A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation.

Osteosarcoma is the most common cancer in bone. Drug resistance is a challenge of current treatments that needs to be improved with novel treatment strategies. In this research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations. GEM is a well-known anticancer agent and CLF is a leprostatic and anti-inflammatory drug recently recognized as effective on cancer. GEM and CLF co-loaded liposomal formulation was achieved with compartmentalization as hydrophilic GEM being in core and lipophilic CLF sequestering in lipid-bilayer. Liposomes had high encapsulation efficiency (above 90%, GEM and above 80%, CLF). CLF release was enhanced while GEM release was slowed down in co-loaded liposomes compared to single cases. GEM/CLF co-loaded liposomes significantly enhanced cytotoxicity than GEM or CLF loaded liposomes on osteosarcoma cell line. CLF and GEM had synergistic effect (CI < 1). Results of flow cytometry showed higher apoptotic cell ratio, caspase-3 activity, mitochondrial membrane depolarized cells' ratio for GEM/CLF co-loaded liposome treatments than other liposomes. Cytotoxicity of CLF on bone cancer cells and also its synergistic effect with GEM on osteosarcoma is reported for the first time with this study. CLF's loading with GEM into liposome was also a new approach for enhancement of anticancer effect on Saos-2 cells. Therefore, GEM/CLF co-loaded liposomal delivery system is proposed as a novel approach for treatment of osteosarcoma.

Epidermal nevus syndrome associated with unusual neurological, ocular, and skeletal features.

Epidermal nevus syndrome (ENS) is a rare disease, the pathogenesis of which is largely elusive. We, hereby, report an exclusive case of a 20-year-old man with verrucous ENS presented with dark colored papules and plaques along the Blaschko's lines present over the head and neck area along with fleshy growth in both eyes since birth. Limb length discrepancy and kyphoscoliosis were remarkable. Skin biopsy was compatible with verrucous epidermal nevus while the biopsy of the ocular lesion confirmed complex choristoma. MRI brain revealed calcification in the right temporal lobe. Bilateral arachnoid cyst in the middle cranial fossa, scleral osteoma in the posterior part of the right eyeball, and deformed calvarium were evident on CECT skull and orbit. The present illustration emphasizes the importance of a punctilious work up of the case.

Ewing's sarcoma with cutaneous metastasis--a rare entity: report of three cases.

Ewing's sarcoma (ES) is a small round cell tumor, usually arising from flat bones and diaphyseal region of long bones. It is commonly found in the first two decades of life. It is curable when diagnosed in the localized stage and requires multimodality treatment. ES is a chemosensitive tumor. It metastasizes commonly to lung, pleura and other bones. Less common sites of metastasis are lymph nodes, CNS and liver. Skin metastasis is extremely uncommon. It occurs in up to 9% of all patients with cancer. Growth pattern of cutaneous metastasis is unpredictable and may not reflect that of primary tumor. We hereby report three cases of Ewing's sarcoma that developed skin metastasis.

Plasma CEA levels in small cell lung cancer. Correlation with stage, distribution of metastases, and survival.

Plasma CEA levels were determined in 61 patients with small cell lung cancer entering chemotherapy protocols between 1976 and 1980. Five quantitative categories were determined: less than 2.5 ng/ml (the standard normal for Hansen assay); 2.6-5.0 ng/ml (the extended normal for smokers); 5.1-20.0 ml; (the intermediate elevation and the transition for the indirect to the direct assay); 20-100 ng/ml; and greater than 100 ng/ml. Forty-seven percent of patients had levels less than 5 ng/ml and only ten of 61 or 16% had levels greater than 20 ng/ml. There was no clearcut relationship of plasma CEA level to stage of disease, in that 40% of patients with extensive disease (32 patients) had levels less than 5 ng/ml and 45% of patients with limited disease (29 patients) had levels greater than 5 ng/ml. Similarly, there was no relationship of CEA level to site of metastases, although levels greater than 100 ng/ml were always associated with liver metastases. The median survival for each quantitative category was similar, ranging from seven to nine months. The use of sequential determinations of CEA to correlate with tumor response was studied in only eight patients with levels greater than 20 ng/ml and a measurable parameter of disease. The qualitative direction of change of CEA was appropriate in those patients responding to treatment but in three nonresponding patients the direction of CEA change paradoxically decreased. In five patients who developed progressive disease, the plasma CEA level predicted the clinical relapse. CEA as a tumor marker for oat cell carcinoma must be applied in conjunction with other tumor parameters and is meaningful in only a small proportion of the total small cell patient population.