Sevket Ruacan

In vitro and in vivo evaluation of PLAGA (50/50) microspheres containing 5-fluorouracil prepared by a solvent evaporation method

Poly (DL-lactide-co-glycolide) PLAGA (50/50) microspheres containing an antineoplastic drug, 5-fluorouracil (5-FU) were prepared by a solvent evaporation process in order to passively target liver carcinomas. The microspheres were spherical with diameters 2–5 μm and encapsulated more than 70% (w/w) of the 5-FU. In vitro release patterns of 5-FU from microspheres were determined for various systems. It was found that drug release depended upon the amount of entrapped drug, the polymer molecular weight and pH of the dissolution medium. The in vitro release mechanism was diffusion controlled and followed a square-root of time relationship. In vivo distribution of 99mTc labeled microspheres after intravenous injection into mice was characterized by an initially high uptake by organs of the mononuclear phagocyte system (MPS). Following i.v. administration of fluorescein-labeled PLAGA microspheres, accumulation was into the MPS, mainly the Kupffer cells cytoplasm and near the liver sinusoids.

Submandibular hydatid cyst

Summary An unusual case of Echinococcus cysticus infection of the submandibular salivary gland is reported. A 41-year-old female patient was admitted with a progressively increasing swelling in the left submandibular region present for two years. There was no pulmonary or hepatic involvement. The site, and that there is no evidence of pulmonary or hepatic involvement is of interest in this patient. Definitive therapy required radical surgery.

Primary Breast Lymphomas: A Retrospective Analysis of Twelve Cases

This study was undertaken to define the natural history and treatment results of patients with primary breast non-Hodgkins lymphoma (NHL). Twelve female patients who had been followed at Hacettepe University Hospital between 1973 and 1997 were retrospectively evaluated. All patients presented with breast masses (6 in the right breast and 6 in the left) that had recently enlarged. The most common histologic subtype was diffuse, small cleaved-cell lymphoma. Chemotherapy regimens were employed in 9 patients. Radiotherapy was delivered to the breast and its lymphatics in 8 patients. Lumpectomy, simple or modified radical mastectomy was performed in 5 cases. An objective response was attained with surgery, chemotherapy, or radiotherapy alone in 2, 1, and 1 cases, respectively. Combined modality treatment including either two or three modalities was successful in 7 cases. The median progression-free and overall survival times were 49 and 56 months, respectively. Although primary NHL of the breast is a rare disease compared to carcinoma, it should be considered in the differential diagnosis of breast masses.

Solvent-dehydrated calvarial allografts in craniofacial surgery.

Craniofacial surgery almost always requires the use of bone grafting. Although autografts are the standard procedure for bone grafting, it is sometimes not possible to harvest bone, and autografts have particular risks. The use of allograft bone provides a reasonable alternative to meet the need for graft material. Solvent dehydration is a multistage procedure in which human cadaveric bone is processed by osmotic exchange baths and gamma sterilization. This processing avoids the risk of infection transmission, decreases antigenicity, and does not weaken the mechanical properties of the bone. Solvent-dehydrated, gamma-irradiated human calvarial bone allografts were used for reconstruction of craniofacial deformities in 24 patients between 1988 and 2002. Resorption of the allografts and results of the surgical intervention were evaluated with plain radiographs and three-dimensional computed tomography 12 months after surgery, in 21 patients. Serologic tests for human immunodeficiency virus-1 antibody, hepatitis B surface antigen, and hepatitis C antigen were also performed. Biopsy specimens were taken from the allografts. Average follow-up in this group was 30 months (range, 8 to 60 months), and results of serologic tests were negative in all patients. Seventy-one percent of the patients (15 of 21) showed no resorption, with partial and complete allograft fusion. One patient had nearly total graft loss and the remaining five patients had 10 to 25 percent graft resorption. Rigid fixation of the allograft, contact with the dura and periosteum, and prevention of dead spaces around the allograft are the most important factors in achieving a satisfactory result. In solvent-dehydrated bone allografts, sterilization and antigenic tissue cleaning are achieved after several steps with a minimal dose of radiation. The result is a nonantigenic, sterile mechanical scaffold that can tolerate external forces. Although autografts are the standard in craniofacial surgery, solvent-dehydrated calvarial bone allografts produced successful results in selected cases.

Dihydropyrimidine Dehydrogenase Enzyme Deficiency: Clinical and Genetic Assessment of Prevalence in Turkish Cancer Patients

Background: Fluorouracil has been reported to induce severe side-effects in particular subjects who have deficiency in dehydropyrimidine dehyrogenase activity, the major enzyme in the catabolism of fluorouracil. Patients and methods: In this study, we aimed to analyze the heterozygote and homozygote frequencies of dehydropyrimidine dehyrogenase gene mutation in 200 patients receiving fluorouracil based chemotherapy together with the assessment of the toxicity profile of these chemotherapy regimens. Results: According to the results of clinical toxicity assessments, grade 3–4 hematologic toxicity was noted in 12% of the patients. Grade 3 gastrointestinal toxicity was present in 5% of the subjects with no grade 4 side effects. The heterozygote (2q(1−q)) and homozygote (q2) frequencies of dehydropyrimidine dehyrogenase gene mutation were calculated as 1.5% (3/200) and 0.000055% (1/18,043) in the analyzed samples. Conclusion: In this report, for the first time we documented the frequency of dehydropyrimidine dehydrogenase gene mutation in Turkish cancer patients. The determination of enzyme activity in suspected individuals and analysis of other mutations on a population basis would be the next steps for our country.

Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland

PURPOSE Mucosa-associated lymphoid tissue lymphoma recently has been defined as a distinct subtype of non-Hodgkins lymphoma with characteristic clinicopathologic features. A 37-year-old woman with systemic lupus erythematosus and unilateral mucosa-associated lymphoid tissue lymphoma of the lacrimal gland is described. METHODS The tumor was totally excised by lateral orbitotomy. Immunohistochemical studies were performed with UCHL-1, CD20 (L26), leukocyte common antigen, cytokeratin (CAM5), and kappa and lambda light chain antibodies. RESULTS The tumor was composed of centrocyte-like lymphocytes, cells with plasmacytoid features, and lymphoepithelial lesions. Most of the cells expressed the CD20 protein and were positive for immunoglobulin kappa light chain. The patient received no supplemental therapy. No systemic dissemination or local recurrence occurred during a follow-up of 26 months. CONCLUSION The features of this case support the association between systemic diseases and the subsequent development of mucosa-associated lymphoid tissue lymphoma.

Solid tumor chemotherapy and in vivo distribution of fluorouracil following administration in poly(L-lactic acid) microspheres.

The physicochemical properties and in vivo distribution of poly(L-lactide) (L-PLA) microspheres containing 5-fluorouracil (5-FU) prepared by a solvent evaporation method were evaluated for potential use in the treatment of liver cancers. Two different molecular weight polymers of L-PLA [L-PLA1 (152,500 Da) and L-PLA2 (52,000 Da)] were used to prepare 5-FU-loaded microspheres. The mean particle size of the microspheres was 3-6 microns, and there was a direct relationship between the mean particle size and the molecular weight of the polymers. The drug release behavior from microspheres exhibited a diffusion mechanism in different dissolution media, with the molecular weight of the polymer being a major factor in controlling the drug release and degradation rates. Following intravenous injection of 99mTc-labeled L-PLA microspheres, with or without 5-FU, or free 5-FU into mice, L-PLA2 microspheres localized mainly in the liver. The disappearance rate of radioactivity from the tissue was very slow in comparison to that of free 5-FU. The results were confirmed by histological examination of liver tissue following administration of fluorescein particles. In addition, growth of a human liver tumor as first transplant generation under the renal capsule of immunocompetent rats and antitumor activity of L-PLA2 microspheres were investigated. Histological examination by optical microscopy showed that there was no neoplastic tissue of the kidney or in other tissues examined after treatment.

PTEN and p27 expression in mature T-cell and NK-cell neoplasms

PTEN is a tumor suppressor gene located on chromosome 10q23 and is amongst the most commonly mutated genes in human cancers. The lipid phosphatase activity of Pten enables it to dephosphorylate PIP3, thereby antagonizing growth factor stimulated PI3-kinase signaling mediated by AKT/PKB. The growth inhibition effect of PTEN has been shown to be mediated by p27 which is one of the important effector molecules downstream of the AKT pathway. Recently the importance of the Pten and AKT pathway in the regulation of the immune system and development of hematological malignancies has been shown. Loss of Pten and p27 expressions were examined immunohistochemically in 45 patients with peripheral T- and NK-cell lymphoma. Partial or complete loss of Pten was detected in 66.7% of the cases of anaplastic large cell lymphoma (ALCL) compared to only 12.5% of all other mature T-/NK-cell lymphomas combined. Loss of p27 was identified in 64.9% of cases, which showed a positive correlation with Pten loss. In this study, we showed that loss of Pten is more frequent in ALCL as compared to other mature T-/NK-cell lymphomas, which strongly correlates with the loss of p27 expression. Our findings provide further evidence for the importance of the deregulation of the PI3K-AKT pathway in ALCL.

Primary gingival leiomyosarcoma.

A case of primary gingival leiomyosarcoma in a 64-year-old woman is presented. The treatment modalities are discussed and the previous literature is reviewed.

Biological Reactions to a Poly(l-lactide)—Hydroxyapatite Composite: A Study in Canine Mandible

In this study, bone response, possible use and ultimate fate of a chemically-synthesized poly (L-lactide)-hydroxyapatite (PLLA-HA) composite was experimented in canine mandible. Bilateral mandibular second premolars were extracted in four dogs. The PLLA-HA composite was placed into left surgical sites, and right extraction sites were used as controls. After three months of healing, bone specimens were harvested from each animal and processed for histological evaluation. Bone uptake of methylene diphosphonate (99mTc-MDP) was calculated as indicators of osteoblastic activity in the surgical sites. Histological evaluation and the amount of 99mTc-MDP uptake showed that all surgical sites had similar levels of cellular activity and the material was biocompatible. The experimental PLLA-HA composite studied is safe to be used as a small-defect filler in applications such as repair of alveolar defects, ridge augmentations, and sinus lift procedures.