Pattern of relapse following three-field lymphadenectomy of esophageal carcinoma and related factors predictive of recurrence.

PURPOSE: For treatment of esophageal carcinoma, the optimal postoperative radiotherapy target volume after three-field lymph node dissection (3-FLD) had not been determined. We analyzed local recurrence pattern of thoracic esophageal carcinoma and risk factors of lymph node recurrence after 3-FLD without prophylactic radiotherapy. MATERIAL AND METHODS: We reviewed 1282 patients with thoracic esophageal squamous cell carcinoma (ESCC) who were treated with 3-FLD without radiotherapy from 2010 to 2018 and analysed local recurrence patterns and risk factors of lymph node recurrence, in order to provide a reference for determination of the radiotherapy target volume for thoracic ESCC. RESULTS: The lymph node recurrence accounted for 91.0% of treatment failures. The mediastinal, cervical and abdominal lymph node recurrence accounted for 84.92%, 36.07% and 22.30%, respectively (χ2=264.776, P=0.000). The superior, middle and inferior mediastinal lymph node recurrence rates were 67.54%, 27.87% and 0.98%, respectively (χ2=313.600, P=0.000). Cervical metastases were significantly associated with N stage and Preoperative cervical lymph node status. Abdominal metastases were significantly associated with the number of preoperative abdominal lymph node metastases (LNM), tumor location and N stage. CONCLUSIONS: The main pattern of local-regional recurrence might be lymph node metastasis after radical 3-FLD without radiotherapy in esophageal carcinoma. The dangerous lymph node recurrence regions included neck, superior and middle mediastinum. The abdominal areas might be irradiated for lower TEC patients with preoperative abdominal LNM.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer was published in 2022. It was therefore decided, by both the ESMO and the Indian Society of Medical and Paediatric Oncology (ISMPO), to convene a virtual meeting in July 2022 to adapt the ESMO 2022 guidelines to take into account the variations in the management of endometrial cancer in Asia. These guidelines represent the consensus opinion of a panel of Asian experts representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). Voting was based on scientific evidence and was conducted independently of the current treatment practices and treatment access constraints in the different Asian countries, which were discussed when appropriate. The aim of this guideline manuscript is to provide guidance for the optimisation and harmonisation of the management of patients with endometrial cancer across the different regions of Asia, drawing on the evidence provided by Western and Asian trials whilst respecting the variations in clinical presentation, diagnostic practices including molecular profiling and disparities in access to therapeutic options, including drug approvals and reimbursement strategies.

[Bibliometric analysis of scientific articles on epidemiological study of burns in China].

Objective: To analyze the current status of epidemiological study of burns in China, and to explore the related strategies. Methods: Retrospective or cross-sectional scientific articles in Chinese or English on epidemiological study of burns in China published from January 2005 to December 2015 were systemically retrieved from 4 databases. The databases include PubMed, Embase, China Biology Medicine disc, and Chinese Journals Full-text Database. From the results retrieved, data with regard to publication year, journal distribution, number of institutions participated in the study, affiliation of the first author and its location, and admission time span and age of patients in all the scientific articles were collected. Furthermore, the definition of age range and the grouping method of age of pediatric patients in English articles on epidemiological study of pediatric burns of China were recorded. Data were processed with descriptive statistical analysis. Results: A total of 256 scientific articles conforming to the study criteria were retrieved, among which 214 (83.59%) articles were in Chinese, and 42 (16.41%) articles were in English; 242 (94.53%) articles were retrospective studies, and 14 (5.47%) articles were cross-sectional studies. During the 11 years, the number of the relevant articles was fluctuant on the whole. The scientific articles were published in 130 journals, with 42 English articles in source journals for SCIENCE CITATION INDEX EXPANDED-JOURNAL LIST, accounting for 16.41%, and 116 Chinese articles in Source Journal for Chinese Scientific and Technical Papers, accounting for 45.31%. Totally 215 (83.98%) articles were single-center studies, and 29 (11.33%) articles were multicenter studies which were conducted by three or more centers. The number of affiliations of the first author of articles was 161 in total. The top 10 institutions regarding the article publishing number published 58 articles, accounting for 22.66%. Scientific articles on epidemiological study of burns were retrieved with location of affiliation of the first author in 31 provinces, autonomous regions, and municipalities directly under the Central Government in Mainland China, and also in Taiwan Province and Hong Kong Special Administrative Region, among which Shanghai ranked first with 24 (9.38%) articles published. The admission time span of patients in the articles ranged from 3 months to 47 years, with 120 (46.87%) articles from 3 months to 5 years, 79 (30.86%) articles from 6 to 10 years, and 57 (22.27%) articles more than 10 years, respectively. Regarding the age of patients in the study, 123 articles were on epidemiological study of pediatric burns, and 16 articles on epidemiological study of elderly burns, accounting for 48.05% and 6.25%, respectively. Further analysis of articles on epidemiological study of pediatric burns in English showed that there was no standard definition of age range or unified grouping method of age for pediatric burn patients. Conclusions: The epidemiological study of burns in China has been carried out nationwide, but the number of institutions conducted relevant study is not that much, and multicenter epidemiological studies remain scanty. The quality of the articles needs to be further improved. The epidemiological study of elderly burns is relatively deficient and calls for more attention. The epidemiological study of burns in China lacks regularity or continuity in time scope. There is an urgent need for the guideline on classification method for items of epidemiological study of burns in China so as to standardize the related research.

[An epidemiological investigation of pediatric patients under 14 with large area burns: a multicenter study].

Objective: To investigate and evaluate the epidemiological characteristics of patients under 14 with large area burns in China. Methods: Data of pediatric patients aged 0-14yr with ≥30% total body surface area (TBSA) burned admitted into 106 burn centers in the mainland of China in 2014 were retrieved. The children were divided into three age groups: 0-3, 4-6 and 7-14 years according to the age. Information of age, gender, time of burn injury, causes of burns, admission time, prehospital emergency care of burn wound, burn area, inhalation injuries, the case fatality rate and length of hospital stay were collected for analysis. Results: Of the 486 cases included, 285 (58.6%) were boys and 201 (41.4%) were girls. The mean age of the children was (3.4±2.8) years. Children under 3 years old accounted for 67.5% of all the cases. 271 of the burn injuries (55.8%) occurred from April through August. Scalds and flames were the main causes of burns, which were the causes of 394 cases (81.1%) and 71 cases (14.6%), respectively. The burn injuries resulted from scalds and flames accounted for 89.6% and 7.3%, 70.8% and 21.9%, 51.6% and 41.9% in the age group of 0-3, 4-6 and 7-14 years respectively. The distribution of burn etiology in different age groups differed significantly (χ(2)=21.239, 59.442, 7.333, all P<0.01). Most of the patients (57.8%) were admitted within 2 hours after injury. However, when it came to the pre-hospital emergency management of burn wound, 164 patients (33.7%) did not use any drug or wound dressing, whereas the wound area of 236 patients (48.6%) were treated improperly with toothpaste, soy sauce, eggs or other non-standard disposal. The mean TBSA area of the patients was (42.1±14.5)%, while 288 (59.3%) of the patients suffered full thickness burns with mean TBSA of (24.5±17.9)%. The case fatality rate (CFR) was 4.1%, and the CFR of patients complicated with inhalation injury was significantly higher than those without (P<0.01). The average length of stay for pediatric burn patients was (52.3±40.2) days. Conclusions: Children under 3 years old are important target population of severe burns. Scald is the most common type of burns, while the proportion of flames increases as age goes up. Most patients are likely to get clinical treatment in time, however, the pre-hospital emergency burn care is not satisfying at present.

[Influences of exendin-4 on the secretion function of islet beta cells from rats in the early stage of severe scald].

Objective: To observe the secretion function changes of islet beta cells isolated from rats in the early stage of severe scald, and to explore the influence of them. Methods: Thirty-six Wistar rats were divided into sham injury (SI) group, sham injury+ exendin-4 (SIE) group, scald (S) group, and scald+ exendin-4 (SE) group according to the random number table, with 9 rats in each group. Rats in groups S and SE were inflicted with 50% total body surface area full-thickness scald by a 12-s immersion of back and a 6-s immersion of abdomen in 94 ℃ hot water. Rats in groups SI and SIE were sham injured through immersion of back and abdomen in 37 ℃ warm water. Rats in groups S and SE were subcutaneously injected with exendin-4 (4 µg/kg) twice a day post injury, while rats in groups SI and SIE were subcutaneously injected with sterile water in the same volume. At post injury hour (PIH) 72, the following detections were performed. Eight rats of each group were respectively selected to measure level of fasting blood glucose with cutting-tail method, and to detect plasma level of glucagon-like peptide 1 (GLP-1) and serum level of insulin by enzyme-linked immunosorbent assay (ELISA). The insulin resistant index (HOMA-IR) was calculated. Six rats of each group were respectively selected for islet isolation. The isolated rat islets were stimulated with RPMI 1640 medium containing 2.8 or 16.7 mmol/L glucose, respectively. Insulin content in supernatant was detected by ELISA, and insulin secretion index was calculated with 6 samples in each group. The isolated islets from 3 rats of each group were selected for the observation of the super-structure of islet beta cells under transmission electron microscope. The number of docked granules in per 10 µm membrane of islet beta cells and the ratio of insulin vesicles to the total insulin granules were calculated with 3 samples in each group. Data were processed with one-way analysis of variance and LSD test. Results: (1) Compared with that in group S, levels of fasting blood glucose of rats in group SI, SIE, and SE were significantly decreased (P<0.05 or P<0.01). (2) Compared with those in group SI, plasma level of GLP-1 of rats in group SIE was significantly increased (P<0.05), while serum level of insulin and HOMA-IR of rats did not change obviously (with P values above 0.05). Plasma levels of GLP-1 of rats in groups S and SE were significantly decreased (with P values below 0.01), while serum levels of insulin and HOMA-IR were obviously increased (with P values below 0.01). Compared with those in group SIE, plasma levels of GLP-1 of rats in groups S and SE were significantly decreased (with P values below 0.01), while serum levels of insulin and HOMA-IR were significantly increased (with P values below 0.01). Compared with those in group S, plasma level of GLP-1 and serum level of insulin of rats in group SE were significantly increased (with P values below 0.01), while HOMA-IR was significantly decreased (P<0.05). (3) There was no statistically significant difference in the insulin secretion content of rats in the 4 groups when stimulated with 2.8 mmol/L glucose (P>0.05). Under stimulation of 16.7 mmol/L glucose, compared with that in group SI, the insulin secretion content of rats in groups SIE and SE were significantly increased (P<0.05 or P<0.01), while in group S it was significantly decreased (P<0.05). Compared with that in group SE, the insulin secretion content of rats in group S was significantly decreased (P<0.01) . Compared with that in group S, the insulin secretion content of rats in group SE was significantly increased (P<0.01). Compared with that in group SI (2.25±0.20), the insulin secretion index of rats in group SE (2.68±0.24) was significantly increased (P<0.05). Compared with that in group SIE (2.47±0.18), the insulin secretion index of rats in group S (2.11±0.28) was significantly decreased (P<0.05). Compared with that in group S, the insulin secretion index of rats in group SE was significantly increased (P<0.01). (4) Compared with those in group SI, the number of docked granules per 10 µm membrane of islet beta cells in group SE was significantly increased (P<0.05), while the ratio of insulin vesicles of rat islet beta cells in group S was significantly increased (P<0.01). Compared with those in group SE, the number of docked granules per 10 µm membrane of islet beta cells in group S was significantly decreased (P<0.01), while the ratio of insulin vesicles of rat islet beta cells was significantly increased (P<0.05). Compared with those in group S, the number of docked granules per 10 µm membrane of islet beta cells in group SE was significantly increased (P<0.01), while the ratio of insulin vesicles of rat islet beta cells was significantly decreased (P<0.05). Conclusions: In the early stage of severe scald in rats, level of GLP-1 is decreased and the insulin secretion function of islet beta cells is injured. Long-lasting GLP-1 analogous exendin-4 can improve the secretion function of isolated islet beta cells from severely scalded rats.

Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator.

Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4(+) helper and CD8(+) cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4(+) helper and CD8(+) cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer.

Impact of lymphadenectomy in uterine endometrioid carcinoma.

AIMS: To investigate the role of lymphadenectomy in uterine endometrioid carcinoma based on the 2009 FIGO staging system. METHODS: Using an institution-maintained cancer registry database, all patients who were treated surgically for endometrial cancer from 1991 to 2008 in two medical centers were analyzed. Kaplan-Meier and Cox proportional hazards methods were used to determine the role of lymphadenectomy. RESULTS: From 961 women with uterine endometrioid carcinoma, 680 underwent lymphadenectomy and 281 did not. Young age, early-stage disease, low-grade tumor, and lymphadenectomy were favorable independent prognostic factors. The five-year disease-specific survival (DSS) of stages IA, IB, II, and III, and the two-year DSS of stage IV patients who underwent lymphadenectomy were 97.8%, 88.3%, 91.5%, 70.5%, and 32.1%, respectively, compared to 98.7%, 70.0%, 73.3%, 42.9%, and 16.6% in those without lymphadenectomy (p > 0.05 for stage IA; p < 0.01 for stages IB-IV, log-rank test). In high-risk patients (i.e., poorly-differentiated, outer-half myometrial invasion, and stages II-IV), more extensive lymph node resection was associated with an improved five-year DSS, from 71.3% (1-10 nodes removed) and 85.3% (11-20 nodes removed) to 86.8% (>20 nodes removed) (p = 0.02, log-rank test). For stage IIIC-IV patients with nodal metastasis, the extent of node resection also significantly improved the five-year DSS, from 34.4% (1-10 nodes removed) and 62.4% (11-20 nodes removed) to 79.6% (>20 nodes removed) (p = 0.04, log-rank test). CONCLUSIONS: Lymphadenectomy improves the survival of patients with uterine endometrioid carcinoma stage IB to stage IV. The extent of lymphadenectomy also improves the survival of high-risk patients and those with nodal disease.

High frequency PMN-PT single crystal focusing transducer fabricated by a mechanical dimpling technique.

High frequency (∼30MHz and ∼80MHz) focusing ultrasound transducers were fabricated using a PMN-0.28PT single crystal by a mechanical dimpling technique. The dimpled single crystal was used as an active element for the focusing transducer. Compared with a plane transducer, the focusing transducer fabricated with a dimpled active element exhibits much broader bandwidth and higher sensitivity. Besides, a high quality image can be obtained by the 30MHz focusing transducer, in which the -6dB axial and lateral resolution is 27µm and 139µm, respectively. These results prove that the dimpling technique is capable to fabricate the high frequency focusing transducers with excellent performance for imaging applications.

Clinical significance of signal pattern of high-risk human papillomavirus using a novel fluorescence in situ hybridization assay in cervical cytology.

The present study aimed to evaluate a novel fluorescence in situ hybridization (FISH) assay for detecting the high-risk human papillomavirus (HR-HPV) DNA and signal pattern in cervical cytology specimens and for identifying cervical intraepithelial neoplasia (CIN) lesions. One hundred and ninety-six liquid-based cytology specimens with CIN were recruited. The signal pattern (punctate, mixed punctate and diffuse, and diffuse) detected by FISH was compared with E6 mRNA and correlated with histological classification. FISH and E6-type specific polymerase chain reaction (PCR) had fair to good agreement for detecting HPV DNA across all grades of CIN (kappa coefficient, 0.37-0.73). Among 44 samples of negative FISH and positive E6 type-specific PCR in HPV 16, 18, 31, 33, 52 and 58, 82% (36/44) of E6 mRNA were not detected, in contrast to 41% (48/118) of positive FISH and positive E6 type-specific PCR (p <0.0001). Among HR-HPV DNA positive cases tested by the FISH assay, the specificity of predicting CIN3 using the punctuate pattern is higher than that using E6 mRNA (96.3% vs. 44.8%). The punctate pattern was 0% in patients with

Brain metastasis as a late manifestation of ovarian carcinoma.

This paper aims to evaluate the clinical characteristics of ovarian cancer patients with cerebral metastases. Ten ovarian cancer patients with brain metastases were retrospectively identified from a total of 539 ovarian cancer patients. Their characteristics before and at the time of diagnosis of cerebral metastases were analysed. The survival of them was also measured. Ten (1.9%) of the 539 ovarian cancer patients had brain metastases in the study period. Nine had stage III or IV tumours with either moderate or poor histological differentiation. The mean time from diagnosis of ovarian cancer to documentation of central nervous system metastasis was 24.3 months, which was 11.1 months if other sites of metastasis were involved before cerebral relapse. All of the patients with intra-cranial tumours suffered from associated neurological defects and relived by treatments. The median survival time after diagnosis of central nervous system involvement was 3 months. In this study, all ovarian cancer patients with cerebral metastases had clinical neurological symptoms. Physicians should pay more attention to ovarian cancer patients with neurological defects and arrange brain imaging studies for the early diagnosis of brain metastases and prompt management to improve quality of life.

Risk of gynaecological malignancies in cytologically atypical glandular cells: follow-up study of a nationwide screening population.

OBJECTIVE: To investigate the relationship between screening status, clinical characteristics and risk of gynaecological malignancies in women with a cytological diagnosis of atypical glandular cells (AGC). DESIGN: Prospective study of a screened population. POPULATION: Case series from nationwide screening population. METHODS: The 8281 women who were diagnosed with cytological AGC for the first time were divided into screened (5386 women) and unscreened (2895 cases) groups according to their screening status. Follow-up histological reports were analysed. MAIN OUTCOME MEASURES: Diagnosis of cervical, uterine, or ovarian cancers. RESULTS: Of the 323 women who developed gynaecological malignancies, 271 had invasive cervical cancers, 40 had uterine cancers and 12 had ovarian cancers, with a mean follow up of 1.9 years and 50 740 person-years. Previous screening status was a strong risk predictor of gynaecological malignancies (hazard ratio 1.69, P = 0.0027). Compared with the general screening population, women with a first diagnosis of cytological AGC had significantly increased ratios of developing gynaecological malignancies (17.85-fold for cervical cancer, 5.68-fold for uterine cancer, and 2.04-fold for ovarian cancer, P < 0.05). When compared with women aged <35 years, those in other age groups had a significantly higher risk of developing gynaecological cancers (age ≥60 years, hazard ratio 1.99, 95% CI 1.20-2.37, P = 0.016). CONCLUSIONS: Comprehensive evaluation for women with cytological AGC, including pelvic examination, ultrasonography, colposcopy, endocervical curettage, cervical biopsy and endometrial biopsy needs to be considered, especially for those with risk factors (i.e. >60 years old, lower educational status, previous Papanicolaou smear interval longer than 2 years, or no previous Papanicolaou smear).

Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine.

Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-gamma-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects.

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.

The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23-3.37) P=0.006) and OS (3.72 (1.64-8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76-125.60), P=0.013) or suboptimal (4.47 (1.83-10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.

A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

Synchronous primary cancers of the endometrium and ovary.

Simultaneous detection of malignancy in the endometrium and ovary represents an uncommon event. The objective of the study was to clarify the possible factors that influenced on the survival. From 1977 to 2005, totally 27 patients fulfilled the criteria and were included in the study. The medical records and the pathologic reports were reviewed. The histologic determination was followed by the World Health Organization Committee classification, and cancer stage was based on the staging system of the FIGO. The Kaplan-Meier survival analyses were generated and compared by the log-rank test. The incidence of synchronous primary endometrial and ovarian cancers was 3.3% in patients with endometrial cancer and 2.7% in patients with ovarian cancer. The mean survival in the group of similar histology (n= 15) was 63 months, and 48 months in the group of dissimilar histology (n= 12) (P= 0.63). The mean survival in the group of early stage (n= 21) was 68 months and 15 months in the group of advanced stage (n= 6) with statistic significance (P= 0.0003). However, the impact of adjuvant therapy on survival did not reach statistic significance (P= 0.15 for chemotherapy; P= 0.69 for radiotherapy). We conclude that the majority of the patients belonged to concordant endometrioid histology in endometrium and ovary, and it tends to be early stage and low grade with favorable prognosis. The stage had more significant influence on the survival than the histology. Adjuvant therapy should be given especially in patients with advanced stage although the optimal management remained to be determined.

Intracerebral hemorrhage as initial presentation of gestational choriocarcinoma: a case report and literature review.

Choriocarcinoma is the most malignant tumor of gestational trophoblastic neoplasia. It grows rapidly and metastasizes to the lung, liver, and, less frequently, to the brain. One rare case of metastatic cerebral choriocarcinoma with initial presentation of intracerebral hemorrhage is reported. A 40-year-old woman initially presented sudden onset of headache. Intracerebral hemorrhage resulting from ruptured pseudoaneurysm was suspected. Emergent surgery with excision of the pseudoaneurysms was performed. Metastatic choriocarcinoma was accidentally found with positive immunohistochemical staining of cytokeratin and beta subunit of human chorionic gonadotropin (beta-HCG). Choriocarcinoma with brain metastases was diagnosed. She then received chemotherapy with regimen of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine (EMACO). Elevated serum beta-HCG (30.3 mIU/mL) and new pulmonary lesions were noted by computed tomography 4 months after completion of EMACO. Salvage chemotherapy with etoposide, methotrexate, actinomycin-D, etoposide, and cisplatin (EMAEP) regimen was given. Seven months later after completion of EMAEP, two new pulmonary lesions were detected by positron emission tomography (PET) scan. So she received video-assisted thoracoscopic surgery with tumor excision. Pathologic report confirmed the diagnosis of lung metastases. The patient recovered well. She is free of disease for 12 months. The diagnosis of metastatic cerebral choriocarcinoma was only made by histopathology after craniotomy. Metastatic choriocarcinoma should be always in the differential diagnosis for women at childbearing age presenting with unexplained stroke-like symptoms. In addition, PET scan may be valuable in detecting occult metastatic lesions of choriocarcinoma.

Human papillomaviral load changes in low-grade squamous intraepithelial lesions of the uterine cervix.

To better predict risk of progression of low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix in women with human papillomavirus (HPV) infections, 294 baseline cervical specimens from women with LSILs were evaluated. Specimens were tested for HPV DNA using hybrid capture 2 (HC2) and PCR-reverse line blotting. 65 LSILs with HPV DNA types 16, 18, 52, or 58 were examined for physical status, E2/E6 ratio and viral load at two time points, along with patient age. Women with LSILs whose viral loads increased between baseline and 6 month follow-up had a 45% risk of developing HSIL (OR=7.6, 95% CI=1.9-29.4, P<0.01), as evaluated by real-time PCR and a 44% risk (OR=6.1, 95% CI=1.6-22.7, P<0.01), as evaluated by HC2. The two viral load measures correlated well (Person's coefficient, r=0.687, P<0.001). Such evaluations of viral load changes (increased or not increased) through repeat HPV DNA testing could predict progression of disease in LSIL cases of HPV types 16, 18, 52, and 58, which correlates to clinical implications.

Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity.

Alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. In this study, we used the replication-defective vaccine vector SIN replicon particles from a new packaging cell line (PCL) to develop SIN replicon particles encoding calreticulin (CRT) linked to a model tumor antigen, human papillomavirus type 16 (HPV16) E7 protein. The linkage of CRT to E7 in SIN replicon particles resulted in a significant increase in E7-specific CD8(+) T-cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated mice. SINrep5-CRT/E7 replicon particles enhanced presentation of E7 through the major histocompatibility complex (MHC) class I pathway by infecting dendritic cells (DCs) directly and pulsing DCs with lysates of cells infected by SINrep5-CRT/E7 replicons. Vaccination of immunocompromised (BALB/c nu/nu) mice with SINrep5-CRT/E7 replicon particles also generated significant reduction of lung tumor nodules, suggesting that antiangiogenesis may contribute to the antitumor effect of SINrep5-CRT/E7 replicon particles. Furthermore, SINrep5-CRT/E7 replicon particles generated long-term in vivo tumor protection effects and antigen-specific memory immunities. We concluded that the CRT strategy used in the context of SIN replicon particles facilitated the generation of a highly effective vaccine for cancer prophylaxis and immunotherapy.

Hypoxia-induced apoptosis in endothelial cells and embryonic stem cells.

BACKGROUND: To evaluate the influence of hypoxia and molecular events in endothelial and embryonic stem cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) and mouse embryoid body (EB) cells were subjected to hypoxic conditions for different time courses. DNA fragmentation assay, quantification of apoptotic cells by TUNEL assay measured by flowcytometry, and Western blot analysis for the molecular events of apoptosis were performed. RESULTS: DNA fragmentation could be identified under hypoxic conditions in HUVECs and mouse EBs. The DNA fragmentation increased when the hypoxic interval was extended. In situ internucleosomal DNA fragmentation-TUNEL assay also found that the percentages of apoptotic cells increased gradually in HUVECs and mouse EBs when the hypoxic interval was extended. Furthermore, the levels of expression of p53 and Bax both increased in hypoxic conditions. CONCLUSIONS: Hypoxia increases both HUVEC and mouse EB apoptosis, which is associated with increase in p53/Bax expression.