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)

Several factors concur in determining outcome for locally advanced gastric cancer patients. Shockingly, geographic origin of the patient seems to play a major role. In Eastern countries, the high level of surgery that can be expected grants a high percentage of success in a strategy that employs surgery as immediate treatment followed by adjuvant chemotherapy, mainly based on oral fluoropyrimidines (S-1 or Capecitabine), with satisfactory results. In Western countries, the expertise of the surgeon maintains its role as predictor of high likelihood of cure. Indeed, patients treated with standard D2 lymph node dissection have a significantly better survival than those who do not obtain the same kind of treatment. For patients who underwent a suboptimal resection (less than a D1) the classical indication is for a combined adjuvant chemoradiotherapy. In patients who obtain a good surgical outcome, the benefit of the addition of adjuvant chemotherapy is still debatable: the gain in survival seems to be small (around 8 % at 5 years) and with noticeable toxicities (usually with dismal compliance for patients treated). On this basis, neoadjuvant treatment is a promising option even if there is a general lack of conclusive data regarding which is the best regimen to use. Even with the limitation of a small number of studies (with difficulties in enrollment), neoadjuvant chemotherapy is usually feasible, allows for a greater chance of receiving chemotherapy at all, and opens the possibility of a downstaging and downsizing of the tumor, allowing an easier surgery. Regarding this strategy preliminary results have also been presented about the addition of monoclonal antibodies. For example, in the TOGA trial, a significant benefit in terms of overall survival, response rate, and progression free survival was observed also for patients with locally advanced gastric cancer and not just for the metastatic ones. In the AVAGAST trial also, the addition of Bevacizumab failed to determine a significant improvement in the primary outcome, overall survival, for patients treated with the combination, but in the subgroup analysis, patients with locally advanced gastric cancer had a significantly better overall survival and response rate. This data was the basis for the newest neoadjuvant trial, of Cunningham et al., the MAGIC2 trial, with the peri-operative use of ECX+Bevacizumab. Finally, an increasing interest in the use of hyperthermic intraperitoneal chemotherapy in other types of solid tumors (including those of the gastrointestinal tract such as colon cancer) has led to evaluate this treatment modality in gastric cancer patients with peritoneal involvement. It should be noted that it is still to be considered an experimental approach, even though it would be intriguing to evaluate if a particular subset of patients, those who are more likely to develop peritoneal metastasis, may benefit from this technique in the adjuvant setting. It should be considered that other than histologic subtype (diffuse vs intestinal) there seems to be a series of polymorphisms of genes usually involved in cell interaction and migration that can explain a different metastatic pattern in resected patients. Further research on these determinants of metastatic spread could be used to select those patients who may benefit from HIPEC and those who may benefit from standard adjuvant or that gain no benefit at all.
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PMID:Selecting the best treatment for an individual patient. 2312 82

A 67-year-old man was diagnosed to have sigmoid colon cancer with peritonitis carcinomatosa. The cancer was surgically resected, and he thereafter underwent chemotherapy with mFOLFOX6+bevacizumab. He complained of gingival swelling throughout treatment and osteonecrosis of the jaw was noted. The bevacizumab therapy was therefore discontinued and the necrotic tissue removed. No recurrent necrosis has occurred. The addition of bevacizumab to the FOLFOX or FOLFIRI chemotherapy regimens has been shown to improve the survival rate and response rate in colorectal cancer. Osteonecrosis of the jaw is a rare toxicity of bevacizumab. Bevacizumab might compromise the microvessel integrity in the jaw, which thus may lead to bone necrosis. Osteonecrosis of the jaw in this case recovered after the discontinuation of bevacizumab and the removal of the necrotic tissue. The pathogenesis and treatment of osteonecrosis have not been elucidated.
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PMID:[A case of osteonecrosis of the jaw during treatment by bevacizumab for sigmoid colon cancer]. 2355 29

A 49-year-old woman was admitted to our hospital because of epigastralgia and abdominal distension. She was diagnosed as advanced colon cancer with para-aortic and common iliac lymph node metastases, without liver and lung metastasis. Extended right hemicolectomy was performed to remove symptoms of stenosis. Bevacizumab (BV) (5 mg/kg) + mFOLFOX6 was performed as the initial postoperative chemotherapy. The tumor marker CEA, CA19-9 decreased, and reduction in the size of distant lymph node metastasis was confirmed, which obtained PR. In July 2009, computed tomography revealed the right pulmonary hilar lymph node metastases and progressive disease was confirmed; therefore, cetuximab and FOLFIRI combination therapy was initiated. However, in October 2009, bilateral inguinal lymph node metastases was seen; therefore we changed chemotherapy to BV (10 mg/kg) and FOLFIRI. Although the abdominal lymph node was decreased slightly after 2 months, chemotherapy was changed to BV (10 mg/kg) and mFOLFOX6 since the inguinal lymph node had enlarged. Skin metastases appeared, and there was no change in the inguinal lymph node and abdominal lymph node. She was deceased due to peritonitis carcinomatosis; however, her survival time exceeded 30 months. There was a possibility that long-term survival could be obtained by increasing the quantity of BV and re-administering it in second-line chemotherapy after PD in BV + FOLFOX first-line chemotherapy.
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PMID:[Long-term survival of a patient with advanced colon cancer and para-aortic lymph node metastases treated with re-administration of high-dose molecular targeted agent bevacizumab]. 2419 80

Nodular regenerative hyperplasia (NRH) consists in diffuse transformation of the hepatic parenchyma into small regenerative nodules without fibrosis, secondary to vascular occlusion and flow alterations. This gives a nodular appearance to theliver, as there is atrophy and compensatory hypertrophy of hepatocytes. We reporta 69-year-old male who suffered of colon cancer and was treated with Oxaliplatin (OX) and Bevacizumab (B). During treatment with B the patient presented a partial thrombosis of the portal vein, that one year later became permeable. Esophageal varices were found in an upper digestive endoscopy. Hepatic tests were normal. Aliver biopsy was performed and informed nodular regenerative hyperplasia. Thus, the different factors that could explain this pathology are analyzed. B, a monoclonal antibody against vascular endothelial growth factor, reduces the anti-apoptotic, anti-inflammatory and survival effects produced by this factor, affecting the vascular protection of the endothelial cell. On the other hand, OX activates metalloproteinasesand depletes sinusoidal glutathione producing sinusoidal lesions. Thus, (OX) would be associated with sinusoidal obstruction and NRH sporadically. It is important to discuss the possible etiologic factors that can cause NRH reviewing the hepatotoxic effects caused by both drugs.
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PMID:[Portal vein thrombosis and nodular regenerative hyperplasia associated with the use of bevacizumab and oxaliplatin. Report of one case]. 2452 66

A 71-year-old man presented with sigmoid colon cancer and multiple unresectable liver metastases. As the sigmoid colon cancer caused anemia, we performed laparoscopic-assisted sigmoidectomy prior to the administration of systemic chemotherapy. Bevacizumab (Bv) plus modified Leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) was administered as first line therapy.At 3 months from the start of chemotherapy, computed tomography revealed that the size of the liver metastases reduced by 49.45%, as evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). The only adverse event observed was Grade 1 peripheral neuropathy after the eighth dose of oxaliplatin.As the progression of peripheral neuropathy was observed at the ninth dose of oxaliplatin, oxaliplatin was omitted from further therapy; the patient was converted to maintenance therapy with simplified biweekly Leucovorin and fluorouracil (sLV5FU2). Bv plus mFOLFOX6 followed by sLV5FU2 for first-line therapy was effective for disease management over 23 months, but a partial response (PR) was the best overall response achieved.
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PMID:[A case of colon cancer with multiple liver metastases showing a long-term response following first-line therapy]. 2573 2

A new generation of anticancer therapeutics called target drugs has quickly developed in the 21st century. These drugs are tailored to inhibit cancer cell growth, proliferation, and viability by specific interactions with one or a few target proteins. However, despite formally known molecular targets for every "target" drug, patient response to treatment remains largely individual and unpredictable. Choosing the most effective personalized treatment remains a major challenge in oncology and is still largely trial and error. Here we present a novel approach for predicting target drug efficacy based on the gene expression signature of the individual tumor sample(s). The enclosed bioinformatic algorithm detects activation of intracellular regulatory pathways in the tumor in comparison to the corresponding normal tissues. According to the nature of the molecular targets of a drug, it predicts whether the drug can prevent cancer growth and survival in each individual case by blocking the abnormally activated tumor-promoting pathways or by reinforcing internal tumor suppressor cascades. To validate the method, we compared the distribution of predicted drug efficacy scores for five drugs (Sorafenib, Bevacizumab, Cetuximab, Sorafenib, Imatinib, Sunitinib) and seven cancer types (Clear Cell Renal Cell Carcinoma, Colon cancer, Lung adenocarcinoma, non-Hodgkin Lymphoma, Thyroid cancer and Sarcoma) with the available clinical trials data for the respective cancer types and drugs. The percent of responders to a drug treatment correlated significantly (Pearson's correlation 0.77 p = 0.023) with the percent of tumors showing high drug scores calculated with the current algorithm.
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PMID:A method for predicting target drug efficiency in cancer based on the analysis of signaling pathway activation. 2632 Jan 81

The use of a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer is known to be effective. However, whether the use of a SEMS as a BTS for obstruction induced by effective chemotherapy (CTx) is useful is unknown. We present the case of a 54-year-old female patient with colorectal cancer who underwent SEMS placement as a BTS for colorectal obstruction induced by bevacizumab-based CTx. The patient was diagnosed as having transverse colon cancer with multiple liver metastases invading the inferior vena cava. Bevacizumab-based CTx was started; however, although it was effective, colonic obstruction occurred at the primary site after 31 months. A SEMS was placed as a BTS, and surgical resection of the primary lesion was performed after cessation of bevacizumab. However, the liver metastases remained unresectable. CTx was restarted after surgery, and 48-month survival was achieved. This case shows that SEMS placement as a BTS for colorectal obstruction induced by a good response to bevacizumab-based CTx was safe and beneficial. With the development of CTx and molecular-targeted agents, the frequency of colorectal obstruction associated with effective CTx is expected to increase. SEMS placement as a BTS might be one of the treatment options.
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PMID:Successful endoscopic stent placement as a bridge to surgery for colonic obstruction induced by bevacizumab-based chemotherapy. 2636 45

The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration. hrRNASET2 also induced full arrest of angiogenin-induced tube formation and brought to a three-fold lower relative HT29 colorectal and A375SM melanoma tumor volume, when compared to Avastin-treated animals. In parallel, mean blood vessel counts were 36.9% lower in hrRNASET2-vs. Avastin-treated mice and survival rates of hrRNASET2-treated mice were 50% at 73 days post-treatment, while the median survival time for untreated animals was 22 days. Moreover, a 60-day hrRNASET2 treatment period reduced mean A375SM lung metastasis foci counts by three-fold when compared to untreated animals. Taken together, the combined antiangiogenic and antitumorigenic capacities of hrRNASET2, seemingly arising from its direct interaction with intercellular and extracellular matrices, render it an attractive anticancer therapy candidate.
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PMID:Human recombinant RNASET2: A potential anti-cancer drug. 2701 25

Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF)-A, is currently used to treat patients with ovarian or colon cancer. While several cardiovascular toxicities related to bevacizumab-containing regimens have been reported, the effect of bevacizumab on the coronary microcirculation has not been fully elucidated. Here we report a case of 54-year-old female patient who developed microvascular angina after a series of bevacizumab-containing chemotherapeutic regimen. The discontinuation of bevacizumab and nicorandil administration was effective in alleviating her chest discomfort and the ischemic changes on her ECG. This highlights the possibility that coronary microvascular angina can be induced in patients treated with bevacizumab-containing chemotherapy. It should also be noted that nicorandil can be effective in managing microvascular angina.
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PMID:Bevacizumab-Related Microvascular Angina and Its Management with Nicorandil. 2896 26

Colorectal carcinoma is the third most common cancer worldwide. Approximately 20% of patients with colorectal cancer will have metastatic disease at the time of initial diagnosis, and approximately 30% to 50% of patients with primary colon cancer will relapse and die of metastatic cancer. The 5-year survival rate of metastatic colorectal cancer remains disappointing at approximately 10%.Angiogenesis plays a significant role in tumor growth and metastasis in colorectal carcinoma. There are currently 4 US Food and Drug Administration-approved antiangiogenic agents for metastatic colorectal cancer. Bevacizumab is the only antiangiogenic agent approved by the US Food and Drug Administration for first-line treatment of metastatic colorectal cancer. Other antiangiogenic agents include ramucirumab, ziv-aflibercept, and regorafenib. We review the data supporting the use of antiangiogenics in this disease.
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PMID:Antiangiogenic Therapy in Colorectal Cancer. 3011 79


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