Biomedical subjects

Antti Mäkitie

Publications and source records attributed to Antti Mäkitie.

10 recordsLinked to original sources

PubMed2006

Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.

Mucoepidermoid carcinomas (MECs) of the salivary and bronchial glands are characterized by a recurrent t(11;19)(q21;p13) translocation resulting in a MECT1-MAML2 fusion in which the CREB-binding domain of the CREB coactivator MECT1 (also known as CRTC1, TORC1 or WAMTP1) is fused to the transactivation domain of the Notch coactivator MAML2. To gain further insights into the molecular pathogenesis of MECs, we cytogenetically and molecularly characterized a series of 29 MECs. A t(11;19) and/or an MECT1-MAML2 fusion was detected in more than 55% of the tumors. Several cases with cryptic rearrangements that resulted in gene fusions were detected. In fusion-negative MECs, the most common aberration was a single or multiple trisomies. Western blot and immunohistochemical studies demonstrated that the MECT1-MAML2 fusion protein was expressed in all MEC-specific cell types. In addition, cotransfection experiments showed that the fusion protein colocalized with CREB in homogeneously distributed nuclear granules. Analyses of potential downstream targets of the fusion revealed differential expression of the cAMP/CREB (FLT1 and NR4A2) and Notch (HES1 and HES5) target genes in fusion-positive and fusion-negative MECs. Moreover, clinical follow-up studies revealed that fusion-positive patients had a significantly lower risk of local recurrence, metastases, or tumor-related death compared to fusion-negative patients (P = 0.0012). When considering tumor-related deaths only, the estimated median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients. These findings suggest that molecularly classifying MECs on the basis of an MECT1-MAML2 fusion is histopathologically and clinically relevant and that the fusion is a useful marker in predicting the biological behavior of MECs.

Adult↗

PubMed2006

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Journal Article↗

PubMed2005

Elective neck treatment versus observation in patients with T1/T2 N0 squamous cell carcinoma of oral tongue.

A retrospective analysis of 80 patients treated for T1/T2 N0 squamous cell carcinoma of oral tongue was performed. The patients were divided into two groups according to the management of the neck: those without (n = 34) and those with elective neck treatment (n = 46). The two groups were compared with respect to overall survival (OS), disease specific survival (DSS), and recurrences. The incidence of occult nodal disease and the results of salvage treatment were analysed. There were significantly fewer regional recurrences in patients with elective neck treatment. Statistical differences in OS or DSS between the treatment groups were not found. Of all the patients with locoregional recurrence, 33% were salvaged. The incidences of occult metastasis for T1 and T2 tumours were 24% and 35%, respectively. The elective neck treatment resulted in better regional control. The results of salvage treatment were poor. The risk for occult cervical metastasis is high in patients with early tongue tumours and only carefully selected patients can be left without prophylactic neck treatment.

Adult↗

PubMed2005

Salivary gland cancer in Finland 1991--96: an evaluation of 237 cases.

CONCLUSION: In this material consisting of various salivary gland carcinomas, stage I, male gender and age were the most powerful predictors of patient outcome. OBJECTIVES: To retrieve the records of all salivary gland cancer (SGC) patients diagnosed in Finland between 1991 and 1996 and to evaluate the incidence, histological type and location of SGC, the treatment given and the outcome. MATERIAL AND METHODS: The records for all SGCs (n =286) diagnosed in Finland between 1991 and 1996 and reported to the Finnish Cancer Registry were retrieved. The histological re-evaluation and retrospective study involved 237 SGC patients. RESULTS: The study population consisted of 125 males and 112 females. The mean age was 59 years (males 61 years, females 58 years). Follow-up was at least 5 years. The commonest tumor location was the parotid gland (n = 152; 64%), followed by the minor salivary glands (n =46; 19%), the submandibular gland (n =38; 16%) and the sublingual gland (n = 1; 0.4%). The most frequent histological types of SGC were adenoid cystic carcinoma (n =65; 27%), mucoepidermoid carcinoma (n =45; 19%) and acinic cell carcinoma (n =41; 17%). Surgery, either alone or in combination with other treatment modalities, was used in 209 cases (88%). Radiotherapy was given to 136 patients (57%), 13 of whom (5%) did not undergo surgery. The 5-year overall survival rate was 56.5%, and for stages I-IV it was 78%, 25%, 21% and 23%, respectively (p <0.001; log-rank test). Of the commonest tumor types, the best 5-year relative survival rate was for patients with acinic cell carcinoma (96%), followed by those with mucoepidermoid (79%) and adenoid cystic carcinoma (74%).

Adolescent↗

PubMed2004

Biweekly escalated, accelerated hyperfractionated radiotherapy with concomitant single-dose mitomycin C results in a high rate of local control in advanced laryngeal and hypopharyngeal cancer.

The purpose of this study is to evaluate the efficacy of a dose-escalated, accelerated, and hyperfractionated radiotherapy schedule with a concomitant single dose of mitomycin C in the treatment of patients with advanced laryngeal or hypopharyngeal cancer. Twenty-one previously untreated patients with advanced squamous cell carcinoma (stage III, n = 6; stage IV, n = 15) were treated with a biweekly dose-escalated, accelerated, and hyperfractionated schedule up to a total dose of 74.4 Gy in 54 fractions over 5 weeks. A single dose of intravenous mitomycin C 10 mg/m2 was given on day 30. The median follow-up after treatment of surviving patients is 48 months (range, 28 to 61 months). All patients showed complete tumor control at the primary site when evaluated 2 months after chemoirradiation by laryngomicroscopy or hypopharyngoscopy and radiologic imaging (CT, MRI). Two laryngectomies were carried out after given therapy: 1 for residual cancer and 1 for suspected residual cancer. After a median follow-up of 43 months (range, 28 to 61 months), a local control rate of 70% and disease-free survival (DFS) rate of 60% were achieved in the laryngeal cancer patients; in patients with hypopharyngeal cancer, the corresponding figures were 64% (82% after salvage surgery) and 36%. The results are promising and warrant comparison with other chemoradiotherapy regimens.

Adult↗

PubMed2003

Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck.

Fresh-frozen biopsies were obtained from 61 patients at diagnosis of squamous cell carcinoma of the head and neck (HNSCC) for study of the prevalence and physical status of human papillomavirus (HPV) DNA. The frequency of HPV DNA and genotypes were determined by SPF10 PCR screening with a general probe hybridization and INNO-LiPA HPV genotyping assay. In addition, a single-phase PCR with primers FAP 59/64 and a nested PCR with primers CP 65/70 and CP 66/69 served to detect particularly cutaneous HPV types. By the sensitive SPF10 PCR and INNO-LiPA assay, 37 of 61 (61%) samples were positive for HPV. HPV-16 was the most frequently detected type (31 of 37, 84%). Multiple infections were found in 8 of 37 (22%) of the HPV-positive samples, and co-infection by HPV-16 and HPV-33 was predominant. No cutaneous HPV types were detected. Patients with HPV-positive tumors had similar prognosis as those with HPV-negative ones. Real-time PCR analysis of the HPV-16 positive samples indicated the presence of integrated (11 of 23, 48%), episomal (8 of 23, 35%) and mixed forms (4 of 23, 17%) of HPV DNA. The viral load of HPV DNA exhibited large variation. The median copy numbers of E6 DNA in tonsillar specimens were approximately 80,000 times higher than that in nontonsillar HNSCC ones. Patients with episomal viral DNA were more frequently found to have large (T3-T4) tumors at diagnosis than were those with integrated or mixed forms.

Adult↗

PubMed2002

O-glycans on human high endothelial CD34 putatively participating in L-selectin recognition.

Leukocyte traffic into lymph nodes and sites of inflammation is guided by L-selectin. Experiments performed in vitro and with gene-deleted mice suggest that CD34 recognizes L-selectin if decorated by 6-sulfo sialyl Lewis x (sLex) saccharides and the MECA-79 epitope. However, very little is known about glycosylation of human L-selectin ligands. We report here on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiles of N- and O-linked oligosaccharide fractions from human tonsillar endothelial CD34. All detected O-glycans were sialylated; some were also monosulfated or monosulfated and monofucosylated. If a given CD34-glycan may carry all requirements for L-selectin recognition, that is, both 6-sulfo-sLex and MECA-79 epitopes, only one O-glycan fraction, O-9, SA(2)Hex(3)HexNAc(3)- Fuc(1)(SO(3))(1), meets the criteria. A candidate structure is SAalpha2-3Galbeta1-4(Fucalpha1-3)(6-sulfo)GlcNAcbeta1-3Galbeta1-3(SAalpha2-3Galbeta1-4GlcNAcbeta1-6)GalNAc. However, if sulfo sLex glycans are supplemented with separate sulfated, nonfucosylated O-glycans, saccharides in O-6, O-8, or O-9, putatively carrying MECA-79 epitopes, could form multiglycan binding epitopes for L-selectin.

Animals↗

PubMed2002

Functional and morphological effects of styrene on the auditory system of the rat.

The effect of inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600, 300 or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks). Auditory sensitivity was tested prior to and after the exposure by auditory brain stem audiometry (ABR) at frequencies of 1.0, 2.0, 4.0 and 8.0 kHz. Inner ear morphological changes were studied by light- and electron-microscopy. Exposure to 600 ppm styrene caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed that 600 ppm styrene caused a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. The inner hair cells were usually intact. Exposure to lower styrene concentrations (100 and 300 ppm) caused no unequivocal functional deficit or hair cell damage. We conclude that there appears to be a concentration threshold for styrene ototoxicity in rats (between 300 and 600 ppm).

Administration, Inhalation↗

PubMed2002

Cervical metastasis of unknown origin: a series of 72 patients.

Cervical metastasis of unknown origin is still a challenging problem because of its relatively poor prognosis and the uncertainty regarding the primary site. We analyzed retrospectively all 72 patients with cervical metastases of unknown origin, diagnosed and treated between 1985 and 1995 in the five university hospitals of Finland in order to analyze survival rates and some prognostic and clinical factors of the disease. The most common sites where the primary tumor was found during follow-up or at autopsy were the lung (8%), the oral and pharyngeal region (7%) and the skin (6%). When the lower neck nodes (regions IV-VI) were affected, the primary tumor was significantly (p < 0.001) more often found from the subclavicular sites. The disease-specific 5-year survival rate was 32%. In multivariate analysis, nodal stage N2c or N3 [adjusted relative hazard of death (HR) 2.43], other metastases found at the time of treatment (HR 2.15) and age > 65 years (HR 2.12) were significantly associated with a poor prognosis. Median survival tended to be longer for patients treated with surgery combined with radiotherapy (39.9 months) compared with those treated with radiotherapy alone (16.8 months), but this difference was not statistically significant (p = 0.153).

Female↗

PubMed2002

Nasal cell micronuclei, cytology and clinical symptoms in stainless steel production workers exposed to chromium.

The objective of the present study was to determine whether workers in stainless steel production with low exposure to various forms of chromium show an increase in micronucleated nasal cells or an excess of nasal symptoms or disease. Altogether, 48 workers employed in a stainless steel production chain were studied, 29 of them in the steel melting shop with exposure to hexavalent chromium (Cr(6+)), 14 in the sintering and crushing departments of the ferrochromium plant with exposure to trivalent chromium (Cr(3+)) and five in the mine with exposure to chromite ore (Cr(3+)). Thirty-nine workers from the cold rolling mill, with very low exposure to chromium, served as referents. All the subjects were never smokers with a minimum of 14 years employment in the same department. There were no significant differences between the exposure groups and the referents regarding the mean frequency of centromere-negative or centromere-positive micronuclei (studied by pancentromeric fluorescence in situ hybridization), nasal diseases and symptoms or mucociliary clearance of the nasal cavity. No statistically significant differences in the incidence of cell atypia or inflammatory cells were detected between the exposed workers and the reference group, except for an increase in lymphocytes among the chromite ore workers. Anterior rhinoscopy indicated slight inflammatory changes in nasal mucosa and secretion more often in the Cr(6+) and Cr(3+) groups than in the referents, the Cr(6+)-exposed workers showing more livid or oedemic epithelium. In conclusion, the stainless steel production workers, with low exposure to dusts or fumes containing hexavalent or trivalent chromium, did not show clinical changes in the nasal mucosa or an increase in nasal cell micronuclei or symptoms of nasal diseases, except for slight changes in the nasal epithelium and secretion.

Adult↗