cel-mir-237 and its homologue, hsa-miR-125b, modulate the cellular response to ionizing radiation.

Elucidating the mechanisms involved in sensitizing radioresistant tumors to ionizing radiation (IR) treatments while minimizing injury to surrounding normal tissue is an important clinical goal. Due to their sequence-derived specificity and properties as gene regulators in IR-affected pathways, microRNAs (miRNAs) could serve as adjuvant therapeutic agents that alter cellular sensitivity to radiation treatment. To identify radiosensitizing miRNAs, we initially utilized the Caenorhabditis elegans vulval cell model, an in vivo system developed to study IR-dependent radiosensitivity as a measure of clonogenic cell death. We tested several candidate miRNA-deletion mutants post γ-irradiation and identified cel-mir-237 as a miRNA which when deleted caused animals to be more resistant to IR, whereas cel-mir-237 overexpressing strains were IR sensitive. In addition, wild-type animals downregulated cel-mir-237 levels post IR in a time-dependent manner. We identified jun-1 (JUN transcription factor homolog) as a novel target of cel-mir-237. Specifically, jun-1 transcript levels increased in wild-type animals post γ-irradiation, and loss of cel-mir-237 also resulted in higher jun-1 expression. As expected, loss of jun-1 resulted in IR sensitivity, similar to the phenotype of cel-mir-237 overexpressors. As miR-237 is the homolog of human miR-125, we validated our findings in MCF-7 and MDA-MB-231 breast cancer cell lines, which harbor lower hsa-miR-125b levels than normal human mammary epithelial cells (HMECs). Forced expression of hsa-miR-125b in these cells resulted in radiosensitivity, as seen by reduced clonogenic survival, enhanced apoptotic activity and enhanced senescence post IR. Finally, re-expression of c-JUN in MDA-MB-231 cells promoted radioresistance and abrogated miR-125-mediated radiosensitization. Our findings suggest that overexpression of cel-mir-237 and its homolog, hsa-miR-125b, functions as sensitizers to γ-irradiation in both a nematode in vivo model and breast cancer cells, and could potentially be utilized as an adjuvant therapeutic to enhance radiation sensitivity.

Nasopharyngeal tuberculosis.

Nasopharyngeal tuberculosis used to be a common disease in the upper aerodigestive system. Before 1920, 1.4 and 6.5 per cent of all adenoids and tonsils removed from asymptomatic patients were infected by tuberculosis. After the introduction of antituberculous chemotherapy and BCG vaccination, this disease was considered uncommon and sporadic cases were reported in the medical literature. Recently, tuberculosis has begun to increase again due to the high global HIV-infected rate and antituberculous drug resistance among these people. To describe and highlight the clinical features of this condition, fifteen Thai patients (7 males and 8 females) from the Department of Otolaryngology, Siriraj Hospital, Bangkok, Thailand were reviewed. Cervical lymphadenopathy was the most common presenting symptom in our series (93.34%), 11 of them were classified as primary nasopharyngeal tuberculosis and most had abnormal nasopharyngeal findings by mirror examination except 2 cases. Although all had histopathological confirmation of nasopharyngeal tuberculosis, sometimes problems occur in the diagnosis between this disease and nasopharyngeal carcinoma, which are also common among Oriental people in many of their clinical similarities. Therefore routine nasopharyngeal biopsy is considered justified and diagnostic.

Detection of Epstein-Barr virus DNA and HHV-6 DNA in tissue biopsies from patients with nasopharyngeal carcinoma by polymerase chain reaction.

A total of 34 tissue biopsies were collected from nasopharyngeal carcinoma (NPC) patients and 5 controls with non-NPC. Extracted DNA from tissue biopsies were analyzed for presence of specific gene sequences to EBV type A and type B, and HHV-6 by polymerase chain reaction (PCR). The different sequences of EBV type A and B were parts from the highly divergent forms of the EBV nuclear antigen 2 (EBNA 2). The PCR amplified products for EBNA 2A and EBNA 2B were 115 and 119 base pairs respectively whereas that of HHV-6 DNA was 776 base pairs. The results demonstrated that EBV DNA was detected in 32 of 34 cases (94.1%): 28 (82.3%) with type A, 2 (5.9%) with type B, and 2 (5.9%) with both types. EBV DNA of type A could be detected 1 (20%) of 5 controls. HHV-6 DNA was in 5 of 34 samples (14.7%) whereas HHV-6 DNA was not detectable in biopsy tissues from controls. The results show that in the NPC patient group, A type of EBV is predominant. Detection of HHV-6 DNA in patients group only might be resulted from reactivation of a latent infection or association with EBV-induction of NPC.

Prevalence of IgA specific antibodies to Epstein-Barr virus capsid and early antigens in nasopharyngeal carcinoma.

Ninety-one patients with nasopharyngeal carcinoma (NPC), and 164 age-matched healthy controls were tested for presence of IgA antibodies to Epstein-Barr virus capsid antigen (VCA) and early antigen (EA) in their sera by indirect ELISA using "EBViral DETECT" commercial test kit. IgA anti-VCA was found in 76 (83.5%) of NPC patients and 16 (9.8%) of the controls. Meanwhile, IgA anti-EA was found in 72 (79.1%) of NPC patients and 21 (12.8%) of the controls. In a parallel study by indirect immunofluorescence test (IIF), IgA anti-VCA was found in 77 of 91 (84.6%) NPC patients and 22 of 142 (15.5%) controls. The prevalence rates of anti-VCA as screened by ELISA and IIF were very similar suggesting that neither one of the two tests can be used alternatively depending on the purpose and facilities in each individual laboratory. IgA antibodies to VCA and EA were more prevalence in NPC patients than those in the controls, the finding which again supported the association between EBV and NPC as was suggested in many other reports.

Glossopharyngeal neuralgia and syncope secondary to neck malignancy.

Glossopharyngeal neuralgia with syncope, secondary to a malignant tumor in the neck, is an extremely rare condition. Dysman, et al more recently described a case in 1980. In this case, it was initially difficult to confirm the proper diagnosis since recurrent tumor was not able to be detected either clinically or radiographically. The patient was initially treated as syncope due to hypotension and bradycardia, but pacemaker therapy failed to control the cardiovascular abnormality. The administration of Dilantin, however, seems to improve the neuralgic pain and syncope. Due to a poor prognosis from the neck tumor recurrence, and patient refusal of further therapy, no surgical control of symptoms was attempted in this patient. This report is presented to make otolaryngologists aware of this condition.

Pharyngeal rhabdomyoma: a clinico-pathological study.

Adult extracardiac rhabdomyomas are rare with only 33 head and neck cases being reported in the world literature. In this select group, only nine cases have been found in the pharynx. We present two cases of pharyngeal rhabdomyoma focusing on the imaging findings, surgical approaches and more specifically on the histopathological and electron microscopic diagnosis of this interesting lesion. It is important to differentiate this tumor from other neoplasms, including granular cell myoblastoma, rhabdomyosarcomas, hamartomas, and fetal rhabdomyomas.