Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

131I is the radionuclide most commonly used in biologically targeted radiotherapy at the present time. Microdosimetric analysis has shown that microtumors whose diameters are less than the beta-particle maximum range absorb radiation energy inefficiently from targeted radionuclides. Micrometastases of diameters < 1 mm are likely to be spared if targeted 131I is used as a single modality. Because of this, combined modality therapy incorporating targeted 131I, external beam total-body irradiation (TBI), and bone marrow rescue has been proposed. In this study, the minimum necessary TBI component is shown to depend on the radiosensitivity of the tumor cells. The analysis shows that the TBI component, to achieve radiocurability, increases directly with tumor radioresistance. For the most radiosensitive tumors, a whole-body TBI treatment dose 2 x 2 Gy is calculated to be obligatory, whereas practical arguments exist in favor of higher doses. For more radioresistant tumors, the analysis implies that a TBI treatment delivery of 5 x 2 Gy is obligatory. In all situations, external beam TBI appears to be an essential factor in providing reasonable probability of cure of disseminated malignant disease. Reasonable prospects of tumor cure by combination strategies incorporating 131I exist for the more radiosensitive tumor types (e.g., neuroblastoma, lymphoma, leukemia, myeloma, seminoma), but more resistant tumors are unlikely to be curable at present. Superior targeting agents, and the possible use of panels of different radionuclides, may be necessary to achieve high cure probabilities for less radiosensitive tumor types.
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PMID:Optimum combination of targeted 131I therapy and total-body irradiation for treatment of disseminated tumors of differing radiosensitivity. 128 26

The production and detailed immunostaining properties of a new rat monoclonal antibody (ICR.2) to epithelial membrane antigen are reported. The antibody was selected for its ability to compete with the polyclonal antiserum (M7), used in the original immunohistological studies, in order that it might serve as a direct replacement in diagnosing epithelial tumours. Most of the staining reactions on normal tissues were identical to those previously reported with M7 but there were some important differences. They included: positivity of renal and adrenal capsular fibroblasts, perineurium, some myoepithelial and smooth muscle cells, occasional osteoblasts and squamous and thyroid follicular epithelium in the normal state. The intercellular canaliculi of sweat glands and secretory canaliculi of gastric oxyntic cells were clearly demonstrated. These staining reactions could be obtained with M7 when a sensitive detection system was used although the results were usually weak and inconsistent. Nearly all adenosquamous and transitional carcinomas were positive. The remaining tumours fell into three major groups: (1) those which were consistently or nearly consistently negative--melanoma, seminoma, rhabdomyosarcoma, alveolar soft part sarcoma, adrenal cortical carcinoma, granulocytic sarcoma, paraganglioma, non-Hodgkin's lymphoma. Hodgkin's disease and embryonal carcinoma: (2) those which were either negative or positive with distinctive patterns of staining--basal cell carcinoma, embryonal tumours: and (3) non-epithelial tumours that were consistently positive--epithelioid sarcoma, synovial sarcoma, osteosarcoma, chordoma and myeloma--or positive in a significant minority of cases--leiomyosarcoma, malignant fibrous histiocytoma, clear cell sarcoma of tendon sheath, various neuroectodermal tumours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detailed investigation of the diagnostic value in tumour histopathology of ICR.2, a new monoclonal antibody to epithelial membrane antigen. 169 88

Traditional treatment for testicular seminoma produces excellent survival. We report five, second non-testicular malignancies which occurred in a group of seminoma patients. A total of 79 men with primary testicular seminoma were available for analysis. All underwent a radical inguinal orchiectomy. Those with Stage I disease received adjuvant radiation therapy to the para-aortic and ipsilateral iliac nodes. The usual dose was 2500 cGy in 15 treatments. Stage II patients also received prophylactic mediastinal radiation therapy to a dose of 2500 cGy. None of the 51 Stage II patients died of tumour, whereas four of the 28 Stage II patients died of their disease. The median follow-up was ten years (range 4-25 years). The second malignancies seen were melanoma (2), myeloma, caecal adenocarcinoma, and retroperitoneal fibrosarcoma. All but one tumour developed within the radiation fields. Based on US SEER data for white males, only 1.5 cancers were expected, giving significantly greater (P = 0.04) relative risk. This observation lends support to observation, rather than elective treatment, in patients with Stage I testicular cancer.
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PMID:Second malignancies following radiotherapy for testicular seminoma. 226 27

A monoclonal anti-testicular carcinoma antibody was obtained via the somatic cell fusion technique by immunization of BALB/c mice with freshly prepared single cell suspension from a patient with testicular embryonal carcinoma with choriocarcinoma components. The hybridoma supernates were screened against the testicular carcinoma cells used in the immunization as well as normal mononuclear white blood cells isolated from the same patient. An antibody (5F9) was selected which bound to fresh tumor cells from two patients with embryonal testicular carcinoma and failed to bind to fresh tumor cells from 24 patients (2 seminoma, 2 melanoma, 3 neck, 2 esophageal, 1 ovarian, 3 colon, 1 prostate, 2 breast, 1 liposarcoma, 3 endometrial, 1 kidney, 1 adrenal, 1 larynx and 1 bladder tumors) or cell suspensions prepared from normal liver, lung, spleen, ovary, testes, kidney, red blood cells or white blood cells. The antibody was tested for its binding to several well established cancer cell lines, and was found to bind to the BeWo human choriocarcinoma and two human embryonal carcinoma cell lines. The antibody did not react with 22 other cell lines or with hCG. The antibody was labeled with 131I and injected into nude mice bearing BeWo tumors and evaluated for tumor localization by performing whole body scans with a gamma camera 5 days later. Six mice injected with the antibody showed positive tumor localization without the need for background subtraction while six mice injected with MOPC-21, a murine myeloma immunoglobulin, demonstrated much less tumor localization. Tissue distribution studies performed after scanning showed specific tumor localization (8:1 tumor: muscle) for the monoclonal antibody and no specific localization for MOPC-21. This antibody thus has selective reactivity with the surface of tumor cells from embryonal carcinoma (testicle) and choriocarcinoma both in vitro and in vivo.
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PMID:Development and characterization of a monoclonal antibody to human embryonal carcinoma. 303 38

Fifty-seven patients with advanced malignant tumours were treated with ifosfamide (Holoxan) and mesna (Uromitexan) in our department from November 1979 to December 1984. This series comprised eight cases of soft tissue sarcoma, nine cases of ovarian carcinoma, five cases of non-seminomatous testicular tumour, 11 cases of bronchogenic carcinoma, three cases of renal carcinoma, seven cases of non-Hodgkin's lymphoma, two cases of skeletal fibrosarcoma, two cases of breast carcinoma, one case each of Ewing's tumour, prostatic carcinoma, seminoma, plasma cell tumour, multiple myeloma, malignant teratoma, nasopharyngeal carcinoma, Wilms's tumour, neuroblastoma and mycosis fungoides. Out of these 57 cases, 53 were evaluable. There were five complete remissions and 20 partial remissions, corresponding to a total response rate of 47%. The overall median survival time (MST) of the 53 evaluable patients was 7.5 months. The responders had a longer survival time (MST 10 months) than the non-responders (MST 4.75 months) (p greater than 0.05). Analysis of the results according to sex, age, dosage of ifosfamide and degree of histological differentiation of the tumour cells failed to show any influence of these factors on the therapeutic results. The response rate to ifosfamide found in this study might be related to the histological origin of the tumours and to whether the primary tumours had been resected. The non-seminomatous testicular tumours, non-Hodgkin's lymphomas and ovarian carcinomas showed a high response rate. The response rate was higher in the group in which the primary tumour had been resected (61%) than in the non-resected group (12%) (except the non-Hodgkin's lymphoma). The side-effects of this regimen were moderate. Dyspepsia, nausea, vomiting, myelodepression, dizziness, and alopecia were common. Cystitis could be prevented nearly completely by concomitant administration of mesna, when given correctly, for preventing side-effects of ifosfamide on the urinary system (haemorrhagic cystitis, etc.).
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PMID:Treatment of advanced malignancies with ifosfamide under protection with mesna. 313 Mar 16

Neoplastic disease arose in 29 of 200 patients infected with human T lymphotropic virus type III (HTLV-III) seen at a suburban hospital. Seventeen patients had Kaposi's sarcoma, one of whom also had colon carcinoma. Nine patients had lymphoproliferative disorders (seven lymphomas, one T suppressor cell chronic lymphocytic leukemia, and one multiple myeloma), including three with concomitant Kaposi's sarcoma and one with colon cancer. One other patient had colon cancer, one had a seminoma, and one had pancreatic cancer. Kaposi's sarcoma as a complication of AIDS occurred mainly in homosexuals (17 of 42 homosexuals, one of 17 drug abusers, one of five heterosexually promiscuous patients, and one of six patients who had previously received transfusions). The high-grade lymphomas did not show a predilection for any particular AIDS risk group. Three of four solid tumors arose in elderly AIDS patients. Twenty-five of 75 patients with CDC-defined AIDS had a neoplastic disorder (26 are still alive and may yet demonstrate malignancy). Few other diseases of man have been associated with as high an incidence of neoplastic transformation as occurs with HTLV-III infection.
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PMID:Neoplastic complications of HTLV-III infection. Lymphomas and solid tumors. 349 90

Human vascular endothelial cells were isolated by collagenase digestion of umbilical veins. Hybridomas secreting monoclonal antibodies were raised by fusing a mouse myeloma cell line to spleen cells from mice immunized with the isolated endothelial cells. A clone was selected which produced an antibody binding strongly to human umbilical vein endothelial cells. This antibody, EN 3, was shown to be directed against a major antigen on the surface of the cells, and appeared to be distinct from other antigens previously described on vascular tissues. The antibody bound to a lesser extent to umbilical artery endothelial cells and syncytiotrophoblast. Capillary endothelial cells in adult oesophageal tissues and tonsil were also labelled by the antibody, as were capillaries in a seminoma and infiltrating duct carcinoma of the breast. This well defined distribution in some foetal, adult and malignant tissues suggests that there is structural heterogeneity amongst endothelial cells in different sites, which may be linked to differences in differentiation or function.
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PMID:A vascular endothelial cell antigen with restricted distribution in human foetal, adult and malignant tissues. 684 Aug 5

We report the cases of six men, 40 to 89 years of age, with testicular (6 cases) or epididymal (1 case) plasmacytoma. Patients presented with a mass in five cases. One tumor was found during evaluation of progressive myeloma. In the final case, the testicular lesion was identified when the patient presented with pathologic fractures. Gross inspection revealed discrete or, less often, ill-defined lesions. Microscopic examination disclosed masses of atypical plasma cells, including binucleated and multinucleated cells and, occasionally, anaplastic cells that obliterated the underlying parenchyma or invaded between seminiferous or epididymal tubules. Immunohistochemical stains on paraffin sections in five cases showed tumor cell expression of monotypic cytoplasmic immunoglobulin. The cells were positive for the leukocyte common antigen (CD45) in three of five cases. All four cases tested were negative for B (CD20) and T (CD3) cell specific antigens and for CD30 and placental alkaline phosphatase. Expression of CD43, CD45RO, and epithelial membrane antigen was found in three, two, and one of four cases respectively. All the patients also had plasma cell neoplasia distant from the testis, identified before (3 cases), concurrent with (3 cases) or after (1 case) the testicular or epididymal plasmacytoma. In one patient a plasmacytoma developed in the contralateral testis three years later; he was alive with plasma cell myeloma 51 months after diagnosis. Another had a plasmacytoma in the contralateral epididymis 8 years later; he also had a nasal cavity plasmacytoma and multiple subcutaneous plasmacytomas, and was alive and well after 26 years. One additional patient was alive with myeloma 6 months later, and four final patients died between 2 months and 3 years after orchiectomy. Three of the four consultation cases in this series were submitted with diagnoses of spermatocytic seminoma, anaplastic seminoma and lymphoma. The diagnosis of plasmacytoma should be borne in mind when examining testicular or paratesticular tumors with a diffuse pattern without glandular differentiation, particularly in men 40 years of age or older.
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PMID:Testicular and epididymal plasmacytoma: a report of 7 cases, including three that were the initial manifestation of plasma cell myeloma. 915 85

Although circulating hematopoietic progenitor cells (HPCs) are frequently used in therapeutic approaches, many aspects of their cellular biochemistry are still unclear. In the present study, the effects of cyclic nucleotide-elevating agents on HPC proliferation and differentiation were investigated. HPCs from different sources, including healthy persons, patients with tumors (medulloblastoma, seminoma, or multiple myeloma), and patients with chronic myelocytic leukemia (CML), were compared. HPCs were isolated by standard leukapheresis procedures and analyzed for proliferation and differentiation into the megakaryocytic and granulocytic lineages. HPCs contained high concentrations of cyclic guanosine monophosphate (cGMP)-dependent and cyclic adenosine monophosphate (cAMP)-dependent protein kinases G and A (PKG and PKA, respectively). Whereas PKG was partly down-regulated during culture, the PKA level remained constant. Stimulation of PKG in HPCs isolated from healthy donors or tumor patients resulted in a biphasic reaction: low cGMP concentrations inhibited proliferation and stimulated differentiation into megakaryocytes, whereas high concentrations revealed the opposite effect. In contrast, differentiation into granulocytes was inhibited in a concentration-dependent manner. Stimulation of PKA inhibited HPC differentiation; however, HPC proliferation was inhibited in controls and stimulated in HPCs from tumor patients. HPCs isolated from CML patients showed a nonhomogeneous reaction pattern to both cyclic nucleotides with high variability between the individual donors. We demonstrated the importance of the source of HPCs for the investigation of proliferation and differentiation. Cyclic nucleotide-regulated pathways are clearly involved in HPC proliferation and differentiation. Pharmacological strategies using cyclic nucleotide-elevating substances to influence HPC growth and differentiation in the bone marrow might support current strategies in HPC recovery from the peripheral blood.
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PMID:Cyclic nucleotide-regulated proliferation and differentiation vary in human hematopoietic progenitor cells derived from healthy persons, tumor patients, and chronic myelocytic leukemia patients. 1820 72

Lymphoglandular bodies (LGBs) have been described as cytoplasmic fragments of lymphocytes and a specific feature of organized lymphoid tissue. The recognition of LGBs is useful in distinguishing malignant lymphomas from carcinomas and sarcomas in cytology specimens, especially in Giemsa-stained tissues. So far, there has been no description of LGBs in hematoxylin and eosin (HE)-stained histologic specimens in the literature. Therefore, we evaluated LGBs in HE sections, especially regarding malignant tumors. We reviewed 110 biopsy and surgical materials including malignant lymphoma, carcinoma, and other malignant tumors and evaluated the frequency, number, size, and significance of LGBs. We also performed the terminal deoxyribosyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method on LGBs. Lymphoglandular bodies were found in about 40% of cases with malignant lymphoma, whereas only 3 (3.8%) nonlymphoma cases showed LGBs. These were undifferentiated carcinoma, seminoma, and multiple myeloma. The size of LGBs was usually less than half the size of a red blood cell. No apoptotic cells were detected in any of the cases by TUNEL method regarding LGBs. Our study suggests that LGBs can be found in HE sections. As observed in cytologic specimens in the literature, the presence of LGBs around cytologically malignant cells favors a diagnosis of malignant lymphoma rather than nonlymphoma malignancies, even in HE histologic sections.
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PMID:Lymphoglandular bodies in malignant tumors: with special reference to histologic specimens. 1862 Sep 90


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