37 research outputs found
R1507, an Anti-Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antibody, and EWS/FLI-1 siRNA in Ewing's Sarcoma: Convergence at the IGF/IGFR/Akt Axis
A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt
Case Report - Primary Pleuro-pulmonary Malignant Germ Cell Tumours
Lungs and pleura are rare sites for malignant germ-cell tumours. Two
cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma
are described in young males who presented with rapid progression of
respiratory symptoms. The malignant mixed germ cell tumour occurred in
the right lung, while the yolk-sac tumour had a pseudomesotheliomatous
growth pattern suggesting a pleural origin. Alpha-foetoprotein was
immunohistochemically demonstrated in both
Role of frozen section evaluation in patients with breast lumps: A study of 251 cases
Context: Frozen section is an invaluable intra-operative tool for
evaluation of breast lumps. Aims: The aim of this study was to (1)
calculate the overall accuracy, false positivity, false negativity for
frozen section of breast lumps, (2) analyze the causes of
discrepancies, and (3) compare the data with that of published
literature on frozen section of breast lumps. Material and Methods:
Two hundred and fifty one frozen sections comprising 237 breast lumps,
10 axillary nodes and 4 lumpectomy margins received for frozen section
in 1997 were analyzed. Pathology reports and slides (of both frozen and
paraffin sections) were reviewed. The values were calculated using
paraffin slides as the gold standard. Results: The 237 lumps received
for primary diagnosis comprised 157 malignant and 80 benign lesions.
The false negativity rate was 0.42%, false positive rate 0%, deferral
rate 0.84%, overall accuracy rate was 99.57%. The false negative
diagnosis was an error of interpretation. False negativity rate for
axillary nodes was 20% and accuracy was 80%. Accuracy for margins was
100%. Conclusion: Frozen section has a role despite the raging
popularity of aspiration cytology in the following settings: (1)
Difficult cytology (2) Evaluation of lumpectomy margins. (3)
Intra-operative nodal status
A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: A rare case report with review of literature
Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such
cases have dealt with molecular analysis. A 19-year-old boy presented
with pain and swelling in his left lower limb of two months duration.
He developed acute urinary retention four days prior to his hospital
admission, wherein radiological examination unraveled a large soft
tissue mass, displacing his pelvic muscles, along with a lytic lesion
involving his right pubic bone. Biopsy showed a cellular spindle cell
sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal
necrosis. Immunohistochemistry (IHC) showed positivity for vimentin,
BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane
antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was
positive. Diagnosis of a poorly differentiated synovial sarcoma was
offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation.
This case highlights the value of molecular analysis in diagnosis of a
synovial sarcoma at rare sites, especially when IHC results are
equivocal and the biopsy material is limited
A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: A rare case report with review of literature
Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such
cases have dealt with molecular analysis. A 19-year-old boy presented
with pain and swelling in his left lower limb of two months duration.
He developed acute urinary retention four days prior to his hospital
admission, wherein radiological examination unraveled a large soft
tissue mass, displacing his pelvic muscles, along with a lytic lesion
involving his right pubic bone. Biopsy showed a cellular spindle cell
sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal
necrosis. Immunohistochemistry (IHC) showed positivity for vimentin,
BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane
antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was
positive. Diagnosis of a poorly differentiated synovial sarcoma was
offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation.
This case highlights the value of molecular analysis in diagnosis of a
synovial sarcoma at rare sites, especially when IHC results are
equivocal and the biopsy material is limited
A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: A rare case report with review of literature
Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such
cases have dealt with molecular analysis. A 19-year-old boy presented
with pain and swelling in his left lower limb of two months duration.
He developed acute urinary retention four days prior to his hospital
admission, wherein radiological examination unraveled a large soft
tissue mass, displacing his pelvic muscles, along with a lytic lesion
involving his right pubic bone. Biopsy showed a cellular spindle cell
sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal
necrosis. Immunohistochemistry (IHC) showed positivity for vimentin,
BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane
antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was
positive. Diagnosis of a poorly differentiated synovial sarcoma was
offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation.
This case highlights the value of molecular analysis in diagnosis of a
synovial sarcoma at rare sites, especially when IHC results are
equivocal and the biopsy material is limited