Purpose: The novel indirubin derivatives 5 ¶-nitro-indirubinoxime, 5 ¶-fluoro-indirubinoxime, and 5 ¶-trimethylacetamino-indirubinoxime were designed and tested for antitumor activity both in vitro and in vivo using rat tumor model. Experimental Design: Three-week-old male Sprague-Dawley rats were inoculated s.c. on the left flank with 10 7 RK3E-ras rat kidney epithelial cells harboring k-ras gene. Alternatively, 5 Â 10 6 RK3E-ras cells were injected into the oral mucosa. Indirubin derivative treatment began on the 3rd or 6th day after oral or s.c. cell injection, respectively. Indirubin derivatives were directly injected into the tumor every other day for a total of five times. Animals were monitored daily and tumor volume was measured by caliper.Results: Indirubin derivatives showed potent antiproliferative activity on various human cancer cells and oncogenic RK3E-ras rat kidney cells, with IC 50 ranging from 1 to 12 Amol/L. Treatment with indirubin derivatives induced the activation of caspase-7 followed by apoptosis in RK3E-ras cells. Indirubin derivatives showed strong antitumor activity in rat solid and oral tumor models. Direct injection of indirubin derivatives every other day for 10 days induced significant inhibition of tumor growth in Sprague-Dawley rats bearing RK3E-ras-induced tumors. Histologically, treatment with indirubin derivatives caused significant inhibition of tumor formation with increased apoptosis and decreased tumor cell proliferation. Conclusions: Our data showed that novel indirubin derivatives 5 ¶-nitro-indirubinoxime, 5 ¶-fluoro-indirubinoxime, and 5 ¶-trimethylacetamino-indirubinoxime effectively arrested the tumor growth by inhibiting cell proliferation and inducing apoptosis.These findings provide the potential value of indirubin derivatives as novel candidates for antitumor agents.
Gelatinous degeneration of the bone marrow is rare, and its pathogenesis is unknown. A 61-year-old man with rectal cancer, who was treated successfully with surgery and chemotherapy 1 year ago, underwent 18F-FDG PET/CT for restaging, which showed a focal hot spot in the left scapula mimicking osseous metastasis. Excision bone biopsy revealed gelatinous degeneration of the bone marrow.
Abstract.To obtain more representative biopsy specimens in glioblastoma, we performed multiple stereotactic biopsies of active tumor and necrosis. We investigated their pathologic differences of diagnosis and also examined the pathologic features that varied with 11 C-methionine uptake on PET. From December 2009 to October 2010, we performed stereotactic biopsies in 12 patients with radiologically heterogeneous, ringenhanced lesions. We biopsied the MR enhanced lesions for active tumor and the MR non-enhanced lesions for necrosis and analyzed differences of pathologic diagnoses between them. As correlating factors of the degree of 11 C-methionine uptake (T/N ratio), the pathologic findings, including cell density, Ki-67 LI, microvessel density, number of endothelial proliferations, the immunopositivity for L-amino acid transporter 1 (LAT1) were analyzed. The final diagnosis of each specimen was glioblastoma. The diagnostic failure rate was 33.3% (4/12 patients) when we selected only active tumors and 40% (4/10 patients) when we selected necrotic lesions. The T/N ratio showed a statistical correlation with cell density depending on the degree of necrosis and LAT1 immunopositivity (P=0.002 and 0.032). LAT1 was localized in the tumor cells, vascular endothelium, and the vicinity of endothelial proliferation. Multiple stereotactic biopsies of active tumor and necrosis could provide the diagnostic yield in glioblastoma. The 11 C-methionine uptake mostly reflected cell densities depending on the degree of necrosis. IntroductionStereotactic brain biopsy is a minimally invasive form of diagnostic technique that uses a three-dimensional coordinate system to locate small targets inside the brain. Magnetic resonance imaging (MRI) provides sharp anatomical details of the pathologic brain and stereotactic operations generally use MRI. However, an inaccurate diagnosis or underestimation of a lesion's pathological grade sometimes occur because clinicians can get only a small amount of tissue to represent the lesion's total features (1-3). Even if the clinician has a provisional radiological diagnosis of high-grade glioma, the pathologist may confirm a low-grade glioma from the small specimen. Gliomas, especially, are histologically heterogeneous, and inadequate localization of the stereotactic biopsy may produce specimens that are irrelevant for identifying and grading the lesions (4). Endothelial proliferation and/or necrosis are essential diagnostic features for the pathological diagnosis of glioblastoma. On enhanced MR images, an enhanced lesion corresponds to a cellular, highly vascularized area of the neoplasm and a non-enhanced lesion corresponds to a necrotic or cystic lesion, with decreased vasculature (5). Therefore, to obtain more representative biopsy specimens, we biopsied the MR enhanced lesions for active tumor and the MR non-enhanced lesions for necrosis to cover the important pathologic features and investigated their pathologic differences of diagnosis. 11C-methionine uptake is regulated by an amino acid trans...
Symmetric bifrontal uptake of bone-seeking agents is usually considered as the main feature of hyperostosis frontalis interna in postmenopausal elderly women. This finding is not uncommon in elderly women because of the change in their hormonal level. However, in the present case, a 66-year-old woman with intra-axial brain metastases of breast cancer showed symmetric bifrontal uptake on bone scintigraphy. Therefore, symmetric bifrontal uptake should not always be considered as a definite indicator of hyperostosis frontalis interna. Further evaluation such as SPECT/CT is needed for evaluation of brain metastases especially in cancer patients.
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