Epidemiologic survey of head and neck cancers in Korea

Head and neck cancers have never been systematically studied for clinical purposes yet in Korea. This epidemiological survey on head and neck cancer patients was undertaken from January to December 2001 in 79 otorhinolaryngology resident-training hospitals nationwide. The number of head and neck cancer patients was 1,063 cases in the year. The largest proportion of cases arose in the larynx, as many as 488 cases, which accounted for 45.9%. It was followed by, in order of frequency, oral cavity (16.5%), oropharynx (10.0%), and hypopharynx (9.5%). The male:female ratio was 5:1, and the mean age was 60.3 yr. Surgery was the predominant treatment modality in head and neck cancers: 204 (21.5%) cases were treated with only surgery, 198 (20.8%) cases were treated with surgery and radiotherapy, 207 cases (21.8%) were treated with combined therapy of surgery, radiotherapy, and chemotherapy. Larynx and hypopharynx cancers had a stronger relationship with smoking and alcohol drinking than other primary site cancers. Of them, 21 cases were found to be metastasized at the time of diagnosis into the lung, gastrointestinal tract, bone, or brain. Coexisting second primary malignancies were found in 23 cases. At the time of diagnosis, a total of 354 cases had cervical lymph node metastasis accounting for 42.0%.     

The characteristics of human papillomavirus DNA in head and neck cancers and papillomas

AIM: To determine the prevalence, type, physical state, and viral load of human papillomavirus (HPV) DNA in cases of head and neck cancer and recurrent respiratory papillomatosis (RRP). METHODS: The prevalence and type of HPV DNA was determined in 27 fresh frozen tissue specimens from patients with head and neck cancers and 16 specimens from 10 patients with RRP by MY09/MY11 and GP5+/GP6+ nested polymerase chain reaction (PCR) and subsequent restriction enzyme cleavage. The physical state of HPV DNA was analysed by E1, E2, and E1E2 specific PCRs and Southern blot hybridisation (SBH). RESULTS: HPV DNA was detected in 13 of 27 cancers and 10 of 10 papillomas. Both low risk HPV-6 and HPV-11 and high risk HPV-16 were present in cancers in low copy numbers, whereas papillomas exclusively harboured low risk HPV-6 and HPV-11. E1E2 PCRs failed to determine the physical state of HPV in cancers except one case where HPV-6 DNA was integrated. In contrast to cancers, all papillomas showed the episomal state of HPV DNA and a relatively higher viral load. CONCLUSIONS: Based on the prevalence, type, physical state, and copy number of HPV DNA, cancers and papillomas tend to show a different HPV DNA profile. The 100% positivity rate of low risk HPV types confirms the role of HPV-6 and HPV-11 in the aetiology of RRP.     

人乳头瘤病毒感染与头颈癌关系的研究进展

人乳头瘤病毒(HPV)与部分头颈癌的发病相关,HPV阳性头颈癌在流行病学、病因学、病理学、分子特征等方面与HPV阴性头颈癌存在明显差异.并且头颈癌中HPV基因组存在形式及转录活性对头颈癌的预后都会产生影响.生物信息手段分析头颈癌中HPV的存在形式成为热点,而采集患者脱落细胞进行HPV检测是另一种简单易行的检测方法.     

Hit and run oncogeneses in head and neck cancers requires greater investigation

Head and neck cancers are unique in so far that two major oncogenic viruses, Epstein Barr virus (EBV) and Human papillomavirus (HPV) infect adjacent anatomy and cause nasopharyngeal and oropharyngeal cancers, respectively. Dominant recognized carcinogens are alcohol and tobacco but some head and neck cancers have been found to have mixed carcinogens (including betel leaf, areca nuts, slaked lime, viruses, etc.) involved in their oncogenesis and conversely, groups of patients with unknown or less dominant carcinogens involved in their development. These cancers may have had viral involvement in the past but then lost most of their viral nucleic acids (be they DNA and/or RNA) below a detection threshold, thus rendering them virus-negative. Some of these virus-negative tumors appear to have mutagenic signatures associated with virus-positive cancers,  for example, from the APOBEC defense mechanism which is known to mutate viral nucleic acids as well as cause collateral damage to host DNA, with subsequent development of strongly viral prejudiced mutational signatures. These mechanisms are likely to be less efficient at oncogenesis than traditional EBV and HPV oncogenes directly driving mutagenesis, thus accounting for the smaller frequencies of these cancers found. More profound investigations of these unusual tumors are warranted to dissect out these mechanistic pathways.     

肱骨头缺损程度与肩关节稳定性影响的研究

目的　探讨肱骨头缺损对肩关节稳定性影响的程度。 方法　8例16侧肩关节的肱骨头后方缺损程度分别设成全部肱骨头的1/8、2/8、3/8、4/8,各4侧标本。检测指标分别为45°和90°外展、40°内旋、中立位、40°外旋等5个指标。检测个缺损的肱骨头由小到大各个角度的外展、内外旋同时作用的结果。肱骨头在各个合力作用下缓慢向前外侧推动,直到脱位。记录肱骨头所移动的距离（distance of 　dislocation,DD）,并作为基本分析数据。 结果 外展角度比较,DD无显著性差异。但外旋40°与中立为和40°内旋比较,有显著性差异。在3/8缺损组,外旋40°外展90°时,DD明显减小。4/8组,外展90°与中立位时,DD均明显减小。而内旋40°者,各组DD未见明显减小。 结论 肱骨头缺损3/8时,当肩关节外展外旋时,肩关节稳定性下降;而当肱骨头缺损4/8时,肩关节中立位和外旋位均会发生关节不稳。     

The relationship between role preferences in decision-making and level of psychological distress in patients with head and neck cancer

Objective

Is there a relationship between decision-making preferences and psychological distress?

Myeloid progenitor cells mediate immune suppression in patients with head and neck cancers.

Patients with squamous cell carcinomas of the head and neck (HNSCC) have profound defects in their immune defenses. We have shown that among the mechanisms that contribute to this immune dysfunction are immune inhibitory CD34+ progenitor cells, whose levels become elevated in the peripheral blood and within the tumor tissue. One goal of our studies is to overcome the immune inhibitory activities of tumor-induced CD34+ progenitor cells by stimulating their differentiation into cells, such as dendritic or monocytic cells, that can stimulate immune reactivity to autologous cancer. Results of in vitro analyses with CD34+ suppressor cells of HNSCC patients and of in vivo studies in animal tumor models have shown the capacity of tumor-induced CD34+ cells to differentiate into cells that phenotypically resemble monocytic or dendritic cells. Whether these cells can differentiate into dendritic cells in HNSCC patients is currently being tested. Less clear is whether the pathway by which the tumor-induced CD34+ cells differentiate will result in cells having the full capacity to function as potent stimulators of immune reactivity to autologous tumor.     

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers

The results of radiation therapy alone in locally advanced head and neck cancers are dismal with 5 year locoregional control rates not exceeding 15%. The addition of concomitant chemotherapy with cisplatin and more recently carboplatin has shown promising results. Twenty patients of inoperable stage III and IV oral or oropharyngeal cancers were treated with concomitant chemoradiation with carboplatin 300 mg/m2 i.v. on days 1, 21 and 42 of radiation therapy. Twelve (60%) patients had a complete remission. Thirteen patients were alive at a median follow up of 11 months. The treatment was well tolerated with only 2 patients requiring treatment interruptions for mucositis. Longer follow up would reveal any improvement in overall survival. The relative ease with which carboplatin/RT was administered suggests that other agents might be added as well.     

Tumor delineation using PET in head and neck cancers: threshold contouring and lesion volumes

Tumor boundary delineation using positron emission tomography (PET) is a promising tool for radiation therapy applications. In this study we quantify the uncertainties in tumor boundary delineation as a function of the reconstruction method, smoothing, and lesion size in head and neck cancer patients using FDG-PET images and evaluate the dosimetric impact on radiotherapy plans. FDG-PET images were acquired for eight patients with a GE Advance PET scanner. In addition, a 20 cm diameter cylindrical phantom with six FDG-filled spheres with volumes of 1.2 to 26.5 cm3 was imaged. PET emission scans were reconstructed with the OSEM and FBP algorithms with different smoothing parameters. PET-based tumor regions were delineated using an automatic contouring function set at progressively higher threshold contour levels and the resulting volumes were calculated. CT-based tumor volumes were also contoured by a physician on coregistered PET/CT patient images. The intensity value of the threshold contour level that returns 100% of the actual volume, I(V100), was measured. We generated intensity-modulated radiotherapy (IMRT) plans for an example head and neck patient, treating 66 Gy to CT-based gross disease and 54 Gy to nodal regions at risk, followed by a boost to the FDG-PET-based tumor. The volumes of PET-based tumors are a sensitive function of threshold contour level for all patients and phantom datasets. A 5% change in threshold contour level can translate into a 200% increase in volume. Phantom data indicate that I(V100) can be set as a fraction, f, of the maximum measured uptake. Fractional threshold values in the cylindrical water phantom range from 0.23 to 0.51. Both the fractional threshold and the threshold-volume curve are dependent on lesion size, with lesions smaller than approximately 5 cm3 displaying a more pronounced sensitivity and larger fractional threshold values. The threshold-volume curves and fractional threshold values also depend on the reconstruction algorithm and smoothing filter with more smoothing requiring a higher fractional threshold contour level. The threshold contour level affects the tumor size, and therefore the ultimate boost dose that is achievable with IMRT. In an example head and neck IMRT plan, the D95 of the planning target volume decreased from 7770 to 7230 cGy for 42% vs. 55% contour threshold levels. PET-based tumor volumes are strongly affected by the choice of threshold level. This can have a significant dosimetric impact. The appropriate threshold level depends on lesion size and image reconstruction parameters. These effects should be carefully considered when using PET contour and/or volume information for radiotherapy applications.     

Differential microRNA expression and identification of putative miRNA targets and pathways in head and neck cancers

MicroRNAs (miRNAs) are small noncoding RNAs that involved in various cancer-related cellular processes. Diverse studies on expression profiling of miRNAs have been performed and the data showed that some miRNAs are up-regulated or down-regulated in cancer. Until now, there are no data published on the miRNA expression in head and neck cancers from Malaysia. Hence, this study aimed to investigate potentially crucial miRNAs in head and neck cancer patients from Malaysian populations. A global miRNA profiling was performed on 12 samples of head and neck cancer tissue using microarray analysis followed by validation using real-time RT-PCR. Microarray analysis identified 10 miRNAs that could distinguish malignant head and neck cancer lesions from normal tissues; 7 miRNAs (hsa-miR-181a-2*, hsa-miR-29b-1*, hsa-miR-181a, hsa-miR-181b, hsa-miR-744, hsa-miR-1271 and hsa-miR-221*) were up-regulated while 3 miRNAs (hsa-miR-141, hsa-miR-95 and hsa-miR-101) were down-regulated. These miRNAs may contribute in a simple profiling strategy to identify individuals at higher risk of developing head and neck cancers, thus helping in the elucidation of the molecular mechanisms involved in head and neck cancer pathogenesis.     

TRIB1与癌症相关性的研究进展

TRIB1是果蝇Tribbles蛋白的一个同源蛋白.在人体内,TRIB1缺乏催化结构域,因此无激酶活性,但可作为支架蛋白,参与蛋白与蛋白之间的相互作用.TRIB1已被证实在多种癌症中发挥作用,包括急性髓细胞白血病、前列腺癌、卵巢癌、结直肠癌等.此文就TRIB1的功能与特点以及在癌症方面的研究进展加以综述.     

DNA promoter hypermethylation contributes to down-regulation of galactocerebrosidase gene in lung and head and neck cancers

Galactocerebrosidase (GALC) is a lysosomal enzyme responsible for glycosphingolipids degradation byproducts of which are important for synthesis of apoptosis mediator ceramide. Reduced expression of GALC has been identified in human malignancies; however, molecular mechanisms underlying down-regulation of GALC expression in cancer remain unknown. We performed methylation and expression analysis on GALC gene in a panel of head and neck cancer (HNC) and lung cancer cell lines, attempting to understand the regulation of GALC in human cancer. QRT-PCR and western blot analysis were performed to detect the expression of GALC in HNC. Bisulfite DNA sequencing and real-time qMSP were used to detect the methylation of GALC in HNC and lung cancer cell lines. 5aza-dC treatment assay was used to analysis the functional effect of GALC methylation on GALC expression in HNC. Reduction or complete absence of GALC expression was observed in more than a half of the tested HNC cell lines (8/14). 7 out of 8 cell lines with down-regulated expression harbored heavy CpG island methylation, while all cell lines with abundant expression of the gene contained no methylation. Hypermethylation was also found in primary HNC tumor tissues and lung cancer cell lines whereas absent in normal oral mucosa tissues. Demethylating treatment demonstrated that 5aza-dC significantly restored GALC expression in cell lines with methylated promoter while showed no effect on cell lines without promoter hypermethylation. Our findings for the first time demonstrated that promoter hypermethylation contributed to down-regulation of GALC Gene, implicating epigenetic inactivation of GALC may play a role in tumorigenesis of cancer.     

The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers

Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer.     

Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers

CD44, a well-documented cell surface receptor, is involved in cell proliferation, migration, signaling, adhesion, differentiation and angiogenesis, which are important properties for normal and cancerous cell function. We recently developed particle clusters coated with hyaluronan (termed gagomers; GAG), and showed that they can deliver the insoluble drug paclitaxel directly into CD44-over-expressing tumors in a mouse tumor model. Here, we tested primary head and neck cancers (HNC) and normal cells taken from the same patient, and found that although CD44 expression in both types of cells was high, GAGs bind only to the cancerous cells in a selective manner. We next formulated the anti cancer agent mitomycin C (MMC) in the GAGs. MMC-based chemoradiation is a potential treatment for HNC, however, due to patient's toxicity, MMC is not part of the standard treatment of HNC. MMC encapsulation efficiency was about 70% with a half-life drug efflux of 1.2 ± 0.3 days. The Ex vivo study of the targeted MMC-GAG showed significant increase in the therapeutic effect on HNC cells (compared to free MMC), while it had no effect on normal cells taken from the same patient. These results demonstrate the specificity of the nanovectors towards head and neck cancers, which might be applicable as future therapy to many CD44-expressing tumors.     

一种新的头颈部常规放疗立体定位装置及其使用方法

目的：介绍一种新的自行 地头颈部肿瘤常规放射治疗的立体定位装置及其使用方法。方法：本装置为附加在患者体外的一个带有三维坐标系的框架结构,在ＣＴ影像上构成建立坐标系的标志呈“Ｖ”型,采用义量法确定扫描范围内任一点相对于该坐标系的空间位置。据此可求出靶中心坐标、不同Ｇａｎｔｒｙ角野的大小及形状等各项放疗参数。应用本装置和方法对一模拟靶的各放疗参数进行确定,并应用模拟定位机对其进行验证。结果：通过本装置     

Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers

The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose–response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless.Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure.