Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant α-GalCer. As results, TgCPC1 DNA vaccine with or without adjuvant α-GalCer showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and IFN-γ in the spleen compared to controls (PBS, pEGFP-C1, and α-Galcer). Upon challenge infection with tachyzoites of T. gondii (RH), pCPC1/α-Galcer immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and α-Galcer). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.
Animals ; B-Lymphocytes ; Cathepsin C* ; Cathepsins* ; DNA* ; Epitopes, T-Lymphocyte ; Immunoglobulin G ; Interleukin-2 ; Mice* ; Peptide Hydrolases ; Spleen ; Toxoplasma* ; Toxoplasmosis* ; Vaccines, DNA*

PURPOSE: To evaluate the prognostic significances of p53 and cathepsin D in the prostatic carcinoma, we compared them to other prognostic factors, such as nuclear grade and clinical stage. MATERIALS AND METHODS: The material consisted of 40 paraffin-embedded, primary prostate carcinomas. We examined the expression of p53 and cathepsin D using immunohistochemical staining and compared their expression with the grade and stage. RESULTS: The expressions of p53 were noted in the nucleus of tumor cells and cathepsin D were noted in the cytoplasm of tumor cells. Thirteen of 40 tumors were positive for p53. There were more expressing p53 in samples (40%) from prostatic cancer with a high Gleason score group than in samples (28%) from prostatic cancer with low Gleason score group. The expression of p53 was 22% in clinical stage B and C groups and 35% in clinical stage D group. These results showed that p53 expression was not statistically correlated with Gleason score and clinical stage, but there were trends to increased p53 expression with high Gleason score and progressed clinical stage (p>0.05). Progressed clinical stage group showed higher expression of cathepsin D than early clinical stage group. However, there were no statistical correlations between expression of cathepsin D and Gleason score, and clinical stage (p>0.05). CONCLUSION: These results suggest that the overexpression of p53 and cathepsin D may be associated with tumor differentiation and clinical stage, but have limited prognostic value in prostatic carcinoma.
Cathepsin D* ; Cathepsins* ; Cytoplasm ; Neoplasm Grading ; Prostate ; Prostatic Neoplasms

Twenty six cases of primary adenocarcinoma of the prostate, ranging from 4 to 9 according to Gleason's summing score, were studied. Immunoreactivity was evaluated using the rabbit polyclonal anti-Cathepsin D antibody (CD), a mouse monoclonal MMP-2 antibody (MMP-2), and a tissue inhibitor metalloproteinase (TIMP) in formalin-fixed, paraffin-embedded prostatic tissue. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). For CD, the tumor cells showed diffuse cytoplasmic immunoreactivity in all 26 cases (100%). For MMP-2 the tumor cells showed cytoplasmic immunoreactivity in 17 of 26 cases (65.38%). As the Gleason grade increased the expression of CD increased (P=0.0027). The reactivity of CD was significantly correlated with the Gleason's score (R=0.65637), but, the reactivity of MMP-2 was not correlated. There were no significant correlations between each of the CD and the MMP-2 scores, and stage. TIMP expression was predominantly localized in the stroma rather than in the cancer cells themselves. We believe that 1) CD and MMP-2, both immunohistochemically detectable in a majority of prostate adenocarcinoma, may play a role in determination of the invasive or metastatic property, 2) the enhanced TIMP expression in the stroma may be associated with the response to cancer invasion.
Adenocarcinoma ; Animals ; Cathepsin D* ; Cathepsins* ; Cytoplasm ; Mice ; Prostate*

Anticancer drugs kill tumor cells and increase host anti-tumor immunity. Interestingly, gemcitabin (Gem) and 5-fluorouracil (5-FU), widely used anticancer drugs, lead to IL-1beta secretion releasing cathepsin B which activates Nlrp3 inflammasome in myeloid derived suppressor cells (MDSCs). MDSC derived IL-1beta enhance secretion of IL-17 by CD4+ T cells. This mechanism limits the antitumor efficacy of the drugs and promotes tumor growth.
Cathepsin B ; Cathepsins ; Fluorouracil ; Interleukin-17 ; T-Lymphocytes

PURPOSE: Cathepsin D, a lysosomal protease has been proposed to play a role in the local invasion and metastatic dissemination in primary breast cancer. Although there are many conflicting results, the overexpression of cathepsin D has been considered to be related with a poorer prognosis of breast cancer. This study was designed to verify whether cathepsin D expression is related to other prognostic factors in breast cancer. METHODS: Cathepsin D was assessed by immunohistochemistry using murine monoclonal anti-cathepsin D antibody (ZyMED) in 79 paraffin-embedded primary breast cancer specimens. Cathepsin D expression was compared to other prognostic parameters such as tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors (ER & PR), p53, c-erb B2, Ki-67, MVD (microvessel density), and Pgp (P-glycoprotein). RESULTS: A high-expression of cathepsin D was found in 35 of 79 patients (44.3%) with primary breast cancer. Cathepsin D expression was not related to tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors, p53, Ki-67, or CD31. However, a significant relationship was found between cathepsin D expression and c-erb B2 (p=0.007), and between cathepsin D expression and Pgp (p=0.003). CONCLUSION: These results suggest that cathepsin D expression may be an indicator of a poor prognosis in breast cancer. However, further studies are required to verify the xact role of cathepsin D in the prognosis of breast cancer.
Breast Neoplasms* ; Breast* ; Cathepsin D* ; Cathepsins* ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis

No abstract available.
Cathepsin D* ; Cathepsins* ; Cell Cycle* ; Flow Cytometry ; Immunohistochemistry ; Proliferating Cell Nuclear Antigen*

PURPOSE: Most treatment decisions for breast cancer patients are based on an assesment of prognostic factors. Tumor markersB (p53, c-erbB2, bcl-2, Cathepsin D) have been evaluated for their prognostic factors and many studies suggest that these factors as assessed by immunohistochemistry (IHC) may be helpful for treatment decisions, while the risk group for high relapse can not be discriminated by single tumor marker alone. In order to obtain useful prognostic information, several tumor marker expressions must be combined and weighted. METHODS: The expressions of ER, PR, p53, c-erbB2, bcl-2, Cathepsin D were detected by IHC on paraffin-embedded sections from 449 primary breast cancer patients treated at Seoul National University Hospital between January 1996 and December 1998. In the present study, tumor marker expressions were analyzed along with conventional clinicopathologic factors. Additionally, correlations between various tumor marker expressions were examined and combinations of tumor marker expressions relating pathologic parameters currently in use for primary breast cancer prognosis were investigated. RESULTS: ER, PR, bcl-2, Cathepsin D expressions were related to smaller tumor size and PR was related to less axillary nodal involvement. ER, PR, bcl-2 expressions were related to good NG and HG, while p53 expression was relatedto poor NG and HG. ER and PR expression were related to bcl-2 expression, c-erbB2 expression was related to p53 expression and c-erbB2 expression was related to Cathepsin D expression. ER-/bcl-2- was more prevalent in NG 1 and HG III tumors. ER+/p53- and p53-/bcl-2+ were more prevalent in NG 2/3 and HG I/II tumors. p53+/c-erbB2+ was more prevalent in NG 1 tumors. CONCLUSION: Combinations of tumor marker expressions ER/bcl-2, ER/p53, p53/c-erbB2, p53/bcl2 provides more detailed information concerning cancer aggressiveness.
Breast Neoplasms* ; Cathepsin D* ; Cathepsins* ; Equidae ; Humans ; Immunohistochemistry ; Prognosis ; Recurrence ; Seoul

PURPOSE: Most treatment decisions for breast cancer patients are based on an assesment of prognostic factors. Tumor markersB (p53, c-erbB2, bcl-2, Cathepsin D) have been evaluated for their prognostic factors and many studies suggest that these factors as assessed by immunohistochemistry (IHC) may be helpful for treatment decisions, while the risk group for high relapse can not be discriminated by single tumor marker alone. In order to obtain useful prognostic information, several tumor marker expressions must be combined and weighted. METHODS: The expressions of ER, PR, p53, c-erbB2, bcl-2, Cathepsin D were detected by IHC on paraffin-embedded sections from 449 primary breast cancer patients treated at Seoul National University Hospital between January 1996 and December 1998. In the present study, tumor marker expressions were analyzed along with conventional clinicopathologic factors. Additionally, correlations between various tumor marker expressions were examined and combinations of tumor marker expressions relating pathologic parameters currently in use for primary breast cancer prognosis were investigated. RESULTS: ER, PR, bcl-2, Cathepsin D expressions were related to smaller tumor size and PR was related to less axillary nodal involvement. ER, PR, bcl-2 expressions were related to good NG and HG, while p53 expression was relatedto poor NG and HG. ER and PR expression were related to bcl-2 expression, c-erbB2 expression was related to p53 expression and c-erbB2 expression was related to Cathepsin D expression. ER-/bcl-2- was more prevalent in NG 1 and HG III tumors. ER+/p53- and p53-/bcl-2+ were more prevalent in NG 2/3 and HG I/II tumors. p53+/c-erbB2+ was more prevalent in NG 1 tumors. CONCLUSION: Combinations of tumor marker expressions ER/bcl-2, ER/p53, p53/c-erbB2, p53/bcl2 provides more detailed information concerning cancer aggressiveness.
Breast Neoplasms* ; Cathepsin D* ; Cathepsins* ; Equidae ; Humans ; Immunohistochemistry ; Prognosis ; Recurrence ; Seoul

BACKGROUND: It is known that cathepsin D expression in host stromal cells is associated with a more aggressive tumor behavior in breast cancers. METHODS: Cathepsin D expression was examined in 222 cases of invasive ductal carcinoma (CA) and 25 cases of ductal carcinoma in situ (DCIS) by the immunohistochemical staining. Cathepsin D expression was evaluated according to the expression site, either in the tumor cells (CD-T) or in the stromal cells (CD-S), and graded according to the immunopositivity. The differences of CD-T and CD-S in each case were evaluated according to the pathologic parameters and estrogen receptor (ER)/progesterone receptor (PR) status. RESULTS: The rate of CD-S was significantly higher in the CA than in the DCIS (p<0.0001). In the CA, the rate of CD-S was higher than that of CD-T, while in the DCIS, the rate of CD-T was higher than that of CD-S. In the CA, the rate of CD-S and the tumor grade showed a positive relationship (p=0.0281). There were positive correlations between the ER positivity and CD-S (p=0.0236), and between the PR positivity and CD-T (p=0.0246). For the DCIS, no significant relationships were noted between the pathologic parameters including ER/PR status and CD-T/CD-S. CONCLUSION: Cathepsin D expression in the stromal cells seems to be related to the invasiveness and aggressive biological behavior in breast cancers. In addition, there might be some relationship betweeen the ER positivity and CD-S, and between the PR positivity and CD-T.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Cathepsin D* ; Cathepsins* ; Estrogens ; Stromal Cells

PURPOSE: Cathepsin D, a lysosomal protease has been proposed to play a role in the local invasion and metastatic dissemination in primary breast cancer. Although there are many conflicting results, the overexpression of cathepsin D has been considered to be related with a poorer prognosis of breast cancer. This study was designed to verify whether cathepsin D expression is related to other prognostic factors in breast cancer. METHODS: Cathepsin D was assessed by immunohistochemistry using murine monoclonal anti-cathepsin D antibody (ZyMED) in 79 paraffin-embedded primary breast cancer specimens. Cathepsin D expression was compared to other prognostic parameters such as tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors (ER & PR), p53, c-erb B2, Ki-67, MVD (microvessel density), and Pgp (P-glycoprotein). RESULTS: A high-expression of cathepsin D was found in 35 of 79 patients (44.3%) with primary breast cancer. Cathepsin D expression was not related to tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors, p53, Ki-67, or CD31. However, a significant relationship was found between cathepsin D expression and c-erb B2 (p=0.007), and between cathepsin D expression and Pgp (p=0.003). CONCLUSION: These results suggest that cathepsin D expression may be an indicator of a poor prognosis in breast cancer. However, further studies are required to verify the exact role of cathepsin D in the prognosis of breast cancer.
Breast Neoplasms* ; Breast* ; Cathepsin D* ; Cathepsins* ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis