Metastatic leiomyosarcoma of the thyroid: A rare entity.

Cancer metastasis to the thyroid gland from non-thyroid sites is a rare presentation in clinical practice. The most frequent primary cancers that metastasise to the thyroid are renal cell carcinoma, followed by colorectal, lung and breast. We report a case of a 64-year-old Malay lady who presented with anterior neck swelling 4 years after an initial diagnosis of uterine leiomyosarcoma. She had undergone a hysterectomy procedure four years ago. Fine needle aspiration cytology of the thyroid mass suggested undifferentiated thyroid carcinoma. After multi-disciplinary discussion, the patient underwent thyroidectomy and the final histopathological diagnosis was metastatic leiomyosarcoma of the thyroid. The diagnosis was aided by an immunohistochemistry panel of positive myogenic markers, negative epithelial markers as well as the previous medical history of uterine leiomyosarcoma. Metastatic leiomyosarcoma of the thyroid may mimic primary undifferentiated (anaplastic) thyroid carcinoma (UTC) with a sarcomatoid pattern, medullary thyroid carcinoma (MTC) with spindle cells morphology and spindle cell tumour with thymus-like differentiation (SETTLE). Hence, a multidisciplinary approach must be practised by pathologists, surgeons and radiologists to consider metastatic lesions of the thyroid gland, especially when a previous history of cancer exists or is suspected.

Protein expression in sera of patients with amoebic liver abscess (ALA): potential use of haptoglobin as a surrogate disease marker.

The protein profile of serum samples from patients with amoebic liver abscess (ALA) was compared to those of normal individuals to determine their expression levels and to identify potential surrogate disease markers. Serum samples were resolved by two dimensional electrophoresis (2-DE) followed by image analysis. The up and down-regulated protein spots were excised from the gels and analysed by MS/MS. The concentration of three clusters of proteins i.e. haptoglobin (HP), α1-antitrypsin (AAT) and transferrin in serum samples of ALA patients and healthy controls were compared using competitive ELISA. In addition, serum concentrations of HP and transferrin in samples of patients with ALA and pyogenic liver abscess (PLA) were also compared. The results of the protein 2-DE expression analysis showed that HP cluster, AAT cluster, one spot each from unknown spots no. 1 and 2 were significantly up-regulated and transferrin cluster was significantly down-regulated in ALA patients' sera (p<0.05). The MS/MS analysis identified the unknown protein spot no.1 as human transcript and haptoglobin and spot no. 2 as albumin. Competitive ELISA which compared concentrations of selected proteins in sera of ALA and healthy controls verified the up-regulated expression (p<0.05) of HP and the down-regulated expression (p<0.01) of transferrin in the former, while there was no significant difference in AAT expression (p> 0.05). However, when ALA and PLA samples were compared, competitive ELISA showed significant increased concentration of HP (p<0.05) while transferrin levels were not different. In conclusion, this study showed that HP is a potential surrogate disease marker for ALA.

Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients.

Colorectal cancer is one of the most common cancers in many countries, including Malaysia. The accumulation of genomic alterations is an important feature of colorectal carcinogenesis. A better understanding of the molecular events underlying the stages of colorectal carcinogenesis might be helpful in the detection and management of the disease. We used a commercially available single-nucleotide polymorphism genotyping array to detect both copy number abnormalities (CNAs) and copy-neutral loss of heterozygosity (LOH) in sporadic colorectal carcinomas. Matched tumor and normal tissues of 13 colorectal carcinomas (Dukes' stages A-D) were analyzed using a 250K single nucleotide polymorphism array. An additional assay was performed to determine the microsatellite instability status by using the National Cancer Institute-recommended BAT-26 panel. In general, copy number gain (92.3%) was most common, followed by copy number loss (53.8%) and copy-neutral LOH (46.2%). Frequent CNAs of gains and losses were observed on chromosomes 7p, 8, 13q, 17p, 18q, and 20q, and copy-neutral LOH was observed on chromosomes 2, 6, 12, 13q, 14q, 17, 20p, 19q, and 22q. Even though genomic alterations are associated with colorectal cancer progression, our results showed that DNA CNAs and copy-neutral LOH do not reflect disease progression in at least 50% tumors. Copy-neutral LOH was observed in both early and advanced tumors, which favors the involvement of these genomic alterations in the early stages of tumor development.

Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous Fungizone.

PURPOSE: Amphotericin B (AMB), an effective antifungal and antileishmanial agent associated with low oral bioavailability (0.3%) and severe nephrotoxicity, was entrapped into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve the oral bioavailability and to minimize the adverse effects associated with it. MATERIALS AND METHODS: The AMB-nanoparticles (AMB-NP) were prepared by nanoprecipitation method employing Vitamin E-TPGS as a stabilizer. In vitro release was carried out using membrane dialysis method. The in vitro hemolytic activity of AMB-NP was evaluated by incubation with red blood cells (RBCs). The acute nephrotoxicity profile and oral bioavailability of AMB-NP were evaluated in rats. RESULTS: The prepared AMB-NP formulation contained monodispersed particles in the size range of 165.6 +/- 2.9 nm with 34.5 +/- 2.1% entrapment at 10% w/w initial drug loading. AMB-NP formulation showed biphasic drug release, an initial rapid release followed by a sustained release. The AMB-NP formulation exerted lower hemolysis and nephrotoxicity as compared to Fungizone. The relative oral bioavailability of the AMB-NP was found to be approximately 800% as compared to Fungizone. CONCLUSION: Together, these results offer a possibility of treating systemic fungal infection and leishmaniasis with oral AMB-NP, which could revolutionize the infectious disease treatment modalities.