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PubMed1982

Gestational trophoblastic disease: treatment results at the Brewer Trophoblastic Disease Center.

Three hundred fifty-nine patients with gestational trophoblastic disease (choriocarcinoma and invasive mole) received complete treatment at the Brewer Trophoblastic Disease Center of Northwestern University Medical School from 1962 through 1978. Data were gathered as of December 31, 1978, to permit a minimum follow-up of 2 years. An overall remission rate of 92% was achieved: 100% (185/185) for nonmetastatic disease and 83% (144/174) for metastatic disease. All 200 patients with invasive mole and 129 of 159 patients (81%) with choriocarcinoma were cured. Chemotherapy was the main form of treatment, with adjuvant surgery and radiation therapy being used in selected patients. Five factors were determined to significantly influence response to treatment in patients with metastatic disease: 1) clinicopathologic diagnosis of choriocarcinoma versus invasive mole (71 versus 100%, P much less than .0005); 2) pretreatment human chorionic gonadotropin titer greater than 100,000 IU/liter and time greater than 4 months from pregnancy event to treatment (62 versus 93%, P much less than .0005); 3) metastases to sites other than lung and/or vagina (37 versus 92%, P much less than .0005); 4) antecedent term gestation compared with hydatidiform mole, abortion, and ectopic pregnancy (56 versus 79%, P less than .02); and 5) prior unsuccessful chemotherapy compared with no previous treatment (48 versus 83%, P much less than .0005). The value of secondary chemotherapy and adjuvant irradiation was evaluated. Relapse from remission was also studied.

Antineoplastic Agents↗

PubMed2004

[Gestational trophoblastic disease, Villous gestational trophoblastic disease].

Gestational trophoblastic disease (GTD) represents a wide range of clinical and pathological distinct entities. The villous forms of GTD includes developmental disorders of the placental tree, like blighted ovum, embryonal, partial and complete moles. The risk of persistent GTD is estimated of 2-14% in partial and up to 50% in complete moles. So, the morphologic differentiation between the different entities of villous forms of GTD is clinical very important. Sometimes, early forms of complete moles (up to 12th weeks of gestation) may represent diagnostic problems, even in the diagnosis of regressive alterations of the placental villous tree after intrauterine retention.

Female↗

PubMed2006

Binding of galectin-1 (gal-1) to the Thomsen-Friedenreich (TF) antigen on trophoblast cells and inhibition of proliferation of trophoblast tumor cells in vitro by gal-1 or an anti-TF antibody.

Galectin-1 (gal-1), a member of the mammalian beta-galactoside-binding proteins, recognizes preferentially Galbeta1-4GlcNAc sequences of several cell surface oligosaccharides. We demonstrate histochemically that the lectin recognizes appropriate glycotopes on the syncytiotrophoblast and extravillous trophoblast layer from second trimester human placenta and on BeWo chorion carcinoma cells. Gal-1 binding to BeWo cells was diminished by the Thomsen-Friedreich (TF)-disaccharide (Galbeta1-3GalNAc-) conjugated to polyacrylamide (TF-PAA). Gal-1 also inhibited BeWo cell proliferation in a concentration-dependent manner. Similar antiproliferative effects were also observed with an anti-TF monoclonal antibody (mAb, A78-G/A7). Therefore, we conclude that ligation of Galbeta1-4GlcNAc and Galbeta1-3GalNAc epitopes on BeWo cells may have regulatory effects on cell proliferation.

Antibodies↗

PubMed2006

Human chorionic gonadotropin expression in human trophoblasts from early placenta: comparative study between villous and extravillous trophoblastic cells.

Human trophoblast differentiates into two pathways: extravillous cytotrophoblasts (EVCT) that invade the uterus wall and villous cytotrophoblasts (VCT) that fuse to form the syncytiotrophoblast (ST) involved in placental exchanges and endocrine function. It is established that hCG is produced and secreted by the ST into the maternal compartment where it plays a key endocrine role and stimulates ST formation in an autocrine manner. Herein, we investigated hCG expression in early placentas by immunohistochemistry using different antibodies. We then compared hCG secretion by primary cultures of VCT and EVCT isolated from the same first trimester human chorionic villi. In situ hCG was immunodetected in EVCT all along their invasive differentiating pathway except in cells near the stromal core of the proximal column. hCG expression was confirmed in vitro by immunocytochemistry and hCG secretion quantified in cell supernatants. Interestingly, whereas hCG secretion increased during VCT differentiation into ST (from 60 to 350UI/L/microg DNA), EVCT secretion remained constant and at a high level during the same culture period (160UI/L/microg DNA). Our data demonstrated that in addition to the ST, invasive EVCT also expressed and secreted high levels of hCG, suggesting a specific paracrine and/or autocrine role for hCG from EVCT origin.

Animals↗

PubMed2001

Altered trophoblastic differentiation and increased trophoblastic invasiveness during delayed development in the short-tailed fruit bat, Carollia perspicillata.

During pregnancy in the short-tailed fruit bat, lengthy post-implantational delays in conceptus development can occur in response to stress in captivity and seasonally in the wild. When comparisons were made between uteri carrying embryos in delay at the primitive streak stage and those growing more rapidly, many differences were noted. During delay the developing chorioallantoic placenta was generally smaller, contained a higher ratio of cytotrophoblast to syncytiotrophoblast, and had been invaded only to a limited extent on its embryonic side by mesoderm. Furthermore, much of the cytotrophoblast appeared relatively undifferentiated, randomly-oriented, linked primarily by primitive junctions, and lacked a basal lamina. In contrast, in placentae serving somite and limb-bud stage embryos, sizeable areas were noted that consisted only of more highly differentiated syncytiotrophoblast perforated by maternal vascular spaces (trophospongium). The first contact of the allantois with the developing placenta was also noted at the somite stage, and this initiated widespread invasion of the placenta by mesenchyme and allantoic blood vessels. Wherever this invasion had occurred, the cytotrophoblast between the mesenchyme and syncytiotrophoblast of the interhaemal barrier consisted of a single, polarized layer of more differentiated cells with an associated basal lamina. Eventually, all of the trophospongium was invaded by cytotrophoblast and vascularized fetal mesenchyme. These observations suggest that in addition to its germinal function, cytotrophoblast in this bat may play a major role in controlling mesenchymal invasion and angiogenesis on the embryonic side of the placenta. During the period of delay, highly invasive trophoblast is also released by the placenta. This invades the myometrium and sometimes extrauterine tissues via interstitial migration along maternal capillaries and veins.

Animals↗

PubMed1987

Antigens of human trophoblast: trophoblast-lymphocyte cross-reactive antigens on platelets.

Human and rabbit antibodies to trophoblast-lymphocyte cross-reactive (TLX) antigens were employed in an enzyme-linked immunosorbent assay (ELISA) to identify and characterize the TLX alloantigen system on human platelets. Neither washing nor extraction in chaotrope or acid altered platelet TLX. The antigen was significantly changed by pronase and trypsin digestion, but Folch extraction yielded antigen in the hydrophilic interface, suggesting carbohydrate. Rabbit antibodies prepared to HLA-negative human syncytiotrophoblast TLX antigens were shown by platelet ELISA to have the same specificity and similar allotypy as anti-TLX antibodies from secondary (2 degrees) spontaneously aborting women. Patients with normal pregnancies before becoming 2 degrees aborters had both IgG and IgM antibodies to TLX. Anti-TLX in patients who never had a normal pregnancy were predominantly IgG. ELISA reactions performed with different concentrations of protein in the buffers detected anti-TLX activity in buffers containing high protein concentrations. This has been observed in studies of blocking antibodies in graft-versus-host disease and immune responses to tumor cells. Platelet TLX offers a new genetic and immunological approach to study similarities of the host-parasite relationships in pregnancy, transplantation, and cancer.

Abortion, Habitual↗

PubMed1988

Synthesis and processing of ovine trophoblast protein-1 and bovine trophoblast protein-1, conceptus secretory proteins involved in the maternal recognition of pregnancy.

Ovine and bovine trophoblast protein-1 (oTP-1 and bTP-1) are newly discovered proteins produced by embryonic tissues for a limited period in early gestation. They appear to act as agents that prevent regression of the corpus luteum during early pregnancy in the ewe and cow. Ovine TP-1 [mol wt (Mr), 17,000] consists of three or four isoelectric variants (pI 5.4-5.7), whereas bTP-1, which cross-reacts with antiserum to oTP-1, is found as two predominant Mr classes (Mr, 22,000 and 24,000), each with several isoelectric variants (in the pI range 6.3-6.8). Cell-free translation of ovine conceptus mRNA yields pre-oTP-1 also consists of three or four isoelectric variants, assumed to have arisen by translation of multiple mRNA species. Ovine TP-1 is not glycosylated. When bovine conceptus mRNA is translated, a group of four or five isoforms of pre-bTP-1 are generated, each with a Mr of 19,000. In the presence of microsomes the Mr shifts upward to about 21,500. Bovine conceptuses cultured in presence of either [3H]glucosamine or [3H]mannose incorporate label into both size classes of bTP-1 (Mr, 22,000 and 24,000). Culture in presence of [35S]methionine and tunicamycin gave rise to a nonglycosylated form of bTP-1 with an apparent Mr of 18,000. Treatment of [35S]methionine-labeled bTP-1 with either endoglycosidase-H or peptide:N-glycosidase F yielded products with Mr of 17,000 and 16,000, respectively. bTP-1, although functionally and structurally related to oTP-1, appears to be a glycoprotein carrying at least two Asn-linked oligosaccharides. The two Mr classes of bTP-1 arise as a result of differences in either the number or structure of the carbohydrate chains. Like oTP-1, bTP-1 is probably translated from multiple mRNA species.

Animals↗

PubMed1987

Metastatic gestational trophoblastic disease: experience at the New England Trophoblastic Disease Center, 1965 to 1985.

This report reviews the results of therapy in 93 patients with metastatic gestational trophoblastic tumor treated from 1965-1985. Complete remission was achieved in all 42 patients with low-risk metastatic disease and in 34 of 51 patients (67%) with high-risk metastatic disease. Single-agent chemotherapy induced complete remission in 38 of 42 patients (91%) with low-risk metastatic disease. Survival of high-risk patients has improved markedly over the past two decades; complete remission was attained in 13 of 24 high-risk patients (54%) from 1965-1975, and in 21 of 27 (78%) from 1976-1985. Survival correlated with the number of high-risk factors, the prognostic score, and the type of treatment. From 1965-1975, 54% (13 of 24) of high-risk patients were treated with single-agent chemotherapy alone, while in the last decade only 7% (two of 27) were so treated. Twenty-one patients with traditional high-risk factors had a prognostic score of 7 or less, and all achieved remission, with 67% (14 of 21) treated with primary single-agent chemotherapy. The prognostic scoring system was more effective than traditional high-risk criteria at predicting which patients require intensive combination chemotherapy to attain remission.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

The trophoblastic Tower of Babel: classification systems for metastatic gestational trophoblastic neoplasia.

There are presently three classifications of metastatic gestational trophoblastic tumors (MGTM). The first is that of low-risk and high-risk neoplasia devised by Hammond, now designated the National Cancer Institute classification. The second is that of FIGO that attempts to conform to the staging of other gynecologic malignancies by that organization. The third is a scoring system adopted by World Health Organization (WHO) from the original devised by Bagshawe. This scoring system is finding the widest acceptance and is increasingly being used for treatment planning. However, different investigators not only define risk groups differently from the WHO recommendation, but also modify the WHO scoring system in novel, individualistic ways that changes the total score and outcome assessment. This results in patients with the same risk factors being placed in different WHO risk groups. Comparison of therapy between center is then invalidated. Furthermore, it would appear preferable that the WHO scoring system is restricted to metastatic neoplasia. To achieve a uniform scoring system for MGTN there needs to be consensus (i) whether lung metastases should be detected by chest X ray or CAT scan; (ii) whether the size of metastases should be measured clinically or radiologically (including ultrasound, CAT scan, and MRI); (iii) are multiple lung or brain metastases counted by CAT scan or MRI; (iv) are ABO blood groups to be included so that the number of points is uniform for different centers; and (v) that idiosyncratic and individual categories are not added or omitted from the score.

Aged↗

PubMed1990

The production, purification, and bioactivity of recombinant bovine trophoblast protein-1 (bovine trophoblast interferon).

Bovine trophoblast protein-1 (bTP-1) is a 172-amino acid interferon- alpha that has a role in maternal recognition of pregnancy in cattle. Here we describe production of bTP-1 by recombinant procedures in Escherichia coli. A bTP-1 gene was constructed which lacked the codons representing the signal sequence and provided a Met initiation codon ahead of the TGT codon encoding Cys1 of the mature protein. This construct was placed under the control of the Trp promoter within the expression vector pTrp2. Expression occurred optimally in E. coli D112 in the absence of tryptophan and in the presence of 0.5% acid-hydrolyzed casein (casamino acids) when 0.5 mM indole acetic acid was included in the medium. The bTP-1 was deposited in inclusion bodies and accounted for as much as 27% of the total cellular protein. The inclusion bodies were isolated by differential centrifugation and washed. The bTP-1 was solubilized by use of guanidinium-HCI and 2-mercaptoethanol and allowed to renature in air. Final purification was achieved by anion exchange chromatography on DEAE-cellulose. The yield of purified product, which had an antiviral activity greater than 10(8) international reference units/mg, was approximately 20 mg/liter. The recombinant bTP-1 was relatively stable to freeze-thawing and frozen storage, and could induce the production of an acidic protein of 70,000 mol wt in cultured explants of endometrium prepared from ewes on day 13 of the estrous cycle. The latter protein is a characteristic product of interferon-alpha action on uterine tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Identification of bovine trophoblast protein-1, a secretory protein immunologically related to ovine trophoblast protein-1.

This paper demonstrates that a group of proteins, representing a major secretory component of cattle conceptuses, is immunologically related to ovine trophoblast protein-1 (oTP-1), a principal product of culture Day 13 to 21 sheep conceptuses. Conceptuses from cows (Day 17-18) and ewes (Day 16-17) were cultured for 24 h in the presence of L-[3H]leucine. By using a rabbit antiserum to oTP-1 and Ouchterlony double-immunodiffusion analysis it was shown that material in the bovine conceptus culture medium was serologically related, but not identical, to oTP-1. A solid-phase radiobinding assay indicated that the cross-reacting bovine secretory component had an affinity for anti-oTP-1 antibody similar to that of oTP-1. Anti-oTP-1 antiserum specifically immunoprecipitated a group of 6-8 polypeptides from culture medium of cow conceptuses which, when analysed by two-dimensional gel electrophoresis, fell into two major molecular weight classes (22,000 and 24,000) with isoelectric points between 6.5 and 6.7. These immunoprecipitated polypeptides, defined as bTP-1, constituted the major secretory products of Day 16-25 cow conceptuses. They were larger and more basic than oTP-1 polypeptides (Mr about 18,000; pI 5.4-5.7). Anti-oTP-1 antiserum also recognized the major translation product of Day 17 bovine conceptus mRNA, a polypeptide significantly smaller (Mr approximately 18,000) than the secreted protein. It is suggested that oTP-1 and the homologous bovine protein may play similar roles in the phenomenon of maternal recognition of pregnancy in the two species.

Animals↗

PubMed1979