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Biomedical subjects

J C Nesbitt

Publications and source records attributed to J C Nesbitt.

At least 19 recordsLinked to original sources
PubMed2001

Superior vena cava syndrome.

Lung cancer is the most common cause of superior vena cava syndrome (SVCS) and requires timely recognition and management. The syndrome is rarely an oncologic emergency in the absence of tracheal compression and airway compromise. Treatment depends on the etiology of the obstructive process. Treatment should also be individualized and should not be undertaken until a diagnosis is obtained. Most patients with SVCS secondary to lung cancer can be treated with appropriately directed chemotherapy or radiotherapy. With the refinement of endovascular stents, percutaneous stenting of the SVC is being increasingly used as primary treatment modality. Thrombotic occlusion can be treated with appropriate lytic agents. In rare circumstances, surgical decompression can be performed; bypass or replacement of the SVC results in immediate improvement in the majority of cases and can be accomplished with low morbidity.

Anticoagulants↗
PubMed2001

Symptomatic persistent post-coronary artery bypass graft pleural effusions requiring operative treatment : clinical and histologic features.

BACKGROUND: More than 85% of patients develop pleural effusions after coronary artery bypass grafting (CABG). Although the majority resolve spontaneously, post-CABG effusions can persist. The cause of these persistent effusions is unknown, and the histology of the pleural changes has seldom been reported. OBJECTIVES: To describe the patient characteristics and pathologic condition of the pleural tissues in patients with persistent post-CABG effusions. SUBJECTS: Eight patients with persistent post-CABG effusions who underwent thoracoscopy or thoracotomy over a 2-year period by one thoracic surgeon. These eight patients were selected as having undergone CABG > 2 months before their thoracic surgery and had no other identifiable causes of effusion. RESULTS: The median time from CABG to pleural surgery was 132 days (range, 74 to 2,258 days). The median left ventricular ejection fraction was 57% (range, 15 to 70%). All patients were dyspneic and had large (> or = 25% of the hemithorax) effusions on chest radiograph. All effusions persisted after two or more thoracenteses. Pleural effusion was left sided in three patients and bilateral in five patients. Pleural fluid was characterized by lymphocytosis (82 to 99%). Four of the eight patients had a visceral peel and trapped lung requiring decortication. Seven of the eight biopsy specimens showed pleural thickening characterized by dense fibrous tissues with associated mononuclear cell infiltration, while the eighth biopsy specimen showed only clotted blood. The degree of inflammation and fibrosis correlated with the interval between CABG and pleural surgery. Early post-CABG patients displayed more inflammation, with abundant lymphocytes in nodular configuration deep in the fibrous tissues away from the surface. Abundant keratin-positive, spindle-shaped cells were present in the fibrous tissues. Late cases showed predominantly mature fibrosis. CONCLUSIONS: Persistent post-CABG effusion can occur. Pleural fluids and pleural tissue in early-stage lesions were characterized by lymphocytosis. With time, the inflammatory changes were replaced by fibrosis that resulted in dyspnea and, at times, trapped lungs requiring surgical intervention.

Aged↗
PubMed2000

Surgical management of early stage lung cancer.

For patients with lung cancer, the greatest hope for cure rests with patients with early stage disease. Surgery has been the standard of care for this group with the best 5-year survival of only 65% being achieved in patients with earliest pathologic Stage IA disease. Using strategies gained from the management of patients with advanced disease, clinicians are investigating the use of perioperative chemotherapy and radiotherapy to improve survival. In addition, biologic and molecular markers are being evaluated to assist in predicting prognosis and to identify those patients at increased risk for recurrent disease. Postoperative surveillance of patients using helical computed tomography (CT) scanning is being investigated to detect early recurrences and second primary lesions. With such treatment and management plans on the horizon, the prognosis of patients with early stage non-small cell lung cancer (NSCLC) may be improved.

Algorithms↗
PubMed2000

Intensive chemotherapy and radical resections for primary nonseminomatous mediastinal germ cell tumors.

BACKGROUND: Primary nonseminomatous germ cell tumors of the mediastinum (PNSGM), unlike malignancies of gonadal origin, have a poor prognosis. We report a single institutional experience over a 5-year period of PNSGM treated with intensive chemotherapy, followed by radical operation in those who responded to this neoadjuvant regimen. METHODS: From 1993 to 1998, 20 patients were referred for the management of PNSGM. All were male, with a median age of 30.5 years (range 18 to 48). Eighteen of 20 (90%) presented with symptoms. Most tumors were large, with a median diameter of 10 cm (range 3 to 20 cm). Thirteen patients (65%) had metastatic disease at the time of presentation. Eleven patients had received no prior treatment (initial group) and 9 were referred for salvage therapy after progression of their tumors, following treatment at other facilities (salvage group). All had elevated serum tumor markers (beta hCG and alpha-fetoprotein). Preoperative chemotherapy included alternating cycles of combinations of 3 or more drugs, including cisplatin, bleomycin, etoposide, vincristine, methotrexate, actinomycin, cyclophosphamide, and doxorubicin. An average of 10 cycles of chemotherapy was given to each patient in the initial group, and six to those in the salvage group. Five patients (25%) developed transient renal insufficiency, and 35% developed pulmonary infiltrates related to bleomycin. There were 3 chemotherapy related deaths. RESULTS: After chemotherapy, 11 patients underwent operation, with 10 complete resections of the residual mediastinal tumors. There were no perioperative deaths. The 2-year survival in the initial group is 72%, and 42% for the salvage group. CONCLUSIONS: An aggressive, multidisciplinary approach of alternating cycles of chemotherapy, followed by complete surgical resection of all remaining disease in patients whose markers normalize, can be associated with prolonged survival in patients with PNSGM.

Adolescent↗
PubMed2000

Cellular and humoral immune responses to adenovirus and p53 protein antigens in patients following intratumoral injection of an adenovirus vector expressing wild-type. P53 (Ad-p53).

The immune responses of 10 patients with advanced non-small cell lung cancer receiving monthly intratumoral injections of a recombinant adenovirus containing human wild-type p53 (Ad-p53) to adenovirus and transgene antigens were studied. The predominate cellular and humoral immune responses as measured by lymphocyte proliferation and neutralizing antibody (Ab) formation were to adenovirus serotype 5 vector antigens, with increased responses in posttreatment samples. Consistent alterations in posttreatment cellular and humoral immune responses to p53 epitopes were not observed, and cytotoxic Abs to human lung cancer cells were not generated. Patients in this study had evidence of an antitumoral effect of this treatment with prolonged tumor stability or regression; however, neither Abs to p53 protein nor increased lymphocyte proliferative responses to wild-type or mutant p53 peptides have been consistently detected.

Adenoviridae↗
PubMed2000

Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer.

PURPOSE: To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay). RESULTS: Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients. CONCLUSION: Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.

Adenoviruses, Human↗
PubMed1999

Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.

BACKGROUND: Preclinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA (Ad-p53). Therefore, in a phase I clinical trial, we administered Ad-p53 to 28 patients with non-small-cell lung cancer (NSCLC) whose cancers had progressed on conventional treatments. METHODS: Patients received up to six, monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection (23 patients) or bronchoscopy (five patients). The doses ranged from 10(6) plaque-forming units (PFU) to 10(11) PFU. RESULTS: Polymerase chain reaction (PCR) analysis showed the presence of adenovirus vector DNA in 18 (86%) of 21 patients with evaluable posttreatment biopsy specimens; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 (46%) of 26 patients. Apoptosis (programmed cell death) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling (TUNEL) staining in posttreatment biopsy specimens from 11 patients. Vector-related toxicity was minimal (National Cancer Institute's Common Toxicity Criteria: grade 3 = one patient; grade 4 = no patients) in 84 courses of treatment, despite repeated injections (up to six) in 23 patients. Therapeutic activity in 25 evaluable patients included partial responses in two patients (8%) and disease stabilization (range, 2-14 months) in 16 patients (64%); the remaining seven patients (28%) exhibited disease progression. CONCLUSIONS: Repeated intratumoral injections of Ad-p53 appear to be well tolerated, result in transgene expression of wild-type p53, and seem to mediate antitumor activity in a subset of patients with advanced NSCLC.

Adenoviridae↗
PubMed1999

A multidisciplinary surgical approach to superior sulcus tumors with vertebral invasion.

BACKGROUND: Vertebral body invasion by superior sulcus tumor has traditionally been considered a contraindication to surgical resection. Attempts at definitive radiation or chemoradiation have not been successful. Recent advances in spinal instrumentation have allowed more complete resection of vertebral body tumors. We, therefore, reviewed our recent experience with vertebral resection of superior sulcus tumors. METHODS: All patients (n = 17) undergoing resection of superior sulcus tumors with T4 involvement of the vertebrae from October 18, 1990 to September 21, 1998 at the University of Texas M.D. Anderson Cancer Center (MDACC) were evaluated. Their clinical and pathologic data were reviewed and analyzed for short- and long-term outcomes. RESULTS: Total vertebrectomy was performed in 7 patients (42%), partial vertebrectomy in 7 (42%), and 3 (18%) underwent neural foramina or transverse process resection. The median hospital stay was 11 days. Postoperative complications occurred in 7 patients (42%) and included pneumonia (6, 36%), arrhythmia (2, 12%), cerebrospinal fluid leak (2, 12%), wound breakdown (1, 6%), and reoperation for bleeding (1, 6%). Sixteen out of 17 patients received preoperative or postoperative radiation therapy. No perioperative mortality occurred. All patients remained ambulatory after spinal reconstruction. Overall actuarial survival at 2 years was 54%, with 11 patients still alive 2 to 50 months after resection. Locoregional tumor recurrence was noted in all 6 patients who had positive surgical margins, as opposed to 1 out of 11 patients (9%) with negative margins (p < 0.006). Additionally, the 2-year actuarial survival of patients with negative microscopic margins was 80% versus 0% for positive margins (p < 0.0006). CONCLUSIONS: An aggressive multidisciplinary approach to superior sulcus tumors with vertebral invasion can lead to long-term survival with acceptable morbidity if negative margins can be obtained. Vertebral body invasion should no longer be considered a contraindication for resection of superior sulcus tumors.

Adult↗
PubMed1998

Genetic polymorphism of CYP2D6 and lung cancer risk.

Previous reports of the association of extensive debrisoquine metabolism, controlled by the cytochrome P450 CYP2D6, with increased lung cancer risk have been conflicting. We examined the hypothesis that genetic polymorphism at the CYP2D6 locus identifies individuals at increased risk for lung cancer in a case-control study of 98 incident Caucasian lung cancer patients and 110 age-, race-, and sex-matched controls conducted at the National Naval Medical Center, Bethesda, MD. Using germ line DNA, we identified inactivating mutations at the CYP2D6 locus (CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6A), as well as those mutations that impair but do not abolish enzyme activity (CYP2D6*9 and CYP2D6*10A). Compared to subjects with homozygous inactivating mutations, no association with lung cancer was observed for those with homozygous or heterozygous functional alleles (odds ratios were 0.4 and 0.7, respectively). Furthermore, no excess risk was seen in any histological group or smoking category, and adjustment for smoking and sociodemographic characteristics did not alter the findings. Although the concept that genetic polymorphisms may contribute to differential lung cancer susceptibility is sound, these data do not support the role of CYP2D6 as a marker for elevated lung cancer risk.

Adenocarcinoma↗
PubMed1998

Gene therapy for non-small cell lung cancer: a preliminary report of a phase I trial of adenoviral p53 gene replacement.

The identification of genetic lesions that lead a normal cell to become malignant presents us with the opportunity of targeting those lesions as a means of therapy. Given the key role played by the tumor suppressor gene p53 in cell cycle regulation and apoptosis, and the evidence linking p53 mutations with non-small cell lung cancer, attempts at p53 replacement are a logical approach to therapy in this disease. In a phase I study, administration of an adenoviral p53 vector (Adp53) to 21 patients with advanced non-small cell lung cancer produced little toxicity. Up to six intratumoral injections at monthly intervals were well-tolerated. Expression of the p53 transgene was evident, along with potentially useful clinical responses. Time to disease progression in the indicator lesion treated with Adp53 appears to be enhanced by higher doses of vector, concomitant cisplatin therapy, and evidence of apoptosis on tumor biopsy specimens. Phase II trials should now be undertaken to determine the response rate to Adp53.

Adenoviridae↗
PubMed1997

The laryngeal mask airway: a new standard for airway evaluation in thoracic surgery.

BACKGROUND: Thoracic surgeons typically perform fiberoptic bronchoscopy (FOB) before thoracotomy, usually on the day of the operation after intubation with a single-lumen endotracheal tube (ETT) and before insertion of a double-lumen ETT. This routine requires two laryngoscopies and two intubations. The laryngeal mask airway (LMA) is an airway device developed in England and approved by the Food and Drug Administration in 1991 for clinical use in the United States. It requires neither mask ventilation nor laryngoscopy and allows FOB visualization of the epiglottis, larynx, and entire trachea. We assessed the LMA as an alternative to a single-lumen ETT for FOB before thoracotomy. METHODS: Through prospective assessment, 50 patients underwent FOB after insertion of an LMA before thoracotomy. Pulse rate, blood pressure, ease of insertion of the LMA, quality of FOB, and complications of LMA insertion were assessed. RESULTS: During LMA insertion, blood pressure and pulse rate increased less than 5% from baseline in all patients. The LMA was inserted successfully in all patients within 10 seconds. No complications occurred as a result of LMA insertion. CONCLUSIONS: Insertion of the LMA causes minimal hemodynamic response. From the time of induction of general anesthesia, insertion of the LMA is quick, simple, and safe and eliminates the need for endotracheal intubation with a single-lumen ETT before double-lumen tube insertion. The LMA, in contrast to the ETT, allows a complete survey of the larynx and trachea. The LMA is autoclavable, reusable, and cost effective. Therefore, in patients who require FOB immediately before thoracotomy, LMA use should be the standard for airway evaluation.

Bronchoscopy↗
PubMed1997

Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus.

BACKGROUND: The optimal management of patients with renal cell carcinoma with inferior vena cava tumor thrombus remains unresolved. Traditional approaches have included resection with or without the use of cardiopulmonary bypass. Chemotherapy has played a minor role except for biotherapeutic agents used for metastatic disease. METHODS: From January 1989 to January 1996, 37 patients with renal cell carcinoma and inferior vena cava tumor thrombus underwent surgical resection. The 27 men and 10 women had a median age of 57 years (range, 29 to 78 years). Thirty-six patients presented with symptoms; 21 had hematuria. Distant metastases were present in 12 patients. Tumor thrombi extended to the infrahepatic inferior vena cava (n = 16), the intrahepatic inferior vena cava (n = 16), the suprahepatic inferior vena cava (n = 3), and into the right atrium (n = 2). All tumors were resected by inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of the vena cavotomy. Cardiopulmonary bypass was necessary in only 2 patients with intraatrial thrombus. RESULTS: Complications occurred in 11 patients, and 1 patient died 2 days postoperatively of a myocardial infarction (mortality, 2.7%). Twenty patients are alive; overall 2- and 5-year survival rates were 61.7% and 33.6%, respectively. For patients without lymph node or distant metastases (stage IIIa), 2- and 5-year survival rates were 74% and 45%, respectively. The presence of distant metastatic disease (stage IV) at the time of operation did not have a significant adverse effect on survival, as reflected by 2- and 5-year survival rates of 62.5% and 31.3%, respectively. Lymph node metastases (stage IIIc) adversely affected survival as there were no long-term survivors. CONCLUSIONS: Resection of an intracaval tumor thrombus arising from renal cell carcinoma can be performed safely and can result in prolonged survival even in the presence of metastatic disease. In our experience, extracorporeal circulatory support was required only when the tumor thrombus extended into the heart.

Adult↗
PubMed1997

Anterior approaches to the thoracic spine in patients with cancer: indications and results.

BACKGROUND: Multidisciplinary surgical teams enable an aggressive approach to tumors involving the thoracic spine. METHODS: From February 1994 to July 1996, 61 patients underwent anterior resections of thoracic spine tumors. Their median age was 56 years. The indications for operation were curative in intent in 7 of 61 and palliative in 54 of 61 (to relieve intractable metastatic bone pain with neurologic compromise [n = 38] and pain alone [n = 16]). Sixteen patients came to our institution unable to ambulate with impending paraplegia. RESULTS: Anterior approaches included combined left side of the neck and median sternotomy for lesions involving vertebrae T-1 through T-3 (n = 9), posterolateral thoracotomy for T-3 through T-10 (n = 39), and thoracoabdominal approach at T-11 and T-12 (n = 13). Median hospital stay was 9.0 days (range, 4 to 57 days). Complications occurred in 18 of 61 (29.5%). In 55 of 61 (90%), pain was significantly improved after the operation. Twelve of the 16 patients who initially presented in wheelchairs regained ambulatory function. There were five perioperative deaths (8.2%). The 1-year cumulative survival for the entire group was 60%. CONCLUSIONS: An aggressive surgical approach in cancer patients with locally advanced or metastatic disease in the thoracic spine was associated with acceptable morbidity and mortality. There was significant improvement in their quality of life by control of intractable pain in 90% and recovery of ambulatory function in 75% of patients who presented with critical spinal cord compromise.

Humans↗
PubMed1997

Nephrectomy and vena caval thrombectomy in patients with metastatic renal cell carcinoma.

OBJECTIVES: To report out experience with performing nephrectomy and vena caval thombectomy in patients with metastatic renal cell carcinoma. METHODS: A retrospective review was performed of 15 patients who underwent surgical excision of the primary tumor and a caval thrombus and treatment of concurrent metastases between 1989 and 1995. The sites of metastases included lungs (n = 8), bone (n = 3), bulky retroperitoneal or mediastinal lymph nodes (n = 2), liver (n = 1), and contralateral adrenal (n = 1). The level of caval involvement was suprahepatic in 3 cases, retrohepatic in 2 cases, and infrahepatic in 10 cases. Three patients had an Eastern Cooperative Oncology Group performance score of 0, 11 had a score of 1, and 1 had a score of 2. Median follow-up was 17 months. RESULTS: Median operative time was 6.5 hours and median hospitalization was 10 days. Two patients required re-exploration for postoperative hemorrhage. There were no perioperative deaths. Four patients underwent surgery for resection of solitary metastases (1 lung, 2 spine, and 1 humerus); 2 of the 4 received adjuvant radiotherapy. Two patients received biologic therapy preoperatively, 3 received it both preoperatively and postoperatively, and 6 received it only postoperatively. The median time to initiation of postoperative biologic therapy was 48 days (range 25 to 110). Eleven patients are currently alive, 7 with no evidence of disease at a median follow-up of 17 months (range 6 to 66) and 4 with stable metastases at 14 months (range 4 to 22). Ten of the 13 symptomatic patients had improved performance scores after surgery. Four patients have died from metastatic disease: 2 from rapid progression at 2 and 5 months after surgery and the other 2 at 17 and 42 months. CONCLUSIONS: Nephrectomy and vena caval thrombectomy can be safely performed in selected patients with metastatic disease. Furthermore, in patients receiving biologic therapy, nephrectomy may enable a better quality of life and prolonged survival.

Aged↗
PubMed1996

Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.

A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was produced to mediate transfer of wild-type p53 into human non-small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector-related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector-p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.

Aged↗
PubMed1996

Expandable stents.

Expandable metallic stents are effective in selected patients with malignant or benign airway stenoses. When used for malignant lesions, the primary purpose of the stent is to improve the quality of life; stents are usually chosen for palliation of symptoms in recognition of the low likelihood of success for other therapy. For patients with benign stenoses, the stents provide a permanent source of structural support to alleviate the narrowed segment. The advantages of the expandable metallic stents are as follows: (1) they can be inserted through an endotracheal tube or under local anesthesia with relative simplicity under fluoroscopic guidance; (2) they do not impair the drainage of sputum because ciliary movement is not interrupted; (3) over a period of a few weeks, the meshwork is gradually covered with mucosa as the stent becomes incorporated into the airway wall; (4) ventilation usually is not impaired if the metallic mesh stent covers another nonstenosed bronchus, because the interstices of the stent are nonobstructive; and (5) they are dynamic and continue to expand over time, particularly if concurrent treatment achieves an effect on the lesion that caused stenosis. Disadvantages of the expandable stent include (1) they often are only temporarily effective for tracheobronchial stenosis due to intraluminal tumor or granulation tissue, both of which can grow between the wires; (2) they are considered permanent stents because removal is difficult; and (3) they can be poorly positioned during placement or can become displaced by progressive migration after placement, and they cannot be repositioned. A relative contraindication to insertion is an inflammatory process or infection that can predispose to granulation formation, particularly at the points of maximal contact pressure of the stent to the airway mucosa. In the presence of inflammation, it may be better to use a silicone prosthesis until the inflammatory process subsides and fibrosis occurs. Granulation tissue is less likely to occur in areas of established scar than in areas of acute inflammation. In circumstances in which it is essential that a stent remain only temporarily, an expandable stent should not be inserted in favor of a silicone stent, which can be removed. In the future, expandable stents may have silicone coverings or may be constructed of materials that facilitate removal. Until that time, expandable stents should be considered permanent and nonremovable. Subtle differences exist among the available stents. Standard is low-profile expandable construction from wire mesh. A relatively minor difference is the slightly wider expansibility of the Gianturco stent, a quality that makes it the best suited of the three stents for lesions that involve tracheomalacia. Perhaps the only major difference between the Wallstent and the Gianturco and Palmaz stents is its better ability to conform to tortuous lesions. In an acutely angled stricture, a Wallstent offers a better opportunity for successful placement than other stents. The filamentous meshwork of the Wallstent allows it to bend and conform better to distorted airways. The Gianturco and Palmaz stents have little longitudinal elasticity, which makes them less effective in a tortuous or highly angulated airway stenosis. Expandable stents have demonstrated their efficacy and exposed their limitations in the treatment of airway stenoses. Refinements in design should help to lessen specific disadvantages and problems. Covered expandable stents, a realistic prospect, have specific advantages over standard expandable stents; they will be removable and prevent tumor ingrowth. Current investigative work with such prostheses for the vascular system may provide the foundation for their investigative use in the airway. In essence, two categories of expandable stents are evolving, covered and uncovered, each having unique features adaptable to the specific clinical needs.

Bronchial Diseases↗
PubMed1996

Retinoic acid receptor- and retinoid X receptor-selective retinoids activate signaling pathways that converge on AP-1 and inhibit squamous differentiation in human bronchial epithelial cells.

Human bronchial epithelial (HBE) cells undergo squamous differentiation in response to a variety of conditions in tissue culture, and retinoid treatment has been shown to reverse this process. Retinoids mediate their effects through the retinoic acid and retinoid X nuclear receptors (RAR and RXR, respectively), which form RAR-RXR heterodimers, RXR homodimers, and heterodimers of RXR and certain orphan receptors. These receptor dimers bind to distinct response elements, activating separate pathways. In this study, we investigated the roles of RAR and RXR signaling pathways in the inhibition of HBE squamous differentiation. After induction of squamous differentiation by confluent growth, HBE cells were treated with retinoids that selectively activate RARs (E-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthaienyl)-1- propenyl] benzoic acid), RXRs (4-[1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl]benzoic acid), or both RARs and RXRs (9-c/s retinoic acid). These retinoids inhibited the mRNA expression of the squamous differentiation markers transglutaminase type I, involucrin, keratin 5, and keratin 13, suggesting that inhibition of HBE squamous differentiation could be mediated by activation of either RAR or RXR signaling pathways. We examined the role of AP-1 as a potential effector of these retinoid pathways. AP-1 transcriptional activity was reduced markedly by these retinoids, and a concomitant, but proportionally smaller, reduction in AP-1 DNA binding was observed. Furthermore, treatment of squamous HBE cells with the retinoid SR11238, which inhibited AP-1 without activating retinoid receptor transcriptional properties, reduced the expression of transglutaminase type I and involucrin. These findings support the hypothesis that, in HBE cells, RAR and RXR signaling pathways inhibit AP-1 transcriptional activity, and this contributes to retinoid-induced reversal of HBE squamous differentiation.

Alitretinoin↗