[Malignant gastrointestinal neuroectodermal tumor: a clinicopathological analysis of three cases].

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.

Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

MiR-424 Inhibits neuronal apoptosis in rats with cerebral infarction through regulating TGF-ß1/Smad3 signaling pathway.

It has been reported that micro ribonucleic acid (miR)-424 is an important molecule in cerebral ischemia. However, the precise mechanism of action and biological effects of miR-424 remain to be further explored. miR-424 mimic and miR-424 inhibitor were injected via the caudal vein in rats, and the effect of miR-424 expression on brain tissue damage induced by middle cerebral artery occlusion (MCAO) was detected. The miR-424 mimic-induced changes in genomic levels were detected via the gene chip assay, and the signaling pathways regulated by miR-424 and its potential targets were explored combined with target prediction. Then the effect of miR-424 mimic on apoptosis of PC12 cells induced by oxygen-glucose deprivation (OGD) was determined using Annexin V/PI assay. Finally, drosophila mothers against decapentaplegic protein 7 (Smad7) was overexpressed to further verify the mechanism of action of miR-424 mimic. Compared with that in the sham group, the expression of miR-424 in brain tissues significantly declined in the model group. The results of 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that the miR-424 mimic obviously reduced the cerebral infarction area and apoptosis level of brain tissues, while the miR-424 inhibitor obviously increased the cerebral infarction area and apoptosis level of brain tissues. It was found, using bioinformatics and KEGG enrichment analysis, that differentially expressed genes induced by miR-424 were significantly enriched in the transforming growth factor-ß (TGF-ß) signaling pathway. According to the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, the miR-424 mimic could evidently lower the expression of Smad7, thus activating the TGF-ß1/Smad3 signaling pathway. Overexpression of Smad7 could weaken the protective effect of miR-424 mimic on ischemic-hypoxic cells. Increasing the expression of miR-424 can inhibit Smad7 to activate the TGF-ß1/Smad3 signaling pathway, thereby exerting a protective effect against the brain tissue damage induced by MCAO.

Genetic Structure Analysis of Y-Chromosome STR and SNP in Population of Wujiang Area, Suzhou City.

ABSTRACT: Objective To analyze the genetic phenotypes of Y-chromosome STR and SNP in Han male population of Wujiang area, Suzhou City and explore the genetic structure of population of Wujiang area for further examination of regional-specific Y-SNP genetic markers ancestor haplogroups. Methods Blood samples of 472 Wujiang area Han males were randomly collected and genotyped by YfilerTM Plus PCR Amplification Kit. The allele frequencies and haplotype frequencies of each locus were obtained using the direct calculation method. Y-SNP haplogroups of each sample were estimated using Y-Predictor software and verified through experiments by amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results A total of 453 haplotypes were found in the 27 Y-STR genetic markers in 472 Han males of Wujiang area. The haplotype diversity （HD） was 0.997 696 93, among which, the highest gene diversity （GD） value was DYF387S1a/b （GD=0.953 1） and the lowest was DYS438 （GD=0.321 8）. Based on genotyping data of 27 Y-STRs and 472 samples, 132 haplogroups from C, D, N, O and Q, etc downstream Y-SNP haplogroups were estimated and then verified through experiments. Conclusion This study is based on Y-chromosome STR haplotypes, and predicts Y-SNP haplogroups by Y-Predictor software, then uses ARMS-PCR to verify. Y-SNP genetic markers were introduced to achieve precise analysis of the genetic structure of male families in population of three towns in Wujiang area.

Effect of chlorhexidine bathing on colonization or infection with Acinetobacter baumannii: a systematic review and meta-analysis.

Healthcare-associated infections (HAIs) caused by multi-drug-resistant Gram-negative bacteria (MDRGNB) have increased prevalence in intensive care units (ICUs). A common strategy to prevent HAIs is bathing patients with chlorhexidine gluconate (CHG). However, the effectiveness of CHG bathing against multidrug-resistant Acinetobacter baumannii (MDRAB) is still controversial. The aim of this study was to perform a systematic review and meta-analysis of the effectiveness of CHG bathing on Acinetobacter baumannii colonization and infection in the ICU setting. A systematic literature search of PubMed, EMBASE, Web of Science and CINAHL was performed from inception through to June 2018. Randomized controlled trials (RCTs), pre-post studies, or interrupted time series (ITS) studies were included. The numbers of patients with/without colonization or infection of A. baumannii in the experimental or control groups were extracted from each study. Quality assessment was performed by the related instruments of National Institute of Health. Pooled risk ratios (RRs) were calculated using the random-effects model. One RCT and 12 pre-post or ITS studies comprising 18,217 patients were included, of which 8069 were in the CHG bathing arm and 9051 in the control arm. CHG bathing was associated with a reduced colonization of A. baumannii (RR, 0.66; 95% confidence interval: 0.57-0.77; P<0.001). Chlorhexidine at 4% showed a better effect than 2% chlorhexidine (meta-regression P=0.044). CHG bathing was associated with a non-significant reduction of infection (pooled RR 0.41, 95% CI: 0.13-1.25). This study suggests that CHG bathing significantly reduces colonization of A. baumannii in the ICU setting. However, more trials are needed to confirm whether CHG bathing can reduce infections with A. baumannii.

Antibiotic management of acute pharyngitis in primary care.

The Centre for Health Protection of the Department of Health has convened the Advisory Group on Antibiotic Stewardship Programme in Primary Care (the Advisory Group) to formulate guidance notes and strategies for optimising judicious use of antibiotics and enhancing the Antibiotic Stewardship Programme in Primary Care. Acute pharyngitis is one of the most common conditions among out-patients in primary care in Hong Kong. Practical recommendations on the diagnosis and antibiotic treatment of acute streptococcal pharyngitis are made by the Advisory Group based on the best available clinical evidence, local prevalence of pathogens and associated antibiotic susceptibility profiles, and common local practice.

[Incidence and influencing factors of continuous positive airway pressure treatment-emergent central sleep apnea in the patients with obstructive sleep apnea syndrome at high altitude].

Objective: To investigate the incidence of treatment-emergent central sleep apnea (TE-CSA), the characteristics of demography and the influencing factors in patients with obstructive sleep apnea syndrome (OSAS) after initial continuous positive airway pressure (CPAP) titration at high altitude. Methods: Clinical data of 297 patients with OSAS which living in plateau areas (1 000 meters or more above sea level) were retrospectively analyzed in this study from January to December, 2015. All of these patients taken an overnight CPAP titration in the Sleep Medicine Center of First People's Hospital of Yunnan Province. They were classified as with TE-CSA group and non TE-CSA group according to the outcome of CPAP titration. Comparisons of demographic characteristic, parameters of polysomnography in CPAP titration night, lung function test and blood gas analysis were made between the two groups, respectively, and statistical analysis was carried. Results: The incidence of TE-CSA was 16.5% (49/297) after initial CPAP titration at high altitude, which was higher in male patients (18.2% vs 6.8%, P=0.061). The incidence of TE-CSA decreased with the increase of age and body mass index (BMI), and the decrease of resident altitude. Multivariate Logistic regression analysis showed that the resident altitude, mixed apnea index (MAI), forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) ratio, functional residual capacity (RV) and total lung capacity (TLC) ratio were the main factors affecting the occurrence of TE-CSA. Among them, the increase of resident altitude and MAI were risk factors [OR=1.16(1.02, 1.32), 1.05(1.01, 1.09)]. The increase of FEV(1)/FVC and RV/TLC were protective factors [OR=0.94(0.89, 0.98), 0.94(0.88, 0.99)]. Conclusion: The incidence of TE-CSA is high at high altitude area, and the increase of resident altitude and MAI are the risk factors for TE-CSA.

[Field investigation of occupational disease diagnosis in Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014: an analysis of 136 cases].

OBJECTIVE: To investigate the characteristics of 136 patients with occupational diseases, to summarize key techniques used in field investigation, and to provide a scientific basis for the development of standard operating procedures for field investigation of occupational disease diagnosis. METHODS: Field investigation and routine data analysis were performed to analyze the cases diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from January 2009 to December 2014. RESULTS: A total of 136 cases of occupational diseases were diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014, and there were 66 cases of leukemia, 18 cases of suspected occupational benzene poisoning, 12 cases of suspected occupational handarm vibration disease, and 11 cases of suspected pneumoconiosis. Of all these patients, 41.91% were engaged in at least three types of work, 70.59% were exposed to at least three types of chemicals, 25.74% experienced changes in technical processes and chemicals, and 47.06% had disputes on the chemicals they were exposed to during verification by both parties. Occupational hazard factors were detected. Most samples (358)were used to measure benzene concentration in workplace air, among which 11.7% had a benzene concentration of >6.00 mg/m(3)(exceeding standard), 13.41% had a benzene concentration of 3.26~6.00 mg/m(3), 75.42% had a benzene concentration of<0.03 to <3.25 mg/m(3). The samples of suspected occupational hand-arm vibration disease, suspected pneumoconiosis, and suspected occupational noiseinduced hearing loss had high overstandard rates (100%, 93.8%, and 83.3%, respectively). CONCLUSION: Field investigation of occupational disease diagnosis reveals large numbers of cases of leukemia, suspected occupational benzene poisoning, suspected occupational hand-arm vibration disease, and suspected pneumoconiosis. The key aspects of field investigation include confirmation of the history of occupational exposure, identification of occupational hazard factors, confirmation of the changes in technical processes and chemicals, detection of occupational hazard factors, sampling and analysis of raw materials, and epidemiological investigation of workers with the same type of work.

[The relevance between obstructive sleep apnea hypopnea syndrome andchronic obstructive pulmonary disease in China: A Meta-analysis].

Objective:To assess the correlation between obstructive sleep apnea hypopnea syndrome(OSAHS) and chronic obstructive pulmonary disease(COPD).Method: Databases such as Chinese Biomedical Literature Database, PubMed, Chinese Academic Journals full-text database, Wanfang Resource Database and Chongqing VIP have been searched to collect literatures about the relationship between OSAHS and COPD. The literature in conference proceedings and certain unpublished articles were also manually retrieved. RCT conformed to the condition was evaluated according to the standards of literature assessment, and the data has been extracted. The RevMan5.3 software was applied to carry out the same Metaanalysis.Result: Totally 19 articles were included, and Metaanalysis reveal that overlap syndrome(OS) patient's apnea hypopnea index is significantly higher than those of OSAHS patients［WMD=7.56, 95%CI（4.19,10.94）, P<0.01］; The LSaO2 of OS patients is significantly lower than OSAHS patients［WMD=-10.50, 95%CI(-11.58, -6.08),P<0.01］; OS patients' FEV1/FVC is significantly lower than COPD patients［WMD=4.65,95%CI（1.15,8.15）,P<0.01］.The results revealed that subgroup analysis according to the sample volume, age, body mass index(BMI) and FEV1/FVC between OS patients and OSAHS patients has heterogeneity, but when analysis with the score of ESS the heterogeneity does not exist. Further, the subgroup analysis according to the sample volume, BMI, AHI,LSaO2 and the time of Oxygen is lower than 90%(T90) those index between OS patients and COPD patients has heterogeneity, and the heterogeneity does not exist when subgroup is analyses with neck circumference. The funnel schema was nearly symmetry with little bias.Conclusion:The experimental results indicate that OSAHS is significantly related with COPD, and they may be the mutual risk factor for each other..

Stereotactic ablative radiotherapy with CyberKnife for advanced thymic carcinoma: a case report.

Thymic carcinoma is a rare but lethal mediastinal cancer. The optimal treatment for advanced thymic carcinoma is not yet established. This report is the first known of stereotactic ablative radiotherapy (sabr) with CyberKnife (Accuray, Sunnyvale, CA, U.S.A.) as definitive therapy for thymic carcinoma. The patient, a 70-year-old woman with thymic carcinoma, invasion into neighboring organs, and pleural metastases-underwent CyberKnife sabr at 40 Gy in 5 fractions for two lesions, one in the thymus and one in the right paraspinal pleura. After 61 months of observation, a partial response was observed in the irradiated fields. However, disease progression in the non-irradiated pleura was noted. The patient underwent salvage CyberKnife sabr for the four initially nonirradiated pleural lesions. Computed tomography images obtained 10 months after the salvage therapy revealed a partial response. The patient is living, with progression-free irradiated lesions and no radiation-related toxicity. CyberKnife sabr is feasible for patients who are unable to undergo either surgery or conventionally fractionated radiation therapy.

The adverse effects of long-term l-carnitine supplementation on liver and kidney function in rats.

Levo-Carnitine (l-carnitine) is widely used in health and food. This study was to focus on the adverse effects of 8-week oral supplementation of l-carnitine (0.3 and 0.6 g/kg) in female and male Sprague Dawley rats. l-carnitine reduced body and fat weights, as well as serum, liver, and kidney lipid levels in rats. Simultaneously, hepatic fatty acid ß-oxidation and lipid synthesis were disturbed in l-carnitine-fed rats. Moreover, l-carnitine accelerated reactive oxygen species production in serum and liver, thereby triggering hepatic NOD-like receptor 3 (NLRP3) inflammasome activation to elevate serum interleukin (IL)-1ß and IL-18 levels in rats. Alteration of serum alkaline phosphatase levels further confirmed liver dysfunction in l-carnitine-fed rats. Additionally, l-carnitine may potentially disturb kidney function by altering renal protein levels of rat organic ion transporters. These observations may provide the caution information for the safety of long-term l-carnitine supplementation.

Demineralized bone matrix as an alternative for mastoid obliteration and posterior canal wall reconstruction: results in an animal model.

HYPOTHESIS: This study was conducted to evaluate the use of Grafton human demineralized bone matrix as a graft material for mastoid cavity obliteration and canal wall reconstruction in an animal model. BACKGROUND: Canal wall down procedures in the treatment of cholesteatoma may result in a problematic mastoid cavity. Elimination of the mastoid cavity by obliteration or canal wall reconstruction can prevent or correct this problem. Many techniques and implant materials have been used for this application, yet no single material has proven to be ideal. METHODS: Athymic rats received tympanic bulla obliteration and lateral bulla wall reconstruction utilizing the Grafton Putty and Flex formulations, respectively. Wound healing was monitored twice a week. Auditory brainstem evoked responses were obtained 8 weeks after implantation. Nine weeks after implantation, the animals were killed, and histologic sections were prepared. A histologic bone formation score (range 0-4) was determined for each implant. RESULTS: Wound healing occurred without complication. Auditory brainstem response thresholds (average 23.5) fell within the normal range for all ears tested. The average histologic bone formation score for all implants was 3.7. The average scores for obliteration implants and wall reconstruction implants were 3.5 and 3.9, respectively. All wall reconstruction implants underwent partial or total collapse into the bulla. CONCLUSIONS: The high level of bone formation obtained by the use of Grafton implants in this study makes this material a promising resource for use in mastoid obliteration. The use of the material for canal wall reconstruction will likely require a sturdier preparation to prevent collapse into the mastoid cavity.

Frequent allelic imbalance and loss of protein expression of the DNA repair gene hOGG1 in head and neck squamous cell carcinoma.

Reactive oxygen species produced by aerobic cellular metabolism or through exposure to environmental carcinogens can cause oxidative DNA damage by generating DNA base lesions and strand breakage. Prime among these base lesions is the conversion of guanine to 8-oxoguanine. Among 20 or so oxidative DNA base lesions, 8-oxoguanine is the most abundant and is critical in terms of mutagenesis because it is capable of mispairing with adenine, which, if not sufficiently repaired, may lead to G:C to T:A transversion upon DNA replication. The gene encoding human 8-oxoguanine DNA glycosylase 1 (hOGG1), capable of excision repair of 8-oxoguanine, has been recently cloned, characterized, and mapped to the short arm of chromosome 3 (3p25-26), a region showing frequent loss of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC). In the present study, we developed a tissue microdissection approach designed for use with formalin-fixed, paraffin-embedded specimens which is capable of detecting and characterizing the hOGG1 allelic loss using two highly informative, intragenic single nucleotide polymorphisms. Among 45 cases of HNSCC, 18 cases were informative. We analyzed these 18 cases and found that 11 showed evidence of hOGG1 allelic loss. By immunohistochemical staining on a total of 71 HNSCC cases using a commercially available anti-hOGG1 antibody, we showed that hOGG1 gene expression was markedly suppressed in up to 38% of the cases. The frequent allelic imbalance and suppression of the hOGG1 gene thus imply that repair for oxidative DNA damages may be relevant in future studies on head and neck squamous carcinogenesis.

Expression of androgen receptor, epidermal growth factor receptor, and transforming growth factor alpha in salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare, highly aggressive neoplasm that primarily affects the major salivary glands. It is a distinct clinicopathological entity characterized by its morphologic resemblance to ductal carcinoma of the breast, a high incidence of regional lymph node metastasis, and distant dissemination. Frequent expression of androgen receptor (AR) but not estrogen receptor or progesterone receptor in SDCs suggests that SDC bears a close immunophenotypic homology with prostatic carcinoma. An AR-mediated autocrine growth pathway consisting of epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor alpha (TGF-alpha), has been implicated in the carcinogenesis of prostatic carcinoma. Androgens, in the presence of AR, mediate their mitogenic effects on prostatic cancer cells by up-regulating the transcriptional and translational activities of EGFR and TGF-alpha. Through an autocrine mode of action, TGF-alpha produced in the tumor cells binds to its receptor, EGFR, which is also expressed by these cells, resulting in a proliferative response. OBJECTIVE: To investigate whether a TGF-alpha/EGFR autocrine pathway is present in SDCs. DESIGN: Retrospective analysis of the expression of AR, EGFR, and TGF-alpha in 12 SDCs. SETTING: An academic medical center. RESULTS: Salivary duct carcinoma expresses AR, TGF-alpha, and EGFR in 11 (92%), 8 (67%), and 11 (92%) of 12 cases, respectively. CONCLUSION: An AR-mediated TGF-alpha/EGFR autocrine pathway may be implicated in the tumorigenesis of SDC.

[The thickness change and clinical significance of tunica intima and smooth muscle in artery after hydrolic dilation].

OBJECTIVE: To study the proliferation change of tunica intima and smooth muscle in artery after hydrolic dilation for potential clinical use. METHODS: Sixten adult New Zealand rabbits were randomly divided into 4 groups, named group A, B, C and D. Right carotid arteries of rabbits of those 4 groups were dilated by hydrolic dilation with different pressures with 0 kPa, 40 kPa, 80 kPa, and 120 kPa respectively. The arterial calibers, thickness of tunica intima and smooth muscle were analyzed by automatic medical photograph analyzer immediately, 1 week and 2 weeks later respectively. RESULTS: The arterial calibers in the experimental group were larger than those in control group after immediate hydrolic dilation and 1 week later (P < 0.01). At 2 weeks, the arterial calibers in group B and D has no significant difference compared to group A (P > 0.05), and those in group C were larger than that of group A (P < 0.01). There were no significant difference in thickness of tunica intima and smooth muscle between the experimental group and control group (P > 0.05) after immediate hydrolic dilation. At 1 and 2 weeks after dilation, there were no significant difference between group A and group B (P > 0.05), and those in group C and D were all larger than those in group A (P < 0.01). No obvious proliferation of tunica intima were observed in group B at 2 weeks after hydrolic dialation, but the proliferation of tunica intima could be observed in group C and D, especially in group D. CONCLUSION: Caliber of artery can be expanded by hydrolic dilation with higher pressure, but the proliferation of tunica intima and smooth muscle may be occurred in hydrolic dilation with higher pressure over 80 kPa, therefore it is safe to use hydrolic dilation with pressure no more than 40 kPa.

Neurilemmomas of the paranasal sinuses.

Within the head and neck region, neurilemmomas are rarely found in the nasal cavity or paranasal sinuses. A 70-year-old man presented with complaints of left-sided epiphora, rhinorrhea, epistaxis, and transient diplopia. Nasal endoscopy showed a large necrotic mass filling the left middle meatus. A computed tomography scan showed a large left ethmoid mass, with erosion of the medial wall of the orbit and the anterior cranial base. Multiple biopsies were nondiagnostic. Complete excision of the tumor was performed with endoscopic techniques. Small dural defects were repaired with a middle turbinate mucosal flap. Postoperatively, the patient was treated with nasal packing and a lumbar spinal drain. Final pathology showed a benign neurilemmoma. There has been no evidence of recurrence or cerebrospinal fluid leakage in follow-up. A review of the literature shows a similar presentation of patients with neurilemmomas of the paranasal sinuses. Bony destruction and intracranial extension is viewed. Lack of encapsulation and locally destructive growth in an otherwise histologically typical neurilemmoma should not suggest malignant potential. Many benign tumors of the paranasal sinuses with bone destruction may be removed by using endoscopic techniques.

Genetic alterations in head and neck cancer: interactions among environmental carcinogens, cell cycle control, and host DNA repair.

Head and neck squamous cell carcinomas (HNSCC) arise as a consequence of cumulative genetic changes brought about by continued exposure to carcinogens associated with tobacco and alcohol use, influenced by viral agents such as human papillomaviruses, in a background of acquired or heritable genetic susceptibility. The presence of widespread genomic instability in HNSCC, such as cytogenetic aberrations, allelic imbalance/loss of heterozygosity, and microsatellite instability, suggests that there is an imperfection in the host DNA repair machinery. Genomic instability with progressive accumulation of detrimental genetic alterations appears to be dependent upon a circuitous interaction between the environmental genotoxic insults and the host DNA repair machinery, the functional integrity of which is governed by the proper cell cycle control and host DNA repair capacity. Thus, it can be hypothesized that continued exposure to environmental carcinogens (ie, longstanding history of smoking and drinking), loss of proper cell cycle control (eg, inactivation of p53 or p16 tumor suppressor genes or amplification of the proto-oncongene cyclin D1), and impaired DNA repair capacity (both inherited and acquired) are prerequisites in head and neck carcinogenesis.

Expression of fas ligand in metastatic prostatic carcinoma: suggestive of possible clonal expansion of subpopulation with metastatic potential.

Fas ligand (FasL) is a type II transmembrane tumor necrosis factor family protein, known to trigger apoptosis in cells that bear the FasL receptor, Fas. The authors found that normal prostate, benign hyperplasia, and most prostatic carcinoma cells at the primary site did not express FasL, whereas metastatic prostatic carcinoma cells in lymph nodes and bone marrow displayed almost uniform, immunohistochemically detectable, FasL expression. However, small foci of FasL-positive prostatic carcinoma cells amid a vast majority of FasL-negative tumor cells were noted at the primary sites in patients with distant metastases. Analysis of the FasL gene and its mRNA by polymerase chain reaction and reverse transcriptase-polymerase chain reaction, respectively, suggested that the expression of immunohistochemically detectable FasL in metastatic tumor cells was not due to mutation in the FasL gene with resulting overexpression. Further, FasL expression was detectable in the acinar epithelial cells of prostates with morphologic atrophic changes, suggesting that FasL also plays a role in the physiologic apoptosis process of noncancerous prostate. The current data suggest that a subpopulation of prostate carcinoma cells clonally expresses FasL, and this subpopulation may have metastatic potential. Evaluation of FasL expression in the primary tumor thus may provide a useful parameter for predicting metastatic potential of the tumor.

[Expression and characterization of two kinds of recombinant snake neurotoxins].

The cDNA encoding the precursor of cobrotoxin was cloned from the venom gland of the Chinese continental cobra (Naja naja atra) by RT-PCR. Its deduced amino acid sequence analysis showed that the mature protein was identical to that identified from the Taiwan cobra (Naja naja atra) by protein sequencing technique. The cDNA encoding the mature protein was then subcloned into the expression vector pMAL-P2. The gene of CM11, which was formed by ligation of the fragments of the synthetic oligonucleotides, was also cloned into the expression vector pMAL-P2. After induction of IPTG, both of the neurotoxins were overexpressed as soluble fusion proteins which were confirmed by SDS-PAGE and western blotting. The expressed fusion proteins was purified by sepharose 6B-amylose affinity chromatography and DEAE-sepharose FF chromatography. Both of the recombinant proteins achieved after digestion by factor Xa showed the in vivo toxicity.

Expression of androgen receptor and prostatic specific markers in salivary duct carcinoma: an immunohistochemical analysis of 13 cases and review of the literature.

Salivary duct carcinoma (SDC) is an uncommon, pathologically distinct entity characterized by its morphologic resemblance to ductal carcinoma of the breast and highly aggressive behavior. Approximately two thirds of patients die within 4 years of initial diagnosis despite aggressive, combined surgical resection and radiotherapy. Review of the literature indicates that androgen receptor (AR), a marker frequently detected in prostatic carcinoma, is expressed in over 90% of SDCs, whereas two common breast carcinoma markers, estrogen and progesterone receptors (ER and PR), are expressed in only 1.3% and 6% of the tumors, respectively, by immunohistochemistry. This hormonal profile suggests that SDC, in contrast to its histiologic similarity to ductal carcinoma of the breast, is immunophenotypically more related to prostatic carcinoma. To substantiate this hypothesis, we performed immunohistochemical staining of 13 cases of SDC for the presence of AR and two prostatic markers, prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Our results showed multifocal, scattered, moderate immunostaining for PAP and diffuse, moderate immunostaining for PSA in seven (58.3%) and two (16.7%) cases, respectively. These results create a potential diagnostic challenge to surgical pathologists who are dealing with a metastatic adenocarcinoma of AR+/PSA+/-/PAP+/- phenotype, particularly in male patients of unknown primary. Metastatic salivary duct carcinoma should be given serious thought if clinical investigation fails to reveal a prostatic primary. The immunophenotypic homology that exists between SDC and prostatic carcinoma also suggests that antiandrogen therapy as used in the treatment of prostatic carcinoma might be beneficial in patients with metastatic SDC when all other conventional modalities fail.