Tumor oxygenation status as a prognostic marker

Tumor oxygenation status is an independent prognostic indicator in cancer because it influences tumor progression and treatment outcome. Its quantitative value is determined by a number of tumor vascular parameters such as microvascular density, blood flow, blood volume, blood oxygen saturation, tumor tissue pO2, and resistance to oxygen diffusion within the tumor. Over the past several years, considerable time and effort have been invested into developing techniques to effectively and reliably measure the oxygenation status of a tumor. The measurement and interpretation of data obtained with currently available methods is complicated by the heterogeneity in tumor oxygenation. Currently available techniques can be broadly classified into direct invasive methods, direct non-invasive methods, and measurement of surrogate endogenous markers of tumor oxygenation. Of these methods, the Eppendorf pO2 histograph is considered the 'gold standard' and even so has several limitations. Given the importance of tumor oxygenation status in therapy and in predicting disease progression, it is imperative that reliable, globally usable, and technically simplistic methods be developed to yield a consistent, comprehensive, and reliable profile of tumor oxygenation. Until newer more reliable techniques are developed, existing independent techniques or appropriate combinations of techniques should be optimized and validated using known endpoints in tumor oxygenation status and/or treatment outcomes.     

Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy.

PURPOSE: A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. EXPERIMENTAL DESIGN: Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. RESULTS: Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (相似文献   

Meningo-encephalocoele of temporal lobe-management by blind SAC closure

Brain herniation into the middle ear and mastoid is rare but is a described complication of chronic ear disease. The diagnosis is mainly clinical and requires a high index of suspicion. This can be confirmed by imaging studies. Different surgical modalities have been described in managing this condition. We present a case managed by combined trans-mastoid mini-craniotomy approach and blind sac closure.     

Oxidized Low Density Lipoproteins-Do We Know Enough About Them?

Since the discovery of oxidized low density lipoprotein (Ox-LDL), over 5,000 articles have appeared on the topic with over 400 articles appearing every year during the past decade. LDL contains esterified polyunsaturated fatty acid containing lipids, such as, phosphatidylcholine (PtdCho) and cholesterol esters (CE). Peroxidation of polyunsaturated fatty acid (PUFA) containing lipids has been known for a long time. Numerous studies have documented that peroxidized lipids as well as products derived from their decomposition, particularly aldehydes, have deleterious biological properties. This concept has been exemplified in the study of atherosclerosis. A plethora of in vitro and animal studies, as well as human epidemiological and correlatory studies, have supported the notion that oxidative processes and the formation of Ox-LDL might contribute to atherosclerosis. Yet the negative outcomes of human clinical trials with α-tocopherol and other antioxidants have convinced even staunch supporters of the hypothesis to take a step backwards and reconsider reasons of their failure and suggest alternative approaches. Ox-LDL is a complex mixture of numerous chemical entities, many of them are yet uncharacterized. Why and how it is formed or its nature in vivo is poorly understood. It is recognized by numerous cell surface receptors, which are ubiquitously expressed in many different cell types. These receptors might perform a variety of functions. In addition, components of Ox-LDL might also have favorable effects that are difficult to dissociate from its pathological effects. In this review, the nature of Ox-LDL and potential problems in inhibiting its formation are discussed.     

Effect of centchroman on cellular and humoral immunity

Centchroman (Ormeloxifene) is a nonsteroidal selective estrogen receptor modulator that is used as once a week oral contraceptive agent. The effect of centchroman on the immune system was evaluated by using different experimental models such as carbon clearance test, cyclophosphamide induced neutropenia, neutrophil adhesion test, effect on serum immunoglobulins, mice lethality test and indirect haemagglutination test. The first three models namely carbon clearance test, cyclophosphamide induced neutropenia and neutrophil adhesion test were used to study cell mediated immunity while the latter three models were used to see the effect on humoral immunity. Centchroman was administered orally at a dose of 5 mg/kg and levamisole (2.5 mg/kg/ p.o) was used as standard drug. Centchroman significantly increased the levels of serum immunoglobulins and also prevented the mortality induced by bovine Pasteurella multocida in mice. It also increased significantly the circulating antibody litre in indirect haemagglunation test. However, it did not show any significant effect on phagocytic index in carbon clearance assay and nor did influence the adhesion of neutrophils in the neutrophil adhesion test. Centchroman was also not effective in preventing the cyclophosphamde induced neutropenia. Hence, it was concluded that centchroman increases humoral immunity with no significant effect on cell mediated immunity.     

Structure‐guided Discovery of a Novel Non‐peptide Inhibitor of Dengue Virus NS2B–NS3 Protease

Dengue fever is a fast emerging epidemic‐prone viral disease caused by dengue virus serotypes 1‐4. NS2B–NS3 protease of dengue virus is a validated target to develop antiviral agents. A major limitation in developing dengue virus protease inhibitors has been the lack of or poor cellular activity. In this work, we extracted and refined a pharmacophore model based on X‐ray crystal structure and predicted binding patterns, followed by a three‐dimensional flexible database filtration. These output molecules were screened according to a docking‐based protocol, leading to the discovery of a compound with novel scaffold and good cell‐based bioactivity that has potential to be further optimized. The discovery of this novel scaffold by combination of in silico methods suggests that structure‐guided drug discovery can lead to the development of potent dengue virus protease inhibitors.     

Hemophagocytic Lymphohistiocytosis in a 19 Year Old Critically Ill Patient

Haemophagocytic lymphohistiocytosis (HLH) describes a clinical syndrome of hyperinflammation resulting in an uncontrolled and ineffective immune response. It presents with a clinical picture of likely sepsis, i.e., fever, laboratory evidence of inflammatory response, coagulopathy and thrombocytopaenia should be appropriately investigated and managed for sepsis, but the possible diagnosis of HLH should be borne in mind. Awareness of the clinical symptoms and of diagnostic criteria for HLH is crucial to starting immunosuppressive/immunomodulatory and cytotoxic drugs in time. We present a case of HLH in a 19 year old male who presented with fever, neurological symptoms, cytopaenias, laboratory markers of inflammation and bone marrow aspirate showed hemophagocytosis.