抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Background The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor. Methods We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide with (143 women) or without trastuzumab (138 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). Results The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 ...

Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

http://science.sciencemag.org/content/sci/259/5091/87.full.pdf

Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance

background Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. methods This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. results Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. conclusions One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (clinicaltrials.gov number, NCT 00045032.)

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Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer

L'invention concerne des composes representes par la structure (I), ainsi que des procedes permettant de preparer de tels composes Ces procedes consistent a faire reagir une diacyldicetopiperazine avec un premier aldehyde afin de produire un compose intermediaire, et a faire reagir ce compose intermediaire avec un second aldehyde afin de produire une classe de composes presentant la structure generique, le premier aldehyde et le second aldehyde etant choisis dans le groupe constitue par un oxazolecarboxaldehyde, un imidazolecarboxaldehyde, un benzaldehyde, des derives imidazolecarboxaldehyde, et des derives de benzaldehyde, de maniere a former le compose decrit ci-dessus R1, R1 , R1 , R2, R3, R4, R5, et R6, X1 et X2, Y, Z, Z1, Z2, Z3, et Z4 peuvent etre definis chacun separement d'une maniere conforme au descriptif L'invention concerne en outre des compositions et des methodes de traitement du cancer et des infections fongiques

Deshydrophenylahistines et analogues de ceux-ci et synthese de ces deshydrophenylahistines et d'analogues de ceux-ci

Disclosed are methods of treating cancer, inflammatory conditions, and/or infectious disease in an animal comprising: administering to the animal, a therapeutically effective amount of a [3.2.0] heterocyclic compound, Preferably a 6-oxa-2-azabicyclo [3.2.0] heptane-3, 7-dione, such as salinosporamide A. The animal is a mammal, preferably a human or a rodent.

Use of (3.2.0) heterocyclic compounds and analogs thereof for the treatment of cancer

L'invention concerne des anticorps contre le recepteur (TN-R2) de type 2 du facteur de necrose de tumeurs. L'invention concerne plus particulierement des anticorps monoclonaux contre le TN-R2 humain qui imitent l'activite du TN de stimulation de la proliferation des lymphocytes T. L'invention concerne en outre l'utilisation de ces anticorps pour stimuler la proliferation de lymphocytes T humains.

Anticorps contre le recepteur du facteur de necrose de tumeurs de type 2

Enantioselective Synthesis of the Antiinflammatory Agent (-)-Acanthoic Acid (I).

L'invention concerne des composes ayant la structure chimique des formules (II) et (IIB) ainsi que leurs esters et sels d'addition d'acide de promedicaments, lesquels sont utiles en tant que modulateurs de l'interleukine-1 et du facteur de necrose tumorale alpha et sont par consequent utiles dans le traitement de diverses maladies, les groupes R etant definis dans les revendications.

Nouveaux modulateurs de l'interleukine-1 et du facteur de necrose tumorale alpha, syntheses desdits modulateurs et methodes d'utilisation desdits modulateurs

Michael A. Palladino

Papers

Deshydrophenylahistines et analogues de ceux-ci et synthese de ces deshydrophenylahistines et d'analogues de ceux-ci

Use of (3.2.0) heterocyclic compounds and analogs thereof for the treatment of cancer

Anticorps contre le recepteur du facteur de necrose de tumeurs de type 2

Enantioselective Synthesis of the Antiinflammatory Agent (-)-Acanthoic Acid (I).

Nouveaux modulateurs de l'interleukine-1 et du facteur de necrose tumorale alpha, syntheses desdits modulateurs et methodes d'utilisation desdits modulateurs