Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo.

Glioblastoma (GBM) is the most frequently diagnosed primary central nervous system tumor in adults. Despite the standard of care therapy, which includes surgical resection, temozolomide chemotherapy, radiation and the newly added tumor-treating fields, median survival remains only ∼20 months. Unfortunately, GBM has a ∼100% recurrence rate, but after recurrence there are no Food and Drug Administration-approved therapies to limit tumor growth and enhance patient survival, as these tumors are resistant to temozolomide (TMZ). Recently, our laboratory reported that lucanthone slows GBM by inhibiting autophagic flux through lysosome targeting and decreases the number of Olig2+ glioma stem-like cells (GSC) in vitro and in vivo. We now additionally report that lucanthone efficiently abates stemness in patient-derived GSC and reduces tumor microtube formation in GSC, an emerging hallmark of treatment resistance in GBM. In glioma tumors derived from cells with acquired resistance to TMZ, lucanthone retains the ability to perturb tumor growth, inhibits autophagy by targeting lysosomes, and reduces Olig2 positivity. We also find that lucanthone may act as an inhibitor of palmitoyl protein thioesterase 1. Our results suggest that lucanthone may function as a potential treatment option for GBM tumors that are not amenable to TMZ treatment. SIGNIFICANCE STATEMENT: We report that the antischistosome agent lucanthone impedes tumor growth in a preclinical model of temozolomide-resistant glioblastoma and reduces the numbers of stem-like glioma cells. In addition, it acts as an autophagy inhibitor, and its mechanism of action may be via inhibition of palmitoyl protein thioesterase 1. As there are no defined therapies approved for recurrent, TMZ-resistant tumor, lucanthone could emerge as a treatment for glioblastoma tumors that may not be amenable to TMZ both in the newly diagnosed and recurrent settings.

A Shepherd's Crook Deformity of Proximal Femur Treated by Valgus Osteotomy and Bone Grafting.

The Shepherd's crook deformity of the proximal femur is a characteristic radiologic feature of fibrous dysplasia. It may be limited to a single bone, which is called monostotic, or may be polyostotic involving multiple bones as seen in McCune-Albright Syndrome. We report a case of a 19-year-old male patient who presented to us with pain in the right hip for one year. He had dysmorphic facies and multiple café-au-lait spots over the back, which were suggestive of McCune-Albright Syndrome. The radiographs of the hip showed varus deformity of the proximal femur. A lateral closing wedge osteotomy was done and the defect was filled with morselised femoral head allografts and fibular strut allografts. At the 14-month follow-up, the patient remained functionally active without any symptoms. The use of morselised femoral head allograft combined with strut fibular allograft ensures both stability and improved biology at the site of the lesion without any donor site morbidity.

A Large Posteromedial Parameniscal Cyst Masquerading a Baker's Cyst: An Unusual Presentation.

INTRODUCTION: Meniscal cysts are rare and strongly associated with a horizontal meniscal lesion. Arthroscopic partial meniscectomy of the meniscus with intra-articular cyst drainage has become the standard of care for small cyst; however, sometimes large cyst requires open excision. CASE PRESENTATION: We report a case of a large symptomatic medial parameniscal cyst in 52-year-old female which was clinically misdiagnosed as Baker's cyst. The patient had swelling over the posteromedial aspect of the right knee with difficulty and pain on squatting. Magnetic resonance imaging (MRI) reported horizontal tear in the posterior horn of medial meniscus and parameniscal cyst adjacent to medial meniscus with features of early osteoarthritis of the knee. She was successfully treated with open excision and repair of the defect of the cyst along with arthroscopic partial medial meniscectomy. CONCLUSION: This case highlights the importance of MRI in diagnosis and planning and the use of a combined approach for successful management of large parameniscal cyst.

A Rare Case Report on Xanthogranulomatous Osteomyelitis of Hip Mimicking Tuberculosis and Review of Literature.

Xanthogranulomatous osteomyelitis (XO) is a rare chronic inflammatory process characterized by the presence of a large number of lipid-containing macrophages with lymphocytes and plasma cells. We present a case of XO of the hip in a 50-year-old woman with pain in the left hip for 28 months. The patient had a history of taking anti-tuberculosis chemotherapy for five months. Laboratory data revealed an increased erythrocyte sedimentation rate and C-reactive protein (CRP) level. Plain radiographs showed the destruction of the femoral head with arthritis and subluxation. Magnetic resonance imaging (MRI) was suggestive of tubercular infection of the left hip and a benign lesion in the left ilium. The histopathologic examination of the specimen demonstrated the presence of dead bone surrounded by lymph-plasma cells, foamy cells, and histocytes, which was consistent with XO, and culture was positive for Staphylococcus aureus infection. The patient was successfully treated with resection arthroplasty and antibiotics. It is important for the surgeons to keep XO in the list of differentials in cases with lytic lesions of bone and assessment should include microbiological culture along with the biopsy.