Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

An 80-year-old man presenting with abdominal distension was admitted to our hospital. He was diagnosed with sigmoid cancer with multiple liver and lung metastases. We first performed a sigmoidectomy to avoid obstruction, and then initiated chemotherapy with S-1(120mg/day). The tumor showed a complete clinical response after 10 courses, but we had to change the regimen after 18 courses because of growth of the lung metastases. After 10 courses of capecitabine(4,200mg/ day)treatment, we again observed growth of the lung metastases; a new nodule, which was also considered to be a metastasis, appeared on the abdominal wall. We then decided to administer mFOLFOX6(5-fluorouracil+Leucovorin+oxaliplatin) after the patient had received oral anticancer drugs for 3 years 4 month. In conclusion, oral chemotherapy drugs may prevent tumor growth over a long period and improve quality of life(QOL)in elderly patients with Stage IV colon cancer.
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PMID:[A case of Stage IV sigmoid colon cancer that achieved long-term survival with oral anticancer drugs]. 2474 89

The mechanisms that allow colon cancer cells to form liver and lung metastases, and whether KRAS mutation influences where and when metastasis occurs, are unknown. We provide clinical and molecular evidence showing that different MAPK signalling pathways are implicated in this process. Whereas ERK2 activation provides colon cancer cells with the ability to seed and colonize the liver, reduced p38 MAPK signalling endows cancer cells with the ability to form lung metastasis from previously established liver lesions. Downregulation of p38 MAPK signalling results in increased expression of the cytokine PTHLH, which contributes to colon cancer cell extravasation to the lung by inducing caspase-independent death in endothelial cells of the lung microvasculature. The concerted acquisition of metastatic traits in the colon cancer cells together with the sequential colonization of liver and lung highlights the importance of metastatic lesions as a platform for further dissemination.
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PMID:Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH. 2548 43

The progression of tumors to the metastatic state involves the loss of metastatic suppressor functions. Finding these, however, is difficult as in vitro assays do not fully predict metastatic behavior, and the majority of studies have used cloned cell lines, which do not reflect primary tumor heterogeneity. Here, we have designed a novel genome-wide screen to identify metastatic suppressors using primary human tumor cells in mice, which allows saturation screens. Using this unbiased approach, we have tested the hypothesis that endogenous colon cancer metastatic suppressors affect WNT-TCF signaling. Our screen has identified two novel metastatic suppressors: TMED3 and SOX12, the knockdown of which increases metastatic growth after direct seeding. Moreover, both modify the type of self-renewing spheroids, but only knockdown of TMED3 also induces spheroid cell spreading and lung metastases from a subcutaneous xenograft. Importantly, whereas TMED3 and SOX12 belong to different families involved in protein secretion and transcriptional regulation, both promote endogenous WNT-TCF activity. Treatments for advanced or metastatic colon cancer may thus not benefit from WNT blockers, and these may promote a worse outcome.
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PMID:A novel genome-wide in vivo screen for metastatic suppressors in human colon cancer identifies the positive WNT-TCF pathway modulators TMED3 and SOX12. 2492 Jun 8

We retrospectively analyzed the efficacy of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer, with particular emphasis on local tumor control. Seven patients with 8 lesions underwent SRT for lung metastasis of colon cancer in our institution between February 2012 and February 2014. We judged the curative effect of SRT on the basis of tumor shrinkage observed on computed tomography (CT) scans. All lung metastases decreased in size, and local recurrence was not observed. SRT is a technique involving three-dimensional radiation, which decreases radiation exposure to neighboring normal tissues. The 2-year local tumor control rate for lung metastasis of colon cancer with SRT is 77.9%, and the 2-year survival rate is 53.7%. Our results, in which all patients achieved local control, suggest that SRT is a minimally aggressive treatment option for lung metastasis of colon cancer in cases where a pneumonectomy is difficult to perform. In the future, results from long-term studies are needed to validate our findings.
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PMID:[A review of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer]. 2573 Dec 19

A 69-year-old man underwent right hemicolectomy and D3 lymphadenectomy for transverse colon cancer in 2009. Under the postoperative pathological diagnosis of Stage IIIb (pT3pN2cM0) cancer, he was given 8 courses of adjuvant chemotherapy with capecitabine. After the chemotherapy, in April 2013, we detected recurrence of the multiple liver and lung metastases; thus, we administered modified 5-fluorouracil, Leucovorin, oxaliplatin (mFOLFOX6) and bevacizumab. Six courses of oxaliplatin infusion were completed uneventfully. However, 3 min after starting the seventh infusion courses, the patient experienced cardiopulmonary arrest. We immediately performed cardiopulmonary resuscitation. The patient's anaphylaxis symptoms resolved after treatment with intravenous epinephrine. He was discharged 3 days after the event with no further complications. Clinicians should be aware that oxaliplatin-induced anaphylactic shock often occurs during the eighth infusion cycle and that this severe hypersensitivity reaction is difficult to predict and prevent.
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PMID:[A case of cardiopulmonary arrest due to hypersensitivity reaction to oxaliplatin for multiple liver and lung metastases of colon cancer]. 2573 49

We describe three cases of resected pulmonary metastasis from postoperative colorectal cancer after preoperative 5-fluorouracil, Leucovorin, oxaliplatin (FOLFOX) chemotherapy. The first case is a 38-year-old man who underwent low anterior resection for rectal cancer in 2003. Subsequently, left lung metastasis occurred in February 2009. FOLFOX chemotherapy was administered, resulting in a partial response (PR) of tumor size. Post-chemotherapy, segmental resection of he S1+2 segments of the left lung was performed in May 2009. A pathological diagnosis of Grade 1b was made. The patient remained recurrence-free 5 years post-surgery. The second case is a 68-year-old man who underwent left half colon resection for descending colon cancer with left lung metastasis in March 2006. FOLFOX chemotherapy was administered, with a PR of lung metastasis size. Post-chemotherapy, a segmental resection of the S4 segment of the left lung was performed in September 2006. A pathological diagnosis of Grade 1b was made. The patient was alive 8 years post-surgery. The third case is a 64-year-old man who underwent low anterior resection for rectal cancer in November 2007. A year later, bilateral lung metastases were detected. FOLFOX+bevacizumab was administered, with a stable disease effect on tumor size. Post-chemotherapy, partial resection of both lungs was performed in March and April 2010. A pathological diagnosis of Grade 1a was made. The patient was recurrence-free at the 4-year follow up. We believe that preoperative FOLFOX chemotherapy may be effective in treating lung metastasis from colon cancer.
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PMID:[Three cases of resected pulmonary metastasis from colorectal cancer after preoperative chemotherapy]. 2573 21

A 61-year-old man presented with lower abdominal pain. Further examination revealed descending colon cancer and multiple liver metastases (S1, S2, and S5). The largest metastatic lesion in S1 showed massive invasion to the inferior vena cava (IVC) and was considered unresectable. Resection of the primary colon cancer was performed in January 2011, followed by several types of systemic chemotherapy(12 courses of capecitabine plus oxaliplatin [XELOX] + bevacizumab[Response Evaluation Criteria In Solid Tumors{RECIST}: PD], 5 courses of folinic acid, fluorouracil, and irinotecan [FOLFIRI] + bevacizumab[RECIST: SD], and 13 courses of FOLFIRI+ panitumumab). After these regimens, the lesions in S1 and S2 substantially decreased in size (RECIST: PR), and the lesion in S5 was no longer visible. The extent of invasion to the IVC significantly reduced, and liver resection(extended left lobectomy)and partial IVC resection were performed in November 2013 without reconstruction of the IVC by using a vascular prosthesis. The patient was discharged uneventfully on postoperative day 16, and administration of tegafur-uracil-Leucovorin (UFT/UZEL) was initiated. After 4 months, a recurrent lesion was found in S5, and partial liver resection was performed. In addition, FOLFIRI+panitumumab was reinitiated for the multiple lung metastases. The patient is alive without progression of disease 3 years and 4 months after colectomy.
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PMID:[A case of hepatic resection after chemotherapy for metastatic colon cancer of the liver with invasion of the inferior vena cava and hepatic vein]. 2573 22

More and more evidences suggest that primary colon and rectum tumors should not be considered as a single disease entity. In this manuscript, we evaluate the metastatic patterns of colon and rectum cancers and analyze the potential distribution of metastatic disease in these two malignancies. Data queried for this analysis include colorectal adenocarcinoma (2010-2011) from the Surveillance, Epidemiology, and End Results Program (SEER) database. Metastatic distribution information was provided for liver, lung, bone and brain. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). All statistical tests were two-sided. Totally, there were 46,027 eligible patients for analysis. We found that colon cancer had a higher incident rate of liver metastasis than rectum cancer (13.8% vs 12.3%), while rectum cancer had a higher incident rate of lung (5.6% vs 3.7%) and bone (1.2% vs 0.8%) metastasis than colon cancer, P<0.001. Colorectal cancer patients with lung metastasis had a higher risk of bone (10.0% vs 4.5%) or brain metastasis (3.1% vs 0.1%) than patients without lung metastases. The 1-year cause-specific survival was not significant different for bone or brain metastasis patients with and without lung metastasis (32.9% vs 38.7%, P=0.3834 for bone, 25.8% vs 36.9%, P=0.6819 for brain). Knowledge of these differences in metastatic patterns may help to better guide pre-treatment evaluation of colorectal cancer patients, especially in making determinations regarding curative-intent interventions.
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PMID:Pattern of distant metastases in colorectal cancer: a SEER based study. 2648 17

Metastatic colorectal cancer (mCRC) carries a poor prognosis with an overall 5-year survival of 13.1%. Therapies guided by tumor profiling have suggested benefit in advanced cancer. We used a multiplatform molecular profiling (MP) approach to identify key molecular changes that may provide therapeutic options not typically considered in mCRC. We evaluated 6892 mCRC referred to Caris Life Sciences by MP including sequencing (Sanger/NGS), immunohistochemistry (IHC) and in-situ hybridization (ISH). mCRC metastases to liver, brain, ovary or lung (n = 1507) showed differential expression of markers including high protein expression of TOPO1 (52%) and/or low RRM1 (57%), TS (71%) and MGMT (39%), suggesting possible benefit from irinotecan, gemcitabine, 5FU/capecitabine and temozolomide, respectively. Lung metastases harbored a higher Her2 protein expression than the primary colon tumors (4% vs. 1.8%, p = 0.028). Brain and lung metastases had higher KRAS mutations than other sites (65% vs 59% vs 47%, respectively, p = 0.07, <0.01), suggesting poor response to anti-EGFR therapies. BRAF-mutated CRC (n = 455) showed coincident high protein expression of RRM1 (56%), TS (53%) and low PDGFR (22%) as compared with BRAF wild-type tumors. KRAS-mutated mCRC had higher protein expression of c-MET (47% vs. 36%) and lower MGMT (56% vs. 63%), suggesting consideration of c-MET inhibitors and temozolomide. KRAS-mutated CRC had high TUBB3 (42% vs. 33%) and low Her2 by IHC (0.5%) and HER2 by FISH (3%, p <0.05). CRC primaries had a lower incidence of PIK3CA and BRAF mutations in rectal cancer versus colon cancer (10% and 3.3%, respectively). MP of 6892 CRCs identified significant differences between primary and metastatic sites and among BRAF/KRAS sub-types. Our findings are hypothesis generating and need to be examined in prospective studies. Specific therapies may be considered for different actionable targets in mCRC as revealed by MP.
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PMID:Molecular profiling of 6,892 colorectal cancer samples suggests different possible treatment options specific to metastatic sites. 2655 11

We report a patient who experienced a weight loss, general fatigue, and appetite loss and had huge hepatic metastases of colon cancer after right lobectomy for hepatic stone. After 2 courses of treatment with high-dose hepatic arterial infusion of 5-FU (HDHAI; 5-FU 6 g/week), the appetite loss decreased, and low anterior resection was performed. Unfortunately, the other symptoms continued, and she received 5 additional courses of HDHAI during about 6 months. Finally, all of the symptoms disappeared, and she could receive systemic chemotherapy and HAI. Bone metastasis at vertebra TH 9 was observed about 9 months after radiotherapy, and local recurrence at the anastomosis site was observed at about 1 year 1 months after radiotherapy. Both the metastasis and local recurrence were well controlled. Although the lung metastases were growing slowly (number and size), the patient was well enough to go to the hospital on her own and her weight loss almost disappeared. If liver metastases were the most threatening factor of life, HDHAI may be effective for the improvement of symptoms.
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PMID:[A Case Report of Huge Liver Synchronous Metastases of Colon Cancer that Occurred after Right Liver Lobectomy]. 2680 43


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