183 research outputs found
Induction of human tumor-associated differentially expressed gene-12 (TADG-12/TMPRSS3)-specific cytotoxic T lymphocytes in human lymphocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer
No full text2008 Dec 31. [Epub ahead of print
Generation of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer.
No full textOverexpression of epithelial cell adhesion molecule in primary, metastatic, and recurrent/chemotherapy-resistant epithelial ovarian cancer: implications for epithelial cell adhesionmolecule-specific immunotherapy.
No full textUWB Air-Coupled Antenna for Ground Penetrating Radar
No full textGround Penetrating Radar (GPR) is a promising technology to detect buried objects beneath or near ground surface. To achieve high-resolution and accurate enough images, the transmitting antenna (TX) in this technology is required to radiate a highly-correlated narrow width pulse towards ground where the targets are hidden. For this application, an ultra-wide bandwidth (0.3?6 GHz) antenna from the family of Vivaldi antennas is designed and optimized. This antenna meets the required features of the TX antenna both in frequency and time domains. Apart from its broadband characteristics, the antenna radiates highly correlated pulse towards its footprint. It, also, shows very low late-time ringing and has narrow width impulse response. The antenna is designed on a 2.33 dielectric permittivity substrate and is fed via a 50 SMA end-launch.Microwave Technology and Systems for RadarTelecommunicationsElectrical Engineering, Mathematics and Computer Scienc
Induction of human tumor-associated differentially expressed gene-12 (TADG-12/TMPRSS3)-specific cytotoxic T lymphocytes in human lymphocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer.
No full texthI-con1, a factor VII-IgGFc chimeric protein targetingtissue factor for immunotherapy of uterine serous papillary carcinoma.
No full textBACKGROUND: Uterine serous papillary adenocarcinoma (USPC) is a highly aggressive variant of endometrial cancer. Human immunoconjugate
molecule (hI-con1) is an antibody-like molecule targeted against tissue factor (TF), composed of two human Factor VII
(fVII) as the targeting domain, fused to human immunoglobulin (Ig) G1 Fc as an effector domain. We evaluated hI-con1 potential
activity against primary chemotherapy-resistant USPC cell lines expressing different levels of TF.
METHODS: A total of 16 formalin-fixed, paraffin-embedded USPC samples were evaluated by immunohistochemistry (IHC) for
TF expression. Six primary USPC cell lines, half of which overexpress the epidermal growth factor type II (HER2/neu) receptor at
3þ levels, were assessed by flow cytometry and real-time PCR for TF expression. Sensitivity to hI-con1-dependent cell-mediated
cytotoxicity (IDCC) was evaluated in 5-hour-chromium release assays. Finally, to investigate the effect of interleukin-2 (IL-2) on
IDCC, 5-h 51Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50–100 IU ml 1).
RESULTS: Cytoplasmic and/or membrane TF expression was observed in all 16 (100%) USPC samples tested by IHC, but not in normal
endometrium. High expression of TF was found in 50% (three out of six) of the USPC cell lines tested by real-time PCR and flow
cytometry when compared with normal endometrial cells (NECs; Po0.001). Uterine serous papillary adenocarcinoma cell lines
overexpressing TF, regardless of their high or low HER2/neu expression, were highly sensitive to IDCC (mean killing±s.d.,
65.6±3.7%, range 57.5–77.0%, Po0.001), although negligible cytotoxicity against USPC was seen in the absence of hI-con1 or in the
presence of Rituximab control antibody. The addition of low doses of IL-2 further increased the cytotoxic effect induced by hI-con1
against chemotherapy-resistant USPC.
CONCLUSION: hI-con1 induces strong cytotoxicity against primary chemotherapy-resistant USPC cell lines overexpressing TF. The
hI-con1 may represent a novel therapeutic agent for the treatment of patients harbouring advanced, recurrent and/or metastatic
USPC refractory to standard treatment modalities
Human papillomavirus type 16 (HPV-16) virus-like particleL1-specific CD8+ cytotoxic T lymphocytes (CTLs) are equally effective as E7-specific CD8+ CTLs in killing autologous HPV-16-positive tumor cells in cervical cancer patients: implications for L1 dendritic cell-based therapeutic vaccines.
No full textPapillomavirus-like particles (VLPs) based on L1 capsid protein represent a promising prophylactic vaccine
against human papillomavirus (HPV) infections. However, cell-mediated immune responses against this
antigen are believed to be of limited therapeutic value in established HPV-infected cervical lesions and, for this
reason, have not been intensively investigated in cervical cancer patients. In this study we analyzed and
quantified by real-time PCR (RT-PCR) the RNA expression levels of E6, E7, and L1 genes in flash-frozen
HPV-16 cervical carcinomas. In addition, the kinetics of expression of E6, E7, and L1 in HPV-16-infected
primary cell lines established as long-term cultures in vitro was also evaluated at RNA and protein levels.
Finally, in order to evaluate the therapeutic potential of L1-specific CD4 and CD8 T lymphocytes responses
in cervical cancer patients, L1 VLP-loaded dendritic cells (DCs) were used to stimulate peripheral blood
lymphocytes from cervical cancer patients and such responses were compared to those elicited by the E7
oncoprotein. We show that 22 of 22 (100%) flash-frozen cervical biopsy samples collected from HPV-16-positive
cervical cancer patients harbor L1, in addition to E6 and E7 RNA, as detected by RT-PCR. E7 RNA copy
number (mean, 176.2) was significantly higher in HPV-16-positive cervical cancers compared to the E6 RNA
copy number (mean, 47.3) and the L1 copy number (mean, 58.3) (P < 0.0001 and P < 0.001, respectively).
However, no significant differences in expression levels between E6 and L1 were found. Kinetic studies of E6,
E7, and L1 RNA and protein expression levels in primary tumors showed a sharp reduction in L1 expression
after multiple in vitro passages compared to E6 and E7. Autologous DCs pulsed with HPV-16 VLPs or
recombinant full-length E7 elicited strong type 1 L1- and E7-specific responses in CD4 and CD8 T cells from
cervical cancer patients. Importantly, L1 VLP-specific CD8 T lymphocytes expressed strong cytolytic activity
against autologous tumor cells and were as effective as E7-specific cytotoxic T lymphocytes in lysing naturally
HPV-16-infected autologous tumor cells. Taken together, these data demonstrate a consistent expression of L1
in primary cervical tumors and the possibility of inducing effective L1/tumor-specific CD4 and CD8
T-lymphocyte responses in patients harboring HPV-infected cervical cancer. These results may have important
implications for the treatment of patients harboring established HPV-infected lesions with L1 VLPs or
combined E7/L1 DC-based vaccinations
A Research on the Coefficincy and Collaboration of Authors in the Journals of Islamic Law and Jourisprudence in Recent Five Years (from 1388 to 1393)
No full textThe purpose of this study is to evaluate the collaboration of authors in published articles in The Journal of Studies in Islamic Law & Jurisprudence, during 2009 â 2013. This study was conducted in Scientometric Method. Descriptive Statistics and data analysis have done by Excel Software. The results of this research show that 73 articles were published by 136 authors in this journal. From gender point of view, 9.6 % of authors were women and 90.4% were men. The finding of this research showed that The University of Mazandran with 11 articles is most prolific among other research institutes and scientific centers. The Universities of Tehran and Semnan, each by 8 articles, place in the 2nd and 3rd positions. Collaboration pattern of authors in this journal shows that the Journal tends to publish collaborative works. Only one article was published by a single author. The results showed that the collaboration coefficient was 0.4
Eradication of chemotherapy-resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of Clostridium perfringens enterotoxin.
No full textBACKGROUND: Emerging evidence has suggested that the capability to sustain tumor formation, growth, and chemotherapy
resistance in ovarian as well as other human malignancies exclusively resides in a small proportion of tumor
cells termed cancer stem cells. During the characterization of CD44þ ovarian cancer stem cells, we found a high
expression of the genes encoding for claudin-4. Because this tight junction protein is the natural high-affinity receptor
for Clostridium perfringens enterotoxin (CPE), we have extensively investigated the sensitivity of ovarian cancer
stem cells to CPE treatment in vitro and in vivo. METHODS: Real-time polymerase chain reaction and flow cytometry
were used to evaluate claudin-3/-4 expression in ovarian cancer stem cells. Small interfering RNA knockdown experiments
and MTS assays were used to evaluate CPE-induced cytotoxicity against ovarian cancer stem cell lines in vitro.
C.B-17/SCID mice harboring ovarian cancer stem cell xenografts were used to evaluate CPE therapeutic activity in
vivo. RESULTS: CD44þ ovarian cancer stem cells expressed claudin-4 gene at significantly higher levels than matched
autologous CD44 ovarian cancer cells, and regardless of their higher resistance to chemotherapeutic agents died
within 1 hour after exposure to 1.0 lg/mL of CPE in vitro. Conversely, small-interfering RNA-mediated knockdown of
claudin-3/-4 expression in CD44þ cancer stem cells significantly protected cancer stem cells from CPE-induced cytotoxicity.
Importantly, multiple intraperitoneal administrations of sublethal doses of CPE in mice harboring xenografts
of chemotherapy-resistant CD44þ ovarian cancer stem cells had a significant inhibitory effect on tumor progression
leading to the cure and/or long-term survival of all treated animals (ie, 100% reduction in tumor burden in 50% of
treated mice; P < .0001). CONCLUSIONS: CPE may represent an unconventional, potentially highly effective strategy
to eradicate chemotherapy-resistant cancer stem cells
Primary cervical carcinoma cell lines overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody
No full textIntroduction: Epithelial cell adhesion molecule (EpCAM) is a surface glycoprotein
highly differentially expressed in many epithelial malignancies. The goal of this study was
to evaluate the expression of EpCAM and the potential of MT201 (adecatumumab), a
human monoclonal antibody targeting EpCAM, against multiple primary cervical carcinoma
cell lines.
Methods: Epithelial cell adhesion molecule expression was evaluated by real-time polymerase
chain reaction and flow cytometry in a total of 8 primary cervical cancer cell lines.
Sensitivity to MT201-mediated cellular cytotoxicity (ADCC) and complement-dependent
cytotoxicity was tested in standard 4-hour 51Cr release assays. To investigate the effect of
interleukin-2 (IL-2) on MT201-mediated ADCC, 4-hour 51Cr release assays were also
conducted in the presence of low doses of IL-2.
Results: High messenger RNA expression by real-time polymerase chain reaction and
high EpCAM surface expression by flow cytometry were detected in 4 (50%) of 8 primary
cervical carcinoma cell lines. With no exception, the primary cell lines derived from
clinically aggressive tumors showed EpCAM overexpression. Whereas these cell lines were
highly resistant to complement-dependent cytotoxicity and natural killer (NK)-dependent
cytotoxicity in vitro (range of killing, 4%Y19%), EpCAM-positive cell lines showed high
sensitivity to MT201-mediated ADCC (range of killing, 23%Y59%). Incubation with IL-2 in
addition to MT201 significantly increased the cytotoxic activity against EpCAM-positive
cervical cancer cell lines (P = 0.007). Addition of human serum also further increased the
MT201-mediated killing of EpCAM-positive cell lines (P = 0.03).
Conclusions: Epithelial cell adhesion molecule is highly expressed in primary cervical
carcinoma cell lines, and these biologically aggressive tumors are highly sensitive to
MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly
effective treatment option for patients with cervical carcinoma, especially for those with
advanced, recurrent, or metastatic disease refractory to standard salvage therapy
- …
