studied using immunohistochemical methods for evaluating the number of different types of lymphocytes (B and T cells), mitotic and apoptotic indexes and the number of Fas-positive lymphocytes. Serum concentrations of the fatty acids examined were unchanged in the blood of the mothers and their offspring. Concentration of both linoleic and oleic acids was significantly higher in the liver of mothers fed the 15% olive-oil or corn-oil diets. This high level was maintained in linoleic acid in offspring of mothers fed the 15% olive-oil diet. Spleen weight was higher in offspring of mothers fed a 15% corn-oil diet compared to those fed the 7% corn-oil diet. The 15% olive-oil diet slightly decreased the weight of the spleen compared to counterparts fed the 15% corn-oil diet. Immunohistochemical studies showed that the olive diet, partially of 15%, significantly stimulated B-cell blast transformation. The finding reflects the reaction of B lymphocyte-producing splenic zones to the carcinogenic effect, though to a weak extent. T lymphocyte-producing zones did not respond to the diets studied, probably due to the weak carcinogenic effect and lack of tumor appearance. The Fas activity of both B and T cells in the spleen was stimulated by the carcinogen and enhanced by feeding the mothers on the olive-oil diet. Maternal feeding with a diet rich in olive oil before pregnancy results in stimulation of morphological and functional attributes of the splenic immune system of the offspring, particularly related to producing of B lymphocytes.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2000

Apoptosis and apoptosis-related proteins (Fas, Fas ligand, Blc-2, p53) in lymphoid elements of human ovarian tumors.

Different types of lymphocytes have different roles in tumor suppression. Thus, their expression of apoptosis-related proteins (ARP - Fas and Fas ligand, bcl-2, p53) in lymphocytes and their apoptosis were analyzed immunohistochemically in ovarian tumors of different grades. Ovaries without oncologic disorders had few lymphocytes, mainly T cells, and no ARP. Benign cysts presented features of weak immune reaction: small lymphoid infiltration and few lymphocytes. The ARP were present in 13.7% to 23.5% of the lymphocytes, and apoptosis was rare. In borderline tumors, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a tenfold rise in total lymphocytes, reflecting intensification of the immune response. Most lymphocytes were T cells (92%) predominated by CD8+ cells that were in direct contact with tumor epithelial cells. ARP species were found in 47% to 65% of the lymphocytes, and apoptosis in 2.2%. In carcinomas with ligh lymphoid infiltration, lymphocytes were 2.5 times more abundant, and the apoptotic index as well as the number of CD20+ and CD25+ lymphocytes rose sharply, whereas bcl-2 positive lymphocytes decreased to 8% of their number in borderline tumors. In carcinomas with low lymphoid infiltration, the total lymphocyte count decreased eightfold compared to carcinomas with high lymphoid infiltration, reflecting the deep subcompensation of the lymphoid system. Few p53-positive lymphocytes were found in the carcinomas. In conclusion, we found a positive correlation between apoptosis and the numbers of CD4+ or CD8+ lymphocytes in epithelial ovarian tumors. This correlation could reflect the antitumor activity of T cells. However, the high expression of ARP studied by immune cells at the vicinity of the tumor ARP reveals the lymphoid vulnerability to apoptosis, resulting in devastation of the lymphoid tissue, and consequently in tumor progression.

Adenocarcinoma↗

PubMed2000

Apoptosis and apoptosis-related proteins (Fas, Fas ligand, bcl-2, p53) in macrophages of human ovarian epithelial tumors.

Apoptosis and the apoptosis-related proteins (ARP) (Fas, Fas ligand (FasL), bcl-2 and p53) were analyzed in macrophages of different human ovarian epithelial tumors. Few macrophages were found in ovaries of women without oncologic disorders. In ovarian benign cysts, macrophagic density reached 4.9+/-1.2 per 50,000 microm2, most were present in lymphoid-macrophagic infiltrates of the sub-epithelial stroma (3.7+/-0.5% of the area of a slide), and 23.4% were Fas and FasL positive. In borderline tumors, the expanse of lymphoid infiltrates increased to 15.6% of the area of a slide, and the number of macrophages increased 2.4-fold compared to benign cysts. Of the macrophages, 83-88% expressed Fas and FasL, few had bcl-2 and CD25 receptors, and isolated ones were apoptotic. In carcinomas with high lymphoid-macrophagic infiltration, the infiltrate occupied 17.5% of the slide and macrophages amounted to 12.1+/-1.5/50,000 microm2. Many macrophages were in regions of grouping apoptosis of tumor epithelial cells and significantly fewer expressed Fas, FasL and bcl-2. Macrophages destroyed by apoptosis accounted for 4.6%. In carcinomas with low lymphoid-macrophageal infiltration, the area of the last was 5.1% of the slide. There were 8.6+/-0.8 macrophages/50,000 microm2, mainly at the margins of zones of necrosis and of tumor cells' grouping apoptosis. Extensive macrophagic infiltration into tumor parenchyma is one way by which the host immune system destroys tumors. Fas and FasL appear in macrophages of benign cysts, but in borderline tumors and in carcinomas with low infiltration their concentration increases sharply, to 79.8% and 96.6%, respectively. In 4.5% of these cells, apoptosis of macrophages was seen. The findings suggest that macrophages participate in the transfer of ARP to tumor epithelial cells, thereby inducing their apoptosis, but undergoing the simultaneous apoptosis.

Aged↗