Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 2 (IL-2) is predominantly produced by T-helper cells (TH1) having the phenotype CD4+, and by subpopulations of thymocytes after antigenic or mitogenic stimulation. IL-2 causes an indefinite growth of T-cells, and its function depends on binding to IL-2 receptors (IL-2R alpha and IL-2R beta). Thus the immune response of T cells is controlled through the expression of the IL-2 receptors and the IL-2 binding. IL-2 receptors are expressed not only by T-cells but also by B-cells, NK cells, monocytes, thymocytes, thymic stroma cells, oligodendrocytes and endothelial cells. This explains the various functions of IL-2, such as increased immunoglobulin production, growth of certain B-cell subpopulations, macrophage-dependent cytotoxicity, growth and differentiation of oligodendrocytes and proliferation of lymphokine activated killer (LAK) cells. Abnormal production of IL-2 may lead to autoimmune diseases, immunodeficiencies and, under certain circumstances, to T-cell leukemia. With antibodies against the IL-2 receptors the binding of IL-2 may be blocked to avoid auto-aggressive destruction in autoimmune diseases. LAK cells increase the growth of NK cells and T-cell cytotoxicity against transformed cells. LAK cells, especially those from tumor infiltrating lymphocytes, in conjunction with IL-2 have already been used with promising initial results in the treatment of distant metastases. In the future LAK cell therapy with IL-2 may be adopted to prevent metastases and second primary tumors in high-risk patients with head and neck cancer.
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PMID:[Interactions and biological mechanisms of action of molecular signal peptides. II. Interleukin 2 (IL-2)]. 183 10

Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants.
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PMID:Experimental studies and preliminary clinical trial of vinorelbine-loaded polymeric bioresorbable implants for the local treatment of solid tumors. 191 58

The chemotactic responsiveness of mononuclear phagocytes has often been found defective in patients with various malignancies. We have previously reported a defective chemotactic responsiveness in patients with head and neck cancer. Low-molecular-weight factors (LMWFs) have been isolated from tumors and can be held responsible for the inhibitory effect on monocyte chemotactic responsiveness. It is an intriguing new finding that these LMWFs can be neutralized by antibodies reactive to P15E, a structural envelope protein of murine leukemia retroviruses. In this report we describe a relatively easy and rapid method for the detection of immunosuppressive P15E-like factors in the sera of patients with head and neck cancer. The test is based on the monocyte polarization assay. Although only nine head and neck cancer patients were included in this study, the findings indicate that the test might be of value for clinical application. An early detection of a recurrence after treatment might be possible by the finding of a reappearance of the P15E-like factors in patients' sera during follow-up.
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PMID:Immunosuppressive retroviral-related factors in sera of patients with head and neck cancer. 227 7

Neutropenic enterocolitis is a recognized complication of immunosuppression or chemotherapy for leukemia. It presents as severe abdominal pain and tenderness, fever, and diarrhea associated with granulocytopenia. Gastrointestinal symptoms associated with chemotherapy for head and neck neoplasms include nausea and emesis, but not acute abdominal distress. We present, to our knowledge, the first case of neutropenic enterocolitis in a patient receiving cisplatin and fluorouracil chemotherapy for metastatic head and neck cancer.
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PMID:Neutropenic enterocolitis. A new complication of head and neck cancer chemotherapy. 229 18

Heteromorphism of Y chromosome was studied in head and neck cancer patients and leukemia patients. The results were compared with similar data obtained for healthy men. It was observed that, compared to the controls, mean lengths of Y chromosome were nonsignificantly higher for leukemia patients and lower for head and neck cancer patients. The euchromatic region of Y chromosome (Y-eu) remained comparable in the controls and the leukemia patients, whereas it was smaller in patients with head and neck malignancies. The heterochromatic region (Y-het) was more or less analogous in controls and head and neck cancer patients, however, it was significantly larger in patients with leukemia (P less than 0.02).
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PMID:Variability of euchromatic and heterochromatic regions of Y chromosome in two types of cancer patients. 261

We have examined the epidermal growth factor (EGF) receptor gene for structural alterations in fresh human tumors. DNA samples from 92 patients with solid tumors (lung cancer, 37; breast cancer, 24; head and neck cancer, 17; other tumors, 14) were analyzed and compared with those from 22 leukemia patients and 14 individuals without malignant neoplasms. When DNA samples were digested with HindIII restriction endonuclease, Southern blot analysis demonstrated 3 distinct polymorphic bands (9.8, 11, and 12 kilobases) after hybridization to the HER-A64-1 probe and another 2 distinct polymorphic bands (4.9 and 5.2 kilobases) after hybridization to the HER-A64-3 probe. Pedigree analysis of 43 members of a single family and comparative analysis of tumor and normal DNA samples from the same patients demonstrated that the variations in fragment size observed were due to 2 independent restriction fragment length polymorphisms in the region of the EGF receptor gene. Amplification of the EGF receptor gene was detected in 3 cases of breast cancer, but not in other tumors studied. We conclude that the human EGF receptor gene has multiple restriction fragment length polymorphisms and that in fresh human tumor samples rearrangement and amplification of the gene occur infrequently, if ever, within the region encompassed by the 2 complementary DNA probes used.
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PMID:Multiple restriction fragment length polymorphisms of the human epidermal growth factor receptor gene. 289 88

The reported incidence of metastatic disease in head and neck cancer is increasing. The most common site of metastatic involvement in squamous carcinoma of the head and neck is the lung followed by liver, mediastinal nodes and bone. The breast is rarely infiltrated by metastatic disease, 2 per cent or less of clinically detected breast lumps being of non-mammary origin, most frequently malignant melanoma, lymphoma/leukaemia and primary lung carcinoma. A 73-year-old female presented with a primary posterior pharyngeal wall squamous carcinoma and bilateral enlarged neck nodes. She developed an isolated breast metastasis while receiving palliative radiotherapy and died seven months after presentation. Clinically detected breast metastasis in head and neck squamous cell carcinoma was first documented by Toombs and Kalisher in 1977. This is the first report of such a case originating in the posterior pharyngeal wall. The prognosis is invariably poor.
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PMID:Breast metastasis from a pharyngeal carcinoma. 292 75

The association of immunosuppression and head and neck cancer is supported by numerous reports demonstrating impaired cell-mediated immunity, depressed T-cell function, decreased lymphocyte responsiveness, and elevated circulating immune complexes. Fanconi's anemia (FA) is a rare autosomal recessive syndrome characterized by progressive pancytopenia, skeletal abnormalities, hyperpigmentation, and other congenital anomalies. Increased chromosomal instability and defective DNA repair have been uniform findings. Several reports suggest associated immune deficiencies. There is an increased frequency of leukemia, hepatocellular carcinoma, and squamous cell carcinoma (SCC), including six cases of head and neck SCC. We reported a young girl with FA who developed SCC of the tongue. Initial studies suggest low lymphocyte counts, but normal lymphocyte responsiveness. More precise characterization of the immune system defects in malignancy prone, genetically determined syndromes may provide clues for the diagnosis and treatment of patients with the more usual but more variable risk factors for SCC of the head and neck.
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PMID:Squamous cell carcinoma in the immunosuppressed patient: Fanconi's anemia. 401 Apr 14

The direct leukocyte migration inhibition (LMI) test was done with leukocytes from healthy women and from patients with primary operable breast cancer, benign breast disease, or head and neck cancer. Purified preparations of murine mammary tumor virus (MuMTV), Mason-Pfizer monkey virus (MPMV), and murine leukemia virus (MuLV) were used. For each virus, the lowest 10th percentile of the LMI responses of controls was used to discriminate positive from negative responses. Leukocytes from 46 of 94 (49%) breast cancer patients responded to MuMTV, which was significantly different from each of the other test groups: Positive reactions were observed in only 9 of 67 (13%) healthy persons, 2 of 32 (6%) patients with benign breast tumors, and 2 of 20 (10%) patients with head and neck cancer. Although leukocytes from 29% of the breast cancer patients responded to MPMV, this response did not significantly differ from that observed in healthy women (14%), in patients with benign disease (20%), or in patients with head and neck cancer (20%). The leukocytes from the breast cancer patients were not reactive to MuLV. LMI tests to both MuMTV and extracts of MCF-7 cultured breast cancer cells were done in 36 breast cancer patients and 40 healthy women simultaneously. Of the breast cancer patients, 75% responded to MuMTV and/or MCF-7 antigen as compared to 18% of the controls (P less than 0.005). These data suggest that leukocytes from breast cancer patients are presensitized to MuMTV and antigen(s) present in MCF-7 breast cancer cell line, but not to MPMV or MuLV.
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PMID:Leukocyte migration inhibition among breast cancer patients in response to various oncogenic viruses. 624 20

There is a clear change in the treatment strategies for solid tumours towards the treatment of early rather than advanced disease. Retinoids represent a potentially useful class of drugs in chemoprevention. Preclinical data and clinical experience suggests that different retinoids may have different spectra of antitumour activity and synergistic interactions between retinoids and cytokines have also been reported. 13-cis retinoic acid has shown some promising activity in preventing the onset of second primary tumours in head and neck cancer and fenretinide is being tested in the prevention of second primary breast cancers. An understanding of the role of the different retinoid receptors could lead to the design of compounds with a better therapeutic index. Despite these early indications that retinoids could be useful in this area, the development of such drugs is far from easy. Appropriate study designs for screening differentiating agents in the clinic, and the relevance of preclinical models of chemoprevention are challenges to be addressed. Unresolved issues include optimal patient selection, long clinical trial times, optimal dose, schedule and treatment duration. The use of biological surrogate markers for longer time-dependent trial endpoints could significantly contribute to more rapid development. Ongoing clinical studies, particularly in tobacco-related diseases, will better define the role of retinoids in this clinical setting. Clinicians should be encouraged to enter patients into large well organized clinical studies.
Leukemia 1994
PMID:Solid tumours--chemoprevention with retinoids. 780 35


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