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Diagnostic value of preoperative RT-PCR-based screening method to detect carcinoembryonic antigen-expressing free cancer cells in the peritoneal cavity from patients with gastric cancer.

BACKGROUND: At present the most reliable method for the diagnosis of peritoneal micrometastasis of gastric cancer is peritoneal wash cytology, but the sensitivity of this method is low. The aim of the present study was to verify whether carcinoembryonic antigen (CEA) reverse transcriptase-polymerase chain reaction (RT-PCR) assay can enhance the sensitivity and specificity of conventional cytology, and to determine how this technique can improve the accuracy of peritoneal recurrence. METHODS: The present study included 230 patients with gastric cancer. Preoperative peritoneal wash was done by a paracentesis, followed by conventional cytology, CEA measurement, and CEA RT-PCR of recovered fluid. RESULTS: The CEA RT-PCR assay yielded 40 (17%) positives, which included none of the 26 patients with benign disease. The incidence of positive cytology and CEA level in wash fluid was 19% and 15%, respectively. Logistic stepwise regression analysis revealed that lymph node status, depth of invasion, venous invasion, and the results of peritoneal cytological examination, and CEA RT-PCR assay were independently related to peritoneal recurrence. The CEA level in the wash fluid was not related to peritoneal recurrence. Peritoneal cytological examination was the most significant predictive factor for peritoneal recurrence with a sensitivity of 46%, specificity of 94% and accuracy of 73%, while the corresponding values of the CEA RT-PCR assay were 31%, 95%, and 73%. Combining cytological examination with CEA RT-PCR assay resulted in a sensitivity rate for peritoneal recurrence of 57%, an 11% improvement over that of cytology alone. CONCLUSION: The data indicate that the use of a combination of CEA RT-PCR and cytological assay is more likely to identify patients who will develop peritoneal recurrence. This may be useful for the classification of patients for the most suitable therapeutic trials.

Adult↗

The clinical relevance of molecular staging for melanoma.

The presence of metastatic disease in the regional nodal basin is the most important prognostic indicator for patients with malignant melanoma. The metastatic status of the sentinel lymph node (SLN), defined as the first node in the basin to drain a primary tumor, has been shown to represent that of the entire basin. Since routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease, a more sensitive assay for detecting tumor cells is needed. We have previously shown that a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) was able to define a population of patients at higher risk for both recurrence and death, compared with routine H&E histology. Recently, we have compared "molecular staging" of patients by RT-PCR with conventional S-100 immunohistochemistry (IHC) staining of the SLNs. In these studies, SLN specimens were bivaled, and half of each specimen was examined by routine histology, including both H&E and S-100 IHC. The other half of each specimen was analyzed by a nested RT-PCR assay. H&E histology alone detected metastatic disease in 36 of 233 (16%) patients tested. Serial sectioning and IHC detected micrometastatic disease in another 16 patients, thus increasing the proportion of patients with nodal disease to 22%. RT-PCR detected micrometastatic disease in 114 of 181 patients who were negative by conventional methods, further increasing the proportion of patients with evidence of nodal disease to 70% overall. The clinical significance of these findings is still uncertain. The value of additional therapy (including elective lymph node dissection and interferon therapy) for patients who are positive only by the molecular method is currently being investigated by the national multi-center Sunbelt Melanoma Trial.

Biomarkers, Tumor↗

Rapid genetic diagnosis with the transcription-reverse transcription concerted reaction system for cancer micrometastasis.

BACKGROUND: Detection of cancer micrometastases is required for improvement of cancer therapy. The aim of this study was to establish a rapid and practical genetic assay to detect micrometastasis in gastric cancer and to assess its clinical significance with respect to prognosis. METHODS: A novel RNA amplification system with transcription-reverse transcription concerted reaction (TRC) was introduced for quantitative detection of cancer-specific carcinoembryonic antigen messenger RNA. The sensitivity and quantitative aspects of the assay were assessed with the full-length carcinoembryonic antigen messenger RNA, a gastric cancer cell line (MKN-45), and metastatic lymph nodes obtained from patients with gastric cancer. Peritoneal lavage fluid specimens that were collected from gastric cancer surgery were subjected to the assay, and the clinical significance of the results was examined for prediction of recurrence and survival. RESULTS: The quantification, sensitivity, and reproducibility of the assay with the TRC reaction were equal to those of quantitative reverse transcriptase-polymerase chain reaction with LightCycler. The most important advantages of the assay were its simplicity and rapidity. Molecular diagnosis of peritoneal lavage fluid by the TRC reaction significantly correlated with depth of invasion, peritoneal metastasis, clinical stage, overall survival, and peritoneal recurrence-free survival. CONCLUSIONS: Molecular diagnosis of peritoneal lavage fluid with the TRC reaction could be a useful prognostic indicator for peritoneal recurrence and survival. Because the TRC reaction is more rapid and simpler than reverse transcriptase-polymerase chain reaction as a format for detecting RNA sequences, it may enhance the genetic diagnosis of cancer micrometastasis and may improve cancer therapy.

Biomarkers, Tumor↗

Serological, clinical and histopathological changes in naturally infected dogs with Leishmania infantum in the Khemisset province, Morocco.

Canine leishmaniasis (canL) is widespread in the north of Morocco and the Leishmania infantum local strains are highly virulent. An epidemiological survey was carried out in 1993-1995 in the Khemisset province. In this region, the severity of the disease was assessed during regular visits to the identified foci by clinical examination of 323 dogs. Clinical signs were protean and occurred in various combinations. Biopsies were made on available sick dogs; the main histological changes were severe infiltration of the spleen, lymph nodes and bone marrow by mononuclear cells and hyperplasia of macrophage cells with amastigotes in their cytoplasm. The seroprevalence among 323 dog sera tested by ELISA showed a rate of 16.71%. The highest prevalence of the disease was 23.6% in the Sid El Ghandour hamlet. A comparison of the results of this study with those from the year following the first examination on the same site (Sid El Ghandour) of 67 dogs showed that the disease prevalence had not increased significantly (23.6% to 25.33%).

Animals↗

Failure patterns of nonseminomatous testicular germ cell tumors: radiographic analysis of 51 cases.

A retrospective analysis was performed of 51 consecutive cases of treatment failure (tumor recurrence) of nonseminomatous germ cell tumors. Twelve patients with clinical stage I disease relapsed after lymph node dissection; 39 with stage II or III disease relapsed after chemotherapy. Routine follow-up consisted of monthly chest radiography and determination of serum tumor marker levels (alpha-fetoprotein and human chorionic gonadotropin), as well as abdominal computed tomography every 6 months. The median recurrence interval was 3 months; 96% of the relapses occurred within 2 years. In 61% of patients, recurrence was in the initial disease site only, in 26% it was in both new and initial sites, and in 13% it was in new sites only. At the time of treatment failure, 47 (92%) of the patients had positive radiologic studies and 44 (86%) had positive serum marker levels. Nine (18%) had positive radiologic studies only, and four (8%) had positive serum marker levels only. The analysis demonstrated the complementary role of radiologic studies and serum tumor-marker assays in detecting treatment failure.

Adolescent↗

Estrogen receptor status and adjuvant polychemotherapy or antiestrogen therapy in patients with high-risk breast cancer.

This pilot study includes 115 consecutive patients admitted in the period from 1978 to 1981. Patients eligible for this study were at high risk according to the TNM classification with stages pT1-pT3 and pN+, MO. Primary therapy included modified radical mastectomy and axillary-node clearance, one or more ipsilateral nodes being involved in routine histology. All tumors were assayed for estrogen and progesterone receptors. According to the result of the estrogen receptor assay, estrogen-receptor-positive patients were treated with Tamoxifen 30 mg/day for a period of 2 years. Estrogen-receptor-negative patients were treated with cytoxan, methotrexate, and 5-fluorouracil or adriblastin, cytoxan. After a median observation time of 36 months, overall there have been 31 recurrences: 9 = 17.3% in the estrogen-receptor-positive group and 22 = 34.9% in the estrogen-receptor-negative group. The analysis of different subgroups showed no significant differences, either in relation to axillary lymph-node status or in relation to menopausal status in the endocrine-treated compared with the polychemotherapy group. This result suggests, especially in the subgroup of patients with involvement of one to three axillary nodes, that estrogen-receptor-positive and estrogen-receptor-negative patients should be considered as separate groups when adjuvant therapy is indicated. Possibly hormone-receptor-positive patients may benefit from endocrine therapy and do not need polychemotherapy.

Adult↗

Pulmonary immune response of dogs after exposure to 239PuO2.

This study evaluated the cell-mediated (CMI) and humoral immune responses in four Beagle dogs five to six years after single inhalation exposures to different monodisperse 239PuO2 aerosols (0.72-1.4 microns activity median aerodynamic diameter). These exposures resulted in initial lung burdens ranging from 19 to 35 kBq. Four nonexposed dogs were used as age-matched controls. Anesthetized dogs were immunized by instillation of sheep red blood cells (SRBC) into selected lung lobes. Cells and fluids were obtained serially from blood samples and by bronchoalveolar lavage of the saline- and SRBC-treated lung lobes at 5-20 days after immunization. The CMI response evaluated by the leukocyte procoagulant activity test was similar in the saline- and SRBC-treated lobes of both groups of dogs. The humoral immune response was measured by the enzyme-linked immunosorbent assay. No differences were shown between the amount of antibody measured in the sera or lung lavages from control or Pu-exposed dogs. Histopathology of the tracheobronchial lymph nodes from the Pu-exposed dogs showed them to be fibrotic with no lymphoid cells, suggesting that these tissues could not respond to the antigen deposited in the lungs. However, both mediastinal and sternal lymph nodes did contain lymphoid tissue, and were likely to be the lymphoid tissues that produced the immunity to the antigen deposited in the lungs of the exposed dogs. Although both exposed and control dogs produced immune responses to the antigen instilled into their lungs, differences were observed in the number of neutrophils in lung lavages from the control and exposed animals. There was a dramatic influx of neutrophils into both the saline- and SRBC-treated lung lobes of the Pu-exposed dogs that was not seen in the age-matched controls. This suggests that the inhaled 239PuO2 produced chronically-active inflammation in the lung which may contribute to recruitment of lymphocytes to the lung following intrapulmonary deposition of antigen. In conclusion, the immune responses induced by lung immunization of dogs that had inhaled 239PuO2 were not suppressed by large doses of chronic alpha irradiation of the lungs and tracheobronchial lymph nodes, indicating that local pulmonary immune responses are preserved despite severe radiation-induced alteration of these tissues.

Administration, Inhalation↗

Comparison of potential protection induced by three vaccination strategies (DNA/DNA, Protein/Protein and DNA/Protein) against Leishmania major infection using Signal Peptidase type I in BALB/c mice.

Signal Peptidase (SPase) is an essential enzyme in both prokaryotes and eukaryotes; which removes signal sequence from secretary proteins. Previously, type I SPase from Leishmania major (Lmjsp) has been isolated and characterized. The sera from cutaneous and visceral forms of leishmaniasis are highly reactive to both the recombinant SPase (rSP) and synthetic SPase (Sy-Sp) antigens. Therefore, the Leishmania SPase, albeit localized intracellularly, is a significant target of the Leishmania specific immune response and highlights its use as a candidate vaccine against cutaneous leishmaniasis (CL). In this study as a first report, the potential protection of Lmjsp was evaluated in three different vaccination strategies (DNA/DNA, Protein/Protein and DNA/Protein), against L. major infection. We demonstrated that vaccination with SPase through all three mentioned strategies induced a parasite specific Th1 response and conferred partial protection against parasite challenge. However, our results indicated that DNA/DNA strategy developed more effective protective responses than the other two approaches and induced 81% reduction in L. major parasite load.

Animals↗

Natural cytotoxicity of lymphocytes from lymph nodes draining breast carcinoma and its augmentation by interferon and OK432.

Lymphocytes isolated from axillary lymph nodes draining breast carcinoma were tested for natural killer (NK) activity against K562 in a 4-h 51Cr-release assay, and the in vitro effects of interferon (IFN) and OK432 (a streptococcal preparation) on their cytotoxicity were examined in comparison with NK activity of autologous peripheral blood lymphocytes (PBL). The levels of NK activity were lower in lymph node lymphocytes (LNL) than in PBL of the same patients. Significant levels of LNL-mediated lysis were recorded in 14 of 42 (33%) lymph node samples and in nine of 14 (64%) patients. Purification of large granular lymphocytes (LGL) from lymph node cells by discontinuous Percoll density gradient centrifugation resulted in an induction or enhancement of cytotoxic activity, with no reactivity in LGL-depleted, small T-lymphocyte populations. Positive reactions were observed with 10 of 13 (77%) LGL samples. The low reactivity of LNL was not attributable to coexistent suppressor cells for NK function, since lymph node cells failed to suppress NK activity of normal PBL. Partially purified human IFN and OK432 augmented NK activity of patients' PBL in approximately 70% and 90% of the cases, respectively, while LNL-mediated lysis was augmented in only 7% and 36% of the lymph node samples by IFN and OK432, respectively. These results indicate that K562-reactive NK cells and/or their precursors may frequently be present at subthreshold levels in the lymph nodes draining breast carcinoma, and that the augmentation of LNL-mediated cytotoxicity by OK432 might provide a local potentiation of natural immune function at the host-tumor interface rather than IFN.

Axilla↗

Expression of MUC1 and its significance in hepatocellular and cholangiocarcinoma tissue.

AIM: To investigate the relation between MUC1 expression, distribution, and prognosis in hepatocellular and cholangiocarcinoma (HCC and CC) and cirrhotic liver tissues, and their significance in HCC and CC diagnosis. METHODS: Expression and distribution of MUC1 were examined by immunohistochemical assay with anti-MUC1 mAb in 59 samples of HCC and 37 samples of CC, 20 samples of cirrhotic liver tissues, and 10 samples of normal liver tissues, seeking possible associations between MUC1 positive expression, distribution in HCC and CC (primary liver cancer, PLC) cases and the studied clinical data. RESULTS: Immunohistochemical analysis of MUC1 expression showed that in the 96 PLC samples, 68 (70.8%) were strong positive, and 6 (6.2%) were weak positive. Only 4 in the 20 cirrhotic liver tissues were found to be weak positive, while no expression of MUC1 was detected in normal liver tissues. Apparently, the high expression rate of MUC1 in PLC tissues was statistically significant in comparison to that in cirrhotic and normal liver tissues. The expressed MUC1 protein, stained in dark brownish or brownish-yellow particles, chiefly localized on the cancer cell membranes or in cytoplasm. In the 68 strong positive samples, 40 were detected on cell membrane and the other 28 were in cytoplasm. In addition, follow-up studies of those PLC cases demonstrated that MUC1 expression on cell membrane or in cytoplasm was closely associated with PLC prognosis. The expression of MUC1 in PLC had little statistical significance in respect of the pathological types and sizes of the tumors, but a strong relationship regarding histological differentiation, metastasis of lymph nodes, portal canal emboli, and post-operational recurrence of the carcinomas. After 3 years of tumor excision, the metastasis rate in MUC1 positive expression group (67.6%) was much higher than that in MUC1 weak expression group (33.3%) and negative expression group (31.8%), and thus the survival rate in MUC1-positive expression group was significantly different from that in weak and negative expression groups. CONCLUSION: Expression and localization of MUC1 proteins in primary liver carcinomas (PLCs) may act as prognostic markers, and MUC1 molecules might be helpful in differential diagnosis.

Adult↗

Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo.

Lymphocyte recirculation through different organs is thought to be regulated by adhesion molecules ("homing receptors") recognizing tissue-specific vascular addressins on endothelium. Here we show that the alpha 4/beta 7-integrin has a key role in the migration of mouse lymphocytes to mucosal sites. Homing to Peyer's patches but not to peripheral lymph nodes is inhibited by Fab fragments of mAb PS/2 against the alpha 4-integrin chain, by mAb DATK32 recognizing a combinatorial epitope on the alpha 4/beta 7-integrin, and by mAb FIB30 against the beta 7-chain. The Abs significantly reduce homing of lymphocytes to the intestine, as well. The migration of immunoblasts to gut and gut-associated lymphoid tissue also involves the alpha 4/beta 7-integrin heterodimer. Another anti-alpha 4 Ab, R1-2, which blocks lymphocyte binding to Peyer's patches in the Stamper-Woodruff frozen section assay and lymphocyte adhesion to VCAM-1 and fibronectin, has only minor effects on lymphocyte traffic in vivo. Anti-VCAM-1 Ab as well as the fibronectin peptide CS-1 are without influence on the migration to Peyer's patches or intestine, in contrast to Ab against the mucosal addressin MAdCAM-1. Thus, homing to gut-associated sites is regulated by the alpha 4/beta 7-integrin heterodimer interacting with the vascular addressin, MAdCAM-1, and not with fibronectin or VCAM-1 as counterstructures. Inhibition of homing to Peyer's patches and intestine by the anti-integrin Abs studied was only partial. L-selectin also participates in the homing of small lymphocytes to mucosal sites, especially Peyer's patches, but does not contribute substantially to the localization of blasts into the intestinal wall. The results support a major, but not exclusive role of the alpha 4/beta 7-integrin in lymphocyte traffic to mucosal sites.

Animals↗

Clinical relevance of urokinase-type plasminogen activator and its inhibitor type 1 (PAI-1) in squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The expression of uPA and PAI-1 as parameters of tumour-associated proteolysis has been implicated in the process of tumour cell invasion and the metastatic process. However, there is limited information on the impact of these parameters in cervical carcinoma. METHODS: Quantitative levels for uPA (n = 114) and PAI-1 (n = 103) were researched in operatively treated, surgically staged squamous cell cancer of the uterine cervix, using an ELISA-technique. Results were assessed regarding their impact in predicting pelvic lymph nodes metastases, tumour recurrence rate and recurrence free survival (RFS) using uni- and multivariate analysis. RESULTS: Median levels of both parameters were significantly higher in tumour tissue than in normal cervical tissue (p < 0.001). Detection of uPA gave no useful prognostic information. PAI-1 concentration showed a positive correlation with advanced tumour stage (p = 0.008), but no significant correlation with nodal status (pN0: 2.6 vs. pN1: 4.0 ng/mg protein; p = 0.092). Using a cut-off level of 2.4 ng/mg protein, patients with elevated PAI-1 levels demonstrated reduced RFS (45.9 versus 52.9 months; p = 0.1). Multivariate analysis, including nodal status, tumour stage, lymphovascular space involvement and grading failed to demonstrate any prognostic impact of uPA and PAI-1. CONCLUSIONS: The results indicate, that PAI-1 expression is of some prognostic impact in cervical cancer, indicating an association of elevated PAI levels with local tumour progression and reduced recurrence-free survival.

Adult↗

Estrogen receptor-negative, progesterone receptor-positive breast carcinoma: poor clinical outcome.

OBJECTIVE: The biological significance of breast carcinomas negative (-) for estrogen receptor (ER), but positive (+) for progesterone receptor (PR) is unclear. It has been proposed that these tumors contain ER whose presence is masked in binding assays by endogenous estrogen. We analyzed the clinical outcome of 17 patients with ER-PR+ tumors. METHODS: The disease-free and overall survival of a series of 300 women with invasive breast carcinoma was followed for 7 to 79 (median 41) months. RESULTS: The recurrence rate was significantly greater in ER-PR+ tumors (8/17 [47%]) than in ER+PR+ tumors (27/177 [15%]), and it was similar to the high recurrence rate of ER-PR- tumors (21/57 [37%]). The cancer-related death rate was 3 1/2 times higher in the ER-PR+ group than in the ER+PR+ group. A significant association between ER-PR+ tumors and tumor recurrence or cancer-related death persisted even after correction for other variables associated with poor outcome (eg, tumor size and lymph node involvement). CONCLUSIONS: Estrogen receptor-negative, progesterone receptor-positive breast carcinomas are biologically different from ER+PR+ tumors and have a poor clinical outcome.

Breast Neoplasms↗

Comparison of metastatic behavior of parental and metastatic pancreatic cancer cell lines in Syrian golden hamsters.

The major cause of death in patients with pancreatic cancer is metastatic disease. In fact, at the time of diagnosis, patients usually have locally advanced or metastatic disease involving lymph nodes, liver, lungs or peritoneum. Therefore, for a better understanding of the tumoral behavior to design prevention or treatment strategies, in vivo models are important. We report here the results of the metastatic behavior of parental and metastatic cell lines in a hamster pancreatic cancer model when implanted orthotopically (OIH,OIM) or into the liver (LIH,LIM). Metastatic sites and survival were studied. Survival ranged from 72 to 105 days. The OIH group showed spontaneous metastases to lymph nodes. The second target organ was the lung. Liver metastases appeared earlier in the OIM group than OIH. LIH showed only metastases to the pancreas while the LIM group showed metastases to pancreas, vas deferens and testis. This study suggests that the metastatic behavior of parental and metastatic cell lines is different. Thus, this should be considered in the planning of clinical or surgical treatment against pancreatic cancer.

Adenocarcinoma↗

Influence of polyamines on in vitro and in vivo features of aggressive and metastatic behavior by human breast cancer cells.

Increased cellular activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) synthesis, is an independent adverse prognostic factor for overall survival in human breast cancer, thus suggesting an important role for PA in tumor progression. The experiments presented here were designed to investigate the role of PA in invasion and metastasis, using the highly aggressive MDA-MB-435 and MDA-MB-231 human breast cancer cell lines. Administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, significantly reduced, in a dose-dependent manner, the invasiveness in matrigel of both MDA-MB-435 and MDA-MB-231 cells by approximately 70%. DFMO treatment also inhibited (P < 0.0001) 'stellate' colony formation (an indicator of aggressive phenotype) by MDA-MB-435 cells plated in the matrigel outgrowth assay. Administration of DFMO (2% in drinking water) reduced the growth rate of both cell lines implanted orthotopically in nude mice. To evaluate metastasis while minimizing effects on proliferation, DFMO-treated mice were sacrificed later to allow their tumors to reach the same size of the tumors in the control mice. The most striking finding was that DFMO, while ineffective in reducing local invasion, nearly totally abolished (P = 0.0152) pulmonary metastasis in mice bearing MDA-MB-435 xenografts. These results support a role of PA in promoting breast cancer aggressiveness, particularly with regard to the development of distant metastasis. Furthermore, the data suggest that PA involvement is distal to local invasion in the metastatic cascade.

Animals↗

Phospholipid metabolite expression by head and neck squamous cell carcinoma.

OBJECTIVE: To characterize the presence and production of various phospholipid metabolites by head and neck squamous cell carcinoma (HNSCC) and squamous cell carcinoma cell lines in vitro and in vivo. DESIGN: The HNSCC tumor homogenates and supernatants of HNSCC tumor cultures and established squamous cell carcinoma cell lines were assayed for prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and platelet activating factor (PAF). In vitro experiments were carried out under baseline conditions or with exposure to several known immunomodulators (epidermal growth factor, bacterial lipopolysaccharide, and interleukin 1). PATIENTS: The HNSCC tumor tissue was obtained from primary tumor or cervical lymph node metastasis of surgical resections. MAIN OUTCOME MEASURES: Prostaglandin E2, LTB4, and PAF were measured in tumor homogenates and cell culture supernatants using standardized radioimmunoassay kits. RESULTS: All tumor homogenates (eight of eight) contained detectable levels of PGE2 (range, 324 to 2258 pg/g of tumor tissue) and LTB4 (range, 790 to 41,900 pg/g of tumor tissue); PAF was detected in six of eight homogenates (range, 7362 to 40,788 pg/g of tumor tissue). All of the short-term primary HNSCC tumor cultures and squamous carcinoma lines produced PGE2 (range, 90 to 1160 pg/10(6) cells), and half of the cultures produced LTB4 (range, 100 to 1700 pg/10(6) cells); none of the cultures or cell lines produced detectable levels of PAF. Interleukin 1 significantly enhanced production of PGE2 by tumor cultures (P < .02). Characterization of tumor cultures with a fibroblast antibody marker, BR2, revealed that 26% to 64% of tumor culture cells were fibroblasts. CONCLUSIONS: Prostaglandin E2, LTB4, and PAF are present in the tumor microenvironment, where they may be involved in the local immunosuppression phenomenon seen in HNSCC. Both PGE2 and LTB4 were produced in vitro by tumor cultures and squamous cell carcinoma cell lines; PAF was not produced by tumor cultures in vitro and therefore may be a product of local immune cells in HNSCC in vivo. Interleukin 1 and PGE2 may interact in immunoregulation in the HNSCC tumor microenvironment.

Aged↗

High endothelial venules present in lymphoid cell accumulations in thyroids affected by autoimmune disease: a study in men and BB rats of functional activity and development.

High endothelial venules (HEVs) derive their name from the cuboidal high walled shape of the endothelial cells and are found in T-cell areas of a wide variety of lymphoid tissues. The function of HEVs is to attract lymphocytes to lymphoid tissues, and they are thus of importance in lymphocyte recirculation. We investigated the immunohistochemical presence and localization of HEVs in thyroid tissue obtained at surgery from 13 patients with Graves' disease and 3 patients with Hashimoto's disease using the monoclonal antibody HECA 452, which reacts with an epitope on human HEVs. HEVs were found in large confined lymphocytic accumulations in 7 of the 13 Graves' disease glands and all of the Hashimoto's disease glands. These lymphocytic accumulations showed a high grade of architecture and were composed of a central B-cell follicle and a T-cell area in which the HEVs were present. The HEV-containing T-cell area formed a corona around the B-cell follicle. Plasma cells were found at the periphery of the intrathyroidally developed lymphoid tissue. In BB rats, an animal model for spontaneous autoimmune thyroid disease, the development of such HEVs containing intrathyroidal lymphoid tissue was a rather late phenomenon in the autoimmune process occurring after the appearance of anticolloid antibodies in the circulation and after initial immune activity of the thyroid draining lymph nodes. The actual development of the intrathyroidal lymphoid tissue was initiated by accumulation of lymphocytes around dendritic cells forming small cellular clusters. These small clusters later developed into larger formation in which HEVs were detectable. The adherence of B- and T-lymphocytes to human intrathyroidal HEVs was additionally studied using an in vitro adherence assay. B-Lymphocytes preferentially adhered to thyroidal HEVs. This adherence pattern is similar to that of HEVs in mucosa-associated lymphoid tissue (tonsils and Peyer's patches). We conclude that lymphoid tissue with a lymphocyte recirculation pattern similar to that of mucosa-associated lymphoid tissue can be found in thyroid glands involved in a process of autoimmune reactivity; the BB rat study suggests that the development of such tissue occurs during the chronic phases of the process.

Adult↗

Combined assay of serum levels of CA125 and CA19-9 in endometrial carcinoma.

Serum levels of CA125 and CA19-9 were examined in 225 cases with endometrial carcinoma before treatment and 32 cases with recurrent endometrial carcinoma. The positive rates in the 225 cases were 27.1% for CA125, 24.0% for CA19-9, and 38.7% for the combined assay. The serum levels of both CA125 and CA19-9 significantly increased with surgical staging. The presence of lymph node metastasis and extrauterine spread exhibited a marked influence on the serum levels of both CA125 and CA19-9. Myometrial invasion and vessel permeation also increased serum levels of CA125, whereas peritoneal cytology and adnexal metastasis exhibited no influence on CA125 levels or CA19-9 levels. Twenty-five of 33 cases who showed either more than 100 U/ml of CA125 level or more than 100 U/ml of CA19-9 level were classified as surgical stage III or IV. The combined assay demonstrated a 71.9% positive rate at the time of detection of the recurrence (65.6% for CA125, 43.7% for CA19-9). In 34.4% of the 32 recurrent cases, elevated levels of the tumor markers were the first sign of recurrence. These data indicate that the use of CA19-9 in combination with CA125 is noteworthy in the management of patients with endometrial carcinoma.

Adult↗