Abstract: The subject matter disclosed herein relates generally to cancer therapy and to anticancer compounds and imaging agents. More specifically, the subject matter disclosed herein relates to agents that target DOR and their use in the treatment of cancer.

Abstract: The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Abstract: A method of treating cancer or inhibiting metastasis in a subject by increasing intratumoral extracellular pH is presented. The method includes administering to the subject a therapeutically effective amount of a buffer having a pKa greater than 6.1. In an advantageous embodiment the pKa of the buffer is about 7.0. Examples of buffers for increasing extracellular pH include NaHCO3, 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA), cholamine chloride, N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), N-Tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES) and 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES). The method can further include the step of pretreating with one or more chemotherapeutic agents.

Abstract: Disclosed are monoacylated Toll-like receptor 2 ligands which can be used in both the development of targeted agents for the imaging and treatment of pancreatic cancer as well as other cancers, and as an adjuvant for cancer immunotherapy. The monoacylated compounds disclosed herein have a higher binding affinity for TLR2 relative to a known potent diacylated agonists, but only ?½ the bioactivity. Competition of the monoacylated compound with the diacylated compound for binding TLR2 was confirmed. Hence, the reported monoacylated compounds are inhibitors/antagonists of TLR2 activation.

Abstract: Disclosed are monoacylated Toll-like receptor 2 ligands which can be used in both the development of targeted agents for the imaging and treatment of pancreatic cancer as well as other cancers, and as an adjuvant for cancer immunotherapy. The monoacylated compounds disclosed herein have a higher binding affinity for TLR2 relative to a known potent diacylated agonists, but only ?½ the bioactivity. Competition of the monoacylated compound with the diacylated compound for binding TLR2 was confirmed. Hence, the reported monoacylated compounds are inhibitors/antagonists of TLR2 activation.

Abstract: The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Abstract: Disclosed is CT or MR contrast agent which comprises a base or carrier scaffold formed of a polyhydroxol compound having a linker to which a Gd-DOTA is covalently bonded. Also disclosed is a method of screening a patient for colon cancer using a CT or MR contrast, which method comprises administering to a patient undergoing screening a compound as above described.

Abstract: The current invention pertains to a molecular conjugate comprising an antagonist of a cell surface receptor specific to a target cell and an immune effector, such as a T cell modulator, conjugated to the antagonist. The target cell can be a cell responsible for development of a disease in a subject, for example, a cancer cell. In certain embodiments, the immune effector is an immune effector protein or an immune effector fragment thereof. The current invention also pertains to a method of treating a disease in a subject, the method comprising administering to the subject a pharmaceutically effective amount of the molecular conjugates of the current invention to the subject. The methods of the current invention can be used to treat cancer, such as breast cancer, ovarian cancer, prostate cancer, lung cancer, pancreatic cancer, or melanoma.

Abstract: The present invention relates to biomarkers for colon cancers, specifically adenomas and adenocarcinomas in the GI tract. The inventors have discovered that the expression and/or overexpression of biomarkers such as CLDN1, GPR56, GRM8, LY6G6D, TLR4 and SLCO1B3 are indicative of adenomas and adenocarcinomas. A method of detecting colon cancer using targeted molecular imaging agents is also presented.

Abstract: The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Abstract: Molecular probes directed to the delta opioid receptor and associated methods of use as non-invasive diagnostics for lung cancer are presented. The molecular probes generally consist of a ligand (Dmt-Tic) that is conjugated to a detection moiety such as a fluorescent dye or a radionuclide by a linker molecule. Once the probe is administered, it may be detected by a molecular imaging device to locate tumors for treatment or removal. Also presented are novel markers for lung cancer including, but not limited to, CA9, CA12, CTAG2, CXorf61, DSG3, FAT2, KISS1R, GPR87, LYPD3, OPRD1, SLC7A11 and TMPRSS4. Probes may be developed that can target these cell surface markers.

Abstract: Cellular targets on cancer cells have been identified that can be used with targeted molecular imaging to detect the cancer cells in vivo. Non-invasive methods for detecting cancer cells, such as metastasized cancer cells, are therefore provided. Also provided are compositions and kits for use in the disclosed methods.

Abstract: The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Abstract: The present invention relates to biomarkers for colon cancers, specifically adenomas and adenocarcinomas in the GI tract. The inventors have discovered that the expression and/or overexpression of biomarkers such as CLDN1, GPR56, GRM8, LY6G6D, TLR4 and SLCO1B3 are indicative of adenomas and adenocarcinomas. A method of detecting colon cancer using targeted molecular imaging agents is also presented.

Abstract: Cellular targets on cancer cells have been identified that can be used with targeted molecular imaging to detect the cancer cells in vivo. Non-invasive methods for detecting cancer cells, such as metastasized cancer cells, are therefore provided. Also provided are compositions and kits for use in the disclosed methods.

Abstract: A method of treating cancer or inhibiting metastasis in a subject by increasing intratumoral extracellular pH is presented. The method includes administering to the subject a therapeutically effective amount of a buffer having a pKa greater than 6.1. In an advantageous embodiment the pKa of the buffer is about 7.0. Examples of buffers for increasing extracellular pH include NaHCO3, 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA), cholamine chloride, N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), N-Tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES) and 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES). The method can further include the step of pretreating with one or more chemotherapeutic agents.

Abstract: Methods that identify cells as pancreatic cancer cells based on assessing the expression of combinations of target molecules expressed preferentially on pancreatic cancer cells are disclosed. Combinations were initially discovered by microarray analysis and selected based upon tumor specificity, relative lack of cross-reactivity with normal tissues, and applicability as targets of multispecific ligands. The claimed methods encompass measuring the expression of three or more specific target molecules in combination and correlating positive expression of the combination with an identification of the cell as a pancreatic cancer cell.

Abstract: Methods that identify cells as pancreatic cancer cells based on assessing the expression of combinations of target molecules expressed preferentially on pancreatic cancer cells are disclosed. Combinations were initially discovered by microarray analysis and selected based upon tumor specificity, relative lack of cross-reactivity with normal tissues, and applicability as targets of multispecific ligands. The claimed methods encompass measuring the expression of three or more specific target molecules in combination and correlating positive expression of the combination with an identification of the cell as a pancreatic cancer cell.

Abstract: A method of writing a pattern, such as a waveguide, in a bulk glass substrate. The bulk glass substrate can be formed from, for example, borosilicate or sulfide or lead glass. A pulsed laser beam is focused within the substrate while the focus is translated relative to the substrate along a scan path at a scan speed effective to induce an increase in the refractive index of the material along the scan path. Substantially no laser induced physical damage of the material is incurred along the scan path. Various optical devices can be made using this method.

Abstract: A detachable fiber optic connector has an improved nose block (800) which enhances cooling of power dissipating components, simplifies assembly, improves yield and reduces cost. The improved nose block (800) includes an upper tray (802) and lower tray (804) which slidingly receive an improved aluminum nitride optical subassembly (700). The subassembly (700) and nose block (800) are held together, properly aligned, and then fixated. The nose block (800) also has symmetrical protrusions (850) which allow the nose block (800) to be placed easily and precisely into mating protrusions (230, 240) in a seal ring (200). The nose block (800) provides a direct thermal pathway between power dissipating components, such as an opto-electronic component (750) and optical driver IC (730), and an aluminum package base (400). Various alternative nose blocks (810, 820, 830) are illustrated, and an alternative base (410) is also shown.