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)

The human KIN17 protein is a chromatin-associated protein involved in DNA replication. Certain tumor cell lines overproduce KIN17 protein. Among 16 cell lines, the highest KIN17 protein level was observed in H1299 non-small cell lung cancer cells, whereas the lowest was detected in MeWo melanoma cells. Cells displaying higher KIN17 protein levels exhibited elevated RPA70 protein contents. High KIN17 protein levels may be a consequence of the tumorigenic phenotype or a prerequisite for tumor progression. Twenty-four hours after exposure to ionizing radiation, after the completion of DNA repair, a co-induction of chromatin-bound KIN17 and RPA70 proteins was detected. Etoposide, an inhibitor of topoisomerase II generating double-strand breaks, triggered the concentration of KIN17 into punctuate intranuclear foci. KIN17 may be associated with unrepaired DNA sites. Flow cytometry analysis revealed that 48 h after transfection the uppermost KIN17-positive RKO cells shifted in the cell cycle toward higher DNA content, suggesting that KIN17 protein induced defects in chromatin conformation. Cells displaying reduced levels of KIN17 transcript exhibited a sixfold increased radiosensitivity at 2 Gy. The KIN17 protein may be a component of the DNA replication machinery that participates in the cellular response to unrepaired DSBs, and an impaired KIN17 pathway leads to an increased sensitivity to ionizing radiation.
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PMID:Depletion of KIN17, a human DNA replication protein, increases the radiosensitivity of RKO cells. 1275 57

In our continuous studies of anticancer activity of steroidal saponins from the rhizomes of Dioscorea collettii var. hypoglauca (Dioscoreaceae), methyl protoneogracillin (NSC-698793) and gracillin (NSC-698787) were tested for cytotoxicity against human cancer cell lines from leukemia and eight solid tumor diseases. As a result, methyl protoneogracillin was cytotoxic against all the test cell lines with GI(50) < 100 micro M, especially selectively against two leukemia lines (CCRF-CEM and RPMT-8226), one colon cancer line (KM12), two central nervous system (CNS) cancer lines (SF-539 and U251), one melanoma line (M14), one renal cancer line (786-0), one prostate cancer line (DU-145), and one breast cancer line (MDA-MB-435), with GI(50) < or = 2.0 micro M. Leukemia, CNS cancer, and prostate cancer were the most sensitive subpanels, while ovarian cancer was the least sensitive subpanels. The preliminary toxicity studies showed that the maximum tolerant dose was 600 mg/kg for methyl protoneogracillin to mice. Gracillin was cytotoxic against most cell lines with GI(50), TGI and LC(50) at micromolar levels, but no activity against EKVX (non-small cell lung cancer), HT29 (colon cancer), OVCAR-5 (ovarian cancer), and SN12C (renal cancer). Based on structure-activity relationship, C-25 R/S con fi guration was critical for leukemia selectivity between methyl protoneogracillin and methyl protogracillin. F-ring was critical to selectivity between furostanol (methyl protoneogracillin and methyl protogracillin) and spirostanol (gracillin) saponins in this study. By an analysis of COMPARE software, no compounds in the NCI's database had similar mean graphs to those of methyl protoneogracillin and gracillin, respectively, indicating potential novel mechanism(s) of action involved. Put all in together, methyl protoneogracillin has been selected as a potential anticancer candidate for hollow fi ber assay to nude mice, but gracillin will not be pursued due to lack of selectivity against human cancer diseases.
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PMID:The cytotoxicity of methyl protoneogracillin (NSC-698793) and gracillin (NSC-698787), two steroidal saponins from the rhizomes of Dioscorea collettii var. hypoglauca, against human cancer cells in vitro. 1282 Feb 29

This study assessed the clinical usefulness of a new technetium-99m labelled somatostatin analogue from the standpoint of oncological diagnostics. The study group comprised 40 patients in whom malignant neoplasms (32 primary and 8 metastatic) had been diagnosed. Among the primary tumours there were 21 cases of lung cancer (2 small cell and 19 non-small cell), seven pituitary adenomas (five hormonally active and two inactive), one liposarcoma, two carcinoids and one breast carcinoma. The metastatic tumours consisted of three malignant melanomas, one phaeochromocytoma, one prostatic cancer, one leiomyosarcoma, one pancreatic carcinoma ectopically secreting ACTH and one carcinoid of the thymus. The radiopharmaceutical 99mTc-EDDA/HYNIC-Tyr3-octreotide was administered i.v. at an activity of 740-925 MBq. The imaging comprised a whole-body scan and a single-photon emission tomography acquisition. Positive scintigrams were obtained in all cases of small cell and non-small cell lung cancer, four out of five hormonally active pituitary adenomas, one out of two cases of carcinoid, the liposarcoma and the breast cancer. Neoplastic metastases were visualised in two out of three patients with melanoma and in patients with phaeochromocytoma, ACTH-secreting pancreatic carcinoma and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, in the leiomyosarcoma and in the case of metastasis from prostatic carcinoma. The results of this pilot study indicate that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for imaging of a wide range of primary and metastatic tumours. Special attention should be paid to the successful imaging of all cases of non-small cell lung cancer.
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PMID:Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a preliminary communication. 1512 15

The development of effective cancer vaccines depends heavily on the ability to deliver target antigens to generate an immune response. Dendritic cells are the most potent antigen-processing cells, capable of sensitizing T cells to new and recall antigens. Dendritic cells express high levels of major histocompatibility complex class I and II antigens, which are crucial to cancer immunotherapy, as well as a variety of important immunomodulatory proteins, adhesins, and a potent cytokine. Dendritic cells must undergo activation to induce an immune response, and this can be achieved through the use of certain carrier proteins, adjuvants, cytokines, or genetically engineered viruses. Dendritic cells are scattered throughout many tissues of the body, as well as bone marrow and peripheral blood. Most studies have used dendritic cells from peripheral blood; however, these cells are not prevalent in peripheral blood mononuclear cells. The cytokine, granulocyte-macrophage colony-stimulating factor, has been found to induce the maturation and enhance the viability of dendritic cells isolated from peripheral blood. Numerous clinical trials of antigen-pulsed dendritic cells have been conducted in various types of cancer, including non-Hodgkin lymphoma, multiple myeloma, prostate cancer, malignant melanoma, colorectal cancer, and non-small cell lung cancer. These studies show that antigen-loaded dendritic cell vaccinations are safe and promising in the treatment of cancer. This review discusses the use of dendritic cells in immunotherapy and some of the clinical trials that have been conducted.
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PMID:Dendritic cell-based cancer immunotherapy. 1288 9

Yondelis (trabectidin, ET-743) is a marine natural product that has shown activity both in preclinical systems and in human malignancies such as soft tissue sarcoma and ovarian cancers that are resistant to previous chemotherapies. Molecular pharmacological studies indicated that Yondelis interacts with DNA and DNA repair systems in a way that is different from Cisplatin (DDP). The current study was designed to investigate the effects of the combination of Yondelis and DDP in human cancer cell lines and in xenografts derived from different tumours. The in vitro studies performed in human TE-671 rhabdomyosarcoma, Igrov-1 and 1A9 human ovarian carcinoma cell lines showed additive effects or slight synergism. Several human tumour xenografts, such as TE-671 rhabdomyosarcoma, SK-N-DX neuroblastoma, FADU head and neck, LX-1 non-small cell lung cancer (NSCLC), H-187 melanoma and SKOV HOC 8 ovarian carcinoma, showed an antitumour effect for the combination that was greater than that of each drug when given as a single agent. No consistent changes in the activity were observed if Yondelis and DDP were given 1 h apart in sequence or simultaneously. An orthotopically transplanted human ovarian cancer HOC 8 growing in the peritoneal cavity of nude mice was used that is insensitive to Yondelis alone and only moderately sensitive to DDP alone. The combination of the two drugs produced a dramatic increase of survival lasting several months. In conclusion, the combination of Yondelis and DDP is synergistic in vivo (i.e. the antitumour effect is greater than that of each drug used as a single agent at the maximum tolerated dose (MTD)) in different human tumour xenografts. The two drugs can be combined at the MTD of each drug, thus indicating there are no overlapping toxicities. These results provide a rationale for testing the combination of Yondelis and DDP in the clinic.
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PMID:The combination of yondelis and cisplatin is synergistic against human tumor xenografts. 1293 57

ABI 007 is an albumin-stabilised nanoparticle formulation of paclitaxel designed to overcome insolubility problems encountered with paclitaxel. This then eliminates the need for toxic solvents like cremophor, which limits the dose of paclitaxel that can be administered and hence effect overall drug efficacy. ABI 007 is being developed for the treatment of a variety of tumour types by American Pharmaceutical Partners. In addition to the standard infusion formulation of ABI 007, oral and pulmonary delivery formulations are also being investigated. American Pharmaceutical Partners, a subsidiary of American BioScience, secured exclusive North American marketing and manufacturing rights to ABI 007 from American BioScience in November 2001. American BioScience completed a phase III study in the US in metastatic breast cancer patients in early 2003. An indication for which ABI 007 was granted fast track status in January 2003. The phase III study directly compared the efficacy of ABI 007 260 mg/m(2) with paclitaxel 175 mg/m(2). Both agents were administered every 3 weeks. ABI 007 was administered as a 30-minute infusion without steroid pretreatment. Paclitaxel-treated patients received steroid pretreatment and the drug was administered over 3 hours. In October 2002, a Data Monitoring Committee concluded that a sample size adjustment of the phase III trial would not be required and that the study can be continued to completion. Enrolment was completed in December 2002 with 460 first- and second-line metastatic breast cancer patients enrolled. The results were expected to be unblinded in mid-2003. A phase II trial of ABI 007 is also underway in metastatic breast cancer patients who have failed taxane therapy. The trial is evaluating a weekly rather than 3-weekly regimen of ABI 007. Earlier, in May 2003, American Pharmaceutical Partners reported that ABI 007 is also being evaluated for the treatment of non-small cell lung cancer, ovarian cancer, melanoma and cervical cancers. However, the phase of development for these indications remains unclear.
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PMID:ABI 007. 1295 99

Platelet endothelial cell adhesion molecule (PECAM-1/CD31), a member of the immunoglobulin superfamily expressed at high levels on endothelial cells, has been recently implicated in angiogenesis. Although antagonism of PECAM-1 inhibited neovascularization in two different animal models of growth factor/chemokine-induced angiogenesis, its participation in tumor angiogenesis has not been established. We therefore investigated its involvement in models of tumor angiogenesis in mice. An antibody against murine PECAM-1 that was shown to block in vitro murine endothelial tube formation inhibited the subcutaneous growth and tumor vascularity of three tumors in mice: A549 human non-small cell lung cancer in SCID mice, B16 murine melanoma in C57BL/6 mice and AB12 murine mesothelioma in Balb/c mice. These studies suggest a possible role for PECAM-1 in the complex process of tumor angiogenesis and provide additional evidence of the importance of endothelial cell adhesion molecules to the formation of new vessels.
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PMID:Antibody against murine PECAM-1 inhibits tumor angiogenesis in mice. 1451 36

Although identification of sentinel lymph nodes (SLN) with dye or radioisotope tracers has become a standard of care in both breast cancer and melanoma, it remains investigational in patients with lung cancer. SLN mapping has been performed in non-small cell lung cancer patients using isosulfan blue and radioisotope. The radioisotope method of SLN mapping appears to be more accurate than the dye technique in lung cancer patients. Several reports have demonstrated the feasibility of identifying the first site of potential nodal metastases of NSCLC. Furthermore, accurate sentinel node identification allows pathologists to focus on examinations with sensitive techniques to validate the SLN and to identify the presence of skip metastasis.
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PMID:[Sentinel lymph node mapping in non-small cell lung cancer]. 1462 15

Cancer/testis (CT) antigens are immunogenic in cancer patients, exhibit highly tissue-restricted expression, and are considered promising target molecules for cancer vaccines. To date, 44 CT gene families have been identified and their expression studied in numerous cancer types. For example, bladder cancer, non-small cell lung cancer, and melanoma are high CT gene expressors, with 11/20 (55%), 17/33 (51%) and 17/32 (53%) of the CT transcripts examined by RT-PCR detected in 20% or more of the specimens examined, respectively. Breast and prostate cancer can be considered moderate CT gene expressors, with 12/32 (37%) and 6/20 (30%) CT transcripts having an expression frequency >20%, respectively, while renal and colon cancer are low CT gene expressors, with only 3/33 (9%) and 4/25 (16%) CT transcripts having an expression frequency >20%, respectively. In normal tissues, standardized RT-PCR experiments showed that 19/43 CT genes were testis-restricted, 10/43 CT genes were tissue-restricted (mRNA detected in 2 or fewer non-gametogenic tissues), 9/43 CT genes were differentially expressed (mRNA detected in 3-6 non-gametogenic tissues), and 5/43 CT genes were ubiquitously expressed. With the exception of testis-restricted CT transcripts, all remaining CT transcripts were expressed in normal pancreas. In terms of immunogenicity, 14/29 testis/tissue-restricted CT gene families have been shown to induce a cellular and/or humoral immune response in humans. In view of the expanding list of CT genes, a CT gene database was created to standardize CT nomenclature and accumulate relevant data regarding their expression profiles, immunogenicity, function (where known), gene structure and location, and orthologous groups.
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PMID:The cancer/testis genes: review, standardization, and commentary. 1473 73

Cisplatin continues to play a central role in cancer chemotherapy in spite of its toxicity. It is used as first-line chemotherapy against epithelial malignancies of lung, ovarian, bladder, testicular, head and neck, esophageal, gastric, colon and pancreatic but also as second- and third-line treatment against a number of metastatic malignancies including cancers of the breast, melanoma, prostate, mesothelioma, leiomyosarcomas, malignant gliomas and others. Cisplatin has become the gold standard treatment against cervical cancer in combination with radiotherapy. This review summarizes the state of the art on clinical trials published mainly in 2002 using cisplatin and carboplatin in their combinations with other anticancer drugs. For most advanced cancers the response rate to chemotherapy is about 50% in first-line treatments and about 15% in second- or third-line treatments; for example response rates of 25-50% have been observed for chemonaive patients with advanced non-small cell lung cancer treated with cisplatin or carboplatin in combination with gemcitabine or taxanes and in exceptional cases these rates are up to 80% with addition of radiotherapy. Response rates are very discouraging in second- or third-line chemotherapy treatments (7-25%). Despite an increase in response rate from the use of modern-day chemotherapy drugs, no major difference in long-term survival has been achieved. It is a high priority to invent novel approaches for cancer treatment. It is hoped that a fraction of the numerous experimental drugs will show virtues in the anticancer arena especially combined with existing treatment regimens. Efforts should focus on diminution of side effects improving the quality of life of the patient. A preferential tumor targeting of chemotherapy treatments would bring a revolution in molecular medicine and would greatly advance cancer therapy in the upcoming years.
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PMID:Recent clinical trials using cisplatin, carboplatin and their combination chemotherapy drugs (review). 1476 8


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