Use of the OLFM4 protein in colorectal cancer diagnosis

The present invention provides a method for diagnosing KRAS mutations in colorectal cancers by measuring the level of OLFM4. In another aspect, the present invention relates a method of predicting the responds to a chemotherapeutic agent of a subject suffering from a colorectal cancer: according to the present invention, the by determining the OLFM4 levels. According to the present invention, the response can be predicted by determining the OLFM4 levels. This result in turn permits the design or the adaptation of a treatment of the said subject with the said chemotherapeutic agent

Synthesis of Colloidal Mn2+:ZnO Quantum Dots and High-TC Ferromagnetic Nanocrystalline Thin Films

We report the synthesis of colloidal Mn2+-doped ZnO (Mn2+:ZnO) quantum dots and the preparation of room-temperature ferromagnetic nanocrystalline thin films. Mn2+:ZnO nanocrystals were prepared by a hydrolysis and condensation reaction in DMSO under atmospheric conditions. Synthesis was monitored by electronic absorption and electron paramagnetic resonance (EPR) spectroscopies. Zn(OAc)2 was found to strongly inhibit oxidation of Mn2+ by O2, allowing the synthesis of Mn2+:ZnO to be performed aerobically. Mn2+ ions were removed from the surfaces of as-prepared nanocrystals using dodecylamine to yield high-quality internally doped Mn2+:ZnO colloids of nearly spherical shape and uniform diameter (6.1 +/- 0.7 nm). Simulations of the highly resolved X- and Q-band nanocrystal EPR spectra, combined with quantitative analysis of magnetic susceptibilities, confirmed that the manganese is substitutionally incorporated into the ZnO nanocrystals as Mn2+ with very homogeneous speciation, differing from bulk Mn2+:ZnO only in the magnitude of D-strain. Robust ferromagnetism was observed in spin-coated thin films of the nanocrystals, with 300 K saturation moments as large as 1.35 Bohr magneton/Mn2+ and TC > 350 K. A distinct ferromagnetic resonance signal was observed in the EPR spectra of the ferromagnetic films. The occurrence of ferromagnetism in Mn2+:ZnO and its dependence on synthetic variables are discussed in the context of these and previous theoretical and experimental results.Comment: To be published in the Journal of the American Chemical Society Web on July 14, 2004 (http://dx.doi.org/10.1021/ja048427j

Individual Fluorouracil Dose Adjustment in FOLFOX Based on Pharmacokinetic Follow-Up Compared With Conventional Body-Area-Surface Dosing: A Phase II, Proof-of-Concept Study

BackgroundTo compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC). Patients And Methods A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FUODPM Protocol). Results The objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group. Conclusions Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC

Influence of 5-fluorouracil-loaded microsphere formulation on efficient rat glioma radiosensitization

PURPOSE: To determine (i) the efficiency of radiosensitizing 5-FU-loaded microspheres and (ii) the impact of microparticle formulation on response to treatment. METHODS: C6 tumor-bearing rats were stereotactically implanted with microspheres and/or allocated to: control groups (untreated) or treatment (only radiotherapy; fast-release 5-FU microspheres + radiotherapy; slow-release 5-FU microspheres + radiotherapy). The next day, fractionated radiotherapy, limited to the hemibrain, was initiated in all treated animals. The irradiation cycle included 36 Gy, given in 9 sessions for 3 consecutive weeks. Tumor development was assessed by T2-weighted MRI. RESULTS: 5-FU microspheres associated with radiotherapy caused a 47% complete remission rate (9/19) as opposed to the 8% rate (1/12) when radiotherapy alone or 0% in control animals. Drug delivery for 3 weeks produced better survival results (57%) compared to one-week sustained release (41%). MR images showed exponentially increasing tumor volumes during the first half of the radiotherapy cycle, followed by a decrease, and the disappearance of the tumor if survival exceeded 120 days. CONCLUSIONS: 5-FU controlled delivery is a promising strategy for radiosensitizing gliomas. Drug delivery system formulation is unambiguously implicated in both the response to treatment and the limitation of toxic side effects

Factors predicting efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU) ± folinic acid in a compassionate-use cohort of 481 5-FU-resistant advanced colorectal cancer patients

A statistical analysis was performed on the patient data collected from two compassionate-use programmes using oxaliplatin (Eloxatin®) + 5-fluorouracil (5-FU) ± folinic acid (FA), to identify predictive factors for oxaliplatin-based salvage treatment in patients with 5-FU-resistant advanced colorectal cancer (ACRC). 481 5-FU-resistant ACRC patients, most with performance status ≤ 2, ≥ 3 involved sites, and ≥ 2 prior lines of chemotherapy, received oxaliplatin + 5-FU ± FA. Prognostic factors associated with overall response rate (ORR), time to progression (TTP) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The ORR was 16% (95% CI: 13–20), the median TTP was 4.2 months (95% CI: 3.4–4.6), and the median OS was 9.6 months (95% CI: 8.6–10.6). The multivariate analysis indicated poor (≥ 2 WHO) performance status (PS), a large number of prior chemotherapy regimens (≥ 3), a low baseline haemoglobin level (< 10 g/dl), and a triweekly (vs biweekly) treatment administration schedule as significantly associated (P< 0.05) with a lower ORR. Sex (male), number of organs involved (≥3) and alkaline phosphatase (AP) level (≥ 2 × the upper limit of normal) were associated (P< 0.05) with shorter TTP. Poor PS, a large number of organs involved, and elevated AP were independently and significantly correlated with shorter OS. Our analysis identified a relationship between efficacy results of oxaliplatin + 5-FU ± FA treatment in 5-FU-resistant ACRC patients and baseline prognostic factors related to PS, extent of disease and number of prior regimens. © 2001 Cancer Research Campaign http://www.bjcancer.co

Assessing the impact of chemotherapy-induced peripheral neurotoxicity on the quality of life of cancer patients: The introduction of a new measure

Item does not contain fulltextPURPOSE: To investigate the impact of chemotherapy-induced neurotoxicity on daily activities and quality of life (QoL) of cancer patients. METHODS: QoL of all patients visiting the oncological outpatient ward of the Maxima Medical Centre in the Netherlands from October 2006 until March 2007 treated with taxanes, vinca-alkaloids and/or platinum compounds (n = 88) was compared with the QoL of patients that did not receive these treatments yet (n = 43). Patient-reported neuropathy symptoms were evaluated with the newly developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx) questionnaire. RESULTS: Patients treated with chemotherapy reported significantly more complaints of neuropathy (p < 0.001) and more paresthesias and dysesthesias in the upper (p < 0.001; p < 0.01) and lower extremities (p < 0.001) compared to those not treated with chemotherapy. They additionally experienced problems with fine motor function (e.g., getting (un)dressed, writing, and picking up small objects). Moreover, cold-induced paresthesias were frequently reported. Overall, patients indicated that their neuropathy had a negative effect on QoL. CONCLUSIONS: The newly developed CINQ and the FACT/GOG-Ntx results suggest a considerable negative impact of patient-reported neuropathy symptoms on daily activities and QoL in cancer patients treated with chemotherapy. However, further validation of the CINQ is needed

Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines

Background Oxaliplatin (L-OHP) is a platinum complex that possesses activity against human and murine cells in vitro and in vivo, including colorectal carcinoma-derived cell lines, and cells that have been selected for resistance to cisplatin. We report two consecutive phase H trials of L-OHP for treatment of patients with advanced colorectal carcinoma. Patients and methods: Fifty-eight patients were entered in study I, and 51 patients in study II. All of the patients had tumor progression when they were treated, prior to their enrolment, with a fluoropyrimidine-containing regimen. In both trials treatment consisted of L-OHP, 130 mg/m2 by i.v. infusion for two hours; the treatment was repeated every 21 days. Results Response to therapy: Study I: Fifty-five patients were assessed for response. The response rate was 11% (95% CI, 0.03-0.19). Study II: All 51 patients were assessed for response. The response rate was 10% (95% CI, 0.017-0.18). The overall response rate for the 106 evaluated patients was 10% (95% CI, 0.046-0.16). Times to disease progression in responders were 4, 4, 4.5+, 5, 5, 6, 6, 6, 6+, 9, and 13 months. The dose-limiting toxic effect was sensory peripheral neuropathy. The incidence of severe peripheral neuropathy grades was: Study I: grade 3, 23% of patients, and grade 4, 8% of patients. Study II: grade 3, 14% of patients, and grade 4, 4% of patients. Severe neuropathy had a favorable course in all of the patients who had long-term neurologic follow-up. Diarrhea and myeloid impairment were minor. Conclusion L-OHP produced modest, but definite antitumor activity in patients with advanced colorectal carcinoma who were previously resistant to chemotherapy including fluoropyrirnidines. Toxicity is within acceptable limits of tolerance at the dose and schedule of oxaliplatin used in this tria