Purpose: Because the combination of multiple modalities for cancer treatment is more likely to generate more potent therapeutic effects for the control of cancer, we have explored the combination of chemotherapy using cisplatin, which is routinely used in chemotherapy for advanced cervical cancer, with immunotherapy using DNA vaccines encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 antigen (CRT/E7) in a preclinical model. Experimental Design: We characterized the combination of cisplatin with CRT/E7 DNA vaccine using different regimen for its potential ability to generate E7-specific CD8 + T-cell immune responses as well as antitumor effects against E7-expressing tumors. Results: Our results indicate that treatment of tumor-bearing mice with chemoimmunotherapy combining cisplatin followed by CRT/E7 DNA generated the highest E7-specific CD8 + T-cell immune response and produced the greatest antitumor effects and long-term survival as well as significant levels of E7-specific tumor-infiltrating lymphocytes compared with all the other treatment regimens. Furthermore, we found that treatment with cisplatin leads to the cellmediated lysis of E7-expressing tumor cells in vitro and increased number of E7-specific CD8 + T-cell precursors in tumor-bearing mice. In addition, we observed that E7-specific CD8 + T cells migrate to and proliferate in the location of TC-1tumors in mice treated with cisplatin. Conclusions: Thus, our data suggest that chemoimmunotherapy using cisplatin followed by CRT/E7 DNA vaccine is an effective treatment against E7-expressing tumors and may potentially be translated into the clinical arena.Multimodality treatments that combine conventional cancer therapies with antigen-specific immunotherapy have emerged as promising approaches for the control of cancer (see refs. 1, 2 for reviews). Antigen-specific immunotherapy is an attractive approach for the treatment of cancers because it has the potency to specifically eradicate systemic tumors and control metastases without damaging normal cells. A favorable approach to antigen-specific immunotherapy is the use of DNA vaccines based on their safety, stability, and ease of preparation (see refs. 3, 4 for review). However, DNA vaccines are poorly immunogenic. Thus, the potency of DNA vaccines needs to be enhanced by using methods to target DNA to the professional antigen-presenting cells and by modifying the properties of antigen-expressing antigen-presenting cells to boost vaccine-elicited immune responses. Several approaches have been developed to enhance DNA vaccine potency (see refs. 5, 6 for review).One particular approach to enhance DNA vaccine potency involves the use of intracellular targeting strategies to enhance MHC class I and class II antigen presentation in dendritic cells. Our previous studies have explored the linkage of calreticulin (CRT), a Ca 2+ -binding protein located in the endoplasmic reticulum (see ref. 7 for review) to a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, for the develo...
Unsupervised word embeddings have been shown to be valuable as features in supervised learning problems; however, their role in unsupervised problems has been less thoroughly explored. In this paper, we show that embeddings can likewise add value to the problem of unsupervised POS induction. In two representative models of POS induction, we replace multinomial distributions over the vocabulary with multivariate Gaussian distributions over word embeddings and observe consistent improvements in eight languages. We also analyze the effect of various choices while inducing word embeddings on "downstream" POS induction results.
We introduce an extension to the bag-ofwords model for learning words representations that take into account both syntactic and semantic properties within language. This is done by employing an attention model that finds within the contextual words, the words that are relevant for each prediction. The general intuition of our model is that some words are only relevant for predicting local context (e.g. function words), while other words are more suited for determining global context, such as the topic of the document. Experiments performed on both semantically and syntactically oriented tasks show gains using our model over the existing bag of words model. Furthermore, compared to other more sophisticated models, our model scales better as we increase the size of the context of the model.
BACKGROUND During follow‐up for patients with cervical carcinoma, elevation of serum squamous cell carcinoma antigen (SCC‐Ag) levels in the absence of detectable recurrent lesions presents a diagnostic and therapeutic challenge. In the current prospective study, the authors evaluated the use of fluorine‐18‐labeled fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET) to detect disease recurrence in this setting. METHODS Women with cervical carcinoma who experienced complete responses to primary treatment or salvage therapy and who had no evidence of recurrent disease as detected by conventional methods but had serum SCC‐Ag levels ≥ 2.0 ng/mL on 2 consecutive occasions were eligible for the study. PET was performed within 2 weeks after the completion of conventional studies for the assessment of recurrence. RESULTS Twenty‐seven consecutive patients were registered for the current study. PET findings were positive for 19 patients: 14 who had a distant lesion or lesions, 2 who had a local lesion or lesions, and 3 who had both local and distant lesions. Of these 19 patients, 17 were confirmed to have recurrent disease; the remaining two were found to be free of disease but had severe anthracosis in the PET‐positive mediastinal lymph nodes. Seven of the eight patients with negative PET findings were not found to have recurrent disease on follow‐up. Overall, PET detected FDG‐avid lesions in 17 (94%; P < 0.001) of the 18 patients with recurrent disease. Seven of these 18 patients received therapy with curative intent; complete control was achieved in 6, four of whom currently are alive and free of disease. The addition of PET in the current setting curbed the use of futile curative therapy and significantly increased overall survival for patients in the current cohort compared with a historical group of 30 consecutive patients who had elevated SCC‐Ag levels as a first sign of recurrence. CONCLUSIONS PET expedited the detection of recurrent cervical carcinoma in patients with unexplained elevation of SCC‐Ag levels. Such expedited detection may have positive effects on patient survival. Cancer 2004. © 2004 American Cancer Society.
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