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Biomedical subjects

Nabil Saba

Publications and source records attributed to Nabil Saba.

12 recordsLinked to original sources
PubMed2005

The role of bisphosphonates in the management of advanced cancer with a focus on non-small-cell lung cancer. Part 2: Clinical studies and economic analyses.

Newer-generation intravenous bisphosphonates have resulted in the reduction of skeletal-related complications, i.e. skeletal-related events (SREs) such as pain, hypercalcemia, pathologic fractures and spinal cord and nerve compression, as well as improvements in the quality of life in patients with metastatic bone disease who are likely to have a prolonged clinical course. Highly potent, nitrogen-containing bisphosphonates such as zoledronic acid reduce SREs in patients with bone metastases from other solid tumors (including lung cancer). Part one of our review discussed the mechanisms of action by bisphosphonates as well as potential roles for bone markers and imaging in lung cancer. In this article, part two of our review, we examine the economic and clinical impact of bisphosphonates in lung cancer, with a focus on the potential role of newer-generation bisphosphonates in the management of advanced, metastatic bone disease of lung cancer.

Antineoplastic Agents↗
PubMed2005

Retinoids as chemoprevention for head and neck cancer: where do we go from here?

The retinoids, natural and synthetic derivatives of vitamin A, have a promising role in the chemoprevention of head and neck squamous cell carcinoma despite facing the limitations of toxicity as well as innate and acquired resistance. Adhering to the concept of field cancerization and following multi-step carcinogenesis, premalignant lesions of the head and neck have long been the focus of intervention with retinoids. Similarly, these agents have been applied towards preventing second primary malignancies from developing following curative therapy for upper aerodigestive cancers. Despite encouraging response rates, the need for overcoming innate and acquired retinoid resistance as well as minimizing retinoid-related toxicity will likely be relegated to the new generation of receptor-selective, synthetic retinoids. In the interim, retinoid-non-retinoid combinations as well as other classes of chemopreventive agents seem to provide promise in curtailing the incidence of aerodigestive malignancies.

Chemoprevention↗
PubMed2005

Technology evaluation: mapatumumab, Human Genome Sciences/GlaxoSmithKline/Takeda.

Human Genome Sciences and GlaxoSmithKline, under license from Cambridge Antibody Technology, are developing mapatumumab, the intravenously administered lead from a series of human monoclonal antibody tumor necrosis factor-related apoptosis-inducing ligand receptor 1 agonists, for the potential treatment of cancer. The therapy is currently undergoing phase II clinical trials. Takeda is developing mapatumumab in Japan.

Antibodies, Monoclonal↗
PubMed2004

The role of bisphosphonates in the management of advanced cancer with a focus on non-small-cell lung cancer. Part 1: Mechanisms of action, role of biomarkers and preclinical applications.

With recent advances in cancer management, patients with metastatic bone disease are likely to have a prolonged clinical course, with skeletal-related events such as pain, hypercalcemia, pathologic fractures, spinal cord and nerve compression. Bisphosphonate use has resulted in the reduction of skeletal-related complications for a number of tumors including breast, prostate and myeloma, and improvements in the quality of life for patients. There is now evidence that newer, highly potent, nitrogen-containing bisphosphonates reduce skeletal complications in patients with bone metastases from other solid tumors (including lung cancer). The early identification of patients at high risk for developing bone metastases may help curtail a complex and costly clinical problem--skeletal-related events. In this article, we review the different mechanisms of bisphosphonates and the potential role of newer-generation bisphosphonates, such as zoledronic acid, in the management of advanced, metastatic bone disease. We include a review of mechanistic studies and preclinical data. Additionally, the utility of evolving concepts such as bone markers and imaging of bone metastases are discussed.

Antineoplastic Agents↗
PubMed2004

Intra-cranial lesions in a patient with Hodgkin lymphoma.

Central nervous system (CNS) lesions in newly diagnosed, advanced Hodgkin's disease (HD) commonly suggest intracranial involvement with HD. However, occasionally this could be the result of a CNS infection. We report a case of concurrent CNS tuberculosis in a patient with stage III E HD the first reported in the English literature. Management of this case and the literature pertaining to infectious complications of HD are reviewed.

Adult↗
PubMed2004

Molecular biological design of novel antineoplastic therapies.

Novel therapies represent a new strategy for the development of anticancer agents. New targets derived from the knowledge of the molecular structure and genetic defects has been useful in developing anticancer drugs that prolong or stabilise the progression of tumours with minimal systemic toxicities. In this review, the mechanism of action and the most significant trials regarding monoclonal antibodies, tyrosine kinase inhibitors, angiogenesis and cyclooxygenase inhibitor-based therapies, farnesyl transferase inhibitors and proteasome inhibitors are discussed. The potential biological end points and toxicities are also described. In conclusion, novel therapies present a promising class of anticancer agents, acting through different mechanisms and offering a new perspective in the treatment of cancer.

Alkyl and Aryl Transferases↗
PubMed2004

Novel targeted agents in the treatment of lung cancer.

Lung cancer is the leading cause of cancer-related mortality in the US. Although an improvement in outcome is possible with the continued advancement of cytotoxic-based treatment, clinical research is currently focused on utilising novel molecular targets with proven efficacy in preclinical models and a low toxicity profile. This is the result of advances in understanding of tumour biology and molecular pathways that have been implicated in cancer pathogenesis and progression. Novel agents targeting cell cycle regulation, angiogenesis and signal transduction pathways have reached clinical testing in lung cancer and are discussed in this review.

Alkyl and Aryl Transferases↗
PubMed2003

Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes.

Blood microparticles (MPs) in sickle cell disease (SCD) are reportedly derived only from erythrocytes and platelets. Yet in SCD, endothelial cells and monocytes are activated and abnormally express tissue factor (TF). Thus, sickle blood might contain TF-positive MPs derived from these cells. With the use of flow cytometry to enumerate and characterize MPs, we found total MPs to be elevated in crisis (P =.0001) and steady state (P =.02) in subjects with sickle cell disease versus control subjects. These MPs were derived from erythrocytes, platelets, monocytes, and endothelial cells. Erythrocyte-derived MPs were elevated in sickle crisis (P =.0001) and steady state (P =.02) versus control subjects, as were monocyte-derived MPs (P =.0004 and P =.009, respectively). Endothelial and platelet-derived MPs were elevated in sickle crisis versus control subjects. Total TF-positive MPs were elevated in sickle crisis versus steady state (P =.004) and control subjects (P <.0001) and were derived from both monocytes and endothelial cells. Sickle MPs shortened plasma-clotting time compared with control MPs, and a TF antibody partially inhibited this procoagulant activity. Markers of coagulation were elevated in patients with sickle cell disease versus control subjects and correlated with total MPs and TF-positive MPs (P <.01 for both). These data support the concept that SCD is an inflammatory state with monocyte and endothelial activation and abnormal TF activity.

Adult↗
PubMed2002

A 39-bp deletion polymorphism in PTEN in African American individuals: implications for molecular diagnostic testing.

Germline mutations in the PTEN/MMAC1/TEP1 tumor suppressor gene cause Cowden syndrome (CS), a hereditary hamartoma-tumor syndrome with an increased risk of breast, thyroid, and endometrial cancers, and seemingly unrelated developmental disorders, such as Bannayan-Riley-Ruvalcaba (BRR) syndrome, Proteus, and Proteus-like syndromes. Data to date suggest that irrespective of the clinical presentation, the identification of a PTEN mutation should trigger medical management which includes cancer surveillance. Clinic-based molecular diagnostic testing for germline PTEN mutations has been available for at least 2 years. This study reports on the finding of a previously unobserved heterozygous alteration (IVS7-15-->53del39) found in an African American individual who had features of CS. Further investigation revealed that 12 of 42 (28.6%) African American controls, but not individuals of Caucasian or Japanese origin, also carried this heterozygous 39-bp deletion in PTEN. Due to its location immediately upstream of the splicing site of exon 8, this polymorphism could be mistaken for a deleterious mutation in the PTEN.

Base Sequence↗
PubMed2002

Bone marrow transplantation for nonmalignant diseases.

Bone marrow transplantation (BMT) has emerged as a major therapeutic option for a number of nonmalignant disorders affecting the bone marrow and leading to clinical manifestations most likely affecting distant organs. Disorders such as autoimmune diseases, metabolic disorders, hemoglobinopathies, immunodeficiencies, and others have been the target of high-dose therapy and autologous or allogeneic bone marrow, stem cell, or cord blood transplantation. Successful results have been reported in a large number of these disorders. In most instances the goal of transplantation is to provide sufficient degree of marrow engraftment to allow long-term amelioration of disease phenotype. For many of these disorders, early diagnosis is crucial in achieving the desired results as transplantation becomes difficult when significant end-organ damage sets in. Major unsolved problems, including toxicity of conditioning regimens, graft-versus-host disease, and donor availability, need to be addressed. We attempt to provide a comprehensive review of BMT and discuss unique features of this modality for treatment of nonmalignant disorders.

Bone Marrow Transplantation↗