The detection of patients at risk of gastrointestinal toxicity during pelvic radiotherapy by electronic nose and FAIMS : a pilot study

It is well known that the electronic nose can be used to identify differences between human health and disease for a range of disorders. We present a pilot study to investigate if the electronic nose and a newer technology, FAIMS (Field Asymmetric Ion Mobility Spectrometry), can be used to identify and help inform the treatment pathway for patients receiving pelvic radiotherapy, which frequently causes gastrointestinal side-effects, severe in some. From a larger group, 23 radiotherapy patients were selected where half had the highest levels of toxicity and the others the lowest. Stool samples were obtained before and four weeks after radiotherapy and the volatiles and gases emitted analysed by both methods; these chemicals are products of fermentation caused by gut microflora. Principal component analysis of the electronic nose data and wavelet transform followed by Fisher discriminant analysis of FAIMS data indicated that it was possible to separate patients after treatment by their toxicity levels. More interestingly, differences were also identified in their pre-treatment samples. We believe these patterns arise from differences in gut microflora where some combinations of bacteria result to give this olfactory signature. In the future our approach may result in a technique that will help identify patients at “high risk” even before radiation treatment is started

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Pilot study of acute toxicity of TDP1 inhibitor

To date, malignant neoplasms are the most pressing medical and social problem both in our country and abroad, despite the introduction of innovative technologies in diagnostics, therapy, and prophylactics. Lung cancer is the most common malignant neoplasm worldwide. Since the beginning of the twentieth century, the incidence of lung cancer has increased, and its growth is especially pronounced in industrially developed countries, where it ranks first in the structure of cancer morbidity. In Russia, over the last ten years, the incidence of lung cancer has decreased, but yet more than 1000000 new cases are diagnosed annually, and lung cancer by remains in first place among all malignant neoplasms among men. Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) that result in stalled Top1 are commonly employed against cancer. Nowadays, major methods are used for the treatment of patients with lung cancer: surgery, radiation, chemoradiation, drugs, and combined methods. Combination chemotherapy with DNA repair inhibitors can potentially improve response to these widely used chemotherapeutics

A pilot study of temsirolimus and body composition.

PurposeBody weight and composition play a role in cancer etiology, prognosis, and treatment response. Therefore, we analyzed the weight, body composition changes, and outcome in patients treated with temsirolimus, an mTor inhibitor that has weight loss as one of its side effects.Patients and methodsSixteen patients with advanced solid tumors treated with temsirolimus were studied; body composition was evaluated utilizing computerized tomography images. Sarcopenia was defined as skeletal muscle index lower than 38.5 cm(2)/m(2) for women and 52.4 cm(2)/m(2) for men.ResultsFive of 16 patients (31 %) were men; median age, 60 years. Forty-four percent (7/16) of patients were sarcopenic. Fatigue, anemia, hyperglycemia, and hyperlipidemia were common. Baseline sarcopenia and body composition did not correlate with worse toxicity or treatment outcome. However, there was a trend for greater loss of adipose area (p = 0.07), fat mass (p = 0.09), and adipose index (p = 0.07) for patients with grade 3 or 4 toxicities versus those with grade 1 and 2 side effects.ConclusionPatients with higher grade toxicities tended to lose more body fat, suggesting a possible end-organ metabolic effect of temsirolimus. These observations merit exploration in a larger cohort of patients

No evidence for a culturable bacterial tetrodotoxin producer in Pleurobranchaea maculata (Gastropoda: Pleurobranchidae) and Stylochoplana sp. (Platyhelminthes: Polycladida)

Tetrodotoxin (TTX) is a potent neurotoxin found in the tissues of many taxonomically diverse organisms. Its origin has been the topic of much debate, with suggestions including endogenous production, acquisition through diet, and symbiotic bacterial synthesis. Bacterial production of TTX has been reported in isolates from marine biota, but at lower than expected concentrations. In this study, 102 strains were isolated from Pleurobranchaea maculata (Opisthobranchia) and Stylochoplana sp. (Platyhelminthes). Tetrodotoxin production was tested utilizing a recently developed sensitive method to detect the C9 base of TTX via liquid chromatography—mass spectrometry. Bacterial strains were characterized by sequencing a region of the 16S ribosomal RNA gene. To account for the possibility that TTX is produced by a consortium of bacteria, a series of experiments using marine broth spiked with various P. maculata tissues were undertaken. Sixteen unique strains from P. maculata and one from Stylochoplana sp. were isolated, representing eight different genera; Pseudomonadales, Actinomycetales, Oceanospirillales, Thiotrichales, Rhodobacterales, Sphingomonadales, Bacillales, and Vibrionales. Molecular fingerprinting of bacterial communities from broth experiments showed little change over the first four days. No C9 base or TTX was detected in isolates or broth experiments (past day 0), suggesting a culturable microbial source of TTX in P. maculata and Stylochoplana sp. is unlikely

Local Delivery of CTLA-4 Blockade Inhibits Growth of Pancreatic Tumors

Immune checkpoint blockade has demonstrated great potential in activating antitumor immunity. Ipilimumab is a monoclonal antibody which targets cytotoxic T-lymphocyte antigen-4. CTLA-4 belongs to the CD28 class of receptors and is found on the surface of CD4+ and CD8+ T cells. CTLA-4 acts to suppress the immune system when bound to CD80 and CD86 receptors on antigen presenting cells. Ipilimumab, or anti-CTLA-4, has shown to be effective in significantly extending the survival of patients with metastatic melanoma. However, systemic delivery of Ipilimumab also induces significant side effects such as: colitis, dermatitis, uveitis, and hypophysitis. In order to minimize toxicity, we and others have hypothesized that intratumoral administration of anti-CTLA-4 at a lower dose can have the same antitumor efficacy as systemic delivery but without the toxicity. This work begins with an investigational pilot study to determine the efficacy of anti-CTLA-4 by delivering 60 µg of anti-CTLA-4 to a group of mice and measuring the tumor growths when compared to an untreated control group. Once efficacy had been demonstrated, a dosing study was conducted to identify an optimal intratumoral dosage delivered to murine models. The groups were given doses of either 30 µg, 60 µg, or 120 µg. From this study, the 60 µg group had the lowest average tumor size of 300 mm3. Our lab has previously demonstrated that IL-12 co-formulated with chitosan has demonstrated prolonged intratumoral retention therefore, 60 µg of anti-CTLA was co-formulated with a chitosan solution investigate the efficacy in a delivery vehicle. Finally, 60 µg of anti-CTLA-4 was delivered in a proprietary hydrogel alone and with Interleukin-12 to examine the effects of controlled release

A randomised trial of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients: the UK-Vanguard Study

Objective: The objective of the trial was to evaluate in a pilot setting the safety and efficacy of interleukin-2 (IL-2) therapy when used without concomitant antiretroviral therapy as a treatment for HIV infection. Design and Setting: This was a multicentre randomised three-arm trial conducted between September 1998 and March 2001 at three clinical centres in the United Kingdom. Participants: Participants were 36 antiretroviral treatment naive HIV-1-infected patients with baseline CD4 T lymphocyte counts of at least 350 cells/mm(3). Interventions: Participants were randomly assigned to receive IL-2 at 15 million international units (MIU) per day ( 12 participants) or 9 MIU/day ( 12 participants) or no treatment ( 12 participants). IL-2 was administered by twice-daily subcutaneous injections for five consecutive days every 8 wk. Outcome Measures: Primary outcome was the change from baseline CD4 T lymphocyte count at 24 wk. Safety and plasma HIV RNA levels were also monitored every 4 wk through 24 wk. The two IL-2 dose groups were combined for the primary analysis. Results: Area under curve (AUC) for change in the mean CD4 T lymphocyte count through 24 wk was 129 cells/mm(3) for those assigned IL-2 ( both dose groups combined) and 13 cells/mm(3) for control participants (95% CI for difference, 51.3 - 181.2 cells/mm(3); p = 0.0009). Compared to the control group, significant increases in CD4 cell count were observed for both IL-2 dose groups: 104.2/mm(3) ( p = 0.008) and 128.4 cells/mm(3) ( p = 0.002) for the 4.5 and 7.5 MIU dose groups, respectively. There were no significant differences between the IL-2 (0.13 log(10) copies/ ml) and control (0.09 log(10) copies/ml) groups for AUC of change in plasma HIV RNA over the 24-wk period of follow- up ( 95% CI for difference, - 0.17 to 0.26; p = 0.70). Grade 4 and dose-limiting side effects were in keeping with those previously reported for IL-2 therapy. Conclusions: In participants with HIV infection and baseline CD4 T lymphocyte counts of at least 350 cells/mm(3), intermittent subcutaneous IL-2 without concomitant antiretroviral therapy was well tolerated and produced significant increases in CD4 T lymphocyte counts and did not adversely affect plasma HIV RNA levels