Nuclear magnetic resonance spectroscopy has detected elevated phosphocholine levels in human tumor tissues and cells, and in cells that were transformed with the activated Ha-ras gene and stimulated in vitro with growth-promoting factors such as platelet-derived growth factor, epidermal growth factor, and phorbol ester. However, the mechanism of the elevation and the function of the increased phosphocholine levels have not been clearly demonstrated. We studied phosphocholine levels enzymatically and analyzed the activity of choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in human colon cancer and adenoma. Both choline kinase activity and phosphocholine levels were increased in colon cancer and adenoma tissue. The activation of choline kinase and the increased levels of choline kinase α α α α were partly responsible for the elevated phosphocholine levels. This study suggests that choline kinase might play a role in growth promotion or signal transduction in carcinogenesis.Key words: Choline kinase -Phosphocholine -Human colon cancerCancer of the colon is one of the most common cancers in developed countries and its prevention is of great interest throughout the world. It is thought that the accumulation of certain mutated genes, including oncogenes, tumor suppressor genes, genes for DNA-repair enzymes, and invasion/metastasis-related genes, is necessary for the onset and progression of cancer. Mutation may cause further malignant changes in cellular proliferation, especially in enzymatic properties and activity.1-3) Some of the changes in enzymatic properties and activity with proliferation may be advantageous to the cancer cells. [4][5][6][7] Studying the cellular properties of cancer cells improves our understanding of the mechanism of cellular growth control and sheds further light on cancer prevention and treatment. 8) Choline kinase is the first enzyme in the cytidine 5′-diphosphate (CDP)-choline pathway for the synthesis of phosphatidylcholine, and phosphorylates choline to phosphocholine using adenosine 5′-triphosphate (ATP) as the phosphate donor. [9][10][11] In vitro studies of oncogenic ras proteins, and products and growth factors have shown that phosphocholine contributes to cellular growth regulation and intracellular signal transduction. Ras proteins play a pivotal role in cellular signal transduction, and help regulate cellular proliferation and terminal differentiation. [12][13][14] Microinjecting the oncogenic Ha-ras gene product p21 ras into Xenopus oocytes causes meiosis, 15) quickly activates choline kinase and elevates phosphocholine levels. 16)Transforming fibroblastic cells with oncogenic Ha-ras also activates choline kinase. [17][18][19] Growth factors essential for cellular growth also activate choline kinase, elevating the intracellular phosphocholine level. Prolactin is one such growth factor for Nb 2 rat node lymphoma cells.20) It has been suggested that platelet-derived growth factor might use a choline kinase-phosphocholine route to promote c...
Cancer cells acquire particular characteristics that benefit their proliferation. We previously reported that human colon cancers examined had increased choline kinase activity and phosphocholine levels. The elevated phosphocholine levels were in part due to both activation of choline kinase and increased choline kinase α α α α protein levels. In this report, we analyzed choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in rat 1,2-dimethylhydrazine (DMH)-induced colon cancer. This study is the first to demonstrate increased choline kinase α α α α enzymatic activity, protein levels, and mRNA levels in DMH-induced colon cancer as well as human colon cancer, although phosphocholine was not increased in DMH-induced rat cancer. The increase in the mRNA level was partly due to an increase in the transcription of the choline kinase α α α α gene. The increased choline kinase activity may be a specific characteristic acquired by cancer cells that benefits their proliferation. Key words: Choline kinase -DMH -CancerCancer of the colon is one of the most common cancers in developed countries and its prevention is of great interest throughout the world. It is thought that an accumulation of mutated genes, including oncogenes, tumor suppressor genes, DNA-repair enzyme genes, and invasion/ metastasis-related genes, is necessary for the generation and progression of cancer. Mutation may cause further malignant changes in cellular proliferation, 1) especially when enzymatic activity and properties are affected. 2-4)Some of the changes that occur in enzymatic properties and activity with proliferation may favor the growth of cancer cells. [5][6][7] Studying the cellular properties of cancer cells furthers our understanding of the mechanisms of cellular growth control and provides clues to strategies for cancer prevention and treatment. 8) 1,2-Dimethylhydrazine (DMH) is widely used for experimental studies of specific colon carcinogenesis in rodents. 9) In the body, the metabolic product of DMH modifies DNA, causes mutation, and leads to carcinogenesis. 10)Choline kinase is the first enzyme in the CDP-choline pathway for the synthesis of phosphatidylcholine, and phosphorylates choline to phosphocholine using adenosine 5′-triphosphate (ATP) as the phosphate donor.11, 12) Ras proteins play a pivotal role in cellular signal transduction, and help regulate cellular proliferation and terminal differentiation. [13][14][15] Microinjection of the oncogenic Ha-ras gene product p21 ras into Xenopus oocytes, which causes meiosis, 16) quickly elevates the phosphocholine level and activates choline kinase.17) Transformation of fibroblastic cells with oncogenic Ha-ras activates choline kinase. [18][19][20] Growth factors essential for cellular growth also activate choline kinase, elevating the intracellular phosphocholine level. It has been suggested that platelet-derived growth factor might use a choline kinase-phosphocholine route to promote cell growth in NIH3T3 fibroblast cells. [21][22][23][24] We pr...
A 59-year-old woman underwent a radical hysterectomy for a metastatic uterine cervix tumor caused by rectal carcinoma, which had been previously resected. Metastatic carcinoma from the large bowel to the uterus is rare. A total of 48 patients (including nine Japanese patients) with metastasis from the large bowel to the uterus were reviewed. The metastatic site of the uterus was the cervix in 27 cases and the corpus in 18. The interval between primary carcinoma and the secondary diagnosis was 17 months. The mean survival after the diagnosis of the secondary deposit was 11 months. Our patient died of lymph node, lung, local and bone metastases 7 months after the diagnosis of the secondary deposit.
Background and Object: Annual mammography and physical examination as the follow-up tests after surgery were recommended to early breast cancer patients based on the two randomized clinical trials (GIVIO and Rosselli Del Turco) which were reported in 1990s. Whereas, radiological imaging and blood test (serum tumor marker) for early detection of recurrence are not recommended due to the lack of evidence from clinical trial. However, the imaging techniques (helical CT, bone scan, PET/CT. MRI et al) to detect minute lesions and therapeutic options for metastatic breast cancer have been remarkably advanced since then. In fact, routine radiological examinations after surgery were performed in several Japanese hospitals for aiming early detection of recurrence as the clinical practice. We here evaluate the possible benefit of early detection of recurrence by radiological and laboratory examinations during post-operative follow-up period. Methods: Clinical information of breast cancer patients who were diagnosed as recurrence after surgery during 2005–2006 was collected from 30 hospitals in Japan. Clinical and pathological characteristics such as molecular subtype of breast cancer, survival time from initial therapy or 1st recurrence, detection methods and symptomatic information when they diagnosed as metastasis were analyzed retrospectively. Results: As the routine examination of post-operative follow-up, serum tumor maker, chest x-ray/CT, abdominal US/CT and bone scan were done in 95%, 57%, 38%, 24% of 30 hospitals, respectively. Of the 698 patients individually evaluated in this analysis, 248 had loco-regional recurrences and 450 had distant metastases. The first distant metastatic site were 35% in bone, 30% in lung, 17% in liver and 11% in lymph node, respectively. All individual patients are divided into symptomatic (45.7%) or asymptomatic groups (54.3%) at the detection of metastases. Asymptomatic metastases were detected by serum tumor marker (26%), bone scan (18%), chest x-ray (17%), chest CT (17%), abdominal US (11%) and abdominal CT (5%), respectively. The median disease-free interval (DFI) was 3.0 years in both groups, but the median survival time after the diagnosis of recurrence to death were 3.7 years in asymptomatic patients and 3.0 years in symptomatic patients, respectively. In addition, asymptomatic group had significantly superior overall survival (from primary surgery to death) than symptomatic group with oligo-metastases such as limited organ disease (P < 0.001). Conclusions: Our data may support the hypothesis that early detection of breast cancer recurrences has beneficial impact on survival. Randomized clinical trial would be warranted to prove this hypothesis, and we are currently planning this. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-06.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.