levoleucovorin and Adenomatous-Polyposis-Coli

NR4A2, an orphan nuclear receptor essential in neuron generation, has been recently linked to inflammatory and metabolic pathways of colorectal carcinoma (CRC). However, the effects of NR4A2 on chemo-resistance and postoperative prognosis of CRC remain unknown.. NR4A2 was transfected into CRC cells to investigate its effects on chemo-resistance to 5-fluorouracil and oxaliplatin and chemotherapeutics-induced apoptosis. We also investigated prostaglandin E2 (PGE2)-induced NR4A2 expression and its effect on chemo-resistance. Tissue microarrays including 51 adenoma, 14 familial adenomatous polyposis with CRC, 17 stage IV CRC with adjacent mucosa and 682 stage I-III CRC specimens were examined immunohistochemically for NR4A2 expression. Median follow-up time for stage I-III CRC patients was 53 months.. Ectopic expression of NR4A2 increased the chemo-resistance, and attenuated the chemotherapeutics-induced apoptosis. Transient treatment of PGE2 significantly up-regulated NR4A2 expression via protein kinase A pathway and increased the chemo-resistance. NR4A2 expression in epithelials consecutively increased from adenoma, adjacent mucosa to CRC (P(trend)<0.001). In multivariate Cox regression analyses, high NR4A2 expression in cancer nuclei (immunoreactive score ≥ 4) significantly predicted a shorter disease-specific survival (DSS) of CRC patients (hazard ratio [HR]=1.88, P=0.024). High NR4A2 expression specifically predicted a shorter DSS of colon cancer patients (dichotomisation, HR=2.55, log-rank test P=0.011), especially for those who received postoperative 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) chemotherapy (3-score range, HR=1.86, log-rank test P=0.020).. High expression of NR4A2 in CRC cells confers chemo-resistance, attenuates chemotherapeutics-induced apoptosis, and predicts unfavorable prognosis of colon cancer patients, especially for those who received postoperative chemotherapy. NR4A2 may be prognostic and predictive for colon cancer.

Topics: Adenoma; Adenomatous Polyposis Coli; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biomarkers, Tumor; Chemotherapy, Adjuvant; Chi-Square Distribution; Colorectal Neoplasms; Dinoprostone; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Fluorouracil; HCT116 Cells; Humans; Intestinal Polyps; Kaplan-Meier Estimate; Leucovorin; Multivariate Analysis; Neoplasm Staging; Nuclear Receptor Subfamily 4, Group A, Member 2; Organoplatinum Compounds; Proportional Hazards Models; Time Factors; Transfection; Treatment Outcome; Up-Regulation

Topics: Adenomatous Polyposis Coli; Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Female; Fibromatosis, Abdominal; Fibromatosis, Aggressive; Fluorouracil; Humans; Irinotecan; Leucovorin; Tomography, X-Ray Computed; Treatment Outcome

Severe (stage IV) duodenal polyposis is difficult to manage in patients with familial adenomatous polyposis (FAP), with no effective medical treatment, complex endoscopic treatment modalities, and a high morbidity and mortality from pancreaticoduodenectomy. We present the case of a 44-year-old woman with FAP, stage IV duodenal polyposis, and with an ileal pouch adenocarcinoma that required surgery and adjuvant chemotherapy. Her duodenal polyposis regressed to stage II after four sessions of FOLFOX4 adjuvant chemotherapy, which avoided the need for aggressive endoscopic therapy or pancreatoduodenectomy in this patient.

Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Chemotherapy, Adjuvant; Colonic Pouches; Duodenal Neoplasms; Duodenoscopy; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Leucovorin; Organoplatinum Compounds; Proctocolectomy, Restorative; Risk Assessment; Treatment Outcome

Topics: Adenoma; Adenomatous Polyposis Coli; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Middle Aged; Treatment Outcome

A 37-year-old man was diagnosed as having a rectal cancer with familial adenomatous polyposis, with the mutation of APC gene, and gastric polyposis, hypertrophy of the retinal pigment epithelium and a lipoma of the left arm. The patient underwent a total colectomy for the rectal cancer and a partial resection of the liver for metastasis (S3) which was detected on laparotomy, followed by cannulation in the hepatic artery. After the operation, 5-FU alone and low doses of CDDP and 5-FU were administered, but the level of serum CEA elevated and CT scanning showed multiple liver metastases. Then, low doses of leucovorin (30 mg/body bolus) and 5-FU (500 mg/body/h) were injected through an injection port every week. After 6 months, the level of serum CEA reduced and CT scanning showed minor response (about 30% on the decrease rate), without side effects, including diarrhea, stomatitis and bone marrow suppression.

Topics: Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fluorouracil; Genes, APC; Hepatic Artery; Humans; Infusion Pumps, Implantable; Leucovorin; Liver Neoplasms; Male; Rectal Neoplasms