Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
Add more filters










Database
Language
Publication year range
1.
Case Rep Pulmonol ; 2018: 9736516, 2018.
Article in English | MEDLINE | ID: mdl-30363701

ABSTRACT

Plastic bronchitis is the expectoration of bronchial casts in the mold of the tracheobronchial tree. It is a rare occurrence of unknown etiology that has been primarily described in children with congenital heart disease. In this case report, we present the first reported case of plastic bronchitis in a patient with pulmonary Kaposi sarcoma and underlying HIV infection.

2.
PLoS One ; 9(1): e86717, 2014.
Article in English | MEDLINE | ID: mdl-24489774

ABSTRACT

BACKGROUND: Contemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC) require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available. METHODOLOGY/PRINCIPAL FINDINGS: Recent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (<20% error) and a precision (CV<25%) down to at least 9 CTC/ml. Using anti-EpCAM antibodies as the capture agent, the platform recovers 78% of MCF7 cells within the linear range. Non specific recovery of background cells is independent of target cell density and averages 55 cells/mL. 10% purity can be achieved with as low as 6 CTCs/mL and better than 1% purity can be achieved with 1 CTC/mL. CONCLUSIONS/SIGNIFICANCE: The LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens the way for clinically relevant genetic profiling of CTCs.


Subject(s)
Cell Separation/methods , Neoplastic Cells, Circulating/metabolism , Antibodies/chemistry , Antigens, Neoplasm/chemistry , Antigens, Neoplasm/genetics , Automation, Laboratory , Cell Adhesion Molecules/chemistry , Cell Adhesion Molecules/genetics , Cell Count , Cell Line, Tumor , Epithelial Cell Adhesion Molecule , Gene Expression , Humans , Magnets , Microfluidic Analytical Techniques , Neoplastic Cells, Circulating/pathology , Rheology
3.
ACS Med Chem Lett ; 1(1): 4-8, 2010 Jan 01.
Article in English | MEDLINE | ID: mdl-20730035

ABSTRACT

Herein we show that San A-amide, a structurally unique molecule, influences a subset of cancer-related pathways involving Hsp90. We show that San A-amide specifically binds to the N-middle domain of Hsp90 allosterically disrupts the binding of proteins thought to interact with the Hsp90 C-terminal domain, while having no effect on an N-terminal domain client protein. This unique mechanism suggests that San A-amide is a potential tool for studying C-terminal binding proteins of Hsp90 as well as a promising lead in the development of new cancer therapeutics.

4.
J Med Chem ; 52(24): 7927-30, 2009 Dec 24.
Article in English | MEDLINE | ID: mdl-20014866

ABSTRACT

Described is the SAR of 18 di-sansalvamide A derivatives and the mechanism of action of the most potent compound. We show that this scaffold is a promising lead in the development of novel cancer therapeutics because it is cytotoxic at nanomolar potency, inhibits a well-established oncogenic target (Hsp90), and does not share structural motifs with current drugs on the market.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Depsipeptides/chemistry , Depsipeptides/pharmacology , Antineoplastic Agents/chemical synthesis , Depsipeptides/chemical synthesis , Drug Delivery Systems , HSP90 Heat-Shock Proteins/antagonists & inhibitors , HeLa Cells , Humans , Structure-Activity Relationship
5.
Bioorg Med Chem ; 17(16): 5806-25, 2009 Aug 15.
Article in English | MEDLINE | ID: mdl-19643615

ABSTRACT

We report an extensive structure-activity relationship (SAR) of 78 compounds active against two pancreatic cancer cell lines. Our comprehensive evaluation of these compounds utilizes SAR that allow us to evaluate which features of potent compounds play a key role in their cytotoxicity. This is the first report of 19 new second-generation structures, where these new compounds were designed from the first generation of 59 compounds. These 78 structures were tested for their cytotoxicity and this is the first report of their activity against two pancreatic cancer cell lines. Our results show that out of 78 compounds, three compounds are worth pursuing as leads, as they show potency of 55% in both cancer cell lines. These three compounds all have a common structural motif, two consecutive d-amino acids and an N-methyl moiety. Further, of these three compounds, two are second-generation structures, indicating that we can incorporate and utilize data from the first generation to design potency into the second generation. Finally, one analog is in the mid nanomolar range, and has the lowest IC(50) of any reported San A derivative. These analogs share no structural homology to current pancreatic cancer drugs, and are cytotoxic at levels on par with existing drugs treating other cancers. Thus, we have established Sansalvamide A as an excellent lead for killing multiple pancreatic cancer cell lines.


Subject(s)
Antineoplastic Agents/chemistry , Depsipeptides/chemistry , Pancreatic Neoplasms/drug therapy , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Cell Line, Tumor , Depsipeptides/chemical synthesis , Depsipeptides/toxicity , Drug Design , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Humans , Structure-Activity Relationship
6.
Bioorg Med Chem Lett ; 18(8): 2549-54, 2008 Apr 15.
Article in English | MEDLINE | ID: mdl-18381239

ABSTRACT

We outline the synthesis of six novel derivatives that are based on a recently discovered HDAC inhibitor FR235222. Our work is the first report utilizing a novel binding element, guanidine, as metal coordinators in HDAC inhibitors. Further, we demonstrate that these compounds show cytotoxicity that parallels their ability to inhibit deacetylase activity, and that the most potent compounds maintain an L-Phe at position 1, and a D-Pro at position 4. Both inhibition of HDAC activity and cytotoxicity against the pancreatic cancer cell line BxPC3 are exhibited by these compounds, establishing that a guanidine unit can be utilized successfully to inhibit HDAC activity.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Histone Deacetylase Inhibitors , Peptides, Cyclic/chemical synthesis , Peptides, Cyclic/pharmacology , Enzyme Inhibitors/chemistry , Histone Deacetylases/metabolism , Molecular Structure , Peptides, Cyclic/chemistry , Structure-Activity Relationship
7.
Org Lett ; 10(2): 177-80, 2008 Jan 17.
Article in English | MEDLINE | ID: mdl-18095697

ABSTRACT

Described are the syntheses of five decapeptides that are C-2-symmetrical derivatives of the natural product pentapeptide sansalvamide A. Derivatives were made using a succinct convergent synthesis. These analogues share no structural homology to current cancer drugs, are cytotoxic at levels on par with existing drugs treating cancers, and demonstrate selectivity for drug-resistant pancreatic cancer cell lines over noncancerous cell lines. These molecules are excellent chemotherapeutic leads in the search for new anticancer agents.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Depsipeptides/chemical synthesis , Depsipeptides/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/classification , Depsipeptides/chemistry , Depsipeptides/classification , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Molecular Structure , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...