Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor effects of human recombinant TNF (PAC-4D) were examined on three human gynecological carcinomas transplanted into CD-1 nude mice (uterine cervical carcinoma: UZ-1-N; ovarian carcinoma: OCl-1-N and OS-4-N). PAC-4D was administered intratumorally at a dose of 1,000 U, 3,000 U or 10,000 U/head from day 0 to day 4. Tumor size, body weight and peripheral WBC were measured on days 0, 4, 8, 12 and 16 and histological studies were made on day 6. The results were as follows: With UZ-1-N, intratumoral administration of PAC-4D at doses of 3,000 U and 10,000 U/head caused a marked inhibition of the tumor growth. Similarly, antitumor activity of PAC-4D against OCl-1-N was remarkable at a dose of 10,000 U/head. The administration of PAC-4D at doses of 3,000 U and 10,000 U/head was not effective against OS-4-N. The histological changes of grade II A-B by Ohboshi-Shimosato criteria of response were observed in the tumor of the effective groups against PAC-4D. There were no influences on the body weight and WBC after administration of PAC-4D. Although tumor cells possessed different sensitivities to PAC-4D, PAC-4D is strongly recommended for the treatment of gynecological malignancies.
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PMID:[Antitumor effects of the tumor necrosis factor (PAC-4D) against human gynecological carcinoma transplanted into nude mice]. 360 53

We previously synthesized the 5'-O-diacylphosphatidyl derivative of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (CNDAC), a novel antitumor nucleoside, and observed it to have a high antitumor activity. Since this compound is readily incorporated into liposomal membranes, we liposomalized the compound using a formulation for conventional and long-circulating liposomes, and investigated the antitumor activity of liposomal 5'-O-dipalmitoylphosphatidyl CNDAC (DPP-CNDAC). Long-circulating liposomes composed of DPP-CNDAC, dipalmitoylphosphatidylcholine, cholesterol and palmityl-D-glucuronide (PGlcUA) (2:2:2:1 as a molar ratio), as well as liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of palmityl-D-glucuronide and those composed of only DPP-CNDAC, were injected intravenously into Meth A sarcoma-bearing mice. DPP-CNDAC showed suppression of tumor growth, whereas CNDAC did not at the same concentration, suggesting that 5'-phosphatidylation is useful to enhance therapeutic efficacy. Furthermore, liposomal DPP-CNDAC reduced the acute toxicity, and liposomes containing PGlcUA showed more enhanced activities of reducing tumor growth and increasing the lifetime of the mice than liposomes containing DPPG. To obtain a higher therapeutic efficacy, we injected long-circulating liposomal DPP-CNDAC 5 times. The tumor growth was suppressed to 13.2% (86.8% inhibition), and the survival time of the tumor-bearing mice increased to 128.5% with one completely cured mouse out of five. Next, the effect of DPP-CNDAC incorporation on the in vivo behavior of PGlcUA and DPPG liposomes was examined by a non-invasive method using positron emission tomography (PET). Liposomes were labeled with [2-(18)F]-2-fluoro-2-deoxy-D-glucose, and administered to tumor-bearing mice. PET images and time-activity curves indicated that DPP-CNDAC/PGlcUA-liposomes tended to accumulate in tumor tissues a little bit more than DPP-CNDAC/DPPG-liposomes, although the difference between the two kinds of liposomal distribution was not as marked as between PGlcUA and DPPG liposomes, suggesting that DPP-CNDAC incorporation partly affected the liposomal behavior in vivo but that the long-circulating character of PGlcUA-liposomes might not be fully abolished. Thus, the enhanced therapeutic efficacy of long circulating liposomalized DPP-CNDAC observed here may be due to passive targeting of DPP-CNDAC to the tumor tissue, making this formulation of DPP-CNDAC useful for cancer chemotherapy.
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PMID:Antitumor activity of 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine is enhanced by long-circulating liposomalization. 970 65

The retinoblastoma (Rb) family consists of the tumor suppressor pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies of the retinoblastoma family of proteins in 235 specimens of lung cancer show the tightest inverse association between the histological grading in the most aggressive tumor types and pRb2/p130. This led us to study a panel of human lung cancers for mutations in the RB2/p130 gene. Mutations in the Rb-related gene RB2/p130 were detected in 11 of 14 (78.5%) primary lung tumors by single-strand conformation polymorphism and sequence analysis. A Moloney leukemia virus-based retroviral system was set up, and a comparable viral concentration of 1 x 10(7) infectious units/ml was obtained. Retrovirus-mediated delivery of wild-type RB2/p130 to the lung tumor cell line H23 potently inhibited tumorigenesis in vitro and in vivo, as shown by the dramatic growth arrest observed in a colony assay and the suppression of anchorage-independent growth potential and tumor formation in nude mice. The tumors transduced with the RB2/p130 retrovirus diminished in size after a single injection, and a 12-fold reduction in tumor growth after RB2/p130 transduction compared with the Pac-transduced tumors (92% reduction, P = 0.003) and lacZ-transduced tumors (93% reduction, P < 0.001) was found to be statistically significant. These findings provide the missing confirmation that RB2/p130 is a "bona fide" tumor suppressor gene and strengthen the hypothesis that it may be a candidate for cancer gene therapy for lung cancer.
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PMID:Mutations in the retinoblastoma-related gene RB2/p130 in lung tumors and suppression of tumor growth in vivo by retrovirus-mediated gene transfer. 1147 39

We previously reported that liposomalized 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (DPP-CNDAC), a hydrophobized derivative of the novel antitumor nucleoside CNDAC, is quite useful for cancer therapy. On the other hand, for anti-neovascular therapy, we recently isolated peptides homing to angiogenic vessels from a phage-displayed random peptide library, and observed that peptide-modified liposomal adriamycin strongly suppressed tumor growth, perhaps through damaging angiogenic endothelial cells. In the present study, we modified DPP-CNDAC-liposomes with one of the angiogenic homing peptides, APRPG, and examined their antitumor activity. Three doses of APRPG-modified DPP-CNDAC-liposomes (15 mg/kg as CNDAC) strongly inhibited tumor growth compared with the same number of doses of unmodified DPP-CNDAC-liposomes. The life span was increased 31.8%, with one completely cured mouse out of the six mice treated. Since the accumulation of liposomes in the tumor tissue was not so much different between APRPG-liposomes and non-modified liposomes, the enhanced therapeutic efficacy may be explained as the alteration of targets, i.e. APRPG-modified DPP-CNDAC-liposomes caused tumor growth suppression through damage of angiogenic endothelial cells. Anti-neovascular therapy promises no drug resistance, and should be effective against essentially any kind of solid tumor; and thus the present results demonstrate another benefit of the therapy, namely, high efficacy of cancer treatment.
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PMID:Anti-neovascular therapy by liposomal DPP-CNDAC targeted to angiogenic vessels. 1204 91

In this review, we discuss the developments of fluorescence in situ hybridization (FISH) and place them in the context of their applications in cancer research. These methods are not only very useful for the causal analysis of the development and spread of certain tumors, they are also efficient tools for tumor diagnosis. Although a review of all of the literature in this field is not possible here, many of the major contributions are summarized along with recent work from our laboratory. Our group contributes to the goal of functional identification of tumor growth antagonizing genes. FISH and molecular analyses have shown that the short arm of human chromosome 3 is frequently deleted in kidney, lung, breast, uterus, testis and ovary carcinomas. Deletion-mapping studies have outlined several separate deletion prone regions in different tumors, namely 3pter-p25, p22-p21.3, p21.1-p14 and p14-p12, which may contain putative tumor suppressor genes (TSGs). Candidate suppressor genes isolated from frequently deleted regions need to be assayed for possible tumor-antagonizing ability by functional tests. We have developed a functional test system, the microcell hybrid (MCH) based "elimination test" (Et). The Et is based on the introduction of a single human chromosome into tumor cells of human or murine origin, via microcell fusion. The MCHs were analyzed by FISH painting and PCR for the elimination or retention of specific human chromosome 3 (chr. 3) regions after one or several passages in severe combined immunedeficient (SCID) mice. We have defined a common eliminated region (CER) on chr. 3p21.3. CER is approximately 1 megabase (Mb) in size. We have covered this region with PACs (bacteriophage PI based artificial chromosome) and used FISH mapping for localization and ordering PACs and cosmids on the chromosome 3 and high-resolution free chromatin/DNA fiber FISH to orient the PAC contig, to measure the lengths of PACs, and to establish their order. Activation of cellular oncogene by chromosomal tanslocation, which brings an oncogene under the influence of a highly active chromosome region, appears to play a pivotal role in the genesis of certain hematopoetic and lymphoid tumors. We have detected specific chromosomal translocations by FISH painting in mouse plamacytoma (MPC), human Burkitt lymphoma (BL) other B-cell derived tumors. We have showed in a murine sarcoma derived line (SEWA) that FISH can be also be used for detection of amplified oncogene (c-myc) and the linked locus (pvt-1). We have also applied the FISH technique for visualization of integrated and episomal Epstein-Barr virus (EBV) genomes and EBV transcripts in EBV-carrying B-cell derived human cell lines.
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PMID:Fluorescence in situ hybridization (FISH) in the molecular cytogenetics of cancer. 1207 27

Among neoplasms, brain tumors are particularly " difficult to treat" because of the partial immune privileged status of the brain and the presence of the blood brain barrier (Selmaj, 1996). Many details of progressive development of brain tumors remain unexplored and elucidation of consequent changes of the immune system with correlated cellular architecture and cell kinetics were the major objectives of the present course of investigations. Our studies have indicated that the primary resistance by the immune system to a growing tumor declines after a certain point, resulting in an immune suppressed state in a tumor bearing individual. The poor prognosis of malignant brain tumors with classical treatments like surgery, radiotherapy and chemotherapy has led to interest in immunotherapeutic protocols. In the present study, an attempt was made to determine the immunomodulatory and antitumor properties of a transmembrane glycopeptide of sheep red blood cells (SRBCs), known as S-LFA3 or T11TS. Young Druckray rat of both sexes aged 3-5 days were injected with N'-N'-ethyl nitrosourea (ENU) (i.p) to induce brain tumors and at 2,4,6,8 and 10 months of age were sacrificed for study of survival, tumor growth kinetics and immunological parameters like lymphocyte rosette formation, denoting CD2 - CD58 interactions and phagocytosis by peripheral macrophages and PMN hint at the changes during tumore development. In order to determine the immunomodulatory role of T11TS, 7 month old ENU induced animals and controls were injected with the compound (1 ml., i.p). The data obtained indicate that administration of T11TS results in increased survival of rats along with a decrease in growth kinetics of tumor cells to the normal level when compared to ENU induced animals of the same age. Pointers to mechanisms involving immunological investigations at the cellular level in these animals indicated improved lymphocyte function in terms of E-rosetting, augmented cytotoxicity and enhanced PMN and macrophage function in terms of phagocytosis. Finally histological examination showed complete reversal from the hyperplastic state to normal cellular homeostasis, indicating antitumor efficacy of T11TS, correlating very well with the data from survival and cell kinetic studies.
Asian Pac J Cancer Prev 2002
PMID:Preclinical Changes in Immunoreactivity and Cellular Architecture during the Progressive Development of Intracranial Neoplasms and an Immunotherapeutic Schedule with a Novel Biological Response Modifier, the T11TS / S-LFA3. 1271 91

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are important neuropeptides in the control of lung physiology. Both of these commonly bind to specific G protein coupled receptors named VPAC(1)-R and VPAC(2)-R, and PAC(1)-R (with higher affinity for PACAP). VIP and PACAP have been implicated in the control of cell proliferation and tumor growth. This study examined the presence of VIP and PACAP receptors in human lung cancer samples, as well as the functionality of adenylyl cyclase (AC) stimulated by both peptides. Results from RT-PCR and immunoblot experiments showed the expression of VPAC(1)-, VPAC(2)- and PAC(1)-R in lung cancer samples. Immunohistochemical studies showed the expression of VPAC(1) and VPAC(2) receptors. These receptors were positively coupled to AC, but the enzyme activity was impaired as compared to normal lung. There were no changes in Galpha(s) or Galpha(i) levels. Present results contribute to a better knowledge of VIP/PACAP actions in lung cancer and support the interest for the development of VIP/PACAP analogues with therapeutic roles.
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PMID:VIP and PACAP receptors coupled to adenylyl cyclase in human lung cancer: a study in biopsy specimens. 1273 41

Because membrane type-1 matrix metalloproteinase (MT1-MMP) is expressed specifically on the angiogenic endothelium as well as tumor cells, an agent possessing the ability to bind to this molecule might be useful as a tool for active targeting of tumor angiogenic vessels. Based on the sequences of peptide substrates of MT1-MMP, which had been determined by using a phage-displayed peptide library, we examined the binding ability of peptide-modified liposomes for endothelial cells and targeting ability for tumor tissues by positron emission tomography (PET). Liposomes modified with stearoyl-Gly-Pro-Leu-Pro-Leu-Arg (GPLPLR-Lip) showed high binding ability to human umbilical vein endothelial cells and accumulated in the tumor about 4-fold more than did the unmodified liposomes. Because we reported previously that liposomalized 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (DPP-CNDAC), a hydrophobized derivative of the novel antitumor nucleoside CNDAC, strongly suppressed tumor growth when delivered in liposomes modified with another angiogenic homing peptide, we examined the antitumor activity of DPP-CNDAC entrapped in GPLPLR-Lip. DPP-CNDAC/GPLPLR-Lip showed significant tumor growth suppression compared to DPP-CNDAC/unmodified liposomes. These results suggest that DPP-CNDAC-liposomes modified with MT1-MMP-targeted peptide are useful for cancer anti-neovascular therapy (ANET), namely, tumor growth suppression by damage to angiogenic endothelial cells.
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PMID:Anti-neovascular therapy by liposomal drug targeted to membrane type-1 matrix metalloproteinase. 1463 19

Disturbances of the ratio between angiogenic inducers and inhibitors in tumor microenvironment are the driving force behind angiogenic switch critical for tumor progression. Angiogenic inhibitors may vary depending on organismal age and the tissue of origin. We showed that alpha(1)-antitrypsin (AAT), a serine protease inhibitor (serpin) is an inhibitor of angiogenesis, which induced apoptosis and inhibited chemotaxis of endothelial cells. S- and Z-type mutations that cause abnormal folding and defective serpin activity abrogated AAT antiangiogenic activity. Removal of the C-terminal reactive site loop had no effect on its angiostatic activity. Both native AAT and AAT truncated on C-terminus (AATDelta) inhibited neovascularization in the rat cornea and delayed the growth of subcutaneous tumors in mice. Treatment with native AAT and truncated AATDelta, but not control vehicle reduced tumor microvessel density, while increasing apoptosis within tumor endothelium. Comparative analysis of the human tumors and normal tissues of origin showed correlation between reduced local alpha(1)-antitrypsin expression and more aggressive tumor growth.
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PMID:Alpha1-antitrypsin inhibits angiogenesis and tumor growth. 1531 42

The Allium genus includes approximately 500 species. Commonly used allium vegetables include garlic, onion, leeks, chives, scallions which are used all over the world in different delicacies. Some allium vegetables have been employed for millenia in the traditional medical practice to treat cardiovascular diseases. They have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents. In recent years, extensive research has focused on the anticarcinogenic potential of allium vegetables and their constituents, viz., allylsulfides and flavonoids (particularly quercetin which is present abundantly in onion). Epidemiological studies have shown that higher intake of allium products is associated with reduced risk of several types of cancers. These epidemiological findings are well correlated with laboratory investigations. Organosulfur compounds present in Allium vegetables, are considered to be responsible for the beneficial effects of these herbs. Several mechanisms have been proposed to explain the cancer-preventive effects of Allium vegetables and related organosulfur compounds. These include inhibition of mutagenesis, modulation of enzyme activities, inhibition of DNA adduct formation, free-radical scavenging, and effects on cell proliferation and tumor growth. Although there is a large body of evidence supporting these mechanisms, they are still speculative, and further research is needed to support causality between such properties and cancer-preventive activity in experimental animals. This article reviews current knowledge concerning allium vegetables and cancer prevention.
Asian Pac J Cancer Prev
PMID:Allium vegetables in cancer prevention: an overview. 1537


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