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Biomedical subjects

H Biran

Publications and source records attributed to H Biran.

At least 19 recordsLinked to original sources
PubMed1995

H19 expression and tumorigenicity of choriocarcinoma derived cell lines.

Certain embryonal tumors demonstrate a loss of heterozygosity at the parentally imprinted region of chromosome 11p15.5. It has been hypothesized that this implicates a tumor suppressor gene at this locus. The human H19 gene maps to 11p15.5, is expressed in fetal tissues including the placenta and is paternally imprinted. Here we show that the abundance of H19 transcripts in cells of two choriocarcinoma derived cell lines (JAr and JEG-3) differs greatly. While JAr cells express high levels of H19 RNA, the expression of H19 in JEG-3 cells is much lower than that of normal trophoblasts. Cells of these two cell lines were subcutaneously injected into nude mice with subsequent tumor formation. A fivefold increase in the H19 RNA level was measured in tumors derived from JEG-3 cell lines as compared to these cells before injection. However this increase in H19 RNA did not alter the clonogenicity in soft agar nor the growth rate of the cells derived from these tumors as compared to the original JEG-3 cells. Nevertheless, the cells retaining the elevated level of H19 transcripts were more tumorigenic than the original cells. We propose that there is a selection of cells expressing high levels of H19 from the total JEG-3 cell population during the microevolution of tumor formation. These observations, together with our previous publications on H19 expression in human cancers, do not support the notion of a tumor suppressor role for the H19 gene.

Animals↗
PubMed1995

Plasma platinum elimination in a hemodialysis patient treated with cisplatin.

The pharmacokinetics of intravenously administrated cisplatin (CDDP) were studied in a patient with meduloblastoma receiving regular hemodialysis for chronic renal failure. The patient received four CDDP infusions of 25 mg/m2 in two courses and underwent hemodialysis before each treatment and in intervals of 48 h thereafter with blood sampling at the beginning and the end of each hemodialysis. The data obtained were compared with the pharmacokinetic data from follow-up studies of 19 CDDP treatments in 15 patients suffering from various malignancies with no renal failure where a biexponential pharmacokinetic curve was recorded. The data of platinum (Pt) elimination of the patient receiving hemodialysis resembled the curve of those who had not, but following the second CDDP treatment in each course the peak Pt level in plasma was doubled, with a somewhat slower rate of elimination.

Adult↗
PubMed1994

Successful resolution of persistent trophoblastic disease after partial mole with the EMA-CO regimen.

A 29-year-old nullipara with partial hydatidiform mole at 8 weeks had pre-evacuation hCG levels of 275,000 mIU/ml. Free beta-hCG levels were measured as 3% (normal value below 4%). The patient developed persistent gestational trophoblastic disease, failed to respond to methotrexate and actinomycin D, but has responded to combination chemotherapy with EMA-CO. Such a response to EMA-CO was not reported previously.

Adult↗
PubMed1994

The radiographic diagnosis and treatment of paraneoplastic central nervous system disease.

Paraneoplastic nervous system syndromes are being identified with increasing frequency because of greater physician awareness and the availability of serodiagnostic tests for some syndromes. Frequently, paraneoplastic syndromes develop in the setting of an indolent, limited stage, or otherwise occult malignancy. As a result, the paraneoplastic disorder often becomes the most disabling part of a patient's disease. Effective treatment appears to require early identification. For these reasons, the ability to diagnose a paraneoplastic syndrome, follow its course, and treat it successfully are important. The authors describe four patients with neurologic paraneoplastic syndromes and identical magnetic resonance imaging abnormalities. Three patients responded to immunosuppressive or immunomodulatory therapy, and in one, corresponding radiographic improvement was documented. Strategies for early diagnosis and options for treatment of paraneoplastic nervous system disorders are discussed.

Aged↗
PubMed1994

Relaxation of imprinting in trophoblastic disease.

Genomic imprinting--the uniparental-dependent transmittance of a genetic trait--has been accepted in recent years as a major mechanism in mammalian genetics. We studied the expression of the H19 gene, a parentally imprinted (maternally expressed) gene, by in situ hybridization in human placenta and trophoblastic disease. Expression was found to be abundant, in a decreasing order, in the intermediate trophoblast (villous and interstitial), the cytotrophoblast, and the syncytiotrophoblast. The villous stroma was also prominently labeled. Partial hydatidiform mole showed a similar pattern of expression as normal placenta. As expected, complete hydatidiform mole, whose genome consists of two haploid sets of paternal origin, was not labeled in the villous stroma and surrounding trophoblastic layer. However, some of the large mononuclear cells in the proliferating groups sprouting from the villous surface were strongly labeled. Prominent expression of H19 was found in placental site trophoblastic tumor and gestational choriocarcinoma. The phenomenon of emergence of expression of alleles subject to repression according to their gamete of origin is termed relaxation of imprinting, and is considered to be relevant to tumorigenesis. We suggest that the expression of the maternally expressed H19 gene in the androgenetic tissue of complete hydatidiform mole represents relaxation of imprinting and may be associated with its malignant potential.

Choriocarcinoma↗
PubMed1994

On the oncodevelopmental role of human imprinted genes.

Genome imprinting has an essential role in normal embryonal mammalian development. Starting early in differentiation, the transcripts of certain human genes, e.g. the paternally-H19 and the maternally-imprinted IGF2, are expressed in specific tissues and organs during fetal life. In several malignant disorders, imprinted genes are, again, unfolded. Characteristically, expression follows the same tissue presentation as during embryogenesis. Clinical paternal disomies, i.e. trophoblastic diseases, and their maternal counterpart, i.e. ovarian teratomas, are associated with apparent relaxation of imprinting once they turn malignant. Paediatric neoplasms, like Wilm's tumor (WT) and rhabdomyosarcoma, often express IGF2 and H19. Recently, we have found H19 expression in invasive urothelial cancer. Evidently, imprinted genes display an oncodevelopmental mode of expression, very much like the classical oncofetal proteins AFP and CEA. Based on available data, including tumor preferential paternal allele retention and chromosome 11 short arm physical linkage with oncogenes like H-ras, we hypothesize that imprinted genes not only accompany cancer but may play a causative role as well.

Antigens, Neoplasm↗
PubMed1994

Human imprinted genes as oncodevelopmental markers.

Imprinted genes mediate unique maternal or paternal genetic roles and their function is essential in prenatal development. The reciprocally imprinted human insulin-like growth factor 2 (IGF2) and H19 genes are expressed during embryonal life, also in the placenta, and are downregulated postnatally. They reexpress in pediatric tumors (e.g. Wilms' tumor) and in inborn developmental syndromes predisposing to such tumors (e.g., Beckwith-Wiedemann syndrome). H19 (RNA transcripts) and IGF2 are manifested in Wilms' tumor, rhabdomyosarcoma, immature ovarian teratoma and gestational trophoblastic diseases. We have found that in the placenta and in urothelial carcinoma, H19 expression reflects the degree of invasiveness. These genes, displaying a tissue-specific oncofetal pattern of expression, are, therefore, tumor markers.

Beckwith-Wiedemann Syndrome↗
PubMed1992

Pneumothorax following induction chemotherapy in patients with lung metastases: a case report and literature review.

A 29-year-old patient presented with bilateral pulmonary lesions following surgery for recurrent placental site trophoblastic tumor (PSTT). On day seven after institution of the 'EMA' regimen (etoposide, medium dose methotrexate with folinic acid rescue and actinomycin-D), complete pneumothorax occurred. Closed-system air drainage brought only transient lung expansion and subsequent talc pleurodesis was needed. During follow-up, complete regression of lung metastases was observed. A literature survey of post-chemotherapy pneumothorax in patients with lung metastases disclosed fourteen hitherto reported cases. Including the present PSTT case, non-epithelial gynecologic malignancy (3 patients) ranks second to osteogenic sarcoma (6 cases) with regard to the primary tumor involved.

Adult↗
PubMed1991

Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer.

The serum and cerebrospinal fluid (CSF) of 8 women with ataxia, 6 of whom also had eye movement abnormalities believed to be opsoclonus, were found to contain a highly specific antineuronal antibody we call anti-Ri. Seven of the 8 women also had or developed cancer: carcinoma of the breast in 5, adenocarcinoma in an axillary lymph node in 1, and carcinoma of the fallopian tube in 1. Four patients presented with the neurological disorder; the cancer was diagnosed first in the other 4. Immunohistochemical studies using serum or CSF from all 8 patients revealed a highly specific antibody interaction with central nervous system neuronal nuclei but not with glial or other cells; the titer ranged from 1:5,000 to 1:320,000 in serum and from 1:2,000 to 1:16,000 in CSF. Biotinylated IgG from the patients' serum reacted with the tumors of 3 of 4 patients with anti-Ri antibody but not with breast cancers from patients without anti-Ri antibody. Immunoblots against cerebral cortex neuronal extracts identified protein antigens of 55-kd and 80-kd relative molecular mass. Serum titers by immunoblot ranged from 1:500 to more than 1:40,000 and CSF titers, from 1:10 to 1:2,000. The relative amount of anti-Ri was always higher in CSF than in serum. The antibody was not present in sera from normal individuals; patients with breast cancer without opsoclonus; other patients with opsoclonus; or patients with other paraneoplastic syndromes related to breast, ovarian, or small-cell lung cancer. We conclude that the presence of anti-Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders (opsoclonus) who usually suffer from breast or other gynecological cancer; the antibody when present is a useful marker for an underlying malignancy.

Aged↗
PubMed1991

Circulating arginine-vasopressin, calcitonin, carcinoembryonic antigen, neuron-specific enolase, and beta-2 microglobulin fluctuations during combined modality induction therapy for small-cell bronchogenic carcinoma. Association of postchemotherapy AVP surge with high tumor response rate and durable remission.

While on combined modality induction therapy, 88 small-cell lung cancer (SCLC) patients were studied longitudinally for changes in circulating tumor-associated substances (TAS). Chemotherapy protocols were CAV (cyclophosphamide, doxorubicin, vincristine), PE (cisplatin, etoposide), sequential CAV greater than PE and alternate CAV/PE. Sixty patients were given prophylactic cranial irradiation (PCI) and 40 remitting patients were irradiated to the primary thoracic tumor. Of 73 evaluable patients, 43 had blood sampling adequate for analysis of treatment-related TAS fluctuations. Fourteen patients demonstrated 16 events of transient arginine-vasopressin surge following chemotherapy. In decreasing order of frequency, the surge occurred after the first (9), second (6) and third (1 event) course of chemotherapy. Three patients had a concomitant increase of one of the following markers: carcinoembryonic antigen (CEA), calcitonin and neuron-specific enolase. Another patient showed an exclusive CEA surge. This group of patients (10 with limited, 4 with extensive disease) had a 93% objective response rate (57% complete, 36% partial) with a median duration of 9 months and a survival of 15 months. Five other patients, 2 with limited and 3 with extensive disease, showed a TAS surge after PCI. Their response was complete in 1 (8 months' duration) and partial in 3 cases (2, 4 and 4 months' duration, respectively) with a median survival lasting only 8 months. This study suggests that a chemotherapy-related TAS surge may be an early indicator of a favorable tumor response in SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Carcinoembryonic antigen, arginine vasopressin and calcitonin as markers of early small-cell lung cancer relapse.

Patients with small-cell lung cancer (SCLC) underwent serial blood monitoring during remission: 66 were tested for carcinoembryonic antigen (CEA) and calcitonin (CTN), including 40 who were concomitantly tested for arginine vasopression (AVP) as well. 83% of the patients had at least one assay elevated prior to induction therapy. By serial monitoring, blood concentrations reflected disease course and reached lowest levels at remission. CEA, AVP and CTN shifted along the course of disease independently of each other; a normal pretreatment titer did not preclude its rise at a later phase, while an initially elevated assay could normalize at remission and stay normal thereafter. The median lead time (LT) to clinically diagnosed relapse, for limited-disease patients, was 229 days for complete and 90 days for partial remitters. Patients with extensive disease had similar LT values. LT to local recurrence was shorter than to distant relapse. Remission AVP titers of up to 6 ng/ml conferred disease-free survival (DFS) longer than that associated with higher titers (median DFS 518 vs. 211 days, respectively; p = 0.045 for curve differences). The relative risk (RR) of relapse associated with pretreatment patient characteristics and with absence or presence of tumor marker normalization at remission was estimated by the Cox proportional hazards model. This analysis revealed that the RR of relapse conferred by pretreatment attributes, e.g. disease extent, was considerably modified by biochemical co-variates at remission, e.g. serum CEA level relative to a 3 ng/ml cutoff point.

Arginine Vasopressin↗
PubMed1989

5-Fluorouracil, doxorubicin (adriamycin) and mitomycin-C (FAM) in advanced gastric cancer: observations on response, patient characteristics, myelosuppression and delivered dosage.

Forty-four patients with advanced gastric adenocarcinoma were treated with the fluorouracil, adriamycin and mitomycin-C (FAM) regimen. One was excluded from response evaluation. Partial (PR) and minor (MR) response rates were 7 and 9% respectively. These patients enjoyed remission for a median of 7.0 months. Stabilization (S) occurred in 25% and lasted a median of 6.0 months. No response (NR) was associated with a median survival of 3 months (p less than 0.001). The predominant pretreatment factors to affect survival were diagnosis to treatment interval and initial CEA serum level. Performance status influenced survival less markedly. Toxicity was mainly myelosuppression, which resulted in death of one patient. 'Responders' had marrow suppression more frequently than NR. Comparison of PR + MR, PR + MR + S and NR patient groups showed median minimum WBC counts of 1.4 x 10(3), 2.6 x 10(3) and 4.3 x 10(3) per mm3 respectively. Leukopenia (less than 3,000/mm3) was associated with a median survival advantage of 9.5 versus 3.5 months (p less than 0.05) and did not depend significantly on given FAM dosage. The median dosage of FAM agents delivered to nonresponders was reduced. A trend of dose-response (including dose-survival) relationship was found but was inconclusive statistically.

Adult↗
PubMed1988

Exposure of cryptantigens on erythrocytes in patients with breast cancer.

One hundred thirty-two patients with breast cancer were examined for exposure of cryptantigens on their erythrocytes (RBC) using a lectin panel consisting of Arachis hypogaea and Glycine soja. Eight had exposed cryptantigens; of the eight, five were classified with additional lectins as T-polyagglutination type and three as Th-polyagglutination. A control group of 300 healthy blood donors had no exposed cryptantigens on their RBC. These findings could not be correlated with the staging of the tumor, extension of metastases, or positive estrogen or progesterone receptors of malignant tumor cells. Only one study has been found that describes the incidence of agglutination of erythrocytes from cancer patients using a monoclonal antibody, which detected an epitope on the RBC from cancer patients and was considered to be distinct from the antigen bound by naturally occurring anti-T. Studies have been made describing polyagglutinable sites on breast cancer tumor cells, where there was a much higher incidence. This discrepancy can be explained either by a difference in the methods used to search for cryptantigen exposure on the various types of cells, or by the existence of a different mechanism, which causes the exposure of cryptantigens on RBC as opposed to malignant breast tumor cells.

Adult↗
PubMed1987

Selective right ventricular dysfunction following doxorubicin therapy.

Cardiotoxicity is one of the major side effects of doxorubicin therapy. The side effect presents in an acute and chronic form. It has been observed mainly when the cumulative dosage exceeds 450 mg/m2 of body surface. The cardiotoxicity presents with a low left ventricular ejection fraction. We report three patients who developed selective right ventricular dysfunction, expressed by low right ventricular ejection fraction as measured by radionuclide angiography. This complication was observed with rather low cumulative dosages of the drug (105 to 318 mg/m2). Two of the patients received concurrent mitomycin-C chemotherapy and the third patient underwent prior mediastinal irradiation. The possible mechanism for this selective cardiotoxicity is discussed. Monitoring of right ventricular performance by radionuclide angiography during doxorubicin therapy is recommended so that therapy can be discontinued before the left ventricle is damaged.

Adult↗
PubMed1986

Serum amyloid A (SAA) variations in patients with cancer: correlation with disease activity, stage, primary site, and prognosis.

Serum amyloid A (SAA) was determined in 160 patients with cancer. Active disease was associated with high titre compared with the titre in non-active condition (31.8 v 5.8 micrograms/ml, respectively; p = 0.0002). SAA value showed a direct correlation with the stage of the disease: it was lowest at stages 1 and 2 and highest at the metastatic stage 4 (stage 1 v 4, p = 0.001; stage 2 v 3, p = 0.05). Cancers of the lung and unknown primary site were characterised by highly increased SAA concentration. Initial SAA value had prognostic significance: a value below 10 micrograms/ml correlated with survival advantage, whereas a higher initial value indicated a greater likelihood of a poor outcome (actuarial survival analysis p less than 0.001). When stage was accounted for, initial SAA value had significant prognostic bearing on survival of patients with advanced disease (stages 3 and 4) but not on that of patients with limited disease (stages 1 and 2). Serial testing showed good concordance between changes in SAA titre and clinical course.

Amyloid↗