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991.
Palmer BD Henare K Woon ST Sutherland R Reddy C Wang LC Kieda C Ching LM 《Journal of medicinal chemistry》2007,50(16):3757-3764
5,6-Dimethylxanthenone-4-acetic acid (1) is scheduled for phase III clinical trials as a vascular disrupting agent. However, its biochemical receptor(s) have yet to be identified. In this report, the synthesis of azido analogues of 1 that could be used for photoaffinity labeling of proteins as an approach toward identifying its molecular targets is described. While 5-azidoxanthenone-4-acetic acid (2) and 5-azido-6-methylxantheone-4-acetic acid (3) were found to have biological activities similar to that of 1, 6-azido-5-methylxanthenone-4-acetic acid (4) was unstable and could not be evaluated. Both azido compounds 2 and 3 activated NF-kappaB, induced the production of tumor necrosis factor in cultured mouse splenocytes, and induced hemorrhagic necrosis of colon 38 tumors in mice. Photoreaction of lysates from spleen cells with tritiated 2 resulted in two radiolabeled protein bands at 50 and 14 kDa that could be competitively inhibited with cold 1 and cold 2. The azido compounds 2 and 3 exhibit all the requirements for use in photoaffinity labeling of potential receptor(s) for 1. 相似文献
992.
Umamaheswara Reddy C Arun A Amalraj A Reddy BS 《The Journal of pharmacy and pharmacology》2007,59(9):1207-1213
N-((4-amino sulfonyl)phenyl)acrylamide (APA) was synthesized using sulfanilamide and acryloyl chloride in the presence of triethyl amine at 0-5 degrees C. Homo- and co-polymerization of 2-hydroxyethyl acrylate (HEA) and acrylic acid (AA) were done by adopting a solution polymerization technique using methyl ethyl ketone (MEK) as a solvent and benzoyl peroxide (BPO) as a free radical initiator at 70 +/- 1 degrees C. All the monomers and polymers were characterized by IR and NMR techniques. These monomers and polymers were tested for their antimicrobial activity against five different ATCC strain microorganisms (Escherichia coli (25922), Pseudomonas aeruginosa (27853), Klebsiella (70063), Salmonella typhi (6539) and Staphylococcus aureus (25923)). The effect of co-monomer, other than the active drug moiety present in the polymeric drug, is discussed. The antimicrobial activity of APA on Gram-positive bacteria was enhanced when copolymerized with AA and HEA. The polymer was made into a film form and that film was used for drug releasing study. The drug releasing rate was monitored by the absorption at 268 nm using a UV spectrophotometer. The effect of pH and the temperature on the drug releasing rate was monitored and found that the releasing rate was dependent on the co-monomer, pH and temperature of the medium. 相似文献
993.
The purpose of this study was to evaluate the risk factors associated with supraclavicular nodal failure (SCF) in patients with one to three positive axillary nodes treated with breast conserving surgery and axillary dissection without supraclavicular node radiation (S/C RT) to aid in the selection of patients for S/C RT. Two hundred two breast conservation patients with one to three positive axillary nodes on axillary dissection treated with breast irradiation without S/C RT and 20 patients with S/C RT between August 1985 and May 2002 were identified and retrospectively evaluated. The Kaplan-Meier method was used to determine SCF-free and overall survival curves. Risk factors for SCF were examined. The median follow-up from surgery was 72 months (range: 4-195). Nine of 202 patients (4%) failed in the ipsilateral breast, 4 (2%) in the ipsilateral supraclavicular lymph nodes, 4 (2%) in the ipsilateral axillary and/or internal mammary nodes and 30 (15%) distantly. The 5- and 10-year SCF-free survival was 97.92%. The overall survival at 5, 10, and 15 years was 91.35%, 75.58%, and 67.18%, respectively. SCFs were associated with high grade or ER negative cancers, but not with number of positive nodes. Two of the four SCFs were associated with distant metastases, and two with local failures. One patient with a SCF was salvaged and is disease-free at 134 months. The overall low incidence of SCF in patients with one to three positive nodes treated with breast radiation alone after breast conserving surgery and adequate axillary dissection suggests that additional S/C RT is unnecessary in this cohort. When it occurs, supraclavicular nodal failure is often associated with distant metastases. 相似文献
994.
995.
Comparative preclinical activity of the folate-targeted Vinca alkaloid conjugates EC140 and EC145 总被引:1,自引:0,他引:1
Leamon CP Reddy JA Vlahov IR Westrick E Parker N Nicoson JS Vetzel M 《International journal of cancer. Journal international du cancer》2007,121(7):1585-1592
EC140 is a water soluble folate conjugate of desacetylvinblastine monohydrazide (DAVLBH), which is constructed with an endosome-cleavable acyl hydrazone bond. This agent has proven to be active and specific against well established, subcutaneous folate receptor (FR)-positive tumors in multiple animal models. Recent structure-activity and optimization studies have yielded a disulfide bond-containing counterpart to EC140, herein referred to as EC145. This new conjugate was found to retain high affinity for FR-positive cells, and it produced specific, dose-responsive activity in vitro. Comparative in vivo efficacy tests confirmed that, like EC140, EC145 displays activity against both syngeneic and xenograft tumor models. However, EC145 was found to be more active and better tolerated than EC140; hence, more durable complete responses were consistently observed in EC145-treated tumor-bearing animals. Furthermore, EC145 was not found to be active against a FR-negative tumor model. Additional preclinical studies are therefore warranted to better understand EC145's breadth of activity against FR-positive tumors. 相似文献
996.
Rini BI Tamaskar I Shaheen P Salas R Garcia J Wood L Reddy S Dreicer R Bukowski RM 《Journal of the National Cancer Institute》2007,99(1):81-83
Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted. 相似文献
997.
Chutika Srisuttiyakorn Jennifer Reeve Swapna Reddy Suguru Imaeda Rossitza Lazova 《Journal of cutaneous pathology》2014,41(5):475-479
Subcutaneous histiocytoid Sweet's syndrome is a rare variant of histiocytoid Sweet's syndrome (SS). We present a 68‐year‐old woman with subcutaneous histiocytoid SS in association with refractory myelodysplastic syndrome transformed to acute myeloblastic leukemia (AML), status post induction chemotherapy and with persistent blasts (50%) in the bone marrow and blood, accompanied with neutropenia. The patient presented to the emergency room with fever and altered mental status. Clinical examination revealed approximately 20 scattered 0.5–2 cm, pink to pink‐purple non‐tender firm nodules on the legs and left arm. The differential diagnosis included Sweet's syndrome (deep), leukemia cutis, infection, polyarteritis nodosa and erythema nodosum. Histopathologic examination of a biopsy from the left arm revealed a nodular infiltrate of neutrophils and histiocytoid mononuclear cells solely in the lobular compartment of the subcutaneous fat with focal areas of necrosis. Most cells in the infiltrate labeled with myeloperoxidase (MPO) including the histiocytoid cells. The cells were negative for CD34 and CD117. All special stains for microorganisms were negative. A diagnosis of subcutaneous histiocytoid SS was made. A subcutaneous histiocytoid SS should be suspected when a neutrophilic/histiocytoid panniculitis, occurring in the setting of myeloid disorders, is encountered and after exclusion of an infectious process and leukemia cutis. 相似文献
998.
999.
Anti‐inflammatory therapy with tumour necrosis factor inhibitors is associated with reduced risk of major adverse cardiovascular events in psoriasis 下载免费PDF全文
1000.