Taxanes (docetaxel and paclitaxel) as well as cisplatin (CDDP) are key chemotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC). Although some indicators of taxane resistance, ...such as beta-tubulin mutations, P-glycoprotein (P-gp) and Bcl-2, have been reported in malignant cells, the mechanisms of taxane resistance in NSCLCs have yet to be fully elucidated. We evaluated in vitro chemosensitivity to docetaxel (DOC) and CDDP in 87 surgically-resected specimens of NSCLC by collagen gel-droplet embedded culture drug sensitivity test (CD-DST). Bcl-2 and P-gp expression in these specimens were also investigated by immunohistochemistry. We examined the association between Bcl-2 and P-gp expression and in vitro chemosensitivity to DOC and CDDP. Out of the 87 NSCLCs that were examined, Bcl-2 and P-gp were expressed in 32 (36.8%) and 28 (32.2%) of the tumors, respectively. Positive Bcl-2 expression was significantly associated with enhanced DOC sensitivity in NSCLCs (p=0.007) while no apparent association was observed between DOC sensitivity and P-gp expression. Interestingly, although DOC, but not CDDP has been reported to be a substrate of P-gp, P-gp expression was significantly inversely correlated with CDDP sensitivity in pulmonary adenocarcinomas (p=0.03). Positive Bcl-2 expression may be a promising indicator in determining in vitro taxane sensitivity in NSCLCs. On the other hand, positive P-gp expression may be an indicator of enhanced in vitro resistance to CDDP in pulmonary adenocarcinomas.
A novel drug delivery system (DDS) compound was formed by binding doxorubicin hydrochloride (DXR) to the macromolecular carrier carboxymethyldextran polyalcohol (CM-Dex-PA) via the peptidyl spacer ...(GGFG: Gly-Gly-Phe-Gly). Its use in a murine tumor model confirmed that the DDS (CM-Dex-PA-GGFG-DXR) was retained in the blood and distributed in tumor tissue. The combined use of hyperthermia (HT: 41-42 degrees C for 40 min) and DXR-conjugate (5, 10 or 20 mg/kg i.v.) on tumor accumulation and efficacy was investigated in a murine model of non-small cell lung cancer. Tumor size was measured and the tumor inhibition rate (IR) was calculated. The mean tumor concentration of conjugated DXR in the DXR-conjugate group was 9.40 microg/g compared with 19.04 microg/g in the DXR-conjugate + HT group (p=0.0008). The antitumor efficacy of the DXR-conjugate was significantly enhanced in the groups receiving the combination therapy (p=0.0039, p=0.0250). Significant differences were found between the groups given DXR and those given DXR-conjugate (p=0.0492, p=0.0104). The results demonstrate that the antitumor efficacy of DXR-conjugate is significantly superior to that of DXR alone and the combined use of DXR-conjugate and HT increases the drug's concentration in the tumor, with significant enhancement of antitumor efficacy.
A 35-year-old woman with a clinical diagnosis of stage T2N2M0 lung adenocarcinoma received 3 courses of preoperative chemotherapy with cisplatin and docetaxel. The treatment response was no change. A ...left inferior lobectomy with mediastinal and hilar lymph-node dissection (ND2a) was performed. The pathological diagnosis was stage T2N2M0 lung cancer. Gefitinib was administered postoperatively. After 2 months of oral treatment, gefitinib was discontinued because of enlarged subcarinal lymph nodes and an elevated level of serum Sialyl LewisX-i antigen (SLX). Starting 4 months after surgery, the mediastinum was irradiated with a total dose of 50 Gy. Chemotherapy with S-1 was started 5 months after surgery. S-1 was administered in a dose of 100 mg/day in two divided doses for 4 weeks, followed by 2 weeks of rest. The patient received 6 courses of chemotherapy with S-1, without increasing the dose. The enlarged mediastinal lymph nodes disappeared, and the serum SLX level returned to normal. The patient had a complete response, and was subsequently followed on an outpatient basis while receiving oral UFT. More than 36 months have elapsed since surgery, with no evidence of recurrence.
Case. The patient was a 74-year-old man who expectorated bloody sputum in July 2003. A diagnosis of squamous cell carcinoma (Class V) was established based on sputum cytology. A nodular lesion 4 mm ...in diameter was detected at the orifice of the left B^3 and was diagnosed as early stage central lung cancer. As surgery was judged difficult due to poor lung function, the tumor was ablated by microwaves. The patient was followed up and regularly underwent sputum cytology and narrow band imaging (NBI) bronchoscopy. However, in December 2008, a 5-mm nodular lesion was detected at the bifurcation between the left B^4 and B^5, and in May 2009, a flat lesion with a diameter of several millimeters was detected at the orifice of the left B^5a. Both lesions were diagnosed with squamous cell carcinoma by biopsy and ablated by microwaves. There has been no recurrence for the last 2 years and the patient is currently being followed up. Conclusion.NBI-supported bronchoscopy may be useful to detect early stage lesions. Microwave coagulation therapy is effective for early stage central lung cancer with a diameter of 5 millimeters.
The volume of lung tumor core biopsy specimens has been restricted because of concerns for complications such as bleeding and air leakage. In this animal experiment, we investigated the possibility ...of larger bore biopsies through the peripheral lung parenchyma.
Lung biopsy was done in male domestic pigs (n= 4) under thoracotomy. A single biopsy using a 12-gauge cutting biopsy needle was done with sheath (sheath group, eight biopsies) or without sheath (nonsheath group, eight biopsies). After biopsy, bleeding time, bleeding amount, and positive airway pressure causing air leakage from the insertion site was compared between groups (Mann-Whitney U test). To observe long-term effects in closed-chest animals, percutaneous lung biopsy with the use of a sheath was carried out percutaneously in male beagles (n = 9). The animals were observed for 3 weeks.
In the pigs (sheath group) after biopsy, bleeding flowed through the sheath and formed a sheath-molded fibrin plug that secured the insertion site. Bleeding time and amount decreased significantly in the sheath group compared with the nonsheath group (115 +/- 108 versus 295 +/- 150 seconds, P = .018, and 37 +/- 41 versus 98 +/- 72 grams, P= .027, respectively). Air leakage pressure was significantly higher in the sheath group compared with the nonsheath group (37 +/- 6 versus 18 +/- 5 cmH2O, P = .001). In the beagles, no complications such as pneumothorax, hemothorax, or airway bleeding was apparent.
Although we have not evaluated lung tumor biopsy per se, lung tumor biopsy with a 12-gauge cutting needle may be possible with a use of a sheath.
Background. For treatment of postintubation and post-tracheostomy tracheal stenosis, resection of the stenotic tracheal region, followed by end-to-end anastomosis has been considered the most ...reliable, but recently, many cases of intratracheal treatment have been reported with favorable outcomes. Objective. Four cases of postintubation and post-tracheostomy tracheal stenosis treated with T-tube stenting were evaluated to investigate the usefulness and limitation of intratracheal treatment. Subjects. The subjects were 3 patients with postintubation tracheal stenosis and 1 patient with post-tracheostomy tracheal stenosis that we encountered at our department between June 2003 and June 2009. Results. The stenotic regions were dilated using microwave coagulation therapy followed by T-tube stenting in all cases. Stenosis was resolved in 2 of the 4 cases, but restenosis occurred in 2, for which T-tube placement was repeated. Conclusion. Dilatation using microwave coagulation therapy was useful as an early treatment to maintain the airway. While the safety and usefulness of the T-tube were confirmed, it may be difficult to achieve healing by stenting when the tracheal cartilage is severely injured and the lesion is accompanied by malacia.
A 17-year-old female complained of dyspnea and left chest pain. Chest film revealed complete atelectasis of the left lung. The bronchofiberscopic examination revealed an endobronchial lesion causing ...a massive obstruction of the left main bronchus, and based on biopsy results, we made a diagnosis of mucoepidermoid carcinoma. Prior to the operation, bronchofiberscopic electrosurgery was performed under general anesthesia, and partial resection of the tumor took place using an electrosurgical snare. This procedure enables observation of the distal part of the left main bronchus. Observation of the distal side of the tumor showed that the tumor originated from the mediastinal side of the left main bronchus and the tumor base was limited to the left main bronchus. Thus, it was possible to perform a sleeve resection of the left main bronchus along with the surrounding healthy bronchial tissue without losing lung parenchyma. We reconstructed the left main bronchus with end to end anastomosis after the resected edges were proven to be tumor-free by frozen section. The resected specimen originating in the left main bronchus and the tissue protruding to the endobronchial lumen were diagnosed as mucoepidermoid carcinoma grade II, according to Conlan's classification.
PDF
