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Regional chemotherapy for bladder neoplasms using continuous intravesical infusion of doxorubicin: impact of concomitant administration of dimethyl sulfoxide on drug absorption and antitumor activity.

BACKGROUND: One objective of regional chemotherapy is to achieve the therapeutic drug levels in local tissues and primary nodal drainage fields, while minimizing systemic drug toxicity. The composition of the drug-delivery vehicle may influence local drug absorption and thereby modulate both tissue drug levels and systemic toxicity. PURPOSE: We evaluated the effect of dimethyl sulfoxide (DMSO) as a drug-delivery vehicle on regional and systemic levels of doxorubicin (DOX) and on the cytotoxicity of DOX following continuous intravesical administration in an invasive rat transitional cell bladder carcinoma model. METHODS: F344 rats received continuous intravesical DOX infusion for a 7-day period using a regional drug administration system. A constant dose of DOX was administered in one of three DMSO concentrations (0%, 10%, or 50%) to groups of animals (N = 20 per group). These concentrations corresponded to target urinary concentrations of 0%, 0.1%, and 0.5%, respectively. DOX levels in urine, serum, muscle, liver, bladder wall, and retroperitoneal lymph nodes were measured using a fluorescence assay on experimental days 0, 2, 4, 6, and 8 (N = four animals/group per day). In vitro assays evaluated the effect of DMSO concentration on the cytotoxicity of DOX against six transitional cell carcinoma cell lines. A final experiment on rats with established bladder tumors compared the cytoreductive effect of continuous intravesical infusion of DOX in 50% DMSO with that of DOX alone and with that in a sham-treated control group; there were 20 rats in each group. RESULTS: Mean and peak tissue and serum levels of DOX increased as a direct function of DMSO concentration. Compared with the results in controls, mean concentrations of DOX in the bladder were increased 7.1-fold and 12.1-fold in the groups given 10% and 50% DMSO, respectively. Average drug concentrations in the lymph nodes were increased 9.6-fold and 9.3-fold in the groups given 10% and 50% DMSO, respectively. In vitro, DMSO synergistically enhanced the cytotoxicity of DOX in two of the six cell lines studied. Solubilizing the test agent in 5% DMSO reduced the IC50 (drug concentration required to reduce cell viability to 50% of control values) to an average of 56% +/- 41% (+/- SD) of control values; 10% DMSO further decreased the average IC50 to 20% +/- 18% (+/- SD) of control values. The mean bladder tumor weight of animals treated with the combination of DOX and DMSO was 0.52 g. This compared with a mean tumor-bearing bladder weight of 2.69 g in the control group (P = .012) and 0.80 g in the group treated with DOX alone (P = .0544). CONCLUSIONS: These results suggest that the use of DMSO as a solvent vehicle for DOX improves drug absorption while simultaneously potentiating DOX cytotoxicity. The use of DMSO as a drug carrier merits further evaluation as a way of enhancing the efficacy of regional chemotherapy regimens.

Administration, Intravesical↗

Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients.

Tumours from 336 breast cancer patients under the age of 50 were analysed for hormone receptor content and by DNA flow cytometry. Sixty-six percent of the tumours were positive for estrogen receptors (ER), 60% were progesterone receptor (PR) positive and 42% showed DNA diploid profiles. DNA hypodiploid tumours were relatively frequent (7%), especially in patients aged 40 years or less (11%). S-phase fraction (SPF), with a mean of 10%, correlated significantly with receptor status, DNA ploidy, lymph node status, tumour size and age. With a median follow-up period of 34 months, the distant recurrence-free interval was independently predicted by lymph node status, tumour size, SPF and PR content. Amongst the 212 patients who had not received adjuvant systemic treatment, receptor status was, in addition to lymph node status and SPF, independently related to distant recurrence rate. A high SPF identified a subgroup with high recurrence rate, comprising approximately one third of the node-negative patients. Similarly, the one third of node-positive patients who had PR-positive tumours with a low S-phase fraction formed a subgroup with low recurrence rate. We conclude that hormone receptor assays and DNA flow cytometry should be useful tools in the management of breast cancer patients less than 50 years of age.

Adult↗

Comparison of HL-A typing with NIH trays and the NIH technique with typing by the fluorochromasia cytotoxicity assay.

A comparison of HL-A phenotypes determined with plates containing predispensed typing sera supplied by the NIH Serum Bank with phenotypes determined by the fluorochromasia cytotoxicity assay using local reagents showed that the NIH plates (as dispensed in 1972) had an insufficient number and variety of typing sera. Using NIH trays, it was difficult to detect HL-A9 and W19, both of which specificities are now known to have subtypes. The NIH trays also appeared to detect more HL-A antigens than were consistent with the current theory of two segregant series, each expressing a maximum of two antigens. The excess antigens could not be comparatively evaluated in view of the small number of sera defining each. With the NIH technique, it was impossible to interpret the reactions if the preparation had too many dead cells. A high proportion of dead cells was occasionally noted when lymphocytes had been previously frozen or obtained from lymph nodes. When the NIH and fluorochromasia techniques were compared using the same antisera and fresh lymphocytes, they proved equivalent in sensitivity.

Cytotoxicity Tests, Immunologic↗

Viruses and Hodgkin lymphoma: no evidence of polyomavirus genomes in tumor biopsies.

The epidemiology of young adult Hodgkin lymphoma (HL) suggests that delayed exposure to a common childhood pathogen may be involved in disease pathogenesis. The Epstein-Barr virus (EBV) is associated with a proportion of cases but cases of young adult HL in westernized countries are less frequently EBV-associated than cases in other age groups and geographical locales. This study investigated the possibility that polyomaviruses might be involved in the etiology of HL by analysing a series of 35 cases of classical HL using both specific and degenerate PCR assays for polyomavirus genomes. No positive results were obtained, indicating that it is highly unlikely that this virus family is directly involved in the pathogenesis of HL.

Adult↗

Primary marginal zone B-cell lymphoma of the lymph node resembling plasmacytoma arising from a plasma cell variant of Castleman's disease. A clinicopathological and immunohistochemical study of seven patients.

Nodal marginal zone B-cell lymphomas (NMZBL) occasionally represent prominent plasma cell differentiation. Recently, we presented a patient with NMZBL who exhibited histological features that resembled plasmacytoma arising from a localized plasma cell variant of Castleman's disease. To further clarify the clinicopathological, immunohistochemical, and genotypical findings, we studied seven such patients. Clinically, these patients were characterized by localized disease and an indolent clinical course with a slowly growing bulky mass in the affected lymph node. Only one patient exhibited paraproteinemia. Histologically, the lesions were characterized by numerous evenly distributed germinal centers in extensive sheets of plasma cells. Various numbers of centrocyte-like (CCL) cells arranged in a marginal zone distribution pattern occupied the peripheral region of the lymph node. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry showed that all of the lesions contained a monoclonal plasma cell population. In three tumors, a number of the CCL cells had a similar light chain restriction pattern to that observed in plasma cells. Two of the four patients evaluated exhibited clonal bands for the IgH gene by polymerase chain reaction assay. Moreover, the presence of surface IgM+, IgD- and CD27+ CCL- cells suggests that these tumors are derived from memory B-lymphocytes.

Adult↗

Serum tissue polypeptide specific antigen (TPS) in locoregional failure and distant metastasis of cervical carcinoma.

Tissue polypeptide specific antigen (TPS) was measured by the ELISA Technique in the sera of 51 patients with locoregional failure and metastasis of squamous cell carcinoma of the cervix in order to evaluate the serum level of TPS in known cases of metastasis and recurrence. There were 32 cases of local residual or recurrent disease and 19 cases of distant metastasis, including lymph nodes (paraaortic and supraclavicular lymph node) and visceral metastasis. The range of TPS levels in the locoregional failure group were 38.2 355.2 micro/l with a mean of 312.5 and 35.7 - 4822 micro/l with a mean of 833.36 micro/l in the metastatic group. With the cut-off value of 90 micro/l, the rates of TPS elevation were 27 in 32 cases (84.37%) of the loco-regional failure group and 16 in 19 cases (84.21%) of the metastatic group. Among the metastatic group, the mean of TPS level in visceral metastasis was much higher than the group of lymph node metastasis (1518.4 micro/l vs 215.1 micro/l). TPS level might be used as the follow-up guide for prediction of locoregional failure and metastasis in squamous cell carcinoma of the cervix after the completion of the treatment. In patients with a significantly high level of serum TPS, the distant metastases or local recurrence should be searched for. However, a prospective study of TPS levels in cervical cancer patients after completion of treatment should be done in order to evaluate the sensitivity and specificity of this tumor marker.

Adult↗

Engraftment of human CD34+ cells leads to widespread distribution of donor-derived cells and correction of tissue pathology in a novel murine xenotransplantation model of lysosomal storage disease.

A novel murine system was developed to study the in vivo localization of xenotransplanted human cells and assess their therapeutic effect in an authentic model of disease. The beta-glucuronidase (GUSB) mutation of the mucopolysaccharidosis type VII (MPSVII) mouse was backcrossed onto the nonobese diabetic/severe combined immunodeficient (NOD/SCID) xenotransplantation strain. The resulting NOD/SCID/MPSVII mice displayed the characteristic features of lysosomal storage disease because of GUSB deficiency and were also capable of engrafting human cells. Human CD34+ hematopoietic progenitor cells from healthy, GUSB+ donors engrafted NOD/SCID/MPSVII mice in a manner similar to that of standard NOD/SCID mice. Six to 12 weeks following transplantation, 1% to 86% of the host bone marrow was positive for human CD45. By using a GUSB-specific histochemical assay, human engraftment was detected with single-cell sensitivity not only in well-characterized hematopoietic tissues like bone marrow, spleen, lymph node, and thymus, but also in other nonhematopoietic organs like liver, kidney, lung, heart, brain, and eye. Quantitative measurements of GUSB activity confirmed this expansive tissue distribution. The GUSB-specific assays were validated for their accuracy in identifying human cells through colocalization of human CD45 expression with GUSB activity in tissues of mice receiving transplants. An analysis of the therapeutic effects of engrafted human cells revealed a reduction of pathologic storage material in host organs, including the bone, spleen, and liver. Such xenotransplantation experiments in the NOD/SCID/MPSVII mouse represent a powerful approach to both study the in vivo biology of human cells and gather preclinical data regarding treatment approaches for a human disease.

Animals↗

Detection of minimal residual cancer to investigate why oral tumors recur despite seemingly adequate treatment.

Improvements in surgery and radiotherapy techniques have led to only a modest increase in the 5-year survival rate for patients with head and neck cancer. This is because the pattern of clinical disease is changing, such that locoregional recurrence now accounts for fewer treatment failures, but more patients develop a second primary cancer or distant metastatic disease. In this study, we have used the p53 phage plaque assay, immunocytochemistry, and mutational analysis to assess the contribution of minimal residual cancer and genetic aberrations in clinically normal upper aerodigestive tract mucosa to treatment failure. Eighteen consecutive patients with oral tumors, with conventional clear margins, have been followed for a minimum of 36 months. Molecular assessment identified tumor-positive surgical margins for 6 of 11 assessable patients and additional tumor-positive lymph nodes for three cases. Disseminated malignant cells were detected in the hematopoietic cell compartment for six cases, and one patient had molecular evidence of field cancerization. Locoregional recurrence developed in five patients with tumors harboring a p53 gene mutation; four of these were associated with tumor-positive surgical margins, and one was associated with molecular evidence of field cancerization. Radiotherapy to the primary site did not prevent development of local recurrence when the residual tumor harbored a p53 gene mutation. Three of six cases with a tumor-positive bone marrow aspirate developed distant metastases. These findings reveal that molecular and immunocytochemical detection of minimal residual cancer and field cancerization can help identify patients who may develop locoregional or distant recurrence and justify further studies to evaluate the contribution of these remaining malignant cells to treatment failure.

Adult↗

Identification of beta-adrenoceptors in rat lymph nodes and spleen: an autoradiographic study.

The anatomical localization of beta 1 and beta 2-adrenoceptors was studied in rat lymphoid tissues by quantitative autoradiography using [125I]cyanopindolol as a ligand. In lymph nodes, a significant density of these receptors was found in the medullary cords and the interfollicular cortex, while only low densities were observed in the paracortex. No detectable binding appeared in the remaining areas. In the spleen, these receptors were mainly localized in the capsule, marginal zone of white pulp and red pulp, while the labelling over the white pulp was extremely low. The subtype beta 2 was predominant in both lymph nodes and spleen. The results suggest that beta-adrenoceptors are present in mature cells in lymphoid tissues and are probably not involved in homing mechanisms.

Adrenergic beta-Antagonists↗

Diagnostic and prognostic value of the new tumour marker CYFRA 21-1 in patients with squamous cell lung cancer.

We wanted to investigate the diagnostic and prognostic significance of serum CYFRA 21-1, especially in predicting the risk of recurrence in patients with operable squamous cell lung cancer. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 76 patients with squamous cell lung cancer (64 operable and 12 with unresectable tumours), 22 with other non-small-cell type (12 with adenocarcinoma and 10 with large-cell type) and 45 with nonmalignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 63% of patients with squamous cell type (SqCC), 33% with adenocarcinoma, and 30% with large-cell carcinoma type. The diagnostic specificity of the assay was 96%. Positive CYFRA 21-1 levels were observed in 33% of stage I, 52% of stage II, 76% of stage IIIa and 83% of stage IIIb patients with SqCC type. Statistically significant differences were obtained between stages I and II and between II and IIIa, but not between stages IIIa and IIIb. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 63% (24/38) versus 92% (24/26) for patients with normal serum CYFRA 21-1 levels. However, the difference was not statistically significant when adjusted for the TNM stage (primary tumour, regional lymph node involvement, occurrence of distant metastasis). In 9 of the 10 patients with increased trend for CYFRA 21-1 during follow-up, elevated serum CYFRA 21-1 levels preceded (7) or coincided (2) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Widespread expression of perlecan proteoglycan in basement membranes and extracellular matrices of human tissues as detected by a novel monoclonal antibody against domain III and by in situ hybridization.

Perlecan, a multidomain heparan sulfate proteoglycan (PG), is an intrinsic component of basement membranes and extracellular matrices. We used a prokaryotic expression vector to generate fusion proteins encoding various domains of human perlecan protein core and these recombinant proteins were used as immunogens to produce mouse anti-human monoclonal antibodies (MAb). One MAb, designated 7B5, was characterized by Western blotting and ELISA and was shown to react specifically with the laminin-like region of perlecan (Domain III) but not with two other fusion proteins encoding Domain II or V. This perlecan epitope was detected by immunoenzymatic staining in the basement membranes of human tissues including pituitary gland, skin, breast, thymus, prostate, colon, liver, pancreas, spleen, heart, and lung. All vascular basement membranes tested contained this gene product. In addition, sinusoidal vessels of liver, spleen, lymph nodes, and pituitary gland expressed high levels of perlecan in the subendothelial region. In situ hybridization, using as probe the same human cDNA-encoding Domain III, localized perlecan mRNA to specific cell types within the tissues and demonstrated that in skin, perlecan appears to be synthesized exclusively by connective tissue cells in the dermal layer. The availability of MAb against precise regions of human perlecan will allow the investigation of this gene product in normal and diseased states.

Animals↗

Diagnostic usefulness of telomerase activity in nasopharyngeal carcinoma.

Telomeres are specialized structures at the ends of eukaryotic chromosomes which are composed of simple repetitive G-rich hexameric sequences. Activation of telomerase, a ribonucleoprotein that synthesizes telomeric DNA, is found in most malignant tumors. However, little data is available concerning the correlation between telomerase activity and NPC (nasopharyngeal carcinoma). In this study, telomerase activation was determined using the TRAP (telomerase repeat amplification protocol) assay in 62 nasopharyngeal biopsies (25 NPC, 25 non-malignant nasopharyngeal lymphoid tissues, 12 post-irradiated nasopharyngeal tissues). The results showed that strong telomerase activity was present in both NPC and non-malignant nasopharyngeal biopsies. Post-irradiated nasopharyngeal samples had a significantly lower telomerase activity than NPC and non-malignant nasopharyngeal lymphoid tissues. It is well known that nasopharyngeal tissue is infiltrated by numerous lymphocytes, which might retain telomerase activity. Therefore, the finding that the telomerase activation was lowest in post-irradiated nasopharyngeal tissues is reasonable because of the destruction of activated lymphocytes and NPC by radiation. NPC biopsies with positive lymph node involvement exhibited higher levels of telomerase compared to those without lymph node involvement. Our data indicate a positive association between telomerase activity and tumor potential for lymphatic spreading in limited local tumors. In addition, telomerase activity may be useful as a diagnostic marker in the detection of tumor cells in recurrent NPC, but not in primary NPC.

Adolescent↗

Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma.

Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, whereas steroid sulfatase (STS) hydrolyzes estrone sulfate to estrone. Both EST and STS have been suggested to play important roles in regulating the in situ production of estrogens in human breast carcinoma tissues. However, the expression of EST has not been examined in breast carcinoma tissues, and the biological significance of EST and STS remains unknown. Therefore, in this study, we examined the expression of EST and STS in 35 specimens of human breast carcinoma tissues using immunohistochemistry, reverse transcription-PCR (RT-PCR), and enzymatic assay. EST and STS immunoreactivity was also correlated with various clinicopathological parameters, including prognosis to examine the biological significance of these enzymes in 113 breast carcinomas. EST and STS immunoreactivity was detected in carcinoma cells and significantly associated with their mRNA levels (P = 0.0027 and 0.0158, respectively), as measured by RT/real-time PCR, and enzymatic activities (P = 0.0005 and 0.0089, respectively) in 35 breast carcinomas. In breast cancer tissues examined by laser capture microdissection/RT-PCR analyses, the mRNA for EST was localized in both carcinoma and intratumoral stromal cells, whereas that of STS was detected only in carcinoma cells. Of the 113 invasive ductal carcinomas examined in this study, EST and STS immunoreactivity was detected in 50 and 84 cases (44.2 and 74.3%), respectively. In these cases, EST immunoreactivity was inversely correlated with tumor size (P = 0.003) or lymph node status (P = 0.0027). In contrast, STS immunoreactivity was significantly correlated with tumor size (P = 0.0047). Moreover, EST immunoreactivity was significantly associated with a decreased risk of recurrence or improved prognosis by both uni (P = 0.0044, and 0.0026, respectively) and multivariate (P = 0.0429 and 0.0149, respectively) analyses. STS immunoreactivity, however, was significantly associated with an increased risk of recurrence (P = 0.0118) and worsened prognosis (P = 0.0325) by univariate analysis. Results from our present study suggest that immunoreactivities for both EST and STS are associated with their mRNA level and enzymatic activity and that EST immunoreactivity is considered to be a potent prognostic factor in human breast carcinoma.

Adult↗

Complexed prostate-specific antigen as a staging tool for prostate cancer: a prospective study in 420 men.

Over time, the parameters commonly used to predict pathological stage in men with localized prostate cancer have changed, and there is now little stratification in pretreatment prostate-specific antigen (PSA) concentrations, clinical stages, and biopsy Gleason scores. This prospective study evaluated the utility of complexed PSA (cPSA ) for predicting organ-confined disease in a contemporary series of subjects. The age range of the 420 men was 39 to 72 years (58.2 +/- 6 years). Specimens were collected before radical prostatectomy, and total and free PSA (Hybritech Tandem assays, Beckman Access; Beckman Coulter, Inc., Brea, CA) and total and cPSA (Bayer Immuno 1; Bayer Corporation, Tarrytown, NY) were measured. Pathologic stage was determined from the prostatectomy specimen. Of the 420 men, 316 (75%) had organ-confined disease, and 104 (25%) had non-organ-confined disease (20.7% had extraprostatic extension, 2.6% had seminal vesicle involvement, and 1.4% had positive lymph nodes). Prebiopsy Gleason score distribution was as follows: organ-confined organ-confined, 6 (87%) and 7 (10%); non-organ-confined, 6 (66%) and 7 (30%). Of patients with organ-confined disease, 75% had clinical stage T1c disease compared with 56% for non-organ-confined disease. Using univariate logistic regression, the following variables predicted organ-confined disease: biopsy Gleason score, clinical stage, total PSA, percent free PSA, cPSA, percent cPSA (P <0.05). A multivariate model with biopsy Gleason score, clinical stage, and cPSA had a receiver operator characteristic area under the curve of 0.69. Replacing cPSA with total PSA in this model provided similar information. cPSA and total PSA were highly correlated (r = 0.985). In summary, cPSA was equivalent to total PSA in predicting organ-confined disease. Present and future models and nomograms using PSA as an indicator of pathological stage could consider use of cPSA.

Adult↗

In vivo cell and tissue tropism of SIVsmmPBj14-bcl.3.

To gain insight into the unique pathogenicity of simian immunodeficiency virus (SIV) variant PBj14, which produces an acutely lethal enteropathic syndrome in infected pigtail macaques, we investigated the cell and tissue tropisms of a highly pathogenic biologic clone (bcl.3) of SIVsmmPBj14. To compare the relative amount of viral antigen in lymphoid organs of infected macaques we used an objective semiquantitative immunohistochemistry (sQIHC) assay. We found that in all animals viral antigen load was greater in alimentary-associated lymphoid tissues (gut-associated lymphoid tissue [GALT], tonsil, mesenteric and retropharyngeal lymph nodes) than in non-alimentary-associated lymphoid tissues (spleen, thymus, inguinal and axillary lymph nodes). Moreover, in six of nine animals examined, virus load in GALT was greater than that in any other lymphoid tissue. To determine whether the acute pathogenicity and prolific replication of SIVsmmPBj14 might be explained by a broader in vivo cell tropism than is typical of SIVs, we used cell subset separation and nested PCR. We found that the primary target cells in mesenteric lymph node for SIVsmmPBj14 were CD4+ T lymphocytes. However, the virus also infected macrophages, as well as CD8+ T cells and B cells, albeit at low frequencies. These results suggest that alimentary lymphoid tissue localization rather than unusual cell phenotype tropism distinguishes the singular pathogenesis of SIVsmmPBj14.

Animals↗

Requirements for in vivo IFN-gamma induction by live microfilariae of the parasitic nematode, Brugia malayi.

Lymphatic filariasis caused by the parasitic nematode, Brugia malayi, is a chronic human disease immunologically characterized by stimulation of Th2 cells and reduced antigen-specific T cell responses. Single stage intra-peritoneal infections with infective larvae (L3) or adult nematodes induce Th2 cells, while the microfilarial stage (Mf) stimulates IFN-gamma and Mf-specific IgG1, IgG2a, IgG2b, IgG3 and IgM, but not IgE. To investigate whether IFN-gamma is elicited by live Mf in their natural site of infected, mice were infected intravenously. Intravenous infection had a striking effect on the response to Mf and high levels of IgE were induced even in the presence of IFN-gamma. Indeed IgE levels to Mf increased markedly with the number of immunizations, higher doses of Mf and prolonged exposure to Mf suggesting that under conditions of chronic antigen exposure, typical of human disease, Mf will stimulate high levels of IgE. The ability of Mf-induced IFN-gamma to modulate or regulate a pre-existing Th2 response, was investigated by infecting mice initially with adult male worms to induce a Th2 response, followed 14 days later by infection with Mf. Although Mf stimulated IFN-gamma in the presence of male adults, the antibody isotypes elicited did not reflect IFN-gamma induction and IgG1 and IgE dominated the response. Although it cannot be discounted that IFN-gamma induction by Mf may act locally as an inflammatory mediator or modulator of Th2 cells, these data suggest that Mf-stimulated IFN-gamma does not have a profound effect overall on progression of the Th2-dominated immune response to filarial infection.

Animals↗

A monoclonal antibody to Lewis lung carcinoma variant H-59 identifies a plasma membrane protein with apparent relevance to lymph node adhesion and metastasis.

Tumors H-59 and M-27, two stable metastatic variants of the Lewis lung carcinoma, differ in their ability to disseminate lymphatically. Tumor H-59 metastasizes to the regional lymph nodes regardless of the local site of growth and gives rise to widespread lymphatic dissemination, whereas tumor M-27 disseminates hematogenously without involvement of the regional nodes (P. Brodt, Cancer Res., 46: 2442-2448, 1986). In a previous paper we reported that this divergent potential to disseminate lymphatically correlated well with adhesion to frozen sections of syngeneic lymph nodes and spleens (P. Brodt, Clin. Exp. Metastasis, 7: 343-352, 1989). A monoclonal antibody (12/50) specific for tumor H-59 was subsequently generated. This antibody (an IgG1) but not three control antibodies, which reacted with tumor H-59, significantly reduced tumor cell binding to the frozen sections. Western blot analysis revealed that it recognized a plasma membrane protein of Mr 37,000 on tumor H-59 cells. No antibody binding was detected when solubilized plasma membrane preparations of tumor M-27 were used. Subsequent enzymatic assays indicated that the binding of monoclonal antibody 12/50 was insensitive to cell treatment with exoglycosidases but could be significantly reduced by pretreatment of the tumor cells with Pronase. Together these results suggest that monoclonal antibody 12/50 recognizes a cell surface adhesion protein relevant to lymphatic dissemination of this tumor.

Animals↗

[Ovarian sex cord stromal tumors with annular tubules: a report of 6 cases].

Six patients with ovarian sex cord stromal tumor with annular tubules (SCTAT) were diagnosed and treated from 1968 through 1988, accounting for 6% of a total of 99 cases of ovarian sex cord stromal tumors admitted during the same period. Of these, 3 were operated on for the first time and 3 were recurrent cases referred from other hospitals. The menstrual disturbance was characterized by menometrorrhagia followed by sustained amenorrhea. Glandular atrophy and decidual change of stromal were observed in 3 of the 4 endometrial samples available for histologic examination. Serum hormone assays carried out in 2 cases revealed elevated levels of both estradiol and progesterone. The primary tumor was unilateral in 5 cases and bilateral in one the recurrent tumors were exclusively retroperitoneal and ipsilateral to the primary ovarian tumors. In these cases, lymphatic metastasis was also observed in the ipsilateral pelvic lymph nodes. Complete and sustained remission has been achieved in all 3 patients receiving primary surgery by unilateral salpingo-oophorectomy. After removal of the metastatic tumors in 3 recurrent cases, 2 have survived with residual diseases for 2 and 9 years respectively and one died 4 years after the secondary surgery.

Adolescent↗