Phyto-Photodynamic Therapy of Prostate Cancer Cells Mediated by Yemenite 'Etrog' Leave Extracts.

Cancer therapy, from malignant tumor inhibition to cellular eradication treatment, remains a challenge, especially regarding reduced side effects and low energy consumption during treatment. Hence, phytochemicals as cytotoxic sensitizers or photosensitizers deserve special attention. The dark and photo-response of Yemenite 'Etrog' leaf extracts applied to prostate PC3 cancer cells is reported here.

Synthesis and anticancer properties of novel dolastatin 10 analogs featuring five-membered heterocyclic rings with a linkable group at the C-terminus.

Dolastatin 10 (Dol-10), a natural marine-source pentapeptide, is a powerful antimitotic agent regarded as one of the most potent anticancer compounds found to date. Dol-10 however, lacks chemical conjugation capabilities, which restricts the feasibility of its application in targeted drug therapy. This limitation has spurred the prospect that chemical structure of the parent molecule might allow conjugation of the derivatives to drug carriers such as antibodies.

Turn-on Coumarin Precursor: From Hydrazine Sensor to Covalent Inhibition and Fluorescence Detection of Rabbit Muscle Aldolase.

Hydrazine, a highly toxic compound, demands sensitive and selective detection methods. Building upon our previous studies with pre-coumarin OFF-ON sensors for fluoride anions, we extended our strategy to hydrazine sensing by adapting phenol protecting groups (propionate, levulinate, and γ-bromobutanoate) to our pre-coumarin scaffold. These probes reacted with hydrazine, yielding a fluorescent signal with low micromolar limits of detection.

Au nanodyes as enhanced contrast agents in wide field near infrared fluorescence lifetime imaging.

The near-infrared (NIR) range of the electromagnetic (EM) spectrum offers a nearly transparent window for imaging tissue. Despite the significant potential of NIR fluorescence-based imaging, its establishment in basic research and clinical applications remains limited due to the scarcity of fluorescent molecules with absorption and emission properties in the NIR region, especially those suitable for biological applications. In this study, we present a novel approach by combining the widely used IRdye 800NHS fluorophore with gold nanospheres (GNSs) and gold nanorods (GNRs) to create Au nanodyes, with improved quantum yield (QY) and distinct lifetimes.

Multifractal analysis of cellular ATR-FTIR spectrum as a method for identifying and quantifying cancer cell metastatic levels.

Cancer is a leading cause of mortality today. Sooner a cancer is detected, the more effective is the treatment. Histopathological diagnosis continues to be the gold standard worldwide for cancer diagnosis, but the methods used are invasive, time-consuming, insensitive, and still rely to some degree on the subjective judgment of pathologists.

Tracking the cellular immune response from early premalignancy to active multiple myeloma in a new model.

To calibrate a murine model to study premalignant to malignant multiple myeloma, mice were inoculated with different amounts of myeloma cells, and changes in the immune profile were tracked for over 200 days. The model highlights the development of T-cell exhaustion and suppressor before the appearance of clinical symptoms.

The non-ionizing electromagnetic stimulation enhanced antibody production (NESEAP) effect - Discovery and technological applications.

The rise of biological therapeutics in the global pharmaceuticals market has escalated the demand for quality monoclonal antibodies for healthcare and scientific applications. Reducing costs while enhancing production yields without compromising quality are the main challenges to the growth of this industry today. Over the last two decades non-ionizing radiation has been demonstrated to elicit targeted biological responses in a frequency and dose dependent manner.

A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules.

How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled physiological conditions. We use amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium at targeted locations. This vessel disruption is performed in conjunction with transient hyperglycemia from a single injection of metabolically active -glucose into healthy mice.

Thioxobimanes.

Dioxobimanes, colloquially known as bimanes, are a well-established family of -heterobicyclic compounds that share a characteristic core structure, 1,5-diazabicyclo[3.3.0]octadienedione, bearing two endocyclic carbonyl groups.

Search for Synergistic Drug Combinations to Treat Chronic Lymphocytic Leukemia.

Finding synergistic drug combinations is an important area of cancer research. Here, we sought to rationally design synergistic drug combinations with an inhibitor of BTK kinase, ibrutinib, which is used for the treatment of several types of leukemia. We (a) used a pooled shRNA screen to identify genes that protect cells from the drug, (b) identified protective pathways via bioinformatics analysis of these gene sets, and (c) identified drugs that inhibit these pathways.

Fractal and textural imaging identify new subgroups of patients with colorectal cancer based on biophysical properties of the cancer cells.

Colorectal cancer (CRC) can been sub-divided, based on the generation of tertiary lymphoid structures (TLS), into CRC with a Crohn's like lymphoid reaction (CLR) representing de novo formation of TLSs or CRC lacking TLSs that show Diffuse Inflammatory infiltration (DII). The association between TLS, early treatment initiation and longer survival highlights the need for deeper patient stratification that could lead to more targeted therapies. We hypothesized that such stratification might be achieved by using digital image analyses.

Novel Cyclic Peptides for Targeting EGFR and EGRvIII Mutation for Drug Delivery.

The epidermal growth factor-epidermal growth factor receptor (EGF-EGFR) pathway has become the main focus of selective chemotherapeutic intervention. As a result, two classes of EGFR inhibitors have been clinically approved, namely monoclonal antibodies and small molecule kinase inhibitors. Despite an initial good response rate to these drugs, most patients develop drug resistance.

The emerging role of selenium metabolic pathways in cancer: New therapeutic targets for cancer.

Selenium (Se) is incorporated into the body via the selenocysteine (Sec) biosynthesis pathway, which is critical in the synthesis of selenoproteins, such as glutathione peroxidases and thioredoxin reductases. Selenoproteins, which play a key role in several biological processes, including ferroptosis, drug resistance, endoplasmic reticulum stress, and epigenetic processes, are guided by Se uptake. In this review, we critically analyze the molecular mechanisms of Se metabolism and its potential as a therapeutic target for cancer.

The Impact of Induction Regimes on Immune Responses in Patients with Multiple Myeloma.

Current standard frontline therapy for newly diagnosed patients with multiple myeloma (NDMM) involves induction therapy, autologous stem cell transplantation (ASCT), and maintenance therapy. Major efforts are underway to understand the biological and the clinical impacts of each stage of the treatment protocols on overall survival statistics. The most routinely used drugs in the pre-ASCT "induction" regime have different mechanisms of action and are employed either as monotherapies or in various combinations.

Long-term survival without graft-versus-host-disease following infusion of allogeneic myeloma-specific Vβ T cell families.

Background: Despite chemo-induction therapy and autologous stem cell transplantation (ASCT), the vast majority of patients with Multiple Myeloma (MM) relapse within 7 years and the disease remains incurable. Adoptive Allogeneic T-cell therapy (ATCT) might be curative for MM, however current ATCT protocols often lead to graft versus host disease (GvHD). Transplanting only tumor reactive donor T cells that mediate a graft-versus-myeloma (GvM) but not GvHD may overcome this problem.

Synthesis of Gold Nanoparticle: Peptide-Drug Conjugates for Targeted Drug Delivery.

Peptide-drug conjugates (PDCs) are being developed for the targeted delivery of drugs to cancer cells. Several approaches are being followed to enhance their stability in biological solutions. Here we describe an effective method to easily couple PDCs to polyethylene-coated gold nanoparticles.

New somatostatin-drug conjugates for effective targeting pancreatic cancer.

Pancreatic cancer poorly responds to available drugs, and finding novel approaches to target this cancer type is of high significance. Here, based on a common property of pancreatic cancer cells to express somatostatin receptors (SSTR), we designed drug conjugates with novel somatostatin-derived cyclic peptides (SSTp) with broad selectivity towards SSTR types to facilitate drug targeting of the pancreatic cancer cells specifically. Uptake of our newly designed SSTps was facilitated by SSTRs expressed in the pancreatic cancers, including SSTR2, SSTR3, SSTR4 and SSTR5.

Gold nanoparticles stabilize peptide-drug-conjugates for sustained targeted drug delivery to cancer cells.

Background: Peptide-drug-conjugates (PDCs) are being developed as an effective strategy to specifically deliver cytotoxic drugs to cancer cells. However one of the challenges to their successful application is the relatively low stability of peptides in the blood, liver and kidneys. Since AuNPs seem to have a longer plasma half-life than PDCs, one approach to overcoming this problem would be to conjugate the PDCs to gold nanoparticles (AuNPs), as these have demonstrated favorable physico-chemical and safety properties for drug delivery systems.

Discovery of peptide drug carrier candidates for targeted multi-drug delivery into prostate cancer cells.

Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells.

Discovery of potent molecular chimera (CM358) to treat human metastatic melanoma.

The resistance of cancer cells to chemotherapeutic agents, whether through intrinsic mechanisms or developed resistance, motivates the search for new chemotherapeutic strategies. In the present report, we demonstrate a facile synthetic strategy towards the discovery of new anti-cancer substances. This strategy is based on simple covalent coupling between known anti-cancer drugs, which results in novel 'chimeric' small molecules.

Recent Innovations in Peptide Based Targeted Drug Delivery to Cancer Cells.

Targeted delivery of chemotherapeutics and diagnostic agents conjugated to carrier ligands has made significant progress in recent years, both in regards to the structural design of the conjugates and their biological effectiveness. The goal of targeting specific cell surface receptors through structural compatibility has encouraged the use of peptides as highly specific carriers as short peptides are usually non-antigenic, are structurally simple and synthetically diverse. Recent years have seen many developments in the field of peptide based drug conjugates (PDCs), particularly for cancer therapy, as their use aims to bypass off-target side-effects, reducing the morbidity common to conventional chemotherapy.

syn-Bimane as a chelating O-donor ligand for palladium(ii).

A cationic Pd(ii) complex containing syn-(Me,Me)bimane as a ligand was prepared and fully characterized. This complex represents the first well-defined case of a bimane scaffold coordinated to a metal center. The strongly-fluorescent syn-bimane chelates the Pd(ii) center via its carbonyl oxygen atoms, affording a non-fluorescent complex.