Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether anti-transferrin (Tf) receptor monoclonal antibodies might be useful in treatment of human solid tumors, in vitro effects of immunoglobulin A (42/6) and immunoglobulin G (B3/25) anti-Tf receptor antibodies on human solid tumor growth were examined. In colony and liquid cultures containing 10% serum, B3/25 did not inhibit growth of melanoma or ovarian carcinoma cell lines. 42/6 caused modest dose-dependent inhibition in colony cultures (maximum inhibition approximately 50%), and slowed growth of melanoma, ovarian carcinoma and epidermoid carcinoma cells in liquid culture. Inhibition was more pronounced in low (1%) serum, and was abrogated by 200 micrograms/ml iron-saturated Tf or 50 microM ferric nitriloacetate. All cells displayed high affinity Tf receptors (4-20 X 10(4)/cell). Cells grown in 1% serum and epidermoid carcinoma cells displayed more receptors, and susceptibility to 42/6 inhibition appeared related to higher receptor number. After culture with anti-Tf receptor antibodies, solid tumor cells showed a 57-93% reduction in surface Tf-binding sites. Tf uptake by cells grown for 24 h in B3/25 was approximately 50% of control, but was reduced to less than 10% of control with 42/6. Immunofluorescence staining of melanoma and HL60 promyelocytic leukemia cells suggested greater heterogeneity of Tf receptor display on melanoma than on leukemia cells. Previous studies showed 42/6 completely blocked blood cell Tf internalization and is a potent inhibitor of hemopoietic cell growth. In contrast, in solid tumor cells, inhibition of Tf uptake and growth inhibition are subtotal. Solid tumor resistance to 42/6 may be due in part to greater heterogeneity of Tf receptor display by proliferating cells. However, responses to iron-saturated Tf and ferric nitriloacetate in the presence of 42/6 also differ in hemopoietic and solid tumor cells, suggesting possible differences in Tf processing or iron growth requirements.
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PMID:Effects of monoclonal anti-transferrin receptor antibodies on in vitro growth of human solid tumor cells. 382 93

Pre- and postimmunization sera from six malignant melanoma and six ovarian carcinoma patients were used to investigate the humoral immune response to antigens expressed in extracts of allogeneic tumor cells and lysates of these same cells infected with virus. Nitrocellulose paper replicas of cell extracts, fractionated by polyacrylamide gel electrophoresis, were used as antigenic targets. Antibodies that bound to tumor cell antigens of defined molecular weight were identified with enzyme-linked probes specific for human immunoglobulins G, A, and M. Prior to therapy, all sera reacted with one or more antigens expressed by the unmodified tumor cells. Postimmunization sera from two malignant melanoma patients and one ovarian carcinoma patient reacted with antigens in extracts of uninfected tumor cells. These same antigens were not detected by preimmunization sera. Most postimmunization antibody responses were directed against antigens associated with the infecting virus itself and antigens found in extracts of virus-infected but not in extracts of uninfected tumor cells. These results suggest that treatment with lysates of virus-infected allogeneic human tumor cells elicits humoral immune responses against: (a) tumor cell-associated antigens; (b) antigens that are specifically virus associated; and (c) antigens that may be virus induced or virus modified cytoplasmic or nuclear antigens.
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PMID:Antibody development to viral and allogeneic tumor cell-associated antigens in patients with malignant melanoma and ovarian carcinoma treated with lysates of virus-infected tumor cells. 394 84

6-[Bis-(2-chloroethyl)-amino]-6-deoxy-D-glucose (C-6) is a new glucose-containing nitrogen mustard that has significant activity for murine P388 leukemia with relative sparing of bone marrow in mice. The in vitro myelotoxicity of C-6 compared with that of melphalan, a clinically active, myelosuppressive nitrogen mustard, was determined in the CFU-C assay in human bone marrow samples obtained from normal volunteers. There was no significant difference between the myelosuppressive actions of C-6 and melphalan at any of the concentrations used except for 4.0 microM, at which C-6 was significantly (P less than 0.05) more toxic than melphalan. Both agents decreased the number of bone marrow cell colonies to approximately 12% of control at 6.6 microM (1 h incubation), which is a good approximation of melphalan's CxT (concentration by time) in man. We used the human tumor stem cell assay (HTSCA) to investigate in vitro antitumor activity. We obtained two specimens of malignant melanoma and two of malignant ovarian carcinoma from patients not previously treated with chemotherapy. The antitumor activity of melphalan was either similar to or greater than that of C-6 at all concentrations utilized against any of the four tumor specimens, except at 1.3 microM for tumor I. In particular, there was no significant difference in the antitumor activities of the two agents at 6.6 microM. These results suggest that C-6 will not be less myelosuppressive than melphalan at doses that produce equivalent antitumor activity in man. In addition, C-6 did not demonstrate increased myelotoxicity for normal human bone marrow cells incubated in glucose-deficient medium as against medium containing 300 mg% glucose at any of the concentrations used. This suggests that C-6 is not transported into normal human bone marrow cells via the glucose transport system, despite the presence of a glucose moiety within the molecule.
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PMID:In vitro comparative studies of the myelotoxicity and antitumor activity of 6-[bis-(2-chloroethyl)-amino]-6-deoxy-D-glucose versus melphalan utilizing the CFU-C and HTSCA assays. 394

A wide variety of tumor types can be successfully grown with the clonogenic assay. However, few tumor types perform adequately for routine drug sensitivity testing, e.g., ovarian carcinoma and malignant melanoma. Because of insufficient in vitro growth, the cloning system cannot help substantially in indicating active substances for epidemiologically frequent tumors that usually have a poor prognosis, such as colorectal cancers and non-small cell lung and breast cancers. The degree of in vitro cell kill that would correspond to complete eradication of micrometastases is unknown. The identification of individual patients sensitive to a given antineoplastic agent becomes more difficult as the tumor becomes more refractory to treatment. At this moment, the clonogenic assay appears most promising for trials dealing with the treatment of ovarian adenocarcinoma.
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PMID:Drug selection for perioperative chemotherapy. 403 71

Cultured human tumor cells of various histologic origins were infected with PR8/A/34 influenza virus. Nonviable crude membrane extracts were derived from the infected and uninfected cells. The extracts were coded and tested for their ability to produce delayed hypersensitivity skin reactions (DHSR) in allogeneic patients with squamous uterine cervical carcinoma, epithelial ovarian carcinoma, and malignant melanoma. Augmented antigen sensitivity to the virus-modified extracts compared with virus alone or to the unmodified extracts was observed in all patient groups. There was insufficient specificity to delineate a response by individual tumor type and related tumor extract, but some of the observed responses suggested tumor or organ site associations. Cervical carcinoma patients reacted more frequently to the virus-modified cervix extract, which also produced a high frequency of response in patients with ovarian carcinoma and melanoma. Ovarian carcinoma patients demonstrated increased sensitivity to both virus-modified ovarian carcinoma extracts, although 14 of 21 patients also showed responsiveness to one of the unmodified ovarian extracts. Malignant melanoma patients showed increased sensitivity to all virus-modified extracts except one of two derived from the ovarian carcinoma, and demonstrated a significantly augmented response to the virus-modified melanoma extract when the response to this extract was compared with that in ovarian carcinoma patients. The augmented reactions appear to be due to an association of the PR8 virus and as yet undetermined cellular components rather than to the virus alone. The possible involvement of tumor-associated determinants and the clinical significance of this phenomenon require further investigation.
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PMID:Virus-augmented delayed hypersensitivity skin tests in gynecological malignancies. 608 33

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
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PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63

The anticancer drug Adriamycin was tested in vitro both in free form and encapsulated in negatively charged liposomes. [3H]-thymidine incorporation and a 72-hour survival test were used for the evaluation of cytotoxicity in a phagocytic human melanoma cell line and a non-phagocytic human ovarian carcinoma cell line. In each case, free Adriamycin induced greater cell damage than did liposomal drug. Stability tests of the liposomes used for subsequent cytotoxicity studies under the exact conditions of the cell culture assay revealed that up to 45 per cent of the originally entrapped drug was released from the lipid vesicles over a 24-hour period.
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PMID:Failure of liposomally encapsulated adriamycin to improve therapeutic efficacy for cancer cells in vitro. 633 27

The toxicity of intravenously administered Corynebacterium parvum was observed in 14 patients with stage II melanoma and in 14 patients with advanced ovarian carcinoma. Those with melanoma were rendered disease-free by surgery prior to treatment. The ovarian cancer patients had failed chemotherapy with alkylating agents and were receiving C. parvum prior to chemotherapy as part of an immunochemotherapy trial. Both clinical and laboratory parameters were observed. The mean daily C. parvum dose for melanoma patients was 2.03 mg/m2 and for ovarian carcinoma patients 2.02 mg/m2. The most important clinical toxic effects noted were fever, chills, blood pressure changes, headache, nausea, vomiting and diaphoresis. Laboratory toxicity was mild, with small decreases in hemoglobin levels, white blood cell counts and uric acid and albumin concentrations occurring in some patients. Serum bilirubin and SGOT levels tended to rise. In addition to determining the frequency of clinical toxic effects by treatment course, consideration was also given to frequency per treatment day, correlation of the occurrence of different toxicities in the same patient, time of onset of each toxicity and, for vital signs, to intensity of change and duration. In this analysis no major differences in toxicity were observed when C. parvum was given to the two patient groups.
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PMID:Corynebacterium parvum toxicity in patients with limited and advanced malignancy. 653 97

A competition radioimmunoassay was developed, utilizing a murine monoclonal antibody to human pancreatic adenocarcinoma cells. Immunoblotting of a standard antigen preparation from either serum or ascites fluid after electrophoresis in 1% agarose showed that the specific DU-PAN-2 activity resided in two major high molecular weight bands. DU-PAN-2 antigen levels were expressed as arbitrary units based on a standard partially purified antigen preparation. The inhibition curve with standard antigen was reproducible (SD less than 10%) and essentially linear from 25 to 200 units/ml. The mean DU-PAN-2 antigen concentration for the sera from 126 normal individuals was 81 units/ml. Sera from pediatric patients with malignancy had a mean of 127 units/ml, while nasopharyngeal, stage III melanoma, and ovarian carcinoma patients had means of 89, 92, and 119 units/ml, respectively. All values in normal subjects as well as the melanoma, nasopharyngeal, ovarian, and pediatric cancer patients were less than 400 units/ml. Intermediate antigen levels were detected in patients with alimentary tract malignancies. Eight of 20 gastric cancer and 8 of 76 colorectal carcinoma patients and 3 patients with benign or nonmalignant gastrointestinal tract disease had DU-PAN-2 values exceeding 400 units/ml. Ascites fluids from 6/6 and pancreatic juice from 2/2 pancreatic cancer patients had values greater than 750 units/ml. Serum from 68% of the 89 pancreatic cancer patients tested had DU-PAN-2 antigen levels greater than 400 units/ml. The mean serum value in this patient population was 4888 units/ml.
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PMID:Detection of a pancreatic cancer-associated antigen (DU-PAN-2 antigen) in serum and ascites of patients with adenocarcinoma. 659 Nov 88

Mild hyperthermia in conjunction with procaine HCl acts as a potentiator of radiation lethality in HeLa cells, with little toxicity for unirradiated cells. The majority of irradiated cells responds extensively within a four hour period of treatment with the two agents. Potentiation of radiation lethality by the combined treatment was also found in a line of human melanoma cells, and to a lesser extent in a line of human ovarian carcinoma cells. The interaction of heat and procaine in the process of potentiation of radiation lethality was assessed from a series of radiation survival curves, with temperatures ranging from 37 to 42 degrees C and procaine concentrations from 1 to 3 mM. The interactive factor was obtained from the ratio of the Dose Reduction Factor (DRF) due to procaine in heated cells, to the DRF due to procaine in unheated cells; a ratio larger than unity denotes interaction of heat and procaine. The largest interaction was observed when individual agents exerted only a minimal radiopotentiating effect, as if increased effectiveness of one agent pre-empted the effectiveness of the other agent.
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PMID:Variable interaction of heat and procaine in potentiation of radiation lethality in mammalian cells of neoplastic origin. 660 36


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