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)

Recent molecular biological approach has revealed the primary structure of some mucin core proteins. Most prominent characteristic is tandemly repeated sequences. cDNA cloning of 8 kinds of mucin core proteins, MUC1-7, have thus been performed. Among them, the entire structure was revealed on MUC1,2 and 7. MUC1 is a type I transmembrane protein with a large number of tandem repeat consisting of 20 amino acids. We have found that mouse MoAb MUSE11 against adenocarcinoma, which detects circulating MUC1 in patients with gastrointestinal and pancreatic cancers, recognizes part of the tandem repeat of MUC1 using synthetic peptides. We have transfected MUC1 cDNA to some cell lines, and they indicated that cell-cell and cell-matrix adhesion, growth rate and reactivity with growth factor were suppressed. To date, some of the MoAbs to adenocarcinoma have been shown to react with PDTRP sequence in the tandem repeat of MUC1 (MUC1 epitope), suggesting that MUC1 epitope could be highly immunogenic in human. Recently, cytotoxic T-cells against MUC1 epitope were established from breast and pancreas cancer patients. We also induce those T-cells from the patient with multiple myeloma. Interestingly, CTL functions in an HLA-unrestricted manner, and may be of use an adoptive immunotherapy. MUC2, a large secretory type mucin, cysteine-rich subdomains located both upstream and downstream of its central repetitive region, and these subdomains have sequence similarity with von Willebrand factor. We have shown that anti MUC2 core-protein MoAb CCP58 reacts intestinal metaplasia and cancer in stomach, but not normal gastric mucous membrane. Recently we established a new monoclonal antibody against purified deglycosylated gastric mucin. This antigen was expressed in the deep portion of metaplastic glands and cancers in the stomach. Two cDNA clones coding for this antigenic molecule were obtained.
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PMID:[New mucin core protein genes and their clinical application]. 864 70

Retinoids and vitamin D are important factors that regulate cellular growth and differentiation. An additive growth-inhibitory effect of retinoids and vitamin D analogues has been demonstrated for human myeloma, leukaemic and breast cancer cells. We set out to study the effects of the vitamin D analogue EB1089 and the retinoids all-trans- and 9-cis-retinoic acid on the human pancreatic adenocarcinoma cell lines Capan 1 and Capan 2 and the undifferentiated pancreatic carcinoma cell line Hs766T. The cell lines investigated expressed vitamin D receptor, retinoic acid receptor (RAR)-alpha and gamma as determined by polymerase chain reaction after reverse transcription. RAR-beta was expressed only in Hs766T cells. Addition of all-trans-retinoic acid increased the amount of RAR-alpha mRNA in the three cell lines and induced RAR-beta mRNA in Capan 1 and Capan 2 cells. All-trans-retinoic acid at a concentration of 10 nM inhibited the growth of Capan 1 and Capan 2 cells by 40% relative to controls. 9-cis-Retinoic acid was less effective. Neither all-trans-retinoic acid nor 9-cis-retinoic acid affected the growth of Hs766T cells. EB1089, if added alone to the cells, did not significantly inhibit growth. However, the combination of 1 nM EB1089 with 10 nM all-trans-retinoic acid exerted a growth-inhibitory effect of 90% in Capan 1 cells and of 70% in Capan 2 cells. Our data suggest that vitamin D analogues together with retinoids inhibit the growth of human pancreatic cancer cells. However, in vivo studies are necessary to examine the potential use of retinoids and vitamin D analogues on pancreatic cancer.
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PMID:Growth-inhibitory effects of vitamin D analogues and retinoids on human pancreatic cancer cells. 864 77

Four monoclonal antibodies (MAbs) from hybridoma obtained by in vitro stimulation of regional lymph node lymphocytes from lung cancer patients and electrofusion of the stimulated cells with murine or human-mouse myeloma cells were reactive to lung cancer cells in enzyme-linked immunoabsorbent assay, and to lung cancer tissue in immunohistochemical analysis using acetone-methyl benzoate-xylene (AMeX) fixed tissue and in immunofluorescence analysis. Three of the MAbs (designated ZLG40, 27D57 and 28K29) recognised cell-surface antigens of the lung adenocarcinoma cell line A549 and the remaining one (designated 29D38) recognised nuclear membrane antigens of the same cell line. The three surface-binding MAbs showed a significant complement-dependent cytotoxicity (CDC) to the A549 cells, but the membrane-binding 29D38 showed no CDC to the A549 cells. Western blotting of the extracts of the A549 or PC6 (small-cell lung cancer) cell lines by the four MAbs showed a 28K29 antigen band at M(r) of approximately 600,000 (+/- 2-ME), a ZLG40 antigen band at M(r) 50,000 (+/- 2-ME), and one 29D38 antigen band at M(r) of more than 1,000,000 (-2-ME) and M(r) between 20,000 and 80,000 (+2-ME), but no detectable band for 27D57 antigen.
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PMID:Generation of human monoclonal antibodies recognising membranous antigens of the lung adenocarcinoma cell line A549 using an AMeX immunohistostaining method. 869 49

A lipid mobilizing factor has been purified from a cachexia-inducing mouse colon adenocarcinoma (MAC16) using a combination of ion exchange (Mono Q), exclusion (Superose) and reverse phase hydrophobic chromatography. The purification process led to a 3,500-fold increase in the specific activity. Serum from mice bearing the MAC16 tumour contained antibodies reactive with fractions containing lipid mobilizing activity and detectable as a 24 kDa immunoreactive band on Western blotting. Serum from mice transplanted with a related tumour, MAC13, not producing cachexia, did not contain antibodies. A similar immunoreactive band was detectable in the urine of patients with cancer cachexia, but was absent from the urine of normal subjects. A monoclonal antibody produced by fusion of splenocytes from mice bearing the MAC16 tumour with mouse Balb/c myeloma cells attenuated the development of cachexia in mice transplanted with the MAC16 tumour and inhibited tumour growth. These results suggest that the M(r) 24 kDa antigen may be important in tumour growth and cachexia.
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PMID:Catabolic factors in cancer cachexia. 874 91

Between 1986 and 1993, 18 patients with complete or impending fractures of the humerus were treated using Hacketall rods in association with semi-liquid methylmetacrylate after excision of the metastatic lesion. Methylmetacrylate was always injected proximally and distally to the curetted bone through drill holes. Fourteen patients had a pathological fracture and four presented with an impending lesion. The mean age at time of surgery was 62 years (range: 42-83). The primary tumour was a breast carcinoma in 10 cases, bronchogenic squamous cell carcinoma in three cases and hypernephroma, multiple myeloma, malignant melanoma, rectal adenocarcinoma and unknown primary tumour in one case each. The left arm was involved in seven cases and the right in 11. All patients experienced immediate relief from the pre-operative pain, although three patients complained of a residual discomfort during motion. In these three cases the residual pain can easily be managed with use of oral non-morphinic drugs. The functional aspect was not evaluated in two patients who died in the early post-operative period as a result of their general condition. In 15 patients, the post-operative range of motion was at least 80% of a normal humerus mobility. One patient encountered motion limitation because of an important lymph oedema. There was no infection, one patient had a temporary radial palsy with a complete restoration after a period of 5 days. No migration of the material was observed during an average follow-up of 9 months (range: 1-24).
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PMID:Treatment of humeral pathological fractures by internal fixation and methylmetacrylate injection. 923 99

The poly(ADP-ribose)polymerase (PADPRP) gene has been implicated in carcinogenesis through its role in DNA repair, replication and recombination. A two-allele polymorphism in the chromosome 13 PADPRP pseudogene has been studied in several racial groups. It has been suggested that the B allele, which results from a 193-bp deletion in the gene, predisposes to myeloma in Blacks. We assessed the association between chromosome 13 PADPRP pseudogene genotype, mutagen sensitivity (a marker reflecting host DNA repair capability), cigarette smoking, and lung cancer risk in a minority lung cancer case-control study. The chromosome 13 PADPRP pseudogene polymorphism was detected by polymerase chain reaction-based analysis. Mutagen sensitivity was measured by an in vitro assay that quantified bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures. We examined 121 cases (80 African-Americans and 41 Mexican-Americans) with previously untreated lung cancer and 171 matched controls. Our results suggested that the distribution of the PADPRP pseudogene genotype frequencies was significantly different among African-American and Mexican-American controls (P < 0.001). The susceptibility genotype (i.e. at least one B allele) was found in 82.5% of African-American cases, 79.4% of African-American controls, 53.7% of Mexican-American cases, and 32.4% of Mexican-American controls. The odds ratios (OR) and 95% confidence intervals for the PADPRP susceptibility genotypes were 2.3 (95% CI = 0.7-8.0) and 3.2 (95% CI = 1.0-10.3) for African-Americans and Mexican-Americans respectively, after adjustment by age, sex, pack-years and mutagen sensitivity. Patients with the susceptibility genotype appeared to have more mutagen-induced breaks than did patients with the other genotype. Only adenocarcinoma was significantly associated with the PADPRP susceptibility genotype (OR = 3.8). Mutagen sensitivity (> or = 1 break/cell) was significantly associated with lung cancer risk for both ethnic groups with increased ORs of above three-fold. On stratified analysis, synergistic interactions were noted for the PADPRP susceptibility genotype, mutagen sensitivity and smoking status. In Mexican-Americans, the ORs for PADPRP susceptibility genotype, mutagen sensitivity and both risk factors combined were 1.3, 2.7 and 17.1 respectively. The combined OR for the PADPRP susceptibility genotype and smoking status was 15.6. Therefore, this polymorphism appears to be associated with lung cancer risk. However, it is likely that no single genotype is sufficiently predictive of risk and that a panel of susceptibility markers is needed to define the high-risk subgroup.
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PMID:Deletion in poly(ADP-ribose)polymerase pseudogene and lung cancer risk. 947 99

A case of extramedullary plasmacytoma of the maxillary sinus, locally aggressive, in a 65 years old man is presented. Clinical diagnosis of adenocarcinoma was suspected but the pathological study showed an anaplastic morphology, with little plasmacytic differentiation and lack of stain with cytokeratins and epithelial membrane antigen (EMA), immunohistochemical marker of plasmatic cells, among others. Definitive diagnosis was based on light chain restriction and lack of multiple myeloma.
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PMID:[Extramedullary anaplastic plasmacytoma]. 962 74

For some patients with spinal metastasis and spinal cord compression, newer surgical techniques are better than laminectomy or radiotherapy alone in relieving pain and restoring function. While radiotherapy remains the standard for spinal metastases due to myeloma, lymphoma, and many types of adenocarcinoma, proper surgical treatment can significantly improve function and outcome in selected patients.
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PMID:Newer management options in patients with spinal metastasis. 967 91

Bone sialoprotein (BSP) is a small, highly posttranslationally modified integrin binding protein found in the mineral compartment of developing bone. The recent discovery that BSP can be detected in a variety of human cancers, particularly those that metastasize preferentially to the skeleton, shed light on potential new biological functions for this protein. The demonstration of a positive association between BSP expression in primary breast tumors and the development of bone metastases suggests that this glycoprotein could play a role in the selective implantation of breast cancer cells in bone. BSP is also expressed in most lung and prostate cancers as well as in multiple myeloma, three other osteotropic malignancies. Because thyroid carcinoma also metastasizes preferentially to the skeleton, we decided to look at the expression of BSP in a collection of 145 thyroid malignant lesions including 24 follicular thyroid carcinomas (FTCs), 55 papillary thyroid carcinomas (PTCs), 19 medullary thyroid carcinomas (MTCs), 23 anaplastic carcinomas (ACs), and 24 poorly differentiated carcinomas (PDCs). BSP expression was evaluated by immunoperoxidase technique using two specific polyclonal antibodies. Most of the thyroid carcinomas (72%) examined expressed high levels of BSP. Expression of BSP was significantly lower in FTCs and MTCs compared with PDCs, which are more aggressive (p = 0.0009 and 0.0003, respectively). Our study demonstrates for the first time that ectopic BSP expression is a common feature of thyroid cancer. The prognostic value of BSP detection in thyroid adenocarcinoma and the potential role of BSP in the propension of this type of cancer to metastasize to bone are currently under investigation.
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PMID:Ectopic expression of bone sialoprotein in human thyroid cancer. 973 56

A 72-year-old woman with a history of early breast cancer suffered a fracture of the eighth thoracic vertebra resulting in paraplegia. Magnetic resonance imaging (MRI) showed spinal cord compression by a tumor between the ninth and tenth thoracic vertebrae. Local radiotherapy was begun under the diagnosis of metastatic breast cancer, but bone marrow aspiration and biopsy subsequently revealed plasma-cell proliferation rather than adenocarcinoma. This case report serves to demonstrate that clinicians should consider multiple myeloma as a cause of lytic bone lesions without extraskeletal metastases even in patients with a history of breast cancer.
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PMID:Multiple myeloma mimicking bone metastasis from breast cancer: report of a case. 987 55


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