Impulse activity of individual sensorimotor cortex neurons in rabbits after microiontophoretic administration of antibodies against acid fibroblast growth factor

We studied the sensitivity of sensorimotor cortex neurons in rabbits to microiontophoretic administration of antibodies against acid fibroblast growth factor (anti-aFGF). Spontaneous activity and reaction of neurons to electrical stimulation of ‘feeding centers’ in the lateral hypothalamic area (LHA) were recorded. We analyzed impulse activity of 52 neurons in the sensorimotor cortex. It was shown that 14 neurons (25%) reacted to microiontophoresis of anti-aFGF (excitation and inhibition in 9 and 5 neurons, respectively). Microiontophoretic administration of anti-aFGF did not change the reaction (excitation or inhibition) of 27 neurons to electrical stimulation of LHA. Initially, 14 neurons did not response to LHA stimulation. After microiontophoretic administration of anti-aFGF, 6 of 14 neurons displayed pronounced reactions to electrical stimulation of LHA (excitation and inhibition in 2 and 4 neurons, respectively). These data suggest that aFGF plays an important physiological role in feeding motivations.     

Use of multiepitope polyproteins in serodiagnosis of active tuberculosis

Screening of genomic expression libraries from Mycobacterium tuberculosis with sera from tuberculosis (TB) patients or rabbit antiserum to M. tuberculosis led to the identification of novel antigens capable of detecting specific antibodies to M. tuberculosis. Three antigens, Mtb11 (also known as CFP-10), Mtb8, and Mtb48, were tested together with the previously reported 38-kDa protein, in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in TB patients. These four proteins were also produced as a genetically fused polyprotein, which was tested with two additional antigens, DPEP (also known as MPT32) and Mtb81. Sera from individuals with pulmonary and extrapulmonary TB, human immunodeficiency virus (HIV)-TB coinfections, and purified protein derivative (PPD)-positive and PPD-negative status with no evidence of disease were tested. In samples from HIV-negative individuals, the ELISA detected antibodies in >80% of smear-positive individuals and >60% smear-negative individuals, with a specificity of approximately 98%. For this group, smears detected 81.6% but a combination of smear and ELISA had a sensitivity of approximately 93%. The antigen combination detected a significant number of HIV-TB coinfections as well as antibodies in patients with extrapulmonary infections. Improved reactivity in the HIV-TB group was observed by including the antigen Mtb81 that was identified by proteomics. The data indicate that the use of multiple antigens, some of which are in a single polyprotein, can be used to facilitate the development of a highly sensitive test for M. tuberculosis antibody detection.     

Outcomes Following Percutaneous Microwave and Cryoablation of Lung Metastases from Adenoid Cystic Carcinoma of the Head and Neck: A Bi-Institutional Retrospective Cohort Study

Annals of Surgical Oncology - The aim of this study was to report outcomes following percutaneous microwave and cryoablation of lung metastases from adenoid cystic carcinoma (ACC) of the head and...     

Pathogenetic role and clinical significance of interleukin-1β in cancer

In recent years, pro-oncogenic mechanisms of the tumour microenvironment (ТМЕ) have been actively discussed. One of the main cytokines of the TМЕ is interleukin-1 beta (IL-1β), which exhibits proinflammatory properties. Some studies have shown an association between an increase in IL-1β levels and tumour progression. The purpose of this review is to analyse the pathogenic mechanisms induced by IL-1β in the TМЕ, as well as the diagnostic significance of the presence of IL-1β in patients with cancer and the efficacy of treatment with IL-1β inhibitors. According to the literature, IL-1β can induce an increase in tumour angiogenesis due to its effects on the differentiation of epithelial cells, pro-angiogenic molecule secretion and expression of adhesion molecules, thus increasing tumour growth and metastasis. IL-1β is also involved in the suppression of anti-tumour immune responses. The expression and secretion of IL-1β has been noted in various types of tumours. In some clinical studies, an elevated level of IL-1β was found to be associated with low efficacy of anti-cancer therapy and a poor prognosis. In most experimental and clinical studies, the use of IL-1β inhibitors contributed to a decrease in tumour mass and an increase in the response to anti-tumour drugs.     

Laparoscopic Cholecystectomy in Obese and Nonobese Patients

Background: From November 1997 to November 1998, 145 cases of laparoscopic cholecystectomy (LC) have been attempted at the District General Hospital of Corfu. Methods: 23 (15.8%) were obese (Group I, BMI >30) and 122 (84.2%) were nonobese patients (Group II, BMI ≤30). One-fifth of these patients suffered from acute cholecystitis. Results: Operative time averaged 95 minutes in Group 1 and 78 minutes in Group II. There were no deaths. There were no significant differences between the obese and nonobese groups in conversion to open procedure (Group1: 0%, Group II: 2.4%), intraoperative and postoperative complications (Group I: 4.3%, Group II: 4.0%), operating time, and length of postoperative hospitalization. Conclusion: LC was a safe and effective treatment for obese patients with symptomatic cholelithiasis.     

Artificial liver

Without transplantation, approximately 90% of patients with fulminant hepatic failure die. If patients receive a liver transplant, there is often a lag between the need for and the availability of a donor liver. Therefore, there is a definite need for a liver support system to support the patient's own liver function in fulminant hepatic failure and while awaiting transplantation. We have developed an artificial liver system that not only eliminates lipophilic toxins such as phenols, fatty acids, and mercaptans, but also hydrophilic ones such as ammonia. This artificial liver system consists of a monitor, an extracorporeal blood circuit that uses a hydrophilic polysulfone high-flux dialyzer to remove water-soluble metabolites, and a novel hydrophilic liquid membrane filter to remove lipophilic toxins. In more than 100 in vitro experiments using porcine (5 I) blood, the system was evaluated for its ability to remove toxins that are normally increased in hepatic failure. We found that phenol, cresol, and short- and medium-chain fatty acids can be almost completely eliminated from the blood within 5 h. In animal experiments using pigs, we also found no significant changes of blood gases, liver parameters, electrolytes, and blood cell counts.     

A clinical laboratory paradigm for evaluating medication effects on alcohol consumption: naltrexone and nalmefene.

Opiate antagonist medications have been shown to improve alcoholism treatment, but few human laboratory-based studies investigating mechanisms for these effects have been conducted on alcohol dependent persons. The present study was designed to determine the impact of two opiate antagonists on alcohol consumption among nontreatment-seeking alcoholics (n=125) and social drinkers (n=90). Participants were randomly assigned to receive placebo, naltrexone (titrated to 50 mg/day), or nalmefene (titrated to 40 mg/day) for 8 days with an alcohol laboratory session on the final day. Alcohol consumption was monitored in the natural environment during the first 5 medication days, and during a choice consumption paradigm following a standard 'priming' alcohol dose in a bar-laboratory setting. Social drinkers consumed less alcohol than alcoholics during the prelab medication period and the laboratory choice consumption paradigm, and they attained lower blood alcohol levels than alcoholics following the priming drink. Both opiate antagonist medications equally reduced drinking amounts and frequency among alcoholics but not social drinkers, relative to placebo, during natural environment and bar-lab alcohol consumption evaluations. Greater medication side effects, mostly mild in nature, were observed in participants taking nalmefene. These findings demonstrate that both naltrexone and nalmefene can lead to reductions in alcohol consumption among alcoholics who are not attempting to reduce drinking. Similar laboratory paradigms may offer substantial advantages for observing these effects during evaluation of other medications as well.     

Multiple myeloma regression mediated by bruceantin.

PURPOSE: Bruceantin has been shown to induce cell differentiation in a number of leukemia and lymphoma cell lines. It also down-regulated c-MYC, suggesting a correlation of down-regulation with induction of cell differentiation or cell death. In the present study, we focused on multiple myeloma, using the RPMI 8226 cell line as a model. EXPERIMENTAL DESIGN: The effects of bruceantin on c-MYC levels and apoptosis were examined by immunoblotting, 4',6-diamidino-2-phenylindole staining, evaluation of caspase-like activity, and 3,3'-dihexyloxacarbocyanine iodide staining. The potential of bruceantin to inhibit primary tumor growth was assessed with RPMI 8226 xenografts in SCID mice, and apoptosis in the tumors was evaluated by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. RESULTS: c-MYC was strongly down-regulated in cultured RPMI 8226 cells by treatment with bruceantin for 24 h. With U266 and H929 cells, bruceantin did not regulate c-MYC in this manner. Apoptosis was induced in the three cell lines. In RPMI 8226 cells, apoptosis occurred through proteolytic processing of procaspases and degradation of poly(ADP-ribose) polymerase. The mitochondrial pathway was also involved. Because RPMI 8226 cells were the most sensitive, they were used in a xenograft model. Bruceantin treatment (2.5-5 mg/kg) resulted in a significant regression of tumors without overt toxicity. Apoptosis was significantly elevated in tumors derived from animals treated with bruceantin (37%) as compared with the control tumors (14%). CONCLUSIONS: Bruceantin interferes with the growth of RPMI 8226 cells in cell culture and xenograft models. These results suggest that bruceantin should be reinvestigated for clinical efficacy against multiple myeloma and other hematological malignancies.     

Positron emission tomography for target volume definition in the treatment of non-small cell lung cancer.

The additional benefit of positron emission tomography (PET) in the initial staging of non-small cell lung cancer (NSCLC) has generated interest in 18F-fluorodeoxyglucose (FDG) PET as a means of defining the extent of primary lung tumour for radiotherapy treatment planning (RTP). A review of published data suggests that PET results in a reduction in the CT-derived GTV for NSCLC primary target volume in 15% of the patients. This is principally due to the ability of PET to distinguish tumour from atelectasis. However, the difficulty of tumour edge definition, limited spatial resolution and tumour motion during image acquisition currently limits the accuracy of PET in target volume delineation in NSCLC without adjacent lung consolidation. This is compounded by the lack of data correlating PET with spatial pathology at the primary tumour site. With the current technical limitations, it is not established that PET can add accuracy to the CT-defined primary target delineation in RTP of NSCLC. It is hoped that advances in PET and combined PET/CT imaging may overcome some of the technical limitations. Future use of PET for primary tumour delineation in NSCLC will also be critically dependent on the detailed studies of imaging-pathology correlation.     

Bexarotene and erlotinib for aerodigestive tract cancer.

PURPOSE: The epidermal growth factor receptor (EGFR) and cyclin D1 are overexpressed in lung carcinogenesis. The rexinoid, bexarotene, represses cyclin D1 and EGFR expression in vitro. It was hypothesized that combining bexarotene with the EGFR inhibitor, erlotinib, would augment clinical activity. PATIENTS AND METHODS: In vitro studies and a phase I clinical trial were performed. Twenty-four patients with advanced aerodigestive tract cancers were enrolled; 79% had non-small-cell lung cancer (NSCLC). The primary objective was to determine the maximum-tolerated dose. Clinical activity was a secondary objective. RESULTS: Combining erlotinib with bexarotene enhanced growth suppression in vitro compared with each single-agent treatment. This cooperatively repressed cyclin D1 expression. Clinically, the most frequent toxicities were mild hypertriglyceridemia and skin rash. Two serious treatment-related adverse events occurred (creatine phosphokinase elevation attributed to antilipid therapy and a case of generalized pain). Five objective responses (four partial and one minor) were observed in NSCLC patients. Responses were observed in males and smokers. EGFR sequence analyses did not reveal activating mutations in tumors from assessable responding patients. Median time to progression was 2.0 months; overall survival time was 14.1 months; and 1-year survival rate was 73.8%. CONCLUSION: The recommended phase II doses are erlotinib 150 mg/d and bexarotene 400 mg/m2/d orally. These agents can be administered in combination at the recommended single-agent doses without added toxicity. Overall survival and clinical features of responding patients differ from prior reports of single-agent erlotinib treatment. These findings are encouraging and warrant further investigation of this regimen.