The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans.
Acute Disease ; Adenocarcinoma/virology ; Cell Line ; DNA, Viral/*genetics/isolation & purification ; Humans ; Korea ; Leukemia/*virology ; Leukemia Virus, Bovine/*genetics ; Leukemia, Lymphocytic, Acute/virology ; Leukemia, Myeloid/virology ; Leukemia, Myeloid, Chronic/virology ; Lung Neoplasms/*virology ; Polymerase Chain Reaction/methods ; Proviruses/*genetics

The pathogenesis of endocervical glandular lesions are not clearly understood. The aims of this study are to evaluate the etiologic role of human papillomavirus (HPV) 16/18 and the relationship of HPV 16/18, p53 and MIB-1 expressions in endocervical glandular dysplasia (EGD), adenocarcinoma in situ (AIS) and adenocarcinoma. The materials included 14 endocervical adenocarcinoma and 5 AIS and 18 high grade EGD and 39 low grade EGD. Immunohistochemistry for p53 and MIB-1, and in situ PCR for HPV 16/18 were done. HPV 16/18 positivity was 84.2%, 16.7% and 17.9% in malignant glandular lesion (adenocarcinoma and AIS), high grade EGD and low grade EGD, respectively. P53 protein expression rates of malignant glandular lesions, high grade EGD and low grade EGD were 31.6%, 11.1%, and 0%, respectively. High MIB-1 labelling index was found in 73.7% of malignant glandular lesions, but in only 5.7% and 3.6% of high and low grade EGD, respectively. There were statistically significant differences in HPV 16/18, p53 and MIB-1 expressions between malignant endocervical glandular lesions and EGD, but no significant difference in p53 and MIB-1 expressions in relation to HPV 16/18 expression. In malignant endocervical glandular lesions, HPV 16/18 infection may be a major causative factor, but not be related to p53 and MIB-1 expressions.
Adenocarcinoma/pathology/physiopathology/*virology ; Carcinoma, Squamous Cell/pathology/physiopathology/virology ; Cervix Neoplasms/pathology/physiopathology/*virology ; Female ; Human ; Nuclear Proteins/analysis/*genetics ; Oncogene Proteins, Viral/genetics ; *Papillomavirus, Human ; Papovaviridae Infections/*pathology/physiopathology ; Protein p53/analysis/*genetics ; Tumor Virus Infections/*pathology/physiopathology

OBJECTIVETo evaluate clinical characteristics, prognosis, prognostic factors, and the ideal treatment of the young patients with cervical malignant tumor.

METHODSWe analyzed retrospectively 52 cervical malignant tumor patients younger than 35 years (study group) and 45 cervical carcinoma patients older than 50 years (control group) who were admitted in Peking Union Medical College Hospital from 1985 to 2002. The data were analyzed statistically by SPSS10.0. The ovarian functions were evaluated by the questionnaire and the serum sex hormone assay.

RESULTSIn study group, the median age was (31.0 +/- 0.6) years old. The most common clinical symptoms were contact bleeding and irregular bleeding; 55.8% of patients had more than one symptom. HPV positive rate was 20.5%, which was higher than control group significantly (P < 0.05). The percentage of advanced stage (stage II b-stage IV b) of disease in study group and control group were 30.8% and 22.2%, respectively, the difference was significant (P < 0.05). The most common histological type was squamous cell carcinoma (71.2%) in study group, while the percentage of non-squamous cell carcinoma (43.8%) in patients younger than 30 years was much higher than control group (P < 0.05). All the histological type was non-squamous cell carcinoma in the patients younger than 25 years. Histological grade showed that G1, G2, and G3 were 21.2%, 54.5%, and 24.2% respectively in study group. The percentage of bulky cervix (tumor diameter > 4 cm) in study group and control group was 27.9% and 2.7% respectively (P < 0.005). The overall 5-year survival rates were 75.7% in study group, lower than control group (P < 0.05). The COX hazards regression model showed histological type (P = 0.003) and bulky cervix (P = 0.001) were of significant prognostic values.

CONCLUSIONSThere are more advanced stage carcinoma and non-squamous cell carcinoma patients with poor prognosis in study group. The treatment to younger patients should be concerned individually, as well as preservation of reproductive and female endocrine function should be considered.

Adenocarcinoma ; diagnosis ; surgery ; virology ; Adult ; Age Factors ; Carcinoma, Squamous Cell ; diagnosis ; surgery ; virology ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Ovarian Function Tests ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; Prognosis ; Regression Analysis ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms ; diagnosis ; surgery ; virology

OBJECTIVESTo evaluate the significance of p16(INK4A) protein expression and positivity for HPV DNA in distinguishing between endocervical and endometrial adenocarcinoma.

METHODSExpression of p16(INK4A) protein in 30 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma was assessed by immunohistochemistry. In-situ hybridization for human papillomavirus (HPV) DNA was also performed in 20 cases of endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma.

RESULTSThe positive rate for p16(INK4A) in endocervical adenocarcinoma was 70% (21/30), as compared with 30% (3/10) in endometrial adenocarcinoma. The tumor cells in endocervical adenocarcinoma showed diffuse and strong expression of p16(INK4A) protein with both cytoplasmic and nuclear staining. In contrast, the endometrial adenocarcinoma cells showed patchy and weak expression of p16(INK4A). On the other hand, HPV DNA (type 16 or 18) was detected by in-situ hybridization in 9 (45%) of the 20 cases of endocervical adenocarcinoma and none of the 10 cases of endometrial adenocarcinoma.

CONCLUSIONSThe expression of p16(INK4A) protein is significantly higher in endocervical adenocarcinoma than in endometrial adenocarcinoma. This expression pattern can serve as a useful immunohistochemical marker in the differential diagnosis. p16(INK4A) protein immunohistochemistry appears to be more sensitive than HPV DNA testing in distinguishing between endocervical and endometrial adenocarcinoma, especially in biopsy or curettage specimens.

Adenocarcinoma ; diagnosis ; genetics ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; DNA, Viral ; analysis ; Endometrial Neoplasms ; diagnosis ; genetics ; virology ; Female ; Gene Expression Regulation, Neoplastic ; Human papillomavirus 16 ; genetics ; Human papillomavirus 18 ; genetics ; Humans ; In Situ Hybridization ; Uterine Cervical Neoplasms ; diagnosis ; genetics ; virology

The relationship between Human papillomavirus (HPV) 16 infection and the natural course of colorectal adenocarcinoma has not been fully defined. In this study, the HPV 16 E7 DNA was detected in 82 patients with primary colorectal adenocarcinoma to study the relationship between HPV 16 infection and colorectal carcinoma. Samples were taken from both the tumors and the adjacent normal mucosa in the same patient. Polymerase chain reaction (PCR) was used to amplify the HPV16 E7 DNA fragment. The PCR products were gel-purified and sequenced for HPV genotyping. DNA sequence analysis indicated that PCR product was 297 bp. It was the equivalent of 562-858th pairs in the HPV 16 primitive sequences. Our results showed HPV16 E7 DNA expression was significantly higher in colorectal carcinoma (42/82) than in adjacent normal mucosa (4/82). The correlation was found between HPV16 E7 expression and tumor's location; the positive rate was 18.18% in the ascending colon carcinoma group and 64.10% in the rectal carcinoma group. High HPV16 E7 expression was also associated with lower Dukes stage (P < 0.01). These results indicated that there was correlation between colorectal adenocarcinoma and HPV 16 infection. HPV16 infection was relatively higher in the colorectal carcinoma and rare in the adjacent normal mucosa. Specimens expressing higher levels of HPV 16 E7 DNA were associated with lower Dukes stage and more distal location.
Adenocarcinoma ; metabolism ; virology ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; virology ; DNA, Viral ; analysis ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Oncogene Proteins, Viral ; biosynthesis ; genetics ; Papillomaviridae ; isolation & purification ; Papillomavirus E7 Proteins ; Papillomavirus Infections ; metabolism ; virology

OBJECTIVETo evaluate the correlation of the expression of homeodomain-interacting protein kinase 2 (HIPK2) with human papillomavirus (HPV) infection and apoptosis in cervical cancer.

METHODSFormalin-fixed, paraffin embedded tissue samples from 50 cervical cancers and 15 normal uterine cervix cases were obtained. Apoptosis was quantified by TdT-mediated dUTP nick end labeling (TUNEL) assay and the expression of HIPK2 as well as HPV by immunohistochemical staining.

RESULTSHIPK2 protein expression was detected in 88.0% (44/50) of cervical cancers and 6.7% (1/15) of normal cervical tissues. HPV was found in 78.0% (39/50) of cervical cancers and 20.0% (3/15) of normal cervical tissue samples. The expression of HIPK2 protein was significantly and positively correlated with HPV presence (r=0.467, P<0.01), but negatively with apoptotic index (r=-0.370, P<0.05).

CONCLUSIONHIPK2 protein expression is positively correlated with HPV infection, but negatively with apoptotic index in cervical cancers. Therefore, HIPK2 may be involved in the mechanism of apoptosis in cervical cancer and may play an important role in cervical carcinogenesis.

Adenocarcinoma ; metabolism ; pathology ; virology ; Apoptosis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Carrier Proteins ; metabolism ; Cervix Uteri ; metabolism ; Female ; Humans ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Proliferating Cell Nuclear Antigen ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology

Adenocarcinoma ; genetics ; pathology ; virology ; Carcinoma in Situ ; genetics ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; genetics ; pathology ; virology ; Cervix Uteri ; pathology ; virology ; Cytological Techniques ; DNA, Viral ; analysis ; Female ; Follow-Up Studies ; Humans ; Neoplasm Grading ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; Uterine Cervical Neoplasms ; genetics ; pathology ; virology

OBJECTIVEThe aim of this study was to investigate the characteristics of p16 and PR immunoreactivity and HPV infection in endocervical adenocarcinoma.

METHODSParaffin blocks of 62 patients with endocervical adnocarcinoma treated in the Cancer Institute and Hospital, Chinese Academy of Medical Sciences from year 2005 to year 2010 were collected. p16 and PR immunostaining and HPV detecting by SPF-10 PCR were conducted on all cases.

RESULTSHPV infection rate of the 62 endocervical adnocarcinoma cases was 74.2% with four cases combined with CIN3. Among the 46 HPV-positive cases, there were 22 cases of HPV18 infection (47.8%), 14 cases of HPV16 infection (30.4%), one case of HPV59 infection (2.2%). and nine multiple HPV infection cases (19.6%). The mean age of the 16 HPV-negative cases was (49.6 ± 10.5)year, while the mean age of the 46 HPV-positive cases was (42.8 ± 9.7)year, showing a significant difference between the two subgroups (P = 0.022). The positive rate of p16 infection was 80.6%. Association analysis showed that the results of p16 and HPV test were independent to each other (P = 0.077). The positive rate of PR was 3.2%. Among the 62 cases, there were 24 cases containing normal cervical glands, with 19 cases PR-positive in the normal cervical glands and the positive rate was 79.2%. The difference of PR positivity between neoplastic glands and normal glands was statistically significant by Chi-square test (P < 0.01) .

CONCLUSIONSThe HPV infection rate of endocervical adnocarcinoma is 74.2%, and the major subtypes were HPV16 and HPV18 infection. p16 immunoreactivity in endocervical adenocarcinoma maybe not the proof of high-risk HPV-related neoplasm. PR staining can be used as a reference designator to differentiate between neoplastic and normal cervical glands.

Adenocarcinoma ; metabolism ; pathology ; virology ; Adult ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Female ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; Immunohistochemistry ; Middle Aged ; Papillomaviridae ; isolation & purification ; Papillomavirus Infections ; virology ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology

OBJECTIVEThe aim of this study was to elucidate the role of EGFR expression and HPV infection and their relationship in the genesis and progression of cervical carcinoma.

METHODSThis analysis included 60 cases of cervical carcinoma, 40 cases of CIN and 30 cases of control group. Patients of cervical carcinoma group were all subjected to radical hysterectomy with bilateral pelvic lymphadenectomy in Tumour Hospital, Zhongshan University from 1997 to 2001. The FIGO stage was I a - II b. EGFR protein was stained by S-P immunohistochemistry, and HPV16/18 DNA was detected by PCR.

RESULTSThe moderate/ strong expression of EGFR was observed in 0, 42.5%, 76.7% of normal cervical epithelium, CIN and cervical tumor tissue, respectively, with a significant difference among them (P < 0.05). The infection of HPV16/18 was observed in 6.7%, 67.5%, 58.3% of normal cervical tissue, CIN and cervical tumors, respectively. The infection rate of CIN or cervical carcinoma was significantly higher than that in normal cervicaltissue (P = 0.000), but no statistically significant difference was observed between cervical carcinoma and CIN. The moderate/strong expression of EGFR demonstrated an association with the cervical invasion depth. The EGFR expression increased significantly as the invasion depth progressed from less than or equal to a half cervical stroma to deeper than that (89.2% vs. 56.5%, P = 0.004). The infection of HPV16/18 demonstrated a correlation with the cervical canal invasion. The infection increased significantly in the cases with cervical invasion than that in the cases without invasion (88.2% vs. 46.5%, P = 0.003). But no significant correlation was observed between EGFR and HPV. Neither EGFR nor HPV had a significant association with carcinoma prognosis.

CONCLUSIONEGFR and HPV demonstrate a significant correlation with genesis and progression of cervical carcinoma. In our study, neither EGFR nor HPV demonstrates a significant association with tumor prognosis, and no significant correlation is observed between EGFR and HPV.

Adenocarcinoma ; metabolism ; surgery ; virology ; Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; surgery ; virology ; Cervical Intraepithelial Neoplasia ; metabolism ; surgery ; virology ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; Middle Aged ; Papillomavirus Infections ; Receptor, Epidermal Growth Factor ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; surgery ; virology ; Young Adult

OBJECTIVETo study the death mode of human hepatocellular carcinoma Hep-3B cells and human lung adenocarcinoma A549 cells induced by bluetongue virus strain HbC3 (BTV-HbC3) and the mechanism of its action.

METHODSBTV-HbC3 was used to infect the tumor cells, and the cytopathic effects (CPE) was observed. TUNEL staining was used to detect the apoptosis of tumor cells induced by BTV-HbC3. The changes of endoplasmic reticulum and nuclei treated with BTV-HbC3 were further examined by laser scanning confocal microscopy. The activities of caspase-3/7, caspase-8 and caspase-9 were determined by fluorescence analysis.

RESULTSHep-3B cells were sensitive to BTV-HbC3. Lots of early apoptotic cells were found by TUNEL staining. The laser scanning confocal microscopic examination showed characteristics of apoptosis, such as pyknotic nuclei, margination of nuclear chromatin and vacuolization of endoplasmic reticulumin in Hep-3B cells exposed to BTV-HbC3. The activity of caspase-3/7 was increased, but the activity changes of caspase-8 and caspase-9 were not found. A549 cells were sensitive to BTV-HbC3 too. But no apoptotic cells were observed by TUNEL staining. The results of laser scanning confocal microscopy showed marked vacuolization of endoplasmic reticulum, but chromatin margination was not found after A549 cells was exposed to BTV-HbC3. The activity of caspase-3/7 and caspase-9 was increased, but the activity of caspase-8 was not changed.

CONCLUSIONBTV-HbC3 induces apoptosis of Hep-3B tumor cells mainly through endoplasmic reticulum signal transduction pathway, and the features of cell death in A549 cells could be described as paraptosis.

Adenocarcinoma ; metabolism ; pathology ; virology ; Apoptosis ; Bluetongue virus ; pathogenicity ; physiology ; Carcinoma, Hepatocellular ; metabolism ; pathology ; virology ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Nucleus ; pathology ; Endoplasmic Reticulum ; pathology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; virology ; Lung Neoplasms ; metabolism ; pathology ; virology ; Oncolytic Viruses ; pathogenicity ; physiology ; Signal Transduction