Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ceramide levels are elevated in mantle cell lymphoma (MCL) cells following treatment with cannabinoids. Here, we investigated the pathways of ceramide accumulation in the MCL cell line Rec-1 using the stable endocannabinoid analogue R(+)-methanandamide (R-MA). We further interfered with the conversion of ceramide into sphingolipids that promote cell growth. Treatment with R-MA led to increased levels of ceramide species C16, C18, C24, and C(24:1) and transcriptional induction of ceramide synthases (CerS) 3 and 6. The effects were attenuated using SR141716A, which has high affinity to cannabinoid receptor 1 (CB1). The CB1-mediated induction of CerS3 and CerS6 mRNA was confirmed using Win-55,212-2. Simultaneous silencing of CerS3 and CerS6 using small interfering RNA abrogated the R-MA-induced accumulation of C16 and C24. Inhibition of either of the enzymes serine palmitoyl transferase, CerS, and dihydroceramide desaturase within the de novo ceramide pathway reversed ceramide accumulation and cell death induced by R-MA treatment. To enhance the cytotoxic effect R-MA, sphingosine kinase-1 and glucosylceramide synthase, enzymes that convert ceramide to the pro-proliferative sphingolipids sphingosine-1-phospate and glucosylceramide, respectively, were inhibited. Suppression of either enzyme using inhibitors or small interfering RNA potentiated the decreased viability, induction of cell death, and ceramide accumulation induced by R-MA treatment. Our findings suggest that R-MA induces cell death in MCL via CB1-mediated up-regulation of the de novo ceramide synthesis pathway. Furthermore, this is the first study were the cytotoxic effect of a cannabinoid is enhanced by modulation of ceramide metabolism.
Mol Cancer Res 2009 Jul
PMID:Potentiation of cannabinoid-induced cytotoxicity in mantle cell lymphoma through modulation of ceramide metabolism. 1960 4

Seven of 30 female dogs diagnosed with inflammatory mammary cancer were given chemotherapy and palliative treatment, and the other 23 received only palliative treatment. The median survival time of the seven dogs given chemotherapy was 57 days, compared with 35 days for the 23 given only palliative treatment.
Vet Rec 2009 Jul 18
PMID:Survival time of dogs with inflammatory mammary cancer treated with palliative therapy alone or palliative therapy plus chemotherapy. 1971 39

High expression of the epidermal growth factor receptor (EGFR) has been implicated in the development of pancreatic cancer. Gefitinib is an orally active and selective EGFR-TKI (EGFR-tyrosine kinase inhibitor) that blocks signal transduction pathways responsible for the proliferation and survival of cancer cells, and other host-dependent processes promoting cancer growth. This study investigated the anticancer effect of gefitinib on human pancreatic cancer cells and the molecular mechanism involved. We first evaluated the effect of gefitinib on cell proliferation with MTT assay and the results demonstrated that gefitinib significantly inhibited the proliferation of pancreatic cancer cells. Flow cytometric analysis showed that gefitinib induced a delay in cell cycle progression and a G0/G1 arrest together with a G2/M block; these were associated with increased expression of p27(Kip1) cyclin-dependent kinase inhibitor combined with decreased expression of aurora B. Besides, luciferase reporter assay revealed that transcriptional mechanism was responsible for the down-regulation of aurora B protein by gefitinib. Overall, the results suggest a mechanistic connection among these events to provide new insights into the mechanism underlying the antiproliferative effect of gefitinib on pancreatic cancer and supplement a theory basis of gefitinib in clinical treatment of pancreatic cancer.
Anat Rec (Hoboken) 2009 Aug
PMID:Gefitinib inhibits the proliferation of pancreatic cancer cells via cell cycle arrest. 1964 12

Most experimental work addressing cyclooxygenase-2 (COX-2) inhibitor has focused on suppressing hematogenic spread. Little is known about the mechanism by which this inhibitor can also block lymphatic metastasis. Here, the effects of COX-2 inhibitor on vascular endothelial growth factor-C (VEGF-C) expression, lymphangiogenesis and lymph node metastasis were investigated. Utilizing the highly metastatic human lung adenocarcinoma cell line Anip973 and its parental line AGZY83-a, which has a low metastatic capacity, we found elevated VEGF-C and COX-2 immunoreactivity in Anip973 cells compared with AGZY83-a cells. Celecoxib down-regulated expression of VEGF-C mRNA and protein in Anip973 cells while PGE(2) up-regulated expression of VEGF-C mRNA and protein in AGZY83-a cells in a concentration-dependent manner. The expression of COX-2 and VEGF-C was significantly increased in xenografted Anip973 tumors compared with AGZY83-a tumors. The Anip973 tumors showed more lymphatic vessels and lymph node metastasis than the AGZY83-a tumors. In vivo, celecoxib decreased VEGF-C expression in Anip973 tumor-treated mice to a similar level to that in the AGZY83-a tumor-treated mice. Consistent with this decrease in VEGF-C expression, the density of lymphatic vessels and lymph node metastasis in Anip973 tumor-treated mice were suppressed to approximately that found in the AGZY83-a tumor-treated ones. Taken together, our results suggest that the differential expression of COX-2 and VEGF-C might help explain the different metastasis phenotype of lung adenocarcinoma cancer, and that COX-2 inhibitor mediates VEGF-C to block lymphangiogenesis and lymph node metastasis. Thus, COX-2 may be a potential therapeutic target for blocking lymph node metastasis in lung adenocarcinoma.
Anat Rec (Hoboken) 2009 Oct
PMID:Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via VEGF-C. 1968 8

Caveolin-1 (CAV-1) has been reported to play an important role in the development of a variety of human cancers. CAV-1 expression is revealed to be reduced or absent in the malignant tumor cells of small cell lung cancers (SCLC). This study was performed to investigate the influences of the stable expression of CAV-1 on the metastasis and proliferation of SCLC in vitro. The wild-type CAV-1 gene was successfully transfected into the NCI-H446 cells and was stably expressed in the NCI-H446 cells. The effects of CAV-1 on the morphology, proliferation, and metastasis potential for NCI-H446 cell were evaluated by crystal violet staining, MTT analysis, transwell assay, and scratch wound assay, respectively. Western blot and gelatin zymography were used to examine the expression changes of the metastasis-related MMP-3 and E-cadherin. Stable expression of CVA-1 was observed in the H446-CAV-1 cells, which enlarged the cell shape with filopodia. The proliferation of H446-CAV-1 was inhibited, while its migration and invasion abilities were promoted in vitro. The re-expression of CAV-1 reduced the expression of E-cadherin, while it increased the protein expression and enzyme activity of MMP-3. Taken together, the cellular proliferation of the NCI-H446 could be inhibited by the re-expression of CAV-1. CAV-1 might increase the cell metastasis potential through the interaction with E-cadherin and MMP-3 genes. These in vitro findings confirm the involvement of CAV-1 in the proliferation and metastasis of SCLC.
Anat Rec (Hoboken) 2009 Oct
PMID:Caveolin-1 is an important factor for the metastasis and proliferation of human small cell lung cancer NCI-H446 cell. 1971 15

Changes in reproductive tract histomorphology, and estrogen (ERalpha) and progesterone receptor (PR) expression throughout the breeding cycle were evaluated in free-ranging stranded female California sea lions (Zalophus californianus). Hormone receptor expression in the ovaries, uterus, cervix, and vagina was evaluated using an immunohistochemical technique with monoclonal antibodies. During a large portion of the cycle, ovaries contained both a corpora lutea (CL) and follicles in varying stages of development. In the periods of pupping and estrus during June and July, and in the spring morphologic features of the endometrium suggested estrogen influence. There were areas of squamous differentiation in the pseudostratified columnar epithelium of the cervix and vagina in some animals during estrus and in the spring. Estrogen receptor immunohistochemical scores were highest during pupping and estrus and in the spring and lowest during embryonic diapause. Cyclic changes in uterine PR expression throughout the cycle were minimal. Both ERalpha and PR were expressed in epithelial and stromal cells throughout the cervix and vagina, however, receptor expression was typically higher in the stroma. Stromal cell hormone receptors may play an important role in epithelial responses to circulating sex hormones. The results of this investigation add to the general knowledge of California sea lion reproduction and establish baseline information on reproductive tract hormone receptors that will aid in determining the factors involved in urogenital cancer development in sea lions.
Anat Rec (Hoboken) 2009 Nov
PMID:The normal genital tract of the female California sea lion (Zalophus californianus): cyclic changes in histomorphology and hormone receptor distribution. 1976 49

Neurogenesis in the embryo involves many signaling pathways and transcriptional programs and an elaborate orchestration of cell cycle exit in differentiating precursors. However, while the neurons differentiate into a plethora of different subtypes and different identities, they also presume a highly polar structure with a particular morphology of the cytoskeleton, thereby making it almost impossible for any differentiated cell to re-enter the cell cycle. It has been observed that dysregulated or forced cell cycle reentry is closely linked to neurodegeneration and apoptosis in neurons, most likely through changes in the neurocytoskeleton. However, proliferative cells still exist within the nervous system, and adult neural stem cells (NSCs) have been identified in the Central Nervous System (CNS) in the past decade, raising a great stir in the neuroscience community. NSCs present a new therapeutic potential, and much effort has since gone into understanding the molecular mechanisms driving differentiation of specific neuronal lineages, such as dopaminergic neurons, for use in regenerative medicine, either through transplanted NSCs or manipulation of existing ones. Nevertheless, differentiation and proliferation are two sides of the same coin, just like tumorigenesis and degeneration. Tumor formation may be regarded as a de-differentiation of tissues, where cell cycle mechanisms are reactivated in differentiated cell types. It is thus important to understand the molecular mechanisms underlying various brain tumors in this perspective. The recent Cancer Stem Cell (CSC) hypothesis also suggests the presence of Brain Tumor Initiating Cells (BTICs) within a tumor population, although the exact origin of these rare and mostly elusive BTICs are yet to be identified. This review attempts to investigate the correlation of neural stem cells/precursors, mature neurons, BTICs and brain tumors with respect to cell cycle regulation and the impact of cell cycle in neurodegeneration.
Anat Rec (Hoboken) 2009 Dec
PMID:From birth till death: neurogenesis, cell cycle, and neurodegeneration. 1994 48

Trichosanthin (TCS) is a type I ribosome-inactivating protein that is isolated from the root tubers of the Chinese medicinal herb Trichosanthes kirilowii Maximowicz. TCS has been used as an abortifacient for 1,500 years in China because of its high toxicity on trophoblasts. Over the past 20 years, TCS has been the subject of much research because of its potential antitumor activities. Many reports have revealed that TCS is cytotoxic in a variety of tumor cell lines in vitro and in vivo. Monoclonal antibody-conjugated TCS could enhance its antitumor efficacy; thus, TCS is considered to be a potential biological agent for cancer treatment. TCS is able to inhibit protein synthesis and consequently induce necrosis. Recent studies have demonstrated that TCS does indeed induce apoptosis in several tumor cell lines. Although TCS-induced apoptosis of tumor cell lines is now well known, the underlying mechanisms remain to be elucidated. The purpose of this review was to investigate the effects of TCS and its possible mechanisms of action, based on published literature and the results of our own studies.
Anat Rec (Hoboken) 2010 Jun
PMID:Possible mechanisms of trichosanthin-induced apoptosis of tumor cells. 2022 1

Microrchidia2 (MORC2) is a member of the MORC protein family that is localized to both the nucleus and cytoplasm when transiently expressed in gastric cancer cells. We identified and analyzed the functional domains of MORC2, which has specific unique structural characteristics compared to the other MORC proteins. Our data showed that nuclear localization signals (NLS) of MORC2 was mainly dependent on the NLS amino acids (aa) 657-781 and cytoplasmic localization of MORC2 was attributed to the nuclear export signal (NES) aa 481-657. Moreover, the NLS appears to predominate over the NES in the localization of full-length human MORC2 indicating that MORC2 is localized mainly in the nucleus. Our results also demonstrated that the NLS (aa 657-781) and proline-rich domain within MORC2 C-terminus were required for the transcriptional repressive role in cancer cells.
Anat Rec (Hoboken) 2010 Jun
PMID:Identification and expression analysis of a novel CW-type zinc finger protein MORC2 in cancer cells. 2022 2

Vinblastine has been widely known as a prominent agent in cancer chemotherapy, and in order to search for more potent drugs, various analogs have been derived from natural products. However, because modifications of natural products have limited classes of derivatives, an efficient synthetic route toward vinblastine has been required.Herein a stereocontrolled total synthesis of (+)-vinblastine is described. The synthesis of the upper half features a stereoselective construction of the tertiary alcohol through a 1,3-dipolar cycloaddition of nitrile oxide and a Baeyer-Villiger oxidation, a facile indole formation utilizing a radical cyclization of o-alkenylthioanilide, and a macrocyclization of 2-nitrobenzenesulfonamide. The crucial coupling of the upper half with synthetic vindoline was successfully performed to furnish the coupling product in nearly quantitative yield, and subsequent transformations provided (+)-vinblastine.
Chem Rec 2010 Apr
PMID:Total synthesis of (+)-vinblastine: control of the stereochemistry at C18'. 2039 3


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