Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of treatment schedule

PURPOSE: The aim of our study was to investigate if oxaliplatin (1-OHP) could be used as a radiosensitizer in vivo. MATERIALS AND METHODS: Experiments were performed in mice (C3D2F1) bearing a transplanted mammary carcinoma in a foot. Drugs, 1-OHP and cis-diammine-dichloro-platinum (CDDP), were administered i.p. Results were analyzed in terms of tumor growth delay (TGD). RESULTS: 1-OHP and CDDP were tested in single doses of 6 and 10 mg/kg body weight. Administration of either 1-OHP or CDDP produced a significant TGD but only with the dose of 10 mg/kg. Single dose combined X-ray (10 Gy) and 1-OHP (6 and 10 mg/kg) treatments were performed with different sequences and time intervals (1 h, 4 h, and 24 h). All TGDs of these combined treatments were uniform among themselves (indicating that sequence and time interval did not influence the results), and did not depend on the drug dose. In X-ray (10 and 20 Gy) and 1-OHP (6 and 10 mg/kg) combined treatment, the TGDs increased only with X-ray dose. Different 1-OHP administration schedules were performed for fractionated experiments: two treatments every 4 days. The least toxic protocol (1-OHP total dose from 6 to 14 mg/kg) was selected for combined treatments with 10 daily X-ray treatments of 2 Gy. A clear drug dose-effect relationship was observed in those treatments with 1-OHP doses from 10 to 14 mg/kg. CONCLUSION: Although low-dose 1-OHP did not induce a TGD when administered alone, in combined protocols it increased X-ray efficacy.     

A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin's lymphoma.

PURPOSE: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)-bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted. EXPERIMENTAL DESIGN: The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting <6 months). I.V. rituximab was given at 375 mg/m(2) (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9). RESULTS: Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcgammaR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy. CONCLUSIONS: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL.     

Hysteroscopic Intact Removal of an Angular Pregnancy with a 5Fr Electrode

Study Objective

Angular pregnancy is a rare and life-threatening condition in which the embryo is implanted in the lateral angle of the uterine cavity, medial to the uterotubal junction and round ligament. Angular pregnancy is associated with a high risk of uterine rupture of about 23% [1]. No consensus has been achieved regarding the diagnostic and therapeutic approach of angular pregnancy [2]. Thus, the aim of this study was to report a case of hysteroscopic treatment of an angular pregnancy in a 34-year-old women.

Prognostic and predictive relevance of microsatellite instability in colorectal cancer

Microsatellite instability (MSI) is the phenotypic hallmark of a deficient DNA mismatch-repair system, observed in 10-20% of sporadic colorectal cancers (CRC). Since the prognostic and predictive value of this genetic alteration has been assessed mainly in non-randomised, uncontrolled studies, we investigated the potential of MSI to predict patient survival and response to adjuvant chemotherapy in tumour specimens from a randomised trial of the Swiss Group for Clinical Cancer Research (SAKK) that tested the value of 5-fluorouracil/mitomycin adjuvant chemotherapy. MSI status was determined in matched normal and tumour tissue samples from 160 patients using a panel of 9 microsatellite markers. There was no correlation between high frequency MSI (MSI-H) and overall (OS) or disease-free survival (DFS) in the untreated control group of patients (HR=1.13, p=0.80; and HR=0.89, p=0.81, respectively). Furthermore, MSI-H phenotype did not predict for a larger benefit of adjuvant chemotherapy on OS or DFS (HR=0.49, p=0.41; HR=0.49, p=0.41, respectively), making a potential value of this molecular marker as a predictive factor in CRC unlikely. Our data do not confirm the prognostic relevance of MSI-H status in colorectal cancer patients found in some other studies. In addition, microsatellite instability did not correlate with the extent of chemotherapy benefit, although we observed a statistically non-significant favourable impact of 5-FU-based treatment in the MSI-H group compared to MSI-L/MSS patients. Larger prospective randomised trials are required to conclusively establish a potential clinical significance of MSI in colorectal cancer.     

Increased plasma aldosterone in patients with clinical depression

BACKGROUND: Clinical depression has been increasingly recognized as an independent risk factor for adverse cardiovascular events, but the biological mechanisms of this association remain unclear. Recent evidence for renin system dysregulation in patients with depression led us to hypothesize that aldosterone--a well-recognized contributor to vascular injury--could be increased in depressed patients. The present study was designed, therefore, to be a cross-sectional investigation of plasma renin and aldosterone levels in depressed patients as compared with healthy controls with no history of psychiatric illness. METHODS: A total of 65 depressed patients and 65 age- and gender-matched control subjects were enrolled. Following a fixed sodium and potassium diet, venous blood samples were obtained at 9:00 a.m. to avoid the influence of circadian rhythms. RESULTS: Although there were no significant differences in plasma level of renin among subjects with depression and controls (7.9 +/- 5.8 vs. 6.4 +/- 4.3 pg/mL, respectively; p=0.10), depressed subjects exhibited greater mean aldosterone levels as compared with control subjects (157.2 +/- 67.5 vs. 125.7 +/- 38.1 pg/mL, respectively; p=0.0014). After adjusting for potential confounders, multivariate logistic regression analysis showed that subjects with depression had 2.77 times higher odds of elevated aldosterone levels compared with healthy control subjects (95% confidence interval, 1.30-5.92, p=0.008). CONCLUSIONS: Our present findings support the hypothesis that hyperaldosteronism could be a common feature among depressed patients, thereby suggesting that increased aldosterone levels may act as a mediator in the pathway linking depression to unfavorable vascular events.     

Laparoscopic management of oesophageal epiphrenic diverticulum: a case report

Epiphrenic diverticuli are rare pulsion "pseudodiverticuli" of the distal oesophagus that are commonly associated with oesophageal motility disorders. Surgical treatment is usually reserved for patients with symptoms. Traditionally, patients are treated with diverticulectomy, myotomy and fundoplication via a left thoracotomy. The aim of this study was to describe the laparoscopic technique and review the international literature on this minimally invasive approach. We report the case of a 66-year-old woman with a 1-year history of retrosternal pain, regurgitation and weight loss caused by an oesophageal epiphrenic diverticulum. The patient underwent barium oesophagography and oesophagogastroduodenoscopy. The oesophageal diverticulum measured 5 cm. We treated the condition with a laparoscopic oesophageal diverticulectomy, Heller myotomy and Dor fundoplication with intraoperative endoscopy. The operative time was 210 minutes. The postoperative course was complicated by a suspected leakage from the staple line, which was not subsequently confirmed. The patient is now totally asymptomatic after 3 months. Laparoscopy offers good access to the distal oesophagus and the inferior mediastinum. Resection of the diverticulum, treatment of the motor disorder and prevention of postoperative reflux can be obtained with this approach. It should be considered as an alternative to the traditional transthoracic approach and may eventually become the standard technique.     

Polymethacrylate Copolymers Containing 4,5‐Dicyanoimidazole‐Based Chromophores and their Nonlinear Optical Behavior

Summary: Two series of methacrylate copolymers were prepared, based on two new nonlinear optically (NLO) active chromophores 2‐[4‐(N‐methacryloyloxyethyl‐N‐methylamino)phenylazo]‐4,5‐dicyanoimidazole (chromophore A ) and 1‐ethyl‐2‐[4‐(N‐methacryloyloxyethyl‐N‐methylamino)phenylazo]‐4,5‐dicyanoimidazole (chromophore B ). Second order NLO properties of the two series of copolymers ( A or B as monomer and methyl methacrylate as the comonomer) were investigated by SHG procedures at the fundamental wavelength 1368 nm; d₃₃ values in the range 0.2–3.3 pm · V⁻¹ were obtained, depending on the chromophore and on its molar content. The dependence of d₃₃ on the molar content of chromophore was investigated in the two cases.