Evaluating [Ac]Ac-FAPI-46 for the treatment of soft-tissue sarcoma in mice.

Purpose: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB.

Methods: [Ga]Ga- and [Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice.

Fibroblast Activation Protein Expression in Sarcomas.

Objectives: Fibroblast activation protein alpha (FAP) is highly expressed by cancer-associated fibroblasts in multiple epithelial cancers. The aim of this study was to characterize FAP expression in sarcomas to explore its potential utility as a diagnostic and therapeutic target and prognostic biomarker in sarcomas.

Methods: Available tissue samples from patients with bone or soft tissue tumors were identified at the University of California, Los Angeles.

Thrombophilic Genetic Anomalies and Their Association With Dialysis Initiation Age in a Cohort of Lebanese Hemodialysis Patients.

Objectives: The relationship between chronic kidney disease and cardiovascular disease is complex and bidirectional. This relationship may be partially linked to thrombophilic genetic anomalies that may predispose to the progression of both diseases.

Materials And Methods: We analyzed blood samples from 102 Lebanese patients with end-stage renal disease and undergoing hemodialysis and 20 randomly selected healthy volunteers for frequencies of 12 cardiovascular disease gene mutations and traditional risk factors.

Could Salivary Cyclosporine Dosage Replace the Whole Blood Cyclosporine Measurements in Renal Transplant Patients?

Background: Cyclosporin (CsA) has been extensively used as the immunosuppressant of choice in renal transplantation. Currently available approaches to assess CsA levels, both in serum and blood, fail to accurately reflect the concentration of the pharmacologically active drug fraction. Free CsA levels in biological fluids (blood or saliva) have been advocated to play an important role.

Bortezomib as a Novel Approach to Early Recurrent Membranous Glomerulonephritis After Kidney Transplant Refractory to Combined Conventional Rituximab Therapy.

We report a case of early recurrent membranous glomerulonephritis after kidney transplant from a deceased donor. The patient received induction therapy and was discharged with a serum creatinine level of 0.78 mg/dL on triple maintenance immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and prednisone.

NeuCode labels for relative protein quantification.

We describe a synthesis strategy for the preparation of lysine isotopologues that differ in mass by as little as 6 mDa. We demonstrate that incorporation of these molecules into the proteomes of actively growing cells does not affect cellular proliferation, and we discuss how to use the embedded mass signatures (neutron encoding (NeuCode)) for multiplexed proteome quantification by means of high-resolution mass spectrometry. NeuCode SILAC amalgamates the quantitative accuracy of SILAC with the multiplexing of isobaric tags and, in doing so, offers up new opportunities for biological investigation.

Organ trafficking and transplant tourism: the role of global professional ethical standards-the 2008 Declaration of Istanbul.

By 2005, human organ trafficking, commercialization, and transplant tourism had become a prominent and pervasive influence on transplantation therapy. The most common source of organs was impoverished people in India, Pakistan, Egypt, and the Philippines, deceased organ donors in Colombia, and executed prisoners in China. In response, in May 2008, The Transplantation Society and the International Society of Nephrology developed the Declaration of Istanbul on Organ Trafficking and Transplant Tourism consisting of a preamble, a set of principles, and a series of proposals.

Experimental and clinical transplantation: a commitment to integrity, accountability, and ethics in publication.

For the past few years, the social, economic, and political issues surrounding the field of organ transplantation have entered into many ethical discussions. Transplant tourism, and organ trade in particular, have finally received the attention they deserve and many commendable developments have ensued. The "Declaration of Istanbul on Organ Trafficking and Transplant Tourism," the result of a collective effort by hundreds of transplant professionals the world over, is one such example and is now considered the universal charter for ethical conduct in the field of transplantation.

A novel approach in clinical immunosuppression monitoring: drug lymphocyte level.

Like others, we have shown a weak correlation between drug blood levels and clinical outcome and immune response. We recently established that in contrast to blood levels, drug lymphocyte levels are strongly associated with therapeutic efficacy. The discordance between the 2 methodologies regarding clinical outcome and immune response is related mainly to the weak association between drug blood level and target-cell content.

Myelodysplastic syndrome and pancytopenia responding to treatment of hyperthyroidism: peripheral blood and bone marrow analysis before and after antihormonal treatment.

Hematological disorders, especially single lineage abnormalities, have been described in hyperthyroidism. Pancytopenia has been reported, without myelodysplastic syndrome or megaloblastic anemia. We studied the peripheral blood smear and the bone marrow aspiration and biopsy of a 65-year-old lady, who presented with pancytopenia and thyrotoxicosis due to multinodular goiter.

Treatment of cyclosporine-induced gingival overgrowth with azithromycin-containing toothpaste.

Objectives: Gingival overgrowth is a complication of cyclosporine therapy following organ transplantation. Oral azithromycin is frequently used to treat this complication. This study examined the efficacy of local azithromycin, in the form of toothpaste, against cyclosporine-induced gingival overgrowth.

Pharmacokinetic conversion study of a new cyclosporine formulation in stable adult renal transplant recipients.

Cyclosporine A (CyA) is a standard component of immunosuppressive regimens. It is a critical-dose drug for which a minor change in absorption can have important clinical consequences. The aim of the study was to compare the pharmacokinetics and safety of the new generic CyA formulation, Equoral capsules, after a switch from original formulation, Neoral capsules, in seventy stable adult renal transplant recipients.

Cyclosporine lymphocyte maximum level: a new alternative for cyclosporine monitoring in kidney transplantation.

Objectives: To determine the relationship between clinical outcome, lymphocyte count (LC), and cyclosporine (CsA) lymphocyte maximum level (LT(m)L) in kidney transplant recipients.

Materials And Methods: CsA LT(m)L was determined in patients with biopsy-proven graft dysfunction and in patients with normal graft function. Clinical outcome was compared according to CsA LT(m)L, dosage, blood trough (C(0)) and maximum (C(max)) levels, hematocrit level, and LC.

Middle East Society for Organ Transplantation (MESOT) Transplant Registry.

During the seventies, sporadic renal transplants were performed in few MESOT-region countries, mainly Turkey, Iran, Egypt, and Lebanon. Since the introduction of cyclosporine in the early eighties, transplantation has become the preferred therapeutic modality for end-stage renal failure. In 1986, the Islamic theologians (Al Aloma) issued what became known as the Amman declaration, in which they accepted brain death and retrieval and transplantation of organs from living and cadaveric donors.

Bioavailability versus bioequivalence: the cyclosporine model.

The quest for a fixed-dose immunosuppressive drug continues. Experience with cyclosporine, tacrolimus and mycophenolate mofetil has taught us that there is no correlation between dose and clinical events. These data indicate that the concentration of the drug at the site of action (bioavailability) of each of these agents differs from one patient to the next.

The generics in transplantation and the rules on their use.

By definition a product identified by its official chemical name rather than an advertised brand name is called a generic. If a drug exert its pharmacological effects at the same site, have the same potency, same dosage form and same bioavailability as a brand name, reference listed drug (RLD), is considered as a generic. However inactive ingredients can differ between brand name and generic.

The mosaic of immunosuppressive drugs.

Graft rejections as well as tolerance are true representation of the specificity, sophistication and redundancy of an elegantly and meticulously designed immune system. Tolerance is in a way similar to the process of self-recognition where lymphoid clones, during development, baring self-reactive receptor are eliminated or rendered in active by "clonal deletion" leading to a state of accommodation and acceptance (anergic). On the other hand, both acute and chronic rejections are manifestation of the purpose of existence of the immune system, which is to defend the host against foreign invaders.

Cyclosporine blood level monitoring. Cross-reactivity of anti-cyclosporine A monoclonal with its sulphate metabolite: an in vitro study.

Cyclosporine is metabolized in the liver by the Cytochrom P450 system. Many of the metabolites have been identified and thoroughly studied. However the sulphate metabolite is the least known.

Quality assurance scheme in monitoring renal transplant patients.

Quality assessment methodologies for cyclosporin (CYA) monitoring in renal transplant patients were evaluated with a view to identifying more appropriate methods for use in the Middle East, Gulf and North African countries. The quality assessment methods used were radioimmunoassays (RIAI(125) and RIAH(3)) and specific (SP) and non- specific (NSP) fluorescence polarization (TDxSP and TDxNSP). Results indicate that TDxSP was the most accurate quality assessment technique while TDxNSP was the least accurate.