[Preliminary observation on the changes of T(1) weighted signal of globus pallidus after multiple intravenous injection of linear gadolinium contrast agent].

Objective: To explore the changes in signal intensity (SI) ratios of globus pallidus (GP) on unenhanced T(1)-weighted(T(1)WI)magnetic resonance imaging (MRI) scans between the first and last MRI using the linear gadolinium-based contrast agent (GBCAs) intravenously. Methods: Clinical and imaging data of 114 patients who underwent at least 4 consecutive enhanced MRI examinations at the Affiliated Hospital of Xuzhou Medical University between January 2016 and April 2018 were analyzed. The SI ratio of GP, thalamus and cerebrospinal fluid (CSF) were measured on unenhanced T(1)WI. The GP to thalamus SI ratio was calculated by dividing the SI in the GP by that in the thalamus, and so was the GP to CSF SI ratio. The difference of SI ratio in the same patient was analyzed by nonparametric tests, linear regression analysis was used to analyze clinical factors. Results: The SI ratio of GP-to-thalamus and GP-to-CSF after multiple enhancement were higher than before, and the difference was statistically significant. The SI ratio of GP-to-thalamus and GP-to-CSF before and after repeated contrast-enhanced were 1.036(1.010, 1.075), 1.104(1.074, 1.168); 4.215(3.590, 5.614), 5.409(4.213, 6.502), all P<0.01. The SI ratio differences showed a significant positive correlation with the number of enhanced examination(pons:b=0.023, P<0.01,CSF:b=0.279,P=0.034), and a significant negative correlation with the interval (pons: b=-0.002,P< 0.01, CSF: b=-0.023, P=0.039). There was no correlation with other clinical factors (all P>0.05). Conclusions: There is an increase in SI in the GP after serial injections of linear GBCAs, and there is a positive correlation with the times of enhanced examination, and a negative correlation with time interval.

Desmoglein-2 overexpression predicts poor prognosis in hepatocellular carcinoma patients.

OBJECTIVE: Desmoglein-2 (Dsg2) plays a crucial role in the assembly and adhesion of desmosomes. The absent or aberrant expression of Dsg2 was reported to be associated with the progression of varies human cancers. However, the expression of Dsg2 in hepatocellular carcinoma (HCC) and its association with tumor prognosis is still unknown. The aim of this study was to evaluate the expression level of Dsg2 in HCC and of the correlation between Dsg2 expression and clinicopathological variables. PATIENTS AND METHODS: A total of 104 patients diagnosed with HCC were enrolled in this study. Real time-quantitative PCR (RT-qPCR) and Western blot were performed to determine the expression level of Dsg2 in HCC tumor tissues and matched noncancerous tissues. Cell proliferation and cell cycle were measured by cell counting kit-8 (CCK-8) assay and flow-cytometry assay, respectively. RESULTS: Our results revealed that Dsg2 expression was significantly higher in HCC tumor tissues than in matched noncancerous tissues (p < 0.01), positively correlated with tumor size (p = 0.035) and tumor stage (p = 0.021). Univariate and multivariate analyses demonstrated Dsg2 expression was an independent prognostic factor for overall survival. Meanwhile, we found knockdown the expression of Dsg2 using small interfering RNA (siRNA) could efficiently impaired HCC cell proliferation rate and cell cycle progression (p < 0.05). CONCLUSIONS: Taken together, our results suggest that increased Dsg2 expression was associated with tumor progression in HCC and may function as a promising biomarker for unfavorable prognosis of HCC.

[Value of texture analysis in evaluating liver cancer recurrence after transarterial chemoembolization].

Objective: To investigate the feasibility of contrast-enhanced computer tomography (CT) texture analysis in predicting early recurrence after transarterial chemoembolization (TACE) in patients with liver cancer. Methods: A retrospective analysis was performed for 47 patients with liver cancer confirmed by liver biopsy and digital subtraction angiography who underwent upper abdominal contrast-enhanced CT scan before TACE, and according to the presence or absence of focal recurrence within half a year, these patients were divided into early recurrence (ER) group and non-early recurrence (NER) group. The texture analysis was used to delineate tumor boundary layer by layer on the axial contrast-enhanced CT image before liver cancer surgery, and related parameters of tumor heterogeneity, including entropy, mean, non-uniformity, skewness, and kurtosis, were obtained. The independent samples t-test was used for comparison of texture parameters between the two groups. The receiver operating characteristic (ROC) curve was used for the analysis of entropy, mean, and non-uniformity, and the area under the ROC curve (ROC), optical cut-off value, sensitivity, and specificity were calculated to evaluate the efficiency of texture analysis in predicting early focal recurrence after TACE. Results: There were 20 patients in the ER group and 27 in the NER group. The ER group had a maximum major axis length of 88.2±36.3 mm and a maximum minor axis length of 41.4±21.4 mm, and the NER group had a maximum major axis length of 66.9±30.2 mm and a maximum minor axis length of 29.3±19.8 mm; the ER group had significantly higher maximum major and minor axis lengths than the NER group (t = 4.89 and 4.62, P < 0.001). The ER group had significantly higher entropy and non-uniformity values than the NER group, and there were no significant differences in skewness and kurtosis between the two groups. Entropy, non-uniformity, and mean had high efficiency in predicting early recurrence after TACE, and the optimal cut-off value of entropy was 4.135. Conclusion: Volumetric texture analysis of contrast-enhanced CT images before liver cancer surgery has a high value in predicting early recurrence after TACE.

Spontaneous uterine perforation mimicking ectopic pregnancy as the initial presentation of placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD), with only 100 cases reported in the literature. Irregular vaginal bleeding has been reported to be the most common presenting symptom, however, spontaneous uterine perforation, mimicking ectopic pregnancy, as the initial presentation is extremely rare, and has not yet been reported in the Chinese literature. Herein, we report a 26-year-old female with PSTT complicating with uterine perforation that mimicked ectopic pregnancy as the initial presentation. She received wide excision of the uterine perforation margin only and now remains disease-free, 2 years after the operation. Reviewing the literature, while most cases of PSTT behave a benign fashion, some exhibit malignant behavior; surgery remains the mainstay of therapy. For patients whose disease is limited to the uterus, simple total abdominal hysterectomy is the treatment of choice. For patients with extensive or metastatic disease, cytoreductive surgery (total abdominal hysterectomy and resection of extrauterine tumor load) combined with chemotherapy should be applied. Etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) chemotherapy appears superior to other available chemotherapeutic regimens in the treatment

Estimating transition probabilities from aggregate samples plus partial transition data.

Longitudinal studies often collect only aggregate data, which allows only inefficient transition probability estimates. Barring enormous aggregate samples, improving the efficiency of transition probability estimates seems to be impossible without additional partial-transition data. This paper discusses several sampling plans that collect data of both types, as well as a methodology that combines them into efficient estimates of transition probabilities. The method handles both fixed and time-dependent categorical covariates and requires no assumptions (e.g., time homogeneity, Markov) about the population evolution.

Sequence variants and functional analysis of human papillomavirus type 16 E5 gene in clinical specimens.

Previously, we found that the E5 protein can be expressed in HPV-16 infected precancerous lesions and cervical cancer. In this study, we investigated the presence of sequence variants of E5 in HPV-16 infected tissues. Toward this end, we amplified the E5 gene by polymerase chain reaction from 29 HPV-16 infected tissues including eight normal tissues, seven high grade neoplastic tissues (high grade squamous intraepithelial lesions (HSIL) and 14 cervical cancer tissues. Sequence analysis demonstrated that there were three mutational hot spots at positions 3979, 4042, and 4077 of the HPV-16 DNA; these and other mutations resulted in six variants in the E5 sequence. This resulted in four E5 protein mutants, named WTE5 [wild type E5 protein], 14E5, 21E5 and 56E5. Functional analysis of these four mutant proteins revealed that the transforming activities of 14E5, 21E5 and 56E5 were 0.95, 0.59, and 0.89 fold of WTE5, respectively. Although E5 was expressed in all of the HSIL and cervical cancer tissues, but in only one of the eight normal tissues tested, only WT E5 protein was found in HSIL while in cervical cancer tissues both WT and mutant E5 proteins were detected. Since these E5 proteins exhibited the same in vitro transforming activity, these data suggest that expression of E5 is important in development and progression toward malignancy but mutation of E5 does not affect the transformation process.

The expression of type I growth factor receptors in the squamous neoplastic changes of uterine cervix.

AIM: The type I family of growth factor receptors includes ErbB1, ErbB2, ErbB3, and ErbB4 which are frequently overexpressed in various human cancer cells. In this study, we systematically investigated the frequency and distribution of these four receptors in relation to neoplastic changes and tumor behaviors in the uterine cervix. MATERIALS: A total 84 of cases including 12 cases of normal cervical tissues, 6 cases of low grade squamous intraepithelial lesion, 10 cases of high grade squamous intraepithelial lesion, and 56 cases of squamous cells carcinoma were examined. RESULTS: Our results show significant difference with increasing grades of dysplasia in terms of these four receptor expressions. No association was found between these four receptors and cell keratinization/differentiation of squamous cell carcinoma of the cervix. Of the four receptors studied, only the expression of erbB2/neu gene was significantly associated with lymph nodal metastasis. Moreover, we find that the coexpression of ErbB1 and ErbB4 was significant in cervical carcinoma. CONCLUSIONS: The coexpression of ErbB1 and ErbB4 in cervical carcinoma suggests that they may be involved in receptor heterodimerization leading to the activation of signaling pathway in the cervical carcinoma.

Benign cystic teratoma of unilateral fallopian tube associated with intrauterine pregnancy: a case report.

Primary teratomas of the fallopian tube are extremely uncommon. To date, only about 50 cases have been reported in the literature. Six of them are reported to have been in conjunction with tubal ectopic pregnancies. Herein we present the first case of benign cystic teratoma of the unilateral fallopian tube associated with an intrauterine term pregnancy, reported in Taiwan.

[Studies on the antimould activity of compound TBZ and its application in paint].

The compound TBZ is a new antimould agent, which contains mainly [2-(4-thiazolyl) benzoimidazole (TBZ)], ethanoic acid and propionic acid. It was shown in laboratory experiment that the compound TBZ had excellent mycostatic effect on all the 10 fungi tested with 70% of the mycostatic zones larger than 6.0 cm. It had obvious inhibitary activity on Alternaria Nees and Aureobasidium Pullulans isolated from mouldy wall. In laboratory condition the surface of fibreboard painted with compound TBZ did not become mouldy in 120 days, while the 20% of that coated with TBZ directly mixed in the paint became mouldy. In practical use, the antimould effect of the wall painted with compound TBZ could maintain more than two years.

Human papillomavirus, cytomegalovirus and herpes simplex virus infections for cervical cancer in Taiwan.

Previously, we had reviewed 43 cases of invasive cancers, adenosquamous cell carcinoma and adenocarcinoma for HPV type infections. With the same cases we extended the investigation to cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. Results show that the prevalence of CMV and HSV infections from these cases of cervical carcinoma was 67 and 76%, respectively, by polymerase chain reaction. The results of the analysis of the association of HPV, CMV and HSV with various clinical characteristics of cervical cancer patients indicated that the correlation between HSV infections and clinical stages of squamous carcinoma was marginally significant (P = 0.068). HSV infections seemed to have a higher association with cell keratinization pattern as compared with the other two viral infections.

Pelvic inflammatory pseudotumor with central infectious abscess: a case report.

Inflammatory pseudotumors (IPT) are a fascinating group of lesions which involve almost all organs and tissues of the body. The clinical manifestations are diverse. Final diagnosis can only be made by meticulous microscopic examination of different areas of the tumor. A 60 year-old woman had a pelvic IPT with central infectious abscess. The lesion involved her urinary bladder, mesentery, terminal ileum, right rudimentary ovary and the abdominal wall. It mimicked malignant tumor clinically, and led to total surgical excision. Early follow-up has shown a favorable results. IPTs are extremely uncommon. The characteristic pathologic picture is a reparative fibroblastic tissue infiltrated by polymorphic inflammatory cells. Pelvic IPT, admixed with central infectious abscess, is even rarer. Prior pelvic surgery and pasteurella hemolytica infection might be causative factors in this reported case.

Coincidental expression of E5a and c-jun in human papillomavirus type 6/11-infected condylomata.

Previously, we have shown that E5a can induce expression of the c-jun gene in human papillomavirus (HPV)-11 E5a transformed NIH 3T3 cells and human epidermal keratinocytes. In this study, we investigated the relationship between expression of the E5a gene and c-jun in pathologically confirmed condylomata specimens using mRNA hybridization in situ. The c-jun RNA concentration was significantly higher in condylomata specimens with E5a mRNA expression than in specimens without E5a mRNA expression, or in normal cervical specimens. The cells with c-jun expression were located predominantly in the basal and parabasal cell layers. These layers were also the primary location of E5a-expressing cells. This is the first demonstration of a strong correlation (74%) between expression of the E5a and c-jun genes in condylomata specimens. This correlation might reflect regulation by HPV-11 E5a of c-jun gene expression in condyloma.

Mutational analysis of human papillomavirus type 11 E5a oncoprotein.

In this study, we investigated the structural basis of human papillomavirus type 11 (HPV-11) E5a transforming activity at the amino acid level. The effects of insertion, deletion , and substitution mutations on teh E5a transforming activity were determined by the assay of anchorage-independent growth. In the conserved Cys-X-Cys structure, substitution of Ser for Cys-73 resulted in indistinguishable transforming activity, whereas substitution of Ser for Cys-75 or Ser for both Cys-73 and Cys-75 retained 50 and 42% transformation, respectively. This suggests that Cys at position 75 may be important for transformation. Charge and structural changes at teh COOH termini of several mutants impaired transformation significantly, but those at the middle region did so only mildly. In addition, the 16,000-molecular-weight pore-forming protein (16K protein) is known to associate with BPV-1, HPV-6, and HPV-16 E5 proteins. In this study, we investigated the correlation between E5a-16K binding affinity and the transforming activity of E5a by the use of 11 E5a mutants. Results show that E5a and these 11 E5a mutants could bind to the 16K protein when these proteins were coexpressed in COS cells, suggesting that simple binding of the 16K protein by E5a may not be sufficient for cell transformation.

Molecular analysis of cellular loci disrupted by papillomavirus 16 integration in cervical cancer: frequent viral integration in topologically destabilized and transcriptionally active chromosomal regions.

To discern the structural features of cellular loci that are disrupted by type 16 human papillomavirus (HPV-16) integration in cervical cancer, a polymerase chain reaction (PCR)-based strategy was employed for direct amplification and sequence analysis of four such cellular loci in cancer biopsy samples. One of the HPV-16-disrupted loci was found to be the microtubule-associated protein (MAP-2) gene and the other three loci were uncharacterized and were designated PID-1 to -3 (for papillomavirus integration-disrupted). The junctional sequences of the viral integration sites in the four loci analyzed are bracketed by long tracts of homogeneous purine or pyrimidine or alternating purine-pyrimidine which are known to destabilize the B-form conformation of the DNA structure. Using a panel of human/hamster hybrid cell DNAs and PCR analysis, the four loci were assigned to chromosomes 2 (MAP-2), 9 (PID-1), 1 (PID-2) and 8 (PID-3), respectively. These chromosomes carry numerous other previously determined viral integration and chromosomal fragile sites and the myc oncogenes. The PID-1 locus was further found in Southern analysis to be rearranged and amplified in another cervical cancer biopsy and a cervical carcinoma cell line (CaSki). On Northern analysis, the PID-1 and -3 probes detected a 3.0- and a 3.6-kb transcript, respectively, in normal cervical cells and in cervical cancer cell lines. The findings suggest that HPV-16 genome integrates frequently into topologically destabilized and transcriptionally active chromosomal sites. It remains to be elucidated whether the MAP-2 and the PID loci contribute to the pathogenesis of cervical cancer.

Jun-B oncogene aberrations in cervical cancer cell lines.

We describe here structural and expression analysis of the jun-B oncogene in two cervical cancer cell lines. In the CC7T-a cell line, results from both Southern analysis and cDNA cloning studies revealed the existence of two structurally altered jun-B alleles besides the normal gene. One of the altered alleles was due to a type 16 human papillomavirus (HPV-16) integration event, whereas the other allele was a consequence of a chromosomal translocation involving chromosome 19 (jun-B) and an EST182 locus residing in chromosome 15. In the HeLa cell line, which contains integrated HPV-18, an apparent structural aberration, a 3-fold amplification and a 3-fold overexpression of the jun-B gene were observed. Our observations suggest that deregulation of the jun-B gene expression may have contributed to the transformation process in these two cervical cancer cell lines.

Genital human papillomavirus infections in Taiwan.

OBJECTIVES: Identification and typing of HPV infections in genital condyloma and normal cytological cervix. METHODS: Cervical cells from 289 Pap cases with normal cytological findings were examined for HPV infection by slot blot hybridization. Fifteen condyloma biopsy specimens were studied by Southern blot hybridization. RESULTS: Thirty-six cases (12.5%) with normal cervical cytology were HPV positive. The predominant HPV type in women with normal cytology is HPV-16. Risk factors for HPV infection in women with normal cytology depend on age and history of pregnancies. Twelve cases (80%) of condyloma contained HPV-6 or -11 sequences. The predominant HPV type in genital condyloma is HPV-11. CONCLUSIONS: HPV detection in population-based screening programs for cervical neoplasia can be an important tool in identifying women who are at risk of developing dysplasia and cervical cancer.

Identification and typing of human papillomavirus in cervical cancers in Taiwan.

BACKGROUND: Although human papillomaviruses (HPV) are associated with cervical cancer, it has yet to be determined if specific HPV types have clinical or prognostic significance. METHODS: Identification and typing of HPV were done by polymerase chain reaction (PCR) and restriction fragment length polymorphism. RESULTS: Of the 43 cases of cervical cancer, 31 (72%) were HPV positive. The results of HPV typing in 40 cases of squamous cell carcinoma of the cervix revealed the presence of HPV-16 in 20 cases (50%), HPV-18 in 2 cases, HPV-11 in 1 case, HPV-33 in 1 case, HPV-52 in 1 case, HPV-58 in 1 case, and unidentified HPV types in 5 cases. Neither HPV-31 nor HPV-42 were present in our study. One case of squamous cell carcinoma had HPV-11 integration. Chi-square analysis revealed significant correlation between HPV genotypes and squamous cell patterns, no significant correlation between HPV genotypes and clinical stages, and cell differentiation of squamous cell carcinoma of cervix. CONCLUSIONS: These findings may contribute to understanding the role of HPV in cancer and the value of typing as a prognostic indicator.