ABSTRACT
BACKGROUND: The immunomodulatory properties of polyuridylic acid (PolyU) make it a promising agent in cancer immunotherapy. However, there is limited information on its direct effects on tumor cells. MATERIALS AND METHODS: TLR8 mRNA and protein expression in soft tissue sarcoma (STS) and bone sarcoma (BS) cell lines were determined by PCR and flow cytometry, respectively. Apoptosis and proliferation assays were performed using annexin V staining and BrdU incorporation assays, respectively. A relative cell enumeration was evaluated with WST-1 reagent. Expression levels of apoptotic proteins were evaluated by Western blotting. RESULTS: We demonstrate that PolyU treatment resulted in a significant decrease in STS and BS cell count by inducing apoptosis and inhibition of cell proliferation. All cell lines examined expressed TLR8 and the effect of PolyU was partially mediated through TLR8. Several apoptotic proteins including caspases were activated or increased in STS cells after treatment with PolyU. Administration PolyU resulted in significant growth inhibition of STS without any observable adverse effects in mouse xenograft tumor models. CONCLUSIONS: These results elucidate the effect of PolyU in STS and BS cells and demonstrate that PolyU may be a potential therapeutic agent for STS and BS.
Subject(s)
Antineoplastic Agents/pharmacology , Bone Neoplasms/drug therapy , Fibrosarcoma/drug therapy , Poly U/pharmacology , Soft Tissue Neoplasms/drug therapy , Animals , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Caspases/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Fibrosarcoma/metabolism , Fibrosarcoma/pathology , Humans , Male , Mice , Mice, SCID , Mitochondria/drug effects , Nerve Sheath Neoplasms/drug therapy , Nerve Sheath Neoplasms/metabolism , Nerve Sheath Neoplasms/pathology , Osteosarcoma/drug therapy , Osteosarcoma/metabolism , Osteosarcoma/pathology , Poly U/metabolism , Rhabdomyosarcoma/drug therapy , Rhabdomyosarcoma/metabolism , Rhabdomyosarcoma/pathology , Sarcoma, Clear Cell/drug therapy , Sarcoma, Clear Cell/metabolism , Sarcoma, Clear Cell/pathology , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/pathology , Toll-Like Receptor 8/metabolism , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: The purpose of the study was to determine the risk of ipsilateral breast carcinoma recurrence (IBCR) and contralateral breast carcinoma (CBC) development in patients with a concurrent diagnosis of ductal carcinoma in situ (DCIS) with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). METHODS: Records of all 307 patients with DCIS treated with breast-conserving treatment (BCT) from 1968 to 1998 were analyzed. Initial pathology reports and all slides available were re-reviewed for evidence of ADH, ALH, or LCIS. Actuarial local recurrence rates were calculated. RESULTS: Fifty-five cases of DCIS were associated with ADH, 11 with ALH or LCIS, and 14 with both ADH and ALH or LCIS. Overall, IBCR occurred in 14% and no significant difference in the IBCR rate was identified for patients with proliferative lesions compared with patients without these lesions (P = 0.38). Development of CBC in patients with concurrent DCIS and ADH was 4.4 times (95% confidence interval [CI], 1.44-13.63) that in patients with DCIS alone (P < 0.01). The 15-year cumulative rate of CBC development was 22.7% in patients with ALH or LCIS compared with 6.5% in patients without these lesions (P = 0.30) and 19% in patients with ADH compared with 4.1% in patients with DCIS alone (P < 0.01). CONCLUSION: The risk of CBC development is higher with concurrent ADH than in patients with DCIS alone, and these patients may therefore be appropriate candidates for additional chemoprevention strategies. Concurrent ADH, ALH, or LCIS with DCIS is not a contraindication to BCT.
Subject(s)
Breast Neoplasms/pathology , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/pathology , Neoplasm Recurrence, Local/pathology , Neoplasms, Multiple Primary/pathology , Precancerous Conditions/pathology , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Carcinoma in Situ/mortality , Carcinoma in Situ/therapy , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/therapy , Carcinoma, Lobular/mortality , Carcinoma, Lobular/therapy , Female , Follow-Up Studies , Humans , Hyperplasia , Mastectomy, Segmental , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasms, Multiple Primary/prevention & control , Precancerous Conditions/therapy , Radiotherapy, Adjuvant , Risk AssessmentABSTRACT
BACKGROUND: The purpose of this study was to determine the utility of breast-imaging studies in identifying cancer and high-risk lesions among patients with spontaneous, single-duct, nipple discharge (SSND). METHODS: The medical records of 168 cases with SSND treated with duct excision between June 1998 and May 2004 were reviewed. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mammogram, ultrasound, and ductogram in predicting high-risk lesions and cancer were calculated. RESULTS: The sensitivity of mammography was 10%, the specificity 94%, the NPV 88%, and the PPV 18%. Ultrasonography had a sensitivity of 36%, specificity of 68%, PPV of 14%, and NPV of 89%. Ductography had a sensitivity of 75%, specificity of 49%, and NPV and PPV of 93% and 18%, respectively. CONCLUSIONS: Conventional imaging studies do not accurately identify cancer or high-risk lesions in patients with SSND. All patients with SSND should be offered duct excision.
