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ABSTRACT: OBJECTIVES: To review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors and immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed. RESULTS AND CONCLUSION: Vogt-Koyanagi-Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations. The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50 years, and females are affected more frequently, with a female:male ratio of 2:1 . The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia. Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes. VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established. Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS. Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.
Autoimmunity reviews 04/2013; · 6.37 Impact Factor
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Otolaryngology Head and Neck Surgery 01/2013; · 1.72 Impact Factor
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ABSTRACT: OBJECTIVES: The objective of our study was to review our current knowledge of the aetiopathogenesis of Cogan's syndrome, including viral infection and autoimmunity, and to discuss disease pathogenesis with relevance to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the aetiopathogenesis and pharmacotherapy of Cogan's syndrome from 1945 to 2012 were analysed. RESULTS AND CONCLUSIONS: Cogan's syndrome is a rare autoimmune vasculitis, and its pathogenesis is unknown. Infection, but primarily autoimmunity, may play contributing roles in the pathogenesis of this disease. It is characterised by ocular and audiovestibular symptoms similar to those of Meniere's syndrome. Approximately 70% of patients have systemic disease, of which vasculitis is considered the pathological mechanism. The immunologic theory is based on the release of auto-antibodies against corneal, inner ear and endothelial antigens, and of anti-nuclear cytoplasmic auto-antibodies (ANCA). Corticosteroids are the first line of treatment, and multiple immunosuppressive drugs have been tried with varying degrees of success. Tumour necrosis factor (TNF)-alpha blockers are a category of immunosuppressive agents representing a recent novel therapeutic option in Cogan's syndrome.
Autoimmunity reviews 07/2012; · 6.37 Impact Factor
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ABSTRACT: OBJECTIVES: To review our current knowledge of the etiopathogenesis of Bell's palsy, including viral infection or autoimmunity, and to discuss disease pathogenesis with respect to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the etiopathogenesis, clinical presentation, diagnosis and histopathology of Bell's palsy from 1975 to 2012 were analysed. RESULTS AND CONCLUSIONS: Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. It accounts for 60 to 75% of all cases of unilateral facial paralysis. The annual incidence of Bell's palsy is 15 to 30 per 100,000 people. The peak incidence occurs between the second and fourth decades (15 to 45years). The aetiology of Bell's palsy is unknown but viral infection or autoimmune disease has been postulated as possible pathomechanisms. Bell's palsy may be caused when latent herpes viruses (herpes simplex, herpes zoster) are reactivated from cranial nerve ganglia. A cell-mediated autoimmune mechanism against a myelin basic protein has been suggested for the pathogenesis of Bell's palsy. Bell's palsy may be an autoimmune demyelinating cranial neuritis, and in most cases, it is a mononeuritic variant of Guillain-Barré syndrome, a neurologic disorder with recognised cell-mediated immunity against peripheral nerve myelin antigens. In Bell's palsy and GBS, a viral infection or the reactivation of a latent virus may provoke an autoimmune reaction against peripheral nerve myelin components, leading to the demyelination of cranial nerves, especially the facial nerve. Given the safety profile of acyclovir, valacyclovir, and short-course oral corticosteroids, patients who present within three days of the onset of symptoms should be offered combination therapy. However it seems logical that in fact, steroids exert their beneficial effect via immunosuppressive action, as is the case in some other autoimmune disorders. It is to be hoped that (monoclonal) antibodies and/or T-cell immunotherapy might provide more specific treatment guidelines in the management of Bell's palsy.
Autoimmunity reviews 06/2012; · 6.37 Impact Factor
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ABSTRACT: Laryngotracheal stenosis is a complex condition that usually requires multiple procedures to restore physiological respiration. The aim of this study was to evaluate the percentage of decannulation compared to different or multiple surgical treatments. We retrospectively reviewed the charts of 70 patients treated between 1990 and 2005 for laryngotracheal stenosis of various aetiology: iatrogenic stenosis (n = 55), post-traumatic stenosis (n = 11) or other causes (autoimmune disease, n = 3; diphtheria, n = 1). In order to maintain laryngotracheal patency, a Montgomery Safe-T tube was used in all patients as a single dilation treatment or associated with endoscopic and/or open-neck surgery. Fifty-four of the 70 patients (77.1%) were eventually decannulated; 39 of these (72.2%) underwent 3 or fewer surgical procedures, showing a significant difference compared to patients who underwent more than 3 surgeries (p = 0.00002). A total of 257 surgeries were performed. Only seven of 54 patients (13%) were decannulated after more than 5 surgical procedures. Patients over 60 years of age and with a higher grade of stenosis showed a significantly lower success rate (p = 0.0017 and p = 0.007, respectively). There was no significant correlation between the rate of decannulation and gender, aetiology, site of stenosis or surgery. Patients undergoing dilation for laryngotracheal stenosis usually require multiple procedures. The T tube plays an important role in the treatment of this pathology. However, if the tracheostomy is not removed within 3 surgical interventions, the odds of decannulating the patient decrease significantly, and additional surgeries may be of questionable therapeutic benefit.
Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 04/2012; 32(3):182-8. · 0.86 Impact Factor
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ABSTRACT: OBJECTIVES: To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Meniere's disease from 1861 to 2011 were analysed. RESULTS AND CONCLUSIONS: Meniere's disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The aetiology and pathogenesis remain unknown. Proposed theories of causation include viral infections and immune system-mediated mechanisms. The immune response in Meniere's disease is focused on inner ear antigens. Approximately one-third of Meniere's disease cases seem to be of an autoimmune origin although the immunological mechanisms involved are not clear. The diagnosis of autoimmune inner ear disease is based either on clinical criteria or on a positive response to steroids. The antiviral approach has virtually eliminated the use of various surgical methods used in the past. Steroid responsiveness is high, and with prompt treatment, inner ear damage may be reversible. The administration of etanercept improves or stabilises symptoms in treated patients. Treatment of antiphospholipid syndrome can be directed toward preventing thromboembolic events by using antithrombotic medications. Only warfarin has been shown to be effective. Gene therapy can be used to transfer genetic material into inner ear cells using viral vectors and to protect, rescue, and even regenerate hair cells of the inner ear.
Autoimmunity reviews 01/2012; 11(10):731-8. · 6.37 Impact Factor
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ABSTRACT: OBJECTIVES: To review our current knowledge of the pathogenesis of sudden sensorineural hearing loss, including viral infection, vascular occlusion and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the pathogenesis of sudden sensorineural hearing loss from 1944 to 2010 were analysed. RESULTS AND CONCLUSIONS: Sudden sensorineural hearing loss is defined as hearing loss of 30 dB in three sequential frequencies over 3 days or less. It can be an isolated symptom or the presenting symptom of a systemic disease. The aetiology and pathogenesis remain unknown. Detailed investigation typically reveals a specific cause in about 10% of patients. Proposed theories of causation include viral infections, vascular occlusion and immune system-mediated mechanisms. A variety of therapies have been proposed based on the various proposed aetiologies.
Autoimmunity reviews 05/2011; 10(12):756-61. · 6.37 Impact Factor
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ABSTRACT: Esthesioneuroblastoma is an uncommon tumour. Due to its low incidence, this neoplasm is difficult to evaluate and its treatment remains a matter of debate. Although the role of post-operative radiation is relatively well-defined, little is reported regarding the role of radiotherapy as the only treatment modality. A retrospective analysis of the literature has been conducted. With reference to the treatment of esthesioneuroblastoma, 55 patients submitted only to radiotherapy have been selected from publications of internationally indexed literature between 1979 and 2006. According to the Kadish classification, 6 patients were in stage A, 12 in stage B, and 37 in stage C. Response to therapy for each stage was assessed. There was no evidence of disease in: 6/6 stage A patients with a median follow-up period of 103.6 months, 7/12 stage B patients with a median followup period of 120 months, and 7/37 stage C patients with a median follow-up period of 77.3 months. A total of 27 patients died due to tumour-related causes and 5 due to intercurrent disease, while 3 patients were alive with disease (local recurrence and cervical lymph node metastasis). In conclusion, esthesioneuroblastoma is a malignant tumour which grows both locoregionally and distantly. For this reason, despite the satisfying results regarding response to radiotherapy alone in stage A patients, irradiation should be used only in early lesions arising below the cribriform plate, whereas all other cases require aggressive and multimodal therapy.
Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 01/2009; 28(6):292-7. · 0.86 Impact Factor
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Archives of otolaryngology--head & neck surgery 08/2006; 132(8):881-882. · 1.92 Impact Factor
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ABSTRACT: Malignant tumours of the parotid gland represent a group of relatively rare lesions. The medical records of 363 patients with parotid swelling treated between 1974 and 2003 at the "G. Ferreri" Department of Otorhinolaryngology, "La Sapienza" University in Rome were retrospectively analysed. Clinical presentation, pre-operative investigations, surgical procedure, histopathology report, post-operative complications, and the oncological results of 19 patients who underwent extended radical parotidectomy for malignant neoplasm of the parotid gland are discussed. Extended radical parotidectomy, reserved for neoplasms in an advanced stage, involves the removal of the entire parotid gland, with sacrifice of the facial nerve and the resection en bloc of the adjacent structures affected by neoplastic infiltration, such as the temporal bone, the mandibular bone, the skin, blood vessels and nerves. In addition to this surgical treatment, a cycle of adjuvant radiotherapy is also necessary. The overall rate of survival at 10 years depends mainly on the histological characteristics of the tumour, and, in this series, is reported to be approximately 58%. These data indicate that total extended radical parotidectomy combined with post-operative radiotherapy, represents the best therapeutic approach with regard both to quality of life and life expectancy, in patients with an advanced stage of malignant neoplasm of the parotid gland.
Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 07/2005; 25(3):169-73. · 0.86 Impact Factor
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ABSTRACT: The aim of subtotal laryngeal surgery (Cricohyoidopexy = CHP and Cricohyoidoepiglottopexy = CHEP) is to create a simplified but functional neolarynx. The neolarynx permits the passage of air, the closure of the airway, and ensures phonation through the vibration of the cricoid and arytenoid mucosa; furthermore, it allows the recovery of swallowing, optimizing the closure of the neoglottis with the movement of the remaining arytenoids. The aim of the present study was to evaluate, on a long-term basis, the efficiency of the swallowing function comparing swallowing times in CHEP and CHP with and without functional neck dissection (FND).
A radiological study was conducted on 48 patients selected from a group of 253, who underwent subtotal laryngectomies at the "G. Ferreri" Department of Otorhinolaryngology, Audiology and Phoniatrics of the University of Rome "La Sapienza". The selection of the 48 patients was carried out based on the following criteria: type of surgery, date of surgery (follow up of at least 12 months), patients who were not treated with radiotherapy before or after surgery, patients who were also examined with fibrolaryngoscopy and videofluoroscopy, patients not affected by motor deficits involving phonatory and swallowing regions (stroke, lesions of the central nervous system), negative follow up (no evidence of disease). The parameters for evaluating the functional recovery were the times the nasogastric tube and tracheotomy tube were kept in place. The functional recovery times of the groups thus formed were compared to one another Through videofluoroscopy the authors evaluated oral transit times (OTT) and pharyngeal transit times (PTT) as parameters of deglutition.
The results consistently showed that swallowing time remains under one second as in individuals with normal swallowing functions.
The study of deglutition times, conducted at least 12 months after surgery, does not show any substantial differences between CHEP and CHP with reference to pharyngeal transit and oral transit times.
Revue de laryngologie - otologie - rhinologie 02/2004; 125(4):223-7.
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ABSTRACT: The prognostic significance of vessel quantification in human solid tumours is still debated, due to the presence of multiple factors modulating neoangiogenesis and the invasiveness of neoplastic cells. This study examined ten supraglottic squamous carcinomas, ten non-small cell lung carcinomas (three squamous, five bronchioloalveolar, two adenocarcinomas), and nine classic (NOS) invasive ductal breast carcinomas. The properties studied in these tumours were vascularity; the immunohistochemical distribution of adhesion molecules such as alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1, alpha6beta4, and ICAM-1 in endothelial cells; extracellular matrix proteins (ECMPs) and laminin alpha2 chain (merosin M chain) in basal membranes of vessels; and gene expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF2), and transforming growth factor beta1 (TGFbeta1), by in situ hybridization. Independently of tumour type and vascularity, laminin alpha2 chain expression was observed in the basal membranes of a limited proportion of vessels. In vitro experiments demonstrated laminin alpha2 chain expression mainly in early endothelial cell cultures, suggesting that laminin alpha2 chain expression in vivo can be considered a marker of early angiogenesis. Stromal and parenchymal vascularity was associated with laminin alpha2 chain expression in supraglottic carcinomas, whereas in the other tumours, laminin alpha2 chain-positive vessels were observed only in the stroma. In supraglottic carcinomas, VEGF-positive cells were mainly represented by neoplastic cells, whereas in the other tumours, the great majority of VEGF-positive cells were macrophages and fibroblasts. FGF2- and TGFbeta1-positive cells were macrophages and fibroblasts in all tumours. These observations suggest that in addition to the quantification and distribution of vessels, evaluation of their maturation may contribute to a better understanding of the role of angiogenesis in the growth and spread potential of solid tumours. In this regard, in supraglottic carcinomas, parenchymal angiogenesis seems to be regulated mainly by neoplastic cells, which may help to explain their high metastatic potential; in solid tumours of different histogenesis, different cells might be responsible for modulating tumour angiogenesis.
The Journal of Pathology 10/2001; 195(2):197-208. · 6.32 Impact Factor
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ABSTRACT: To evaluate the effectiveness of extended total laryngectomy for the treatment of recurrences of laryngeal cancer.
We conducted a retrospective clinical study of patients who had undergone extended total laryngectomy and were seen over a 15-year period. The follow-up period ranged from 3 to 15 years.
Academic tertiary referral medical center.
We observed 15 patients who were affected by a recurrence of laryngeal cancer that extended to the overlying soft tissue. All patients were male. The mean age was 61.5 years. Thirteen patients had previously undergone partial laryngeal surgery, and 2 patients had undergone radiation therapy, without success.
All patients underwent total laryngectomy extending to the soft tissue, including the overlying skin.
Five of the 15 patients died of local recurrence, and 1 patient died of massive postoperative hemorrhaging. An actuarial survival rate of 60% was observed at 5 years.
Total laryngectomy extending to the soft tissues seems to be an effective procedure for treating local recurrences of laryngeal cancer after partial laryngectomy or failure of radiation therapy.
Archives of Otolaryngology - Head and Neck Surgery 08/2001; 127(7):786-9. · 1.63 Impact Factor
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ABSTRACT: Ectopic lingual thyroid is an uncommon embryological aberration characterized by the presence of thyroid tissue located in a site different from the pretracheal region as in the normal. Lingual thyroid is the most frequent ectopic location of the thyroid gland, although its clinical incidence varies between 1:3000 and 1:10,000. We present the case of a 26-year-old woman who presented severe dysphagia caused by a mass located on the base of the tongue in the midline. An endoscopic partial removal of the ectopic tissue allowed her to rapidly regain her swallowing capacity. The literature regarding the incidence and diagnosis of lingual thyroid is reviewed and the possibilities of treatment discussed.
Dysphagia 02/2001; 16(3):220-3. · 1.39 Impact Factor
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ABSTRACT: A wide spectrum of lesions ranging from dysplasia to in situ carcinoma have to be considered when dealing with laryngeal precancerous conditions. Recently the concept of laryngeal intraepithelial neoplasia (LIN) was introduced.
A series of 259 consecutive cases of laryngeal keratosis was studied from 1976 to 1994. All patients entered the study after microlaryngoscopy and biopsy. Histologic diagnoses were subdivided into keratosis without dysplasia (KWD), with mild dysplasia (LIN 1), with moderate dysplasia (LIN 2), and with severe dysplasia or carcinoma in situ (LIN 3). The follow-up period ranged from 15 months to 19 years (mean, 101 months).
KWD had the best prognosis with the lowest recurrence rate (12.5%) after stripping of laryngeal mucous membrane. The recurrence rate after stripping was higher for LIN 1 (25%) and LIN 2 cases (68.7%). The recurrence rate after CO2 laser cordectomy was 16.6% for LIN 2 and 18.7% for LIN 3. The incidence of progression to infiltrative carcinoma was 4.19% for KWD, 7.14% for LIN 1, 21.42% for LIN 2, and 9.37% for LIN 3.
KWD and LIN 1 can be successfully treated by stripping the mucous membrane, close follow-up, and a change in smoking habits. On the contrary, LIN 2 and LIN 3 need a more aggressive therapeutical approach.
Head & Neck 02/2001; 23(1):42-7. · 2.40 Impact Factor
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Otolaryngology Head and Neck Surgery 12/2000; 123(5):661-2. · 1.72 Impact Factor
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ABSTRACT: We recorded the symptoms and disposition of every patient who visited the otorhinolaryngology emergency department at our hospital in Rome, Italy, during 1996. During that time, our ENT specialists saw 21,548 patients. Only 311 of these patients (1.4%) required immediate hospitalization, while another 2,391 patients (11.1%) received treatment and were released. The other 18,846 patients (87.5%) did not have any pathology or condition that qualified as an actual emergency, and they were examined and released, often with a prescription or instructions for home care. These patients could have easily been treated by a family physician. The fact that emergency care in Italy is rendered free of charge (unlike ambulatory care, for which fees are charged) provides patients with a strong incentive to misuse the system. Such overutilization drives up the cost of health care and stretches the capacity of the medical staff. Steps need to be taken to redirect patients who misuse emergency services to seek medical care in ambulatory care centers.
Ear, nose, & throat journal 04/2000; 79(3):155-8, 160. · 0.66 Impact Factor
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ABSTRACT: Head and neck carcinomas are characterized by tumor-infiltrating lymphocytes (TIL) producing cytokines. Adhesion molecules, extracellular matrix proteins (ECMPs), and cytokines regulate cell-cell and cell-ECMPs interactions. We investigated the distribution of these proteins to contribute to better understanding of their role in local tumor invasion and metastasis.
Distribution of integrins, laminin, type IV collagen, tenascin, and fibronectin was immunohistochemically evaluated in 13 supraglottis carcinomas. Cytokines gene expression was assessed by reverse-transcriptase-polymerase chain reaction (RT-PCR).
Neoplastic cells were alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1 positive. Normal and metaplastic epithelium was alpha5beta1 negative; the stroma of primary and metastatic tumors was tenascin and fibronectin positive. TGFbeta1 and IFNgamma gene expression was observed in the majority of tumors.
Because TGFbeta1 is known to down-modulate immune processes and to increase alpha2beta1, alpha5beta1, and tenascin distribution, we propose that their expression in neoplastic cells of supraglottis carcinoma might represent an immune-related process able to help tumor growth and progression.
Head & Neck 02/2000; 22(1):48-56. · 2.40 Impact Factor
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ABSTRACT: Head and neck squamous cell carcinomas are highly immunogenic tumors in which tumor-infiltrating lymphocytes (TIL) consist largely of CD4, Th1, and Th2 lymphocytes and a minor proportion of other immune effector cells, such as macrophages and B cells. Interleukin (IL)-12 release and antigen presentation from macrophages induce Thl and Th2 differentiation. Gene expression for IL-12, interferon (IFN)gamma, IL-4, and other cytokines was studied by reverse transcriptase-polymerase chain reaction in tissue sections from laryngeal carcinomas to evaluate the mechanisms of Th1 and Th2 lymphocyte differentiation. Local effects of cytokines were probed evaluating immunohistochemically the presence of inducible nitric oxide synthase positive tumor-infiltrating macrophages in 13 cases of laryngeal carcinomas. IL-12 gene expression was observed in five cases and that for IFNgamma in nine cases. These cytokines were coexpressed in four specimens. IL-4 and transforming growth factor-beta1 were detected in 5 and 11 cases, respectively. These findings show that IL-12, IFNgamma, IL-4, and IL-6 in laryngeal carcinomas have different patterns of gene expression, suggesting distinct pathways of Th1 and Th2 lymphocyte differentiation to indicate that their exogenous modulation might be utilized in adoptive immunotherapy.
Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 02/2000; 257(5):290-4. · 1.29 Impact Factor
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ABSTRACT: Tumor-infiltrating lymphocytes (TIL) consist of T helper 1 (Th1) and T helper 2 (Th2) cells producing interferon-gamma (IFN-gamma) and interleukin4 (IL-4), respectively. Interleukin-12 (IL-12) induces Th1 and Th2 differentiation. Therefore, IL-12, IFN-gamma, and IL-4 gene expression were evaluated by reverse transcriptase-polymerase chain reaction in carcinomas of the breast (n = 10), lung (n = 17), and larynx (n = 13) to investigate whether TIL activation is IL-12-related. IL-12 and IFN-gamma were codistributed in breast carcinomas, and IL-4 was demonstrated in three instances. IL-12 and IFN-gamma were detected in 15 and 13 lung carcinomas, respectively, and were codistributed in 11 cases; IL-4 was observed in 9 cases and was codistributed with IL-12 and IFN-gamma in 7 instances. IL-12 and IFN-gamma expression was observed in five and nine larynx carcinomas, respectively, and were codistributed in four cases; IL-4 was detected in five instances. These data indicate that breast, lung, and larynx carcinomas are characterized by different patterns of IL-12, IFN-gamma, and IL4 gene expression and suggest that Th1 activation may be induced, at least in part, by the neoplastic microenvironment.
Cancer Detection and Prevention 02/2000; 24(5):422-34. · 2.52 Impact Factor
