Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effect of isoflurane and sevoflurane on respiratory system resistance (Rmin,rs) in patients with chronic obstructive pulmonary disease (COPD). The diagnosis of COPD rests on the presence of airway obstruction, which is only partially reversible after bronchodilator treatment. Ninety-six consecutive patients undergoing thoracic surgery for peripheral lung cancer were enrolled. They were divided into two groups: preoperative forced expiratory volume in 1 s/forced vital capacity ratio <70% or >70%. Rmin,rs was measured after 5 and 10 min of maintenance anesthesia by using the constant flow/rapid occlusion method. Maintenance of anesthesia was randomized to thiopental 0.30 mg . kg(-1) . min(-1) or 1.1 minimum alveolar anesthetic concentration end-tidal isoflurane or sevoflurane. Eleven patients were excluded: two because anesthesia was erroneously induced with propofol and nine because of an incorrect tube position. Maintenance with thiopental failed to decrease Rmin,rs, whereas both volatile anesthetics were able to decrease Rmin,rs in patients with COPD. The percentage of patients who did not respond to volatile anesthetics was larger in those with COPD as well. In conclusion, we have demonstrated that isoflurane and sevoflurane produce bronchodilation in patients with COPD.
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PMID:The effect of volatile anesthetics on respiratory system resistance in patients with chronic obstructive pulmonary disease. 1567 54

Efaproxiral [RSR 13, GSJ 61, JP 4, KDD 86, RS 4] is a synthetic, small-molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treatment of cancer. It works by binding and allosterically stabilising deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen uptake of the tumour tissue and restores its sensitivity to radiation therapy, making therapy potentially more successful. This first-of-its-class compound is particularly applicable for the treatment of certain tumour types that lack oxygen, such as brain metastases. In contrast to conventional chemotherapeutic agents or radiation sensitisers, there is no requirement for efaproxiral to be administered directly into tumours or to cross the blood-brain barrier for it to display efficacy. Efaproxiral is under review for approval in the US and EU as an adjunct to whole-brain radiation therapy (WBRT) for the treatment of brain metastases originating from breast cancer. It is also under clinical evaluation for a variety of other cancers, including glioblastoma, non-small cell lung cancer (NSCLC) and cervical cancer. Allos is seeking partnership opportunities for efaproxiral's development and marketing. The company has indicated that the development of efaproxiral would be in cooperation with a corporate partner, according to its 2003 Annual Report. In 1994, Allos Therapeutics acquired exclusive worldwide rights to intellectual property relating to efaproxiral from the Center for Innovative Technology (CIT). Allos has entered into arrangements with two contract manufacturers for the supply of efaproxiral, and a third manufacturer for the supply of the formulated drug product. Hovione FarmaCiencia is the primary supplier of efaproxiral, and is contracted to manufacture sufficient quantities on a commercial scale. In addition, a second manufacturer, Raylo Chemicals, is also producing quantities of efaproxiral. In December 2003, Allos entered into a long-term development and supply agreement with Baxter Healthcare who will formulate the efaproxiral into an injection. Allos is also seeking to establish an alternate supplier of efaproxiral injection. Allos submitted a rolling NDA to the US FDA consisting of three data components. Submission began in the third quarter of 2003 and was completed by the fourth quarter of 2003. The first part of the application containing non-clinical information was submitted on 5 August 2003. The second part of the NDA containing information about efaproxiral's chemistry, manufacture and controls (CMC) was submitted in October 2003. Allos submitted its final component of the rolling NDA in December 2003. In February 2004, Allos announced that the FDA had accepted the company's NDA under priority review status. The FDA granted efaproxiral orphan drug status in August 2004 as an adjunct to WBRT for the treatment of brain metastases among breast cancer patients. Efaproxiral also received fast-track status in November 2000 for the same indication in the US. In February 2004, Allos initiated a phase III trial, called ENRICH (Enhancing Whole Brain Radiation Therapy In Patients with Breast Cancer and Hypoxic Brain Metastases) to investigate efaproxiral as an adjunct to WBRT for the treatment of brain metastases. Median survival time is the primary endpoint of the study. The National Breast Cancer Coalition (NBCC) is collaborating with the company to support trial enrolment and to gain additional insight about ways to improve radiation treatment in this patient population. The ENRICH trial protocol was approved by the FDA under a Special Protocol Assessment process; as part of the protocol, two interim analyses for safety and efficacy will be performed.This multicentre, randomised, open-label study has a target enrolment of approximately 360 patients at >100 medical centres across the US, Canada, Europe and South America. Allos announced in September 2004 that recruitment of clinical sites for the trial is ongoing across the US and Canada. Completion of trial enrolment in North America is anticipated in December 2005. Subsequently, Allos announced in January 2005 that recruitment into the ENRICH trial has commenced and is ongoing in Europe; enrolment at European sites is expected to conclude by the third quarter of 2006. Allos Therapeutics announced in June 2004 that it had filed an MAA with the EMEA for marketing of exaproxiral as an adjunct to WBRT for treatment of patients with brain metastases originating from breast cancer. The application is based on positive data from a pivotal phase III (REACH, RT-009) trial in this indication. The completed REACH trial investigated efaproxiral among patients with brain metastases undergoing WBRT. The trial was conducted at multiple sites in 11 countries, including the US, Canada, Europe and Australia. In August 2002 Allos completed the enrolment of 538 patients in the study. Initially only 408 patients were to be enrolled, but the company increased the size of the trial to conduct an appropriately powered subgroup analysis in patients with brain metastases from breast and NSCLC. The study was designed to demonstrate a 35% increase in median survival in the subgroup of patients compared with standard WBRT alone. The primary endpoint was survival. Allos began screening US patients for a phase III trial in NSCLC in early 2003. However, in May 2003, the company announced that as part of its revised operating plan it had suspended the screening of patients for this trial. The trial, which was known as ELITE (Enhanced Lung cancer treatment with Induction chemotherapy and Thoracic radiation and Efaproxiral), was comparing induction chemotherapy followed by thoracic radiation therapy with supplemental oxygen, with or without efaproxiral. The trial was enrolling patients with locally advanced, unresectable NSCLC. ELITE was planned to enrol up to 600 patients across North America and Western and Eastern Europe. Phase II trials in patients with inoperable NSCLC have been conducted in the US and Canada. Patient enrolment in one of these studies was completed in August 2000, with a total of 52 patients enrolled. This was an open-label, multicentre study of induction therapy with paclitaxel plus carboplatin followed by chest irradiation and efaproxiral in patients with locally advanced NSCLC. Positive results from this study were reported at the annual meeting of the European Society for Therapeutics Radiology and Oncology in September 2002. Efaproxiral has completed phase I trials as a treatment of surgical hypoxia in elective surgery patients receiving general anaesthesia. However, no recent development has been reported for these indications. In 1994, Allos signed an agreement with CIT for the exclusive worldwide rights to 17 US patents, a European patent covering the UK, France, Italy and Germany plus two pending patents in these territories, two issued patents in Japan, and a pending patent in Canada. These patents cover methods of allosterically modifying haemoglobin with efaproxiral and other compounds, the binding site of efaproxiral and therapy in certain indications including cancer, ischaemia and hypoxia. In addition to the licensed patents from CIT, Allos exclusively owns two patent families with pending applications directed to a formulation of efaproxiral and to methods of its use in BLOD MRI (blood oxygenation level-dependent magnetic resonance imaging) applications. These patents are pending in the US, Canada and Europe, and include an international patent application. In a May 2002 interview with the Wall Street Transcript, the CEO of Allos estimated the overall market for radiation therapy to be approximately 750 000 patients/year. Of this, brain metastases, NSCLC and glioblastoma therapy accounts for about 170 000, 140 000 and 6000 patients, respectively. Allos intend to use a speciality sales force to market efaproxiral directly to radiation therapists in North America. To penetrate the non-oncology market in the US, the company will seek partnership with one or more pharmaceutical companies with direct sales forces and with established distribution systems. Allos is also hoping to secure an oncology marketing partner for non-North American territories. At the time, the company had been issued 21 patents in the US, Canada, Europe and Japan.
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PMID:Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13. 1586 22

A case of low back pain syndrome was diagnosed due to spinal metastasis with unknown primary origin. During anesthesia for surgical stabilization, unexpected airway obstruction occurred after endotracheal intubation. Fiber-optic bronchoscopic examination showed narrowing of the trachea and main bronchi caused by extrinsic compression. After administration of neostigmine to reverse neuromuscular blockade, the patient resumed spontaneous breath. Airway obstruction was relieved thereafter. The extrinsic lesion was diagnosed as mediastinal lung cancer. The mechanism and management of this airway compromise caused by mediastinal tumor is discussed.
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PMID:Airway obstruction by a metastatic mediastinal tumor during anesthesia. 1601 46

Fas-Fas Ligand (FasL) is one of the major mediator system that activates programmed cell death. Cleavage of membranebound FasL by a metalloproteinase-like enzyme resulted in the formation of soluble FasL (sFasL). sFasL as well as the transmembrane form of FasL binds to Fas and transduces apoptotic signal in Fas-expressing cells. It's suggested that soluble Fas (sFas) and sFasL has an impact on tumor progress and immune escape feature of tumor cells from the host immune system. Since Fas antigen expression in the lungs has been localized to alveolar and bronchial epithelial cells, in this study we aimed to investigate the sFas (pg/mL) and sFasL levels (pg/mL) of bronchoalveolar lavage (BAL) fluid in lung cancer patients. Study population was consisted of 27 patients with lung cancer (mean age 62.9 +/- 10.7 years, 25 control subjects (mean age 47.9 +/- 13.9 years). BAL was performed under local anesthesia, on the unaffected lung of patients; either subsegments of right middle or lingula. BAL sFas and sFasL were evaluated by using ELISA method. The mean levels of sFas was 60.8 +/- 56.8 in lung cancer patient and 39.5 +/- 25.9 in control subjects (p> 0.05). The mean levels of sFasL was 51.6 +/- 39.2 in cancer patient and 41.2 +/- 27.4 in control subjects (p> 0.05). In conclusion, although we did not observe any significant difference between two groups, higher BAL levels of sFas and sFasL levels in lung cancer patients than control subjects, made us thought that apoptosis might have a role development and progression of lung cancer.
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PMID:The evaluation of soluble Fas and soluble Fas ligand levels of bronchoalveolar lavage fluid in lung cancer patients. 1610 Jun 48

We report a postpneumonectomy patient who underwent partial lobectomy. A 74-year-old man was scheduled for right partial lobectomy because of metastatic lung cancer. He had undergone left pneumonectomy 19 months before because of lung cancer. Anesthesia was maintained with intravenous propofol and thoracic epidural block. During surgery, respiration was maintained with mechanical and intermittent manual ventilation. Percutaneous cardiopulmonary support and high frequency jet ventilation were at hand but were not needed. There was no intraoperative hypoxia and the postoperative course was uneventful.
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PMID:[Anesthetic management for partial lobectomy in a postpneumonectomy patient]. 1629 71

The aim of this study was to assess the dynamics of osteoclast migration and the degradation of unmineralized extracellular matrix in an osteolytic metastasis by examining a well-standardized lung cancer metastasis model of nude mice. SBC-5 human lung small carcinoma cells were injected into the left cardiac ventricle of 6-week-old BALB/c nu/nu mice under anesthesia. At 25-30 days after injection, the animals were sacrificed and their femora and/or tibiae were removed for histochemical analyses. Metastatic lesions were shown to occupy a considerable area extending from the metaphyses to the bone marrow region. Tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts were found in association with an alkaline phosphatase (ALPase)-positive osteoblastic layer lining the bone surface, but could also be localized in the ALPase-negative stromal tissues that border the tumor nodules. These stromal tissues were markedly positive for osteopontin, and contained a significant number of TRAPase-positive osteoclasts expressing immunoreactivity for CD44. We thus speculated that, mediating its affinity for CD44, osteopontin may serve to facilitate osteoclastic migration after their formation associated with ALPase-positive osteoblasts. We next examined the localization of cathepsin K and matrix metallo-proteinase-9 (MMP-9) in osteoclasts. Osteoclasts adjacent to the bone surfaces were positive for both proteins, whereas those in the stromal tissues in the tumor nests showed only MMP-9 immunoreactivity. Immunoelectron microscopy disclosed the presence of MMP-9 in the Golgi apparatus and in vesicular structures at the baso-lateral cytoplasmic region of the osteoclasts found in the stromal tissue. MMP-9-positive vesicular structures also contained fragmented extracellular materials. Thus, osteoclasts appear to either select an optimized function, namely secreting proteolytic enzymes from ruffled borders during bone resorption, or recognize the surrounding extracellular matrix by mediating osteopontin/CD44 interaction, and internalize the extracellular matrices. Microsc.
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PMID:Histochemical evidence of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells. 1645 38

Although modern techniques in anesthesia and surgery have reduced morbidity and mortality for pulmonary resection, some physicians still consider advanced age a contraindication to resection of lung cancer. We examined our experience with VATS lobectomy in octogenarians at Cedars-Sinai Medical Center over 12 years (1992-2004). There were 159 patients. Mean age was 83 years (range, 80-94 years) consisting of 61 males (38%) and 96 females (62%). Operations included 153 lobectomies (96%), 3 bilobectomies (2%), and 3 pneumonectomies (2%). Two operations were converted to thoracotomy (1%), one due to bleeding, and one due to poor visualization. Median hospital stay was 4.00 +/- 6.39 days. One hundred thirty-one patients (82%) had no complications. The most common complication was arrhythmias occurring in 8/159 (5%) patients. There were three perioperative deaths (1.8%). Pathology revealed 104 adenocarcinomas (65%), 25 squamous cell carcinomas (16%), 5 adeno-squamous carcinomas (3%), 7 bronchoalveolar carcinomas (4%), 7 large cell carcinomas (4%), 4 carcinoid tumors (3%), 4 non-small cell lung cancer (NSCLC) (3%), 1 mucoepidermoid carcinoma (< 1%), 1 lymphoma (< 1%), and 1 pulmonary metastasis (< 1%). Median follow-up was 29 months. The results of this series show that age alone is not a contraindication to the surgical treatment of lung cancer.
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PMID:VATS anatomic pulmonary resection in octogenarians. 1646 20

A 33-year-old woman pregnant with twins was diagnosed with metastatic lung cancer during pregnancy. Her multidisciplinary care raised many medical and ethical issues. To help decide on the best anaesthetic technique for caesarean section, a literature search of published case reports of pregnancy associated with lung cancer was performed. Thirty-five cases of primary lung cancer associated with pregnancy were found. Anaesthetic technique was reported in only five of the 20 patients who underwent caesarean section: one spinal, three epidurals and one general anaesthetic. Of the 11 patients who delivered vaginally, only one was reported to have received epidural analgesia. As published data regarding anaesthesia and analgesia are limited for women with lung cancer in pregnancy, we describe our perioperative approach and review the potential challenging aspects of management in a pregnant patient with metastatic lung cancer.
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PMID:Anaesthesia for caesarean section in a woman with lung cancer: case report and review. 1712 96

A 61-year-old man who had undergone left pneumonectomy 7 years before for lung cancer was scheduled for thoracoscopic partial pulmonary resection of the right lung because of pneumothorax. Anesthesia was induced with propofol and maintained with sevoflurane and thoracic epidural block. He was monitored with electrocardiogram, direct arterial pressure, pulse oximetry and capnogram. Arterial blood gas sampling was done as required. During the operation, ventilation was maintained with mechanical and intermittent manual ventilation. Hemodynamic status was stable and intra- and post-operative course was uneventful. PCPS, ECLS, CVC and PAC were not required. A successful and satisfactory anesthetic management was accomplished by good cooperation between anesthesiologists and surgeons.
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PMID:[Anesthetic management of surgical intervention for contralateral pneumothorax after left pneumonectomy]. 1724 51

Empyema toracis can be defined as a purulent pleural effusion. From 1998 to 2003 we treated 106 patients (87 men and 19 women), aged between 23 and 82 years, affected by localized empyema toracis. All of them received initially a chest tube and 73 of them (60 men and 13 women), in combination with selected antibiotics, had an uneventful recovery. Twenty three patients (17 men and 5 women) underwent thoracotomy and pleural decortication, and 7 patients (6 men and 1 woman) underwent open drainage, that means a thoracostoma. All these 7 patients were affected by chronic empyema: 3 of them with residual post-pneumectomy empyema (1 for lung cancer and 2 for tubercular lung disease); 3 had destroyed lung and 1 was suffering for multiorgan deficiency (respiratory, cardiac and chronic renal insufficiency). The thoracostoma procedure was under general tube anaesthesia with tracheal intubation. The mean surgical time was 26 minutes. The mean postoperative hospital stay was 10 days. In this period of time no death has been recorded or any kind of complication. Before the dismission all of them were teached with their familiars how to take care of the remaining thoracostoma. After the dismission all the patients were followed as outpatients for a variable period, for 14 and 36 months. During this period there were neither complications nor recidives, and all the patients have accepted the "thoracostoma" as a new way of life. Therefore thoracostoma appears as an acceptable, useful and no dangerous solution for the treatment of the chronic thoracic empyema.
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PMID:Therapy of the empyema thoracis. Why not thoracostoma? 1799 Jun 6


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