Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of a long-acting somatostatin analogue SMS 201.995 (SMS; Sandoz) on basal and gastrin-stimulated growth of 4 human colon cancer lines was studied in vitro and in vivo. Proliferation assay was done with overnight [75Se]selenomethionine uptake after 5 days of incubation. Gastrin concentrations used were 5e-10 M and 1e-7 M. SMS concentrations were from 2e-12 M to 2e-7 M. Cell lines LIM 1215, LIM 2405, and LIM 2412 were inhibited dose-dependently in both basal and gastrin-stimulated groups. LIM 1863 was slightly stimulated. Based on in vivo growth characteristics, LIM 2412 and LIM 2405 were selected for xenograft study. The dose of 50 micrograms/kg/day was arrived at after a preliminary experiment showed it to be safe and effective. The LIM 2412 xenografts in the SMS-treated animals were 473.3 +/- 99.9 (SD) versus 838.1 +/- 111.3 mm3 in control (P less than 0.05) after 20 days. The LIM 2405 tumors were also significantly inhibited (81.2 +/- 30.0 versus 245.7 +/- 48.3 mm3, P less than 0.01). The effect of SMS appeared to be reversible. Oral SMS at 200 micrograms/kg/day was not absorbed. This study suggests that SMS may have direct antitumor effects in human colon cancer.
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PMID:SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer. 173 55

5-fluorouracil (5-FU) is still the most effective cytotoxic agent for the treatment of human colorectal cancer. Response rates, however, vary between 5-20%. One attempt to improve the effect of 5-FU is through biomodulation. We have previously found the somatostatin analogue, SMS 201.995 (Sandostatin, Sandoz), to inhibit both the in-vitro and in-vivo growth of some human colon cancer cell lines. It may act specifically by means of receptors on the surface of tumour cells, or by reducing the concentration of some growth factors. We report that, when 5-FU at 0.125 and 0.25 micrograms/ml was combined with SMS 201.995 at 10(-12) x 2 to 10(-8) x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved. Effects were measured using [3H]-thymidine uptake and by a colorimetric assay of cellular respiration (MTT, Promega, Sydney). SMS 201.995 alone has minimal inhibitory effects, whilst 5-FU alone shows inhibition as low as 39.6% of control. When 5-FU was then combined with SMS 201.995, a 10-30% inhibition occurred compared to the 5-FU control. The combination of 5-FU and SMS 201.995 may be a useful method of improving response to human colorectal cancer therapy.
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PMID:SMS 201.995 (Sandostatin) enhances in-vitro effects of 5-fluorouracil in colorectal cancer. 785 48

The effects of somatostatin analogues RC-160 and SMS-201-995 on tyrosine phosphatase and cell proliferation were investigated in COS-7 and NIH 3T3 cells expressing human somatostatin receptor subtype 1 or 2 (SSTR1 or SSTR2). Binding experiments were performed on membranes from COS-7 cells expressing human SSTR1 or SSTR2 using 125I-labeled [Tyr11]S-14 or [Tyr3]SMS-201-995, respectively. The somatostatin analogues RC-160 and SMS-201-995 exhibited low affinity for SSTR1 (IC50 of 0.43 and 1.5 microM, respectively) and high affinity for SSTR2 (IC50 of 0.27 and 0.19 nM). Addition of these analogues to cells expressing either SSTR1 or SSTR2 did not result in an inhibition of adenylate cyclase activity. In SSTR2-expressing cells, both analogues induced a rapid stimulation of a tyrosine phosphatase activity (EC50: RC-160, 2 pM; SMS-201-995, 6 pM) and an inhibition of serum-stimulated proliferation (EC50: RC-160, 6.3 pM; SMS-201-995, 12 pM). In SSTR1-expressing cells, only RC-160 induced stimulation of a tyrosine phosphatase activity. Both analogues caused an inhibition of cell proliferation at a concentration higher than 10 nM in accordance with their affinities for the SSTR1 receptor subtype. A good correlation between the affinities of RC-160 and SMS-201-995 for each receptor subtype and their potencies to inhibit cell proliferation suggests the involvement of these receptors in cell growth regulation. Tyrosine phosphatase was stimulated by both these analogues in SSTR2 and by RC-160 in SSTR1 at affinities similar to their ability to inhibit growth and bind to receptors, implicating tyrosine phosphatase as a transducer of the growth inhibition signal. We also found that mRNAs of receptor subtypes were variably expressed in different pancreatic and colon cancer cell lines, indicating the necessity of a precise analysis of receptor subtypes in target tissues before therapy with analogues.
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PMID:Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. 790 95

This study investigated the effect of SMS 201.995 on CEA secretion of human colon cancer cell lines in vitro and as xenografts in nude mice. Using the two cell lines which secreted significant amounts of CEA in the media, there was a 40% and 54% decrease in CEA level at 2e-10M and 2e-9M concentrations of SMS 201.995, respectively, after five days of incubation for LIM 2412 cell line (P < 0.05, both). There was a 13% decrease in CEA at 2e-9M concentration of SMS with the LoVo cell line (P > 0.05). In vivo, there was a direct correlation between the mean volume of the LIM 2412 xenografts and serum CEA level (r = 0.92). When the growth of xenografts was inhibited by SMS, there was a corresponding drop in serum CEA. On the other hand, when tumor sizes remained unchanged, whether after a short duration of SMS treatment or with the oral route, serum CEA was unaffected. Thus, CEA concentration reflected cell number in vitro and tumor size in vivo as a response to treatment with SMS 201.995. The CEA level may therefore be a useful marker during somatostatin treatment to monitor tumor response.
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PMID:Somatostatin inhibits both in-vitro and in-vivo carcinoembryonic antigen secretion by human colon cancer. 849 20

The activity of the synthetic somatostatin analogue SMS 201-995 was investigated in vitro on the growth of SW480 and SW620 human colon adenocarcinoma cell lines. The inhibition of cell proliferation was significant in SW480 cells (-19.6 +/- 1.4% at SMS 201-995 10-9 M, P < 0.05), but not in SW620 cells (-5.5 +/- 0.8% at SMS 201-995 10-8 M) as compared to untreated cultures. Moreover, SMS 201-995 10-8 M decreased the mitogenic effect of epidermal growth factor (EGF) on the SW480 cell line (-26.6 +/- 3.4% vs. cells exposed to EGF 10 ng ml-1 alone, P < 0.05). The effect of combining SMS 201-995 plus the cytokines interleukin-2 (IL-2) or gamma-interferon (gamma-IFN) on SW480 and SW620 cancer cell growth was also evaluated. The treatment produced a synergistic antiproliferative effect against SW620 cells as compared to untreated cultures, with growth inhibition being -20.2 +/- 1.2 and -19.3 +/- 1.3%, at SMS 201-995 10-8 M plus IL-2 or gamma-IFN 100 IU ml-1, respectively, but did not increase the activity of SMS 201-995 against the SW480 cells. In conclusion, the effect of SMS 201-995 on colon cancer cell growth can be enhanced by its combination with cytokines in SW620 but not in SW480 colon adenocarcinoma cells.
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PMID:Inhibitory effect of the somatostatin analogue SMS 201-995 and cytokines on the proliferation of human colon adenocarcinoma cell lines. 874 43

There is much evidence of the antiproliferative activity of somatostatin (SS) and melatonin (Mel) upon the normal and neoplastic tissues. It has also been found, that both substances are able to alter, under certain conditions, apoptotic processes. Recently, it has been postulated that apoptosis plays a pivotal role in the control of tumour growth. So far, there is no data about the effect of SS analogue--octreotide (Sandostatin, SMS) and Mel on the apoptosis of colon cancer cells. The aim of this study is to examine the effects of SMS and Mel administered separately or together on apoptosis, bromodeoxyuridine incorporation and weight of tumours in the murine transplantable Colon 38 cancer. The male mice were implanted subcutaneously (s.c.) with a suspension of Colon 38 cells. After 6 days, the animals were subcutaneously injected with SMS, Mel, SMS and Mel together (once daily at 6-8 p.m., for 6 days). The incorporation of bromodeoxyuridine (BrDU) into cell nuclei was used as an index of cell proliferation (labelling index-LI). The in situ labelling of nuclear DNA fragmentation according to TUNEL method was considered as an apoptotic index (AI). Given separately, both SMS and Mel significantly decreased the LI and increased the AI. However, we have not observed any additive effect of SMS and Mel on either BrDU incorporation or apoptosis. The mean AI in the group treated jointly with SMS and Mel was significantly lower than in groups treated separately with SMS or Mel. It was also found, that the proliferation/apoptosis ratio were significantly lower in the group treated with SMS or MEL, which means that the imbalance between these two processes changed in favour of cell death. Possibly, the observed antitumour effects of these two substances could be due to this alteration.
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PMID:Somatostatin analogue octreotide and melatonin inhibit bromodeoxyuridine incorporation into cell nuclei and enhance apoptosis in the transplantable murine colon 38 cancer. 985 48

ZCH-2B8a (IgG2a) is a novel monoclonal antibody (McAb) generated in laboratory of Children Hospital of Medical College, Zhejiang University recently using human myeloblastic leukemia cell line KG1a as immunogen. This antibody has been submitted to the 8th International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA8) and the results showed that the antibody recognized an unknown molecule on the surface of some blood cells. The aim of this study was to investigate the reactivity of this antibody on normal blood cells and malignant cell lines and to explore its possible application in clinical practice. The multi-parameter flow cytometry was used to analyze the expression pattern of 2B8a antigen in triplicate on normal blood components including T cells, B cells, natural killers (NK), neutrophils, monocytes, dendritic cells (DC), red blood cells (RBC), platelets (Plt), hematopoietic stem/progenitor cells derived from either bone marrow or G-CSF mobilized peripheral blood CD34(+) cells and malignant cell lines including 14 hematopoietic, 5 neuroblastoma, 1 colon cancer and 1 amniotic epithelium cell lines. The amount of positive cells > or = 20% was considered as positivity. The results showed that 2B8a antibody reacted to 3/3 specimens of blood B cells with a positive rate of 26.29% and 2/3 specimens of monocytes with an average positive rate of 59.84%. 2B8a was weakly reactive to neutrophils (23.72%) and negative for T cells, NK, DC, RBC and Plt. The antibody reacted to all 3 marrow CD34(+) cells with an average positive rate of 39.33% while it was negative for G-CSF-mobilized CD34(+) peripheral blood stem/progenitor cells (PBSC, 1.25%). Cell line analysis showed that the antibody notably reacted to three out of 4 cell lines (Raji, SMS-SB, Nalm-6 and Nall-1) with the positive rates of 98.78%, 98.61%, 94.93% respectively and weakly to one of them with 5.68% in B lineage cell lines and monoblastic cell line (U937, 67.78%) while it was only weakly positive or negative for other myeloid leukemia cell lines including Meg01 (33.40%), HL-60 (29.70%), K562 (28.19%), KG1a (16.23%) and HEL92.1.7 (8.02%). Among 4 T lineage leukemia, 5 neuroblastoma and 1 colon cancer cell lines tested, only Molt-3 was found weakly positive (31.40%) for 2B8a, while the remaining 3 T cell lines (Molt4, JM and CCRF-CEM), 5 neuroblastoma cell lines (LA-N1, KCNR, BE, SK-N-SH, SK-N-AS) and the colon cancer cell line (HR8348) tested were negative. An amniotic epithelium cell line (FL) was showed positive for the antibody (45.03%). It is concluded that 2B8a antibody primarily reacts to B lineage and monocytic lineage cells which may bear the diagnostic and therapeutic applications among different types of hematopoietic malignancies.
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PMID:[Reactivity of a novel monoclonal antibody ZCH-2B8a on normal hematopoietic cells and malignant cell lines and its significance]. 1709 4

Colorectal cancer is the third most incidental cancer worldwide, and the response rate of current treatment for colorectal cancer is very low. Genome-scale metabolic models (GEMs) are systems biology platforms, and they had been used to assist researchers in understanding the metabolic alterations in different types of cancer. Here, we reconstructed a generic colorectal cancer GEM by merging 374 personalized GEMs from the Human Pathology Atlas and used it as a platform for systematic investigation of the difference between tumor and normal samples. The reconstructed model revealed the metabolic reprogramming in glutathione as well as the arginine and proline metabolism in response to tumor occurrence. In addition, six genes including ODC1, SMS, SRM, RRM2, SMOX, and SAT1 associated with arginine and proline metabolism were found to be key players in this metabolic alteration. We also investigated these genes in independent colorectal cancer patients and cell lines and found that many of these genes showed elevated level in colorectal cancer and exhibited adverse effect in patients. Therefore, these genes could be promising therapeutic targets for treatment of a specific colon cancer patient group.
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PMID:Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling. 3141 67